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An unexpected cause of fever and seizures
... Recently, the deaths due to P. vivax monoinfection have also been established by histopathological confirmation of autopsy specimens [32][33] . In some of these studies, the diagnosis of P. vivax monoinfection was established by polymerase chain reaction (PCR) examination thereby negating any chance of coinfection with P. falciparum 5,6,9,[12][13][14][15][17][18][19]28 and have undertaken exhaus-tive clinical, biochemical and radiological studies to rule out associated comorbid conditions 6,[12][13][14][17][18]28 . ...
... In majority of these studies, the diagnosis was established by peripheral blood film (PBF) examination only thereby not providing enough strength in clinical and species diagnosis 7, 10-11 . Earlier, we have carried out hospital-based prospective observational study to describe the clinical presentation of PCR confirmed cases of severe vivax malaria in children and adults 6,9,14,18 . In this prospective hospital-based observational study on adult patients of PCR diagnosed severe malaria (P. ...
Background & objectives:
Description of severe vivax malaria and mixed species infection requires good clinical study. The present study was undertaken to evalute the characteristics of severe malaria patients in Bikaner, northwest India.
Methods:
This prospective study included 539 admitted adult patients of severe malaria (Plasmodium falciparum 274, P. vivax 221, and mixed infection of Pv + Pf 44). The diagnosis was confirmed by polymerase chain reaction. The categorization of severe malaria was done strictly as per WHO criteria.
Results:
The distribution of severe manifestation was similar in severe vivax, falciparum and mixed infections except more cases of thrombocytopenia in P. vivax (p=0.030) and in mixed infection (p=0.004). The risk of developing severe malaria was greatest in patients of mixed infection [53.01% (44/83)] in comparison to Plasmodium falciparum malaria [49.37% (274/555), RR= 1.135; p=0.616] and P. vivax malaria [45.38% (221/ 487), RR = 1.299, p=0.243]. Hepatic dysfunction was the commonest pernicious syndrome [P. falciparum 50% (137/274), P. vivax 43.89% (97/221), and mixed infections 54.55% (24/44)]. Multiorgan dysfunction was present in 40.26% (217/539) patients, the risk was greatest in mixed infection [90.90% (40/44)] in comparison to P. falciparum monoinfection [37.59% (103/274), RR = 12.238; p=0.0001] or P. vivax monoinfection [33.48% (74/ 221), RR = 13.25; p=0.0001]. The risk of mortality in severe malaria was 6.31% (34/539) in which mixed infection had greater risk [9.09% (4/44)] in comparison to P. falciparum [7.30% (20/274); OR = 1.270 (CI 0.347-4.217); p=0.757] or P. vivax [4.52% (10/221); 0R 2.110 (CI 0.527-7.826); p=0.260].
Interpretation & conclusion:
Severe vivax or falciparum malaria had almost similar features and prognosis including mortality. Risk of developing severe malaria, multiorgan dysfunction and mortality was more in patients of mixed infection in comparison to P. falciparum or P. vivax monoinfection. A multicentric study on larger number of patients requires further confirmation.
... Cerebral malaria was observed in five patients; this has also been reported in one patient in Pakistan (Beg et al. 2002) and in three patients in India (Kochar et al. 2005) in malaria caused by P. vivax. Status epilepticus has also been reported in Turkey (Ozen et al. 2006) and India (Kochar et al. 2007a, b). In our study generalized tonic–clonic convulsions were observed in two patients infected with P. falciparum. ...
... Author's personal copy syndrome causing bilateral facial paralysis (Kochar et al. 2007a, b), have not been reported in the present study. ...
One hundred and sixty patients having clinical features of severe malaria reported during monsoon season-August–October 2010 at this tertiary care center of north India. Of these 110 (68.75 %) had Plasmodium vivax infection, 30 (18.75 %) were infected with P. falciparum and 20 (12.5 %) had co-infection due to P. vivax and P. falciparum. The diagnosis was made using Rapid Card Test and was confirmed by peripheral smear examination of thick and thin films. Several complications such as acute kidney injury, jaundice, severe anemia, metabolic acidosis, shock, hyperpyrexia, hypoglycemia, generalized tonic–clonic convulsions etc. were found to be more prevalent in patients with P. vivax infection. These symptoms were until recently known to be associated with falciparum malaria.
... Incidence of convulsions is 10-20% but there may be presenting symptom of an acute relapse 1,2 . Although Plasmodium vivax usually causes benign uncomplicated malaria, it can occasionally result in severe disease with life-threatening, end-organ involvement including cerebral malaria manifesting as convulsions 3 . This case is a rare presentation of severe vivax malaria and exemplifies the dilemma associated with diagnosis and treatment of convulsions when it occurs in a case of AIP. ...
