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Malaria Mortality Rates in South Asia and in Africa: Implications for Malaria Control
Abstract
Malaria mortality in human populations varies greatly under different circumstances. The intense malaria transmission conditions found in many parts of tropical Africa, the much lower malaria inoculation rates currently sustained in areas of southern Asia, and the epidemic outbreaks of malaria occasionally seen on both continents, present highly contrasting patterns of malaria-related mortality. Here Harsha Alles, Kamini Mendis and Richard Carter examine malaria-related mortality under different circumstances and discuss implications for the management of malaria in these settings. They emphasize the power of rapid case treatment to save lives at risk under virtually all circumstances of malaria transmission.
... In endemic areas with stable malaria, because of regular inoculations every person receives, a strong protective immunity against overt illness and risk of death from malaria is acquired usually by the age of 4 or 5 years. Therefore, most of the morbidities and mortalities occur before this age 30,31 . This is especially true in the presence of P. falciparum. ...
... Determination of malaria mortality rates in settled human populations living in endemic areas without access to drug treatment is very difficult and is usually done through three ways: (1) information collected from direct observation of deaths within a community; (2) data from malaria eradication and its effect on total mortality; and (3) calculation of the expected mortality rate that can be deduced from the gene frequency of alleles which cause protection against malaria 31 . Obviously, in the current study the third method could not be used, since it depends on the "malaria hypothesis", itself, the validity of which is tested herein. ...
... Obviously, in the current study the third method could not be used, since it depends on the "malaria hypothesis", itself, the validity of which is tested herein. Estimations of the mortality rate reported differently from study to study from 5 to 114 deaths per 10,000 population per year 2,24,[30][31][32][33][34][35] . ...
In 1954, Allison proposed that hemoglobin S (HbS) gene causes protection against fatal malaria. This would explain the high HbS gene frequency observed in certain regions hyperendemic for malaria, so-called “malaria hypothesis”. This in silico study was conducted to examine the feasibility of the hypothesis under more realistic initial conditions, where a mutant gene with heterozygous advantage against malaria (e.g., HbS) was introduced in a group of Neolithic hunter-gatherers who decided to start agriculture nearby water where malaria killed a proportion of population. The tribe population size, number of children born to each woman in each generation, mortality from malaria and sickle cell disease, the protection factor provided by the gene carriers against malaria, the probability of mating between the members of the parent and offspring populations, population growth, and increased fertility in women heterozygous for HbS, were also considered. For effectively confer protection against malaria within the shortest possible period, the mutation needs to be happened in a small population. For a large population, the process would take around 100 generations (~ 2500 years) or more to provide an effective protection. Even then, the probability that the new gene could survive and propagate to future generations is about 35%. Conventional population genetics equations with differential or difference equations, give totally incorrect estimates of the gene frequency in small populations; discrete mathematics should be used, instead. After introduction of the advantageous mutation, the gene frequency increased until a steady state value. This value is far less than the gene frequency reported in certain tribes of Africa. It seems that the malaria hypothesis, per se, could not explain such a high observed gene frequency, unless HbS is associated with lower mortality from other causes too.
... In regions of low to moderate transmission, as in Sri Lanka, immunity is low and most individual inoculation results in infection and disease at all ages (Alles et al., 1998). It is dependent on the intensity and stability of transmission within the respective region. ...
... Acquired human immunity is developed with increasing age due to number of years of chronic exposure (Mendez et al., 2000). This high clinical tolerance allows no case fatalities after 10 -15 years of age (Alles et al., 1998). Critically it can be lost within a year in the absence of reinfection, such as during periods of schooling or employment abroad. ...
Social factors of malaria were examined using the case-study of malaria incidence in Sri Lanka. Sri Lanka has currently achieved eradication of malaria but as it is a small island, developing country, it is vulnerable to climate change threats. Therefore the social influences, host immunity, anti-malarial resistance, prosperity and travel, were investigated with particular reference to potential climate change-induced malaria. Development of immunity depends on the intensity and stability of transmission within the region. Although Sri Lanka recently eradicated malaria, it was previously considered a region of low to moderate transmission, with most individual inoculation resulting in infection and disease at all ages. Self-medication when unrequired is particularly significant in contributing to the global issue of anti-malarial resistance. Despite known drug resistance, distribution continues to be widespread due to low over-the-counter cost and rapid relief of symptoms. Poverty promotes transmission of malaria and in turn malaria impedes economic growth. Malaria imposes economic loss beyond direct medical costs and associated effects to macroenomic costs by impacts on worker productivity, school children performance, etc. However improved economic growth is insufficient to eradicate malaria e.g. Oman. Air travel is a vital factor in malaria transmission due to conveyance of asymptomatic carriers from endemic to non-endemic countries, leading to outbreaks of epidemic malaria. Incidence of imported malaria has been observed mainly due to lapse or absence of prophylaxis. The management of malaria was examined under the categories of public healthcare services and mitigation measures. Mitigation measures were evaluated in relation to social factors, to determine their efficacy in the event of resurgent malaria. Mitigation techniques of prominence were anti-malarial therapy, Indoor Residual Spraying, Insecticide Treated Nets and Long Lasting Insecticide Treated Nets and lastly environmental management. Malaria is borne out of multiple risks; both environmental (i.e. climate change and environmental degradation) and social (i.e. anti-malarial resistance, migration and poverty). As observed in Sri Lanka, strong political commitment in prioritising malaria control with sustained resource allocation is vital to eliminate malaria. A multi-measure approach cross cutting public health care services and malaria interventions has proven effective despite some evident climate change impacts
... Vector groups for both human malaria (Anopheles mosquitoes) and avian malaria (Culex mosquitoes, Culex quinquefasciatus and C. univitattus) demonstrate sensitivity to temperature changes [7]. Further complexity in the epidemiology of avian malaria is introduced by other unknowns, such as the blood meal frequency of infected mosquitoes, transmission rates, and the ratio of vectors to birds in a given habitat [8][9][10]. Research indicates that anthropogenic activities often alter water quality and availability, and may influence the amount of rainfall that a locality or region receives [11,12]. ...
... Temperature and pH displayed the most marked variations between seasons (Table 2), which is consistent with previous findings [43,44]. Temperature varied with vector abundance, which was also consistent with previous findings on associations between water quality and malaria vectors [10,15]. These elements did not display any apparent influence on either mosquito or Plasmodium prevalence (see Figures 1 and 5). ...
The close relationship between vector-borne diseases and their environment is well documented, especially for diseases with water-dependent vectors such as avian malaria. Mosquitoes are the primary vectors of avian malaria and also the definitive hosts in the disease life cycle. Factors pertinent to mosquito ecology are likely to be influential to observed infection patterns; such factors include rainfall, season, temperature, and water quality.
The influence of mosquito abundance and occurrence on the prevalence of Plasmodium spp. in the Ploceidae family (weavers) was examined, taking into account factors with an indirect influence upon mosquito ecology. Mosquitoes and weaver blood samples were simultaneously collected in the Western Cape, South Africa over a two-year period, and patterns of vector abundance and infection prevalence were compared. Dissolved oxygen, pH, temperature and salinity measurements were taken at 20 permanent waterbodies. Rainfall during this period was also quantified using remotely sensed data from up to 6 months prior to sampling months.
Sixteen wetlands had weavers infected with avian malaria. More than half of the mosquitoes caught were trapped at one site; when this site was excluded, the number of mosquitoes trapped did not vary significantly between sites. The majority of mosquitoes collected belonged to the predominant vector species group for avian malaria (Culex culex species complex). Seasonal variation occurred in infection and mosquito prevalence, water pH and water temperature, with greater variability observed in summer than in winter. There was a significant correlation of infection prevalence with rainfall two months prior to sampling months. Mosquito prevalence patterns across the landscape also showed a close relationship to patterns of rainfall. Contrary to predictions, a pattern of asynchronous co-variation occurred between mosquito prevalence and infection prevalence.
Overall, salinity, rainfall, and mosquito prevalence and season were the most influential vector-related factors on infection prevalence. After comparison with related studies, the tentative conclusion drawn was that patterns of asynchronous variation between malaria prevalence and mosquito abundance were concurrent with those reported in lag response patterns.
... and Gilman 2002 ) . For a recent , broad overview of the malaria burden throughout India see also Kumar et al . ( 2007 ) . 9 In the same year , 214 malaria deaths were reported . Malaria mortality rates in India are much lower than in many malarious African countries , due to the relatively better vector - control and health care system in India ( Alles et al . 1998 ) . 10 The study blocks were chosen because the corresponding district medical officers did not plan free ITN disbursals in those areas . 11 The reason for this choice is that the data are part of the baseline survey for a randomized controlled trial carried out in collaboration with BISWA . 12 The sampling scheme generates different pr ...
... 9 In the same year, 214 malaria deaths were reported. Malaria mortality rates in India are much lower than in many malarious African countries, due to the relatively better vector-control and health care system in India (Alles et al. 1998) categories—is Rs 655, which is approximately twice as large as the poverty line in rural Orissa in 2004-05. 14 The mean number of bednets per head is close to 0.3, but very few of these are treated with insecticide, so that the overall mean number of ITNs per head is only 0.04. ...
We study the identification and estimation of key parameters in a basic model of technology adoption when specifically collected information on subjective beliefs and expectations about the technology’s impact is available. We discuss identification with both non-parametrically and parametrically specified utility as well as parametric and semi-parametric specifications for unobserved heterogeneity. We propose parametric and semi-parametric estimation methods to recover underlying preferences and use the model to study the adoption of bednets among poor useholds in rural Orissa (India). We carry out counter-factual exercises to examine the effects of price and belief changes on net ownership decisions. The results suggest that net purchase decisions are relatively insensitive to changes from current prices and beliefs. The methods proposes here should have applicability to other discrete choice settings with non-linear indices.
... When P. falciparum is involved in an epidemic, death rates can become very high. A single untreated attack of P. falciparum malaria in a nonimmune individual carries a risk of death that may be anywhere from a few percent to at least 20 to 30% according to circumstances (3,12,21). These higher rates are the kinds of mortality rate that occur during P. falciparum malaria epidemics (30, 45a, 49, 67, 75, 219). ...
... Under whatever condition of endemicity malaria occurs, much, and according to the evidence of a number of analyses, generally most (74,134,142,219), of the malaria-related mortality has in the past been an indirect result of the effects of malarial infection combined with other infections and conditions. Wherever interventions have been conducted for the reduction of malaria transmission, reductions in total mortality rates have been several times greater than the malaria-related death rates as estimated prior to the interventions (3,134). Some of this discrepancy may be due to failures to detect or account for all the deaths in which malaria would have been an apparent cause. ...
Malaria is among the oldest of diseases. In one form or another, it has infected and affected our ancestors since long before the origin of the human line. During our recent evolution, its influence has probably been greater than that of any other infectious agent. Here we attempt to trace the forms and impacts of malaria from a distant past through historical times to the present. In the last sections, we review the current burdens of malaria across the world and discuss present-day approaches to its management. Only by following, or attempting to follow, malaria throughout its evolution and history can we understand its character and so be better prepared for our future management of this ancient ill.
... There are differences between P falciparum malaria risk and resulting morbidity and mortality outcomes experienced in different populations of the world. 105 It is beyond the scope of this review to attempt to model morbidity and mortality globally. Reconciling NfP estimates with national level malaria reporting is a logical and important extension of this work. ...
