No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Acute Pulmonary Edema Complicating Ovale Malaria
... However, ARDS is not restricted solely to Plasmodium falciparum infection. This potentially grave complication has also been reported in malaria caused by Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi and Plasmodium ovale56789101112. Due to its limited geographical distribution [13], as well as the much lower morbidity [14], P. ovale has been overshadowed by other human malaria parasites in the field of medicine and medical research. ...
... Here, bacterial infection was ruled out as the primary cause of ARDS in patient B as the bacteriological culture showed positive results as late as day 15, whereas he showed symptoms of acute lung injury as early as day 4. Undoubtedly, the bacterial infection that occurred at such critical timing would worsen the health condition of the patient, which acted as the secondary contributing factor towards the fatal end for this case. Another point worth mentioning was the onset of the ARDS symptoms after the initiation of anti-malarial therapy, which was similar to many cases of malaria-associated ARDS reported previously [9,10,3031323334. The pulmonary injury seen in this case was likely to be a post-treatment related pulmonary inflammation. ...
... Severe ovale malaria is not commonly found. There are a few reports of P. ovale infection with ARDS9101112, and one case of ovale malaria with splenic complication [60]. Fatal ovale malaria is even rarer. ...
Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research.
Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure.
Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi.
In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted.
Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission.
... These febrile episodes may occur in intervals of time that can reach several months or years [3,5] and which require a specific treatment with primaquine for complete clearance, obtained after several cures. Severe cases have rarely been described, but could occur nonetheless [6,7] . Plasmodium ovale diagnosis is difficult for several reasons , particularly due to a frequent low level of parasit- aemia [8], and the errors of microscopic diagnosis with other malarial species. ...
... The P. ovale species are considered as neglected. However , severe cases pertaining to acute respiratory symptoms have been reported [6,293031. Other severe cases describe spleen rupture [32,33]. ...
Background
Plasmodium ovale is one of the five malaria species infecting humans. Recent data have shown that the name of this neglected species masks two distinct genotypes also called curtisi and wallikeri. Some authors show that these species could be sympatric. These two subspecies are not differentiated by microscopy techniques and malaria rapid diagnostic tests. This diagnostic defect is the result of low parasitaemia, antigenic polymorphism and absence of antibodies performance and requires the use of sequencing techniques. An accurate and easy discrimination detection method is necessary.
Methods
A new molecular assay was developed to easily identify the two genotypes of P. ovale. This tool allowed the study of 90 blood samples containing P. ovale, confirmed by molecular biology techniques, which were obtained from patients with imported malaria.
Results
The new marker was validated on well genotyped samples. The genotype of 90 P. ovale samples mainly imported from the Ivory Coast and the Comoros Islands was easily and quickly realized. The distribution of the two subspecies was described with a significant number of samples and showed that the two genotypes were present in the studied countries.
Conclusion
This work confirms the presence of the two species in the same country for the first time, in the Ivory Coast and the Comoros Islands. A better genotyping of P. ovale types may improve a better characterization of the clinical pathophysiology for each.
... While patients with uncomplicated malaria usually present with fever and non-specific symptoms, severe and complicated malaria is characterised by multiorgan involvement including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [8][9][10] . Recent years have witnessed a shift in the profile of patients with complicated malaria 5,9 ; multiorgan system failure, ALI and ARDS are being increasingly reported in falciparum malaria 8,9,11,12 and in malaria caused by the species hitherto considered benign, P. vivax [13][14][15][16] , and in P. ovale 17 and P. malariae 18 also. ...
... Pulmonary involvement in vivax and ovale malaria is increasingly being recognised although less frequently than in falciparum malaria 11,12 . While some of these cases could be attributed to mixed infections, published data also point out that ALI/ARDS can develop primarily due to vivax, ovale and malariae malaria [13][14][15][16][17][18] . As compared with patients with severe complicated falciparum malaria with ALI/ARDS, the prognosis is relatively better in ALI/ARDS in patients with benign forms of malaria. ...
Malaria is an important treatable cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the tropics and in the returning traveller in the non-endemic areas. ARDS is an important complication in severe, complicated falciparum malaria and has been described in P. vivax and P. ovale malaria also. Malarial ALI/ARDS is more common in adults than in children. Pregnant women and non-immune individuals are more prone to develop this condition. Increased alveolar capillary permeability resulting in intravascular fluid loss into the lungs appears to be the key pathophysiologic mechanism. In malaria, ARDS can develop either at initial presentation or after initiation of treatment when the parasitaemia is falling and the patient is improving. Patients present with acute onset dysnoea that can rapidly progress to respiratory failure. The diagnosis of malaria is confirmed by slide microscopy supported by the use of rapid antigen tests. Patients with malarial ARDS should be managed in an intensive care unit. Careful attention must be paid to haemodynamic stabilisation and optimising fluid balance. Currently, specific treatment choices for malaria include parenteral artemisinins or intravenous quinine along with doxycycline. Respiratory failure requires endotracheal intubation and assisted mechanical ventilation. Co-existent bacterial sepsis is frequently present in patients with malarial ARDS eventhough an obvious focus may not be evident. Appropriate broad spectrum antibiotic therapy must be started when there is a clinical suspicion after procuring the microbiological specimens. ARDS in malaria is a disease with a high mortality. Early diagnosis, institution of specific antimalarial treatment and assisted ventilation can be life-saving.
... Until recently, it was thought that vivax malaria did not cause pulmonary complications; however, there are now 8 reported cases of ARDS occurring after commencement of therapy for Plasmodium vivax malaria [21][22][23][24][25][26][27][28] and 1 case of ARDS complicating Plasmodium ovale malaria [29]. Microvascular sequestration of parasitized red blood cells is thought to be the pathophysiological mechanism underlying most extrapulmo- nary organ-specific manifestations of severe falciparum malaria. ...
... It is likely that ARDS, now recognized to occur in both falciparum [4,15,16,[55][56][57][58][59][60] and vivax/ovale [21][22][23][24][25][26][27][28][29] malaria, is the extreme end of a predominantly subclinical spectrum of alveolar-capillary pathology in malaria [60,61]. The mechanisms underlying malaria ARDS are not clear. ...
Despite recognition of acute respiratory distress syndrome in both falciparum and vivax malaria, disease-related changes in
pulmonary function have not been defined, and underlying mechanisms are not well understood. Respiratory symptoms, pulmonary
function, pulmonary phagocytic cell activity, and longitudinal changes were examined in 26 adults with uncomplicated falciparum,
vivax, and ovale malaria after treatment. Self-limiting cough occurred in both falciparum (36%) and vivax or ovale (53%) malaria.