... The causation of unconsciousness and convulsions in this patient could be complex including acute porphyric crisis 1 , cerebral malaria due to P. vivax 3,6 and/or the use of artemether that has been associated with prolongation of coma and more incidence of seizures 7 . ...
... However, we consider that, the patients' blood could have been subjected to polymerase chain reaction (PCR) analysis to confirm the P. vivax mono-infection. The 18S rRNA PCR diagnostics has been employed in some of the severe vivax malaria case studies reported from India, which is particularly important to evaluate the actual burden of vivax malaria [2,3,4]. In a recent observational and prospective PCR-based study conducted at a tertiary care hospital in Northwestern India, the involvement of P. vivax mono-infection has clearly been proven unequivocally among thirteen children with cerebral malaria and multi-organ dysfunction [5]. ...
... In contrast to Africa, malaria transmission in India is more limited, both adolescents and adults are at risk of severe malaria, and a substantial proportion of cases are infected with P. vivax rather than the traditionally more virulent P. falciparum. Although many expansive and comprehensive studies have been carried out in Africa [9][10][11][12][13][14] and Southeast Asia [15][16][17][18][19][20] to examine pathogenesis and mortality determinants in malaria-positive patients, a more limited number of such studies, generally smaller in scope, have been conducted within India [21][22][23][24][25][26][27][28][29]. ...
Background
Malaria remains an important cause of morbidity and mortality in India. Though many comprehensive studies have been carried out in Africa and Southeast Asia to characterize and examine determinants of Plasmodium falciparum and Plasmodium vivax malaria pathogenesis, fewer have been conducted in India. MethodsA prospective study of malaria-positive individuals was conducted at Goa Medical College and Hospital (GMC) from 2012 to 2015 to identify demographic, diagnostic and clinical indicators associated with P. falciparum and P. vivax infection on univariate analysis. ResultsBetween 2012 and 2015, 74,571 febrile individuals, 6287 (8.4%) of whom were malaria positive, presented to GMC. The total number of malaria cases at GMC increased more than two-fold over four years, with both P. vivax and P. falciparum cases present year-round. Some 1116 malaria-positive individuals (mean age = 27, 91% male), 88.2% of whom were born outside of Goa and 51% of whom were construction workers, were enroled in the study. Of 1088 confirmed malaria-positive patients, 77.0% had P. vivax, 21.0% had P. falciparum and 2.0% had mixed malaria. Patients over 40 years of age and with P. falciparum infection were significantly (p < 0.001) more likely to be hospitalised than younger and P. vivax patients, respectively. While approximately equal percentages of hospitalised P. falciparum (76.6%) and P. vivax (78.9%) cases presented with at least one WHO severity indicator, a greater percentage of P. falciparum inpatients presented with at least two (43.9%, p < 0.05) and at least three (29.9%, p < 0.01) severity features. There were six deaths among the 182 hospitalised malaria positive patients, all of whom had P. falciparum. Conclusion
During the four year study period at GMC, the number of malaria cases increased substantially and the greatest burden of severe disease was contributed by P. falciparum.
... 8 Studies of vivax morbidity and mortality from across the vivax-endemic world have reported the full spectrum of pathologies commonly attributed exclusively to P. falciparum, including both sequestration-related and nonsequestrationrelated complications. [13][14][15][16]149,[151][152][153] A diagnosis of acute severe vivax malaria, therefore, includes one or more of the following (numerous case reports of each exist in the literature) 8,10,13,19,149,154,155 : 1) neurological conditions, notably coma or repeated general seizures and altered consciousness; 2) hematological conditions, particularly severe anemia (< 5 mg Hb/dL), severe thrombocytopenia (< 50,000 platelets/ μL), and hemoglobinuria; 3) systemic symptoms such as circulatory collapse or shock; and 4) vital organ failure, including respiratory dysfunction and acute respiratory distress syndrome, acute renal failure, splenic rupture, hepatic dysfunction, and jaundice. ...
This manuscript is part of an upcoming journal supplement about the control and elimination of Plasmodium vivax malaria. In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue. This is an open-These authors contributed equally to this work. Abstract. Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum. Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded.
... The non-falciparum species are P. vivax, P. ovale, P. malariae and P. knowlesi, of which P. vivax is even more widespread than P. falciparum [10,11], P. ovale has recently been shown to comprise two species [14] and P. knowlesi has been recognised as a concern only recently [15]. The World Health Organization [16] defines severe and cerebral forms of falciparum malaria and, while non-falciparum malaria may also have severe or cerebral forms [17][18][19][20][21], they are not necessarily explicitly acknowledged in non-falciparum malaria and some authors explicitly discount the possibility [22,23]. ...