... It is perhaps worth noting, however, that while mortality rates from P falciparum infection are on average nine per 1000 in the under-five populations of AFRO, 31,106 they range from 0·1-1 per 1000 and 0·01-0·1 per 1000 (in all age groups) in SEARO countries such as Myanmar (Burma) and Sri Lanka, respectively. 105 This order of magnitude difference in mortality risk means that most malaria mortality is likely still to be in AFRO. The absolute magnitude of populations at risk outside of AFRO (table 2 and table 4), however, indicate that malariaattributable mortality will not be trivial, particularly in SEARO, and that morbidity is likely to be substantial. ...
The aim of this review was to use geographic information systems in combination with historical maps to quantify the anthropogenic impact on the distribution of malaria in the 20th century. The nature of the cartographic record enabled global and regional patterns in the spatial limits of malaria to be investigated at six intervals between 1900 and 2002. Contemporaneous population surfaces also allowed changes in the numbers of people living in areas of malaria risk to be quantified. These data showed that during the past century, despite human activities reducing by half the land area supporting malaria, demographic changes resulted in a 2 billion increase in the total population exposed to malaria risk. Furthermore, stratifying the present day malaria extent by endemicity class and examining regional differences highlighted that nearly 1 billion people are exposed to hypoendemic and mesoendemic malaria in southeast Asia. We further concluded that some distortion in estimates of the regional distribution of malaria burden could have resulted from different methods used to calculate burden in Africa. Crude estimates of the national prevalence of Plasmodium falciparum infection based on endemicity maps corroborate these assertions. Finally, population projections for 2010 were used to investigate the potential effect of future demographic changes. These indicated that although population growth will not substantially change the regional distribution of people at malaria risk, around 400 million births will occur within the boundary of current distribution of malaria by 2010: the date by which the Roll Back Malaria initiative is challenged to halve the world's malaria burden.
... Similar relations hold for asymptomatic patients and τ HA , α HA , and δ HA . For previously unexposed patients, case-mortality is on the order of at least 1 − 2%, even when there is access to treatment, and is more generally in the 5 − 20% range [5]. Despite treatment, case-fatality rates are quite high in children suffering from severe disease, who have limited (if any) immunity, and was 8.5% in one trial of sub-Saharan children receiving highly effective artesunate [28]. ...
Malaria is mainly a tropical disease and its transmission cycle is heavily influenced by environment: The life-cycles of the Anopheles mosquito vector and Plasmodium parasite are both strongly affected by ambient temperature, while suitable aquatic habitat is necessary for immature mosquito development. Therefore, how global warming may affect malaria burden is an active question, and we develop a new ordinary differential equations-based malaria transmission model that explicitly considers the temperature-dependent Anopheles gonotrophic and Plasmodium sporogonic cycles. Mosquito dynamics are coupled to infection among a human population with symptomatic and asymptomatic disease carriers, as well as temporary immunity. We also explore the effect of incorporating diurnal temperature variations upon transmission. Rigorous analysis of the model show that the non-trivial disease-free equilibrium is locally-asymptotically stable when the associated reproduction number is less than unity (this equilibrium is globally-asymptotically for a special case with no density-dependent larval and disease-induced host mortality). Numerical simulations of the model, for the case where the ambient temperature is held constant, suggest a nonlinear, hyperbolic relationship between the reproduction number and clinical malaria burden. Moreover, malaria burden peaks at 29.5 C when daily ambient temperature is held constant, but this peak decreases with increasing daily temperature variation, to about 23–25 C. Malaria burden also varies nonlinearly with temperature, such that small temperature changes influent disease mainly at marginal temperatures, suggesting that in areas where malaria is highly endemic, any response to global warming may be highly nonlinear and most typically minimal, while in areas of more marginal malaria potential (such as the East African highlands), increasing temperatures may translate nearly linearly into increased disease potential. Finally, we observe that while explicitly modelling the stages of the Plasmodium sporogonic cycle is essential, explicitly including the stages of the Anopheles gonotrophic cycle is of minimal importance.
... 9 In the same year, 214 malaria deaths were reported. Malaria mortality rates in India are much lower than in many malarious African countries, due to the relatively better vector-control and health care system in India (Alles et al. 1998). 10 The study blocks were chosen because the corresponding district medical officers did not plan free ITN disbursals in those areas. ...
... falciparum (Delacollette et al. 1993); (Snow et al. 1997); (Alles et al. 1998); (Gupta et al. 1999); (Modiano et al. 1998). Severe anaemia represents the primary cause of malaria-related death where the highest risk of infection prevails, while death due to cerebral malaria predominates in areas where infection risk is lower. ...
... One major consideration regarding highland malaria, as well as a possible mechanism by which highland malaria may more successfully become established, is a lack of resistance to the I parasite among highland residents. While lower altitude dwellers in malaria-endemic regions would have been exposed to the parasite since childhood and thereby gained some immunity to the parasite (Alles et al. 1998;Gupta et al. 1999;Hviid 2005), highland dwellers would not have received regular exposure to the parasite. Indeed, a lack of immunity was observed among highlanders in two studies, in both Kenya and Rwanda (Loevinsohn 1994;Minakawa et al. 2006). ...
... This is primarily based on a literature review conducted by Alles et. al. which demonstrated that the fatality rate for P. falciparum malaria is at least 2% and as high as 20% [1]. I have applied this 6% mortality rate evenly across the 60 days during the course of the 91-day course of infection which correspond to heightened parasite densities, under the assumption that mortality is much more likely to die during this period. ...
We present a theoretical study of the spread of multiple strains of malaria according to within-host parasite dynamics. The disease transmission mechanism is modeled in two parts. Transmission from the host to a mosquito depends upon the host's para-site density and a transmission-to-vector probability function, while transmission from mosquitoes to new hosts depends upon a general transmission parameter which de-scribes the behavior of these vectors. Collaborators have provided data which describe the density of parasites in the blood for two dierent clones of rodent malaria over the course of a typical infection; these data have been modied to reect characteristics of the human form of the disease. The transmission-to-vector probability function is based on a half-saturation parameter which aects the overall shape of the transmission prob-ability curves. By stochastically simulating the model over a range of half-saturation and transmission parameters, we have found that there is large region of this parameter space in which coinfections dominate the host population at equilibrium.
... En Asie, l'intensité de la transmission du paludisme varie beaucoup et, si l'on trouve des foyers de transmission intense, cette partie du monde n'en est pas moins généralement considérée comme présentant de faibles taux de transmission (35,36). Dans les camps de réfugiés karens de la province de Tak (Thaïlande), on a estimé le TIE à 0,3 piqûre infectante par an ; les enfants de 2 à 15 ans contractent en moyenne une infection à falciparum tous les 2 à 3 ans (37). ...
... MALARIA incidence is on the rise and the clinical disease caused by Plasmodium falciparum is widely distributed and entrenched in areas worldwide where climates are suitable for transmission 1,2 . It was estimated 1 , by the use of epidemiological, demographic and geographical parameters, that there were 515 million clinical attacks of P. falciparum malaria in the year 2002. ...
The Plasmodium falciparum malaria is responsible for about 500 million clinical attacks and one million deaths each year, mostly in Africa and southeast Asia. On account of the parasite having become resistant to the conventional antimalarials, artemisinin-based combination therapy (ACT) is the only reliable treatment option. The Roll Back Malaria (RBM) and Millennium Development Goals (MDG) campaigns of WHO and UNDP, respectively, have made little headway, mainly because of paucity of artemisinin in world market. Here we show that the cultivation and processing of Artemisia annua, presently the only resource of artemisinins, in India, in partnerships, can help build a sound supply chain of artemisinin.
... Decreases in the mid twentieth century were often attributable to the global malaria eradication campaign, particularly in India and Latin America. In sub-Saharan Africa, however, the numbers of deaths are increasing (6,53,54,55,56). Reasons for increasing mortality are likely to be complex, and may include combinations of deterioration in health systems where utilisation has in some cases decreased because of user fees, increasing drug resistance (57,58,59,60,61), climate change with increasing frequency and extent of epidemics in the East African highlands and changed rainfall patterns in southern Africa and large-scale population movements and complex emergencies (for instance, extremely high mortality rates were recorded in Eastern Democratic Republic of Congo in 2000). ...
... This effort requires indepth knowledge of the ecology and behavior of these vectors. To gauge levels of malaria control necessary to achieve meaningful public health improvements in Africa, it will be necessary to quantitatively define the extent to which site-specific entomological inoculation rates (EIRs) must be reduced to correspondingly reduce malaria prevalence131415 . A foundation of malaria vector control is that actions to decrease vector-host contact through methods including larval habitat modification, insecticide treatment of larval habitats, spraying insides of houses with residual insecticides, insecticide-treated bed nets, or the use of repellents will have correspondingly beneficial outcomes in terms of reduction in morbidity and mortality. ...
Background
The scaling up of malaria vector control efforts in Africa has resulted in changing the malaria vectorial systems across different ecological settings. In view of the ongoing trends in vector population dynamics, abundance, species composition and parasite infectiousness, there is a need to understand vector distribution and their contribution to malaria transmission to facilitate future planning of control strategies. We studied indoor and outdoor malaria transmission dynamics and vector population variability of Anopheles mosquitoes in Taveta district along the Kenyan Coast.
Methods
Anopheles mosquitoes were collected indoors and outdoors in 4 ecologically different villages using CDC light traps (both indoor and outdoor) and aspiration method (day resting indoors; DRI) methods. Mosquitoes were examined for infection with P. falciparum sporozoites and blood feeding preferences using enzyme linked immunosorbent assay (ELISA). The An. gambiae and An. funestus complexes were identified by PCR technique to determine the sibling species composition.
Results
A total of 4,004 Anopheles mosquitoes were collected consisting of 34.9%% (n = 1,397) An. gambiae s.1., 28.1% (n = 1,124) An. funestus s.l., 33.5% (n = 1,340) An. coustani and 3.6% (n = 143) An. pharoensis. A total of 14,654 culicine mosquitoes were collected, mainly Cx. quinquefasciatus. Of the total Anopheles collected, 3,729 were tested for P. falciparum sporozoite infection. The sporozoite transmission was found to be occurring both indoors and outdoors. The overall sporozoite infectivity was 0.68% (n = 2,486) indoors and 1.29% (n = 1,243) outdoors. Indoor and outdoor sporozoite infectivity and the vectorial systems varied across the 4 ecological villages. Entomological inoculation rates for the 4 villages indicate that there was site-to-site variation. In the 4 villages, Mwarusa had the highest EIRs with An. arabiensis, An. funestus and An. coustani contributing to 23.91, 11.96 and 23.91 infectious bites per person per year ib/p/year respectively. In Kiwalwa and Njoro outdoor EIR was significantly higher than indoors.
Conclusions
This study shows that malaria transmission is occurring both indoors and outdoors. The main vectors are An. arabiensis, An. funestus and An. coustani indoors while An. coustani is playing a major role in outdoor transmission. Effective malaria control programmes, should therefore include tools that target both indoor and outdoor transmission.
... Plasmodium falciparum malaria is a major cause of morbidity and responsible for over one million deaths annually among children under 5 years of age in sub-Saharan Africa. 1 The spectrum of disease prevalent differs in geographical areas; cerebral malaria and severe anemia is more common in Africa 2 and multiple organ dysfunction is reported to be more prevalent in Asia. 3 Both host and parasite determinants were attributed to severe malarial disease. [4][5][6] Several studies have shown the involvement of proinflammatory cytokines in pathogenesis of severe falciparum malaria where high plasma TNF-alpha, IL-1beta, IL-6, IL-10, and IFN-gamma levels were associated with severe disease. ...
