Community case management of fever due to malaria and pneumonia in children under five in Zambia: a cluster randomized controlled trial

Kojo Yeboah-Antwi, Portipher Pilingana, William B Macleod, Katherine Semrau, Kazungu Siazeele, Penelope Kalesha, Busiku Hamainza, Phil Seidenberg, Arthur Mazimba, Lora Sabin, Karen Kamholz, Donald M Thea, Davidson H Hamer, Kojo Yeboah-Antwi, Portipher Pilingana, William B Macleod, Katherine Semrau, Kazungu Siazeele, Penelope Kalesha, Busiku Hamainza, Phil Seidenberg, Arthur Mazimba, Lora Sabin, Karen Kamholz, Donald M Thea, Davidson H Hamer

Abstract

Background: Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs).

Methods and findings: Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14-0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19-8.94). There were two deaths in the intervention and one in the control arm.

Conclusions: The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.

Trial registration: ClinicalTrials.govNCT00513500

Conflict of interest statement

DHH owns shares in Inverness Medical Innovations, Inc., a company that makes diagnostic products including a malaria rapid diagnostic test. However, the rapid diagnostic tests we used in this study were not produced by Inverness Medical innovations, Inc.

Figures

Figure 1. Study profile.
Figure 1. Study profile.
Figure 2. Treatment algorithm for Intervention Community…
Figure 2. Treatment algorithm for Intervention Community Health Workers.
Figure 3. Treatment algorithm for Control Community…
Figure 3. Treatment algorithm for Control Community Health Workers.

