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Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Research

Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses

Authors: George Mtove, Ilse CE Hendriksen, Ben Amos, Hedwiga Mrema, Victor Mandia, Alphaxard Manjurano, Florida Muro, Alma Sykes, Helena Hildenwall, Christopher JM Whitty, Hugh Reyburn

Published in: Malaria Journal | Issue 1/2011

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Abstract

Background

WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa.

Methods

Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days.

Results

Over the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7) and specificity of 96.3% (95%CI 96.3-98.4).

Conclusions

Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever.
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Literature
1.
go back to reference Chandramohan D, Jaffar S, Greenwood B: Use of clinical algorithms for diagnosing malaria. Trop Med Int Health. 2002, 7: 45-52. 10.1046/j.1365-3156.2002.00827.x.CrossRefPubMed Chandramohan D, Jaffar S, Greenwood B: Use of clinical algorithms for diagnosing malaria. Trop Med Int Health. 2002, 7: 45-52. 10.1046/j.1365-3156.2002.00827.x.CrossRefPubMed
2.
go back to reference D'Acremont V, Lengeler C, Mshinda H, Mtasiwa D, Tanner M, Genton B: Time to move from presumptive malaria treatment to laboratory-confirmed diagnosis and treatment in African children with fever. PLoS Med. 2009, 6: e252-10.1371/journal.pmed.0050252.PubMedCentralCrossRefPubMed D'Acremont V, Lengeler C, Mshinda H, Mtasiwa D, Tanner M, Genton B: Time to move from presumptive malaria treatment to laboratory-confirmed diagnosis and treatment in African children with fever. PLoS Med. 2009, 6: e252-10.1371/journal.pmed.0050252.PubMedCentralCrossRefPubMed
3.
go back to reference Wongsrichanalai C, Baird K: Linking malaria rapid diagnostic test (RDT) and new drug combinations. BMJ. 2004,bmj.com July 23., Wongsrichanalai C, Baird K: Linking malaria rapid diagnostic test (RDT) and new drug combinations. BMJ. 2004,bmj.com July 23.,
4.
go back to reference Yeung S, Van Damme W, Socheat D, White NJ, Mills A: Cost of increasing access to artemisinin combination therapy: the Cambodian experience. Malar J. 2008, 7: 84-10.1186/1475-2875-7-84.PubMedCentralCrossRefPubMed Yeung S, Van Damme W, Socheat D, White NJ, Mills A: Cost of increasing access to artemisinin combination therapy: the Cambodian experience. Malar J. 2008, 7: 84-10.1186/1475-2875-7-84.PubMedCentralCrossRefPubMed
5.
go back to reference Zurovac D, Ndhlovu M, Sipilanyambe N, Chanda P, Hamer DH, Simon JL, Snow RW: Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study. Malar J. 2007, 6: 31-10.1186/1475-2875-6-31.PubMedCentralCrossRefPubMed Zurovac D, Ndhlovu M, Sipilanyambe N, Chanda P, Hamer DH, Simon JL, Snow RW: Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study. Malar J. 2007, 6: 31-10.1186/1475-2875-6-31.PubMedCentralCrossRefPubMed
6.
go back to reference Lubell Y, Reyburn H, Mbakilwa H, Mwangi R, Chonya K, Whitty CJ, Mills A: The cost-effectiveness of parasitologic diagnosis for malaria-suspected patients in an era of combination therapy. Am J Trop Med Hyg. 2007, 77: 128-132.PubMed Lubell Y, Reyburn H, Mbakilwa H, Mwangi R, Chonya K, Whitty CJ, Mills A: The cost-effectiveness of parasitologic diagnosis for malaria-suspected patients in an era of combination therapy. Am J Trop Med Hyg. 2007, 77: 128-132.PubMed
7.
go back to reference Yeung S, Van Damme W, Socheat D, White NJ, Mills A: Access to artemisinin combination therapy for malaria in remote areas of Cambodia. Malar J. 2008, 7: 96-10.1186/1475-2875-7-96.PubMedCentralCrossRefPubMed Yeung S, Van Damme W, Socheat D, White NJ, Mills A: Access to artemisinin combination therapy for malaria in remote areas of Cambodia. Malar J. 2008, 7: 96-10.1186/1475-2875-7-96.PubMedCentralCrossRefPubMed