Plasma levels of pro- and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n = 62) and uncomplicated malaria (UM; n = 69) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P<0·01), IL-6 (P<0·01), and IL-10 (P<0·05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n = 14) were significantly higher than those of the UM patients (P<0·001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n = 34) and SM (n = 34) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNF-alpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P<0·05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.
... Fundamental to the development of sound malaria control programmes is an understanding of how malaria transmission intensity affects malaria prevalence, incidence , severe disease, and mortality123. To gauge levels of malaria control necessary for achieving meaningful public health improvements, it is necessary to quantitatively define the extent to which site-specific malaria transmission indices must be reduced. ...
Background
Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya.
Methods
Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates.
Results
Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90–0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010.
Conclusion
Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission.
... In controlled experimental trials, increased survival rates among African children sleeping under insecticide-impregnated bed-nets, (IBNs) have been consistently reported (Alonso et al., 1991; Binka et al., 1996; Curtis, 1996; Nevill et al., 1996). This is probably because in very young children in whom significant levels of immunity have not yet developed, protection against the sheer numbers of malaria attacks that IBNs would afford reduces the risk of a fatal infection at this very vulnerable age (Alles et al., 1998). Other strategies aimed at reducing malaria transmission are the genetic manipulation of mosquito vectors (Clarke, 2002; CNN, 2002; Holt et al., 2002; Hoffman et al., 2002a; NS, 2004). ...
Plasmodium infection in man is caused by the bite of an infected female Anopheles mosquito. This results in the disease, malaria. Malaria has serious debilitating effects on man. It adversely affects man's health, strength and productivity. Here, a review of Plasmodium infection in man including the life cycle transmiss on, immunity, symptoms, diagnosis, pathology, prevention, control and treatment is given. Only by knowing about Plasmodium infection, the burden of infection on man and the prevention and control options can we understand the disease better and so be better prepare for the future management of this disease. , i
... Despite similar levels of nutrition and health care access, in Sri Lanka, case fatality is 0.01% in endemic areas versus 1% in non-endemic areas because of quicker diagnosis in endemic areas (Alles et al., 1998). In endemic areas malaria fatalities are mostly restricted to children, while in areas that experience periodic outbreaks of malaria, malaria fatalities heavily affect all age groups. ...
The childhood disease burden depends on the prevalence of infectious diseases, their case fatalities, and long-term morbidity. We propose a quantity-quality model of fertility choice under uncertainty that emphasizes morbidity and mortality from infectious disease. The fer- tility response to a decline in child mortality depends on the morbidity effect of the disease, the prevalence rate, and whether the prevalence or case fatality rate declines. Fertility fol- lows mortality and morbidity but since mortality and morbidity do not always move in the same direction, the fertility response may be dampened or non-monotonic. Disease-specific evidence from sub-Saharan Africa supports these theoretical predictions.
... In the case of acute attacks of Plasmodium falciparum malaria, it is possible that a degree of immunity to some aspects of severe, life-threatening disease may be achieved after only one or two infections [10]. It is noted that a single untreated attack of P. falciparum malaria in a non immune individual carries a risk of death that may be anywhere from a few percent to at least 20 –30% according to circumstances [1]. Incidence of malaria disease tends to decline uniformly with age such that children living in areas of high endemicity experience less frequent episodes of malaria after the age of 5 years [20]. ...
We use a model to study the dynamics of malaria in the human and mosquito population to explain the stability patterns of malaria. The model results show that the disease-free equilibrium is globally asymptotically stable and occurs whenever the basic reproduction number, R0 is less than unity. We also note that when R0>1, the disease-free equilibrium is unstable and the endemic equilibrium is stable. Numerical simulations show that recoveries and temporary immunity keep the populations at oscillation patterns and eventually converge to a steady state.
... Malaria is one of the major public health problems of many countries of world123. According to WHO report, almost 300 million cases of malaria occur worldwide and more than one million people die due to malaria every year [4]. ...
This paper studies the determinants of utilization of health care services, especially for treatment of febrile illness in the malaria endemic area of north-east India.
An area served by two districts of Upper Assam representing people living in malaria endemic area was selected for household survey. A sample of 1,989 households, in which at least one member of household suffered from febrile illness during last three months and received treatment from health service providers, were selected randomly and interviewed by using the structured questionnaire. The individual characteristics of patients including social indicators, area of residence and distance of health service centers has been used to discriminate or group the patients with respect to their initial and final choice of service providers.
Of 1,989 surveyed households, initial choice of treatment-seeking for febrile illness was self-medication (17.8%), traditional healer (Vaidya)(39.2%), government (29.3%) and private (13.7%) health services. Multinomial logistic regression (MLR) analysis exhibits the influence of occupation, area of residence and ethnicity on choice of health service providers. The traditional system of medicine was commonly used by the people living in remote areas compared with towns. As all the febrile cases finally received treatment either from government or private health service providers, the odds (Multivariate Rate Ratio) was almost three-times higher in favour of government services for lower households income people compared to private.
The study indicates the popular use of self-medication and traditional system especially in remote areas, which may be the main cause of delay in diagnosis of malaria. The malaria training given to the paramedical staff to assist the health care delivery needs to be intensified and expanded in north-east India. The people who are economically poor and living in remote areas mainly visit the government health service providers for seeking treatment. So, the improvement of quality health services in government health sector and provision of health education to people would increase the utilization of government health services and thereby improve the health quality of the people.
... 2,4 This effect is thought partially to explain the lower mortality rates from P. falciparum seen in the Asia-Pacific region compared with Africa. 5 A recent study has shown that sera from a volunteer experimentally infected with P. vivax suppressed the growth of P. falciparum in vitro. 6 This effect was mediated via IgM antibodies, and could be the means by which P. vivax infection protects against P. falciparum. ...
We describe a case of mixed malaria infection in a returning traveller. We suggest that our patient had a chronic infection with Plasmodium vivax, which reduced the severity of an acute infection with P. falciparum-an example of cross-species immunity.
... Incidence is lowest in the 0 – 4 year olds and then gradually increases and peaks at the age of 30 – 39 years, after which it gradually decreases again. In populations that lack immunity a predominantly flat age profile is expected [14] which is different from high endemicity malaria areas where the distribution of numbers and severity of malaria episodes is distinctly skewed towards the age group of the under-fives [26]. A study conducted in KwaZulu-Natal, using data from the malaria reporting system for the period mid- 1990 to mid-1999, reported on the variation in the pattern of age-specific malaria incidence [12]. ...
Malaria is endemic in the low-altitude areas of the northern and eastern parts of South Africa with seasonal transmission. The aim of this descriptive study is to give an overview of the malaria incidence and mortality in Limpopo Province for the seasons 1998-1999 to 2006-2007 and to detect trends over time and place.
Routinely collected data on diagnosed malaria cases and deaths were available through the provincial malaria information system. In order to calculate incidence rates, population estimates (by sex, age and district) were obtained from Statistics South Africa. The Chi squared test for trend was used to detect temporal trends in malaria incidence over the seasons, and a trend in case fatality rate (CFR) by age group. The Chi squared test was used to calculate differences in incidence rate and CFR between both sexes and in incidence by age group.
In total, 58,768 cases of malaria were reported, including 628 deaths. The mean incidence rate was 124.5 per 100,000 person-years and the mean CFR 1.1% per season. There was a decreasing trend in the incidence rate over time (p < 0.001), from 173.0 in 1998-1999 to 50.9 in 2006-2007. The CFR was fairly stable over the whole period. The mean incidence rate in males was higher than in females (145.8 versus 105.6; p < 0.001); the CFR (1.1%) was similar for both sexes. The incidence rate was lowest in 0-4 year olds (78.3), it peaked at the ages of 35-39 years (172.8), and decreased with age from 40 years (to 84.4 for those > or = 60 years). The CFR increased with increasing age (to 3.8% for those > or = 60 years). The incidence rate varied widely between districts; it was highest in Vhembe (328.2) and lowest in Sekhukhune (5.5).
Information from this study may serve as baseline data to determine the course and distribution of malaria in Limpopo province over time. In the study period there was a decreasing trend in the incidence rate. Furthermore, the study addresses the need for better data over a range of epidemic-prone settings.
... Knowledge and practices regarding the management of nonsevere and severe or complicated malaria were significantly associated with the literacy level. Thus, improving literacy to at least primary school level, coupled with health awareness campaigns, has the potential to improve mothers' ability to recognize childhood malaria-related morbidity, and thus reduce mortality (Alles et al. 1998). ...
Prior to an intervention on improving the quality of malaria case management, we assessed mothers' abilities to recognize nonsevere and severe/complicated malaria in children when a child has fever with other physiological and behavioural symptoms associated with malaria. Malaria was mentioned as the commonest febrile illness (94. 1%), convulsions the least (11.4%). Fever and enteric symptoms featured as the most important symptoms of childhood malaria at frequencies of 93.5% and 73.8%, respectively. The need for laboratory diagnosis was very high (98.3%), the reason being to get accurate diagnosis and treatment (89.4%). Poor outcome of treatment was ascribed to incorrect diagnosis and prescription, noncompliance at home and ineffective drugs (62.1%). Most mothers (86.6%) would take antipyretic measures first when a child has fever, and subsequently the majority (92.9%) would seek care at a modern health facility. About 50% of the mothers would give traditional treatments for childhood convulsions and wait till fits cease before the next action. A high proportion of the mothers (75%) held the belief that an injection in a child with high fever would precipitate convulsions or death. The implications of these findings for chemotherapeutic malaria control in holoendemic areas within the context of the Integrated Management of Childhood Illnesses (IMCI) strategy are discussed.
... Targeted interventions for malaria control in various environments and at various levels of endemicity. It has been suggested that the reduction of malaria inoculation rates in areas where transmission is intense, notably in tropical Africa, is neither desirable, because of the early acquisition of protective immunity, nor achievable, because of overwhelming vectorial capacities (48). Moreover, under these conditions, since individuals are overwhelmingly superinfected with malaria regardless of the location and other environmental factors, little difference is to be expected in case incidences between locations or households. ...
Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control.
... The intensity of malaria transmission varies greatly in Asia, and foci of intense transmission can be found, but Asia is generally considered to have low transmission rates (35,36). The EIR in the Karen refugee camps in Tak Province, Thailand, has been estimated to be 0.3 infective bites per year; children aged 2-15 years experience an average of one falciparum infection every 2 to 3 years (37). ...
The development of resistance to drugs poses one of the greatest threats to malaria control. In Africa, the efficacy of readily affordable antimalarial drugs is declining rapidly, while highly efficacious drugs tend to be too expensive. Cost-effective strategies are needed to extend the useful life spans of antimalarial drugs. Observations in South-East Asia on combination therapy with artemisinin derivatives and mefloquine indicate that the development of resistance to both components is slowed down. This suggests the possibility of a solution to the problem of drug resistance in Africa, where, however, there are major obstacles in the way of deploying combination therapy effectively. The rates of transmission are relatively high, a large proportion of asymptomatic infection occurs in semi-immune persons, the use of drugs is frequently inappropriate and ill-informed, there is a general lack of laboratory diagnoses, and public health systems in sub-Saharan Africa are generally weak. Furthermore, the cost of combination therapy is comparatively high. We review combination therapy as used in South-East Asia and outline the problems that have to be overcome in order to adopt it successfully in sub-Saharan Africa.
