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Background There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. Methods Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. Results Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of Conclusions In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children Trial registration Reported in individual primary studies.

BACKGROUND: The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. METHODS: In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. FINDINGS: Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p

The main objective of this study was to assess whether training of private health providers and community sensitization on the importance of effective prompt care seeking and the need for referral could improve treatment of sick children in the private health sector in Uganda. Private providers were trained to diagnose and treat sick children according to the integrated community case management (iCCM) guidelines. In the control arm, routine services were offered. The outcomes were seeking care within 24 hours of onset of symptoms and appropriate case management for malaria, pneumonia, and diarrhea among children aged < 5 years. A total of 10,809 sick children (5,955 in the intervention arm and 4,854 in the control arm) presented for diagnosis and treatment. The percentage seeking care within 24 hours of onset of symptoms was 45.4% (95% CI 36.0-48.8) in the intervention arm versus 43.9% (95% CI 38.1-49.8) in the control arm (P = 0.04). Adherence to malaria rapid diagnostic test (mRDT) results was high, with 1,459 (94.3%) in the intervention arm versus 1,402 (83.0%) in the control arm (P = 0.04). Appropriate treatment of mRDT-positive children with artemisinin-based combination therapy was seen in 93.1% (95% CI 88.5-97.7) in the intervention arm versus 85.1% (95% CI 78.6-91.7) in the control arm (P = 0.03). Adherence to iCCM guidelines was very high: 89.1% of children with diarrhea in the intervention arm and 80.4% in the control arm were given oral rehydration salts and zinc (P = 0.01). Of the children with a respiratory rate > 40 breaths/minute, 1,596 (85.1%) in the intervention arm versus 104 (54.5%) in the control arm were given amoxicillin (P = 0.01). In conclusion, the intervention improved treatment of malaria, pneumonia, and diarrhea because of provider adherence to treatment guidelines. The policy implications of these findings are to initiate a dialogue at district and national levels on how to scale up the intervention in the private sector. NCT02450630 registered with ClinicalTrials.gov: May 9, 2015.

In Sub-Saharan Africa, malaria remains a major cause of morbidity and mortality among children under 5, due to lack of access to prompt and appropriate diagnosis and treatment. Many countries have scaled-up community health workers (CHWs) as a strategy towards improving access. The present study was a cost-effectiveness analysis of the introduction of malaria rapid diagnostic tests (mRDTs) performed by CHWs in two areas of moderate-to-high and low malaria transmission in rural Uganda. CHWs were trained to perform mRDTs and treat children with artemisinin-based combination therapy (ACT) in the intervention arm while CHWs offered treatment based on presumptive diagnosis in the control arm. Data on the proportion of children with fever ‘appropriately treated for malaria with ACT’ were captured from a randomised trial. Health sector costs included: training of CHWs, community sensitisation, supervision, allowances for CHWs and provision of mRDTs and ACTs. The opportunity costs of time utilised by CHWs were estimated based on self-reporting. Household costs of subsequent treatment-seeking at public health centres and private health providers were captured in a sample of households. mRDTs performed by CHWs was associated with large improvements in appropriate treatment of malaria in both transmission settings. This resulted in low incremental costs for the health sector at US$3.0 per appropriately treated child in the moderate-to-high transmission area. Higher incremental costs at US$13.3 were found in the low transmission area due to lower utilisation of CHW services and higher programme costs. Incremental costs from a societal perspective were marginally higher. The use of mRDTs by CHWs improved the targeting of ACTs to children with malaria and was likely to be considered a cost-effective intervention compared to a presumptive diagnosis in the moderate-to-high transmission area. In contrast to this, in the low transmission area with low attendance, RDT use by CHWs was not a low cost intervention.

