Starting at the community: Treatment-seeking pathways of children with suspected severe malaria in Uganda.

Community health workers (CHW) usually refer children with suspected severe malaria to the nearest public health facility or a designated public referral health facility (RHF). Caregivers do not always follow this recommendation. This study aimed at identifying post-referral treatment-seeking pathways that lead to appropriate antimalarial treatment for children less than five years with suspected severe malaria. An observational study in Uganda enrolled children below five years presenting to CHWs with signs of severe malaria. Children were followed up 28 days after enrolment to assess their condition and treatment-seeking history, including referral advice and provision of antimalarial treatment from visited providers. Of 2211 children included in the analysis, 96% visited a second provider after attending a CHW. The majority of CHWs recommended caregivers to take their child to a designated RHF (65%); however, only 59% followed this recommendation. Many children were brought to a private clinic (33%), even though CHWs rarely recommended this type of provider (3%). Children who were brought to a private clinic were more likely to receive an injection than children brought to a RHF (78% vs 51%, p<0.001) and more likely to receive the second or third-line injectable antimalarial (artemether: 22% vs. 2%, p<0.001, quinine: 12% vs. 3%, p<0.001). Children who only went to non-RHF providers were less likely to receive an artemisinin-based combination therapy (ACT) than children who attended a RHF (odds ratio [OR] = 0.64, 95% CI 0.51-0.79, p<0.001). Children who did not go to any provider after seeing a CHW were the least likely to receive an ACT (OR = 0.21, 95% CI 0.14-0.34, p<0.001). Health policies should recognise local treatment-seeking practices and ensure adequate quality of care at the various public and private sector providers where caregivers of children with suspected severe malaria actually seek care.

Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

[This corrects the article DOI: 10.1371/journal.pmed.1004189.].

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

BACKGROUND: For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years. METHODS AND FINDINGS: This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study. CONCLUSIONS: Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03568344).

Acceptability of pre-referral rectal artesunate for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda.

BACKGROUND: For children below 6 years with suspected severe malaria attending a health care provider unable to provide parenteral malaria treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out. Yet to date, there is limited literature on RAS acceptability. This study aimed to determine the acceptability of RAS by health care providers and child caregivers in communities where quality assured RAS was rolled out. This study was nested within the comprehensive multi-country observational research project Community Access to Rectal Artesunate for Malaria (CARAMAL), implemented in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Data from three different sources were analysed to understand RAS acceptability: interviews with health workers during three health care provider surveys (N = 341 community health workers and 467 primary health facility workers), with caregivers of children < 5 years of age during three household surveys (N = 9332 caregivers), and with caregivers of children < 5 years of age who were treated with RAS and enrolled in the CARAMAL Patient Surveillance System (N = 3645 caregivers). RESULTS: RAS acceptability was high among all interviewed stakeholders in the three countries. After the roll-out of RAS, 97-100% heath care providers in DRC, 98-100% in Nigeria and 93-100% in Uganda considered RAS as very good or good. Majority of caregivers whose children had received RAS for pre-referral management of severe malaria indicated that they would want to get the medication again, if their child had the same illness (99.8% of caregivers in DRC, 100% in Nigeria and 99.9% in Uganda). In three household surveys, 67-80% of caregivers whose children had not previously received RAS considered the medication as useful. CONCLUSION: RAS was well accepted by health workers and child caregivers in DRC, Nigeria and Uganda. Acceptability is unlikely to be an obstacle to the large-scale roll-out of RAS in the studied settings.

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study.

BACKGROUND: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. METHODS: An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. RESULTS: Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35-6.92 and aOR=2.16, 95% CI 1.11-4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45-0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). CONCLUSIONS: Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov : NCT03568344.

Care Seeking and Treatment of Febrile Children with and without Danger Signs of Severe Disease in Northern Uganda: Results from Three Household Surveys (2018-2020).

