Transactions of the Royal Society of Tropical Medicine and Hygiene Volume 99, Issue 4, Pages 243-319 (April 2005)
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Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission • ARTICLE Pages 243-251 H.A. Giha, G. ElGhazali, T.M.E. A-Elgadir, I.E. A-Elbasit, E.M. Eltahir, O.Z. Baraka, M.M. Khier, I. Adam, M. Troye-Blomberg, T.G. Theander and M.I. Elbashir
Ecological mechanisms that promote arbovirus survival: a mathematical model of Ross River virus transmission • ARTICLE Pages 252-260 K. Glass
Periodic deworming with albendazole and its impact on growth status and diarrhoeal incidence among children in an urban slum of India • ARTICLE Pages 261-267 D. Sur, D.R. Saha, B. Manna, K. Rajendran and S.K. Bhattacharya
Echinococcosis in Tunisia: a cost analysis • ARTICLE Pages 268-278 Meghan M. Majorowski, Hélène Carabin, Mohamed Kilani and Afif Bensalah
A randomized, double-blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three-monthly, against Onchocerca volvulus: ophthalmological results • ARTICLE Pages 279-289 Grace Fobi, Jacques Gardon, Joseph Kamgno, Laurence Aimard-Favennec, Christian Lafleur, Nathalie Gardon-Wendel, Brian O.L. Duke and Michel Boussinesq
Laboratory-based influenza surveillance in New Caledonia, 1999–2003 • ARTICLE
Pages 290-300 Alain Berlioz-Arthaud and Ian G. Barr
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Associations between filarial and gastrointestinal nematodes • ARTICLE Pages 301-312 Helen Faulkner, Joseph Turner, Jerzy Behnke, Joseph Kamgno, Marie-Claire Rowlinson, Janette E. Bradley and Michel Boussinesq
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Comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether • CORRESPONDENCE Pages 313-314 Ushma Mehta, Karen I. Barnes, Harsha Kathard, Michèle van Vugt and David Durrheim
Reply to comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether • CORRESPONDENCE Pages 314-315 Stephen Toovey
Comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether • CORRESPONDENCE Pages 315-316 Harald Reinhart, Colin Hughson and Patricia Ibarra de Palacios
Reply to comment on: Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether • CORRESPONDENCE Pages 316-317 Stephen Toovey
[] Ian Maudlin, Peter H. Holmes and Michael A. Miles (Eds). The Trypanosomiases CABI Publishing, Wallingford, 2004, 624 pp., hardback, ISBN: 0-85199-475-X (£99.50/US$185.00). • BOOK REVIEW Page 318 Wendy Gibson
Application for admission as a fellow • MISCELLANEOUS Page 319 Copyright © 2006 Royal Society of Tropical Medicine and Hygiene
Transactions of the Royal Society of Tropical Medicine and Hygiene (2005) 99, 243—251
Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission H.A. Gihaa,∗, G. ElGhazalia, T.M.E. A-Elgadira, I.E. A-Elbasita, E.M. Eltahira, O.Z. Barakab,c, M.M. Khierc, I. Adamd, M. Troye-Blomberge, T.G. Theanderf, M.I. Elbashira a
Malaria Research Centre (MalRC), Department of Biochemistry, and Department of Microbiology and Immunology, Faculty of Medicine, University of Khartoum, P.O. Box 102, Khartoum, Sudan b The Malaria Administration, Federal Ministry of Health, Khartoum, Sudan c Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan d Obstetrics and Gynaecology Unit, New-Halfa Hospital, Sudan e Department of Immunology, The Wenner-Gren Institute, Stockholm University, Sweden f Centre for Medical Parasitology, Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark Received 23 December 2003 ; received in revised form 14 April 2004; accepted 21 April 2004 Available online 25 December 2004 KEYWORDS Severe malaria; Plasmodium falciparum; Unstable transmission; Sudan
Summary 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/L, respectively) than patients with severe anemia (24 637parasites/L) or hypotension (13 667 parasites/L). 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. © 2004 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +249 9129 075 20; fax: +249 183 775351.
E-mail address:
[email protected] (H.A. Giha).
0035-9203/$ — see front matter © 2004 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2004.04.002
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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 subSaharan 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
H.A. Giha et al. 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 seen, free of charge, by medical doctors at an outpatient malaria clinic. Blood slides were prepared from suspected malaria patients and examined for the presence of malaria parasites. Based on clinical assessment, patients with severe falciparum malaria were admitted and patients with uncomplicated disease were treated as outpatients. All patients who satisfied the WHO criteria of severe malaria were enrolled in the study after obtaining
Clinical pattern of severe Plasmodium falciparum informed consent from the patients or the guardian. Some patients who did not fulfil the WHO criteria were also admitted, but were not enrolled in the study. Patients with severe malaria had certain investigations done routinely, e.g. blood glucose level (electronic glucometer, Accutrend), blood insulin measured by radioimmunoassay (kit IMK-414, Beijing, China; Morgan and Lazarow, 1962) and complete hemogram. Other diagnostic investigations were done: each was selected based on the clinical presentation of the patients, e.g. chest X-ray, blood and spinal fluid culture, serum/plasma creatinine, lactate, urea and electrolytes. The results and the clinical data were entered into a database program, Microsoft Access. The patients were discharged from hospital when they had improved clinically and had the ability to continue the treatment orally at home under medical supervision. Patients were followed-up, clinically and parasitologically up to day 28 after diagnosis, and were advised to visit our malaria clinic if symptoms recurred thereafter. This study had National Ethical Clearance and National Endorsement from the Ministry of Health, Sudan.
2.3. Malaria definition and diagnosis A patient was defined as suffering from malaria if he/she complained of fever or had body temperature measured with an oral probe of >37.5 ◦ C plus microscopically detected asexual parasitemia. For diagnosis, thick and thin blood films were collected, stained with Giemsa and examined for malaria parasites under a magnification of ×1000. Films were considered negative after examination of 200 thick film fields without detection of parasites. For positive films, parasite counts were done. Uncomplicated cases of malaria were treated with chloroquine and/or fansidar, while patients with asymptomatic malaria were rare in the area and were not included in the study. All patients with severe malaria were treated with quinine injections for at least 24 hours, and then given quinine tablets for a total duration of seven days. Patients with severe malarial anemia were further treated with cross-matched, infection-screened blood transfusion.
2.4. Characterization and grouping of patients with severe malaria Using the clinical information (symptoms and signs) and the laboratory results available, the patients were allocated to the different categories of severe malaria according to the WHO criteria for se-
245 vere and complicated malaria (WHO, 2000). Patients with severe anemia had normocytic anemia with hematocrit