References

    1. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:1969–1987.
    1. Kinney MV, Kerber KJ, Black RE, Cohen B, Nkrumah F, et al. Sub-Saharan Africa's mothers, newborns, and children: where and why do they die? PLoS Med. 2010;7:e1000294. doi: .
    1. Schellenberg JA, Victora CG, Mushi A, de Savigny D, Schellenberg D, et al. Inequities among the very poor: health care for children in rural southern Tanzania. Lancet. 2003;361:561–566.
    1. Victora CG, Wagstaff A, Schellenberg JA, Gwatkin D, Claeson M, et al. Applying an equity lens to child health and mortality: more of the same is not enough. Lancet. 2003;362:233–241.
    1. WHO/UNICEF. Joint statement: management of pneumonia in community settings. WHO/FCH/CAH/04.06. Geneva: WHO; 2004b.
    1. UNICEF/WHO. Pneumonia the forgotten killer of children. ISBN-13:978-92-806-4048-9. New York: UNICEF; 2006.
    1. Winch PJ, Gilroy KE, Wolfheim, Starbuck ES, Young MW, et al. Intervention models for the management of children with signs of pneumonia or malaria by community health workers. Health Policy Plan. 2005;20:199–212.
    1. Sazawal S, Black RE Pneumonia Case Management Trials Group. Effect of pneumonia case management on mortality in neonates, infants, and preschool children: a meta-analysis of community-based trials. Lancet Infect Dis. 2003;3:547–556.
    1. Garg R, Omwomo W, Witte JM, Lee LA, Deming MS. Care seeking during fatal childhood illnesses: Siaya District, Kenya, 1998. Am J Public Health. 2001;91:1611–1613.
    1. Fauveau V, Stewart MK, Chakraborty J, Khan SA. Impact on mortality of a community-based programme to control acute lower respiratory tract infections. Bull World Health Organ. 1992;70:109–116.
    1. Kidane G, Morrow RH. Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial. Lancet. 2000;356:550–555.
    1. Pagnoni F, Convelbo N, Tiendrebeogo J, Cousens S, Esposito F. A community-based programme to provide prompt and adequate treatment of presumptive malaria in children. Trans R Soc Trop Med Hyg. 2005;91:512–517.
    1. WHO. WHO guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. Geneva: WHO; 2006.
    1. Ogbonna A, Uneke CJ. Artemisinin-based combination therapy for uncomplicated malaria in sub-Saharan Africa: the efficacy, safety, resistance and policy implementation since Abuja 2000. Trans R Soc Trop Med Hyg. 2008;102:621–627.
    1. Hopkins H, Bebell L, Kambale W, Dokomajilar C, Rosenthal PJ, et al. Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda. J Infect Dis. 2008;197:510–518.
    1. Hopkins H, Asiimwe C, Bell D. Access to antimalarial therapy: accurate diagnosis is essential to achieving long term goals. BMJ. 2009;339:b2606.
    1. Bisoffi Z, Gobbi F, Angheben A, Van den Ende J. The role of rapid diagnostic tests in managing malaria. PLoS Med. 2009;6:e1000063. doi: .
    1. 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.
    1. Källander K, Nsungwa-Sabiiti J, Peterson S. Symptom overlap for malaria and pneumonia—policy implications for home management strategies. Acta Tropica. 2004;90:211–214.
    1. Harvey SA, Jennings L, Chinyama M, Masaninga F, Mulholland K, et al. Improving community health worker use of malaria rapid diagnostic tests in Zambia: package instructions, job aid and job aid-plus-training. Malar J. 2008;7:160. doi: .
    1. Enserink M. Combating malaria. Malaria treatment: ACT Two. Science. 2007;318:560–563.
    1. Elmardi KA, Malik EM, Abdelgardi T, Ali SH, Elsyed AH, et al. Feasibility and acceptability of home-based management of malaria strategy adapted to Sudan's conditions using artemisinin-based combination therapy and rapid diagnostic test. Malar J. 2009;8:39. doi: .
    1. Yasuoka J, Poudel KC, Poudel-Tandukar K, Ngoun C, Ly P, et al. Assessing the quality of service of village malaria workers to strengthen community-based malaria control in Cambodia. Malar J. 2010;9:109. doi: .
    1. Degefie T, Marsh D, Gebremariam A, Tefera W, Osborn G, et al. Community case management improves use of treatment for childhood diarrhea, malaria and pneumonia in a remote district of Ethiopia. Ethiop J Health Dev. 2009;23:120–126.
    1. Kelly JM, Osamba B, Garg RM, Hamel MJ, Lewis JJ, et al. Community health worker performance in the management of multiple childhood illnesses: Siaya District, Kenya, 1997–2001. Am J Public Health. 2001;91:1617–1624.
    1. Central Statistical Office (CSO)Ministry of Health (MOH)Tropical Diseases Research Centre (TDRC)University of Zambia, and Macro International Inc. Zambia Demographic and Health Survey 2007. Calverton (Maryland): CSO and Macro International Inc; 2009.
    1. Siavonga DHMT. District Health Management Team Disease Incidence Report 2005. Siavonga: Siavonga DHMT; 2005.
    1. Mazabuka DHMT. District Health Management Team Disease Incidence Report 2005. Mazabuka: Mazabuka DHMT; 2005.
    1. Kent RJ, Thuma PE, Mharakurwa S, Norris DE. Seasonality, blood feeding behavior, and transmission of Plasmodium falciparum by Anopheles arabiensis after an extended drought in southern Zambia. Am J Trop Med Hyg. 2007;76:267–274.
    1. Bechem NN, Leke RF, Tietche F, Taylor DW. Evaluation of a rapid diagnostic for histidine rich protein 2 for diagnosis of Pf infection in Cameroonian. Trans R Soc Trop Med. 1999;93:46.
    1. World Health Organization: Malaria rapid diagnostic test performance: results of WHO product testing of malaria RDTs: round 1 (2008). World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases. Geneva: WHO; 2009.
