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. Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study. Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Impact of pre-packaging antimalarial drugs and counselling on compliance with malaria treatment at Port Moresby General Hospital Adult Outpatient Department. Effectiveness of feedback for improving case management of malaria, diarrhoea and pneumonia--a randomized controlled trial at provincial hospitals in Lao PDR. Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial. The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial. Home management of malaria with artemether-lumefantrine compared with standard care in urban Ugandan children: a randomised controlled trial. The impact of retail-sector delivery of artemether-lumefantrine on malaria treatment of children under five in Kenya: a cluster randomized 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. The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria is being suggested to improve diagnostic efficiency in peripheral health care settings in Africa. Such improved diagnostics are critical to minimize overuse and thereby delay development of resistance to artemisinin-based combination therapies (ACTs). Our objective was to study the influence of RDT-aided malaria diagnosis on drug prescriptions, health outcomes, and costs in primary health care settings.
                We conducted a cross-over validation clinical trial in four primary health care units in Zanzibar. Patients of all ages with reported fever in the previous 48 hours were eligible and allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Statistical analyses with multilevel modelling were performed. A total of 1,887 patients were enrolled February through August 2005. RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%) (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03-0.05, p<0.001). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5-2.2, p<0.001), respectively. Reattendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3-0.9, p = 0.005). Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD alone, respectively.
                RDTs resulted in improved adequate treatment and health outcomes without increased cost per patient. RDTs may represent a tool for improved management of patients with fever in peripheral health care settings.
                (Clinicaltrials.gov) NCT00549003. The emergence and spread of Plasmodium falciparum resistance to commonly used antimalarials such as chloroquine and sulphadoxine/pyrimethamine poses major challenges to malaria control in sub-Saharan Africa. We undertook a study on the efficacy of some antimalarial drugs in 2003 with the view of supporting the National Malaria Control Programme in the review of the antimalarial drug treatment policy in Ghana. Children aged 6-59 months with signs/symptoms of uncomplicated malaria including axillary temperature > or =37.5 degrees C; mono infection with P. falciparum; and parent's willingness to give consent, were randomized into four treatment groups and followed up for a maximum of 28 days. The treatment groups were chloroquine (CHQ), sulphadoxine/pyrimethamine (SP), amodiaquine+artesunate (ADQ+ART) combination, and artemether+lumefantrine (Coartem) combination. Clinical evaluation of 168 children studied showed that cumulative pcr-corrected cure rates on day 28 were 100% for ADQ+ART; 97.5% for coartem, 60% for SP and 25% for CHQ. The artemisinin-based combinations effected rapid fever and parasite clearance. Prevalence of gametocytaemia was highest in the SP group whilst the CHQ group did not show any significant changes in haemoglobin levels during the follow-up period. The findings are in agreement with current recommendations for using artemisinin-based combinations for treating uncomplicated malaria in areas of high CHQ failure such as Ghana. We investigated the impact of pre-packaging antimalarial drugs and counselling on compliance with treatment of malaria at the Adult Outpatient Department of Port Moresby General Hospital. Adult patients who were prescribed standard antimalarial drugs following clinical and microscopic diagnosis of malaria were randomly assigned to one of three groups: an intervention group, where pre-packaging and counselling instructions were applied; control group A, with counselling but no pre-packaging; and control group B, with neither counselling nor pre-packaging. Patients were interviewed on two occasions, day 1 of treatment and day 4 post treatment. Of a total of 436 patients, 322 patients (179 males and 143 females) completed the study. Our data indicate an increase of 18% in compliance with treatment in the intervention group and 16% in control group A, when compared with control group B. While compliance with treatment was gender independent, the language spoken and used for giving instructions and counselling may have influenced patients' behaviour on prescribed medication. The results of our study indicate that a simple pre-packaging system and proper counselling could improve compliance with antimalarial drug treatment. As an additional beneficial observation, pre-packaging is likely to eliminate errors and possible contamination of the products during dispensing. Standard Treatment Guidelines were introduced to all prescribers at provincial hospitals in Lao PDR and treatment indicators were developed within the National Drug Policy programme to monitor compliance.
                To evaluate the effects of an educational intervention to improve treatment practices of malaria, diarrhoea and pneumonia.
                Randomized controlled trial with prescribers at 24 departments at eight provincial hospitals, matched into four pairs. The three departments of internal medicine, paediatrics and out-patients in each pair were randomized into intervention or control group. The 6-month intervention was conducted by members of the Drug and Therapeutics Committees, and comprised monthly audit sessions in the form of outcome feedback using indicator scores on recorded treatment of malaria, diarrhoea and pneumonia. We measured treatment indicator scores 6 months after the end of the intervention compared with baseline.
                The aggregated mean scores for all diseases, and for malaria and diarrhoea, improved significantly. For pneumonia, improvement was seen in both the intervention and control groups. Record keeping was improved for all three diseases. For malaria, there were improvements in recording patients' history, and in frequency of microscope testing; for diarrhoea, regarding weight measurements, palpation of the fontanel for children under 2 years, and reduction of irrational use of anti-diarrhoeals and antibiotics; for pneumonia, in recording respiratory count, and reducing irrational use of anti-histamines and anti-cough medications.
                Audit-feedback systems to improve quality of care are feasible and effective also in hospital settings in low-income countries. 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. To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria-related morbidity in children <5 years of age who already had access to home-based management of malaria (HMM) for presumptive treatment of fevers.
                Thirty community-based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate-amodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross-sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children.
                During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: -9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2-78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration.
                In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.
                © 2010 Blackwell Publishing Ltd. 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. 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- 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.