8.
go back to reference Murray CK, Gasser RA, Magill AJ, Miller RS: Update on rapid diagnostic testing for malaria. Clin Microbiol Rev. 2008, 21: 97-110. 10.1128/CMR.00035-07.PubMedCentralCrossRefPubMed Murray CK, Gasser RA, Magill AJ, Miller RS: Update on rapid diagnostic testing for malaria. Clin Microbiol Rev. 2008, 21: 97-110. 10.1128/CMR.00035-07.PubMedCentralCrossRefPubMed
9.
go back to reference WHO: Guidelines for malaria diagnosis and treatment. WHO-Roll Back Malaria. 2010, WHO-Geneva, vol. ISBN: 9789241547925 WHO: Guidelines for malaria diagnosis and treatment. WHO-Roll Back Malaria. 2010, WHO-Geneva, vol. ISBN: 9789241547925
10.
go back to reference Chandler CI, Jones C, Boniface G, Juma K, Reyburn H, Whitty CJ: Guidelines and mindlines: why do clinical staff over-diagnose malaria in Tanzania? A qualitative study. Malar J. 2008, 7: 53-10.1186/1475-2875-7-53.PubMedCentralCrossRefPubMed Chandler CI, Jones C, Boniface G, Juma K, Reyburn H, Whitty CJ: Guidelines and mindlines: why do clinical staff over-diagnose malaria in Tanzania? A qualitative study. Malar J. 2008, 7: 53-10.1186/1475-2875-7-53.PubMedCentralCrossRefPubMed
11.
go back to reference Bernard J, Mtove G, Mandike R, Mtei F, Maxwell C, Reyburn H: Equity and coverage of insecticide-treated bed nets in an area of intense transmission of Plasmodium falciparum in Tanzania. Malar J. 2009, 8: 65-10.1186/1475-2875-8-65.PubMedCentralCrossRefPubMed Bernard J, Mtove G, Mandike R, Mtei F, Maxwell C, Reyburn H: Equity and coverage of insecticide-treated bed nets in an area of intense transmission of Plasmodium falciparum in Tanzania. Malar J. 2009, 8: 65-10.1186/1475-2875-8-65.PubMedCentralCrossRefPubMed
12.
go back to reference Maxwell CA, Chambo W, Mwaimu M, Magogo F, Carneiro IA, Curtis CF: Variation of malaria transmission and morbidity with altitude in Tanzania and with introduction of alphacypermethrin treated nets. Malar J. 2003, 2: 28-10.1186/1475-2875-2-28.PubMedCentralCrossRefPubMed Maxwell CA, Chambo W, Mwaimu M, Magogo F, Carneiro IA, Curtis CF: Variation of malaria transmission and morbidity with altitude in Tanzania and with introduction of alphacypermethrin treated nets. Malar J. 2003, 2: 28-10.1186/1475-2875-2-28.PubMedCentralCrossRefPubMed
13.
go back to reference Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN: High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993, 61: 315-320. 10.1016/0166-6851(93)90077-B.CrossRefPubMed Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN: High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol. 1993, 61: 315-320. 10.1016/0166-6851(93)90077-B.CrossRefPubMed
14.
go back to reference Nadjm B, Amos B, Mtove G, Ostermann J, Chonya S, Wangai H, Kimera J, Msuya W, Mtei F, Dekker D, Malahiyo R, Olomi R, Crump JA, Whitty CJ, Reyburn H: WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ. 2010, 340: c1350-10.1136/bmj.c1350.PubMedCentralCrossRefPubMed Nadjm B, Amos B, Mtove G, Ostermann J, Chonya S, Wangai H, Kimera J, Msuya W, Mtei F, Dekker D, Malahiyo R, Olomi R, Crump JA, Whitty CJ, Reyburn H: WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ. 2010, 340: c1350-10.1136/bmj.c1350.PubMedCentralCrossRefPubMed
15.
go back to reference Njama-Meya D, Clark TD, Nzarubara B, Staedke S, Kamya MR, Dorsey G: Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children. Malar J. 2007, 6: 7-10.1186/1475-2875-6-7.PubMedCentralCrossRefPubMed Njama-Meya D, Clark TD, Nzarubara B, Staedke S, Kamya MR, Dorsey G: Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children. Malar J. 2007, 6: 7-10.1186/1475-2875-6-7.PubMedCentralCrossRefPubMed
16.