... Reported malaria case-fatality rates from a wide variety of situations were studied in reaching these estimates (Alles HK, unpublished data; Vietnamese Government, unpublished data). [58][59][60][61] On the basis of these studies, estimated P. falciparum case-fatality rates in the endemic countries were used in the range 0.01-0.3%. ...
We estimate that the global burden of malaria due to Plasmodium vivax is approximately 70-80 million cases annually. Probably approximately 10-20% of the world's cases of P. vivax infection occur in Africa, south of the Sahara. In eastern and southern Africa, P. vivax represents around 10% of malaria cases but < 1% of cases in western and central Africa. Outside of African, P. vivax accounts for > 50% of all malaria cases. About 80-90% of P. vivax outside of Africa occurs in the Middle East, Asia, and the Western Pacific, mainly in the most tropical regions, and 10-15% in Central and South America. Because malaria transmission rates are low in most regions where P. vivax is prevalent, the human populations affected achieve little immunity to this parasite; as a result, in these regions, P. vivax infections affect people of all ages. Although the effects of repeated attacks of P. vivax through childhood and adult life are only rarely directly lethal, they can have major deleterious effects on personal well-being, growth, and development, and on the economic performance at the individual, family, community, and national levels. Features of the transmission biology of P. vivax give this species greater resilience than the less robust Plasmodiumfalciparum in the face of conditions adverse to the transmission of the parasites. Therefore, as control measures become more effective, the residual malaria burden is likely increasingly to become that of P. vivax.
... Availability of and access to effective antimalarial drugs are the cornerstones to the reduction of childhood malaria morbidity and mortality (Alles et al. 1999). However, use of antimalarials is in¯uenced by socio-behavioural factors such as familiarity with the drug and perceived ef®cacy (Le Grand et al. 1999). ...
Prior to policy change from chloroquine (CQ) to sulphadoxine/pyrimethamine (S/P; Fansidar) we assessed the perception of CQ efficacy and the alternative treatment options for malaria in children among parents/guardians (N=527) of under-fives attending first level health facilities on account of fever. It was hypothesized that the long experience with CQ and its antipyretic effect (lacking in S/P) might impede acceptance of S/P for wider use as first-line drug. Malarial fevers in children were most commonly treated with CQ (92.8%), followed by quinine (60.7%) and S/P (28.7%). A 63.2% knew the reasons for non-response to antimalarial treatment, and only 50% were aware that CQ could fail to treat malaria, and 57.1% knew alternative treatment options, namely quinine (52.2%) and S/P (20.5%). Generally, decreased efficacy of CQ had been noticed, and quinine was prescribed for both suspected and proven CQ failures in first level health facilities and the district hospital. S/P was judged to be more effective than quinine, but too strong for children, and was the least known drug in the study area. All formulations of S/P cost more per dose for a child and an adult than CQ. The implications of these findings on the change of malaria treatment policy are discussed.
... Wide accessibility to health cares and effective treatment of malaria infections have played a significant role in reducing malaria morbidity and mortality in Asian countries (Alles et al., 1998). In Sri Lanka, point prevalence was less than 1% in areas with EIR of one per annum, whereas similar inoculation rates in Africa are associated with much high prevalence (Carter et al., 2000). ...
The prevalence of Plasmodium falciparum malaria in African communities can be high and stable even in areas of relatively low transmission where people expose to only a few infectious bites per year. We show in this field study conducted in 30 sites along the coastal Kenya that prevalence in school children was consistently high, although there were many sites where transmission intensity measured by exposure to infectious bites was less than 10 per year. Statistical analyses revealed that prevalence was significantly correlated with the infectious exposure occurring 10-11 months previously, suggesting that long-lived infections were commonplace and one of the major contributors for the stability of malaria in these sites. Using mechanistic models of malaria transmission, we found that the association of high prevalence and low transmission could be due to low recovery rates. Therefore, significant reductions of malaria prevalence and burden require substantial reductions of the duration of acquired infections, even in areas that have quite low transmission intensities by the standards of sub-Saharan Africa. Infection control featured by active detection and drug treatment as well as vector control is critical to combat malaria in areas of relatively low transmission intensity.
During the erythrocytic cycle of human malaria caused by Plasmodium falciparum, merozoites released from mature schizonts attach to and invade red blood cells. Understanding this invasion process may identify suitable chemotherapy or vaccine targets with which to combat malaria. On the merozoite surface is a complex of polypeptides derived by proteolytic cleavage from merozoite surface protein-1 (MSP-1), and two unrelated 36kDa and 22kDa polypeptides derived from MSP-6 and MSP-7 respectively. On erythrocyte invasion the majority of the MSP-1 complex is shed into the blood stream. This shed complex contains MSP-636, MSP-722, and a 19kDa polypeptide (MSP-719) proposed to be the product of N-terminal cleavage of MSP-722. MSP-1 is a major vaccine candidate, hence any proteins complexed to it, such as MSP-722, are potential vaccine targets and warrant further research. To study MSP-722 and its relationship with MSP-1, it was necessary to clone the msp-7 gene. A combination of genome database searches and Vectorette PCR steps were used to obtain the gene coding for MSP-7, and confirmed that MSP-719 is related to MSP-722. RT-PCR was used to examine msp-7 for the presence of introns, and the precursor's 351 amino acid sequence analysed using structure and function prediction programmes. The msp-7 gene was cloned and sequenced from several lines of P. falciparum and found to be highly conserved. To obtain antibodies with which to study MSP-7 biosynthesis, GST-fusion proteins were produced using bacterial expression systems, and used to immunise mice, producing anti-sera and a specific monoclonal antibody. The pattern of MSP-7 transcription throughout the erythrocytic cycle was analysed by Northern blotting. The translation of 48 kDa MSP-7 precursor and subsequent processing events were determined by western blotting, immunofluorescence and immunoprecipitation techniques. These suggested that the MSP-7 precursor associated with the MSP-1 precursor in schizonts and subsequently underwent three proteolytic processing steps. The time and kinetics of MSP-1 and MSP-7 precursor complex formation, and processing events, were analysed by immunoprecipitation, pulse chase and sensitivity to Brefeldin A. Preliminary experiments were performed to determine the relationship between MSP-1 and MSP-7 processing in merozoites.
Recent dramatic declines in global malaria burden and mortality can be largely attributed to the large-scale deployment of insecticidal-based measures, namely long-lasting insecticidal nets (LLINs) and indoor residual spraying. However, the sustainability of these gains, and the feasibility of global malaria eradication by 2040, may be affected by increasing insecticide resistance among the Anopheles malaria vector. We employ a new differential-equations based mathematical model, which incorporates the full, weather-dependent mosquito lifecycle, to assess the population-level impact of the large-scale use of LLINs, under different levels of Anopheles pyrethroid insecticide resistance, on malaria transmission dynamics and control in a community. Moreover, we describe the bednet-mosquito interaction using parameters that can be estimated from the large experimental hut trial literature under varying levels of effective pyrethroid resistance. An expression for the basic reproduction number, \({\mathcal {R}}_0\), as a function of population-level bednet coverage, is derived. It is shown, owing to the phenomenon of backward bifurcation, that \({\mathcal {R}}_0\) must be pushed appreciably below 1 to eliminate malaria in endemic areas, potentially complicating eradication efforts. Numerical simulations of the model suggest that, when the baseline \({\mathcal {R}}_0\) is high (corresponding roughly to holoendemic malaria), very high bednet coverage with highly effective nets is necessary to approach conditions for malaria elimination. Further, while >50% bednet coverage is likely sufficient to strongly control or eliminate malaria from areas with a mesoendemic malaria baseline, pyrethroid resistance could undermine control and elimination efforts even in this setting. Our simulations show that pyrethroid resistance in mosquitoes appreciably reduces bednet effectiveness across parameter space. This modeling study also suggests that increasing pre-bloodmeal deterrence of mosquitoes (deterring them from entry into protected homes) actually hampers elimination efforts, as it may focus mosquito biting onto a smaller unprotected host subpopulation. Finally, we observe that temperature affects malaria potential independently of bednet coverage and pyrethroid-resistance levels, with both climate change and pyrethroid resistance posing future threats to malaria control.
Background: The Plasmodium falciparum transmission occurs mainly at night. Anopheles mosquitoes that transmit P. falciparum are those that have taken blood feed and laid eggs several times. Unfortunately, the biting behavior of these mosquitoes is little known. This study aims to assess the impact of the biting behavior of multiparous vectors on malaria transmission. Methods: Mosquitoes were collected by hour from 21. 00 hours to 05. 00 hours in two villages, Abomey-Takplikpo and Itassoumba, south-easten Benin. Anopheles gambiae s.l. was morphologically identified and dissected using the method of Polovodova and oil injection technique. The head-thoraces were assessed using enzyme-linked immunosorbent assay (ELISA CSP) and the others body parts were used for molecular identification by Polymerase Chain Reaction (PCR). Results: Among the parous An. gambiae s.l. collected at Abomey-Takplikpo and Itassoumba, old An. gambiae s.l. that laid eggs several times bite more frequently in the second half of the night (p<0.05) than young An. gambiae s.l. that were more likely to bite earlier in the houses. On the 1008 and 868 head-thoraces of An. gambiae s.s. confirmed by PCR and analyzed by the ELISA-CSP respectively at Itassoumba and Abomey-Takplikpo, 2.98% (n = 30) and 2.53% (n = 22) were tested positive for the circumsporozoitic antigen of P. falciparum. Overnight, the infectivity distribution is homogeneous in both localities (P> 0.05). However, in the second half of the night, infectious mosquitoes were more frequent. At Itassoumba and Abomey-Takplikpo, the biting behavior of multiparous females explains respectively 89.51% (R² = 0.8951) and 90.17% (R² = 0.9017) of the variability of mosquitoes' infectivity. Conclusion: Young Anopheles gambiae s.s. bite earlier in houses than old An. gambiae s.s. that bite more in the second half of the night. Infectious An. gambiae s.s. bite at any time of the night but more frequent after midnight. In addition, the biting behavior of multiparous An. gambiae s.s. was significantly associated with P. falciparum transmission.