Malaria is often associated with hyponatraemia, but neither the extent nor the probability of hyponatraemia has been estimated and it is not clear whether they depend on the infective species. Analysis of reports of hyponatraemia shows that it tends to be less severe in non-falciparum malaria than it is in falciparum malaria. However, the probability of observing serum sodium concentrations of less than 130 mM decreases in the sequence cerebral falciparum = severe falciparum > vivax > non-severe falciparum > knowlesi and falciparum > non-falciparum. In addition to a greater probability of hyponatraemia in severe falciparum malaria than in non-severe falciparum malaria, the probability of hypernatraemia in falciparum malaria is slightly greater than it is for healthy individuals.
... Over 50% of malaria cases caused by this species occur in India and thus makes her the major contributing country to the worldwide burden of P. vivax (Joshi et al., 2008; Kumar et al., 2007). P. vivax is still primarily considered to be the cause of benign tertian malaria; however, recent studies have documented the existence of patients with complications pathologically similar to those seen in severe Plasmodium falciparum malaria (Alexandre et al., 2010; Kochar et al., 2009 Kochar et al., , 2007 Kochar et al., , 2005 ). Very little is known about molecular mechanisms involved in complicated P. vivax malaria. ...
... Seizures have been repeatedly observed in severe vivax malaria, and the cause has been attributed to the possible cerebral malaria, hypoglycemia, hyponatremia and lactic acidosis (Kochar et al. 2007b). Cerebral malaria in P. vivax infection has been linked to metabolic changes instead of sequestration (Rogerson and Carter 2008). ...
A patient was admitted with fever, vomiting, restlessness and convulsions. He was febrile and unconscious. Laboratory tests
showed a low platelet count and ruled out enteric fever and dengue. His peripheral blood smear was positive for Plasmodium vivax. The presence of P. vivax monoinfection was confirmed by polymerase chain reaction and DNA sequencing. The report highlights the importance of considering
the possibility of complications even in P. vivax malaria and formulation of strategies accordingly.
... However, we consider that, the patients' blood could have been subjected to polymerase chain reaction (PCR) analysis to confirm the P. vivax mono-infection. The 18S rRNA PCR diagnostics has been employed in some of the severe vivax malaria case studies reported from India, which is particularly important to evaluate the actual burden of vivax malaria [2,3,4]. In a recent observational and prospective PCR-based study conducted at a tertiary care hospital in Northwestern India, the involvement of P. vivax mono-infection has clearly been proven unequivocally among thirteen children with cerebral malaria and multi-organ dysfunction [5]. ...
Dear Sir,
Even though Plasmodium vivax is highly prevalent in India, the studies are limited not only due to its benign nature but also because of the magnitude of severity caused by P. falciparum malaria. In a recent interesting case report published in this journal it has been reported that this is the first reported case of vivax malaria associated with acute pancreatitis, which resulted in mortality [1]. In this case report, the diagnosis has been made on the basis of traditional smear microscopy and malaria rapid diagnostic test. However, we consider that, the patients’ blood could have been subjected to polymerase chain reaction (PCR) analysis to confirm the P. vivax mono-infection. The 18S rRNA PCR diagnostics has been employed in some of the severe vivax malaria case studies reported from India, which is particularly important to evaluate the actual burden of vivax malaria [2, 3, 4]. In a recent observational and prospective PCR-based study conducted at a tertiary care hospital in Northwestern India, the involvement of P. vivax mono-infection has clearly been proven unequivocally among thirteen children with cerebral malaria and multi-organ dysfunction [5]. Similarly, there is an urgent need for multi-centric and prospective studies by using PCR detections of severely ill malaria patients along with traditional detection methods to assess the genuine burden of severe and fatal disease associated with vivax malaria.
... Malaria caused by the Plasmodium species, poses major health concerns in many regions of the world. Reports on severe manifestations caused by Plasmodium vivax (Kochar et al., 2005Kochar et al., , 2007Kochar et al., , 2009 Alexandre et al., 2010), one of the major human malaria parasites, has highlighted the need to further study and identify novel and more effective therapeutic drug targets against this studied parasite. Targets for drug design are conventionally nuclear genome encoded products. ...
