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The anaemia of Plasmodium vivax malaria

Nicholas M Douglas, Nicholas M Anstey, Pierre A Buffet and 4 more

Malaria Journal · 2012 · Review

Abstract

Plasmodium vivax threatens nearly half the world's population and is a significant impediment to achievement of the millennium development goals. It is an important, but incompletely understood, cause of anaemia. This review synthesizes current evidence on the epidemiology, pathogenesis, treatment and consequences of vivax-associated anaemia. Young children are at high risk of clinically significant and potentially severe vivax-associated anaemia, particularly in countries where transmission is intense and relapses are frequent. Despite reaching lower densities than Plasmodium falciparum, Plasmodium vivax causes similar absolute reduction in red blood cell mass because it results in proportionately greater removal of uninfected red blood cells. Severe vivax anaemia is associated with substantial indirect mortality and morbidity through impaired resilience to co-morbidities, obstetric complications and requirement for blood transfusion. Anaemia can be averted by early and effective anti-malarial treatment.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 21, 2026. Paragraph numbers are ours, so an answer can point at one.

Background

1Plasmodium vivax threatens approximately 2.8 billion people globally and, because of its particular biological characteristics, will be more difficult to eradicate than Plasmodium falciparum. Over recent years, case series, surveillance studies and reviews have linked vivax malaria with a number of severe manifestations similar to those found in P. falciparum infection; observations that challenge the notion that vivax malaria is a benign disease. The causative role of P. vivax in some of these severe manifestations remains to be proven and many are sufficiently rare that they are unlikely to represent significant public health problems. Anaemia, on the other hand, is a common and frequently severe consequence of vivax infection. This review explores the epidemiology, pathophysiological mechanisms, relationship to transmission dynamics and consequences of anaemia caused by vivax malaria (highlighting similarities and differences as compared with P. falciparum). The impact of anti-malarial treatment on haematological recovery is also described.

Epidemiology

2Endemic P. vivax is transmitted throughout the tropics in much the same geographical pattern as P. falciparum. The major exception is West Africa where P. vivax is largely absent. This has been attributed to selection over many millennia of individuals lacking the Duffy red blood cell surface antigen - an important mediator of P. vivax red cell invasion. Menard and colleagues’ recent discovery of vivax malaria in Duffy negative Malagasy people suggests that P. vivax may have escaped its dependence on the Duffy antigen in certain regions.

3Where P. falciparum and P. vivax co-exist, both the incidence of infection and severity of haematological morbidity attributable to P. vivax tends to peak at a younger age than for falciparum malaria and in many regions, before the end of the second year of life. This pattern probably reflects greater parasite exposure through frequent relapse and consequently more rapid acquisition of immunity to vivax malaria. In tropical regions, relapses may occur as often as every three weeks. In Papua, Indonesia, an area of comparatively high-level P. vivax transmission, approximately a quarter of infants hospitalized with vivax malaria have severe anaemia (haemoglobin less than 5 g/dL), whereas in individuals 45 years or older this proportion decreases to less than 5%. Infants with vivax malaria in this region have 2.4-fold greater odds of severe anaemia than those with falciparum malaria.

4Females are at greater risk of hospitalization with P. vivax malaria than males and in one large analysis were more likely to present with anaemia (unpublished data). Both phenomena may be, at least partially, explained by the fact that post-pubertal women have a lower mean haemoglobin concentration than men and therefore have a greater chance of being tipped over the threshold for anaemia following a haematological insult. Pregnant women with P. vivax infection have a ~2-fold higher risk of moderate anaemia than uninfected pregnant women. Whether the haematological impact of vivax malaria in pregnancy is greater than in non-pregnant women of child-bearing age is unknown.

5Several red blood cell and haemoglobin variants have been associated with reduced susceptibility to anaemia caused by falciparum malaria, the best known being sickle cell anaemia. Hypothesized mechanisms for this protection include reduced red blood cell invasion, relative inhibition of intracellular parasite replication, more efficient removal of infected red blood cells by the spleen and more efficient presentation of parasite antigens to the immune system. The high erythrocyte counts and relative microcytosis seen in conditions such as alpha-thalassaemia result in a lower proportional reduction in haemoglobin with falciparum malaria. Both alpha- and beta-thalassaemia have been associated with an increased risk of P. vivax parasitaemia in cross sectional studies but their effect on vivax anaemia is unknown. Preliminary work suggests South-East Asian ovalocytosis may protect against P. vivax parasitaemia and vivax-associated anaemia whereas the effects of Gerbich blood group are unclear. Glucose-6-phosphate dehydrogenase deficiency is associated with protection against clinical disease and reduced parasite density in P. vivax infections. The rarity of such polymorphisms in migrant Highland Papuan populations has been hypothesized to contribute to the higher risk of severe anaemia from P. vivax in Southern Papua compared with elsewhere in New Guinea.

6Gastrointestinal helminth infections may cause anaemia through chronic blood loss, but the interaction with malarial anaemia is complex. In Africa, hookworm and P. falciparum malaria coinfection has been shown to cause an additive reduction in haemoglobin in children and pregnant mothers when compared with monoinfection with either parasite alone. Helminthiasis may also be a risk factor for P. falciparum parasitaemia but evidence is conflicting. Few studies have addressed the effect of intestinal helminthiasis on the risk of P. vivax infection and vivax-associated anaemia. Boel and colleagues showed a positive association between Ascaris lumbricoides infection during pregnancy and risk of vivax malaria. Another small study found that the reduction in haemoglobin associated with P. vivax infection in children between five and 14 years of age was attenuated by coinfection with hookworm, A. lumbricoides and Trichuris trichuria.

7The haematological effects of chronic blood loss caused by intestinal helminthiasis are exacerbated by nutritional iron deficiency which in turn may interact with the haematological effects of P. vivax malaria. Iron deficiency is protective against P. falciparum infection whereas iron supplementation increases the risk of falciparum malaria and high parasitaemia infections. The evidence for a link between iron supplementation and morbidity associated with vivax malaria is conflicting. One large prospective study from Thailand showed that pregnant women given supplemental iron and folate were at increased risk of P. vivax infection compared to those who did not receive supplementation. A randomized controlled trial from Peru showed that iron plus zinc reduced vivax-associated morbidity in children under five years of age, but iron supplementation increased morbidity in those over five years. In Papua New Guinea, 16 weeks of supplemental iron in prepubescent school children provided an overall haematological benefit compared with placebo and had no effect on the risk of morbidity associated with vivax malaria. Large, multi-centre trials including both pre- and post-pubescent participants are required to firmly establish whether an association between iron status and vivax anaemia exists.

Pathophysiology and mechanisms

8The primary target of human Plasmodium species is the red blood cell. Plasmodium vivax has a very strong predilection for red blood cells that have emerged from the bone marrow within the last 14 days, in particular reticulocytes, whereas P. falciparum has only a moderate predilection for young red blood cells and significant ability to infect older cells. The natural history of erythrocytes infected by either species is to host the replicating parasite for approximately 48 hours before bursting and releasing daughter merozoites. The range of peripheral parasitaemia in P. vivax infections is lower than in symptomatic P. falciparum malaria and parasitaemia >2% is rare. Despite this, mathematical models suggest that premature death of infected reticulocytes due to P. vivax infection should be sufficient to lead to extreme anaemia over a period of several months by choking the supply of mature red blood cells. Direct evidence from two malariatherapy patients studied in detail shows that severe anaemia may develop much more rapidly than this and that the proportion of infected reticulocytes after two to three weeks of vivax malaria can be less than 10%. These observations suggest that other mechanisms of anaemia are likely to be important. In P. falciparum malaria, these include increased removal of infected, and to a greater extent, uninfected red blood cells from circulation, compounded, in subacute and chronic forms, by impaired erythropoiesis. The same general processes appear to be important in vivax malaria but many of the cellular mechanisms differ (see Figure 1).

Removal of red blood cells from circulation

9Although parasitaemia is typically lower in vivax compared with falciparum infections, the absolute number of red blood cells removed from circulation, and hence the degree of anaemia resulting from infection by the two species, is often similar. This is because in P. vivax malaria, approximately 34 non-infected cells are cleared for every one infected cell whereas in P. falciparum malaria, this ratio is closer to 8 to 1. These figures are derived from observations in non-immune adults treated for neurosyphilis and Thai patients over 5 kg in weight. There are no data on the proportional removal of uninfected red blood cells in infants, the age group bearing the greatest burden of anaemia due to vivax malaria. Although removal of uninfected red blood cells is an important component of vivax-associated anaemia, the mechanisms of removal are not fully understood.

10As in falciparum malaria, vivax-infected erythrocytes adhere to uninfected red blood cells (rosetting) but unlike falciparum-infected cells, they have limited propensity to adhere to endothelial cells and, therefore, sequestration in the deep microvasculature is not a major factor in the pathogenesis of vivax malaria. Erythrocytes parasitized by P. falciparum become less deformable than uninfected red cells and have reduced capacity to pass through narrow inter-endothelial slits in the wall of splenic sinuses (mean dimensions 1.89 × 0.65 μm). Vivax-infected cells become more deformable as the parasite matures and are thought to retain the ability to squeeze through splenic slits. In falciparum malaria, red blood cell sequestration reduces the proportion of parasitized red blood cells that traverse the spleen. Increased deformability of infected red blood cells in vivax malaria may limit the proportion of red cells that are removed during passage through the splenic microcirculation. Thus, it appears that P. falciparum and P. vivax have evolved two different means of escaping splenic filtration. In both vivax and falciparum malaria, parasitized, and possibly non-parasitized, red cells are hypothesized to be more fragile than red cells in non-infected individuals and more prone to damage from shear stresses. This process is potentially a more important cause of red cell loss in falciparum malaria since in this disease, major sequestration in the microvasculature impedes the passage of circulating erythrocytes and erythrocyte rosettes.