In infection with eachmalaria species, admission measures of airflow and gas transfer were lower than predicted, and mean
lung 99mtechnetium-sulfur-colloid uptake was significantly increased. Changes were most evident in falciparum malaria, with treatment
resulting in initial worsening of airflow obstruction and gas transfer. Altered pulmonary function in malaria is common and
includes airflow obstruction, impaired ventilation, impaired gas transfer, and increased pulmonary phagocytic activity, and
its occurrence in both vivax and falciparum malaria suggests that there may be common underlying inflammatory mechanisms.
... The splenic rupture was usually accompanied by internal haemorrhage and highly associated with severe malaria infection [56]. Splenectomy was usually performed due to such complications [57]. ...
Plasmodium knowlesi (P. knowlesi), is a simian malaria parasite and currently the dominant species in the Malaysian Borneo of Sabah and Sarawak. This parasite is transmitted by Anopheles balabacensis and the macaques of Macaca fascicularis and Macaca nemestrina, and monkeys of Presbytis melalophos are the reservoir hosts. The zoonotic disease, infection by P. knowlesi infection can cause a wide range of immunological responses in human comparable to other human malaria parasites including acute respiratory distress syndrome (ARDS), acute renal failure (ARF) and cerebral malaria (CM), leading to the pathological consequences in humans and macaques alike. Similar to other malaria species especially P. falciparum, pathological features such as sequestration of parasitised red blood cells (pRBC) and mononuclear cells-containing haemozoin, deposition of haemozoin on numerous tissues and petechial and/or focal haemorrhage could be observed in P. knowlesi infection. Diagnosis of P. knowlesi mainly involves microscopic examination on both thick and thin blood smears stained with Giemsa, nevertheless confirmation test by using Polymerase Chain Reaction (PCR) is compulsory. Most P. knowlesi cases are treated with artemisinin-combination therapy (ACT) or chloroquine in uncomplicated cases while artesunate followed by ACT in complicated or severe cases. Without accurate and timely means of diagnosis and treatment, the outcomes of death might happen. The pathological features of P. knowlesi malaria infection in multiple organs are described in this review.
... The relapsing human malaria parasites P. vivax and P. ovale are difficult to distinguish morphologically (Wenk and Stephens, 2000) and have both common and unique characteristics. The natural host of both parasites is man, both parasites are thought to form dormant liver stages [hypnozoites (Garnham et al., 1955;Coatney, 1976;Krotoski, 1985;Soulard et al., 2015)] that unpredictably reactivate in a strain-dependent manner (Battle et al., 2014;Veletzky et al., 2018) to produce relapses (Chin and Contacos, 1966;Chin and Coatney, 1971;Goljan et al., 2003;Centers for Disease and Prevention, 2005;Richter et al., 2010;Morgan et al., 2012;Groger et al., 2017) and form sexual transmissible stages called gametocytes from the very beginning of the sometimes still asymptomatic blood stage infection (Mckenzie et al., 2007;Mueller et al., 2009); both are characterized by a reticulocyte-restricted invasion phenotype (Kitchen, 1938;Rutledge et al., 2017;Thomson-Luque et al., 2019) and a clinical course that had originally been described as mild and benign (Kitchen, 1946;Kitchen, 1949;Collins and Jeffery, 2002;Collins and Jeffery, 2005) but can in fact be very severe (Maguire and Baird, 2010) including spontaneous spleen rupture (Facer and Rouse, 1991;Cinquetti et al., 2010;Zidouh et al., 2017), acute respiratory distress syndrome (Rojo-Marcos et al., 2008;Haydoura et al., 2011;Lacerda et al., 2012;Lau et al., 2013;Guerpillon et al., 2019) and lung injury (Lee and Maguire, 1999;Anstey et al., 2002;Anstey et al., 2007), acute pericarditis (Coton et al., 2011), myocardial infarction (Martin Polo et al., 2020), severe anemia (Erel et al., 1997;Hemmer et al., 2006;Douglas et al., 2012;Johnson et al., 2013;Graciaa et al., 2019), and cerebral malaria (Tanwar et al., 2011). ...
Malaria remains a serious health concern across the globe. Historically neglected, non-Falciparum human malarias were put back on the agenda by a paradigm shift in the fight against malaria from malaria control to malaria eradication. Here, we review the modeling of the relapsing parasites Plasmodium vivax (P. vivax) and Plasmodium ovale (P. ovale) in non-human primates with a specific focus on the contribution of these models to our current understanding of the factors that govern parasite-host interactions in P. vivax and P. ovale parasite biology and pathophysiology.
... Severe complications, sometimes with fatal outcome, can be caused by other malaria parasites as well. Severe malaria can manifest in the form of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), splenic rupture, hypoglycaemia, placental malaria, hypotension and shock, thrombocytopaenia, hyperparastiaemia, as well as severe anaemia (Martell et al., 1979;Lee et al., 1999;Tanois et al., 2001;Prakash et al., 2003;Trampuz et al., 2003;Lomar et al., 2005;Anstey et al., 2007;Uneke et al., 2007;Cox-Singh et al., 2008;Das, 2008;Mohan et al., 2008;Rojo-Marcus et al., 2008;Thapa et al., 2009;Lacerda et al., 2011;Deroost et al., 2013;Hachimi et al., 2013;Lau et al., 2013;Lee et al., 2013a). ...
Rosette formation is one of the unique biological phenomena that have been linked to
pathobiology of malaria. It is believe to be associated with the severe outcomes of
falciparum malaria. Most of the knowledge about rosetting is obtained from in-depth
studies conducted on Plasmodium falciparum. However, the rosetting phenomenon and
pathobiology of vivax malaria is not well studied. This research project aimed at
deciphering the unknown aspects behind rosetting phenomenon of P. vivax, and
investigating the role of rosette formation in pathobiology of vivax malaria. In total, 121
fresh P. vivax isolates, 48 cryopreserved P. vivax isolates, 122 fresh P. falciparum
isolates and 5 cryopreserved P. falciparum isolates were recruited into this research
project. A novel technique suitable for reticulocyte characterization and rosetting assay
in field setting was developed from this research project. Based on the field studies
conducted, rosette formation is common in P. vivax. However, rosetting is not
significantly correlated to clinical parameters such as reticulocyte count and
parasitaemia. Besides, cryopreservation and thawing processes affect the rosetting
capability of P. vivax isolates. Rosette formation was found to be initiated at the early
trophozoite stage of P. vivax and the rosetting development reached plateau at the end
of the erythrocytic maturation. Giant rosettes were found more frequently in P. vivax
than P. falciparum. In addition, gametocytes were found to be involved in rosette
formation. Unlike P. falciparum, the rosetting phenomenon of P. vivax is independent
of human ABO blood groups and complement receptor 1 (CR1/CD35). However,
rosetting phenomena of P. vivax and P. falciparum are dependent on the BRIC4 region
of human glycophorin C (CD236R), strongly indicating the BRIC4 region of CD236R
as another rosetting coreceptor for P. vivax and P. falciparum. On elucidating the roles
of rosette formation in pathobiology of malaria, the significantly high preference for
normocytes instead of reticulocytes in rosette formation clearly shows that rosetting is
unlikely to assist merozoite reinvasion in vivax malaria. Furthermore, increased
rosetting rates upon exposure to anti-malaria drug compounds and human white blood
cells suggest that the rosetting phenomenon may serve as an intrinsic protective
mechanism of the malaria parasites against their environmental threats.