The apicomplexan parasite Plasmodium vivax is responsible for causing more than 70% of human malaria cases in Central and South America, Southeastern Asia and the Indian subcontinent. The rising severity of the disease and the increasing incidences of resistance shown by this parasite towards usual therapeutic regimens have necessitated investigation of putative novel drug targets to combat this disease. The apicoplast, an organelle of procaryotic origin, and its circular genome carrying genes of possible functional importance, are being looked upon as potential drug targets. The genes on this circular genome are believed to be highly conserved among all Plasmodium species. Till date, the plastid genome of P. falciparum, P. berghei and P. chabaudi have been detailed while partial sequences of some genes from other parasites including P. vivax have been studied for identifying evolutionary positions of these parasites. The functional aspects and significance of most of these genes are still hypothetical. In one of our previous reports, we have detailed the complete sequence, as well as structural and functional characteristics of the Elongation factor encoding tufA gene from the plastid genome of P. vivax. We present here the sequences of large and small subunit rRNA (lsu and ssu rRNA) genes, sufB (ORF470) gene, RNA polymerase (rpo B, C) subunit genes and clpC (casienolytic protease) gene from the plastid genome of P. vivax. A comparative analysis of these genes between P. vivax and P. falciparum reveals approximately 5-16% differences. A codon usage analysis of major plastid genes has shown a high frequency of codons rich in A/T at any or all of the three positions in all the species. TTA, AAT, AAA, TAT, and ATA are the major preferred codons. The sequences, functional domains and structural analysis of respective proteins do not show any variations in the active sites. A comparative analysis of these Indian P. vivax plastid genome encoded genes has also been done to understand the evolutionary position of the Indian parasite in comparison to other Plasmodium species.
... Malaria caused by the Plasmodium species, poses major health concerns in many regions of the world. Reports on severe manifestations caused by Plasmodium vivax (Kochar et al., 2005Kochar et al., , 2007Kochar et al., , 2009 Alexandre et al., 2010), one of the major human malaria parasites, has highlighted the need to further study and identify novel and more effective therapeutic drug targets against this studied parasite. Targets for drug design are conventionally nuclear genome encoded products. ...
... For example, in low malaria transmission areas of Asia and South America CM, severe malaria anemia (SMA), acute renal failure (also known as acute kidney injury), jaundice and multi organ failure are common while in Africa, severe manifestations include CM, SMA, respiratory distress and acidosis [8]. While it was previously thought that only P. falciparum caused SM, recent reports have challenged this notion by demonstrating that severe and complicated malaria is also observed with P. vivax infection91011121314151617 underscoring the huge public health impact of SM. ...
Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children) every year. One life-threatening complication of malaria is cerebral malaria (CM). Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review here what is currently known regarding biomarkers for CM outcomes.
A Pub Med literature search was performed using the following search terms: “malaria,” “cerebral malaria,” “biomarkers,” “mortality” and “neurological sequelae.” This search revealed a paucity of usable biomarkers for CM management. We propose three main areas in which researchers can attempt to identify CM biomarkers: 1) early biomarkers, 2) diagnostic biomarkers and 3) prognostic biomarkers.
... The problem is further compounded by the development of chloroquine resistance against P. vivax (Dua et al., 1996;Singh, 2000). Severe and com-plicated forms of P. vivax malaria causing cerebral malaria, renal failure, severe anaemia, jaundice and even death in some patients are reported from Western India (Kochar et al., 2005(Kochar et al., , 2007. ...
The aim of this preliminary study was to investigate the plasma cytokine profiles in a group of patients suffering from Plasmodium vivax malaria during the peak of its transmission season. Plasma samples of 173 P. vivax patients and 34 healthy individuals were analyzed for IFN-gamma, TNF-alpha, IL-10 and IP-10 levels by ELISA. Levels of both pro- and anti-inflammatory cytokines were significantly higher in P. vivax patients compared to controls. Children with P. vivax infection had significantly higher levels of IFN-gamma than adults (P=0.017). Asexual parasitaemia versus TNF-alpha (r=-0.31, P=0.01), IL-10 (r=-0.30, P=0.015) and gametocytaemia versus IFN-gamma (r=-0.26; P=0.034) levels showed significant negative correlation in children compared to adults. The median concentrations of IFN-gamma (P=0.001), IL-10 (P=0.032) and IP-10 (P</=0.05) were higher in children reported with chills and rigors, whereas in adults only IFN-gamma levels was higher (P<0.0001). The median plasma concentrations of IFN- gamma (P=0.02), IL-10 (P<0.0001) and IP-10 (P=0.068) were higher in patients with mild anaemia compared to non-anaemic patients. The results indicated that both pro- and anti-inflammatory cytokine responses are associated with clinical signs of mild anaemia and paroxysm during symptomatic P. vivax malaria in Central India.
... Further, the possibility of coincidental rheumatoid factor causing false positive results can not be excluded [24,25]. Among non-falciparum infections, P. vivax is no longer considered a mild infection [26][27][28]. Analysis revealed a relatively large number of non falciparum infections false positive too. The reasons for the false positivity of RDTs for non falciparum infections are unknown. ...