go back to reference d'Acremont V, Malila A, Swai N, Tillya R, Kahama-Maro J, Lengeler C, Genton B: Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Infect Dis. 2010, 51: 506-511. 10.1086/655688.CrossRefPubMed d'Acremont V, Malila A, Swai N, Tillya R, Kahama-Maro J, Lengeler C, Genton B: Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Infect Dis. 2010, 51: 506-511. 10.1086/655688.CrossRefPubMed
17.
go back to reference Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, Mwerinde O, Saganda K, Shao J, Kitua A, Olomi R, Greenwood BM, Whitty CJ: Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. Bmj. 2004, 329: 1212-10.1136/bmj.38251.658229.55.PubMedCentralCrossRefPubMed Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, Mwerinde O, Saganda K, Shao J, Kitua A, Olomi R, Greenwood BM, Whitty CJ: Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. Bmj. 2004, 329: 1212-10.1136/bmj.38251.658229.55.PubMedCentralCrossRefPubMed
18.
go back to reference Konate AT, Yaro JB, Ouedraogo AZ, Diarra A, Gansane A, Soulama I, Kangoye DT, Kabore Y, Ouedraogo E, Ouedraogo A, Tiono AB, Ouedraogo IN, Chandramohan D, Cousens S, Milligan PJ, Sirima SB, Greenwood B, Diallo DA: Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011, 8: e1000408-10.1371/journal.pmed.1000408.PubMedCentralCrossRefPubMed Konate AT, Yaro JB, Ouedraogo AZ, Diarra A, Gansane A, Soulama I, Kangoye DT, Kabore Y, Ouedraogo E, Ouedraogo A, Tiono AB, Ouedraogo IN, Chandramohan D, Cousens S, Milligan PJ, Sirima SB, Greenwood B, Diallo DA: Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011, 8: e1000408-10.1371/journal.pmed.1000408.PubMedCentralCrossRefPubMed
19.
go back to reference Kallander K, Nsungwa-Sabiiti J, Peterson S: Symptom overlap for malaria and pneumonia--policy implications for home management strategies. Acta Trop. 2004, 90: 211-214. 10.1016/j.actatropica.2003.11.013.CrossRefPubMed Kallander K, Nsungwa-Sabiiti J, Peterson S: Symptom overlap for malaria and pneumonia--policy implications for home management strategies. Acta Trop. 2004, 90: 211-214. 10.1016/j.actatropica.2003.11.013.CrossRefPubMed
20.
go back to reference O'Dempsey TJ, McArdle TF, Laurence BE, Lamont AC, Todd JE, Greenwood BM: Overlap in the clinical features of pneumonia and malaria in African children. Trans R Soc Trop Med Hyg. 1993, 87: 662-665. 10.1016/0035-9203(93)90279-Y.CrossRefPubMed O'Dempsey TJ, McArdle TF, Laurence BE, Lamont AC, Todd JE, Greenwood BM: Overlap in the clinical features of pneumonia and malaria in African children. Trans R Soc Trop Med Hyg. 1993, 87: 662-665. 10.1016/0035-9203(93)90279-Y.CrossRefPubMed
21.
go back to reference English M, Punt J, Mwangi I, McHugh K, Marsh K: Clinical overlap between malaria and severe pneumonia in Africa children in hospital. Trans R Soc Trop Med Hyg. 1996, 90: 658-662. 10.1016/S0035-9203(96)90423-X.CrossRefPubMed English M, Punt J, Mwangi I, McHugh K, Marsh K: Clinical overlap between malaria and severe pneumonia in Africa children in hospital. Trans R Soc Trop Med Hyg. 1996, 90: 658-662. 10.1016/S0035-9203(96)90423-X.CrossRefPubMed
22.
go back to reference Hildenwall H, Rutebemberwa E, Nsabagasani X, Pariyo G, Tomson G, Peterson S: Local illness concepts--implications for management of childhood pneumonia in eastern Uganda. Acta Trop. 2007, 101: 217-224. 10.1016/j.actatropica.2007.02.003.CrossRefPubMed Hildenwall H, Rutebemberwa E, Nsabagasani X, Pariyo G, Tomson G, Peterson S: Local illness concepts--implications for management of childhood pneumonia in eastern Uganda. Acta Trop. 2007, 101: 217-224. 10.1016/j.actatropica.2007.02.003.CrossRefPubMed
23.