The objective of this thesis is to model highland malaria in western Kenya using dynamical systems. Two mathematical models are formulated ; one, on differentiated susceptibility and differentiated infectivity in a metapopulation setting with age structure, the other, a saturated vector feeding rate model with disease induced deaths and varying host and vector populations. In the first model, we consider the different ecosystems identified as malaria hotspots in the western Kenya highlands and consider the ecosystems as different patches. The population in each patch is classified as, either child or, adult. The model will aid in examining the role of ecosystem heterogeneity and age structure to the persistent malaria epidemics in the highlands. We formulate the differentiated susceptibility and infectivity model that extend to multiple patches the well known epidemiological models in one patch. Classifying the hot spots as n patches, we give its mathematical analysis using the theory of triangular system, monotone non-linear dynamical systems, and Lyapunov-Lasalle invariance principle techniques. Key to our analysis is the definition of a reproductive number, Ro, the number of new infections caused by one individual in an otherwise fully susceptible population throughout the duration of the infectious period. The existence and stability of disease-free and endemic equilibrium is established. We prove that the disease free state of the systems is globally asymptotically stable when the basic reproduction number Ro<1, and when Ro>1 an endemic equilibrium is established which is locally and globally asymptotically stable. The model shows that the age structuring reduces the magnitude of infection. Using relevant data we did some simulation, to demonstrate the role played by metapopulation and age structuring on the incidence and Ro. In the second part we formulate a model for malaria with saturation on the vector feeding rates that lead to a nonlinear function in the infection term. The vector feeding rate is assumed, as in the predator prey models, to rise linearly as a function of the host-vector ratio until it reaches a threshold Qv, after which the vector feeds freely at its desired rate. The two populations are variable and drive malaria transmission, such that when the vectors are fewer than hosts, the rate of feeding is determined by the vectors feeding desire, whereas, when the hosts are more than the vectors, the feeding rate is limited by host availability and other feeding sources may have to be sought by the vector. Malaria induced deaths are introduced in the host population, while the vector is assumed to survive with the parasite till its death. We prove that the Disease Free Equilibrium is locally and globally asymptotically stable if Ro<1 and when Ro>1, an endemic equilibrium emerges, which is unique, locally and globally asymptotically stable. The role of the saturated mosquito feeding rate is explored with simulation showing the crucial role it plays especially on the basic reproduction number
This chapter provides standard methods for the incrimination of Anopheles mosquito species serving as malaria vectors and associated methods for measuring the intensity of transmission. In any malaria-endemic area, one or more species of Anopheles mosquitoes serve as malaria vectors. To show that an Anopheles mosquito species serves as a malaria vector in nature, it is necessary to demonstrate: 1. An association in time and space between the Anopheles species of mosquito and cases of malaria in humans. After study sites are selected, longitudinal field studies are established to sample mosquito populations. Adult mosquitoes are sampled by using trapping techniques such as landing/biting collections, light traps, pyrethrum spray catches inside houses, and outdoor aspiration collections. Larval mosquitoes developing in aquatic habitats normally are sampled by dipping methods. Mosquitoes are identified by standard taxonomic methods and also by molecular methods if mosquitoes belong to a species complex. The standard methods for performing landing/biting collections are described in this chapter; other types of mosquito trapping methods are described in refs. 1 and 3. 2. Evidence of direct contact between the Anopheles species and humans. Catching a mosquito biting humans through landing/biting catches conclusively establishes contact between that mosquito species and humans. A second method involves immunologically identifying human blood in the abdomen of field-captured Anopheles mosquitoes. A direct enzyme-linked immunosorbent assay (ELISA) suitable for bloodmeal identification of African malaria vectors is described in this chapter (3). 3. Evidence that the Anopheles species harbors malaria sporozoites in the salivary glands. Sporozoites may be detected in mosquitoes through the dissection and microscopic examination of mosquito salivary glands (4) or through ELISA methods (5). Both methods are described in this chapter.
Background & objectives: Generally, indepth understanding of the epidemiology of malaria is considered a prerequisite for planning effective control measures in the endemic regions like sub-Saharan Africa. This study focuses on the relationship of entomological inoculation rates (EIRs) to malaria incidence and prevalence rates across eco-vegetational zones in Bayelsa State, Nigeria.
Methods: Mosquito sampling was undertaken in seven towns/villages in seven local government areas (LGAs) in three eco-vegetational zones. Adults were collected twice quarterly by the pyrethrum spray catch (PSC) technique. Anophelines were separated morphologically and the sibling species were identified using PCR. Detection of circumsporozoite (CS) antigen by ELISA was used for determining mosquito infection rates. Man-biting, sporozoite and entomological inoculation rates were calculated by standard methods. Simultaneously, malaria incidence and prevalence rates were calculated using data obtained from hospitals and by examination of blood smears from consenting adults.
Results: The estimated mean man-biting rate (MBR) over a 2-yr period was 6.88 bites/person/night. The highest MBR of 16.9 was in the mangrove coastal water forest and the least, 11.3, was in brackish water swamp forest; differences were significant (t = 12.083; p1.5 or unstable when EIR was ≤ 1.5. Although, earlier studies have shown correlation between EIRs and malaria PR, this study demonstrated a significant correlation between EIRs and malaria incidence rates.
The Plasmodium falciparum malaria has assumed epidemic proportions. Now there are 500 million cases of malaria resulting in 1 million deaths, each year. The parasite has developed multi-drug resistance against the conventional quinoline and antifolate antimalarials and artemisinins are the only drugs that are effective. The WHO recommended artemisinin based combination therapy (ACT) for combating malaria is awaiting a supply chain of artemisinin. Here, it is shown that indigenously developed technologies for cultivation and processing of Artemisia annua crops to produce artemisinin drugs and industrial partnerships can meet the challenges of artemisinin supply for the launch of the international Roll Back Malaria (WHO) and Millennium Development Goal (UNDP) programmes to control malaria worldwide.
The objective of this thesis is to model highland malaria in Western Kenya using dynamical systems. Two mathematical models are formumated, one, on differentiated susceptibility and differentiated infectivity in a metapopulation setting, two, a saturated vector feeding rate model with disease induced deaths and varying host and vector populations. In the first model, we consider the different ecosystems identified as malaria hotspots in the Western Kenya highlands and consider the ecosystems as different patches. The population in each patch is classified as, either, child (age 0-5 years), or, adult (over ( years of age). Our results are compared with some published results
Malaria intensity in rural areas of Nigeria is of public health significance. In this study, the prevalence of malaria parasitaemia in Umuchieze and Uturu rural communities of Abia State, Southeast Nigeria were investigated in order to provide epidemiological data on malaria in the study communities for effective management programme. A total of 620 individuals (310 in each community) were examined for malaria parasites using standard methods. The results showed that a total of 455 (73.39%) among the studied individuals were infected. Infection rates in Umuchieze and Uturu were 72.58 and 74.19%, respectively but the difference was not statistically significant (p>0.05). Also, the infection rates recorded for males (73.87%) and females (72.90%) in both communities did not differ statistically (p>0.05). Members of the age cohorts 11-20 years recorded the highest rate of infection, 82.61% and 88.24 in Umuchieze and Uturu, respectively. The highest rate of prevalence of malaria parasitaemia was identified among farmers in Umuchieze (85.60%) while in Uturu it was identified among students (81.33%). Plasmodium falciparum, Plasmodium vivax and Plasmodium malarias were found among the positive cases in both study areas with Plasmodium falciparum being the highest with infection rate of 52.26% in Umuchieze and 53.55% in Uturu. Overall, the infection rate of Plasmodium species in both study communities is 72.09, 19.56 and 8.35% for P. falciparum, P. vivax and P. malariae, respectively. The results showed that Umuchieze and Uturu Communities were endemic for malaria.
Febrile illness is the most common symptom experienced by patients suspected of having malaria, especially in the malaria endemic areas of northeast India. Hospital-based data from two districts of upper Assam, namely Golaghat and Tinsukia, were analysed to assess the prevalence of malaria among inpatients who reported to health centres with febrile illness.
A total of 16 hospitals were selected for the study. These included six government hospitals (three in rural and three in urban areas) and 10 private hospitals, which included four tea-garden hospitals. Selection was dependant on the availability of patients and inpatient treatment facilities. During the study, a total of 350 inpatients reported to the selected hospitals with fever; 324 were suspected of having malaria and were interviewed and included in the study.
The average age of patients was 24.2±15.2 years and 63.3% (205/324) of them were male. The majority of patients (77.5%; 251/324) belonged to the lower household income category (<5000 Indian rupees) and travelled to the nearest town or city for treatment. Overall, the prevalence of malaria (as diagnosed by clinical examination and blood tests) across the different categories such as location, types of hospitals and household income was found to be 29.9% (97/324). Multivariate analysis revealed that the adjusted odds ratios (AOR) of malaria cases was higher based on location (2.13), type of health centre (1.75) and the distance travelled to a health centre (2.09). The mean duration of hospital treatment was 4.2±3.6 days and the delay in reporting to hospital was 3.9±2.6 days.
The study emphasises the need to strengthen and improve the treatment facilities for malaria in government hospitals, and to create more awareness among people regarding early treatment, especially in the rural periphery villages of the endemic areas.
Epidemiologic patterns of malaria infection are governed by environmental parameters that regulate vector populations of Anopheles mosquitoes. The intensity of malaria parasite transmission is normally expressed as the entomologic inoculation rate (EIR), the product of the vector biting rate times the proportion of mosquitoes infected with sporozoite-stage malaria parasites. Malaria transmission intensity in Africa is highly variable with annual EIRs ranging from < 1 to > 1,000 infective bites per person per year. Malaria control programs often seek to reduce morbidity and mortality due to malaria by reducing or eliminating malaria parasite transmission by mosquitoes. This report evaluates data from 31 sites throughout Africa to establish fundamental relationships between annual EIRs and the prevalence of Plasmodium falciparum malaria infection. The majority of sites fitted a linear relationship (r2 = 0.71) between malaria prevalence and the logarithm of the annual EIR. Some sites with EIRs < 5 infective bites per year had levels of P. falciparum prevalence exceeding 40%. When transmission exceeded 15 infective bites per year, there were no sites with prevalence rates < 50%. Annual EIRs of 200 or greater were consistently associated with prevalence rates > 80%. The basic relationship between EIR and P. falciparum prevalence, which likely holds in east and west Africa, and across different ecologic zones, shows convincingly that substantial reductions in malaria prevalence are likely to be achieved only when EIRs are reduced to levels less than 1 infective bite per person per year. The analysis also highlights that the EIR is a more direct measure of transmission intensity than traditional measures of malaria prevalence or hospital-based measures of infection or disease incidence. As such, malaria field programs need to consider both entomologic and clinical assessments of the efficacy of transmission control measures.
We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas.
The incidence density of infection and disease caused by Plasmodium falciparum in children aged six to 24 months living in the holoendemic Sahel of northern Ghana was measured during the wet and dry seasons of 1996 and 1997. At the beginning of each season, a cohort composed of 259 and 277 randomly selected children received supervised curative therapy with quinine and Fansidar and primaquine for those with normal glucose-6-phosphate dehydrogenase activity. The 20 weeks of post-therapy follow-up consisted of three home visits weekly and examination of Giemsa-stained blood films once every two weeks. Blood films were also taken from children brought to clinic with illness. The incidence density of parasitemia after radical cure was 4.7 infections/person-year during the dry season and 7.1 during the wet season (relative risk = 1.51, 95% confidence interval [CI] = 1.25-1.81; P = 0.00001). Although the mean parasitemia count at time of reinfection in the dry season (3,310/microl) roughly equaled that in the wet season (3,056/microl; P = 0.737), the risk ratio for parasitemia > 20,000/microl during the wet season was 1.71 (95% CI = 1.2-2.4; P = 0.0025). The risk ratio for parasitemia > 20,000/microl with fever during the wet season was 2.45 (95% CI = 1.5-4.1; P = 0.0002). The risk ratio for anemia (hemoglobin < 8 g/dl) at first post-radical cure parasitemia showed no difference between seasons (1.0; 95% CI = 0.73-1.4; P = 0.9915). We did not see seasonal differences in anemia known to exist in this region, probably because the longitudinal cohort design using first parasitemia as an end point prevented the subjects from developing the repeated or chronic infections required for anemia induction. These findings bear upon the design of malaria drug and vaccine trials in holoendemic areas.
