World Health Organization, 2013. World Health Statistics. Available at: http://apps.who.int/gho/data/node.main.ChildMortDistRegion?lang=en. Accessed November 19, 2014.
O'Meara WP, Mangeni JN, Steketee R, Greenwood B, 2010. Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect Dis 10: 545–555.
Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD, 2012. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 379: 413–431.
Mwangangi JM, Mbogo CM, Orindi BO, Muturi EJ, Midega JT, Nzovu J, Gatakaa H, Githure J, Borgemeister C, Keating J, Beier JC, 2013. Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years. Malar J 12: 13.
Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, Ooi EE, Maro VP, Saganda W, Kinabo GD, Muiruri C, Bartlett JA, 2013. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis 7: e2324.
Leslie T, Mikhail A, Mayan I, Anwar M, Bakhtash S, Nader M, Chandler C, Whitty CJ, Rowland M, 2012. Overdiagnosis and mistreatment of malaria among febrile patients at primary healthcare level in Afghanistan: observational study. BMJ 345: e4389.
Katz MA, Lebo E, Emukule G, Njuguna HN, Aura B, Cosmas L, Audi A, Junghae M, Waiboci LW, Olack B, Bigogo G, Njenga MK, Feikin DR, Breiman RF, 2012. Epidemiology, seasonality, and burden of influenza and influenza-like illness in urban and rural Kenya, 2007–2010. J Infect Dis 206 (Suppl 1): S53–S60.
Yazdanbakhsh M, Kremsner PG, 2009. Influenza in Africa. PLoS Med 6: e1000182.
Gessner BD, Shindo N, Briand S, 2011. Seasonal influenza epidemiology in sub-Saharan Africa: a systematic review. Lancet Infect Dis 11: 223–235.
Majanja J, Njoroge RN, Achilla R, Wurapa EK, Wadegu M, Mukunzi S, Mwangi J, Njiri J, Gachara G, Bulimo W, 2013. Impact of influenza A (H1N1) pdm09 virus on circulation dynamics of seasonal influenza strains in Kenya. Am J Trop Med Hyg 88: 940–945.
Waitumbi JN, Kuypers J, Anyona SB, Koros JN, Polhemus ME, Gerlach J, Steele M, Englund JA, Neuzil KM, Domingo GJ, 2010. Outpatient upper respiratory tract viral infections in children with malaria symptoms in western Kenya. Am J Trop Med Hyg 83: 1010–1013.
Feikin DR, Njenga MK, Bigogo G, Aura B, Aol G, Audi A, Jagero G, Muluare PO, Gikunju S, Nderitu L, Balish A, Winchell J, Schneider E, Erdman D, Oberste MS, Katz MA, Breiman RF, 2012. Etiology and incidence of viral and bacterial acute respiratory illness among older children and adults in rural western Kenya, 2007–2010. PLoS ONE 7: e43656.
D'Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, Lengeler C, Cherpillod P, Kaiser L, Genton B, 2014. Beyond malaria—causes of fever in outpatient Tanzanian children. N Engl J Med 370: 809–817.
Berkley JA, Munywoki P, Ngama M, Kazungu S, Abwao J, Bett A, Lassauniére R, Kresfelder T, Cane PA, Venter M, Scott JA, Nokes DJ, 2010. Viral etiology of severe pneumonia among Kenyan infants and children. JAMA 303: 2051–2057.
Marijon E, Mirabel M, Celermajer DS, Jouven X, 2012. Rheumatic heart disease. Lancet 379: 953–964.
Carapetis JR, Steer AC, Mulholland EK, Weber M, 2005. The global burden of group A streptococcal diseases. Lancet Infect Dis 5: 685–694.
Zuhlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, Mauff K, Islam S, Joachim A, Daniels R, Francis V, Ogendo S, Gitura B, Mondo C, Okello E, Lwabi P, Al-Kebsi MM, Hugo-Hamman C, Sheta SS, Haileamlak A, Daniel W, Goshu DY, Abdissa SG, Desta AG, Shasho BA, Begna DM, ElSayed A, Ibrahim AS, Musuku J, Bode-Thomas F, Okeahialam BN, Ige O, Sutton C, Misra R, Abul Fadl A, Kennedy N, Damasceno A, Sani M, Ogah OS, Olunuga T, Elhassan HH, Mocumbi AO, Adeoye AM, Mntla P, Ojji D, Mucumbitsi J, Teo K, Yusuf S, Mayosi BM, 2014. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J. doi:http://dx.doi.org/10.1093/eurheartj/ehu449.
Poverty Rates by County, 2005/6. Kenya Bureau of Statistics. Available at: https://www.opendata.go.ke/Counties/Poverty-Rates-by-County/z6za-e7yb. Accessed November 19, 2014.
Obala AA, Mangeni JN, Platt A, Aswa D, Abel L, Namae J, O'Meara WP, 2015. What is threatening the effectiveness of insecticide-treated bednets? A case-control study of environmental, behavioral, and physical factors associated with prevention failure. PLoS One (under review).
Kim C, Ahmed JA, Eidex RB, Nyoka R, Waiboci LW, Erdman D, Tepo A, Mahamud AS, Kabura W, Nguhi M, Muthoka P, Burton W, Breiman RF, Njenga MK, Katz MA, 2011. Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays. PLoS ONE 6: e21610.
Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR, 2010. Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J 9: 269.
1992. Guidelines for the diagnosis of rheumatic fever. Jones criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. JAMA 268: 2069–2073.
Bassat Q, Machevo S, O'Callaghan-Gordo C, Sigaúque B, Morais L, Díez-Padrisa N, Ribó JL, Mandomando I, Nhampossa T, Ayala E, Sanz S, Weber M, Roca A, Alonso PL, 2011. Distinguishing malaria from severe pneumonia among hospitalized children who fulfilled integrated management of childhood illness criteria for both diseases: a hospital-based study in Mozambique. Am J Trop Med Hyg 85: 626–634.
Mayxay M, Castonguay-Vanier J, Chansamouth V, Dubot-Pérès A, Paris DH, Phetsouvanh R, Tangkhabuanbutra J, Douangdala P, Inthalath S, Souvannasing P, Slesak G, Tongyoo N, Chanthongthip A, Panyanouvong P, Sibounheuang B, Phommasone K, Dohnt M, Phonekeo D, Hongvanthong B, Xayadeth S, Ketmayoon P, Blacksell SD, Moore CE, Craig SB, Burns MA, von Sonnenburg F, Corwin A, de Lamballerie X, González IJ, Christophel EM, Cawthorne A, Bell D, Newton PN, 2013. Causes of non-malarial fever in Laos: a prospective study. The Lancet Global Health 1: e46–e54.
Taylor SM, Molyneux ME, Simel DL, Meshnick SR, Juliano JJ, 2010. Does this patient have malaria? JAMA 304: 2048–2056.
Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, Martin JM, Van Beneden C, 2012. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 55: e86–e102.
Pondei K, Kunle-Olowu OE, Peterside O, 2013. The aetiology of non-malarial febrile illness in children in the malaria-endemic Niger Delta Region of Nigeria. Asian Pacific Journal of Tropical Disease 3: 56–60.
Bergmark R, Bergmark B, Blander J, Fataki M, Janabi M, 2010. Burden of disease and barriers to the diagnosis and treatment of group a beta-hemolytic streptococcal pharyngitis for the prevention of rheumatic heart disease in Dar Es Salaam, Tanzania. Pediatr Infect Dis J 29: 1135–1137.
Carapetis JR, McDonald M, Wilson NJ, 2005. Acute rheumatic fever. Lancet 366: 155–168.
Wachira J, Ndege S, Koech J, Vreeman R, Ayuo P, Braitstein P, 2013. HIV testing uptake and prevalence among adolescents and adults in a large home-based HIV testing program in western Kenya. J Acquir Immune Defic Syndr 65: e58–e66.