Malaria-endemic countries have implemented community health worker (CHW) programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. However, there is limited evidence describing the referral practices of CHWs. We examined the impact of malaria rapid diagnostic tests (mRDTs) on CHW referral in two cluster-randomized trials, one conducted in a moderate-to-high malaria transmission setting and one in a low-transmission setting in Uganda, between January 2010 and July 2012. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) for malaria and recognize signs and symptoms for referral to health centers. CHWs in the control arm used a presumptive diagnosis for malaria based on clinical symptoms, whereas intervention arm CHWs used mRDTs. CHWs recorded ACT prescriptions, mRDT results, and referral inpatient registers. An intention-to-treat analysis was undertaken using multivariable logistic regression. Referral was more frequent in the intervention arm versus the control arm (moderate-to-high transmission, P < 0.001; low transmission, P < 0.001). Despite this increase, referral advice was not always given when ACTs or prereferral rectal artesunate were prescribed: 14% prescribed rectal artesunate in the moderate-to-high setting were not referred. In addition, CHWs considered factors alongside mRDTs when referring. Child visits during the weekends or the rainy season were less likely to be referred, whereas visits to CHWs more distant from health centers were more likely to be referred (low transmission only). CHWs using mRDTs and ACTs increased referral compared with CHWs using a presumptive diagnosis. To address these concerns, referral training should be emphasized in CHW programs as they are scaled-up.

Background Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. Methods Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010–July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers’ referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. Results CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings

Background Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. Methods Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever ‘appropriately treated of malaria with ACT’ was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors, community sensitisation, supervision and provision of mRDTs and ACTs to drug shops. Household costs of treatment-seeking were captured in a representative sample of drug shop customers. Findings The introduction of mRDTs in drug shops was associated with a large improvement of diagnosis and treatment of malaria, resulting in low incremental costs for the health sector at US $0.55 per patient appropriately treated of malaria. High expenditure on non-ACT drugs by households contributed to higher incremental societal costs of US$3.83. Sensitivity analysis showed that mRDTs would become less cost-effective compared to presumptive diagnosis with increasing malaria prevalence and lower adherence to negative mRDT results. Conclusion mRDTs in drug shops improved the targeting of ACTs to malaria patients and are likely to be considered cost-effective compared to presumptive diagnosis, although the increased costs borne by households when the test result is negative are a concern.

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400–432,513). mRDTs were associated with significantly lower ACT prescription (range 8–69% versus 20–100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

Background: In Uganda, referral of sick children seeking care at public health facilities is poor and widely reported. However, studies focusing on the private health sector are scanty. The main objective of this study was to assess referral practices for sick children seeking care at private health facilities in order to explore ways of improving treatment and referral of sick children in this sector. Methods: A survey was conducted from August to October 2014 in Mukono district, central Uganda. Data was collected using a structured questionnaire supplemented by Focus Group Discussions and Key Informant interviews with private providers and community members. Results: A total of 241 private health facilities were surveyed; 170 (70.5%) were registered drug shops, 59 (24.5%) private clinics and 12 (5.0%) pharmacies. Overall, 104/241 (43.2%) of the private health facilities reported that they had referred sick children to higher levels of care in the two weeks prior to the survey. The main constraints to follow referral advice as perceived by caretakers were: not appreciating the importance of referral, gender-related decision-making and negotiations at household level, poor quality of care at referral facilities, inadequate finances at household level; while the perception that referral leads to loss of prestige and profit was a major constraint to private providers. Conclusion: In conclusion, the results show that referral of sick children at private health facilities faces many challenges at provider, caretaker, household and community levels. Thus, interventions to address constraints to referral of sick children are urgently needed.

Background Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a snap shot of medicine quality in a specific geographical area. This review presents an overview of the screening tests typically employed in surveys to assess anti-malarial medicine quality, summarizes the analytical methods used, how findings have been reported and proposes a reporting template for future studies. Methods A systematic search of the peer-reviewed and grey literature available in the public domain (including national and multi-national medicine quality surveys) covering the period 1990–2016 was undertaken. Studies were included if they had used screening techniques to assess the quality of anti-malarial medicines. As no standardized set of guidelines for the methodology and reporting of medicine quality surveys exist, the included studies were assessed for their standard against a newly proposed list of criteria. Results The titles and abstracts of 4621 records were screened and only 39 were found to meet the eligibility criteria. These 39 studies utilized visual inspection, disintegration, colorimetry and Thin Layer Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF) MiniLab® or as individual tests. Overall, 30/39 studies reported employing confirmatory testing described in international pharmacopeia to verify the quality of anti-malarials post assessment by a screening test. The authors assigned scores for the 23 criteria for the standard of reporting of each study. Conclusions There is considerable heterogeneity in study design and inconsistency in reporting of field surveys of medicine quality. A lack of standardization in the design and reporting of studies of medicine quality increases the risk of bias and error, impacting on the generalizability and reliability of study results. The criteria proposed for reporting on the standard of studies in this review can be used in conjunction with existing medicine quality survey guidelines as a checklist for designing and reporting findings of studies. The review protocol has been registered with PROSPERO (CRD42015026782). Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1852-6) contains supplementary material, which is available to authorized users.