11In addition to these mechanical processes, activation of the innate, cell-mediated and humoral immune systems in response to the presence of P. vivax antigens enhances the detection and removal of infected and abnormal uninfected red blood cells. The non-specific immune response for a given parasitaemia is greater for P. vivax than P. falciparum and may partially explain the greater proportional removal of non-parasitized cells and lower fever threshold in vivax malaria. This is a relatively weak speculation however since in severe falciparum malarial anaemia, cytokine levels are generally lower than in cerebral or uncomplicated attacks and cytokine concentrations have not been found to correlate with the degree of anaemia in P. vivax infections. Macrophage hyperplasia and increased phagocytic activity in both falciparum and vivax malaria results in a highly oxidative environment and may contribute to the shortened lifespan of non-infected erythrocytes. To compound the problem, reduced glutathione, which is necessary for protecting red cells against damaging oxygen species, is reported to be depleted in vivax malaria. Infection with P. falciparum causes altered expression of complement components and deposition of parasite proteins on infected and uninfected red blood cells (the latter sometimes associated with presence of specific immunoglobulins); facilitating opsonization and complement-mediated phagocytosis. It is unknown whether these processes also occur in vivax anaemia.

12Whatever the mechanisms leading to red blood cell alteration, the spleen is the most important site for the filtration, retention and phagocytosis of non-sequestered erythrocytes parasitised or altered by P. falciparum. Splenic activity limits parasite density thereby reducing the risk of severe malaria. However, the more stringent the splenic clearance, the greater the likelihood of severe anaemia. This may explain why concomitant severe malarial anaemia with spleen enlargement and cerebral malaria is relatively unusual with cerebral manifestations being more common in acute, fulminant infections and anaemia being more likely in chronic infections. The role of the spleen in vivax malaria is poorly understood though splenic enlargement in this infection appears to be similar to falciparum malaria. Indeed vivax malaria carries a very low but well-known risk of splenic rupture; considered greater than for falciparum malaria. In 1974, Littman described a single patient with hereditary spherocytosis who developed severe anaemia secondary to vivax malaria. A relapse five months later after a splenectomy did not cause anaemia suggesting that the spleen was the primary site of red blood cell removal (though the effect of strain specific immunity could not be excluded). A study from Papua showed that plasma haemoglobin concentrations in adults with uncomplicated vivax malaria were not increased compared to controls and were significantly lower than in falciparum malaria (unpublished data). This suggests that in adults with vivax malaria, the degree of intravascular haemolysis may be less than in falciparum malaria and that a greater proportion of uninfected red blood cells undergo extravascular removal.

13Increased removal and destruction of both infected and uninfected red cells in vivax malaria is most prominent during the early stages of infection however enhanced removal of uninfected cells persists for five weeks or more after effective treatment of blood-stage infection. In chronic, asymptomatic vivax parasitaemia, common in vivax-endemic areas, removal of both infected and uninfected red cells is likely to persist for the duration of infection.

Impaired production of red blood cells

14Patients with vivax or falciparum malaria have bone marrow abnormalities reflecting impaired erythropoiesis. In the earliest stages of both infections, the typical marrow finding is of decreased cellularity. In those with more chronic infections, marrow cellularity tends to be normal or increased but there is ineffective erythropoiesis, as indicated by impaired iron utilization, presence of morphologically abnormal erythroblasts as a result of cellular injury, and phagocytosis of erythroblasts by marrow macrophages.

15The exact mechanisms and functional importance of impaired erythropoiesis in vivax malaria are unclear. Using electron microscopy, Ru and colleagues have shown parasitization and subsequent degradation of erythroblasts in two patients with uncomplicated vivax malaria. Yoeli demonstrated morphologically normal, but non-pigmented, intracellular P. vivax parasites in a sternal tap specimen but not in peripheral blood smears in a single patient with vivax malaria. Wickramasinghe did not find any P. vivax parasites in the marrows of nine Thai adults with uncomplicated P. vivax infections. Because of the absence of any bone marrow data in children, or at any age with severe vivax-associated anaemia, the importance of P. vivax parasitization of erythroblasts in severe vivax anaemia is not known. Hypoxia of the bone marrow resulting from obstruction of marrow sinusoids by parasitized red blood cells and inadequate erythropoietin production or response have been hypothesized to contribute to impaired erythropoiesis in P. falciparum infections. In vivax malaria, hypoxia of the bone marrow is unlikely to be significant as there is minimal schizont sequestration. Erythropoietin metabolism is yet to be studied in this disease.

16Wickramasinghe and colleagues proposed that P. vivax has a directly toxic effect on erythroblasts or their precursors. Alternatively P. vivax may exert its effect on bone marrow macrophages leading to increased phagocytic activity and/or release of locally cytotoxic molecules damaging surrounding haematopoietic cells. Whatever the cause, some degree of impaired erythropoiesis has been shown to persist for at least two weeks after treatment of vivax malaria and therefore the effects of these putative factors must be long-lasting.

Effects of transmission intensity, relapse patterns, and strain diversity

17Since a significant proportion of the anaemia of vivax malaria, at least in the acute phase, can be explained by removal of uninfected red cells in response to immune system activation, the magnitude of the immune response (of which intensity of symptoms can be taken as a proxy) is likely to be an important determinant of haematological impairment. Untreated primary sporozoite-induced infection in non-immune adult patients with neurosyphilis typically results in paroxysmal fever lasting 3–8 weeks followed by an extended period of increasing clinical ‘tolerance’ to persistent parasitaemia. Anti-parasite immunity that suppresses parasitaemia to subpatent levels takes significantly longer to develop, in many cases more than 200 days. Collins and colleagues have reviewed the natural history of haemoglobin changes associated with untreated Plasmodium vivax infection in adult neurosyphilis patients. There was an exponential decay in mean haemoglobin concentrations during the first 4–5 weeks followed by a gradual climb in concentrations coinciding with development of parasite tolerance (see Figure 2). With persistent infection, mean haemoglobin levels had still not returned to normal by week 11 though the trajectory of the changes suggests that they might eventually have done so.

18Repeat infection with the homologous P. vivax strain, whether due to reinfection, recrudescence or relapse, during the period of parasite tolerance may result in a transient rise in parasitaemia but rarely recurrent or exacerbated symptoms. Homologous re-exposure after an extended period of parasite exposure (approximately 6 months for the St Elizabeth strain) from untreated or inadequately treated primary infection, relapse or reinfection results in neither patent parasitaemia nor clinical symptoms. Since homologous re-exposure in tolerant or immune individuals causes little non-specific immune system activation, the haematological effects of this are likely to be minimal.

19Heterologous immunity however, is weak and exposure to a new strain following primary infection will usually result in clinical malaria with non-specific immune system activation, recurrent symptoms and presumably a repeat haematological insult. If this occurs before an individual’s haemoglobin concentration has returned to normal following primary infection, the haematological effects are likely to be additive though direct evidence supporting this postulate is limited. The likelihood of repeat heterologous infection, and the probability that it occurs before complete haematological recovery, is a function of, among other things, the relapse pattern of local P. vivax strains and the entomological inoculation rate, both of which are also likely to affect the rate of genetic recombination and hence parasite population diversity.

20In endemic regions, a high proportion of P. vivax relapses are known to be caused by heterologous strains (with regard to the previous vivax infection). This is likely to be particularly common in areas with relatively intense P. vivax transmission and/or extensive parasite strain diversity. In such regions, there will also be a greater chance of simultaneous inoculation of two different strains of P. vivax which has been shown to cause deficient homologous immunity and therefore presumably greater susceptibility to the haematological effects of future homologous infection.

21Different P. vivax strains have markedly different relapse patterns and in some instances may not even cause a primary infection. In tropical regions, relapses tend to occur regularly every three to four weeks and rarely persist for more than four years from the time of initial inoculation. In temperate climes, the period between relapses may be significantly longer and more variable with some strains showing a bimodal frequency pattern. Tropical strains with short relapse intervals will be more likely to cause repeat blood stage infection before complete haematological recovery has occurred and may therefore be expected to have the greatest haematological impact.

22The virulence of an individual parasite strain may also modulate its haematological effects. There is some evidence that the Chesson strain causes fever at lower parasitaemia than other strains and therefore that it may be more immunogenic. In 1947, Whorton and colleagues described the anaemia associated with this strain as “striking” stating that “after the second week of malaria [in malariatherapy patients], it was difficult to maintain patients’ erythrocyte count above 2 million per cmm [corresponding to a haemoglobin concentration of approximately 6 g/dL] in spite of frequent erythrocyte transfusions”.

23Given the aforementioned evidence, one might predict that the severest haematological impact of vivax malaria would be seen in tropical regions with high entomological inoculation rates and virulent circulating strains. These features are perhaps best exemplified by P. vivax on the island of New Guinea where the frequently relapsing Chesson strain is endemic and local populations experience particularly severe haematological impairment from vivax malaria. In these regions, broad anti-disease immunity to all circulating parasite strains is also likely to develop more rapidly and therefore the haematological burden of vivax malaria will be most heavily skewed to very young children.

