Acute rheumatic fever (ARF) and its chronic sequela, rheumatic heart disease (RHD), have become rare in most affluent populations, but remain unchecked in developing countries and in some poor, mainly indigenous populations in wealthy countries. More than a century of research, mainly in North America and Europe, has improved our understanding of ARF and RHD. However, whether traditional views need to be updated in view of the epidemiological shift of the past 50 years is still to be established, and improved data from developing countries are needed. Doctors who work in populations with a high incidence of ARF are adapting existing diagnostic guidelines to increase their sensitivity. Group A streptococcal vaccines are still years away from being available and, even if the obstacles of serotype coverage and safety can be overcome, their cost could make them inaccessible to the populations that need them most. New approaches to primary prevention are needed given the limitations of primary prophylaxis as a population-based strategy. The most effective approach for control of ARF and RHD is secondary prophylaxis, which is best delivered as part of a coordinated control programme.

SummaryNitric oxide (NO)-related activity has been shown to be protective against Plasmodium fakiparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NO~)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-c~ and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NO• excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NO x levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.

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