... L'infection à P. ovale est généralement bénigne mais peut récidiver après des mois. Trois cas de paludisme grave à P. ovale ont été néanmoins rapportés (Lee et Maguire, 1999 ;Rojo-Marcos et al., 2008 ;Rozé et al., 2011). Stinton et Mulligan (1932) est génétiquement proche de P. vivax et infecte naturellement les macaques (Singh et al., 2004). ...
À Anonkoua-kouté, les fréquences des génotypes de Plasmodium falciparum conférant la résistance à la SP et à la CQ ont atteint des niveaux comparables entre isolats d’écoliers asymptomatiques et ceux issus d’enfants symptomatiques en 2008. Les seules différences significatives ont concerné les génotypes AAKAA (35,7 % parmi les enfants asymptomatiques) et SGKAA (32,3 % au sein des participants symptomatiques). A Bonoua et Samo, des niveaux comparables de fréquences ont été aussi déterminés entre individus symptomatiques malgré la différence des faciès épidémiologiques. La diversité allélique a été plus grande dans la localité rurale de Samo avec plusieurs génotypes dont les doubles mutant FAKAS (3,3 %), YAKAS (3,3 %), ou le triple mutant AGKAS (3,3 %). Les isolats issus de Bonoua ont une diversité allélique très réduite avec 4 génotypes du gène pfdhfr, trois génotypes pour le gène pfdhps dont le mixte SL-GKAA (58,5 %), et le génotype CVIET (100 %) pour le gène pfcrt. Les fréquences des mutants IRNI, SGKAA et CVIET ont été plus élevées à Anonkoua-kouté et à Ayamé, tandis que le génotype sensible CVMNK a été prédominant à Dabakala. Au cours de la période 2002 à 2008, les prévalences ont augmenté à Anonkoua-kouté (Test de Cochrane-Armitage ; z > 0) pour les allèles Asn-108 (p = 0,023) et Gly-437 (p = 0,028).Des tendances contraires ont été mises en évidence (Test de Cochrane-Armitage ; z < 0) pour les allèles sensibles Ser-108 (p = 0,017) et Ala-437 (p = 0,043). De même, une baisse significative (Test de Cochrane- Armitage ; z < 0) de la prévalence du génotype NCSI (p < 0,0001) a été aussi mise en évidence. Une augmentation significative (Test de Cochrane-Armitage ; z > 0) des prévalences du génotype AGKAA (p = 0,036 ; z > 0) a été déterminée en même temps que la baisse significative du génotype sensible SAKAA (p = 0,027 ; z < 0). Enfin, le nombre minimum de parasites détectés par infection est passé de 3 à 2 clones entre 2002 et 2008 à Anonkoua-kouté.
... This results in the accumulation of monocytes and the aftermath effects lead to malaria-associated ALI/ARDS. In human malaria infection, there have been reported cases of ALI/ARDS associated with P. falciparum (Genrich et al., 2007;Maguire et al., 2005), P. vivax (Anstey et al., 2007;Tan et al., 2008;Valecha et al., 2009) and P. ovale (Lee & Maguire, 1999;Rojo-Marcos et al., 2008). Also, several murine model studies have been used to demonstrate the pathogenesis of malaria-associated ALI/ARDS (Deroost et al., 2013;Hee et al., 2011;Helegbe et al., 2011;Lovegrove et al., 2008). ...
Co-infection with multiple different parasites is a common phenomenon in both human and animals. Among parasites that frequently co-infect the same hosts, are the filarial worms and malaria parasites. Despite this, the mechanisms underlying the interactions between these parasites is still relatively unexplored with very few studies available on the resulting pathologies due to co-infection by filarial nematodes and malaria parasites. Hence, this study investigated the histopathological effect of Brugia pahangi and Plasmodium berghei ANKA (PbA) infections in gerbil host. Gerbils grouped into B. pahangi-infected, PbA-infected, B. pahangi and PbA-coinfected, and uninfected control, were necropsied at different time points of post PbA infections. Brugia pahangi infections in the gerbils were first initiated by subcutaneous inoculation of 50 infective larvae, while PbA infections were done by intraperitoneal injection of 10 6 parasitized red blood cells after 70 days patent period of B. pahangi. Organs such as the lungs, kidneys, spleen, heart and liver were harvested aseptically at the point of necropsy. There was significant hepatosplenomegaly observed in both PbA-infected only and coinfected gerbils. The spleen, liver and lungs were heavily pigmented. Both B. pahangi and PbA infections (mono and co-infections) resulted in pulmonary edema, while glomerulonephritis was associated with PbA infections. The presence of both parasites induced extramedullary hematopoiesis in the spleen and liver. These findings suggest that the pathologies associated with coinfected gerbils were synergistically induced by both B. pahangi and PbA infections.
... We encountered subconjunctival haemorrhages with purpura and/or urticaria in four cases, symptoms suggestive of shock lung in 3, pulmonary oedema in 2, severe anaemia (HB less than 4 g% Furthermore, ARDS is now being increasingly observed even in species which were considered benign, i.e., P. vivax, P. ovale and P. malariae. 19,20 Lung injury in malaria occurs as a result of erythrocyte sequestration and destruction, the release of parasite and erythrocyte material into the circulation, and the host response to these events. The rupture of meronts (meronts divide to produce merozoites) release proinflammatory mediators such as TNF-α, IL -1, IL-6 and IL -8. ...