24Most populations at risk of P. vivax infection are also exposed to P. falciparum and co-infection (not necessarily patent) with these two species is common. In Thailand, mixed infection with P. falciparum and P. vivax has been shown to attenuate the risk of severe anaemia associated with falciparum malaria – possibly due to some degree of cross-species immunity. Recent work has shown that in Papua New Guinea and Papua, Indonesia, mixed infection causes more severe haematological impairment than infection with either species alone. The explanation for these opposing findings probably lies in the different transmission dynamics in these regions. In Thailand, severe falciparum malaria is usually the result of a single, fulminant infection in a non-immune individual and therefore earlier induction of suppressive non-specific immunity provided by coincident P. vivax infection, however minor, is likely to have a protective effect. In New Guinea, where transmission is more intense, severe anaemia in those older than one year is more likely to be the result of repeated or continuous infections due to either species. In this situation, the haematological effects of infection with both species are more likely to be additive and any immunomodulatory effects relatively minor.

Effects of anti-malarial treatment

25Early treatment of malaria can truncate the impending reduction in haemoglobin and accelerate haematological recovery. Despite the overall benefits of treatment, haemoglobin typically falls slightly following initiation of an anti-malarial drug reaching a nadir between days three to 7 following treatment. Data are sparse but there is some evidence that this initial fall may be less pronounced following treatment of vivax malaria with chloroquine (which gives faster clinical and parasitological responses against sensitive strains) compared with either sulfadoxine + pyrimethamine or chlorproguanil + dapsone. The artemisinin derivatives cause an extremely rapid reduction in P. vivax parasite biomass. They also temporarily reduce red blood cell production. In falciparum malaria, evidence suggests that the haematological benefit of the greater efficacy of the artemisinin drugs negates or outweighs the detrimental effects of this bone marrow suppression. The only published comparative assessment of the acute haematological effects of treatment with an artemisinin derivative in patients with vivax malaria showed that artesunate + pyronaridine was associated with a greater mean reduction in haemoglobin at days 3 and 7 when compared with chloroquine alone, although no tests of statistical significance were given.

26Complete removal of blood stage parasites following blood schizontocidal treatment allows faster haematological recovery (pre-infection haemoglobin concentrations are generally achieved in approximately 4–5 weeks following effective treatment) but reduces total parasite exposure and hence limits the development of homologous immunity. Treated individuals are therefore more likely to develop clinical malaria with significant haematological impairment following repeat homologous infection. Highly efficacious blood schizontocidal regimens containing slowly eliminated drugs (such as chloroquine, piperaquine or mefloquine) minimize the risk of recrudescence and also provide extended post-treatment prophylaxis against recurrent infection, allowing more time for full haematological recovery. The haematological benefit of the long elimination half-life is likely to be greatest in equatorial regions where P. vivax strains relapse as often as every three weeks.

27Plasmodium vivax has developed high-grade resistance to chloroquine in parts of Oceania, Asia, Africa and Latin America and sulfadoxine + pyrimethamine in parts of South-East Asia. Clinically, drug resistance is manifest by delayed parasite clearance times, an increased likelihood of incomplete parasite clearance and subsequent recrudescence as well as a shorter period of post-treatment prophylaxis against early recurrence. These factors are likely to result in a greater haematological insult associated with the initial infection (as demonstrated in P. falciparum malaria) but may facilitate earlier development of anti-disease immunity.

28Primaquine is a hypnozoitocidal drug that, if administered correctly, can prevent P. vivax relapses and thus reduce the total haematological impact of a given infection. Unfortunately this medication has the potential to cause lysis of old red blood cells in all patients, but particularly those with glucose-6-phosphate dehydrogenase deficiency. G6PD deficiency is the most common heritable enzymopathy in the world, with a prevalence ranging from 7.5% in Africa as a whole to 2.9% in the Pacific. Although G6PD deficiency increases the susceptibility of erythrocytes to oxidative damage this alone is not sufficient to account for primaquine-induced haemolysis. Generally, the more severe the enzyme deficiency, the greater the severity of haemolysis. Individuals who have less than 10% of normal enzyme activity are at risk of life-threatening haemolysis after as little as one dose of primaquine whereas those with milder variants may have negligible effects. Weekly, as opposed to daily, dosing schedules mitigate primaquine-induced haemolysis whilst retaining efficacy though adherence to such regimens is likely to be poor unless therapy is supervised. In mildly deficient individuals, continuous daily primaquine dosing causes acute but self-limited haemolysis for approximately 10 days followed by reactive reticulocytosis and haematological recovery as the population of old, susceptible, red blood cells is replaced by young erythrocytes. Since this is not an immunological phenomenon, repeat challenge with primaquine after a period of time in such patients causes equally severe haemolysis. In severely deficient patients, haemolysis is progressive and can have a fatal outcome unless primaquine therapy is stopped and blood transfusion given.

Consequences of vivax anaemia

29The impact of Plasmodium vivax infection on haemoglobin concentration varies from negligible to dramatic. The clinical consequences of the reduction in haemoglobin depend on the haemoglobin concentration prior to infection. For example, an absolute reduction of 2 g/dL would be more likely to have dramatic consequences if the initial haemoglobin was 6 g/dL than if it was 12 g/dL.

30In Papua New Guinea, 1.6% of children under 5 years of age presenting to rural health clinics for treatment of vivax malaria were severely anaemic (haemoglobin <5 g/dL). Across the border in Indonesian Papua, 22% of patients of all ages who were admitted to hospital with vivax malaria fulfilled criteria for severe anaemia. In the D’Entrecasteaux Islands off Papua New Guinea, a cross-sectional survey of children between 0 and 6 years of age showed that the mean haemoglobin in those with P. vivax parasitaemia was 8.7 g/dL, 0.3 g/dL lower than the equivalent value for those infected with P. falciparum. In contrast, on the Thai-Myanmar border, less than 0.2% of patients presenting for treatment of vivax malaria were severely anaemic.

31Although the spectrum of anaemia seen with vivax infection is reasonably well documented, the clinical, developmental, and socioeconomic consequences are largely unknown. Severe anaemia in isolation is associated with a ~2-fold increased risk of death in African children with falciparum malaria and has an even higher mortality when combined with other manifestations of severe disease such as cerebral malaria or respiratory distress. Severe anaemia of any cause in hospitalized children under five years has been associated with a case fatality of between 2% and 29.3% and moderate or severe anaemia has been associated with a maternal case fatality of between <1% and >50% in hospital-based studies.

32Population-based estimates of mortality in severely anaemic individuals with vivax malaria have not been established but recent studies from Latin America, New Guinea and the Indian subcontinent have identified deaths in patients with severe vivax anaemia. The authors did not establish the extent to which anaemia contributed to those deaths.

33Anaemia caused by vivax malaria is associated with requirement for blood transfusion. Screening of blood products for pathogens is well known to be incomplete in many low and middle income countries and therefore has a significant attendant risk of pathogen transmission. For example, in Sub-Saharan Africa, estimates for the risk of transfusion-associated infection with HIV, hepatitis B and hepatitis C are 1, 4.3 and 2.5 infections per 1,000 units of blood respectively.

34Pregnant women with haemoglobin concentrations under 8 g/dL in Papua New Guinea were at 2.4-fold higher risk of delivering a low birth weight baby than non-anaemic mothers. In this study, primigravidae with anaemia and parasitaemia at the time of delivery had the greatest risk of low birth weight. Although vivax malaria is endemic in Papua New Guinea, attribution of these effects specifically to this species is not possible. In Papua, Indonesia, P. vivax parasitaemia at delivery is associated independently with an increased risk of moderate anaemia and a mean reduction in birth weight of 108 g.

35Although evidence is lacking it seems plausible that severe vivax anaemia may reduce resilience to other infectious and non-infectious diseases and therefore may be associated with indirect mortality. In 1938, Swellengrebel and de Buck reported that 62 (7.7%) of a series of 807 patients with syphilis who were treated with induced P. vivax infections subsequently died; those with other comorbidities were at particularly great risk.

36Chronic or repeated episodes of malarial anaemia due to any Plasmodium species have been associated with adverse effects on physical and cognitive development as well as school attendance; all of which may be exacerbated by concomitant malnutrition. Again, whether these outcomes are generalizable to vivax malaria, and more specifically the haematological effects of this species, is unknown.

Conclusions

37Haematological morbidity associated with P. vivax infection is greatest in young children, especially in tropical countries such as Papua New Guinea and Eastern Indonesia where transmission is intense and local parasite strains relapse very frequently. In these regions, vivax malaria is commonly associated with severe anaemia both in the health care and community setting. The haematological effects of vivax malaria are likely to have complex interactions with gastrointestinal helminth infection, haemoglobin and red blood cell abnormalities and malnutrition.

38Removal of uninfected red blood cells is a particularly important mechanism of anaemia in acute vivax malaria. Plasmodium vivax-infected red blood cells are minimally adherent and are more deformable than P. falciparum-infected erythrocytes resulting in relatively little red blood cell sequestration in the microvasculature and marrow sinuses and passage of a greater proportion of red cells through the spleen and other reticuloendothelial organs. The role of the spleen in the pathogenesis of vivax anaemia, particularly the removal of uninfected red blood cells, is an important area for future research (Figure 3).

39As the global control and elimination of malaria progresses, P. vivax is set to become the dominant Plasmodium species, yet the health, developmental and socioeconomic consequences of vivax malaria and vivax–associated anaemia have received very little attention. Severe vivax anaemia may cause significant morbidity and indirect mortality via association with impaired resilience to infectious and non-infectious comorbidities, obstetric complications and requirement for blood transfusion (with attendant risk of blood-borne pathogen transmission). Early treatment with an efficacious blood schizontocide can reduce the initial fall in haemoglobin associated with vivax infection and thus help to prevent adverse outcomes associated with severe anaemia. Reliable prevention of recurrent haematological insults caused by relapses will require hypnozoitocidal therapy. Primaquine is the only licensed hypnozoitocidal agent available and can exacerbate haemolysis in individuals with G6PD deficiency. Policymakers need to weigh the potential benefits of this drug against the risks based on the local prevalence of this enzymopathy as well as the availability of G6PD testing. Vivax-associated anaemia is an important public health concern that underscores the importance of reducing global transmission of P. vivax.

Competing interests

40All authors declare they have no competing interests.

Authors’ contributions

41NMD, PAB, NMA and RNP searched the relevant literature. NMD wrote the first draft of the manuscript. All authors appraised and revised the manuscript. All authors gave final approval for submission of the manuscript.

References 203

1.
The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009 · 2010
No notice
2.
Carter R Mendis KN Evolutionary and historical aspects of the burden of malariaClin Microbiol Rev2002 15564594
Not in our library10.1128/cmr.15.4.564-594.2002
3.
Galinski MR Barnwell JW Plasmodium vivax: who cares?Malar J2008 7Suppl 1S9
Not in our library10.1186/1475-2875-7-s1-s9
4.
Price RN Tjitra E Guerra CA Yeung S White NJ Anstey NM Vivax malaria: neglected and not benignAm J Trop Med Hyg2007 777987
Not in our library
5.
Douglas NM Anstey NM Angus BJ Nosten F Price RN Artemisinin combination therapy for vivax malariaLancet Infect Dis2010 10405416
Not in our library10.1016/s1473-3099(10)70079-7
6.
Rosenberg R Plasmodium vivax in Africa: hidden in plain sight? [erratum appears in Trends Parasitol 2007; 23:304]Trends Parasitol2007 23193196
Not in our library10.1016/j.pt.2007.02.009
7.
Mendis K Sina BJ Marchesini P Carter R The neglected burden of Plasmodium vivax malariaAm J Trop Med Hyg2001 6497106
Not in our library10.4269/ajtmh.2001.64.97
8.
Guerra CA Snow RW Hay SI Mapping the global extent of malaria in 2005Trends Parasitol2006 22353358
Not in our library10.1016/j.pt.2006.06.006
9.
McKenzie FE Jeffery GM Collins WE Plasmodium vivax blood-stage dynamicsJ Parasitol2002 88521535
Not in our library10.1645/0022-3395(2002)088[0521:pvbsd]2.0.co;2
10.
Kochar DK Das A Kochar SK Saxena V Sirohi P Garg S Kochar A Khatri MP Gupta V Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in Northwestern IndiaAm J Trop Med Hyg2009 80194198
Not in our library
11.
Beg MA Sani N Mehraj V Jafri W Khan MA Malik A Menezes E Hussain R Smego R Comparative features and outcomes of malaria at a tertiary care hospital in Karachi, PakistanInt J Infect Dis2008 123742
Not in our library10.1016/j.ijid.2007.04.006
12.
Plasmodium vivax Malaria · 2005
No notice
13.
Lawn SD Krishna S Jarvis JN Joet T Macallan DC Case reports: pernicious complications of benign tertian malariaTrans R Soc Trop Med Hyg2003 97551553
Not in our library10.1016/s0035-9203(03)80024-x
14.
Plasmodium vivax and Mixed Infections Are Associated with Severe Malaria in Children: A Prospective Cohort Study from Papua New Guinea · 2008
No notice
15.
Barcus MJ Basri H Picarima H Manyakori C Sekartuti Elyazar I Bangs MJ Maguire JD Baird JK Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in Northeastern Indonesian PapuaAm J Trop Med Hyg2007 77984991
Not in our library
16.
Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia · 2008
No notice
17.
Rodriguez-Morales AJ Benitez JA Arria M Malaria mortality in Venezuela: focus on deaths due to Plasmodium vivax in childrenJ Trop Pediatr2008 5494101
Not in our library10.1093/tropej/fmm074
18.
Price RN Douglas NM Anstey NM New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistanceCurr Opin Infect Dis2009 22430435
Not in our library10.1097/qco.0b013e32832f14c1
19.
Baird JK Neglect of Plasmodium vivax malariaTrends Parasitol2007 23533539
Not in our library10.1016/j.pt.2007.08.011
20.
Maguire JD Baird JK The 'non-falciparum' malarias: the roles of epidemiology, parasite biology, clinical syndromes, complications and diagnostic rigour in guiding therapeutic strategiesAnn Trop Med Parasitol2010 104283301
Not in our library10.1179/136485910x12743554760027
21.
Baird JK Severe and fatal vivax malaria challenges 'benign tertian malaria' dogmaAnn Trop Paediatr2009 29251252
Not in our library10.1179/027249309x12547917868808
22.
Anstey NM Russell B Yeo TW Price RN The pathophysiology of vivax malariaTrends Parasitol2009 25220227
Not in our library10.1016/j.pt.2009.02.003
23.
Tan LKK Yacoub S Scott S Bhagani S Jacobs M Acute lung injury and other serious complications of Plasmodium vivax malariaLancet Infect Dis2008 8449454
Not in our library10.1016/s1473-3099(08)70153-1
24.
Bassat Q Alonso PL Defying malaria: fathoming severe Plasmodium vivax diseaseNat Med2011 174849
Not in our library10.1038/nm0111-48
25.
Rodriguez-Morales AJ Sanchez E Vargas M Piccolo C Colina R Arria M Anemia and thrombocytopenia in children with Plasmodium vivax malariaJ Trop Pediatr2006 524951
Not in our library10.1093/tropej/fmi069
26.
Rodriguez-Morales AJ Sanchez E Vargas M Piccolo C Colina R Arria M Franco-Paredes C Is anemia in Plasmodium vivax malaria more frequent and severe than in Plasmodium falciparum?Am J Med2006 119e9e10
Not in our library10.1016/j.amjmed.2005.08.014
27.
Poespoprodjo JR Fobia W Kenangalem E Lampah DA Hasanuddin A Warikar N Sugiarto P Tjitra E Anstey NM Price RN Vivax malaria: a major cause of morbidity in early infancyClin Infect Dis2009 4817041712
Not in our library10.1086/599041
28.
Miller LH Mason SJ Clyde DF McGinniss MH The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFyN Engl J Med1976 295302304
Not in our library10.1056/nejm197608052950602
29.
Menard D Barnadas C Bouchier C Henry-Halldin C Gray LR Ratsimbasoa A Thonier V Carod JF Domarle O Colin Y Bertrand O Picot J King CL Grimberg BT Mercereau-Puijalon O Zimmerman PA Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy peopleProc Natl Acad Sci U S A2010 10759675971
Not in our library10.1073/pnas.0912496107
30.
Michon P Cole-Tobian JL Dabod E Schoepflin S Igu J Susapu M Tarongka N Zimmerman PA Reeder JC Beeson JG Schofield L King CL Mueller I The risk of malarial infections and disease in Papua New Guinean childrenAm J Trop Med Hyg2007 769971008
Not in our library
31.
Differential Patterns of Infection and Disease with P. falciparum and P. vivax in Young Papua New Guinean Children · 2010
No notice
32.
Ladeia-Andrade S Ferreira MU de Carvalho ME Curado I Coura JR Age-dependent acquisition of protective immunity to malaria in riverine populations of the Amazon Basin of BrazilAm J Trop Med Hyg2009 80452459
Not in our library
33.
Hill E Amatuzio DS Southwest Pacific vivax malaria: clinical features and observations concerning duration of clinical activityAm J Trop Med1949 s1-29203214
Not in our library
34.
Coatney GR Cooper WC Young MD Studies in human malaria. XXX. A summary of 204 sporozoite-induced infections with the Chesson strain of Plasmodium vivaxJ Natl Malaria Soc1950 9381
Not in our library
35.
Poespoprodjo JR Fobia W Kenangalem E Lampah DA Warikar N Seal A McGready R Sugiarto P Tjitra E Anstey NM Price RN Adverse pregnancy outcomes in an area where multidrug-resistant Plasmodium vivax and Plasmodium falciparum infections are endemicClin Infect Dis2008 4613741381
Not in our library10.1086/586743
36.
Nosten F McGready R Simpson JA Thwai KL Balkan S Cho T Hkirijaroen L Looareesuwan S White NJ Effects of Plasmodium vivax malaria in pregnancyLancet1999 354546549
Not in our library10.1016/s0140-6736(98)09247-2
37.
Rodriguez-Morales AJ Sanchez E Vargas M Piccolo C Colina R Arria M Franco-Paredes C Pregnancy outcomes associated with Plasmodium vivax malaria in Northeastern VenezuelaAm J Trop Med Hyg2006 74755757
Not in our library
38.
Luzzatto L Nwachuku-Jarrett ES Reddy S Increased sickling of parasitised erythrocytes as mechanism of resistance against malaria in the sickle-cell traitLancet1970 1319321
Not in our library10.1016/s0140-6736(70)90700-2
39.
Roth EF Friedman M Ueda Y Tellez I Trager W Nagel RL Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malariaScience1978 202650652
Not in our library10.1126/science.360396
40.
Weatherall DJ Miller LH Baruch DI Marsh K Doumbo OK Casals-Pascual C Roberts DJ Malaria and the red cellHematology2002 3557
Not in our library10.1182/asheducation-2002.1.35
41.
Fowkes FJI Allen S Allen A Alpers MP Weatherall DJ Day KP Increased microerythrocyte count in homozygous alpha + −thalassaemia contributes to protection against severe malarial anaemiaPLoS Med2008 5e56
Not in our library10.1371/journal.pmed.0050056
42.
Williams TN Maitland K Bennett S Ganczakowski M Peto TE Newbold CI Bowden DK Weatherall DJ Clegg JB High incidence of malaria in alpha-thalassaemic childrenNature1996 383522525
Not in our library10.1038/383522a0
43.
O'Donnell A Premawardhena A Arambepola M Samaranayake R Allen SJ Peto TE Fisher CA Cook J Corran PH Olivieri NF Weatherall DJ Interaction of malaria with a common form of severe thalassemia in an Asian populationProc Natl Acad Sci U S A2009 1061871618721
Not in our library10.1073/pnas.0910142106
44.