The observation that many people in Africa seek care for febrile illness in the retail sector has led to a number of public health initiatives to try to improve the quality of care provided in these settings. The potential to support the introduction of rapid diagnostic tests for malaria (mRDTs) into drug shops is coming under increased scrutiny. Those in favour argue that it enables the harmonisation of policy around testing and treatment for malaria and maintains a focus on market-based solutions to healthcare. Despite the enthusiasm among many global health actors for this policy option, there is a limited understanding of the consequences of the introduction of mRDTs in the retail sector. We undertook an interpretive, mixed methods study with drug shop vendors (DSVs), their clients and local health workers to explore the uses and interpretations of mRDTs as they became part of daily practice in drug shops during a trial in Mukono District, Uganda. This paper reports the unintended consequences of their introduction. It describes how the test engendered trust in the professional competence of DSVs; was misconstrued by clients and providers as enabling a more definitive diagnosis of disease in general rather than malaria alone; that blood testing made drug shops more attractive places to seek care than they had previously been; was described as shifting treatment-seeking behaviour away from formal health centres and into drug shops; and influenced an increase in sales of medications, particularly antibiotics. Trial registration number NCT01194557; Results.

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.Setting CHERG birth cohorts from 14 population based sites in low and middle income countries.Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%.Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries.

BACKGROUND: Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions. METHODS: Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators. RESULTS: Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges. CONCLUSIONS: Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.

Objectives\ud To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. \ud Design\ud Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).\ud Setting\ud Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.\ud Participants\ud 522 480 children and adults with acute febrile illness.\ud Interventions\ud Rapid diagnostic tests for malaria.\ud Main outcome measures\ud Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.\ud Results\ud Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined. [Abstract copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.]

Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review we have adopted an empirical approach to investigating the geography and epidemiology of co-infection, and associations between patterns of co-infection and haemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hookworm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women – groups among the highest risk of anemia - would benefit from an integrated approach to malaria and helminth control.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.

OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety in the private health sector in Uganda. METHODS: A survey was conducted within 57 parishes from August to October 2014 in Mukono District, Uganda. Data was captured on the following variables: drug shop characteristics, training of staff in management of pneumonia, availability of guidelines and basic equipment, available antibiotics, knowledge on treatment of pneumonia in children aged METHODS: A survey was conducted within 57 parishes from August to October 2014 in Mukono District, Uganda. Data was captured on the following variables: drug shop characteristics, training of staff in management of pneumonia, availability of guidelines and basic equipment, available antibiotics, knowledge on treatment of pneumonia in children aged RESULTS: A total of 170 registered drug shops were surveyed between August and October 2014. The majority of drug shops, 93.5% were prescribing antibiotics, especially amoxicillin and trimethoprim-sulfamethoxazole (septrin). The professional qualification of a provider was significantly associated with this practice, p=0.04; where lower cadre staff (nursing assistants and enrolled nurses) overprescribed antibiotics. A third, 29.4% of drug shop providers reported that antibiotics were the first-line treatment for children with diarrhoea; yet the standard guideline is to give oral rehydration salts and zinc tablets. Only few providers, 8.2%, had training on antibiotics, with 10.6% on pneumonia case management. Further to this, 7.1% drug shops had WHO-Integrated Management of Childhood Illness guidelines, and a negligible proportion (CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets.