Kasper MR, Blair PJ, Touch S, Sokhal B, Yasuda CY, Williams M, Richards AL, Burgess TH, Wierzba TF, Putnam SD, 2012. Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia. Am J Trop Med Hyg 86: 246–253.
Hertz JT, Munishi OM, Ooi EE, Howe S, Lim WY, Chow A, Morrissey AB, Bartlett JA, Onyango JJ, Maro VP, Kinabo GD, Saganda W, Gubler DJ, Crump JA, 2012. Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania. Am J Trop Med Hyg 86: 171–177.
Sutherland LJ, Cash AA, Huang YJ, Sang RC, Malhotra I, Moormann AM, King CL, Weaver SC, King CH, LaBeaud AD, 2011. Serologic evidence of arboviral infections among humans in Kenya. Am J Trop Med Hyg 85: 158–161.
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In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1–3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed.
Financial support: This study was supported by a pilot grant from Duke Global Health Institute.
Authors' addresses: Wendy P. O'Meara, Division of Infectious Diseases and International Health, Duke University Medical Center, Duke Global Health Institute, Durham, NC, and Moi University School of Public Health, College of Health Sciences, Eldoret, Kenya, E-mail: wpo@duke.edu. Joshua A. Mott, Barry Fields, and Kabura Wamburu, Centers for Disease Control and Prevention, Nairobi, Kenya, E-mails: zud9@cdc.gov, bsf2@cdc.gov, and WKabura@kemricdc.org. Jeremiah Laktabai and Janice Armstrong, Moi University School of Medicine, College of Health Sciences, Eldoret, Kenya, E-mails: drlaktabai@yahoo.com and janasimiyu@yahoo.com. Steve M. Taylor and Christopher W. Woods, Division of Infectious Diseases and International Health, Duke University Medical Center, Duke Global Health Institute, Durham Veterans Affairs Medical Center, Durham, NC, E-mails: steve.taylor@duke.edu and chris.woods@duke.edu. Charles MacIntyre, Reeshi Sen, and William Pan, Duke Global Health Institute, Durham, NC, E-mails: cwmacintyre@gmail.com, reeshisen00@gmail.com, and william.pan@duke.edu. Diana Menya, Moi University School of Public Health, College of Health Sciences, Eldoret, Kenya, E-mail: dianamenya@gmail.com. Bradly P. Nicholson, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham Veterans Affairs Medical Center, Durham, NC, E-mail: brad.nicholson@duke.edu. Thomas L. Holland, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, NC, E-mail: Thomas.Holland@duke.edu.
World Health Organization, 2013. World Health Statistics. Available at: http://apps.who.int/gho/data/node.main.ChildMortDistRegion?lang=en. Accessed November 19, 2014.
O'Meara WP, Mangeni JN, Steketee R, Greenwood B, 2010. Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect Dis 10: 545–555.
Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD, 2012. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 379: 413–431.
Mwangangi JM, Mbogo CM, Orindi BO, Muturi EJ, Midega JT, Nzovu J, Gatakaa H, Githure J, Borgemeister C, Keating J, Beier JC, 2013. Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years. Malar J 12: 13.
Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, Ooi EE, Maro VP, Saganda W, Kinabo GD, Muiruri C, Bartlett JA, 2013. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis 7: e2324.
Leslie T, Mikhail A, Mayan I, Anwar M, Bakhtash S, Nader M, Chandler C, Whitty CJ, Rowland M, 2012. Overdiagnosis and mistreatment of malaria among febrile patients at primary healthcare level in Afghanistan: observational study. BMJ 345: e4389.
Katz MA, Lebo E, Emukule G, Njuguna HN, Aura B, Cosmas L, Audi A, Junghae M, Waiboci LW, Olack B, Bigogo G, Njenga MK, Feikin DR, Breiman RF, 2012. Epidemiology, seasonality, and burden of influenza and influenza-like illness in urban and rural Kenya, 2007–2010. J Infect Dis 206 (Suppl 1): S53–S60.
