Volume 98, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



The clinical epidemiology of severe malaria among patients presenting to peripheral health centers has not been well described. We conducted a prospective, observational cohort study to describe the epidemiology and clinical manifestations of severe malaria in a highland area of declining transmission intensity in Western Uganda. Individuals presenting with a history of fever were screened with a malaria rapid diagnostic test (RDT). We prepared blood smears and conducted clinical and laboratory testing for those with a positive RDT. We defined severe malaria in accordance with World Health Organization guidelines for research and epidemiological studies. A total of 6,641 individuals underwent testing for malaria. Ninety-six of 1,462 (6.6%) participants with confirmed parasitemia satisfied the criteria for severe malaria. The incidence of severe malaria peaked between 2 and 3 years of age (incidence rate ratio = 17.1, 95% confidence interval = 8.4–34.9, < 0.001) and then declined steadily until age 10. However, we also found a second peak among those ≥ 50 years of age. Severe anemia was uncommon, detected in only 5.3% of cases. Instead, shock (22.2%) and lactic acidosis (19.4%) were most frequently encountered. Our results suggest that the clinical characteristics of severe malaria presenting to rural, peripheral health centers may be different than previously observed in referral centers. These findings merit further investigation into the optimal methods for identification and management of severe malaria in rural health centers in the region.