Zimmerman PA Woolley I Masinde GL Miller SM McNamara DT Hazlett F Mgone CS Alpers MP Genton B Boatin BA Kazura JW Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New GuineaProc Natl Acad Sci U S A1999 961397313977
Not in our library10.1073/pnas.96.24.13973
45.
Cattani JA Gibson FD Alpers MP Crane GG Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New GuineaTrans R Soc Trop Med Hyg1987 81705709
Not in our library10.1016/0035-9203(87)90001-0
46.
Rosanas-Urgell A Lin E Manning L Rarau P Laman M Senn N Grimberg BT Tavul L Stanisic D Aponte J Daboud E Reeder JC Siba P Zimmerman PA Davis TME King CL Michon P Mueller I Reduced risk ofPlasmodium vivaxmalaria in Papua New Guinean children with South East Asian ovalocytosisMolecular Approaches to Malaria; Lorne, Victoria2012 Walter and Eliza Hall Institute, Melbourne107
Not in our library
47.
Patel SS King CL Mgone CS Kazura JW Zimmerman PA Glycophorin C (Gerbich antigen blood group) and band 3 polymorphisms in two malaria holoendemic regions of Papua New GuineaAm J Hematol2004 7515
Not in our library10.1002/ajh.10448
48.
Louicharoen C Patin E Paul R Nuchprayoon I Witoonpanich B Peerapittayamongkol C Casademont I Sura T Laird NM Singhasivanon P Quintana-Murci L Sakuntabhai A Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast AsiansScience2009 32615461549
Not in our library10.1126/science.1178849
49.
Leslie T Briceno M Mayan I Mohammed N Klinkenberg E Sibley CH Whitty CJ Rowland M The impact of phenotypic and genotypic G6PD deficiency on risk of Plasmodium vivax infection: a case–control study amongst Afghan refugees in PakistanPLoS Med2010 7e1000283
Not in our library10.1371/journal.pmed.1000283
50.
Brooker S Akhwale W Pullan R Estambale B Clarke SE Snow RW Hotez PJ Epidemiology of Plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining controlAm J Trop Med Hyg2007 778898
Not in our library
51.
Nacher M Singhasivanon P Yimsamran S Manibunyong W Thanyavanich N Wuthisen R Looareesuwan S Intestinal helminth infections are associated with increased incidence of Plasmodium falciparum malaria in ThailandJ Parasitol2002 885558
Not in our library10.1645/0022-3395(2002)088[0055:ihiaaw]2.0.co;2
52.
Spiegel A Tall A Raphenon G Trape JF Druilhe P Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malariaTrans R Soc Trop Med Hyg2003 97198199
Not in our library10.1016/s0035-9203(03)90117-9
53.
Boel M Carrara VI Rijken M Proux S Nacher M Pimanpanarak M Paw MK Moo O Gay H Bailey W Singhasivanon P White NJ Nosten F McGready R Complex interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese borderPLoS Negl Trop Dis2010 4e887
Not in our library10.1371/journal.pntd.0000887
54.
Melo GC Reyes-Lecca RC Vitor-Silva S Monteiro WM Martins M Benzecry SG Alecrim MG Lacerda MV Concurrent helminthic infection protects schoolchildren with Plasmodium vivax from anemiaPLoS One2010 5e11206
Not in our library10.1371/journal.pone.0011206
55.
Nyakeriga AM Troye-Blomberg M Dorfman JR Alexander ND Back R Kortok M Chemtai AK Marsh K Williams TN Iron deficiency and malaria among children living on the coast of KenyaJ Infect Dis2004 190439447
Not in our library10.1086/422331
56.
Sazawal S Black RE Ramsan M Chwaya HM Stoltzfus RJ Dutta A Dhingra U Kabole I Deb S Othman MK Kabole FM Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trialLancet2006 367133143
Not in our library10.1016/s0140-6736(06)67962-2
57.
Nacher M McGready R Stepniewska K Cho T Looareesuwan S White NJ Nosten F Haematinic treatment of anaemia increases the risk of Plasmodium vivax malaria in pregnancyTrans R Soc Trop Med Hyg2003 97273276
Not in our library10.1016/s0035-9203(03)90140-4
58.
Richard SA Zavaleta N Caulfield LE Black RE Witzig RS Shankar AH Zinc and iron supplementation and malaria, diarrhea, and respiratory infections in children in the Peruvian AmazonAm J Trop Med Hyg2006 75126132
Not in our library10.4269/ajtmh.2006.75.1.0750126
59.
Harvey PW Heywood PF Nesheim MC Galme K Zegans M Habicht JP Stephenson LS Radimer KL Brabin B Forsyth K Alpers MP The effect of iron therapy on malarial infection in Papua New Guinean schoolchildrenAm J Trop Med Hyg1989 401218
Not in our library10.4269/ajtmh.1989.40.12
60.
Kitchen SF The infection of reticulocytes by Plasmodium vivaxAm J Trop Med Hyg1938 s1-18347359
Not in our library
61.
Vryonis G Observations on the parasitization of erythrocytes by Plasmodium vivax, with special reference to reticulocytesAm J Hyg1939 304148
Not in our library
62.
Simpson JA Silamut K Chotivanich K Pukrittayakamee S White NJ Red cell selectivity in malaria: a study of multiple-infected erythrocytesTrans R Soc Trop Med Hyg1999 93165168
Not in our library10.1016/s0035-9203(99)90295-x
63.
McQueen PG McKenzie FE Age-structured red blood cell susceptibility and the dynamics of malaria infectionsProc Natl Acad Sci U S A2004 10191619166
Not in our library10.1073/pnas.0308256101
64.
McQueen PG Population dynamics of a pathogen: the conundrum of vivax malariaBiophys Rev2010 2111120
Not in our library10.1007/s12551-010-0034-3
65.
Antia R Yates A de Roode JC The dynamics of acute malaria infections. I. Effect of the parasite's red blood cell preferenceProc Biol Sci2008 27514491458
Not in our library10.1098/rspb.2008.0198
66.
Abdalla S Weatherall DJ Wickramasinghe SN Hughes M The anaemia of P. falciparum malariaBr J Haematol1980 46171183
Not in our library10.1111/j.1365-2141.1980.tb05956.x
67.
Jakeman GN Saul A Hogarth WL Collins WE Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytesParasitology1999 119127133
Not in our library10.1017/s0031182099004564
68.
Weatherall DJ Abdalla S The anaemia of Plasmodium falciparum malariaBr Med Bull1982 38147151
Not in our library10.1093/oxfordjournals.bmb.a071751
69.
Wickramasinghe SN Abdalla SH Blood and bone marrow changes in malariaBaillieres Best Pract Res Clin Haematol2000 13277299
Not in our library10.1053/beha.1999.0072
70.
Price RN Simpson JA Nosten F Luxemburger C Hkirijaroen L ter Kuile F Chongsuphajaisiddhi T White NJ Factors contributing to anemia after uncomplicated falciparum malariaAm J Trop Med Hyg2001 65614622
Not in our library10.4269/ajtmh.2001.65.614
71.
Hemolysis is associated with low reticulocyte production index and predicts blood transfusion in severe malarial anemia. · 2010
Not checked
72.
Selvam R Baskaran G Hematological impairments in recurrent Plasmodium vivax infected patientsJpn J Med Sci Biol1996 49151165
Not in our library10.7883/yoken1952.49.151
73.
Collins WE Jeffery GM Roberts JM A retrospective examination of anemia during infection of humans with Plasmodium vivaxAm J Trop Med Hyg2003 68410412
Not in our library
74.
Prommano O Chaisri U Turner GD Wilairatana P Ferguson DJ Viriyavejakul P White NJ Pongponratn E A quantitative ultrastructural study of the liver and the spleen in fatal falciparum malariaSoutheast Asian J Trop Med Public Health2005 3613591370
Not in our library
75.
Bruetsch WL The histopathology of therapeutic (tertian) malariaAm J Psychiatry1932 891965
Not in our library
76.
Wickramasinghe SN Looareesuwan S Nagachinta B White NJ Dyserythropoiesis and ineffective erythropoiesis in Plasmodium vivax malariaBr J Haematol1989 729199
Not in our library10.1111/j.1365-2141.1989.tb07658.x
77.
Srichaikul T Wasanasomsithi M Poshyachinda V Panikbutr N Rabieb T Ferrokinetic studies and erythropoiesis in malariaArch Intern Med1969 124623628
Not in our library
78.
Ru YX Mao BY Zhang FK Pang TX Zhao SX Liu JH Wickramasinghe SN Invasion of erythroblasts by Pasmodium vivax: a new mechanism contributing to malarial anemiaUltrastruct Pathol2009 33236242
Not in our library10.3109/01913120903251643
79.
Yoeli M Non-pigmented malaria parasites in the bone marrow from a mixed infection of Leishmania and Plasmodium vivaxTrans R Soc Trop Med Hyg1948 4299101
Not in our library10.1016/0035-9203(48)90355-1
80.
Marchiafava E Bignami A On summer-autumnal malaria fevers1894 The New Sydenham Society, London
Not in our library
81.
Handayani S Chiu DT Tjitra E Kuo JS Lampah D Kenangalem E Renia L Snounou G Price RN Anstey NM Russell B High deformability of Plasmodium vivax-infected red blood cells under microfluidic conditionsJ Infect Dis2009 199445450
Not in our library10.1086/596048
82.
Dondorp AM Angus BJ Chotivanich K Silamut K Ruangveerayuth R Hardeman MR Kager PA Vreeken J White NJ Red blood cell deformability as a predictor of anemia in severe falciparum malariaAm J Trop Med Hyg1999 60733737
Not in our library10.4269/ajtmh.1999.60.733
83.
Li J Huang YX Ji T Tu M Mao X Chen WX Chen GW Non-invasive in situ simultaneous measurement of multi-parameter mechanical properties of red blood cell membraneActa Biochim Biophys Sin (Shanghai)2005 37391395
Not in our library10.1111/j.1745-7270.2005.00056.x
84.
Buffet PA Milon G Brousse V Correas JM Dousset B Couvelard A Kianmanesh R Farges O Sauvanet A Paye F Ungeheuer MN Ottone C Khun H Fiette L Guigon G Huerre M Mercereau-Puijalon O David PH Ex vivo perfusion of human spleens maintains clearing and processing functionsBlood2006 10737453752
Not in our library10.1182/blood-2005-10-4094
85.
Cranston HA Boylan CW Carroll GL Sutera SP Williamson JR Gluzman IY Krogstad DJ Plasmodium falciparum maturation abolishes physiologic red cell deformabilityScience1984 223400403
Not in our library10.1126/science.6362007
86.
Deplaine G Safeukui I Jeddi F Lacoste F Brousse V Perrot S Biligui S Guillotte M Guitton C Dokmak S Aussilhou B Sauvanet A Cazals Hatem D Paye F Thellier M Mazier D Milon G Mohandas N Mercereau-Puijalon O David PH Buffet PA The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitroBlood2011 117e88e95
Not in our library10.1182/blood-2010-10-312801
87.
Safeukui I Correas JM Brousse V Hirt D Deplaine G Mule S Lesurtel M Goasguen N Sauvanet A Couvelard A Kerneis S Khun H Vigan-Womas I Ottone C Molina TJ Treluyer JM Mercereau-Puijalon O Milon G David PH Buffet PA Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleenBlood2008 11225202528
Not in our library10.1182/blood-2008-03-146779
88.
Pouvelle B Buffet PA Lepolard C Scherf A Gysin J Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytesNat Med2000 612641268
Not in our library10.1038/81374
89.
Goka BQ Kwarko H Kurtzhals JA Gyan B Ofori-Adjei E Ohene SA Hviid L Akanmori BD Neequaye J Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malariaTrans R Soc Trop Med Hyg2001 95545549
Not in our library10.1016/s0035-9203(01)90036-7
90.
Pawluczkowycz AW Lindorfer MA Waitumbi JN Taylor RP Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malariaJ Immunol2007 17955435552
Not in our library10.4049/jimmunol.179.8.5543
91.
Waitumbi JN Opollo MO Muga RO Misore AO Stoute JA Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemiaBlood2000 9514811486
Not in our library
92.
Awah N Balogun H Achidi E Mariuba LA Nogueira PA Orlandi P Troye-Blomberg M Gysin J Berzins K Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian childrenParasite Immunol2011 33104115
Not in our library10.1111/j.1365-3024.2010.01259.x
93.
Bhattacharya J Swarup-Mitra S Reduction in erythrocytic GSH level and stability in Plasmodium vivax malariaTrans R Soc Trop Med Hyg1987 816466
Not in our library10.1016/0035-9203(87)90285-9
94.
Nuchsongsin F Chotivanich K Charunwatthana P Omodeo-Sale F Taramelli D Day NP White NJ Dondorp AM Effects of malaria heme products on red blood cell deformabilityAm J Trop Med Hyg2007 77617622
Not in our library
95.
Omodeo-Sale F Motti A Dondorp A White NJ Taramelli D Destabilisation and subsequent lysis of human erythrocytes induced by Plasmodium falciparum haem productsEur J Haematol2005 74324332
Not in our library10.1111/j.1600-0609.2004.00352.x
96.
Kurtzhals JA Adabayeri V Goka BQ Akanmori BD Oliver-Commey JO Nkrumah FK Behr C Hviid L Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malariaLancet1998 35117681772
Not in our library10.1016/s0140-6736(97)09439-7
97.
Thuma PE van Dijk J Bucala R Debebe Z Nekhai S Kuddo T Nouraie M Weiss G Gordeuk VR Distinct clinical and immunologic profiles in severe malarial anemia and cerebral malaria in ZambiaJ Infect Dis2011 203211219
Not in our library10.1093/infdis/jiq041
98.
Layez C Nogueira P Combes V Costa FT Juhan-Vague I da Silva LH Gysin J Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineageBlood2005 10636323638
Not in our library10.1182/blood-2005-04-1574
99.
de Mast Q Syafruddin D Keijmel S Riekerink TO Deky O Asih PB Swinkels DW van der Ven AJ Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malariaHaematologica2010 9510681074
Not in our library10.3324/haematol.2009.019331
100.
Burchard GD Radloff P Philipps J Nkeyi M Knobloch J Kremsner PG Increased erythropoietin production in children with severe malarial anemiaAm J Trop Med Hyg1995 53547551
Not in our library10.4269/ajtmh.1995.53.547
101.
Kurtzhals JA Rodrigues O Addae M Commey JO Nkrumah FK Hviid L Reversible suppression of bone marrow response to erythropoietin in Plasmodium falciparum malariaBr J Haematol1997 97169174
Not in our library10.1046/j.1365-2141.1997.82654.x
102.
Burgmann H Looareesuwan S Kapiotis S Viravan C Vanijanonta S Hollenstein U Wiesinger E Presterl E Winkler S Graninger W Serum levels of erythropoietin in acute Plasmodium falciparum malariaAm J Trop Med Hyg1996 54280283
Not in our library10.4269/ajtmh.1996.54.280
103.
el Hassan AM Saeed AM Fandrey J Jelkmann W Decreased erythropoietin response in Plasmodium falciparum malaria-associated anaemiaEur J Haematol1997 59299304
Not in our library10.1111/j.1600-0609.1997.tb01690.x
104.
Gwamaka M Fried M Domingo G Duffy PE Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemiaMalar J2011 10386
Not in our library10.1186/1475-2875-10-386
105.
Fernandes AA Carvalho LJ Zanini GM Ventura AM Souza JM Cotias PM Silva-Filho IL Daniel-Ribeiro CT Similar cytokine responses and degrees of anemia in patients with Plasmodium falciparum and Plasmodium vivax infections in the Brazilian Amazon regionClin Vaccine Immunol2008 15650658
Not in our library10.1128/cvi.00475-07
106.
Chotivanich KT Pukrittayakamee S Simpson JA White NJ Udomsangpetch R Characteristics of Plasmodium vivax-infected erythrocyte rosettesAm J Trop Med Hyg1998 597376
Not in our library10.4269/ajtmh.1998.59.73
107.
Udomsanpetch R Thanikkul K Pukrittayakamee S White NJ Rosette formation by Plasmodium vivaxTrans R Soc Trop Med Hyg1995 89635637
Not in our library10.1016/0035-9203(95)90422-0
108.
del Portillo HA Lanzer M Rodriguez-Malaga S Zavala F Fernandez-Becerra C Variant genes and the spleen in Plasmodium vivax malariaInt J Parasitol2004 3415471554
Not in our library10.1016/j.ijpara.2004.10.012
109.
Anstey NM Handojo T Pain MCF Kenangalem E Tjitra E Price RN Maguire GP Lung injury in vivax malaria: pathophysiological evidence for pulmonary vascular sequestration and posttreatment alveolar-capillary inflammationJ Infect Dis2007 195589596
Not in our library10.1086/510756
110.
Suwanarusk R Cooke BM Dondorp AM Silamut K Sattabongkot J White NJ Udomsangpetch R The deformability of red blood cells parasitized by Plasmodium falciparum and P. vivaxJ Infect Dis2004 189190194
Not in our library10.1086/380468
111.
Bass CC An attempt to explain the greater pathogenicity of Plasmodium falciparum as compared with other speciesAm J Trop Med1921 s1-12933
Not in our library
112.
Kumaresan PR Selvam R The haematology of Plasmodium vivax before and after chloroquine and primaquine treatment in North Madras areaIndian J Malariol1991 28115120
Not in our library
113.
Karunaweera ND Wijesekera SK Wanasekera D Mendis KN Carter R The paroxysm of Plasmodium vivax malariaTrends Parasitol2003 19188193
Not in our library10.1016/s1471-4922(03)00036-9
114.
Mendis KN Carter R The role of cytokines in Plasmodium vivax malariaMem Inst Oswaldo Cruz1992 87Suppl 35155
Not in our library10.1590/s0074-02761992000700006
115.
Yeo TW Lampah DA Tjitra E Piera K Gitawati R Kenangalem E Price RN Anstey NM Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: a prospective study in Papua, IndonesiaJ Infect Dis2010 202109112
Not in our library10.1086/653211
116.
Hemmer CJ Holst FGE Kern P Chiwakata CB Dietrich M Reisinger EC Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale then in Plasmodium falciparum malariaTrop Med Int Health2006 11817823
Not in our library10.1111/j.1365-3156.2006.01635.x
117.
Meera S Rao AV D'Souza V Rao SB In vitro studies on peroxidative changes leading to hemolysis of erythrocytes infested with malarial parasite Plasmodium vivaxIndian J Exp Biol1999 37729730
Not in our library
118.
Erel O Kocyigit A Avci S Aktepe N Bulut V Oxidative stress and antioxidative status of plasma and erythrocytes in patients with vivax malariaClin Biochem1997 30631639
Not in our library10.1016/s0009-9120(97)00119-7
119.
Ekvall H Malaria and anemiaCurr Opin Hematol2003 10108114
Not in our library10.1097/00062752-200303000-00002
120.
Greve B Kremsner PG Lell B Luckner D Schmid D Malarial anaemia in African children associated with high oxygen-radical productionLancet2000 3554041
Not in our library10.1016/s0140-6736(99)04761-3
121.
Griffiths MJ Ndungu F Baird KL Muller DP Marsh K Newton CR Oxidative stress and erythrocyte damage in Kenyan children with severe Plasmodium falciparum malariaBr J Haematol2001 113486491
Not in our library10.1046/j.1365-2141.2001.02758.x
122.
Fulton JD Grant PT The sulphur requirements of the erythrocytic form of Plasmodium knowlesiBiochem J1956 63274282
Not in our library10.1042/bj0630274
123.
Lamikanra AA Brown D Potocnik A Casals-Pascual C Langhorne J Roberts DJ Malarial anemia: of mice and menBlood2007 1101828
Not in our library10.1182/blood-2006-09-018069
124.
Buffet PA Safeukui I Milon G Mercereau-Puijalon O David PH Retention of erythrocytes in the spleen: a double-edged process in human malariaCurr Opin Hematol2009 16157164
Not in our library10.1097/moh.0b013e32832a1d4b
125.
Buffet PA Safeukui I Deplaine G Brousse V Prendki V Thellier M Turner GD Mercereau-Puijalon O The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiologyBlood2011 117381392
Not in our library10.1182/blood-2010-04-202911
126.
Looareesuwan S Ho M Wattanagoon Y White NJ Warrell DA Bunnag D Harinasuta T Wyler DJ Dynamic alteration in splenic function during acute falciparum malariaN Engl J Med1987 317675679
Not in our library10.1056/nejm198709103171105
127.
Severe falciparum malariaTrans R Soc Trop Med Hyg2000 94S1S90
Not in our library
128.
Giha HA Elghazali G Elgadir TM Elbasit IE Elbashir MI Severe malaria in an unstable setting: clinical and laboratory correlates of cerebral malaria and severe malarial anemia and a paradigm for a simplified severity scoringEur J Clin Microbiol Infect Dis2009 28661665
Not in our library10.1007/s10096-008-0665-5
129.
Marsh K Forster D Waruiru C Mwangi I Winstanley P Marsh V Newton C Winstanley P Warn P Peshu N Pasvol G Snow R Indicators of life-threatening malaria in African childrenN Engl J Med1995 33213991404
Not in our library10.1056/nejm199505253322102
130.
Crane GG Pryor DS Malaria and the tropical splenomegaly syndrome in New GuineaTrans R Soc Trop Med Hyg1971 65315324
Not in our library10.1016/0035-9203(71)90006-x
131.
Crane GG Gardner A Hudson P Hudson B Voller A Malarial antibodies in tropical splenomegaly syndrome in Papua New GuineaTrans R Soc Trop Med Hyg1977 71308314
Not in our library10.1016/0035-9203(77)90106-7
132.
Imbert P Rapp C Buffet PA Pathological rupture of the spleen in malaria: analysis of 55 cases (1958–2008)Travel Med Infect Dis2009 7147159
Not in our library10.1016/j.tmaid.2009.01.002
133.
Ozsoy MF Oncul O Pekkafali Z Pahsa A Yenen OS Splenic complications in malaria: report of two cases from TurkeyJ Med Microbiol2004 5312551258
Not in our library10.1099/jmm.0.05428-0
134.
Littman E Splenectomy in hereditary spherocytosis: effect on course of relapsing vivax malariaAm J Med Sci1974 2675356
Not in our library10.1097/00000441-197401000-00008
135.
Looareesuwan S Merry AH Phillips RE Pleehachinda R Wattanagoon Y Ho M Charoenlarp P Warrell DA Weatherall DJ Reduced erythrocyte survival following clearance of malarial parasitaemia in Thai patientsBr J Haematol1987 67473478
Not in our library10.1111/j.1365-2141.1987.tb06171.x
136.
Woodruff AW Ansdell VE Pettitt LE Cause of anaemia in malariaLancet1979 110551057
Not in our library10.1016/s0140-6736(79)92952-0
137.
Gandapur AS Malik SA Raziq F Bone marrow changes in human malaria: a retrospective studyJ Pak Med Assoc1997 47137139
Not in our library
138.
Chang K-H Stevenson MM Malarial anaemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malariaInt J Parasitol2004 3415011516
Not in our library10.1016/j.ijpara.2004.10.008
139.
Vedovato M De Paoli Vitali E Dapporto M Salvatorelli G Defective erythropoietin production in the anaemia of malariaNephrol Dial Transplant1999 1410431044
Not in our library10.1093/ndt/14.4.1043
140.
Boyd MF The threshold of parasite density in relation to clinical activity in primary infections with Plasmodium vivaxAm J Trop Med1938 s1-18497503
Not in our library
141.
Coatney GR Cooper WC Ruhe DS Young MD Burgess RW Studies in human malaria: XVIII. The life pattern of sporozoite-induced St. Elizabeth strain vivax malariaAm J Epid1950 51200
Not in our library
142.
Boyd MF Kitchen SF On the efficiency of the homologous properties of acquired immunity to Plasmodium vivaxAm J Trop Med1936 s1-16447457
Not in our library
143.
Boyd MF Criteria of immunity and susceptibility in naturally induced vivax malaria infectionsAm J Trop Med1942 s1-22217226
Not in our library
144.
Collins WE Jeffery GM Roberts JM A retrospective examination of reinfection of humans with Plasmodium vivaxAm J Trop Med Hyg2004 70642644
Not in our library
145.
Boyd MF Stratman-Thomas WK Kitchen SF On the duration of acquired homologous immunity to Plasmodium vivaxAm J Trop Med1936 s1-16311315
Not in our library
146.
Boyd MF Kitchen SF Recurring clinical activity in infections with the McCoy strain of Plasmodium vivaxAm J Trop Med1937 s1-17833843
Not in our library
147.
Boyd MF Matthews CB Further observations on the duration of immunity to the homologous strain of Plasmodium vivaxAm J Trop Med1939 s1-196367
Not in our library
148.
Boyd MF Kitchen SF Renewed clinical activity in naturally induced vivax malariaAm J Trop Med1944 s1-24221234
Not in our library
149.
Young MD Ellis JM Stubbs TH Some characteristics of foreign vivax malaria induced in neurosyphilitic patientsAm J Trop Med1947 s1-27585596
Not in our library
150.
Douglas NM Nosten F Ashley EA Phaipun L van Vugt M Singhasivanon P White NJ Price RN Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kineticsClin Infect Dis2011 52612620
Not in our library10.1093/cid/ciq249
151.
Cui L Escalante AA Imwong M Snounou G The genetic diversity of Plasmodium vivax populationsTrends Parasitol2003 19220226
Not in our library10.1016/s1471-4922(03)00085-0
152.
Imwong M Snounou G Pukrittayakamee S Tanomsing N Kim JR Nandy A Guthmann JP Nosten F Carlton J Looareesuwan S Nair S Sudimack D Day NP Anderson TJ White NJ Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoitesJ Infect Dis2007 195927933
Not in our library10.1086/512241
153.
Chen N Auliff A Rieckmann K Gatton M Cheng Q Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervalsJ Infect Dis2007 195934941
Not in our library10.1086/512242
154.
Boyd MF Kupper WH Matthews CB A deficient homologous immunity following simultaneous inoculation with two strains of Plasmodium vivaxAm J Trop Med1938 s1-18521524
Not in our library
155.
Hankey DD Jones R Coatney GR Alving AS Coker WG Garrison PL Donovan WN Korean vivax malaria. I. natural history and response to chloroquineAm J Trop Med Hyg1953 2958969
Not in our library
156.
Whorton CM Yount E Jones R Alving AS The Chesson strain ofPlasmodium vivaxmalaria III: clinical aspectsJ Infect Dis1947 80237249
Not in our library10.1093/infdis/80.3.237
157.
Looareesuwan S White NJ Chittamas S Bunnag D Harinasuta T High rate of Plasmodium vivax relapse following treatment of falciparum malaria in ThailandLancet1987 210521055
Not in our library10.1016/s0140-6736(87)91479-6
158.
Siripoon N Snounou G Yamogkul P Na-Bangchang K Thaithong S Cryptic Plasmodium falciparum parasites in clinical P. vivax blood samples from ThailandTrans R Soc Trop Med Hyg2002 967071
Not in our library10.1016/s0035-9203(02)90246-4
159.
Brown AE Kain KC Pipithkul J Webster HK Demonstration by the polymerase chain reaction of mixed Plasmodium falciparum and P. vivax infections undetected by conventional microscopyTrans R Soc Trop Med Hyg1992 86609612
Not in our library10.1016/0035-9203(92)90147-5
160.
Maitland K Williams TN Newbold CI Plasmodium vivax and P. falciparum: biological interactions and the possibility of cross-species immunityParasitol Today1997 13227231
Not in our library10.1016/s0169-4758(97)01061-2
161.
Luxemburger C Ricci F Nosten F Raimond D Bathet S White NJ The epidemiology of severe malaria in an area of low transmission in ThailandTrans R Soc Trop Med Hyg1997 91256262
Not in our library10.1016/s0035-9203(97)90066-3
162.
Mayxay M Pukrittayakamee S Newton PN White NJ Mixed-species malaria infections in humansTrends Parasitol2004 20233240
Not in our library10.1016/j.pt.2004.03.006
163.
Ratcliff A Siswantoro H Kenangalem E Maristela R Wuwung M Laihad F Ebsworth EP Anstey NM Tjitra E Price RN Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparisonLancet2007 369757765
Not in our library10.1016/s0140-6736(07)60160-3
164.
Price RN Nosten F Drug resistant falciparum malaria: clinical consequences and strategies for preventionDrug Resist Updat2001 4187196
Not in our library10.1054/drup.2001.0195
165.
Leslie T Mayan MI Hasan MA Safi MH Klinkenberg E Whitty CJ Rowland M Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trialJAMA2007 29722012209
Not in our library10.1001/jama.297.20.2201
166.
Kongpatanakul S Chatsiricharoenkul S Khuhapinant A Atipas S Kaewkungwal J Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteersInt J Clin Pharmacol Ther2009 47579586