    1. Hayes RJ, Bennett S. Simple sample size calculation for cluster-randomized trials. Int J Epidemiol. 1999;28:319–326.
    1. Hayes RJ, Moulton LH. Cluster randomised trials. Boca Raton (Florida): CRC Press; 2009. pp. 219–221.
    1. Dawson P, Pradhan YV, Houston R, Karki S, Poudel D, et al. From research to national expansion: 20 years' experience of community-based management of childhood pneumonia in Nepal. Bull World Health Organ. 2008;86:339–343.
    1. Khan AJ, Khan JA, Akbar M, Addiss DG. Acute respiratory infections in children: a case management intervention in Abbottabad District, Pakistan. Bull World Health Organ. 1990;68:577–585.
    1. Bang AT, Bang RA, Tale O, Sontakke P, Solanki J, et al. Reduction in pneumonia mortality and total childhood mortality by means of community-based intervention trial in Gadchiroli, India. Lancet. 1990;336:201–206.
    1. BASICS. Scaling up community-based treatment in Senegal. Washington (D.C.): BASICS and USAID; 2006.
    1. Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, et al. Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ. 2004;329:1212.
    1. Amexo M, Tolhurst R, Barnish G, Bates I. Malaria misdiagnosis: effects on the poor and vulnerable. Lancet. 2004;364:1896–1898.
    1. Hume JC, Barnish G, Mangal T, Armázio L, Streat E, et al. Household cost of malaria overdiagnosis in rural Mozambique. Malar J. 2008;7:33.
    1. Msellem MI, Mårtensson A, Rotllant G, Bhattarai A, Strömberg J, et al. Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study. PLoS Med. 2009;6:e1000070. doi: .
    1. Van Dillen J, De Jager AJ, De Jong I, Wendte JF. Overdiagnosis of malaria in hospitalized patients in Namibia. Trop Doct. 2007;37:185–186.
    1. Chandler CI, Mwangi R, Mbakilwa H, Olomi R, Whitty CJ, et al. Malaria overdiagnosis: is patient pressure the problem? Health Policy Plan. 2008;23:170–178.
    1. Whitty CJ, Chandler C, Ansah E, Leslie T, Staedke SG. Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities. Malar J. 2008;7:S7.
    1. Mosha JF, Conteh L, Tediosi F, Gesase S, Bruce J, et al. Cost implications of Improving malaria diagnosis: findings from north-eastern Tanzania. PLoS ONE. 2010;5:e8707. doi: .
    1. Premji Z, Minjas JN, Shiff CJ. Laboratory diagnosis of malaria by village health workers using the rapid manual ParaSight-F test. Trans R Soc Trop Med Hyg. 1994;88:418.
    1. Drakeley C, Reyburn H. Out with the old, in with the new: the utility of rapid diagnostic tests for malaria diagnosis in Africa. Trans R Soc Trop Med Hyg. 2009;103:333–337.
    1. Hamer DH, Ndhlovu M, Zurovac D, Fox M, Yeboah-Antwi K, et al. Improved diagnostic testing and malaria treatment practices in Zambia. JAMA. 2007;297:2227–2231.
    1. Reyburn H, Mbakilwa H, Mwangi R, Mwerinde O, Olomi R, et al. Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial. BMJ. 2007;334:403.
    1. Lubell Y, Reyburn H, Mbakilwa H, Mwangi R, Chonya S, et al. The impact of response to the results of diagnostic tests for malaria: cost–benefit analysis. BMJ. 2008;336:202–205.
    1. Skarbinski J, Ouma PO, Causer LM, Karuiki SK, Barnwell JW, et al. Effect of malaria rapid diagnostic tests on the management of uncomplicated malaria with artemether-lumefantrine in Kenya; a cluster randomized trial. Am J Med Hyg. 2009;80:919–926.
    1. Lemma H, Byass P, Desta A, Bosman A, Costanzo G, et al. Deploying artemether-lumefantrine with rapid testing in Ethiopian communities: impact on malaria morbidity, mortality and health care resources. Trop Med Int Health. 2010;15:241–250.
    1. Ansah EK, Narh-Bana S, Epokor M, Akanpigbiam S, Quartey AA, et al. Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana. BMJ. 2010;340:c930.
    1. Simoes EA, Peterson S, Gamatie Y, Kisanga FS, Mukasa G, et al. Management of severely ill children at first-level health facilities in sub-Saharan Africa when referral is difficult. Bull World Health Organ. 2003;81:522–531.
    1. Kalter HD, Salgado R, Moulton LH, Nieto P, Contreras A, et al. Factors constraining adherence to referral advice for severely ill children managed by the Integrated Management of Childhood Illness approach in Imbabura Province, Ecuador. Acta Paediatr. 2003;92:103–110.
    1. Stock R. Distance and the utilization of health facilities in rural Nigeria. Soc Sci Med. 1983;17:563–570.
    1. Theodoratou E, Al-Jilaihawi S, Woodward F, Ferguson J, Jhass A, et al. The effect of case management on childhood pneumonia mortality in developing countries. Int J Epidemiol. 2010;39:i155–171.
    1. Marsh DR, Gilroy KE, Van de Weerdt R, Wansi, Qazi S. Community case management of pneumonia: at a tipping point? Bull World Health Organ. 2008;86:381–389.
    1. Gomes MF, Faiz MA, Gyapong JO, Warsame M, Agbenyega T, et al. Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet. 2009;373:557–66.
    1. Hazir T, Fox LM, Nisar YB, Fox MP, Ashraf YP, et al. Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial. Lancet. 2008;371:49–56.
    1. Rutebemberwa E, Nsabagasani X, Pariyo G, Tomson G, Peterson S, et al. Use of drugs, perceived drug efficacy and preferred providers for febrile children: implications for home management of fever. Malar J. 2009;8:131. doi: .
    1. Friberg IK, Kinney MV, Lawn JE, Kerber KJ, Odubanjo MO, et al. Sub-Saharan Africa's mothers, newborns, and children: how many lives could be saved with targeted health interventions? PLoS Med. 2010;7:e1000295. doi: .

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe