The natural history of complicated falciparum malaria--a prospective study.

Objective: Despite a substantial disease burden, little is known about the natural history of complicated falciparum malaria. Therefore, the present prospective study was undertaken to assess the clinical course, outcome, and resolution time of various complications of falciparum malaria.

Methods: This prospective study has been conducted in a tertiary health care institution with high prevalence of malaria. A cohort of 608 patients of complicated falciparum malaria with single and multiple complications were enrolled. After discharge, all patients were followed up for 1 month except patients with anaemia who were followed up for 3 months. The onset time, interval of progression of one complication to other, resolution time of complications and mortality were determined.

Results: At the time of admission there were 288 (46.8%) patients with single complication (SC) and 320 (53.2%) patients with multiple complications (MC). Majority (n=214, 74.3%) of patients with SC had cerebral malaria, followed by jaundice (14.6%), anaemia (6.9%), hypoglycaemia (2.1%), and respiratory distress (2.1%). The multiple complications were found in various combinations and majority (n=136, 42.5%) had constellation of 3 different complications. Cerebral malaria, jaundice, and renal failure (102 of 136, 75.3%) were the most common combination. Regardless of number of complications, cerebral malaria was present in 91.6% (293 of 320) patients with MC. As the population of patients progressed from single to multiple complications, increasing proportions had jaundice, renal failure, and anaemia. 12.8% to 36.2% of patients in any category progressed from one complication to other complication within 72 hrs. There mortality rate was 14.6%, 21.3%, 30.9%, 38.5%, 100%, and 100% among patients with 1, 2 , 3, 4, 5, and 6 complications respectively.

Conclusion: This is the first prospective study that provides the clinical evidence that complicated malaria represents a hierarchical continuum of abnormalities resulting from malaria infection. All complications developed within 5 days (median 72 hrs, range-2 to l20 hrs.) of onset of fever. Pre-pernicious stage had been recognised in cases of cerebral malaria. Each complication is unique in its onset and recovery time. Not only the number but also the type of complication influences the outcome of complicated malaria.