The dependence of cell-mediated immune activation in malaria on age and endemicity

In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline.