Anaemia and malaria

Abstract

Malaria is a major cause of anaemia in tropical areas. Malaria infection causes haemolysis of infected and uninfected erythrocytes and bone marrow dyserythropoiesis which compromises rapid recovery from anaemia. In areas of high malaria transmission malaria nearly all infants and young children, and many older children and adults have a reduced haemoglobin concentration as a result. In these areas severe life-threatening malarial anaemia requiring blood transfusion in young children is a major cause of hospital admission, particularly during the rainy season months when malaria transmission is highest. In severe malaria, the mortality rises steeply below an admission haemoglobin of 3 g/dL, but it also increases with higher haemoglobin concentrations approaching the normal range. In the management of severe malaria transfusion thresholds remain uncertain. Prevention of malaria by vector control, deployment of insecticide-treated bed nets, prompt and accurate diagnosis of illness and appropriate use of effective anti-malarial drugs substantially reduces the burden of anaemia in tropical countries.

Fig. 1

Relationship of severe falciparum malaria manifestations to age at different levels of malaria transmission

Fig. 2

Age patterns of average haemoglobin concentrations in young children in Demographic and Health Surveys (DHS) from four African countries with moderate to high malaria transmission (Reproduced from Crawley J, with permission [11])

Fig. 3

Estimated contributions of falciparum and vivax malaria to severe anaemia in Papua. Shows adjusted population attributable fractions with 95% confidence bands of severe anaemia (Hb < 5 g/dL) by Plasmodium species and by age (From Douglas et al. with permission [9])

Fig. 4

The delayed reticulocyte response to anaemia in Thai adults with acute uncomplicated falciparum malaria [28]. Shows mean and SE values, and dashed line represents time to parasite clearance assessed by microscopy

Fig. 5

Correlation between admission values of mean red blood cell deformability (RCD) at a shear stress (SS) of 30 Pa and the lowest haemoglobin (Hb) concentration reached during hospitalization in Thai patients with severe falciparum malaria (correlation coefficient 0.49, P = 0.002). When patients with a microcytic anaemia (MCV,80fL: red circles) were excluded, the correlation coefficient was 0.64, P < 0.001) [49]

Fig. 6

Augmented splenic clearance function for rigid erythrocytes associated with splenic enlargement in Thai adults with acute malaria [61]. Clearance curves of ⁵¹Cr-labelled heated autologous erythrocytes after intravenous injection to 10 uninfected volunteers, 9 patients with no detectable splenomegaly and 16 with palpable spleens (mean ± SD)

Fig. 7

Reduction in haemoglobin concentrations, corresponding increases in pitted erythrocytes, reticulocyte responses and plasma LDH in relation to anti-malarial drug treatment (artesunate or quinine) in African children in Kinshasa, DRC, admitted to hospital with hyperparasitaemic falciparum malaria [70]

Fig. 8

Development of anaemia and subsequent recovery in Karen patients with acute falciparum malaria treated on the Thailand-Myanmar border [33]

Fig. 9

Untreated Plasmodium vivax infections in Australian army volunteers [102]. Numbers of subjects are given along the top. The haemoglobin concentrations reached a nadir during the 5th week of illness but then rose despite continuing parasitaemia

Fig. 10

The relationship between admission haemoglobin and mortality in outpatients and hospitalized patients in Papua showing the substantially higher mortality of falciparum malaria with very severe anaemia compared with malaria caused by other Plasmodium species. Figures generated by multiple fractional polynomial regression analyses with the following covariables: Plasmodium species, hemoglobin, age, sex, ethnic group, and year. Bands represent 95% CIs (From Douglas et al. [9] with permission)

Fig. 11

Overall relationship between haemoglobin concentrations on admission and outcomes in 6451 adults and children with severe falciparum malaria studied in Africa and Asia between 1980 and 2015 who were admitted with a parasite density of > 10,000/μL. Below 5 g/dL (vertical blue dashed line) anaemia itself was a criterion for severe malaria. Inset is shown this same relationship in the subgroup of 2729 patients with cerebral malaria and the same parasitaemia range

Fig. 12

Time to death in children and adults admitted to hospitals in Asia and Africa with severe falciparum malaria