Acute Respiratory Distress Syndrome (ARDS) constitutes a heterogeneous group of disorders characterised by increased permeability of pulmonary capillary endothelial cells and alveolar epithelial cells, leading to hypoxemia that is refractory to usual oxygen therapy. This leads to acute pulmonary insufficiency, leading to respiratory failure with high mortality, even in this era of lung protective ventilation.1 ARDS was first described in 1967 in a series of 12 patients, seven of whom had sustained multiple trauma; one had acute pancreatitis while four had unspecified (possibly viral) pneumonia or drug ingestion.2 The definition of ARDS has evolved over time since its first inception in 1994 by the American-European Consensus Conference (AECC).3 The most recent Berlin Definition of ARDS defines ARDS as " acute onset respiratory failure with PaO2/FiO2 ≤ 300 with PEEP or CPAP ≥5 cm H2O originating within 1 week of a known clinical insult or new or worsening respiratory symptoms, characterised by bilateral opacities – not fully explained by effusions, lobar/lung collapse, or nodules and not fully explained by cardiac failure of fluid overload. " 4 Lung injury in ARDS occurs due to both direct and indirect mechanisms, arising as a result of several medical, surgical and obstetric disorders. Among these, pulmonary infections and sepsis are the most common. Of particular importance in the tropical regions are the tropical infections, poisoning and inhalational injuries, many of which are unique to this part of the world, as listed in table 1. Tuberculosis Tuberculosis (TB) remains a major and global health disease which usually has a subacute or chronic clinical presentation. In India, the annual incidence is 168 per lakh and the prevalence is 249 per lakh population. WHO estimated TB mortality of 23 per lakh population in 2009 in India.5 TB rarely may present with respiratory failure and ARDS; this is more common in advanced tubercular bronchopneumonia and miliary TB. Prolonged illness, absolute lymphocytopenia and elevated transaminases protend higher risk.6 Miliary TB with ARDS has a high mortality ranging between 33-90% and duration of miliary TB beyond 20 days tends to markedly increase the risk of ARDS.7,8 In a retrospective study from South Korea, in 90 patients with TB who presented with ARDS, those with miliary TB were younger, required fewer days on mechanical ventilation, were more likely to have extrapulmonary involvement and a lesser incidence of DIC as a complication. The mortality was lower in the group with military TB than those with TB bronchopneumonia (58% vs 68%).
... Indeed, it is considered by some to be "the benign malaria," with less complicated course (4). However there have been many well documented case reports of severe complications associated with P. ovale such as acute respiratory distress syndrome (ARDS), acute renal failure (ARF) and splenic infarction [22][23][24]. Globalization, international travel, and migration have increased the incidence of imported malaria in industrialized countries. For example, P. ovale infections represent up to 8% of imported malaria cases in Italy (mainly from West Africa) [25]. ...
Accurate diagnosis of malaria infections continues to be challenging and elusive, especially in the detection of submicroscopic infections. Developing new malaria diagnostic tools that are sensitive enough to detect low-level infections, user friendly, cost effective and capable of performing large scale diagnosis, remains critical. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. ovale by real-time PCR. In our study, a total of 173 clinical samples, consisting of different malaria species, were utilized to test this novel PET-PCR primer. The sensitivity and specificity were calculated using nested-PCR as the reference test. The novel primer set demonstrated a sensitivity of 97.5% and a specificity of 99.2% (95% CI 85.2–99.8% and 95.2–99.9% respectively). Furthermore, the limit of detection for P. ovale was found to be 1 parasite/μl. The PET-PCR assay is a new molecular diagnostic tool with comparable performance to other commonly used PCR methods. It is relatively easy to perform, and amiable to large scale malaria surveillance studies and malaria control and elimination programs. Further field validation of this novel primer will be helpful to ascertain the utility for large scale malaria screening programs. © 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
... Nevertheless, severe cases of P. ovale sp. pertaining to acute respiratory symptoms and renal failure have been reported [27][28][29]. Plasmodium ovale cases have the potential to relapse if misdiagnosed as P. falciparum and incorrect treatment provided. Furthermore, treatment based on an incorrect diagnosis leads to misuse of anti-malarial drugs as well as drug wastage. ...
Background
Following initiation of China’s National Malaria Elimination Action Plan in 2010, indigenous malaria infections in Jiangsu Province decreased significantly. Meanwhile imported Plasmodium infections have increased substantially, particularly Plasmodium ovale and Plasmodium malariae. Given the risk for malaria resurgence, there is an urgent need to understand the increase in imported P. ovale and P. malariae infections as China works to achieve national malaria elimination. Methods
An observational study of imported malaria cases in Jiangsu Province, China was carried out for the period of 2011–2014. ResultsA total of 1268 malaria cases were reported in Jiangsu Province from 2011 to 2014. Although imported Plasmodium falciparum cases (n = 1058) accounted for 83.4 % of all reported cases in Jiangsu, P. ovale cases (14, 19, 30, and 46) and their proportion (3.7, 9.6, 8.8, and 13.0 %) of all malaria cases increased over the 4 years. Similarly, P. malariae cases (seven, two, nine, and 10) and proportion (1.9, 1.0, 2.6, and 2.8 %) of all malaria cases increased slightly during this time. A total of 98 cases of Plasmodium ovale curtisi (47/98, 48 %) and Plasmodium ovale wallikeri (51/98, 52 %) were identified as well. Latency periods were significant among these Plasmodium infections (p = 0.00). Also, this study found that the latency periods of P. ovale sp., P. malariae and Plasmodium vivax were significantly longer than P. falciparum. However, for both P. ovale curtisi and P. ovale wallikeri infections, the latency period analysis was not significant (p = 0.81). Misdiagnosis of both P. ovale and P. malariae was greater than 71.5 and 71.4 %, respectively. The P. ovale cases were misdiagnosed as P. falciparum (35 cases, 32.1 %), P. vivax (43 cases, 39.4 %) by lower levels of CDCs or hospitals. And, the P. malariae cases were misdiagnosed as P. falciparum (ten cases, 35.7 %), P. vivax (nine cases, 32.1 %) and P. ovale sp. (one case, 3.6 %). Geographic distribution of imported P. ovale sp. and P. malariae cases in Jiangsu Province mainly originated from sub-Saharan Africa such as Equatorial Guinea, Nigeria, and Angola. Conclusions
Although the vast majority of imported malaria cases were due to P. falciparum, the increase in other rare Plasmodium species originating from sub-Saharan Africa and Southeast Asia should be closely monitored at all levels of health providers focusing on diagnosis and treatment of malaria. In addition to a receptive vector environment, long latency periods and misdiagnosis of P. malariae and P. ovale sp. increase the risk of re-introduction of malaria in China.
... Lung involvement in malaria has been described most often in non-immune individuals, with infection by Plasmodium falciparum [6][7][8][9], Plasmodium ovale [7,10,11], Plasmodium vivax and Plasmodium malariae [6,7,[12][13][14][15][16]. While the alveoli and airways can also be involved in mild infection [17], acute alveolar injury and acute respiratory distress syndrome (ARDS) are major sequelae of severe malaria and have significant morbidity and mortality [3,[17][18][19]. Malaria-associated ARDS (MA-ARDS) has been reported in infection with all human malarial parasites, although the greatest number of cases is caused by P. falciparum and P. vivax [17,20,21]. ...
