Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severe P. falciparum malaria patients in Sri Lanka.

Plasma levels of pro- and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n = 62) and uncomplicated malaria (UM; n = 69) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P < 0·01), IL-6 (P < 0·01), and IL-10 (P < 0·05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n = 14) were significantly higher than those of the UM patients (P < 0·001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n = 34) and SM (n = 34) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNF-alpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P < 0·05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.

ABO-blood-group types and protection against severe, Plasmodium falciparum malaria.

Although the ABO blood group of the human host has been reported to influence malarial infection, there have been few clinical observations on this effect. A hospital-based, comparative study was therefore performed to investigate the relationship between blood-group type and severe disease i nPlasmodium falciparum malaria. Overall, 243 cases of malaria (163 uncomplicated and 80 severe) and 65 patients with severe, non-malarial infections were studied. In terms of ABO-blood-group composition, the patients with severe malaria were significantly different from the patients with the uncomplicated disease (P<0.001) and also from a population control described previously (P<0.0001). The patients with uncomplicated malaria or severe but non-malarial disease were, however, similar to the population control. The cases of severe malaria were significantly less likely to be of blood group O (P=0.0003), and significantly more likely to be of group AB (P<0.0001), than the patients with nonsevere malaria. It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection.

TNFalpha*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans.

We have investigated the association between alleles of the genes for tumour necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease during malarial (Plasmodium falciparum) and other infections in the Sri Lankan population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicated infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-alpha and TNF-beta allelic types were identified using the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes and restriction enzyme digestion. The odds in favour of carrying the TNFalpha*2 allele, mainly of the heterozygous genotype (TNFalpha*1,*2), were two to three times greater among individuals with severe disease, of either malarial or other infectious origin, relative to healthy controls or to those with uncomplicated malarial infections. No significant risk was associated with either of the alleles of TNF-beta.

Malaria mortality rates in South Asia and in Africa: implications for malaria control.

Malaria mortality in human populations varies greatly under different circumstances. The intense malaria transmission conditions found in many parts of tropical Africa, the much lower malaria inoculation rates currently sustained in areas of southern Asia, and the epidemic outbreaks of malaria occasionally seen on both continents, present highly contrasting patterns of malaria-related mortality. Here Harsha Alles, Kamini Mendis and Richard Carter examine malaria-related mortality under different circumstances and discuss implications for the management of malaria in these settings. They emphasize the power of rapid case treatment to save lives at risk under virtually all circumstances of malaria transmission.