Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission

Abstract
A hospital-based study was carried out in Gedarif town, eastern Sudan, an area of markedly unstable malaria transmission. Among the 2488 diagnosed malaria patients, 4.4% fulfilled the WHO criteria for severe malaria, and seven died of cerebral malaria. The predominant complication was severe malarial anemia (45.4%), followed by convulsions (21%), cerebral malaria (16. 4%) and hypotension (11.8%). Severe malaria was recognized in all age groups, but 44.5% of patients were aged 2 to 4 years. The mean ages of patients with severe anemia (5.6 years) and convulsions (5.9 years) were significantly lower than the mean ages of patients with cerebral malaria (14.1 years) or hypotension (35.2 years). Patients with convulsions and cerebral malaria had significantly higher mean parasite count (69 972 and 56 110 parasites/μL, respectively) than patients with severe anemia (24 637parasites/μL) or hypotension (13 667 parasites/μL). The mean blood glucose level was higher in patients with cerebral malaria than in patients with anemia, and higher in patients who died than in patients who survived. In this setting, the clinico-epidemiological pattern of severe malaria varies considerably from that of hyperendemic regions in sub-Saharan Africa, and there is considerable variation between the individual complications of severe malaria. Keywords Severe malaria Plasmodium falciparum Unstable transmission Sudan 1 Introduction Plasmodium falciparum malaria is one of the most common causes of morbidity and mortality in tropical and subtropical regions of the world. In sub-Saharan Africa, complications of P. falciparum malaria, namely cerebral malaria and severe malarial anemia, are leading causes of mortality ( WHO, 2000 ). The epidemiological profile and clinical pattern of severe malaria in Africa has been shown to be modulated by the intensity of exposure and pattern of transmission ( Snow et al., 1997 ). In regions holo- or hyperendemic for malaria, the greatest suffering is borne by children less than 5 years of age, whereas in areas of low endemicity, with special reference to central Sudan, the disease affects all age groups ( Giha et al., 2000 ). In areas of high endemicity, although individuals more than 5 years of age continue to harbor malaria parasites, the frequency of severe disease is greatly reduced. This protection from disease in older children and the development of clinical immunity is not usually reached in regions where there is low or seasonal exposure to the parasite ( MacDonald, 1957; Miller et al., 1994 ). The acquisition of immunity is slow, requiring many years of exposure to the parasite, and numerous disease episodes. Even then, the acquired immunity is practically never complete, and residents of malaria-endemic areas continue to experience sporadic episodes of clinical disease throughout life, but with reduced frequency ( Trape et al., 1994 ). According to the latest WHO report, malaria causes 3000 deaths per day, an annual total that exceeds one million deaths worldwide ( WHO, 2002 ), which is attributed solely to the complications of infection with P. falciparum . The vast majority of deaths occur among children in Africa and approximately 2% of clinical attacks of malaria at this age are estimated to lead to severe and complicated disease ( Greenwood et al., 1991 ). It is not known what determines the outcome of individual infections or how the outcome of an infection with P. falciparum varies depending on the level of exposure or transmission ( Snow et al., 1997 ). In Southeast Asia, severe malaria occurring during adulthood has a distinct clinical pattern, where the mortality is mostly due to respiratory distress syndrome, renal failure and cerebral malaria ( Mohanty et al., 2003 ). In sub-Saharan Africa, different levels of malaria transmission were related to different forms of disease manifestation ( Snow et al., 1997 ). Accordingly, identification of severe disease within each community is critical for the rational design and effectiveness of interventions. Although it is well established that genetic factors of both parasites and hosts control the outcome of malaria infections, the nature of the host genes regulating anti-parasite immune responses is poorly understood ( Abel et al., 1992; Miller et al., 1994 ). Studies of West African sympatric ethnic groups demonstrated considerable differences in clinical consequences (morbidity and mortality) of infection with P. falciparum , regardless of the epidemiological and geographical variations (reviewed by Modiano et al., 1999 ). Most of the clinico-epidemiological data on severe malaria has been derived either from areas of intense transmission in Africa, or from areas of seasonal transmission in Asia. However, the present study revealed a pattern of severe malaria morbidity and mortality which is different from what was reported from sub-Saharan Africa. This imposes a distinction between the wet sub-Saharan Africa and the dry savanna of sub-Saharan Africa, like central Sudan. 2 Materials and methods 2.1 Study area This study was carried out over two successive malaria seasons between September 2000 and January 2002, in Gedarif Hospital. Gedarif town (350 to 400 thousand inhabitants) is situated on the Sudanese Savanna, at an altitude of about 600 m a.s.l., and is 350 km from the capital, Khartoum. The epidemiology of febrile uncomplicated malaria episodes in the area has been reported before ( Giha et al., 2000 ). Malaria in the area is highly seasonal, and follows the annual June–October rains; the seasonal incidence of malaria varies considerably from year to year ( Theander, 1998 ). Anopheles arabiensis is the sole malaria vector in the area. The entomological inoculation rate in Gedarif has not been measured, but was found to be very low and difficult to measure by conventional methods in the surrounding villages ( Hamad et al., 2002 ). 2.2 Study design Patients reporting to Gedarif Hospital were...

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