Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children.

BACKGROUND: Presumptive treatment of malaria in febrile children is widely advocated in Africa. This may occur in the absence of diagnostic testing or even when diagnostic testing is performed but fails to detect malaria parasites. Such over-treatment of malaria has been tolerated in the era of inexpensive and safe monotherapy. However, with the introduction of new artemisinin-based combination therapy (ACT), presumptive treatment becomes economically and clinically less acceptable. METHODS: The risks and benefits of only treating children with microscopy confirmed malaria using a prospective cohort design were investigated. A representative sample of 601 children between one and 10 years of age were recruited from a census population in Kampala, Uganda and were followed for all of their health care needs in a study clinic. Standard microscopy was performed each time a child presented with a new episode of fever and antimalarial therapy given only if the blood smear was positive. RESULTS: Of 5,895 visits for new medical problems 40% were for febrile illnesses. Of the 2,359 episodes of new febrile illnesses, blood smears were initially reported as negative in 1,608 (68%) and no antimalarial therapy was given. Six of these initially negative smears were reported to be positive following quality control reading of all blood smears: four of these patients were subsequently diagnosed with uncomplicated malaria and two cleared their parasites without antimalarial treatment. Of the 1,602 new febrile illnesses in which the final blood smear reading was classified as negative, only 13 episodes (0.8%) were diagnosed with malaria in the subsequent 7 days. All 13 of these episodes of malaria were uncomplicated and were successfully treated. CONCLUSION: In this urban setting, malaria was responsible for only 32% of febrile episodes. Withholding antimalarial therapy in febrile children with negative blood smears was safe and saved over 1,600 antimalarial treatments in 601 children over an 18-month period. In the era of expensive ACT, directing resources towards improving diagnostic and treatment practices may provide a cost-effective measure for promoting rational use of antimalarial therapy

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Anti-malarial prescription practices among outpatients with laboratory-confirmed malaria in the setting of a health facility-based sentinel site surveillance system in Uganda.

BACKGROUND: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. METHODS: Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients ≥ 4 months of age and ≥ 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. RESULTS: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). CONCLUSIONS: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa

Taking opportunities, taking medicines:Antibiotic use in rural Eastern Uganda

The ways in which dimensions of health and healthcare intersect with economics and politics in particular contexts requires close attention. In this article we connect concerns about antibiotic overuse in Uganda to the social milieu created through policies that follow President Museveni's vision for a population who kulembeka, "tap wealth." Ethnographic fieldwork in rural Eastern Uganda illustrates how taking medicines in rural households reflects a wider landscape of everyday imperatives to "tap" opportunities in a context of acute precarity. We argue for a closer connection between medical and economic anthropology to push forward understanding of health, medicines and wellbeing in Africa

Data value and care value in the practice of health systems: A case study in Uganda.

In anthropology, interest in how values are created, maintained and changed has been reinvigorated. In this case study, we draw on this literature to interrogate concerns about the relationship between data collection and the delivery of patient care within global health. We followed a pilot study conducted in Kayunga, Uganda that aimed to improve the collection of health systems data in five public health centres. We undertook ethnographic research from July 2015 to September 2016 in health centres, at project workshops, meetings and training sessions. This included three months of observations by three fieldworkers; in-depth interviews with health workers (n = 15) and stakeholders (n = 5); and six focus group discussions with health workers. We observed that measurement, calculation and narrative practices could be assigned care-value or data-value and that the attempt to improve data collection within health facilities transferred 'data-value' into health centres with little consideration among project staff for its impact on care. We document acts of acquiescence and resistance to data-value by health workers. We also describe the rare moments when senior health workers reconciled these two forms of value, and care-value and data-value were enacted simultaneously. In contrast to many anthropological accounts, our analysis suggests that data-value and care-value are not necessarily conflicting. Actors seeking to make changes in health systems must, however, take into account local forms of value and devise health systems interventions that reinforce and enrich existing ethically driven practice

Adherence to treatment with artemether-lumefantrine or amodiaquine-artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial.

