Name: Tarimo, Donath S. Home Country: Tanzania Research Country: Tanzania Project Period: 1998-2001   Title Paediatric malaria case management under the strategy of integrated management of childhood illness (IMCI) and malaria control policy in Tanzania   Abstract Appropriate and timely case management of malaria is fundamental to malaria control and the strategy of integrated management of childhood illness (IMCI) in malaria endemic areas. However, case management is often inadequate due to diagnostic constraints as a result of the non-specificity in the presentation of malarial disease in children, and therapeutic constraints as a result of drug resistance. Therefore, to identify the factors that might contribute towards improvements in case management of malarial disease at the community and facility levels under the IMCI strategy and malaria control policy; a comprehensive epidemiological study was carried out in the transition to policy change from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP). The goal was to describe case management practices by the community and the health system, to explore clients’ perspectives on CQ efficacy and familiarity to SP, and assess the efficacy of SP monotherapy versus SP plus CQ combination therapy so as to identify the factors that might influence acceptance of SP as the replacement of CQ. The performance of the rapid diagnostic tests of ICT and OptiMal for the support of malaria diagnosis, antimalarial drugs prescribing and dispensing practices, and the in vivo SP selection for resistance as a limitation to its useful life span, were also investigated.   Fever due to malaria was reported as the commonest health problem in children < 5 years of age, conceivably attributed to high chloroquine resistance, as two in three children receiving chloroquine would get a recrudescence within two weeks. Two potential barriers to the use of formal health services were identified: fear of treatment by injections that is perceived to precipitate death to children with high fever and/or convulsions, and the initial use of tradition methods in the home management of convulsions (a symptom / sign of cerebral malaria). Such barriers have the potential to delay attainment of appropriate care.   Malaria case management was problematic, as the cardinal signs of fever and pallor used in the IMCI strategy are highly sensitive but non-specific. Nevertheless, the signs were significantly associated with parasitaemia level (> 2000/ml) that has optimal sensitivity and specificity for the definition of a clinical episode. The rapid tests of ICT & OptiMal had very high sensitivity and specificity, thus being potential for the support of malaria diagnosis in children. OptiMal was superior to ICT as it only detects viable parasites with a diagnostic reliability approaching an ideal test and had the highest diagnostic likelihood ratio. Being non- quantitative, both tests are of no prognostic significance, cannot be used in efficacy studies, and their high cost is prohibitive too. There were inadequacies in the prescription and dispensing of antimalarial drugs at 1st level public health facilities due to incorrect dosage prescriptions and the lack of instructions on dosage schedules, lack of counselling for follow up and therefore lack of continuity of care, interrupted drug availability, as well as lack of supervision and in-service training.   Although sulfadoxine-pyrimethamine (SP) monotherapy has a slow fever clearance, in the absence of resistance, parasites clearance is rapid, as at the end of 72 hours three in four children receiving SP had cleared parasites indicating a rapid action. The in vivo antipyretic effect of chloroquine (CQ) was demonstrated. Thus, irrespective of resistance to CQ, fever clearance by the SP plus CQ combination was faster than by SP monotherapy because of the antipyretic effects of CQ. Although paracetamol is antipyretic, it also prolongs parasites clearance. CQ however, apart from its antipyretic effects, is potentially synergistic to SP in parasites clearance. There were two potential barriers to the acceptance of the wider use of SP: the lack of familiarization to this drug as quinine is oftenly prescribed for CQ failures, and SP is judged to be too strong, particularly to children; the other barrier is on symptoms relief that is slower for SP than CQ hence the notion that SP is slow acting.   Mutations in the dihydrofolate reductase and dihydropteroate synthetase genes that confer resistance to SP were shown to exist in P.falciparum infections that cleared after treatment supporting the view that these mutations alone are insufficient to cause resistance to SP. A strong in vivo selective pressure for resistance was shown to operate under the conditions of supervised drug administration and optimal dosage.   The study showed that despite introduction of the IMCI strategy, in holoendemic areas, case management of malaria is still problematic as the confirmation of diagnosis is logistically not feasible. Clearly, there was the need to change policy from CQ to SP. While availability and accessibility to SP have the potential of providing a more cost effective child health care, the potential limitations for the wider use of SP as the 1st line drug, in particular the anticipated short useful life span, need to be taken into consideration and alternatives be sought in preparation for the next policy change.    Involved research institution(s) Centre for Medical Parasitology, University of Copenhagen   Supervisor(s) Ib Bygbjerg, Department of International Health, University of Copenhagen   Correspondence