• Are afebrile malaria infections truly asymptomatic, benign, or even beneficial to the individual? The evidence suggests the contrary.• So-called “asymptomatic” malaria infections are associated with recurrent episodes of symptomatic parasitemia, chronic anemia, maternal and neonatal mortality, co-infection with invasive bacterial disease, cognitive impairment, and ongoing transmission of the parasite.• “Asymptomatic” malaria infections have significant health and societal consequences, and we propose that they should be renamed “chronic” malaria infections.• Targeting chronic malaria infections poses major scientific, operational, and ethical challenges.• We call for the malaria community to work with malaria control and elimination programs to target all malaria infections, irrespective of their density or presentation. The operational challenges to detect and treat chronic infections are significant, but accomplishing this is likely to result in substantial gains to both the individual and society.

Pregnant women and their unborn children are vulnerable to malaria, increasing the risk of maternal anaemia, low birthweight (LBW) and intrauterine growth retardation. There is little evidence on the cost-effectiveness of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated bednets (ITN) in areas of low transmission. A randomised controlled trial with three arms was conducted in antenatal clinics in Kabale District (Uganda), an epidemic-prone highland area of low malaria transmission. The interventions were: (i) IPTp with sulfadoxine/pyrimethamine (SP) given twice during pregnancy (IPTp-SP); (ii) ITNs alone; and (iii) a combined intervention with both ITNs and IPTp-SP. Primary health outcomes were LBW and maternal anaemia. The costs of providing IPTp-SP and ITNs as well as treatment of malaria episodes were captured from all health centres in the study area. There were no significant differences in health outcomes among the three interventions. The cost-effectiveness analysis and sensitivity analyses performed did not provide convincing support for replacing IPTp-SP (current policy) by ITNs alone or by a combined intervention in this low-transmission setting on economic grounds. The cost per pregnant woman of providing the services was lowest for the IPTp-SP intervention (US$0.79 per woman) followed by ITNs (US$1.71) and the combined intervention of IPTp-SP + ITNs (US$2.48). The relative cost-effectiveness of antenatal distribution of ITNs might improve if the cost savings accruing from continued use of a long-lasting insecticidal net after pregnancy as well as positive externalities were also taken into account, and this warrants further study. [ClinicalTrials.gov identifier: NCT00142207].

Knowledge of malaria and treatment-seeking behaviour was investigated in an area of low transmission in Uganda to help health services to plan for appropriate interventions to control malaria. Although knowledge of malaria symptoms, preventive methods and malaria risks was widespread, few were actually using insecticide-treated nets. Many patients (25%) had received treatment prior to visiting a health facility, with drug shops and general stores being the main sources of treatment. Some shops dispensed quinine, a second-line drug recommended for complicated malaria. Prescription practices of health staff often did not comply with guidelines. Only 30% of patients received treatment at a health facility within 24h of onset of symptoms. Findings indicate a need for community-level information campaigns on prompt treatment and introduction of home-based management of fever. Measures are needed to protect second-line drugs from misuse. Failure to comply with drug policy in both the private and public sectors is of concern in an era of rapidly evolving drug policy changes and highlights the need for reorientation and training of health staff and drug vendors to improve malaria diagnostic and treatment skills.

Large parts of African and American countries are colonized by Mansonella, a very common but poorly described filarial nematode. Bloodsucking flies of the genus Culicoides are suspected to be the vector of Mansonella perstans, but no study in Senegal has confirmed that Culicoides can transmit the parasite. Designed specific real-time quantitative polymerase chain reaction (qPCR) can be used to identify microfilaria in stained blood smears. This study was performed in July and December 2010 in the southeastern Senegal, which is known to be endemic for M. perstans. We analyzed 297 blood smears from febrile and afebrile resident people by qPCR. The global prevalence of M. perstans was approximately 14.5% in both febrile and afebrile individuals. The age group of > 30 years had the highest prevalence (22.0%). No Culicoides among 1,159 studied specimens was positive for M. perstans and its vector in Senegal still requires identification.

BACKGROUND: Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops.METHODS: A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT.FINDINGS: A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 - 50·9), pCONCLUSION: Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT.TRIAL REGISTRATION: ClinicalTrials.gov NCT01194557.