In Togo, chloroquine (CQ) remains the first-line drug for the treatment of uncomplicated, Plasmodium falciparum malaria. In the absence of recent data on the level of parasite resistance to antimalarial drugs, Togo's National Malaria Control Programme (NMCP) decided to assess the current efficacy of CQ in the treatment of uncomplicated, P. falciparum malaria at three sentinel sites in the north of the country. Between the September and November of 2001, the World Health Organization's standard 14-day protocol was used to investigate 153 malarious children aged 6-59 months old (46 from Sokode, 54 from Niamtougou and 53 from Dapaong). Of the subjects from Sokode, Niamtougou and Dapaong, early treatment failure was observed in 0%, 7% and 12%, late treatment failure in 0%, 11% and 17%, and overall parasitological failure in 0%, 45% [with a 95% confidence interval (CI) of 39%-51%] and 62% (CI=54%-70%), respectively. Even within northern Togo, there is clearly considerable geographical variation in the level of resistance to CQ. Before an efficient antimalarial-drug policy can be developed, there is an urgent need to develop and use the national surveillance system further, to collect relevant data on the efficacies of CQ and other antimalarial drugs, such as amodiaquine and sulfadoxine-pyrimethamine.
New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast.
Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11 000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995.
The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7–51%) and severe, life-threatening malaria among children aged 1–59 months (PE 44%, CI 19–62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.
To describe severe and complicated malaria, including the common complications, causes of death and predictors of poor outcome.
Retrospective case series.
King Edward VIII Hospital, Durban, Natal, a referral centre.
One hundred and forty-three consecutive patients (88 males, 55 females; median age 25 years, range 2-86 years) admitted with a microscopic diagnosis of Plasmodium falciparum malaria from 1984 to 1991.
A univariate analysis comparing survival and death for categorical and continuous data for various complications was performed using the t-test or chi 2-test (or Fisher's exact test in the case of small cell sizes). Variables that showed significance on univariate analysis (P < 0.1) were used in a multivariate analysis to determine which contributed independently to survival or death.
The case fatality rate was 11.1% (15/135) and the commonest complications were hyperparasitaemia (30%), renal failure (17%), acidaemia (14%), jaundice (10.4%) and cerebral malaria (6%). The commonest complications in patients who died were renal failure (10 patients), cerebral malaria (7), hyperparasitaemia (6) and severe anaemia (5). Multivariate analysis using a logistic regression model showed a high parasite load and cerebral malaria (relative risks of 11.9 and 51.8 respectively) and high urea levels to be the significant predictors of poor outcome (95% confidence intervals 1.53-91.9, 2.74-100.0 and 1.01-1.09, respectively).
Patients with high parasite densities, cerebral involvement and renal dysfunction need urgent attention with parenteral chemotherapy, intravenous fluid replacement and early referral to a tertiary hospital with facilities for intensive monitoring and supportive treatment.
This paper reports on the features of recrudescent infections of chloroquine-resistant Plasmodium falciparum (CQRPf) malaria from a study in vivo of patients from a malaria endemic (n = 527) and non-endemic (n = 129) region of Sri Lanka where the incidence of RI resistance was 30% and 55%, respectively. In both groups of patients,
the recrudescent infections which emerged after treatment of the primary infection with chloroquine (CQ) and primaquine had
significantly lower peripheral parasitaemia (0·036% and 0·108% in endemic and non-endemic patients, respectively) compared
to their primary infections (mean parasitaemia 0·13% and 0·49%; P = 0·021 and 0·002, respectively). The recrudescences of CQ resistant infections also gave rise to clinical disease of markedly
reduced severity (average clinical scores of 10·1 and 8·2) compared to their primary infections (average clinical scores of
12·4 and 12·3; P = 0·003 and 0·001, respectively, in endemic and non-endemic patients). CQ resistant recrudescent infections therefore had
a lower probability of being diagnosed and treated. In endemic patients, a higher proportion of CQRPf infections (57%) had
gametocytaemia compared to the chloroquine sensitive ones (29%) (P = 0·014, χ2 = 5·96) and were significantly more infective to mosquitoes (P = 0·047). These findings imply that, in areas where CQ resistance is prevalent, the continued use of the drug may confer
a survival and propagation advantage on resistant parasites and favour the rapid expansion of their reservoir. In support
of this, we also present epidemiological evidence showing that, in endemic areas, the proportion of P. falciparum patients carrying gametocytes has increased significantly since the emergence of chloroquine resistance. These findings are
relevant to the management of drug resistance and malaria control in countries where P. falciparum is only partially resistant to CQ.
Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted.
We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison.
3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity.
We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.
Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria parasites were detected microscopically and by polymerase chain reaction (PCR) in a series of cross-sectional surveys. PCR revealed submicroscopical infections during the dry season, particularly among individuals who had recovered from a malaria episode following successful drug treatment. Clinical and subclinical infections were contrasted by assaying for allelic polymorphism at 2 gene loci, MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that clinical malaria is associated with infection with novel parasite genotypes not previously detected in that host, or alternatively, that clinical malaria episodes are associated with an increased number of clones in an infection. We detected more mixed infections among clinical isolates, but people carrying parasites during the dry season were not found to have an increased risk of disease in the following malaria season. There was a clear association of disease with the appearance of novel parasite genotypes.
Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that α thalassaemia provides protection against severe malaria. Quite unexpectedly, at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life.
A retrospective study was performed on all cases of malaria recorded in the Federal Republic of Germany between 1963 and 1988. The questionnaires evaluated by the Federal Bureau of Public Health showed a total of 8049 cases, of which 3991 concerned malaria tropica, and 173 deaths. During this 26-year period, 90% of the patients suffering from malaria tropica had contracted the disease in Africa. Deaths from malaria had shown a constant figure of almost 10% between 1963 and 1978, but after that there was a distinct drop. Differentiated analysis revealed that between 1979 and 1988 the death rate for malaria tropica acquired in Africa had been 3.3%. This was clearly dependent on chemoprophylaxis behaviour, on the time of initiation of treatment and on the age of the patients; if tablets were taken regularly, the death rate was 2.3%, rising to 3.1% on irregular intake and to 5.4% without chemoprophylaxis. If therapeutic measures were initiated on the 1st to 5th day of onset, the death rate was 0.6%, on the 6th to 10th day 2.4%, on the 11th to 15th day 2.5% and on the 16th to 20th day 16.7%. In the age group between 60 and over 60 years the lethality was 15.9%. In the course of this study the authors worked out a new malaria questionnaire for the Federal Bureau of Public Health.
The authors present a map of malaria transmission intensity in Brazzaville from which they analyse the impact of urbanization
on anopheline density and transmission of malaria. Whereas at first each new human settlement promotes the introduction or
the proliferation of A. gambiae, the major vector of malaria in Central Africa, urban growth later proves to be unfavourable to this vector. Apart from the
canalization of surface water and improvement in sanitation, it is the increase in population density which seems, by its
direct or indirect consequences in urban areas, to determine the decrease in malaria transmission intensity. By favouring
the absorption of the last remaining open spaces and by the accompanying domestic pollution, urbanization tends to eliminate
an increasing number of A. gambiae breeding places; by limiting the dispersion of anopheles from breeding sites, it tends to focus malaria transmission and
by thinning out the subsisting anopheline population among a denser human population, it tends to reduce the degree of exposure
of each person.
There have been few attempts to examine the relationship between the intensity of transmission and the ensuing burden of disease or mortality from Plasmodium falciparum in Africa. Bob Snow and Kevin Marsh here present the available data on malaria-specific mortality and severe morbidity among African children in relation to estimates of annual rates of falciparum inoculation. These data suggest that cohort mortality from malaria may remain similar between areas experiencing over 100-fold differences in transmission pressure. The authors raise doubts about the possible long-term benefits to children living in areas of high transmission of control strategies aimed at sustained reduction in human-vector contact, for example insecticide-treated bednets.
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The epidemiology of malaria has always varied between different parts of the world because of widely varying vectorial capacity. Mortality from malaria can be measured from clinical records or the rise of mortality during an epidemic, but better from observing the fall of mortality during control or from the population frequency of protective host genes. Holoendemic malaria may have doubled the infant and young-child mortality rate in Africa in the recent past, but death rates have fallen because of chemotherapy. The epidemiological pattern is changing. In the Sahel, water-resource developments tend to lengthen the transmission season, though less than might be expected, and urbanization tends to decrease transmission in Africa, not in Asia. The spread of multiple drug resistance of the parasites is making case management harder and deaths may rise. Malaria control has always been unsatisfactory in sub-Saharan Africa owing to the highly effective vector. The main current hopes for control are the use of the effective insecticide- impregnated bed nets and better case management. No simple concept of an epidemiological transition can reflect the very diverse changes occurring in human malaria worldwide.
This paper is an attempt to relate modifications observed in general and infant mortality rates with the dynamic changes in transmission induced by malaria control measures. The observations indicated relationships between the efficacy of control and a decrease in mortality. The daily parasitological inoculation rate was reduced from 0.00958 infective bites per individual before treatment to 0.00037 after treatment (a decrease of 96%). In two years, general mortality decreased from 23.9 to 13.5 deaths per 1000 population and infant mortality decreased from 157 to 93 per 1000 live births. This indirect benefit of malaria control deserves attention in a wider assessment of measures directed against vector-borne diseases.
Insecticide treatment of bed nets ("mosquito nets") may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria. In a rural area of The Gambia, bed nets in villages participating in a primary health-care (PHC) scheme were treated with permethrin at the beginning of the malaria transmission season. Additionally, children aged 6 months to 5 years were randomised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season. We measured mortality in children in PHC villages before and after the interventions described, and compared this with mortality in villages where no interventions occurred (non-PHC villages). About 92% of children in PHC villages slept under insecticide-treated bed nets. In the year before intervention, mortality in children aged 1-4 years was lower in non-PHC villages. After intervention, the overall mortality and mortality attributable to malaria of children aged 1-4 in the intervention villages was 37% and 30%, respectively, of that in the non-PHC villages. Among children who slept under treated nets, we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths. Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria.
A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.
The occurrence of malaria infections due to Plasmodium vivax and P. falciparum was monitored in a population of 3,023 people living in six contiguous villages in Kataragama, an area of endemic malaria in southern Sri Lanka, over a period of 17 months. The annual incidence of malaria in this population during the study period was 25.8%. Malaria attacks were clustered, occurring more frequently than expected in certain individuals and housing groups and less frequently than expected in others. In one of these villages, the distribution of cases was examined in relation to locality and to the type of house construction. There was a strong association between the malaria incidence and house construction, independent of location. The risk of getting malaria was greater for inhabitants of the poorest type of house construction (incomplete, mud, or cadjan (palm) walls, and cadjan thatched roofs) compared to houses with complete brick and plaster walls and tiled roofs. Houses that were better constructed had a significantly lower malaria incidence rate (10.5%) than those that were poorly constructed (21.2%; P less than 0.01, by Student's t-test). There was also a significantly higher number of indoor resting mosquitoes collected from the poorly constructed houses than from those better constructed; the average (geometric mean) of mosquito densities found in houses of better versus poor construction were 0.97 and 1.89 per collection in the dry season, and 1.95 and 3.42 per collection in the wet season, respectively (P less than 0.05 in both seasons). This indicated that the higher malaria risk associated with poorly constructed houses was at least partly due to higher human-mosquito contact among their inhabitants.
