Community case management of fever due to malaria and pneumonia in children under five in Zambia: a cluster randomized controlled trial. Home-based management of fever and malaria treatment practices in Uganda. Process and effects of a community intervention on malaria in rural Burkina Faso: randomized controlled trial. Using community health workers for malaria control: experience in Zaire. Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial. Malaria rapid testing by community health workers is effective and safe for targeting malaria treatment: randomised cross-over trial in Tanzania. Community-based malaria control in Saradidi, Kenya: description of the programme and impact on parasitaemia rates and antimalarial antibodies. The impact of retail-sector delivery of artemether-lumefantrine on malaria treatment of children under five in Kenya: a cluster randomized controlled trial. Home management of malaria with artemether-lumefantrine compared with standard care in urban Ugandan children: a randomised controlled trial. Effectiveness of a community intervention on malaria in rural Tanzania - a randomised controlled trial.
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).
                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.
                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.
                ClinicalTrials.govNCT00513500 The Home-Based Management of Fever/Malaria (HBMF) strategy in rural Uganda was evaluated in a quasi-experimental study. The intervention consisted of volunteers educating mothers and providing a 3-day course of pre-packaged chloroquine plus sulfadoxine/pyrimethamine tablets (HOMAPAK), free of charge, for the treatment of under-five fevers. Using a structured questionnaire, information was obtained on care-seeking and treatment practices before (n=498) and 18 months after the introduction of HBMF (n=587). Assessment of the intervention effect indicated 13.5% improvement in the accumulated proportion of patients (1) treated, (2) treated within 24h of illness onset, (3) treated with the recommended antimalarials, (4) treated at an adequate dosage and (5) treated for the correct duration. Combining this with the antimalarial drug efficacy resulted in a 10.4% improvement in the community effectiveness of malaria treatment. HOMAPAK use was reported in 25% of 156 febrile children; 23% in the most poor compared with 50% in the least poor. Using HOMAPAK instead of other allopathic antimalarials increased the likelihood of completing all steps (odds ratio 37, 95% CI 4.8-286). Similar to other large-scale public health interventions, this study demonstrates modest practice changes at the population level. However, practices improved markedly among HOMAPAK users, suggesting that intensifying implementation efforts to increase HOMAPAK use, especially among the poorest, would be beneficial. In the rural areas of sub-Saharan Africa, the majority of young children affected by malaria have no access to formal health services. Home treatment through mothers of febrile children supported by mother groups and local health workers has the potential to reduce malaria morbidity and mortality.
                A cluster-randomized controlled effectiveness trial was implemented from 2002-2004 in a malaria endemic area of rural Burkina Faso. Six and seven villages were randomly assigned to the intervention and control arms respectively. Febrile children from intervention villages were treated with chloroquine (CQ) by their mothers, supported by local women group leaders. CQ was regularly supplied through a revolving fund from local health centres. The trial was evaluated through two cross-sectional surveys at baseline and after two years of intervention. The primary endpoint of the study was the proportion of moderate to severe anaemia in children aged 6-59 months. For assessment of the development of drug efficacy over time, an in vivo CQ efficacy study was nested into the trial. The study is registered under http://www.controlled-trials.com (ISRCTN 34104704).
                The intervention was shown to be feasible under program conditions and a total of 1.076 children and 999 children were evaluated at baseline and follow-up time points respectively. Self-reported CQ treatment of fever episodes at home as well as referrals to health centres increased over the study period. At follow-up, CQ was detected in the blood of high proportions of intervention and control children. Compared to baseline findings, the prevalence of anaemia (29% vs 16%, p < 0.0001) and malaria parameters such as prevalence of P. falciparum parasitaemia, fever and palpable spleens was lower at follow-up but there were no differences between the intervention and control group. CQ efficacy decreased over the study period but this was not associated with the intervention.