go back to reference Weber MW, Dackour R, Usen S, Schneider G, Adegbola RA, Cane P, Jaffar S, Milligan P, Greenwood BM, Whittle H, Mulholland EK: The clinical spectrum of respiratory syncytial virus disease in The Gambia. Pediatr Infect Dis J. 1998, 17: 224-230. 10.1097/00006454-199803000-00010.CrossRefPubMed Weber MW, Dackour R, Usen S, Schneider G, Adegbola RA, Cane P, Jaffar S, Milligan P, Greenwood BM, Whittle H, Mulholland EK: The clinical spectrum of respiratory syncytial virus disease in The Gambia. Pediatr Infect Dis J. 1998, 17: 224-230. 10.1097/00006454-199803000-00010.CrossRefPubMed
24.
go back to reference Weber MW, Mulholland EK, Greenwood BM: Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health. 1998, 3: 268-280. 10.1046/j.1365-3156.1998.00213.x.CrossRefPubMed Weber MW, Mulholland EK, Greenwood BM: Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health. 1998, 3: 268-280. 10.1046/j.1365-3156.1998.00213.x.CrossRefPubMed
25.
go back to reference English M, Esamai F, Wasunna A, Were F, Ogutu B, Wamae A, Snow RW, Peshu N: Delivery of paediatric care at the first-referral level in Kenya. Lancet. 2004, 364: 1622-1629. 10.1016/S0140-6736(04)17318-2.CrossRefPubMed English M, Esamai F, Wasunna A, Were F, Ogutu B, Wamae A, Snow RW, Peshu N: Delivery of paediatric care at the first-referral level in Kenya. Lancet. 2004, 364: 1622-1629. 10.1016/S0140-6736(04)17318-2.CrossRefPubMed
26.
go back to reference Reyburn H, Mwakasungula E, Chonya S, Mtei F, Bygbjerg I, Poulsen A, Olomi R: Clinical assessment and treatment in paediatric wards in the north-east of the United Republic of Tanzania. Bull World Health Organ. 2008, 86: 132-139.PubMedCentralCrossRefPubMed Reyburn H, Mwakasungula E, Chonya S, Mtei F, Bygbjerg I, Poulsen A, Olomi R: Clinical assessment and treatment in paediatric wards in the north-east of the United Republic of Tanzania. Bull World Health Organ. 2008, 86: 132-139.PubMedCentralCrossRefPubMed
27.
go back to reference Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, Lowe B, Bauni E, English M, Berkley JA, Scott JA: Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet. 2006, 367: 482-488. 10.1016/S0140-6736(06)68180-4.CrossRefPubMed Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, Lowe B, Bauni E, English M, Berkley JA, Scott JA: Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet. 2006, 367: 482-488. 10.1016/S0140-6736(06)68180-4.CrossRefPubMed
28.
go back to reference Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Ngetsa C, Slack MP, Njenga S, Hart CA, Maitland K, English M, Marsh K, Scott JA: Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med. 2005, 352: 39-47. 10.1056/NEJMoa040275.CrossRefPubMed Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Ngetsa C, Slack MP, Njenga S, Hart CA, Maitland K, English M, Marsh K, Scott JA: Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med. 2005, 352: 39-47. 10.1056/NEJMoa040275.CrossRefPubMed
29.
go back to reference Diez-Padrisa N, Bassat Q, Machevo S, Quinto L, Morais L, Nhampossa T, O'Callaghan-Gordo C, Torres A, Alonso PL, Roca A: Procalcitonin and C-reactive protein for invasive bacterial pneumonia diagnosis among children in Mozambique, a malaria-endemic area. PLoS One. 2010, 5: e13226-10.1371/journal.pone.0013226.PubMedCentralCrossRefPubMed Diez-Padrisa N, Bassat Q, Machevo S, Quinto L, Morais L, Nhampossa T, O'Callaghan-Gordo C, Torres A, Alonso PL, Roca A: Procalcitonin and C-reactive protein for invasive bacterial pneumonia diagnosis among children in Mozambique, a malaria-endemic area. PLoS One. 2010, 5: e13226-10.1371/journal.pone.0013226.PubMedCentralCrossRefPubMed
Metadata
Title
Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses
Authors
George Mtove
Ilse CE Hendriksen
Ben Amos
Hedwiga Mrema
Victor Mandia
Alphaxard Manjurano
Florida Muro
Alma Sykes
Helena Hildenwall
Christopher JM Whitty
Hugh Reyburn
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-290

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