Yazdanbakhsh M, Kremsner PG, 2009. Influenza in Africa. PLoS Med 6: e1000182.
Gessner BD, Shindo N, Briand S, 2011. Seasonal influenza epidemiology in sub-Saharan Africa: a systematic review. Lancet Infect Dis 11: 223–235.
Majanja J, Njoroge RN, Achilla R, Wurapa EK, Wadegu M, Mukunzi S, Mwangi J, Njiri J, Gachara G, Bulimo W, 2013. Impact of influenza A (H1N1) pdm09 virus on circulation dynamics of seasonal influenza strains in Kenya. Am J Trop Med Hyg 88: 940–945.
Waitumbi JN, Kuypers J, Anyona SB, Koros JN, Polhemus ME, Gerlach J, Steele M, Englund JA, Neuzil KM, Domingo GJ, 2010. Outpatient upper respiratory tract viral infections in children with malaria symptoms in western Kenya. Am J Trop Med Hyg 83: 1010–1013.
Feikin DR, Njenga MK, Bigogo G, Aura B, Aol G, Audi A, Jagero G, Muluare PO, Gikunju S, Nderitu L, Balish A, Winchell J, Schneider E, Erdman D, Oberste MS, Katz MA, Breiman RF, 2012. Etiology and incidence of viral and bacterial acute respiratory illness among older children and adults in rural western Kenya, 2007–2010. PLoS ONE 7: e43656.
D'Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, Lengeler C, Cherpillod P, Kaiser L, Genton B, 2014. Beyond malaria—causes of fever in outpatient Tanzanian children. N Engl J Med 370: 809–817.
Berkley JA, Munywoki P, Ngama M, Kazungu S, Abwao J, Bett A, Lassauniére R, Kresfelder T, Cane PA, Venter M, Scott JA, Nokes DJ, 2010. Viral etiology of severe pneumonia among Kenyan infants and children. JAMA 303: 2051–2057.
Marijon E, Mirabel M, Celermajer DS, Jouven X, 2012. Rheumatic heart disease. Lancet 379: 953–964.
Carapetis JR, Steer AC, Mulholland EK, Weber M, 2005. The global burden of group A streptococcal diseases. Lancet Infect Dis 5: 685–694.
Zuhlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, Mauff K, Islam S, Joachim A, Daniels R, Francis V, Ogendo S, Gitura B, Mondo C, Okello E, Lwabi P, Al-Kebsi MM, Hugo-Hamman C, Sheta SS, Haileamlak A, Daniel W, Goshu DY, Abdissa SG, Desta AG, Shasho BA, Begna DM, ElSayed A, Ibrahim AS, Musuku J, Bode-Thomas F, Okeahialam BN, Ige O, Sutton C, Misra R, Abul Fadl A, Kennedy N, Damasceno A, Sani M, Ogah OS, Olunuga T, Elhassan HH, Mocumbi AO, Adeoye AM, Mntla P, Ojji D, Mucumbitsi J, Teo K, Yusuf S, Mayosi BM, 2014. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J. doi:http://dx.doi.org/10.1093/eurheartj/ehu449.
Poverty Rates by County, 2005/6. Kenya Bureau of Statistics. Available at: https://www.opendata.go.ke/Counties/Poverty-Rates-by-County/z6za-e7yb. Accessed November 19, 2014.
Obala AA, Mangeni JN, Platt A, Aswa D, Abel L, Namae J, O'Meara WP, 2015. What is threatening the effectiveness of insecticide-treated bednets? A case-control study of environmental, behavioral, and physical factors associated with prevention failure. PLoS One (under review).
Kim C, Ahmed JA, Eidex RB, Nyoka R, Waiboci LW, Erdman D, Tepo A, Mahamud AS, Kabura W, Nguhi M, Muthoka P, Burton W, Breiman RF, Njenga MK, Katz MA, 2011. Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays. PLoS ONE 6: e21610.
Rantala AM, Taylor SM, Trottman PA, Luntamo M, Mbewe B, Maleta K, Kulmala T, Ashorn P, Meshnick SR, 2010. Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women. Malar J 9: 269.
1992. Guidelines for the diagnosis of rheumatic fever. Jones criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. JAMA 268: 2069–2073.
Bassat Q, Machevo S, O'Callaghan-Gordo C, Sigaúque B, Morais L, Díez-Padrisa N, Ribó JL, Mandomando I, Nhampossa T, Ayala E, Sanz S, Weber M, Roca A, Alonso PL, 2011. Distinguishing malaria from severe pneumonia among hospitalized children who fulfilled integrated management of childhood illness criteria for both diseases: a hospital-based study in Mozambique. Am J Trop Med Hyg 85: 626–634.
Mayxay M, Castonguay-Vanier J, Chansamouth V, Dubot-Pérès A, Paris DH, Phetsouvanh R, Tangkhabuanbutra J, Douangdala P, Inthalath S, Souvannasing P, Slesak G, Tongyoo N, Chanthongthip A, Panyanouvong P, Sibounheuang B, Phommasone K, Dohnt M, Phonekeo D, Hongvanthong B, Xayadeth S, Ketmayoon P, Blacksell SD, Moore CE, Craig SB, Burns MA, von Sonnenburg F, Corwin A, de Lamballerie X, González IJ, Christophel EM, Cawthorne A, Bell D, Newton PN, 2013. Causes of non-malarial fever in Laos: a prospective study. The Lancet Global Health 1: e46–e54.
Taylor SM, Molyneux ME, Simel DL, Meshnick SR, Juliano JJ, 2010. Does this patient have malaria? JAMA 304: 2048–2056.
Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, Martin JM, Van Beneden C, 2012. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 55: e86–e102.
Pondei K, Kunle-Olowu OE, Peterside O, 2013. The aetiology of non-malarial febrile illness in children in the malaria-endemic Niger Delta Region of Nigeria. Asian Pacific Journal of Tropical Disease 3: 56–60.
Bergmark R, Bergmark B, Blander J, Fataki M, Janabi M, 2010. Burden of disease and barriers to the diagnosis and treatment of group a beta-hemolytic streptococcal pharyngitis for the prevention of rheumatic heart disease in Dar Es Salaam, Tanzania. Pediatr Infect Dis J 29: 1135–1137.
Carapetis JR, McDonald M, Wilson NJ, 2005. Acute rheumatic fever. Lancet 366: 155–168.
Wachira J, Ndege S, Koech J, Vreeman R, Ayuo P, Braitstein P, 2013. HIV testing uptake and prevalence among adolescents and adults in a large home-based HIV testing program in western Kenya. J Acquir Immune Defic Syndr 65: e58–e66.
Kasper MR, Blair PJ, Touch S, Sokhal B, Yasuda CY, Williams M, Richards AL, Burgess TH, Wierzba TF, Putnam SD, 2012. Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia. Am J Trop Med Hyg 86: 246–253.
Hertz JT, Munishi OM, Ooi EE, Howe S, Lim WY, Chow A, Morrissey AB, Bartlett JA, Onyango JJ, Maro VP, Kinabo GD, Saganda W, Gubler DJ, Crump JA, 2012. Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania. Am J Trop Med Hyg 86: 171–177.
Sutherland LJ, Cash AA, Huang YJ, Sang RC, Malhotra I, Moormann AM, King CL, Weaver SC, King CH, LaBeaud AD, 2011. Serologic evidence of arboviral infections among humans in Kenya. Am J Trop Med Hyg 85: 158–161.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 105 | 105 | 20 |
Full Text Views | 551 | 193 | 0 |
PDF Downloads | 231 | 51 | 0 |