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      Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial

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          Abstract

          In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective.

          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.gov NCT00513500

          Please see later in the article for the Editors' Summary

          Editors' Summary

          Background

          Every year, about 11 million children die before their fifth birthday. Most of these deaths are in developing countries and most are due to a handful of causes—pneumonia (lung inflammation usually caused by an infection), malaria (a parasitic disease spread by mosquitoes), measles, diarrhea, and birth-related problems. In sub-Saharan Africa, pneumonia and malaria alone are responsible for nearly a third of deaths in young children. Both these diseases can be treated if caught early—pneumonia with antibiotics such as amoxicillin and malaria with artemisinin-based combination therapy (ACT), a treatment that contains several powerful antimalarial drugs. Unfortunately, parents in rural areas in sub-Saharan Africa rarely have easy access to health facilities and sick children are often treated at home by community health workers (CHWs, individuals with some medical training who provide basic health care to their communities), drug sellers, and traditional healers. This situation means that ongoing global efforts to reduce child mortality will require innovative community level interventions if they are to succeed.

          Why Was This Study Done?

          One community level intervention that the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recently recommended is integrated management of malaria and pneumonia in countries where these diseases are major childhood killers. One such country is Zambia. In rural areas of Zambia, CHWs treat suspected cases of uncomplicated (mild) malaria with artemether-lumefantrine (AL, an ACT) or with sulfadoxine-pyrimethamine (a non-ACT antimalarial drug combination) and refer children with suspected pneumonia to the nearest health facility. However, because uncomplicated malaria and pneumonia both cause fever, many children are treated inappropriately. This misdiagnosis is worrying because giving antimalarial drugs to children with pneumonia delays their treatment with more appropriate drugs and increases the risk of drug-resistant malaria emerging. The use of rapid diagnostic tests (RDTs) for malaria might be one way to improve the treatment of malaria and pneumonia by CHWs in Zambia. Here, the researchers investigate the feasibility and effectiveness of this approach in a cluster randomized controlled trial, a study that compares the outcomes of groups (clusters) of patients randomly allocated to different interventions.

          What Did the Researchers Do and Find?

          The researchers randomly allocated 31 community health posts (fixed locations where CHWs provide medical services to several villages) to the study's intervention and control arms. CHWs in the intervention arm did RDTs for malaria on all the children under 5 years old who presented with fever and/or difficult or fast breathing (symptoms of pneumonia), treated test-positive children with AL, and treated those with nonsevere pneumonia (an increased breathing rate) with amoxicillin. CHWs in the control arm did not use RDTs but treated all children with fever with AL and referred those with signs of pneumonia to the nearest health facility. About 3,000 children with fever were treated during the 12-month study. 99.1% of the children in the control arm received AL compared with 27.5% of the children in the intervention arm, a 4-fold reduction in treatment for malaria. Importantly, the CHWs in the intervention arm adhered to treatment guidelines and did not give AL to children with negative RDT results. Of the children classified with nonsevere pneumonia, 13.3% of those in the control arm received early and appropriate treatment with amoxicillin compared to 68.2% of those in the intervention arm, a 5-fold increase in the timely treatment for pneumonia.

          What Do These Findings Mean?

          These findings indicate that CHWs in Zambia are capable of using RDTs, AL, and amoxicillin to manage malaria and pneumonia. They show that the intervention tested in this study has the potential to reduce the overuse of AL and to provide early and appropriate treatment for nonsevere pneumonia. Although this approach needs to be tested in other settings, these findings suggest that the use of CHWs might be a feasible and effective way to provide integrated management of pneumonia and malaria at the community level in developing countries. Importantly, these results also support the evaluation of the treatment by CHWs of other major childhood diseases and raise the possibility of saving the lives of many children in sub-Saharan Africa and other developing regions of the world through community level interventions.

          Additional Information

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000340.

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          Most cited references43

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          Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study.

          To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. Prospective observational study of children and adults over the course a year. 10 hospitals in north east Tanzania. 17,313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged > or = 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.
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            Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial.

            To compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients. Randomised trial. Outpatient departments in northeast Tanzania at varying levels of malaria transmission. 2416 patients for whom a malaria test was requested. Staff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopy Proportion of patients with a negative test prescribed an antimalarial drug. Of 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P<0.001). More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria. Although many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians' management of febrile illness are essential but will not be easy. Clinical trials NCT00146796 [ClinicalTrials.gov].
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              • Record: found
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              • Article: not found

              Malaria misdiagnosis: effects on the poor and vulnerable.

              Effective and affordable treatment is recommended for all cases of malaria within 24 h of the onset of illness. Most cases of "malaria" (ie, fever) are self-diagnosed and most treatments, and deaths, occur at home. The most ethical and cost-effective policy is to ensure that newer drug combinations are only used for true cases of malaria. Although it is cost effective to improve the accuracy of malaria diagnosis, simple, accurate, and inexpensive methods are not widely available, particularly in poor communities where they are most needed. In a recent study in Uganda, Karin Kallander and colleagues emphasise the difficulty in making a presumptive diagnosis of malaria, and highlight the urgent need for improved diagnostic tools that can be used at community and primary-care level, especially in poorer populations (Acta Trop 2004; 90: 211-14). WHERE NEXT? Health systems need strengthening at referral and community level, so that rapid accurate diagnosis and effective treatment is available for those who are least able to withstand the consequences of illness. Indirect evidence strongly suggests that misdiagnosis of malaria contributes to a vicious cycle of increasing ill-health and deepening poverty. Much better direct evidence is needed about why and how misdiagnosis affects the poor and vulnerable.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                September 2010
                September 2010
                21 September 2010
                : 7
                : 9
                : e1000340
                Affiliations
                [1 ]Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts, United States of America
                [2 ]Chikankata Mission Hospital, Chikankata, Southern Province, Zambia
                [3 ]Child Health Unit, Ministry of Health, Lusaka, Zambia
                [4 ]National Malaria Control Center, Ministry of Health, Lusaka, Zambia
                [5 ]Center for International Health and Development-Zambia, Lusaka, Zambia
                [6 ]Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts, United States of America
                [7 ]Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America
                London School of Hygiene and Tropical Medicine, United Kingdom
                Author notes

                ICMJE criteria for authorship read and met: KYA PP WBM KS KS PK BH PS AM LS KK DMT DHH. Agree with the manuscript's results and conclusions: KYA PP WBM KS KS PK BH PS AM LS KK DMT DHH. Designed the experiments/the study: KYA PP LS DMT DHH. Analyzed the data: KYA PP WBM KS PK BH PS DHH. Collected data/did experiments for the study: KYA PP KS. Enrolled patients: PP KS. Wrote the first draft of the paper: KYA PK DHH. Contributed to the writing of the paper: KYA PP WBM KS KS PK BH PS LS KK DMT DHH. Responsible for day to day field activities: PP. Contributed to editing the manuscript: AM.

                Article
                10-PLME-RA-4240R4
                10.1371/journal.pmed.1000340
                2943441
                20877714
                8a230cfc-4517-4457-aa28-b92e042ae72d
                Yeboah-Antwi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 4 March 2010
                : 12 August 2010
                Page count
                Pages: 13
                Categories
                Research Article
                Evidence-Based Healthcare
                Infectious Diseases/Respiratory Infections
                Pediatrics and Child Health
                Public Health and Epidemiology/Health Policy

                Medicine
                Medicine

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