Background Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/ 2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. Methods ACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. Results Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. Conclusion Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained.This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Fil: Kaur, Harparkash. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Allan, Elizabeth Louise. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Mamadu, Ibrahim. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Hall, Zoe. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Ibe, Ogochukwu. University of Nigeria; Nigeria Fil: El Sherbiny, Mohamed. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Van Wyk, Albert. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Yeung, Shunmay. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Swamidoss, Isabel. US Centers for Disease Control and Prevention; Estados Unidos Fil: Green, Michael D.. US Centers for Disease Control and Prevention; Estados Unidos Fil: Dwivedi, Prabha. US Centers for Disease Control and Prevention; Estados Unidos Fil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina Fil: Calrke, Sian. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Schellenberg, David. London School of Hygiene & Tropical Medicine; Reino Unido Fil: Fernández, Facundo M.. Georgia Institute of Techology; Estados Unidos Fil: Onwujekwe, Obina. University of Nigeria; Nigeria

We conducted an efficacy study of chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and a combination of both (SP + CQ) for the treatment of uncomplicated malaria in an area of low transmission with low drug pressure. On day 3, fever clearance was 97.4% (95% CI, 86.8-99.9), 100% (95% CI, 87.2-100) and 96.6% (95% CI, 82.2-99.9) in the CQ, SP and SP + CQ groups, respectively, (P = 0.65). On day 14, clinical success was 92.5% (95% CI, 79.6-98.4), 100% (95% CI, 87.2-100) and 100% (95% CI, 88.1-100) in the CQ, SP and CQ + SP groups, respectively. Clinical failure was seen in 7.5% with 5% (95% CI, 0.61-16.9) early treatment failure and 2.5% (95% CI, 0.06-13.2) late treatment failure of cases in the CQ group and 0% in the SP and SP + CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI, 2.8-23.7), 18.5% (95% CI, 6.3-38.1) and 6.9% (95% CI, 0.85-22.8) for the CQ, SP and SP + CQ, respectively (P = 0.37). There was no age-dependent difference in clinical failure or parasitological resistance in any of the treatment groups and prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The findings of this study suggest that CQ is still effective for the treatment of uncomplicated malaria in this area of low transmission and SP. However, combination therapy of SP + CQ is recommended to delay the development SP resistance, and regular surveillance for emerging CQ and SP resistance is needed to plan for alternative antimalarial drug regimens.

OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts.DESIGN: A comparative case study approach, analysing variation in outcomes across different settings.SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case.PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria.INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation.OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial).RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs.CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce.

BACKGROUND: An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities (patients) and the public sector (health facility staff and district officials) to the behavioral changes in diagnosis, treatment and referral being introduced in drug shops. The intervention was designed to be evaluated through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature.METHODS: Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops, and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities. The intervention required careful design with the intention to be acceptable, sustainable and effective. Critical components of intervention were: community sensitization and creating awareness, training of drug shop vendors to diagnose malaria with mRDTs, treat and refer customers to formal health facilities, giving pre-referral rectal artesunate and improved record-keeping. The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT, evaluated against microscopy on a research blood slide.RESULTS: Introducing mRDTs in drug shops may seem simple, but our experience of intervention design, conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological, social science and health economics methodologies. The trial was conducted in phases sequenced such that each benefited from the other.CONCLUSIONS: The main challenges in designing this trial were maintaining a balance between a robust intervention to support effective behaviour change and introducing practices that would be sustainable in a real-life situation in tropical Africa; as well as achieving a detailed evaluation without inadvertently influencing prescribing behaviour.Trial registration: Trial registration: NCT01194557 registered with ClinicalTrials.gov 2 September 2010.

BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial. METHODS: A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 - 40) with substantial between-cluster variation, ranging from 1% to 55%. CONCLUSION: In this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets.