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  1. Gething PW, 2016. Mapping Plasmodium falciparum mortality in Africa between 1990 and 2015. N Engl J Med 375: 24352445. [Google Scholar]
  2. WHO, 2016. World Malaria Report. Geneva, Switzerland: World Health Organization.
  3. Maitland K, , 2016. Severe malaria in African children—the need for continuing investment. N Engl J Med 375: 24162417. [Google Scholar]
  4. Snow RW, Bastos de Azevedo I, Lowe BS, Kabiru EW, Nevill CG, Mwankusye S, Kassiga G, Marsh K, Teuscher T, , 1994. Severe childhood malaria in two areas of markedly different falciparum transmission in east Africa. Acta Trop 57: 289300. [Google Scholar]
  5. Slutsker L, Taylor TE, Wirima JJ, Steketee RW, , 1994. In-hospital morbidity and mortality due to malaria-associated severe anaemia in two areas of Malawi with different patterns of malaria infection. Trans R Soc Trop Med Hyg 88: 548551. [Google Scholar]
  6. Modiano D, Sirima BS, Sawadogo A, Sanou I, Pare J, Konate A, Pagnoni F, , 1998. Severe malaria in Burkina Faso: influence of age and transmission level on clinical presentation. Am J Trop Med Hyg 59: 539542. [Google Scholar]
  7. Reyburn H, 2005. Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria. JAMA 293: 14611470. [Google Scholar]
  8. Cserti-Gazdewich CM, Dhabangi A, Musoke C, Ssewanyana I, Ddungu H, Nakiboneka-Ssenabulya D, Nabukeera-Barungi N, Mpimbaza A, Dzik WH, , 2013. Inter-relationships of cardinal features and outcomes of symptomatic pediatric Plasmodium falciparum malaria in 1,933 children in Kampala, Uganda. Am J Trop Med Hyg 88: 747756. [Google Scholar]
  9. Uganda Bureau of Statistics (UBOS) and ICF International, 2015. Uganda Malaria Indicator Survey 2014–15. Kampala, Uganda: UBOS and ICF International.
  10. Achan J, Tibenderana J, Kyabayinze D, Mawejje H, Mugizi R, Mpeka B, Talisuna A, D’Alessandro U, , 2011. Case management of severe malaria–a forgotten practice: experiences from health facilities in Uganda. PLoS One 6: e17053. [Google Scholar]
  11. Sundararajan R, Mwanga-Amumpaire J, Adrama H, Tumuhairwe J, Mbabazi S, Mworozi K, Carroll R, Bangsberg D, Boum Y, 2nd Ware NC, , 2015. Sociocultural and structural factors contributing to delays in treatment for children with severe malaria: a qualitative study in southwestern Uganda. Am J Trop Med Hyg 92: 933940. [Google Scholar]
  12. Chuma J, Okungu V, Molyneux C, , 2010. Barriers to prompt and effective malaria treatment among the poorest population in Kenya. Malar J 9: 144. [Google Scholar]
  13. Uganda Bureau of Statistics (UBOS), 2014. Uganda National Household Survey 2012/2013. Kampala, Uganda: UBOS.
  14. Yeka A, 2012. Malaria in Uganda: challenges to control on the long road to elimination: I. Epidemiology and current control efforts. Acta Trop 121: 184195. [Google Scholar]
  15. Uganda Bureau of Statistics (UBOS) and ICF International, 2010. Uganda Malaria Indicator Survey 2009. Calverton, MD: Uganda Bureau of Statistics (UBOS) and ICF International.
  16. WHO, Research Malaria Microscopy Standards Working Group, 2015. Microscopy for the Detection, Identification and Quantification of Malaria Parasites on Stained Thick and Thin Films. Geneva, Switzerland: World Health Organization.
  17. Murungi M, 2017. Improving the specificity of Plasmodium falciparum malaria diagnosis in high-transmission settings with a two-step rapid diagnostic test and microscopy algorithm. J Clin Microbiol 55: 15401549. [Google Scholar]
  18. Uganda Ministry of Health, 2012. National Guidelines for the Management of Common Conditions. Kampala, Uganda: Uganda Ministry of Health.
  19. WHO, 2014. Severe malaria. Trop Med Int Health 19: 7131. [Google Scholar]
  20. WHO, 2015. Guidelines for the Treatment of Malaria. Geneva, Switzerland: World Health Organization.
  21. English M, Esamai F, Wasunna A, Were F, Ogutu B, Wamae A, Snow RW, Peshu N, , 2004. Assessment of inpatient paediatric care in first referral level hospitals in 13 districts in Kenya. Lancet 363: 19481953. [Google Scholar]
  22. Reyburn H, Mwakasungula E, Chonya S, Mtei F, Bygbjerg I, Poulsen A, Olomi R, , 2008. Clinical assessment and treatment in paediatric wards in the north-east of the United Republic of Tanzania. Bull World Health Organ 86: 132139. [Google Scholar]
  23. Dondorp AM, AQUAMAT Group , 2010. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376: 16471657. [Google Scholar]
  24. Hawkes MT, 2015. Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial. Malar J 14: 421. [Google Scholar]
  25. Kremsner PG, 2016. Intramuscular artesunate for severe malaria in African children: a multicenter randomized controlled trial. PLoS Med 13: e1001938. [Google Scholar]
  26. Day NP, Phu NH, Mai NT, Chau TT, Loc PP, Chuong LV, Sinh DX, Holloway P, Hien TT, White NJ, , 2000. The pathophysiologic and prognostic significance of acidosis in severe adult malaria. Crit Care Med 28: 18331840. [Google Scholar]
  27. Dondorp AM, 2008. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis 47: 151157. [Google Scholar]
  28. Calis JC, 2008. Severe anemia in Malawian children. N Engl J Med 358: 888899. [Google Scholar]
  29. Kamya MR, 2015. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg 92: 903912. [Google Scholar]
  30. Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, , 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 22102219. [Google Scholar]
  31. Wiens MO, 2015. A cohort study of morbidity, mortality and health seeking behavior following rural health center visits by children under 12 in southwestern Uganda. PLoS One 10: e0118055. [Google Scholar]
  32. Wiens MO, 2015. Postdischarge mortality in children with acute infectious diseases: derivation of postdischarge mortality prediction models. BMJ Open 5: e009449. [Google Scholar]
  33. Roca-Feltrer A, Carneiro I, Smith L, Schellenberg JR, Greenwood B, Schellenberg D, , 2010. The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings. Malar J 9: 282. [Google Scholar]
  34. Boyce R, Reyes R, Matte M, Ntaro M, Mulogo E, Siedner M, , 2017. Use of a dual-antigen rapid diagnostic test to screen children for severe Plasmodium falciparum malaria in a high-transmission, resource-limited setting. Clin Infect Dis 65: 15091515. [Google Scholar]

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Supplemental Table

  • Received : 26 Aug 2017
  • Accepted : 21 Nov 2017
  • Published online : 26 Dec 2017

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