Background:
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a potentially lethal complication of clinical malaria. Acute lung injury in MA-ARDS shares features with ARDS triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. Mechanisms and physiologic alterations in MA-ARDS can be examined in murine models of this syndrome. Integrin αDβ2 is a member of the leukocyte, or β2 (CD18), sub-family of integrins, and emerging observations indicate that it has important activities in leukocyte adhesion, accumulation and signalling. The goal was to perform analysis of the lungs of mice wild type C57Bl/6 (a D (+/+) ) and Knockout C57Bl/6 (a D (-/-) ) with malaria-associated acute lung injury to better determine the relevancy of the murine models and investigate the mechanism of disease.
Methods:
C57BL/6 wild type (a D (+/+) ) and deficient for CD11d sub-unit (a D (-/-) ) mice were monitored after infection with 10(5) Plasmodium berghei ANKA. CD11d subunit expression RNA was measured by real-time polymerase chain reaction, vascular barrier integrity by Evans blue dye (EBD) exclusion and cytokines by ELISA. Protein and leukocytes were measured in bronchoalveolar lavage fluid (BALF) samples. Tissue cellularity was measured by the point-counting technique, F4/80 and VCAM-1 expression by immunohistochemistry. Respiratory function was analysed by non-invasive BUXCO and mechanical ventilation.
Results:
Alveolar inflammation, vascular and interstitial accumulation of monocytes and macrophages, and disrupted alveolar-capillary barrier function with exudation of protein-rich pulmonary oedema fluid were present in P. berghei-infected wild type mice and were improved in αDβ2-deficient animals. Key pro-inflammatory cytokines were also decreased in lung tissue from α D (-/-) mice, providing a mechanistic explanation for reduced alveolar-capillary inflammation and leak.
Conclusions:
The results indicate that αDβ2 is an important inflammatory effector molecule in P. berghei-induced MA-ARDS, and that leukocyte integrins regulate critical inflammatory and pathophysiologic events in this model of complicated malaria. Genetic deletion of integrin subunit αD in mice, leading to deficiency of integrin αDβ2, alters lung inflammation and acute lung injury in a mouse model of MA-ARDS caused by P. berghei.
... The accurate diagnosis of P. ovale infection, in fact of all malaria infection, is crucial to avoid the delay of treatment and clinical complications. Though ovale malaria is thought to be rather benign, associated severe complications such as acute respiratory distress syndrome (ARDS) [31,32], splenic complication [33], acute renal failure and ultimately, death [18,34] have been reported. There are certain clinical features slightly distinctive of the two different forms of P. ovale. ...
Plasmodium ovale is rare and not exactly known to be autochthonous in Malaysia. There are two distinct forms of the parasite, namely P. ovale curtisi (classic form) and P. ovale wallikeri (variant form). Here, the first sequence confirmed case of an imported P. ovale wallikeri infection in Malaysia is presented. Microscopy found Plasmodium parasites with morphology similar to P. ovale or Plasmodium vivax in the blood films. Further confirmation using polymerase chain reaction (PCR) targeting the small-subunit rRNA gene of the parasite was unsuccessful. Genus-specific PCR was then performed and the product was sequenced and analysed. Sequence analyses confirmed the aetiological agent as P. ovale wallikeri. New species-specific primers (rOVA1v and rOVA2v) were employed and P. ovale wallikeri was finally confirmed. The findings highlight the need to look out for imported malaria infections in Malaysia and the importance of a constantly updated and validated diagnostic technique.
... These include presentations with ARDS, jaundice, renal failure, incipient bleeding, metabolic acidosis, hypotension, splenic rupture and splenic infarction; with death occurring in three out of 10 cases reported. 4,[9][10][11][12][13][14][15][16][17] Our patient was diagnosed with P. ovale infection complicated with jaundice, thrombocytopenia, hypotension and acute renal failure and responded excellently with IV artesunate, which is the treatment of choice for severe malaria according to WHO guidelines. As P. ovale is known to cause relapse after 2 to 3 years, prophylaxis with Primaquine was also prescribed for the patient. ...
Malaria has emerged as a major public health problem worldwide. Complications are commonly seen in Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax) infection, but due to Plasmodium ovale (P. ovale) infection is rarely described in literature. Here we report a case of severe disease due to P. ovale infection complicated with jaundice, thrombocytopenia, hypotension and acute renal failure.
© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
... 35 Respiratory distress may occur in up to 20% of adults with severe falciparum malaria, though less frequently with vivax and ovale malaria. 36,37 Respiratory compromise is usually a multifactorial process arising from a combination of severe anemia, non-cardiogenic pulmonary edema, coexisting pneumonia, and the respiratory compensation resulting from the metabolic acidosis. Respiratory failure can progress to acute lung injury (ALI) or adult respiratory distress syndrome (ARDS) and the need for mechanical ventilation. ...
Malaria is a life-threatening infectious disease caused by the Plasmodium parasite. Increased global travel has resulted in an escalation in the number of imported cases seen in developed countries. Patients with malaria may present for surgery in both endemic and non-endemic countries. This article reviews the perioperative considerations when managing patients with malaria.
A literature review of anesthesia, perioperative care, and malaria-related articles was performed using the MEDLINE(®), EMBASE™, and Web of Science databases to identify relevant articles published in English during 1945-2014. Of the 303 articles matching the search criteria, 265 were excluded based on title and abstract. Eleven of the remaining 38 articles were relevant to anesthesia/perioperative care, and 27 articles were identified as having direct relevance to critical care medicine.
The majority of imported malaria cases are caused by the falciparum species, which is associated with the greatest degree of morbidity and mortality. Various organ systems may be impacted as a consequence of changes in the structure and function of parasitized erythrocytes. Preoperative assessment should focus on establishing the species of malaria, the severity of disease, assessing the degree of end-organ impairment, and initiating treatment of malaria prior to surgery. Intravenous artesunate is the treatment of choice for severe falciparum malaria. Quinine is a second-line agent but has a narrow therapeutic index and particularly hazardous side effects. Intraoperatively, attention should focus on fluid management, dynamics of cerebral blood flow, and avoidance of hypoglycemia. Postoperative care of severe cases should ideally take place in a critical care unit as there may be ongoing requirements for multi-organ support, including renal replacement therapy, ventilation, and/or inotropic support. The safety of neuraxial anesthesia has not been well studied in the setting of malaria.