BACKGROUND: National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (

In an analysis of four datasets from East Africa, Tanya Marchant and colleagues investigate the neonatal mortality risk associated with preterm birth and how this changes with weight for gestational age., Background Low birth weight and prematurity are amongst the strongest predictors of neonatal death. However, the extent to which they act independently is poorly understood. Our objective was to estimate the neonatal mortality risk associated with preterm birth when stratified by weight for gestational age in the high mortality setting of East Africa. Methods and Findings Members and collaborators of the Malaria and the MARCH Centers, at the London School of Hygiene & Tropical Medicine, were contacted and protocols reviewed for East African studies that measured (1) birth weight, (2) gestational age at birth using antenatal ultrasound or neonatal assessment, and (3) neonatal mortality. Ten datasets were identified and four met the inclusion criteria. The four datasets (from Uganda, Kenya, and two from Tanzania) contained 5,727 births recorded between 1999–2010. 4,843 births had complete outcome data and were included in an individual participant level meta-analysis. 99% of 445 low birth weight (, Editors' Summary Background Worldwide, every year around 3.3 million babies die within their first month of life and the proportion of under-five child deaths that are now in the neonatal period (the first 28 days of life) has increased in all regions of the world and is currently estimated at 41%. Of these deaths, over 90% occur in low- and middle-income countries, and a third of all neonatal deaths occur in sub-Saharan Africa. Low birth weight (defined as

Background National malaria control programmes and international agencies are keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria. The high proportion of the Ugandan population seeking care at drug shops makes these outlets attractive as providers of malaria RDTs. However, there is no precedent for blood testing at drug shops and little is known about how such tests might be perceived and used. Understanding use of drug shops by communities in Uganda is essential to inform the design of interventions to introduce RDTs. Methods We conducted a qualitative study, with 10 community focus group discussions, and 18 in-depth interviews with drug shop attendants, health workers and district health officials. The formative study was carried out in Mukono district, central Uganda an area of high malaria endemicity from May-July 2009. Results Drug shops were perceived by the community as important in treating malaria and there was awareness among most drug sellers and the community that not all febrile illnesses were malaria. The idea of introducing RDTs for malaria diagnosis in drug shops was attractive to most respondents. It was anticipated that RDTs would improve access to effective treatment of malaria, offset high costs associated with poor treatment, and avoid irrational drug use. However, communities did express fear that drug shops would overprice RDTs, raising the overall treatment cost for malaria. Other fears included poor adherence to the RDT result, reuse of RDTs leading to infections and fear that RDTs would be used to test for human immune deficiency virus (HIV). All drug shops visited had no record on patient data and referral of cases to health units was noted to be poor. Conclusion These results not only provide useful lessons for implementing the intervention study but have wide implications for scaling up malaria treatment in drug shops.

Intermittent preventive treatment of malaria during pregnancy (IPTp) and insecticide-treated nets (ITN) are recommended malaria interventions during pregnancy; however, there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa. An individually-randomised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp, ITNs alone, or ITNs used in combination with IPTp on maternal anaemia and low birth weight (LBW) in a highland area of southwestern Uganda. The overall prevalence of malaria infection, maternal anaemia and LBW was 15.0%, 14.7% and 6.5%, respectively. Maternal and fetal outcomes were generally remarkably similar across all intervention groups (P>0.05 for all outcomes examined). A marginal difference in maternal haemoglobin was observed in the dual intervention group (12.57g/dl) compared with the IPTp and ITN alone groups (12.40g/dl and 12.44g/dl, respectively; P=0.04), but this was too slight to be of clinical importance. In conclusion, none of the preventive strategies was found to be superior to the others, and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed. With ITNs offering a number of advantages over IPTp, yet showing comparable efficacy, we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission.

In Uganda, around two thirds of medicines are procured from the private sector, mostly from drug shops. The introduction of malaria rapid diagnostic tests (RDTs) at drug shops therefore has the potential to make a significant contribution to targeting antimalarial drugs to those with malaria parasites. We undertook formative research in a district in Uganda in preparation for a randomised trial of RDTs in drug shops. In May to July 2009, we interviewed 9 drug shop workers, 5 health workers and 4 district health officials and carried out 10 focus group discussions with a total of 75 community members to investigate the role of drug shops and the potential for implementation of RDTs at these health care outlets. Drug shops were seen to provide an important service to community members, the nature of which is determined by responsiveness to client demands. However, drug shops hold a liminal status: in the eyes of different actors, these outlets are at once a shop and clinic; legitimate and illegitimate; and trusted and distrusted. Malaria treatment was found to be synonymous with diagnosis. Diagnostic testing was deemed useful in theory, and community members were curious about the results, with the expectation that a test would decrease uncertainty and help secure an end to illness. However, whether testing would be sought as a routine step in treatment decisions in practice is uncertain, since the appeal of the tests waned in light of their costs and potential for results to conflict with presumed diagnosis. Interventions that increase awareness of multiple causes and management of malaria-like illness will be needed to support the new rationalisation for malaria treatment represented by parasitological diagnosis.

Anaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10–21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission.

Understanding local variability in malaria transmission risk is critically important when designing intervention or vaccine trials. Using a combination of field data, satellite image analysis, and GIS modeling, we developed a high-resolution map of malaria entomological inoculation rates (EIR) in The Gambia, West Africa. The analyses are based on the variation in exposure to malaria parasites experienced in 48 villages in 1996 and 21 villages in 1997. The entomological inoculation rate (EIR) varied from 0 to 166 infective bites per person per rainy season. Detailed field surveys identified the major Anopheles gambiae s.l. breeding habitats. These habitats were mapped by classification of a LANDSAT TM satellite image with an overall accuracy of 85%. Village EIRs decreased as a power function based on the breeding areas size and proximity. We use this relationship and the breeding habitats to map the variation in EIR over the entire 2500-km(2) study area.

Background Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1) passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2) a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases. Results Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May-July 2002. Household surveys of cases and age-matched controls were conducted to collect information on household construction, exposure factors and socio-economic status. Household geographical location and altitude were determined using a hand-held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.

It has recently been suggested that helminth infections may adversely influence susceptibility to other infections, including malaria. To investigate this hypothesis in a sub-Saharan African setting, surveys of helminth infections were conducted in 2003 among individuals who had been under weekly active case detection for clinical malaria during the preceding 18 months in four villages in Kabale District, southwest Uganda. Overall, 47.3% of individuals had at least one intestinal nematode species infection: hookworm, Ascaris lumbricoides and Trichuris trichiura were detected in 32.1, 17.4 and 8.1% of individuals, respectively. We found evidence of significant household clustering of A. lumbricoides, T. trichiura and hookworm, and clustering of heavy infection of each species. The association between helminth infection and clinical malaria was investigated in two villages and no evidence for an association was observed between the presence of infection or heavy infection and risk of malaria.

Home treatment with antimalarials is a common practice in many countries, and may save lives by ensuring that more malaria cases receive prompt treatment. Through retrospective surveys we found that home treatment of young children with antimalarials was uncommon in rural Gambia. Few families kept medicines in the home in case of illness, 28% kept paracetamol and only 8% kept chloroquine. Less than 10% of cases of childhood 'malaria' had been treated with chloroquine at home, and 69% of those giving home medication did not know the correct dosage for a child. The most common course of treatment was the use of paracetamol and/or tepid sponging to reduce fever, before the child was taken to a government health facility. Treating a child with antimalarials at home was more costly than other forms of treatment. The low cost associated with the use of health services for children and the limited availability of antimalarials outside major towns contribute to the high use of government health services. This shows that that home treatment cannot be assumed to be the predominant mode of malaria treatment throughout Africa, and highlights the need for country-specific policies based on accurate local knowledge of treatment practices in both rural and urban areas.

The causes of local variation in the prevalence of malaria were investigated in rural Gambia. Cross-sectional prevalence surveys were carried out among 1184 young children (aged 6 months-5 years) in 48 villages, at the end of the transmission season in 1996. Villages were categorized according to distance from the nearest vector breeding sites, and the patterns of malaria transmission, infection and disease compared. Children living in villages within 3 km of breeding sites experienced more infective bites, and higher prevalences of parasitaemia and spleen enlargement than less-exposed children living further away. Clinical illness, in contrast, was more common among infected children who were less exposed. Infected children living 3 km or more from breeding sites were more likely to have high-density parasitaemia (odds ratio [OR] = 1.98), fever (OR = 2.60) and high-density parasitaemia together with fever (OR = 3.17). Clinical attacks did not decline in older children, as seen amongst children who were more exposed. These findings show that significant differences in the risk of infection and clinical attacks can occur over very short distances. The age at which protective immunity is acquired may be delayed in villages where transmission intensity is lower, thus increasing the risk of a clinical attack following infection. Communities with the lowest vector densities may be those at greatest risk of disease.