Malaria presents a diagnostic challenge in tribal belt of central India where two Plasmodium species, Plasmodium falciparum and Plasmodium vivax, are prevalent. In these areas, rapid detection of the malaria parasites and early treatment of infection remain the most important goals of disease management. Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response(R) Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis between P. falciparum with other Plasmodium species in remote villages of Jabalpur district.
A finger prick blood sample was collected to prepare blood smear and for testing with the RDT after taking informed consent. The figures for sensitivity, specificity, accuracy and predictive values were calculated using microscopy as gold standard.
Analysis revealed that overall, the RDT was 93% sensitive, 85% specific with a positive predictive value (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and J-index was 0.74. For P. falciparum, the sensitivity and specificity of the test were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity, specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and a NPV of 97%.
The RDTs are easy to use, reliable and simple to interpret. RDTs are more suited to health workers in situations where health services are deficient or absent. Therefore, the test can be used as an epidemiological tool for the rapid screening of malaria.
Introduction: The renal involvement has been reported in Plasmodium falciparum, Plasmodium malariae, and recently in Plasmodium vivax infection. Although malaria is highly endemic in the rural locality of Odisha and a significant proportion of severe malaria causes acute renal complication, there is no definite study on the survival of malarial acute kidney injury (AKI) in children of the setup of the current study. Objective: The objective of the study was to find out the survival of malarial AKI in children. Methods: A prospective analytical study was conducted from October 2016 to September 2018 in the postgraduate department of pediatrics, of a tertiary care hospital in Odisha, after approval from the Institutional Ethics Committee. Children with smear-positive and/or quantitative buffy coat (QBC) positive malaria were included in the study. All the relevant data (age, gender, duration of hospital stays, stages of AKI, signs, and symptoms of AKI, serum urea and creatinine, electrolytes, and routine hemogram) were collected, validated and results were analyzed in terms of one-way ANOVA and Kaplan–Meier survival analysis. Results: Out of 202 malarial cases, 50.4% (102) cases were found to be suffering from malarial AKI. Out of 102 malarial AKI children, 68% were affected due to falciparum infection, 12% due to vivax, and rest 20% due to mixed infection. The median duration of survival in days between three stages of AKI was significant as evidenced by Tarone-Ware Chi-square=48.365 (df=2), p=0.000. Conclusion: Mortality was 6% and all of these deaths belong to Stage 3 AKI; furthermore, the morbidities are more in Stage 3 as compared to other stages.
The 28S rRNA gene was amplified and sequenced from P. falciparum and P. vivax isolates collected from northwest India. Based upon the sequence diversity of the Plasmodium 28SrRNA gene in comparison with its human counterpart, various nested polymerase chain reaction (PCR) primers were designed from the 3R region of the 28SrRNA gene and evaluated on field isolates. This is the first report demonstrating the utility of this gene for species-specific diagnosis of malaria for these two species, prevalent in India. The initial evaluation on 363 clinical isolates indicated that, in comparison with microscopy, which showed sensitivity and specificity of 85·39% and 100% respectively, the sensitivity and specificity of the nested PCR assay was found to be 99·08% and 100% respectively. This assay was also successful in detecting mixed infections that are undetected by microscopy. Our results demonstrate the utility of the 28S rRNA gene as a diagnostic target for the detection of the major plasmodial species infecting humans.
To evaluate microscopy, OptiMAL® and multiplex PCR for the identification of Plasmodium falciparumm (P. falciparum) and Plasmodium vivax (P. vivax) from the field isolates of Bikaner, Rajasthan (Northwest India).
In this study, a multiplex PCR (P. falciparum and P. vivax) was further developed with the incorporation of Plasmodium malariae (P. malariae) specific primer and also a positive control. The performance of microscopy, plasmodium lactate dehydrogenase (pLDH) based malaria rapid diagnostic test OptiMAL® and 18S rRNA gene based multiplex PCR for the diagnosis of P. falciparum and P. vivax was compared.
The three species multiplex PCR (P. falciparum, P. vivax and P. malariae) with an inbuilt positive control was developed and evaluated. In comparison with multiplex PCR, which showed the sensitivity and specificity of 99.36% (95%CI, 98.11%-100.00%) and 100.00% (95%CI, 100.00%-100.00%), the sensitivity and specificity of microscopy was 90.44% (95%CI, 88.84%-95.04%) and 99.22% (95%CI, 97.71%-100.00%), and OptiMAL® was 93.58% (95%CI, 89.75%-97.42%) and 97.69% (95%CI, 95.10%-100.00%). The efficiencies were 99.65%, 95.10% and 95.45% for multiplex PCR, microscopy and OptiMAL®, respectively.