Malaria remains one of the most devastating infectious diseases worldwide. Multiple organ systems can be impacted as a consequence of changes in structure and function of parasitized erythrocytes. Safe perioperative management requires a sound knowledge of all these potential system effects.
... Literature describing severe or complicated cases of P. ovale infection is limited. These rare reports include six cases complicated by acute respiratory distress syndrome (ARDS)(one of which further complicated by renal failure and metabolic acidosis), two cases of splenic rupture, and a single case of splenic infarction [16][17][18][19][20][21][22][23][24][25]. Clinical and therapeutic data for these cases are shown in Table 1. ...
Severe malaria is most commonly associated with Plasmodium falciparum. Plasmodium vivax is increasingly recognized as being capable of causing severe disease. In contrast, Plasmodium ovale is considered as a cause of benign disease and evidence supporting the occurrence of severe or complicated ovale infection is rare. This report describes a case of severe P. ovale infection in a patient presenting with jaundice, respiratory distress, severe thrombocytopenia, petechiae, and hypotension. He had no apparent underlying risk factors for severe disease.
... Severe ARDS most commonly complicates P. falciparum infection and is rarely a complication of P. vivax or P. ovale infection. This could be related to differences in cyto-adhesion of infected erythrocytes [26][27][28][29]. However, it should be stressed that it is difficult to definitely establish malaria as the sole etiology for severe ARDS, fully excluding bacterial co-infection. ...
Severe malaria may be complicated by the acute respiratory distress syndrome (ARDS), which is associated with a high mortality. In the present report, a series of three cases of imported malaria complicated by refractory severe ARDS supported with extracorporeal membrane oxygenation (ECMO) is presented.
One female and two male adult patients (ages 39 to 53) were included. Two patients had Plasmodium falciparum infection and one patient had Plasmodium vivax and Plasmodium ovale co-infection. Anti-malarial therapy consisted in intravenous quinine (in two patients) and intravenous quinidine (in one patient), plus clindamycin or doxycycline.
Despite lung protective ventilation, a conservative strategy of fluid management, corticosteroids (two patients), prone position (two patients) and inhaled nitric oxide (one patient), refractory severe ARDS supervened (PaO2 to FiO2 ratio 68) and venovenous ECMO was then initiated. In one patient, a bicaval dual-lumen cannula was inserted; in the two other patients, a two-site configuration was used. Two patients survived to hospital-discharge (duration of ECMO support: 8.5 days) and one patient died from nosocomial sepsis and multi-organ failure after 40 days of ECMO support.
ECMO support allowed adequate oxygenation and correction of hypercapnia under lung protective ventilation, therefore reducing ventilator-induced lung injury. ECMO referral should be considered early in malaria complicated by severe ARDS refractory to conventional treatment.
... Radiographic and CT findings are consistent with noncardiogenic pulmonary edema. Pleural effusion, diffuse interstitial edema, and lobar consolidation may also be seen (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Occasionally, bronchiolitis obliterans organizing pneumonia has been reported (22). ...
A broad spectrum of parasitic infections frequently affects the lungs, mediastinum, and thoracic wall, manifesting with abnormal
imaging findings that often make diagnosis challenging. Although most of these infections result in nonspecific abnormalities,
familiarity with their imaging features and the diagnostic pathways help the radiologist to formulate an adequate differential
diagnosis and to guide diagnosticians in reaching a definitive diagnosis.
... Recent years have witnessed a shift in the profile of patients with complicated malaria (reviewed in [3]). Multi-organ system failure and respiratory complications are being increasingly reported not only for P. falciparum infections but also for malaria caused by P. vivax [26,27,28,29], P. ovale [30] and P. malariae [31], usually considered benign Plasmodium species. In fact, it has been suggested that as many as 5% of patients with uncomplicated malaria and 20–30% of patients with severe and complicated malaria requiring intensive care unit admission may develop ALI/ ARDS, often after treatment has been initiated [3]. ...
The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.
... Patients with falciparum malaria who develop respiratory distress have a relatively poor prognosis [13], and both of our patients who died developed this complication. Respiratory distress has also been reported as a rare complication of vivax [15][16][17] and ovale [18,19] malaria. We cannot explain the disproportionate number of female patients with this complication in the P. knowlesi group. ...
Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections.
In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.
Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).
Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.
... P. ovale usually causes mild disease without complications, and only one case of ARDS has been reported up to now in the medical literature. 2 Here we present the second description of this pulmonary complication in a P. ovale acute infection. ...
Acute respiratory distress syndrome is a well-known complication in Plasmodium falciparum infection. It is less frequently described in Plasmodium vivax, and only one case is reported in Plasmodium ovale. Here we present the second description of this pulmonary complication in a P. ovale acute infection.
The fatality of malaria is quite prominent worldwide, which is majorly affecting developing nations having subtropical to tropical climate. The disease burden is quite hefty and its eradication is of utmost importance for the economic development of nations. Many chemical control methods have been used in the past decades, but these methods have been turned obsolete due to the development of resistance of the parasite Plasmodium and the vector Anopheles sp. A new potent method has been developed which focuses on the elimination of the parasite, using the mutualistic interactions between the naturally present microbiota in the mosquito midgut and the mosquito itself; which is termed as symbiotic control. Here we focus on the yeast Wickerhamomyces anomalus and elucidate its mutualistic interactions with Anopheles sp. which can help eradicate the fatal malarial infection.
Malaria, a major global public health problem, is mainly caused by Plasmodium falciparum and Plasmodium vivax, and is responsible for nearly half a million deaths annually. Although P. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome (ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex (P = 0.013), having any comorbidity (P = 0.036), lower body temperature (P = 0.032), lower hemoglobin (P = 0.043), and oxygen saturation (P = 0.053) values were significantly associated with mortality. Plasmodium vivax malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of P. vivax malaria and its associated respiratory complications.
The prevalence of malaria is becoming polarized. This chapter first deals with the malaria-causing parasite, Plasmodium falciparum, its epidemiology, and the clinical manifestation and disease pathogenesis. Susceptibility to severe malaria manifestations varies across individuals, with underlying host immunity as a major determinant of susceptibility. Malaria-infected hosts can generate a wide range of immune responses to malaria parasites and/or parasite antigens. Host antibody response is one of the most important components of protective immunity in malaria. The chapter then discusses other parasites P. vivax, P. malariae, P. ovale, and P. knowlesi. Accurate diagnosis of malaria is essential, particularly in areas where there is resistance to control measures. The chapter also discusses treatment, prevention and control of malaria, and ends with a note on the re-emergence of malaria.
Background
Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale—nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi—largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. Methods and resultsThis systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. Conclusions
Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale’s first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.