The effect of zooprophylaxis on malaria transmission has not been studied on the African continent despite that the World Health Organization has recommended this intervention method since 1982. The effect of passive zooprophylaxis on malaria vector abundance, mosquito feeding preferences, and infectivity was studied in an area of moderate seasonal transmission in The Gambia. A paired cohort of 204 children

Bednets are thought to offer little, if any, protection against malaria, unless treated with insecticide. There is also concern that the use of untreated nets will cause people sleeping without nets to receive more mosquito bites, and thus increase the malaria risk for other community members. Regular retreatment of nets is therefore viewed as critical for malaria control. However, despite good uptake of nets, many control programmes in Africa have reported low re-treatment rates. We investigated whether untreated bednets had any protective benefit (in October and November 1996) in The Gambia where nets, although widely used, are mostly untreated. Cross-sectional prevalence surveys were carried out in 48 villages and the risk of malaria parasitaemia was compared in young children sleeping with or without nets. Use of an untreated bednet in good condition was associated with a significantly lower prevalence of Plasmodium falciparum infection (51% protection [95% CI 34-64%], P < 0.001). This finding was only partly explained by differences in wealth between households, and children in the poorest households benefited most from sleeping under an untreated net (62% protection [14-83%], P = 0.018). There was no evidence that mosquitoes were diverted to feed on children sleeping without nets. These findings suggest that an untreated net, provided it is in relatively good condition, can protect against malaria. Control programmes should target the poorest households as they may have the most to gain from using nets.

In a typically elegant analysis comparing the cost-effectiveness of vaccines and insecticide impregnation of mosquito nets for the prevention of malaria, Patricia Graves recently estimated that the costs per death averted for a vaccine would be US$252 compared to US$ 711 with impregnated nets1xComparison of the cost-effectiveness of vaccines and insecticide impregnation of mosquito nets for the prevention of malaria. Graves, P.M. Ann. Trop. Med. Parasitol. 1998; 92: 399–410Crossref | PubMed | Scopus (26)See all References1. The estimates for the mosquito-net costs were based on the costs of re-impregnation with insecticide every six months. Recently, an insecticide-impregnated wash-proof mosquito net has been developed that is sold at the same price as an untreated net. The costs, therefore, of using such a net in a similar analysis would be nil. As such, the conclusion that malaria-vaccine research and development should be the highest priority for investment might need to be reconsidered.Of course, there are a number of other factors (both pro and contra) that need to be considered in the arguments and analyses. For example, the actual amount of investment needed to develop a vaccine (which probably runs into billions rather than millions of US$) was ignored. Similarly, it was assumed that everyone already possessed a net (which is a considerable capital cost), that all nets were re-impregnated every six months (when in fact re-impregnation rates are generally less than a third) and that people used their nets all the time. Other perceived end-user benefits from using a net [such as a good night's sleep (the GNS factor), controlling bed bugs, scabies or other diseases, such as filariasis and kal-azar] were also not included in the overall evaluation.Graves was worried in case impregnation programs became so entrenched that it might be difficult to switch to more effective strategies (such as a vaccine program) when they become available. Many control methods (including vaccines and mosquito nets) are, however, complementary and, in an integrated program, they would all have their place.We can already faintly hear the voices of dissent talking about the possibilities of insecticide resistance developing when large numbers of wash-proof nets are in use. This issue could perhaps be addressed by persuading the manufacturers to incorporate two insecticides on the nets. This should reduce the likelihood of resistance developing against either insecticide in much the same way that combined therapy should work against the parasite.Ultimately, strategies to avoid malaria will be in the hands of the people affected by the disease. The best way of ensuring that all of the available techniques are used appropriately is that people know the likely personal costs and benefits of the different strategies they might adopt. As such, the role of education, particularly for the younger generation, cannot be over emphasized.