Not in our library10.5414/cpp47579
167.
Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial. · 2011
Not checked
168.
Finaurini S Ronzoni L Colancecco A Cattaneo A Cappellini MD Ward SA Taramelli D Selective toxicity of dihydroartemisinin on human CD34+ erythroid cell differentiationToxicology2010 276128134
Not in our library10.1016/j.tox.2010.07.016
169.
Sowunmi A Balogun ST Gbotosho GO Happi CT Effects of amodiaquine, artesunate, and artesunate-amodiaquine on Plasmodium falciparum malaria-associated anaemia in childrenActa Trop2009 1095560
Not in our library10.1016/j.actatropica.2008.09.022
170.
Yeka A Banek K Bakyaita N Staedke SG Kamya MR Talisuna A Kironde F Nsobya SL Kilian A Slater M Reingold A Rosenthal PJ Wabwire-Mangen F Dorsey G Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in UgandaPLoS Med2005 2e190
Not in our library10.1371/journal.pmed.0020190
171.
Pukrittayakamee S Imwong M Chotivanich K Singhasivanon P Day NP White NJ A comparison of two short-course primaquine regimens for the treatment and radical cure of Plasmodium vivax malaria in ThailandAm J Trop Med Hyg2010 82542547
Not in our library10.4269/ajtmh.2010.09-0428
172.
Anderson TJC Nair S Nkhoma S Williams JT Imwong M Yi P Socheat D Das D Chotivanich K Day NPJ White NJ Dondorp AM High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in Western CambodiaJ Infect Dis2010 20113261330
Not in our library10.1086/651562
173.
Yount EH Coggeshall LT Status of immunity following cure of recurrent vivax malariaAm J Trop Med1949 s1-29701705
Not in our library10.4269/ajtmh.1949.s1-29.701
174.
Hasugian AR Purba HLE Kenangalem E Wuwung RM Ebsworth EP Maristela R Penttinen PMP Laihad F Anstey NM Tjitra E Price RN Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malariaClin Infect Dis2007 4410671074
Not in our library10.1086/512677
175.
Karunajeewa HA Mueller I Senn M Lin E Law I Gomorrai PS Oa O Griffin S Kotab K Suano P Tarongka N Ura A Lautu D Page-Sharp M Wong R Salman S Siba P Ilett KF Davis TME A trial of combination antimalarial therapies in children from Papua New GuineaN Engl J Med2008 35925452557
Not in our library10.1056/nejmoa0804915
176.
Imwong M Pukrittayakamee S Looareesuwan S Pasvol G Poirriez J White NJ Snounou G Association of genetic mutations in Plasmodium vivax dhfr with resistance in sulfadoxine-pyrimethamine: geographical and clinical correlatesAntimicrob Agents Chemother2001 4531223127
Not in our library10.1128/aac.45.11.3122-3127.2001
177.
Ekvall H Premji Z Bjorkman A Chloroquine treatment for uncomplicated childhood malaria in an area with drug resistance: early treatment failure aggravates anaemiaTrans R Soc Trop Med Hyg1998 92556560
Not in our library10.1016/s0035-9203(98)90913-0
178.
Baird JK Hoffman SL Primaquine therapy for malariaClin Infect Dis2004 3913361345
Not in our library10.1086/424663
179.
Beutler E The hemolytic effect of primaquine and related compounds: a reviewBlood1959 14103139
Not in our library
180.
Nkhoma ET Poole C Vannappagari V Hall SA Beutler E The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysisBlood Cells Mol Dis2009 42267278
Not in our library10.1016/j.bcmd.2008.12.005
181.
Baird JK McCormick GJ Canfield CJ Effects of nine synthetic putative metabolites of primaquine on activity of the hexose monophosphate shunt in intact human red blood cells in vitroBiochem Pharmacol1986 3510991106
Not in our library10.1016/0006-2952(86)90145-0
182.
Beutler E G6PD: population genetics and clinical manifestationsBlood Rev1996 104552
Not in our library10.1016/s0268-960x(96)90019-3
183.
Reeve PA Toaliu H Kaneko A Hall JJ Ganczakowski M Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiencyJ Trop Med Hyg1992 95349351
Not in our library
184.
Alving AS Johnson CF Tarlov AR Brewer GJ Kellermeyer RW Carson PE Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administrationBull World Health Organ1960 22621631
Not in our library
185.
Leslie T Mayan I Mohammed N Erasmus P Kolaczinski J Whitty CJ Rowland M A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of Plasmodium vivax in Northwest Frontier Province, PakistanPLoS ONE2008 3e2861
Not in our library10.1371/journal.pone.0002861
186.
Clyde DF Clinical problems associated with the use of primaquine as a tissue schizontocidal and gametocytocidal drugBull World Health Organ1981 59391395
Not in our library
187.
Zalusky R Drug-associated hemolytic anemiaBull N Y Acad Med1970 46427437
Not in our library
188.
Severe Plasmodium vivax Malaria, Brazilian Amazon · 2010
No notice
189.
Luxemburger C Thwai KL White NJ Webster HK Kyle DE Maelankirri L Chongsuphajaisiddhi T Nosten F The epidemiology of malaria in a Karen population on the western border of ThailandTrans R Soc Trop Med Hyg1996 90105111
Not in our library10.1016/s0035-9203(96)90102-9
190.
Spencer TE Haemoglobin levels in the D'Entrecasteaux Islands in relation to malaria and nutritionMed J Aust1966 210931097
Not in our library10.5694/j.1326-5377.1966.tb91854.x
191.
Brabin BJ Hakimi M Pelletier D An analysis of anemia and pregnancy-related maternal mortalityJ Nutr2001 131604S614Sdiscussion 614S-615S
Not in our library10.1093/jn/131.2.604s
192.
Brabin BJ Premji Z Verhoeff F An analysis of anemia and child mortalityJ Nutr2001 131636S645Sdiscussion 646S-648S
Not in our library10.1093/jn/131.2.636s
193.
Global database on blood safety: report 2004–20052008 World Health Organization, Geneva
Not in our library
194.
Jayaraman S Chalabi Z Perel P Guerriero C Roberts I The risk of transfusion-transmitted infections in sub-Saharan AfricaTransfusion2010 50433442
Not in our library10.1111/j.1537-2995.2009.002402.x
195.
Brabin BJ Ginny M Sapau J Galme K Paino J Consequences of maternal anaemia on outcome of pregnancy in a malaria endemic area in Papua New GuineaAnn Trop Med Parasitol1990 841124
Not in our library10.1080/00034983.1990.11812429
196.
Swellengrebel NH de Buck A Malaria in The Netherlands1938 Scheltema & Holkema Ltd., Amsterdam
Not in our library
197.
Brooker S Guyatt H Omumbo J Shretta R Drake L Ouma J Situation analysis of malaria in school-aged children in Kenya - what can be done?Parasitol Today2000 16183186
Not in our library10.1016/s0169-4758(00)01663-x
198.
Fernando D Wickremasinghe R Mendis KN Wickremasinghe AR Cognitive performance at school entry of children living in malaria-endemic areas of Sri LankaTrans R Soc Trop Med Hyg2003 97161165
Not in our library10.1016/s0035-9203(03)90107-6
199.
Fernando SD Gunawardena DM Bandara MR De Silva D Carter R Mendis KN Wickremasinghe AR The impact of repeated malaria attacks on the school performance of childrenAm J Trop Med Hyg2003 69582588
Not in our library
200.
Fernando D de Silva D Wickremasinghe R Short-term impact of an acute attack of malaria on the cognitive performance of schoolchildren living in a malaria-endemic area of Sri LankaTrans R Soc Trop Med Hyg2003 97633639
Not in our library10.1016/s0035-9203(03)80093-7
201.
Williams TN Maitland K Phelps L Bennett S Peto TE Viji J Timothy R Clegg JB Weatherall DJ Bowden DK Plasmodium vivax: a cause of malnutrition in young childrenQJM1997 90751757
Not in our library10.1093/qjmed/90.12.751
202.
Sachs J Malaney P The economic and social burden of malariaNature2002 415680685
Not in our library10.1038/415680a
203.
Van den Eede P Soto-Calle VE Delgado C Gamboa D Grande T Rodriguez H Llanos-Cuentas A Anne J D'Alessandro U Erhart A Plasmodium vivax sub-patent infections after radical treatment are common in Peruvian patients: results of a 1-year prospective cohort studyPLoS One2011 6e16257
Not in our library10.1371/journal.pone.0016257

Cited by papers we hold 8

Estimating the burden of α-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia · 2019
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Growing evidence of Plasmodium vivax across malaria-endemic Africa · 2019
Corrected
Anaemia and malaria · 2018
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Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity · 2018
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“Asymptomatic” Malaria: A Chronic and Debilitating Infection That Should Be Treated · 2016
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Global Epidemiology of Plasmodium vivax · 2016
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Is Plasmodium vivax Malaria a Severe Malaria?: A Systematic Review and Meta-Analysis · 2014
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Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study · 2013
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