Malaria is an infectious disease caused by one or more of several species of the protozoan parasite Plasmodium including P. falciparum, P. vivax, P. ovale, P. malariae [1] and occasionally other Plasmodium species, notably monkey malaria P. knowlesi [2]. The infection is primarily transmitted by the bite of an infected Anopheles mosquito but may also be transmitted via transfusion of infected blood products and congenitally. Malaria is a global public health problem with the highest burden in tropical and subtropical countries including India. In 2010, an estimated 3.3 billion population were at risk for malaria, with 216 million cases diagnosed and 655,000 deaths. Most deaths occurred in African children [3]. India accounts for 66 % of the 2.4 million confirmed malaria cases in Southeast Asia, with P. falciparum causing 50 % of them. Malaria is imported into temperate zones, with 10,000 cases per year in western Europe and approximately 1,500 cases per year in the United States [4, 5]. Although malaria is a preventable and treatable disease, controlling and eradicating the disease remain elusive goals.
Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P. vivax and P. ovale have also rarely caused pulmonary edema.
Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.
Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial sepsis that may not be clinically obvious. Clinicians should employ a low threshold for starting broad spectrum antibacterials in such patients, after taking pertinent microbiologic specimens. Despite optimal management, the prognosis of severe malaria with ARDS is poor.
ALI/ARDS in pediatric malaria appears to be rare. However, falciparum malaria with severe metabolic acidosis or acute pulmonary edema may present with a clinical picture of pneumonia, i.e. with tachypnea, intercostal recession, wheeze or inspiratory crepitations. This results in diagnostic confusion and suboptimal treatment. Whilst this is increasingly being recognized in malaria-endemic countries, clinicians in temperate zones should be aware that malaria may be a possible cause of ‘pneumonia’ in a visiting or returning child.
We report the first evidence of sympatric distribution of Plasmodium ovale curtisi and P. ovale wallikeri from India.
Fingerprick blood samples were collected from fever cases in district Bastar, Chhattisgarh State for malaria screening by microscopy and PCR.
Two cases of mono infection of P. ovale, and a fatal case of cerebral malaria with a mixed infection of P. vivax, P. falciparum and P. ovale were confirmed by PCR. Sequencing analysis revealed the presence of P. ovale curtisi and P. ovale wallikeri.
This study highlights the need of molecular diagnosis of malaria cases in forested areas for treatment and control.
© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Severe malaria causes nearly one million deaths annually in endemic areas and is a public health priority worldwide. Severity associated with the occurrence of acute respiratory distress syndrome (ARDS) is a well-known complication of infection with Plasmodium falciparum and can reach 25% of infected adults. However, ARDS is less often described with other Plasmodium species. We report the case of a young Moroccan soldier who died in an array of ARDS related to malaria of Plasmodium ovale 7 months after his return from an endemic country.
Severe malaria causes nearly one million deaths annually in endemic areas and is a public health priority worldwide. Severity associated with the occurrence of acute respiratory distress syndrome (ARDS) is a well-known complication of infection with Plasmodium falciparum and can reach 25% of infected adults. However, ARDS is less often described with other Plasmodium species. We report the case of a young Moroccan soldier who died in an array of ARDS related to malaria of Plasmodium ovale 7 months after his return from an endemic country.
Copyright © 2013. Published by Elsevier Masson SAS.
Respiratory distress develops in up to 25% of adults and 40% of children with severe falciparum malaria. Its diverse causes include respiratory compensation of metabolic acidosis, noncardiogenic pulmonary edema, concomitant pneumonia, and severe anemia. Patients with severe falciparum, vivax, and knowlesi malaria may develop acute lung injury (ALI) and ARDS, often several days after antimalarial drug treatment. ARDS rates, best characterized for severe Plasmodium falciparum, are 5% to 25% in adults and up to 29% in pregnant women; ARDS is rare in young children. ARDS pathophysiology centers on inflammatory-mediated increased capillary permeability or endothelial damage leading to diffuse alveolar damage that can continue after parasite clearance. The role of parasite sequestration in the pulmonary microvasculature is unclear, because sequestration occurs intensely in P falciparum, less so in P knowlesi, and has not been shown convincingly in P vivax. Because early markers of ALI/ARDS are lacking, fluid resuscitation in severe malaria should follow the old adage to "keep them dry." Bacteremia and hospital-acquired pneumonia can complicate severe malaria and may contribute to ALI/ARDS. Mechanical ventilation can save life in ALI/ARDS. Basic critical care facilities are increasingly available in tropical countries. The use of lung-protective ventilation has helped to reduce mortality from malaria-induced ALI/ARDS, but permissive hypercapnia in unconscious patients is not recommended because increased intracranial pressure and cerebral swelling may occur in cerebral malaria. The best antimalarial treatment of severe malaria is IV artesunate.
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.
46year old female presented with a one week history of high grade fever, chills, cough, and severe nausea. The patient had been admitted a month earlier with severe lower gastrointestinal bleeding from hemorrhoids necessitating transfusion of 7 units of packed red blood cells. Initial work-up was unremarkable. Because of persistent symptoms, the patient was admitted 2 days later. Malaria smear was positive. Due to the severity of her symptoms, she was managed as falciparum malaria and was started on intravenous quinine and oral doxycycline. On the second day of treatment the patient developed respiratory failure, requiring intubation and ventilatory support with new bilateral pulmonary infiltrates. Antimalarial treatment was continued for a total of 7 days followed by primaquine for 14 days once the blood smear results revealed Plasmodium ovale infection. The patient remained intubated in the intensive care unit (ICU) for 16 days, and was later extubated successfully with a clear chest x-ray after a total of one month hospitalization. To our knowledge, this is the first case of acute respiratory distress syndrome (ARDS) secondary to blood transfusion related P. ovale malaria infection in a non-endemic country.
Malaria remains a major health problem in much of Asia and Africa. A steady number of cases of imported malaria are also seen in many countries of the developed world. Plasmodium falciparum malaria and to some extent malaria caused by other species of Plasmodium can lead to many complications such as acute respiratory distress syndrome (ARDS), cerebral malaria, acute renal failure, severe anemia, thrombocytopenia, and bleeding complications. About 10% of patients with severe malaria die, usually as a result of multiorgan dysfunction. Critical care physicians should be aware of the complications and management of severe malaria. There has been significant progress in the understanding of pathogenesis of severe malaria over the last decade. Effective management of severe malaria includes early suspicion, prompt diagnosis, early institution of appropriate antimalarial chemotherapy, and supportive care, preferably in an intensive care unit. In this article, we review the different manifestations of severe malaria as relevant to critical care physicians and discuss the principles of laboratory diagnosis and management.