                The decreasing prevalence of malaria morbidity including anaemia over the study period can be explained by an overall increase of malaria prevention and treatment activities in the study area. The lack of effectiveness of the intervention was likely caused by contamination, pre-existing differences in the coverage of malaria treatment in both study groups and an unexpectedly rapid increase of resistance against CQ, the first-line treatment drug at the time of the study. The potential for using community health workers (CHW) for administering timely and effective treatment for presumptive malaria attacks was evaluated in the Katana health zone in Zaire. In each of the 12 villages of an intervention area (area A) with 13000 inhabitants, a CHW was trained in the use of a simple fever management algorithm. The CHWs performed their services under the supervision of the nurse in charge of the area's health centre (HC). Malaria morbidity and mortality trends were monitored during 2 years in area A and in an ecologically comparable control area (area B), where malaria treatment continued to be available at the HC only. Health care behaviour changed dramatically in the intervention area, and by the end of the observation period 65% of malaria episodes were treated at the community level. Malaria morbidity declined 50% in area A but remained stable in the control area. Parasitological indices showed similar trends. Malaria-specific mortality rates remained, however, at essentially the same levels in both areas. The non-comprehensiveness of the CHWs' care and their ambiguous position in the health care system created problems that compromise the sustainability of the intervention. No satisfactory strategy for reducing high child mortality from malaria has yet been established in tropical Africa. We compared the effect on under-5 mortality of teaching mothers to promptly provide antimalarials to their sick children at home, with the present community health worker approach.
                Of 37 tabias (cluster of villages) in two districts with hyperendemic to holoendemic malaria, tabias reported to have the highest malaria morbidity were selected. A census was done which included a maternity history to determine under-5 mortality. Tabias (population 70,506) were paired according to under-5 mortality rates. One tabia from each pair was allocated by random number to an intervention group and the other was allocated to the control group. In the intervention tabias, mother coordinators were trained to teach other local mothers to recognise symptoms of malaria in their children and to promptly give chloroquine. In both intervention and control tabias, all births and deaths of under-5s were recorded monthly.
                From January to December 1997, 190 of 6383 (29.8 per 1000) children under-5 died in the intervention tabias compared with 366 of 7294 (50.2 per 1000) in the control tabias. Under-5 mortality was reduced by 40% in the intervention localities (95% CI from 29.2-50.6; paired t test, p<0.003). For every third child who died, a structured verbal autopsy was undertaken to ascribe cause of mortality as consistent with malaria or possible malaria, or not consistent with malaria. Of the 190 verbal autopsies, 13 (19%) of 70 in the intervention tabias were consistent with possible malaria compared with 68 (57%) of 120 in the control tabias.
                A major reduction in under-5 mortality can be achieved in holoendemic malaria areas through training local mother coordinators to teach mothers to give under-5 children antimalarial drugs. Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients.
                Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients.
                RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.
                ClinicalTrials.gov NCT00301015. A community-based malaria control programme initiated in Saradidi, Kenya in 1982 is described. Antimalarial treatment provided by volunteer community health workers was made available in each village. Malaria was holoendemic. Parasitaemia rates by age were high and did not change after the control programme began. Plasmodium falciparum was the most common species and was present alone or mixed in 98.2% of 8105 infections. Virtually all (98.5%) of 2040 blood samples collected in May 1981 were positive (reciprocal titre greater than or equal to 80) to P. falciparum by the indirect fluorescent antibody (IFA) test. Seropositivity rates to P. falciparum in the IFA test or the enzyme-linked immunosorbent assay (ELISA) were high in all age groups and did not change significantly in longitudinal surveys or in a cohort of children zero to nine years old followed at intervals. While the malaria control programme was successful in bringing treatment to each village, malaria prevalence was not reduced. Parasitologic and serologic studies alone were not adequate to describe the impact of the community-based malaria control programme in Saradidi. Morbidity and mortality rates caused by malaria can decline, significantly improving the health of the population, in the absence of any decrease in parasitaemia rates. It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether-lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3-59 months.
                We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3-59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p = 0.0002, adjusted p = 0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child's fever by source, or in the child's adherence to AL.
                Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale.
                Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07. Home management of malaria-the presumptive treatment of febrile children with antimalarial drugs-is advocated to ensure prompt effective treatment of the disease. We assessed the effect of home delivery of artemether-lumefantrine on the incidence of antimalarial treatment and on clinical outcomes in children from an urban setting with fairly low malaria transmission.
                In Kampala, Uganda, 437 children aged between 1 and 6 years from 325 households were randomly assigned by a computer-generated sequence to receive home delivery of prepackaged artemether-lumefantrine for presumptive treatment of febrile illnesses (n=225) or current standard of care (n=212). Randomisation was done by household after a pilot period of 1 month. After randomisation, study participants were followed up for an additional 12 months and information on their health and treatment of illnesses was obtained by use of monthly questionnaires and household diaries, which were completed by the participants' carers. The primary outcome was treatment incidence density per person-year. Analysis of the primary outcome was done on the modified intention-to-treat population, which included all participants apart from those excluded before data collection. This trial is registered with ClinicalTrials.gov, number NCT00115921.
                Eight participants in the home management group and four in the standard care group were excluded before data collection; therefore, the primary analysis was done in 217 and 208 participants, respectively. The home management group received nearly twice the number of antimalarial treatments as the standard care group (4.66 per person-year vs 2.53 per person-year; incidence rate ratio [IRR] 1.72, 95% CI 1.43-2.06, p<0.0001), and nearly five times the number given to children with microscopically confirmed malaria in a comparable cohort of children (4.66 per person-year vs 1.03 per person-year, IRR 5.19, 95% CI 4.24-6.35, p<0.0001). Clinical data were available for 189 children in the home management group and 176 in the control group at study end; the main reasons for exclusion were movement out of the study area or loss to follow-up. The proportion of participants with parasitaemia at final assessment in the intervention group was lower than in the control group (four [2%] vs 17 [10%], p=0.006), but there were no other differences in standard malariometric indices, including anaemia. Serious adverse events were captured retrospectively. One child died in each group (home management-severe pneumonia and possible septicaemia; standard care-presumed respiratory failure).
                Although home management of malaria led to prompt treatment of fever, there was little effect on clinical outcomes. The substantial over-treatment suggests that artemether-lumefantrine provided in the home might not be appropriate for large urban areas or settings with fairly low malaria transmission.
                Gates Malaria Partnership. Malaria infections are a major public health problem in Africa and prompt treatment is one way of controlling the disease and saving lives.
                This cluster-randomised controlled community intervention conducted in 2003-2005 aimed at improving early malaria case management in under five children. Health workers were trained to train community-based women groups in recognizing malaria symptoms, providing first-line treatment for uncomplicated malaria and referring severe cases. Evaluation was through a pre- (2004) and a post-intervention survey (2005). Anaemia prevalence was the primary outcome.
                1715 children aged 6-59 months were included in the pre-intervention survey and 2169 in the post-intervention survey. The prevalence of anaemia decreased significantly from 37% [95% CI 34.7-39.3] to 0.5% [95% CI 0.2-0.7] after the intervention (p<0.001); slightly more in the intervention (from 43.9% to 0.8%) than in the control (30.8% to 0.17%) group (p=0.038). Fever and reported fever decreased significantly and the mean body weight of the children increased significantly over the study period in both control and intervention groups.
                The decrease in anaemia was significantly associated with the intervention, whereas the fever and body weight trends might be explained by other malaria control activities or seasonal/climate effects in the area. The community intervention was shown to be feasible in the study context.
Home- or community-based interventions which provide antimalarial drugs free of charge probably improve prompt access to antimalarials, and there is moderate quality evidence from rural Ethiopia that they may impact on childhood mortality when implemented in appropriate settings.
Programmes which treat all fevers presumptively with antimalarials lead to overuse antimalarials, and potentially undertreat other causes of fever such as pneumonia. Incorporating RDT diagnosis into home- or community-based programmes for malaria may help to reduce this overuse of antimalarials, and has been shown to be safe under trial conditions.