Our results raise concerns over the overall sensitivities of microscopy and OptiMAL®, when compared to the multiplex PCR and thus stress the need for new molecular interventions in the accurate detection of the malarial parasites. This further highlights the fact that further developments are needed to improve the performance of rapid diagnostic tests at field level.
The 28S rRNA gene was amplified and sequenced from P. falciparum and P. vivax isolates collected from northwest India. Based upon the sequence diversity of the Plasmodium 28SrRNA gene in comparison with its human counterpart, various nested polymerase chain reaction (PCR) primers were designed from the 3R region of the 28SrRNA gene and evaluated on field isolates. This is the first report demonstrating the utility of this gene for species-specific diagnosis of malaria for these two species, prevalent in India. The initial evaluation on 363 clinical isolates indicated that, in comparison with microscopy, which showed sensitivity and specificity of 85.39% and 100% respectively, the sensitivity and specificity of the nested PCR assay was found to be 99.08% and 100% respectively. This assay was also successful in detecting mixed infections that are undetected by microscopy. Our results demonstrate the utility of the 28S rRNA gene as a diagnostic target for the detection of the major plasmodial species infecting humans.
Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure.
Background:
Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce.
Methods:
From 1996 to 2010, 19 patient deaths with a clinical diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs).
Results:
Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung.
Conclusions:
In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease.
The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed to look for early signs of systemic complications.
In fact, severe malaria is a life threatening but treatable disease. The protean and nonspecific clinical findings occurring in malaria (fever, malaise, headache, myalgias, jaundice and sometimes gastrointestinal symptoms of nausea, vomiting and diarrhoea) may lead physicians who see malaria infrequently to a wrong diagnosis, such as influenza (particularly during the seasonal epidemic flu), dengue, gastroenteritis, typhoid fever, viral hepatitis, encephalitis. Physicians should be aware that malaria is not a clinical diagnosis but must be diagnosed, or excluded, by performing microscopic examination of blood films. Prompt diagnosis and appropriate treatment are then crucial to prevent morbidity and fatal outcomes. Although Plasmodium falciparum malaria is the major cause of severe malaria and death, increasing evidence has recently emerged that Plasmodium vivax and Plasmodium knowlesi can also be severe and even fatal.
Plasmodium vivax is causing increasingly more cases of severe malaria worldwide. There is an urgent need to reexamine the clinical spectrum and burden of P. vivax so that adequate control measures can be implemented against this emerging but neglected disease. Herein, we report a case of renal acute cortical necrosis and acute kidney injury (AKI) associated with P. vivax monoinfection. Her initial serum creatinine was 7.3 mg/dL on admission. Modification of Diet in Renal Disease (MDRD) Study glomerular filtration rate (GFR) value was 7 mL/min/1.73 m(2) (normal kidney function-GFR above 90 mL/min/1.73 m(2) and no proteinuria). On follow-up, 5 months later, her SCr. was 2.43 mg/dl with no proteinuria. MDRD GFR value was 24 mL/min/1.73 m(2) suggesting severe chronic kidney disease (CKD; GFR less than 60 or kidney damage for at least 3 months), stage 4. Our case report highlights the fact that P. vivax malaria is benign by name but not always by nature. AKI associated with P. vivax malaria can lead to CKD. Further studies are needed to determine why P. vivax infections are becoming more severe.
Severe and complicated malaria is usually caused by Plasmodium falciparum malaria (PF) but it has been increasingly observed that Plasmodium vivax malaria (PV), which was otherwise considered to be benign malaria, with a low case-fatality ratio, can also occasionally result in severe disease as with PF malaria. There is an urgent need to re-examine the clinical spectrum and burden of PV so that adequate control measures can be implemented against this emerging but neglected disease. We report a case of severe PV malaria with multi-organ dysfunction. Patients exhibited acute kidney injury, severe anemia/thrombocytopenia, jaundice, hypoglycemia, hyponatremia, and pulmonary edema. Peripheral blood microscopy by trained and expert pathologist and rapid diagnostic test showed the presence of PV and absence of PF. The patient recovered completely with anti-malarial drugs, supportive measures, and hemodialysis.Recent microrheologic research that analyzed malaria severity in PV clearly demonstrated enhanced aggregation, erythrocyte clumping, and reduced deformability affecting microcirculation. Our case report highlights the fact that PV malaria is benign by name but not always by nature. PV can lead to unusual and potentially life-threatening complications. Further large-scale multi-centric studies are needed to define this less known entity.