Parasitological and entomological parameters of malaria transmission were monitored for 17 months in 3,625 residents in a Plasmodium vivax malaria endemic region in southern Sri Lanka; the study area consisted of 7 contiguous villages where routine national malaria control operations were being conducted. Malaria was monitored in every resident; fever patients were screened and 4 periodical mass blood surveys were conducted. An annual malaria incidence rate of 23.1% was reported during the period: 9.3% was due to P. vivax and 13.8% was due to P. falciparum; there had been a recent epidemic of the latter in this region, whereas the P. falciparum incidence rate in the previous 10 years had been negligible. There was a wide seasonal fluctuation in the malaria incidence, with the peak incidence closely following the monsoon rains. The prevalence of malaria due to both species detected at the 4 mass blood surveys ranged from 0.98% (at low transmission) to 2.35% (at peak transmission periods). Adults and children developed acute clinical manifestations of malaria. Entomological measurements confirmed a low degree of endemicity with estimated inoculation rates of 0.0029 and 0.0109 (infectious bites/man/night) for P. vivax and P. falciparum, respectively. Several anopheline species contributed to the transmission, and the overall man biting rates (MBR) showed a marked seasonal variation. Malaria at Kataragama, typical of endemic areas of Sri Lanka, thus presents characteristics of "unstable" transmission. Malaria was clustered in the population. There was a low clinical tolerance to P. falciparum malaria, to which most had only been at risk, compared to P. vivax, to which most had had a life-long exposure.
Mortality and morbidity from malaria were measured among 3000 children under the age of 7 years in a rural area of The Gambia, West Africa. Using a post-mortem questionnaire technique, malaria was identified as the probable cause of 4% of infant deaths and of 25% of deaths in children aged 1 to 4 years. The malaria mortality rate was 6.3 per 1000 per year in infants and 10.7 per 1000 per year in children aged 1 to 4 years. Morbidity surveys suggested that children under the age of 7 years experienced about one clinical episode of malaria per year. Calculation of attributable fractions showed that malaria may be responsible for about 40% of episodes of fever in children. Although the overall level of parasitaemia showed little seasonal variation, the clinical impact of malaria was highly seasonal; all malaria deaths and a high proportion of febrile episodes were recorded during a limited period at the end of the rainy season.
The current incidence of pernicious attacks and of mortality due to malaria were studied in Brazzaville. The results of this study, which concerned all the medical units of the town, were analysed in terms of previous studies on the epidemiology of malaria transmission in the various districts of the town.
It was estimated that the annual incidence of pernicious attacks in children in Brazzaville is 1·15 per thousand between 0 and 4 years, 0·25 per thousand between 5 and 9 years and 0·05 per thousand between 10 and 14 years. The annual mortality due to malaria was estimated at 0·43 per thousand between 0 and 4 years and 0·08 per thousand between 5 and 9 years. These values are about 30 times lower than those expected from the results of previous studies of the mortality due to malaria in intertropical Africa.
Whereas considerable differences in intensity of malaria transmission exist in the different districts of Brazzaville, the incidence of pernicious attacks and the resulting mortality are remarkably unvarying whatever the level of transmission. In particular, similar results were observed for the sector Mfilou-Ngamaba-Ngangouoni, where malaria is holoendemic with over 100 infective bites per person per year and a parasite rate of 80·95% in schoolchildren, and the central sector of Poto-Poto-Ouenze-Moungali, where malaria is hypoendemic with less than one infective bite per person every three years and a parasite rate of less than 4% in schoolchildren.
These results are discussed in terms of previous observations in urban and surrounding rural areas. The authors consider that at the present time there is a dramatic drop in mortality due to malaria despite the maintenance in rural areas and numerous urban districts of very high transmission ensuring a stable holoendemicity. Thus drop is attributed to the widespread use of antimalarial drugs by the population.
The authors present a map of malaria transmission intensity in Brazzaville from which they analyse the impact of urbanization on anopheline density and transmission of malaria. Whereas at first each new human settlement promotes the introduction or the proliferation of A. gambiae, the major vector of malaria in Central Africa, urban growth later proves to be unfavourable to this vector. Apart from the canalization of surface water and improvement in sanitation, it is the increase in population density which seems, by its direct or indirect consequences in urban areas, to determine the decrease in malaria transmission intensity. By favouring the absorption of the last remaining open spaces and by the accompanying domestic pollution, urbanization tends to eliminate an increasing number of A. gambiae breeding places; by limiting the dispersion of anopheles from breeding sites, it tends to focus malaria transmission and by thinning out the subsisting anopheline population among a denser human population, it tends to reduce the degree of exposure of each person.
Military records make it possible to study the cause of death of British and French soldiers in West Africa and the Caribbean between about 1819 and 1914. These records are significant because they trace the quantitative pattern of immunity, or lack of it, among soldiers recruited in one region and serving in another. In the Caribbean, a childhood Caribbean disease environment produced no greater immunity to malaria than childhood in the British isles did. Childhood in West Africa, however, produced a degree of immunity to malaria is the Caribbean. For soldiers whose childhood disease environment was in Europe, increased deaths in the tropics were greater in West Africa than they were in the West Indies. The relative importance of malaria as a cause of death increased over this century, largely because death from other causes in the tropics declined faster than malaria deaths did. The greatest improvement in malaria death rates took place between the 1840s and 1870s as a result of empirical public health measures-not after the discovery of the mosquito vector at the end of the century.
Tumour-necrosis factor-alpha (TNF-alpha) is believed to have an important role in the pathogenesis of severe infectious disease and fatal cerebral malaria is associated with high circulating levels of this cytokine. In a large case-control study in Gambian children we find that homozygotes for the TNF2 allele, a variant of the TNF-alpha gene promoter region, have a relative risk of 7 for death or severe neurological sequelae due to cerebral malaria. Although the TNF2 allele is in linkage disequilibrium with several neighbouring HLA alleles, we show that this disease association is independent of HLA class I and class II variation. These data suggest that regulatory polymorphisms of cytokine genes can affect the outcome of severe infection. The maintenance of the TNF2 allele at a gene frequency of 0.16 in The Gambia implies that the increased risk of cerebral malaria in homozygotes is counterbalanced by some biological advantage.
This report documents the effects of malaria epidemic and how it was controlled in one highland district of Kenya. The effects of the epidemic are presented in terms of mortality, morbidity and school absenteeism; information is from routine and verbal reports. Treatment with chloroquine, amodiaquine and sulphonamide pyrimethamine combinations, limited vector control, and health education were used to control the epidemic. Hospital mortality per month increased by 8.6 times during the epidemic while morbidity went up by 3.7 times. Of the 103 deaths attributed to malaria, 64 (62.1%) occurred in hospital and 39 (37.9%) at home. Most of the home deaths (92.3%), occurred in areas that border the malaria endemic Lake Victoria Basin. The rate of pupil absenteeism ranged from 17.6% to 54.4% in primary schools. The policy implications of the report are discussed.
A retrospective study was performed on all cases of malaria recorded in the Federal Republic of Germany between 1963 and 1988. The questionnaires evaluated by the Federal Bureau of Public Health showed a total of 8049 cases, of which 3991 concerned malaria tropica, and 173 deaths. During this 26-year period, 90% of the patients suffering from malaria tropica had contracted the disease in Africa. Deaths from malaria had shown a constant figure of almost 10% between 1963 and 1978, but after that there was a distinct drop. Differentiated analysis revealed that between 1979 and 1988 the death rate for malaria tropica acquired in Africa had been 3.3%. This was clearly dependent on chemoprophylaxis behaviour, on the time of initiation of treatment and on the age of the patients; if tablets were taken regularly, the death rate was 2.3%, rising to 3.1% on irregular intake and to 5.4% without chemoprophylaxis. If therapeutic measures were initiated on the 1st to 5th day of onset, the death rate was 0.6%, on the 6th to 10th day 2.4%, on the 11th to 15th day 2.5% and on the 16th to 20th day 16.7%. In the age group between 60 and over 60 years the lethality was 15.9%. In the course of this study the authors worked out a new malaria questionnaire for the Federal Bureau of Public Health.
Malaria continues to be a serious health risk for travellers. The malaria parasites which infect humans can only be naturally transmitted by female mosquitoes of the genus Anopheles. Travellers to malaria endemic areas require detailed advice on appropriate chemoprophylaxis against malaria and personal protection against mosquito bites. The decision on an appropriate chemoprophylaxis or standby therapy regimen should reflect the malaria risk, pattern of drug resistance, and the toxicity of available drugs. Currently travellers encounter a number of problems in protecting themselves against malaria. Advice is often both inadequate and inaccurate; and all the recommended drug regimens are associated with minor, and occasionally major adverse reactions. Because of poor compliance to drug prophylaxis and to reduce the impact of drug resistance, protection against mosquitoes has a critical role in protecting travellers from malaria. Compliance to methods of personal protection not only reduces the malaria risk but also limits the nuisance and loss of sleep from biting insects.
A community-based randomized, controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana, between July 1993 and June 1995, to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use. The district around Navrongo was divided into 96 geographical areas and in 48 randomly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months. A longitudinal demographic surveillance system was used to record births, deaths and migrations, to evaluate compliance and to measure child mortality. The use of permethrin impregnated bednets was associated with 17% reduction in all-cause mortality in children aged 6 months to 4 years (RR = 0.83; 95% CI 0.69-1.00; P = 0.05). The reduction in mortality was confined to children aged 2 years of younger, and was greater in July-December, during the wet season and immediately after (RR = 0.79; 95% CI 0.63-1.00), a period when malaria mortality is likely to be increased, than in the dry season (RR = 0.92, 95% CI 0.73-1.14). The ready acceptance of bednets, the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implications for programmes to control malaria in sub-Saharan Africa.
Studies of the prevalence and incidence of malaria were conducted in children <10 years old living in 10 rural villages on
the island of Espiritu Santo, Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout the year but
the relative contributions of the 2 major species were highly dependent on season. Plasmodium falciparum predominated in the long wet season (November–May) and P. vivax in the dry season (June–October). Case definitions for malaria, derived using a multiple logistic regression method, showed
that parasite densities associated with clinical disease were low; case definitions for P. falciparum (>1000 parasites/μL in children > 1 year old and >500/μL in infants) and P. vivax (>500 parasites/μL at all ages) were both associated with a specificity and sensitivity of >90%. Like prevalence data, malaria
morbidity was highly seasonal; 80% of clinical P. falciparum infections occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed infections were rare. Malaria was an important cause of morbidity with children <5 years old experiencing
1.3–2.0 episodes of clinical malaria per year and 23% of fevers being attributable to malaria in this age group. Children
aged 5–9 years continued to suffer one episode of clinical malaria per year. The peak incidence of P. vivax malaria occurred earlier in life than the peak incidence of P. falciparum malaria. The possible interactions between these 2 parasite species are discussed.
A study of the cost of malaria at the household level, community perceptions, preventive measures and illness behaviour linked
to the disease was undertaken in 5 villages in the dry zone of Sri Lanka. The surveyed community had a high knowledge of malaria,
although side effects of antimalarial drugs were often confused with symptoms of the disease. The community sought prompt
diagnosis and treatment at ‘western-type’ facilities, with 84% making use of government facilities as their first choice and
16% preferring private facilities. The preventive measures used were burning coils (54% of families) and special leaves (69%
of families), and 93% of the families had their houses sprayed with insecticides. Average direct expenditure on a single malaria
episode was US$3, with some families spending more than 10% of the annual household net income per episode. The highest expenditure
was on special diets for the sick person, to neutralize the perceived heating effect of the disease and its treatment.