BACKGROUND: Prompt, effective treatment of confirmed malaria cases with artemisinin-based combination therapy (ACT) is a cornerstone of malaria control. Maximizing adherence to ACT medicines is key to ensuring treatment effectiveness. METHODS: This open-label, randomized trial evaluated caregiver adherence to co-formulated artemether-lumefantrine (AL) and fixed-dose amodiaquine-artesunate (AQAS) in Sierra Leone. Children aged 6-59 months diagnosed with malaria were recruited from two public clinics, randomized to receive AL or AQAS, and visited at home the day after completing treatment. Analyses were stratified by site, due to differences in participant characteristics and outcomes. RESULTS: Of the 784 randomized children, 680 (85.6%) were included in the final per-protocol analysis (340 AL, 340 AQAS). Definite adherence (self-reported adherence plus empty package) was higher for AL than AQAS at both sites (Site 1: 79.4% AL vs 63.4% AQAS, odds ratio [OR] 2.16, compared to probable adherence plus probable or definite non-adherence, 95% confidence interval [CI] 1.34-3.49; p = 0.001; Site 2: 52.1% AL vs 37.5% AQAS, OR 1.53, 95% CI 1.00-2.33, p = 0.049). However, self-reported adherence (ignoring drug package inspection) was higher for both regimens at both sites and there was no strong evidence of variation by treatment (Site 1: 96.6% AL vs 95.9% AQAS, OR 1.19, 95% CI 0.39-3.63, p = 0.753; Site 2: 91.5% AL vs 96.4% AQAS, OR 0.40, 95% CI 0.15-1.07, p = 0.067). In Site 2, correct treatment (correct dose + timing + duration) was lower for AL than AQAS (75.8% vs 88.1%, OR 0.42, 95% CI 0.23-0.76, p = 0.004). In both sites, more caregivers in the AQAS arm reported adverse events (Site 1: 3.4% AL vs 15.7% AQAS, p < 0.001; Site 2: 15.2% AL vs 24.4% AQAS, p = 0.039). CONCLUSIONS: Self-reported adherence was high for both AL and AQAS, but varied by site. These results suggest that each regimen has potential disadvantages that might affect adherence; AL was less likely to be taken correctly at one site, but was better tolerated than AQAS at both sites. Measuring adherence to anti-malarials remains challenging, but important. Future research should focus on comparative studies of new drug regimens, and improving the methodology of measuring adherence. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01967472. Retrospectively registered 18 October 2013, https://clinicaltrials.gov/ct2/show/NCT01967472

The PROCESS study: a protocol to evaluate the implementation, mechanisms of effect and context of an intervention to enhance public health centres in Tororo, Uganda.

BACKGROUND: Despite significant investments into health improvement programmes in Uganda, health indicators and access to healthcare remain poor across the country. The PRIME trial aims to evaluate the impact of a complex intervention delivered in public health centres on health outcomes of children and management of malaria in rural Uganda. The intervention consists of four components: Health Centre Management; Fever Case Management; Patient- Centered Services; and support for supplies of malaria diagnostics and antimalarial drugs. METHODS: The PROCESS study will use mixed methods to evaluate the processes, mechanisms of change, and context of the PRIME intervention by addressing five objectives. First, to develop a comprehensive logic model of the intervention, articulating the project's hypothesised pathways to trial outcomes. Second, to evaluate the implementation of the intervention, including health worker training, health centre management tools, and the supply of artemether-lumefantrine (AL) and rapid diagnostic tests (RDTs) for malaria. Third, to understand mechanisms of change of the intervention components, including testing hypotheses and interpreting realities of the intervention, including resistance, in context. Fourth, to develop a contextual record over time of factors that may have affected implementation of the intervention, mechanisms of change, and trial outcomes, including factors at population, health centre and district levels. Fifth, to capture broader expected and unexpected impacts of the intervention and trial activities among community members, health centre workers, and private providers. Methods will include intervention logic mapping, questionnaires, recorded consultations, in-depth interviews, focus group discussions, and contextual data documentation. DISCUSSION: The findings of this PROCESS study will be interpreted alongside the PRIME trial results. This will enable a greater ability to generalise the findings of the main trial. The investigators will attempt to assess which methods are most informative in such evaluations of complex interventions in low-resource settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01024426

Targeting malaria control to schoolchildren

Commen

Plasmodium infection and its risk factors in eastern Uganda

BACKGROUND: Malaria is a leading cause of disease burden in Uganda, although surprisingly few contemporary, age-stratified data exist on malaria epidemiology in the country. This report presents results from a total population survey of malaria infection and intervention coverage in a rural area of eastern Uganda, with a specific focus on how risk factors differ between demographic groups in this population. METHODS: In 2008, a cross-sectional survey was conducted in four contiguous villages in Mulanda, sub-county in Tororo district, eastern Uganda, to investigate the epidemiology and risk factors of Plasmodium species infection. All permanent residents were invited to participate, with blood smears collected from 1,844 individuals aged between six months and 88 years (representing 78% of the population). Demographic, household and socio-economic characteristics were combined with environmental data using a Geographical Information System. Hierarchical models were used to explore patterns of malaria infection and identify individual, household and environmental risk factors. RESULTS: Overall, 709 individuals were infected with Plasmodium, with prevalence highest among 5-9 year olds (63.5%). Thin films from a random sample of 20% of parasite positive participants showed that 94.0% of infections were Plasmodium falciparum and 6.0% were P. malariae; no other species or mixed infections were seen. In total, 68% of households owned at least one mosquito although only 27% of school-aged children reported sleeping under a net the previous night. In multivariate analysis, infection risk was highest amongst children aged 5-9 years and remained high in older children. Risk of infection was lower for those that reported sleeping under a bed net the previous night and living more than 750 m from a rice-growing area. After accounting for clustering within compounds, there was no evidence for an association between infection prevalence and socio-economic status, and no evidence for spatial clustering. CONCLUSION: These findings demonstrate that mosquito net usage remains inadequate and is strongly associated with risk of malaria among school-aged children. Infection risk amongst adults is influenced by proximity to potential mosquito breeding grounds. Taken together, these findings emphasize the importance of increasing net coverage, especially among school-aged children