Malaria is one of the most common infectious diseases in the world, and severe respiratory complications have been described mainly in association with Plasmodium falciparum. We describe a case of acute respiratory distress syndrome complicating infection with P. vivax in the setting of relatively low parasitemia in a 47-yr-old woman after a brief trip to Papua New Guinea. A review of the literature shows that pulmonary complications of P. vivax are rare but occur more frequently than generally acknowledged. Pathogenic mechanisms of these complications are discussed.
Pulmonary edema that results from increased pulmonary capillary permeability is the most important pulmonary manifestation of malaria. It is a common feature of severe malaria but also occurs rarely in milder disease. Mortality rate is high. The pathophysiologic basis is unclear. In the field, there is much clinical overlap between malaria and pneumonia in children. For physicians in nonmalarial areas, malaria always should be considered in the differential diagnosis of a sick patient who has traveled to a malaria-endemic area. More research is needed to better define and tailor treatments for malarial and nonmalarial ALI and ARDS.
Acute respiratory distress (ARD) in two nonimmune adults with imported mixed and vivax malarial infections with low and resolving parasite load is described. Malarial pulmonary edema exacerbated by hypoalbuminemia and fluid redistribution without overload occurred in the latter patient. ARD led to mortality in one of the two. ARD should be promptly recognized and managed.
Parasitic infections are distributed worldwide and affect hundreds of millions of individuals-primarily those living in endemic areas or in regions with a high rate of immigration from endemic areas-causing significant morbidity and mortality. A broad spectrum of parasitic infections (eg, amebiasis, malaria, trypanosomiasis, ascariasis, strongyloidiasis, dirofilariasis, cystic echinococcosis, schistosomiasis, paragonimiasis) frequently affect the lungs, mediastinum, and thoracic wall, manifesting with abnormal imaging findings that often make diagnosis challenging. Although most of these infections result in nonspecific abnormalities, familiarity with their imaging features as well as their epidemiologic, clinical, and physiopathologic characteristics may be helpful to the radiologist in formulating an adequate differential diagnosis.
Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P.vivax and P.ovale have also rarely caused pulmonary edema.Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial sepsis that may not be clinically obvious. Clinicians should employ a low threshold for starting broad spectrum antibacterials in such patients, after taking pertinent microbiologic specimens. Despite optimal management, the prognosis of severe malaria with ARDS is poor.ALI/ARDS in pediatric malaria appears to be rare. However, falciparum malaria with severe metabolic acidosis or acute pulmonary edema may present with a clinical picture of pneumonia, i.e. with tachypnea, intercostal recession, wheeze or inspiratory crepitations. This results in diagnostic confusion and suboptimal treatment. Whilst this is increasingly being recognized in malaria-endemic countries, clinicians in temperate zones should be aware that malaria may be a possible cause of 'pneumonia' in a visiting or returning child.
Malaria is caused by infection with one of four species of Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, and P. malariae ), which are transmitted by the bite of an infective female Anopheles sp. mosquito. Most malarial infections in the United States occur in persons who have traveled to areas (i.e., other countries) in which disease transmission is ongoing. However, cases are transmitted occasionally through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to adapt prevention recommendations.
Cases with onset of symptoms during 1994.
Malaria cases confirmed by blood smear are reported to local and/or state health departments by health-care providers and/or laboratories. Case investigations are conducted by local and/or state health departments, and the reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), which was the source of data for this report. Numbers of cases reported through NMSS may differ from those reported through other passive surveillance systems because of differences in the collection and transmission of data.
CDC received reports of 1,014 cases of malaria with onset of symptoms during 1994 among persons in the United States or one of its territories. This number represented a 20% decrease from the 1,275 cases reported for 1993. P. vivax, P. falciparum, P. malariae, and P. ovale accounted for 44%, 44%, 4%, and 3% of cases, respectively. More than one species was present in five persons (<1% of the total number of patients). The infecting species was not determined in 50 (5%) cases. The number of reported malaria cases in U.S. military personnel decreased by 86% (i.e., from 278 cases in 1993 to 38 cases in 1994). Of the U.S. civilians who acquired malaria during travel to foreign countries, 18% had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Five persons became infected while in the United States; the infection was transmitted to two of these persons through transfusion of infected blood products. The remaining three cases, which occurred in Houston, Texas, were probably locally acquired mosquitoborne infections. Four deaths were attributed to malaria.
The 20% decrease in the number of malaria cases from 1993 to 1994 resulted primarily from an 86% decrease in cases among U.S. military personnel after withdrawal from Somalia. Because most malaria cases acquired in Somalia during 1993 resulted from infection with P. vivax, there was a proportionately greater decrease during 1994 in the number of cases caused by P. vivax relative to those caused by P. falciparum.
Additional information was obtained concerning the four fatal cases and the five cases acquired in the United States. Malaria prevention guidelines were updated and distributed to health-care providers. Persons traveling to a geographic area in which malaria is endemic should take the recommended chemoprophylactic regimen and should use protective measures to prevent mosquito bites. Persons who have a fever or influenza-like illness after returning from a malarious area should seek medical care; medical evaluation should include a blood smear examination for malaria. Malarial infections can be fatal if not promptly diagnosed and treated. Recommendations concerning prevention and treatment of malaria can be obtained from CDC.
Malaria parasite species circulating in immune inhabitants of the Democratic Republic of São Tomé e Principe (DRSTP) and those acquired by non-immune travellers returning from this country have been compared. Using sensitive detection and species identification by PCR, Plasmodium parasites were found in the blood of 16 of the 43 travellers, who reported during the first 8 months of 1995 to a clinical diagnosis laboratory in Lisbon. Plasmodium vivax was found in four (25%) and Plasmodium ovale in ten (63%) of these patients. The observed prevalence of these two species in infected patients of DRSTP during 1995/1996 was <2%.
During 4 months, from June to September 1990, the population of Dielmo village, Senegal, an area of intense and perennial malaria transmission, was enrolled in a follow-up study including daily clinical surveillance and bi-weekly malaria parasitaemia monitoring. Thick blood film examinations indicated that 48.5% of children (49/101) and 32.4% of adults (34/105) were infected at least once by Plasmodium ovale during the study period; 148 distinct episodes of patent parasitaemia were observed, with estimated maximum durations of 3-115 d. The mean duration at first decreased significantly with age, from 11.4 d in children under 5 years old to 4.2 d in adults aged 40-59 years, but then increased in older adults to 7.0 d. In all age groups, most infections were asymptomatic. Only high parasitaemias were significantly associated with fever; 3 clinical malaria attacks due to P. ovale were seen during the study period.