Because of recent declining malaria transmission in Latin America, some authorities have recommended against chemoprophylaxis for most travelers to this region. However, the predominant parasite species in Latin America, Plasmodium vivax, can form hypnozoites sequestered in the liver, causing malaria relapses. Additionally, new evidence shows the potential severity of vivax infections, warranting continued consideration of prophylaxis for travel to Latin America. Individualized travel risk assessments are recommended and should consider travel locations, type, length, and season, as well as probability of itinerary changes. Travel recommendations might include no precautions, mosquito avoidance only, or mosquito avoidance and chemoprophylaxis. There are a range of good options for chemoprophylaxis in Latin America, including atovaquone-proguanil, doxycycline, mefloquine, and--in selected areas--chloroquine. Primaquine should be strongly considered for nonpregnant, G6PD-nondeficient patients traveling to vivax-endemic areas of Latin America, and it has the added benefit of being the only drug to protect against malaria relapses.
Severe Plasmodium vivax malaria in adults has been reported from Bikaner (northwestern India) but the reports on children are scanty. This prospective study was done on 303 admitted children of malaria. The diagnosis was done by peripheral blood smear and rapid diagnostic test. Further confirmation of severe P. vivax monoinfection was done by polymerase chain reaction (PCR). The proportion of P. falciparum, P. vivax, and mixed (P. falciparum and P. vivax) infection was 61.01%, 33.99%, and 4.95%, respectively. Severe disease was present in 49.5% (150/303) children with malaria, with the risk greatest among P. vivax monoinfection (63.1% [65/103]) compared with P. falciparum, either alone (42.7% [79/185]; odds ratio [OR] = 2.3 [95% confidence interval (CI) = 1.40-3.76], P = 0.001) or mixed infections (40% [6/15]; OR = 2.57 [95% CI = 0.88-7.48]). In children < 5 years of age, the proportion of severe malaria attributable to P. vivax rose to 67.4% (31/46) compared with 30.4% (14/46) of P. falciparum (OR = 4.7 [95% CI = 2.6-8.6], P < 0.0001) and 2.2% (1/46) of mixed infection (OR = 92 [95% CI = 24.6-339.9], P < 0.0001). The proportion of patients having severe manifestations, which included severe anemia, thrombocytopenia, cerebral malaria, acute respiratory distress syndrome, hepatic dysfunction, renal dysfunction, abnormal bleeding was significantly high in association with P. vivax monoinfection in 0-5 year age group, while the same was significantly high in association with P. falciparum monoinfection in 5-10 year age group. Similarly P. vivax monoinfection had greatest propensity to cause multiorgan dysfunction in 0-5 year age group (34.1% [17/41], P < 0.0001) in comparison to P. falciparum monoinfection, which had similar propensity in 5-10 year age group (36.8% [35/95], P = 0.039). Plasmodium vivax monoinfection was almost equally serious to cause significant mortality in comparison to P. falciparum (case fatality rate of severe P. vivax was 3.9% versus 3.2% of severe P. falciparum malaria; P = 1.0). This study reaffirms the evidence of severe P. vivax malaria in children in Bikaner.
Building a mathematical model of population dynamics of pathogens within their host involves considerations of factors similar to those in ecology, as pathogens can prey on cells in the host. But within the multicellular host, attacked cell types are integrated with other cellular systems, which in turn intervene in the infection. For example, immune responses attempt to sense and then eliminate or contain pathogens, and homeostatic mechanisms try to compensate for cell loss. This review focuses on modeling applied to malarias, diseases caused by single-cell eukaryote parasites that infect red blood cells, with special concern given to vivax malaria, a disease often thought to be benign (if sometimes incapacitating) because the parasite only attacks a small proportion of red blood cells, the very youngest ones. However, I will use mathematical modeling to argue that depletion of this pool of red blood cells can be disastrous to the host if growth of the parasite is not vigorously check by host immune responses. Also, modeling can elucidate aspects of new field observations that indicate that vivax malaria is more dangerous than previously thought.
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Epidemiologic studies and clinical description of severe Plasmodium vivax malaria in adults living in malaria-endemic areas are rare and more attention is needed to understand the dynamics and its interaction with the immune system. This observational study included 1,091 adult patients admitted to medical wards of S. P. Medical College and associated group of hospitals in Bikaner, India from September 2003 through December 2005. The diagnosis of P. vivax malaria was established by peripheral blood film (PBF), rapid diagnostic test (RDT), and polymerase chain reaction (PCR), and severe malaria was categorized as per World Health Organization guidelines. Of 1,091 patients with malaria, 635 had P. falciparum malaria and 456 had P. vivax malaria. Among patients with severe manifestations, 40 had evidence of monoinfection of P. vivax malaria diagnosed by PBF, RDT, and PCR. Complications observed were hepatic dysfunction and jaundice in 23 (57.5%) patients, renal failure in 18 (45%) patients, severe anemia in 13 (32.5%) patients, cerebral malaria in 5 patients (12.5%), acute respiratory distress syndrome in 4 patients (10%), shock in 3 patients (7.5%), and hypoglycemia in 1 (2.5%) patient. Thrombocytopenia was observed in 5 (12.5%) patients, and multi-organ dysfunction was detected in 19 (47.5%) patients. Further large-scale multicentric epidemiologic studies are needed to define the basic pathology of this less known entity.
We report 11 cases of severe Plasmodium vivax malaria in Bikaner (western India). Patients exhibited cerebral malaria, renal failure, circulatory collapse, severe anemia, hemoglobinurea, abnormal bleeding, acute respiratory distress syndrome, and jaundice. Peripheral blood microscopy, parasite antigen-based assays, and parasite 18s rRNA gene-based polymerase chain reaction showed the presence of P. vivax and absence of P. falciparum.
The mechanisms underlying lung injury in vivax malaria are not well understood. Inflammatory responses to Plasmodium falciparum and P. vivax, to our knowledge, have not previously been compared at an organ level.
Respiratory symptoms and physiological aspects were measured longitudinally in Indonesian adults with uncomplicated vivax (n=50) and falciparum (n=50) malaria. Normal values were derived from 109 control subjects. Gas transfer was partitioned into its alveolar-capillary membrane (D(M)) and pulmonary capillary vascular (V(C)) components, to characterize the site and timing of impaired gas transfer.
Mean baseline V(C) volume was significantly reduced in vivax and falciparum malaria, improving with treatment in each species. Baseline D(M) function was not impaired in either species. The progressive deterioration in D(M) function after treatment was statistically significant in vivax malaria but not in uncomplicated falciparum malaria. Oxygen saturation deteriorated after treatment in vivax but improved in falciparum malaria.
The baseline reduction in V(C) volume but not in D(M) function suggests encroachment on V(C) volume by parasitized erythrocytes and suggests that P. vivax-infected erythrocytes may sequester within the pulmonary microvasculature. Progressive alveolar-capillary dysfunction after treatment of vivax malaria is consistent with a greater inflammatory response to a given parasite burden in P. vivax relative to that in P. falciparum.
Among the Plasmodium variants that cause human malaria, vivax malaria is considered to be non-malignant. Recent research has indicated that severe vivax infection can turnout to be as pathological as falciparum. This review evidences microrheologic pathology in vivax malaria, similar to that as seen in malignant falciparum. The parasite invasion, internalization and growth in the RBC lead to membrane rigidification and progressive loss of deformability, rosetting and cytoadherence, enhanced aggregation, clumpy, non-deforming, sticky aggregates and chronic sedimentation profiles. A model that reflects the net effect of these changes is of clinical value to establish disease severity in specific malaria. In this respect an artificial neural network (ANN) model, implemented in malaria severity analysis, is discussed. Results of this model suggest that a good degree of severity classification (60 to 100%) can be achieved even with small sample size (malaria samples n = 12, normal = 10). With larger sample size, ANN may be very apt as microrheological model for severity analysis.
Multiple, prolonged, generalized, or focal seizures are common in children with severe malaria, with or without coma. In other contexts, such seizures have been associated with the development of epilepsy. The relation between falciparum malaria and epilepsy is undetermined; thus we measured the prevalence and characteristics of epilepsy in children with a history of severe malaria.
We took a detailed epilepsy history from the parents of 487 children (aged 6-9 years) to compare the prevalence of epilepsy between three exposure groups: children with a history of cerebral malaria (CM), malaria and complicated seizures (M/S), or those unexposed to either complication. Each child had an EEG and was classified as having active, inactive, or no epilepsy.
An increased prevalence of epilepsy was seen in children previously admitted with CM [9.2%; OR, 4.4; 95% confidence interval (CI), 1.4-13.7] or M/S (11.5%; OR, 6.1; 95% CI, 2.0-18.3) compared with the unexposed group (2.2%). The most commonly reported seizure types were tonic-clonic (42%), focal becoming secondarily generalized (16%), and both (21%). Twenty-six percent of the active epilepsy group initially had EEG abnormalities.
These results suggest that children exposed to CM or M/S have an increased propensity for epilepsy relative to children unexposed to these complications. The prevalence of epilepsy associated with CM is similar to that reported after other severe encephalopathies. The prevalence associated with M/S is more than twice that reported after complicated febrile seizures.