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Müller, Tara Catharina (2013): Non-malaria febrile illness: a cross-sectional, observational study in rural areas of Cambodia. Dissertation, LMU München: Faculty of Medicine



In Cambodia, the number of reported malaria cases, as well as case fatality rates, continue to decrease since the implementation of large scale malaria programs in the country 10 years ago. However, with the introduction and wide distribution of rapid diagnostic tests (RDTs) for malaria, it also turned out that in many of the clinically suspected malaria cases, no malaria parasites could be detected. As a first step towards developing an algorithm for malaria-RDT negative fever management at peripheral health posts, a cross-sectional, prospective, observational study was designed to investigate the causes of acute malaria-negative febrile illness in rural areas of Cambodia. From January 2008 to December 2010, 1475 study subjects were recruited in three different sites throughout the country. Among the study subjects, 1193 were febrile out-patients and 282 were non-febrile individuals who have been recruited as a control group. A battery of test was run on the samples in the central laboratory in Phnom Penh. In 73.2% of the 1193 febrile outpatient samples, at least one pathogen was identified. In 26.8% of these samples the etiology of the fever remained unknown. Most frequent pathogens detected by molecular diagnostics were P. vivax (26.4%), P. falciparum (20.7%), Leptospira (9.5%), Dengue Virus (5.4%), Influenza Virus A (5.9%), O. tsutsugamushi (3.7%), Influenza Virus B (1.8%), Rickettsia (0.2%) and bacteria from blood culture (Salmonella spp., E. coli, S. pneumoniae, E. cloacae) (0.8%). Conclusions: Malaria is still amongst the principal causes of undifferentiated fever in this setting, even though RDTs did not prove sufficient to diagnose cases of low parasitemia and infections with P. vivax. RDT-negative fever cases should be tested for malaria using microscopy or ideally PCR. If malaria is ruled out, diagnostic tools are needed to distinguish between either viral or bacterial etiology of the fever. Leptospirosis and rickettsial diseases showed to play an important role and are easily treatable with the right antibiotics. However, more research and better diagnstic tools are needed to understand and map the incidence of these diseases in Cambodia.