The potential of using malaria incidence data routinely collected from endemic regions for disease control and research has increased with the availability of advanced computer-based technologies, but will depend on the quality of the data itself. We report here an investigation into the relevance of malaria statistics provided by the routine data collection system in Moneragala, a rural malaria-endemic region in Sri Lanka. All patients (n = 321) treated for malaria in 2 clusters of health care centres (HCCs) of both the private and the public sector in the administrative regions of Moneragala and Buttala Divisional Secretariat (D.S.). Divisions were studied in December 1995/ January 1996. The catchment area of these HCCs included a population resident in 53 Grama Niladhari (GN) areas, the smallest administrative units of the country. Almost equal numbers of malaria patients were detected and treated at Government and private health care institutions, and in 70% of them treatment was based on a diagnosis confirmed by microscopy. The routine data recording system, however, included only statistics from the Government sector, and only of patients whose diagnosis was microscopically confirmed. In compiling data, the origin of a case of malaria is attributed to the D.S. Division in which the institution (at which the patient was treated) was located, rather than the area in which the patient was resident, which was inaccurate because 90% of malaria patients sought health care at institutions located closest to their residence, thus crossing administrative boundaries. It also led to a loss of resolution of spatial data because patients' addresses recorded at the Government HCCs to the village-level are replaced in the statistics by the D.S. Division, which is a coarse spatial unit. Modifications to the system for malaria case recording needed to correct these anomalies are defined here. If implemented, these could result in major improvements to the quality of data, a valuable resource for the future of malaria control. The paper reiterates the call for the use of a standard spatial unit within a country to facilitate exchange of data among health and other sectors for the control of tropical diseases.
Two case-control studies, one on mortality and the other on malaria morbidity, were carried out in order to evaluate the impact of the Gambian National Insecticide Bed Net Programme during the second year of intervention and to explore the feasibility of such a study for the evaluation of programme effectiveness. For the mortality study, children 1-9 years old who died during the 1993 rainy season were matched by age and sex with 2 healthy controls from the same village. For the morbidity study, children 1-9 years old attending Fatoto or Jahalia Health Centres in The Gambia and who had fever and parasitaemia > or = 5000/microL were matched by age with a child attending the health centres without fever or parasitaemia. An additional healthy control was recruited from the case's village. No impact of insecticide-treated bed nets on mortality was detected and this was in keeping with the results obtained by prospective surveillance. A protective effect of insecticide-treated nets on malaria morbidity was detected when cases were compared with controls recruited at the health centres. However, this disappeared when cases were compared with controls recruited from the cases' villages. The mortality case-control study suggested that reducing the time between onset of disease and treatment may have an important impact on childhood mortality. In order to calculate programme cost-effectiveness, important for informed resource allocations to be made by health managers, it is essential to obtain evidence of effectiveness. This can be done by means of case-control studies, which are easier to carry out and require fewer resources than prospective surveillance. Nevertheless, it is necessary to be conscious of their pitfalls, particularly of the bias involved in the choice of cases and controls. The measurement of insecticide on the nets of the cases or controls is essential for such studies.
That there are so few examples of the use of epidemiological maps in malaria control may be explained by the lack of suitable, spatially defined data and of an understanding of how epidemiological variables relate to disease outcome. However, recent evidence suggests that the clinical outcomes of infection are determined by the intensity of parasite exposure, and developments in geographical information systems (GIS) provide new ways to represent epidemiological data spatially. In the present study, parasitological data from 682 cross-sectional surveys conducted in Kenya were abstracted and spatially defined. Risks of infection with Plasmodium falciparum among Kenyan children, estimated from combinations of parasitological, geographical, demographic and climatic data in a GIS platform, appear to be low for 2.9 million, stable but low for another 1.3 million, moderate for 3.0 million and high for 0.8 million. (Estimates were not available for 1.4 million children.) Whilst the parasitological data were obtained from a variety of sources across different age-groups and times, these markers of endemicity remained relatively stable within the broad definitions of high, moderate and low transmission intensity. Models relating ecological and climatic features to malaria intensity and improvements in our understanding of the relationships between parasite exposure and disease outcome will hopefully provide a more rational basis for malaria control in the near future.
Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that alpha thalassaemia provides protection against severe malaria. Quite unexpectedly at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life.
Malaria can, a priori, kill on its own ('direct' malaria mortality) or in conjunction with some other cause(s) ('indirect' malaria mortality). There are three distinct approaches to the measurement of malaria mortality: (1) measurement of malaria-specific mortality (based on attributing each death to a single cause) or its surrogate, the admission rate for life-threatening malaria; (2) measurement of the reduction in all-cause mortality after removal (or near removal) of malaria; and (3) the estimation of the malaria mortality required to explain the observed frequency of the HbS gene. There is a strong indication that approaches (2) and (3) yield estimates of total (direct and indirect) malaria mortality which are at least twice as high as those obtained using approach (1), which probably measures mostly direct malaria mortality. There is currently a controversy about the long-term impact on mortality of reducing the intensity of malaria transmission from 'high' to 'intermediate', given the expected loss of immunity. Certain geographical comparisons (of the results of 'nature's experiment') indicate that, when the intensity of transmission is high, the incidence of life-threatening malaria falls. However, the seasonal variation in the intensity of transmission decreases with increases in the intensity; low seasonal variation is probably beneficial, allowing a smoother transition from passive to active immunity, but is unlikely to be reversed by preventive measures. It also seems likely that geographical comparisons produce estimates of predominantly direct mortality, which might not run in parallel with the indirect mortality. A tentative numerical exploration of the problem, using a simple demographic model, indicates that, if indirect malaria mortality is important and the other causes of death are concentrated in early life, the long-term impact on all-cause mortality of reducing exposure (although less than the short-term) will probably always be beneficial, even if there is some increase in direct malaria mortality.
2 series of investigations into the incidence and degree of malarial infection in 551 African parturient women in Lagos an urban and semi urban area of Southern Nigeria and their newborn infants were carried out during 1948-50. The routine technique of the investigation consisted of taking blood slides from the peripheral circulation of the mother and her newborn within 6-24 hours of delivery. A blood slide was made from a deep layer of a piece of the maternal placenta excised near the center. The weight of all newborn infants was recorded and whenever possible the progress of the infants was followed up throughout the neonatal period. The weight of all newborn infants was recorded and whenever possible the progress of the infants was followed up throughout the neonatal period. The mean incidence of malarial parasitaemia (mainly due to Plasmodium falciparum) in the sample of 323 Africa parturient women was found to be 33% somewhat higher than the usual parasite rate of the adult indigenous population. The incidence of malarial infection of the placenta was 23.8%. There were no cases of congenital malaria in 332 babies born of these mothers. The mean weight at birth of 237 babies born of mothers whose placentae were noninfected was 145 mg higher than that of 73 babies born of mothers whose placentae were found to be infected. The difference was statistically significant. There was no apparent correlation between neonatal mortality and infection of the placenta. Periodic investigation of a sample of 138 African infants followed up from the age of about 1 month through the 1st year of life and through part of the 2nd year showed that the mean parasite rate due principally to P. falciparum increased from 2.2% during the 1st quarter year to 20% in the 2nd quarter to 60-70% during the 3rd and 4th quarters and to over 80% thereafter. The infection rate when calculated in relation to the known length of exposure to infection shows that an equally long exposure leads to different frequencies of infection in the various age groups of the sample of infants investigated and that in the age group 1-3 months the parasite rate was significantly lower than might have been expected. Periodic follow-up of the mean weight curves of infection and noninfected infants indicated that the curves of both groups showed a considerable flattening out at about 5 months of age and later and that the flattening out is more pronounced in the infected group than in the noninfected. Records of 3540 autopsies performed upon children in Lagos during the years 1933-50 revealed that acute malaria can be incriminated as the cause of death in 9% of infants in 14% of children aged 1-4 years in 9% of children aged 5-7 years in 4% of older children and in 2% of adolescents. The number of deaths due to direct effects of malaria in the Nigerian population under 15 years of age amount to 35000/annum.
An epidemic of malaria, covering about 100,000 square miles in four central provinces in the highlands of Ethiopia and portions of the highlands of five other provinces, was observed in Ethiopia between June and December of 1958. The altitudinal limits of the epidemic ranged approximately between 1,600 to 2,150 meters elevation, in which area the communal immunity of the habitants is low for the most part. The estimate of the number of malaria cases attributed to the epidemic is estimated to be not less than three million cases. Deaths from malaria may have exceeded 150,000.
Anopheles gambiae was the only vector involved. Plasmodium falciparum was the predominant malaria parasite. It accounted for the severe acute illness which characterized the clinical syndrome of most cases and the high mortality observed in many districts. Food shortages in 1958, due to 1957 crop failures in some areas, also indirectly contributed to high mortality.
The main precipitating cause of the 1958 epidemic appears to have been unusual weather conditions in the highland areas of Ethiopia. Rainfall exceeded all other previous years on record, and abnormally high atmospheric temperature and relative humidity prevailed.
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There have been few attempts to examine the relationship between the intensity of transmission and the ensuing burden of disease or mortality from Plasmodium falciparum in Africa. Bob Snow and Kevin Marsh here present the available data on malaria-specific mortality and severe morbidity among African children in relation to estimates of annual rates of falciparum inoculation. These data suggest that cohort mortality from malaria may remain similar between areas experiencing over 100-fold differences in transmission pressure. The authors raise doubts about the possible long-term benefits to children living in areas of high transmission of control strategies aimed at sustained reduction in human-vector contact, for example insecticide-treated bednets.
Jean-François Trape and Christophe Rogier present epidemiological data and an analysis of the relationship between transmission, morbidity and mortality from malaria which suggest that any intervention aiming to reduce transmission will not, on a long-term basis, reduce the burden of malaria in the majority of epidemiological contexts observed in tropical Africa.
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Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they are relevant and appropriate but comments will not be edited. The ultimate decision on publication of an online comment is at the Editors' discretion. Formatting: Please include a title for the comment and your affiliation. Note that symbols (e.g. Greek letters) may not transmit properly in this form due to potential software compatibility issues. Please spell out the words in place of the symbols (e.g. replace “α” with “alpha”). Comments should be no more than 8,000 characters (including spaces ) in length. References may be included when necessary but should be kept to a minimum. Be careful if copying and pasting from a Word document. Smart quotes can cause problems in the form. If you experience difficulties, please convert to a plain text file and then copy and paste into the form.
The relationship between resistance to Plasmodium falciparum infection and the frequency and distribution of the sickle-cell gene in populations exposed to endemic malaria transmission is reducible to clear and quantifiable terms. In this review, Trevor Jones examines the prediction of gene frequency changes under selective pressure, the selective advantage to the heterozygote (balanced polymorphism) that the sickle-cell gene provides to individuals in areas with malaria transmission, and the relationship between sickle-cell gene frequency and malaria, as measured by, for example, sporozoite rate and basic reproduction rate. He seeks to clarify what one can infer about malaria transmission from an analysis of the distribution and inheritance patterns of the sickle-cell gene and sickle-cell disease and under what circumstances these inferences should be made.
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