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.

https://espace.cdu.edu.au/eserv/cdu:38333/Douglas_38333.pdf

The anaemia of Plasmodium vivax malaria

The prevalence of anaemia during pregnancy was investigated in relation to parasite and spleen rates of pregnant women living in a defined study area in rural Madang, Papua New Guinea. The effects in pregnancy of anaemia, iron deficiency and malaria on the foetus were investigated. There is a high prevalence of anaemia in this population, with 44% of primigravidae and 29% of multigravidae having severe anaemia [haemoglobin (Hb) less than 8 g dl-1] after 28 weeks gestation. The odds ratio for severe anaemia at 0-16 weeks gestation in pregnant compared to non-pregnant women was 4.7 (P less than 0.0001). Forty-seven per cent of primigravidae and 32% of multigravidae had evidence of iron deficiency with high free erythrocyte protoporphyrin values (greater than 35 micrograms dl-1 whole blood) at antenatal booking. The risk of severe anaemia was significantly associated with splenomegaly and iron deficiency for all gravidae (splenomegaly P less than 0.05; iron deficiency, P less than 0.0002). Hb values at delivery were higher than at first attendance, with the greatest difference between groups malaria-positive at booking and malaria-negative at delivery (primigravidae 1.5 g dl-1, P less than 0.01; multigravidae, 0.7 g dl-1, P less than 0.01), indicating that malaria prophylaxis was an important factor in controlling anaemia. Two Hb groups were defined on the basis of the cut-off at 8 g dl-1, which corresponded to the lower quartile value at booking and delivery. A significantly increased risk of low birthweight was shown for primigravidae with values below 8 g dl-1 (65% v. 27%, P less than 0.025), but the prematurity rate was not significantly increased, indicating that the majority of babies were growth-retarded. Early pregnancy anaemia and iron deficiency were related to the risk of low birthweight in primigravidae. Current parasitaemia at delivery appeared a less important factor, although primigravidae with severe anaemia and parasitaemia at delivery had the lowest birthweights. The extent to which malaria control, using drug treatment and chemoprophylaxis, can reduce the risk of low birthweight will vary in relation to the prevalence and causes of anaemia in women.

Consequences of maternal anaemia on outcome of pregnancy in a malaria endemic area in Papua New Guinea.

Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with ⩾50% oval red cells matched by age, sex and village of residence with controls having ⩽30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0·009), for P. falciparum (P = 0·044), and for all species of malaria parasites (P = 0·013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0·01 < P < 0·025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.

Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea

Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome)

Prevention and treatment of malaria

Levels of species and class-specific malarial antibody were studied in 249 New Guineans with tropical splenomegaly syndrome (TSS) and in 87 control subjects living in the same area. Titres of IgG and IgM antibody to Plasmodium falciparum, P. vivax and P. malariae were estimated by indirect immunofluorescence. Both IgG and IgM antibody levels were higher in subjects with TSS than in controls; IgM titres were highest in those with the greatest splenic enlargement. Responses to all three species were comparable. It is concluded that there is no evidence from this study to incriminate any one species of malaria parasite in the production of tropical splenomegaly syndrome.

Malarial antibodies in tropical splenomegaly syndrome in Papua New Guinea.

Metabolic studies using 131I-labelled human serum albumin have been performed in 19 adult inhabitants of the Upper Watut Valley of New Guinea, all of whom were suffering from tropical splenomegaly syndrome with at least Grade III splenomegaly. Albumin synthesis was generally increased, the mean synthesis rate being 1·45 times the Caucasian mean. This resulted in an increase in total body albumin, most of which was retained in the intravascular space. There was a tendency for highest synthesis rates to occur in subjects with the greatest expansion in plasma volume, though the correlation coefficient was not statistically significant.

The rǒle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome I. Metabolism of 131I-labelled albumin

The effect of alterations in serum protein levels on plasma volume in tropical splenomegaly syndrome has been investigated by determining plasma volume, serum albumin, globulin and immunoglobulin levels in 64 adult New Guineans suffering from this disease. Plasma volumes ranged from 51.2 to 129 ml./kg. Significant positive correlations were found between plasma volume and intravascular pools of albumin, IgG and IgM. Multiple regression analysis demonstrated that 70% of the variance in plasma volume in this series was attributable to increases in these three pools, IgM and IgG accounting for 42% of the total and albumin for 28%. It is probable that the unexplained 30% of plasma volume expansion arises through a splenic arterio-venous shunt effect. It is suggested that initially in tropical splenomegaly syndrome the splenic shunt and immunoglobulin overproduction combine to produce expansion of plasma volume and a fall in intravascular colloid osmotic pressure; that the latter provides the stimulus to increased albumin synthesis, and that this further aggravates the plasma volume expansion and the consequent dilutional anaemia commonly seen in this disease.

The rôle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome. III. The interrelationships of albumin, immunoglobulins and plasma volume.

G.G. Crane

Papers

Malarial antibodies in tropical splenomegaly syndrome in Papua New Guinea.

The rǒle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome I. Metabolism of 131I-labelled albumin

The rôle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome. III. The interrelationships of albumin, immunoglobulins and plasma volume.

Pathogenesis of anemia in coastal New Guineans

Pathogenesis of anemia in coastal New Guineans1 international nutrition