Identification, stabilization, and prompt referral of children with signs of severe febrile disease (danger signs) in rural communities are crucial for preventing complications and death from severe malaria, pneumonia, and diarrhea. We set out to determine the treatment-seeking practices and treatment patterns for children < 5 years of age with an acute febrile illness, with or without danger signs of severe disease, in a highly malaria-endemic area of northern Uganda. Three household surveys were conducted from November through December each year in 2018, 2019, and 2020. Overall, 30% of the children in the study were reported to have had a WHO-classified danger sign including convulsions, unconsciousness/unusually sleepy, inability to feed or drink, and vomiting everything. Only half of the children in this study sought care from a health provider. However, significantly more children with danger signs of severe disease sought and received treatment and diagnostics from a health provider, compared with those without danger signs (adjusted odds ratio: 1.6, 95% confidence interval: 1.2-2.0; P < 0.01). In the total population studied, care seeking in the public sector was 26% and similar to care seeking in the private sector (24%). Community health workers were used as the first source of care by 12% of the children. Approximately 38% of the children who were reported to have danger signs of severe disease requiring prompt referral and treatment did not seek care from a health provider. Understanding and addressing barriers to accessing healthcare could contribute to better treatment seeking practices.

Prereferral rectal artesunate and referral completion among children with suspected severe malaria in the Democratic Republic of the Congo, Nigeria and Uganda.

INTRODUCTION: Children who receive prereferral rectal artesunate (RAS) require urgent referral to a health facility where appropriate treatment for severe malaria can be provided. However, the rapid improvement of a child's condition after RAS administration may influence a caregiver's decision to follow this recommendation. Currently, the evidence on the effect of RAS on referral completion is limited. METHODS: An observational study accompanied the roll-out of RAS in three malaria endemic settings in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Community health workers and primary health centres enrolled children under 5 years with suspected severe malaria before and after the roll-out of RAS. All children were followed up 28 days after enrolment to assess their treatment-seeking pathways. RESULTS: Referral completion was 67% (1408/2104) in DRC, 48% (287/600) in Nigeria and 58% (2170/3745) in Uganda. In DRC and Uganda, RAS users were less likely to complete referral than RAS non-users in the pre-roll-out phase (adjusted OR (aOR)=0.48, 95% CI 0.30 to 0.77 and aOR=0.72, 95% CI 0.58 to 0.88, respectively). Among children seeking care from a primary health centre in Nigeria, RAS users were less likely to complete referral compared with RAS non-users in the post-roll-out phase (aOR=0.18, 95% CI 0.05 to 0.71). In Uganda, among children who completed referral, RAS users were significantly more likely to complete referral on time than RAS non-users enrolled in the pre-roll-out phase (aOR=1.81, 95% CI 1.17 to 2.79). CONCLUSIONS: The findings of this study raise legitimate concerns that the roll-out of RAS may lead to lower referral completion in children who were administered prereferral RAS. To ensure that community-based programmes are effectively implemented, barriers to referral completion need to be addressed at all levels. Alternative effective treatment options should be provided to children unable to complete referral. TRIAL REGISTRSTION NUMBER: NCT03568344; ClinicalTrials.gov.

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda.

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s, allowing for rapid initiation of life-saving antimalarial treatment before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact. From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda (registered on ClinicalTrials.gov as NCT03568344). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. A number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed tracking of cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS. Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript does not intend to present key study results, but provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and costing of the RAS intervention.

Access to Functional Handwashing Facilities and Associated Factors among South Sudanese Refugees in Rhino Camp Settlement, Northwestern Uganda.

Background: Hand hygiene in refugee camp settlements remains an important measure against diarrhoeal infections. Refugee settings are characterised by overcrowding and inadequate access to water and hygiene facilities which favour proliferation of faecal-oral diseases. Handwashing with soap and water is therefore an effective way of preventing such diseases. Despite this knowledge, there is limited information about access to functional handwashing facilities in these settings and associated factors in Uganda. Methods: Quantitative data were collected from 312 refugee households in Rhino Camp Settlement, Northwestern Uganda, using a semistructured interviewer-administered questionnaire. A modified Poisson regression was used to obtain prevalence ratios (PRs) and 95% confidence intervals (CIs) for the determinants of access to a functional handwashing facility among refugee households. All analyses were performed using STATA 14.0 statistical software. Results: Of the 312 households, 123 (39.4%) had access to a handwashing facility, but only 72 (23.1%) of households had handwashing facilities that were functional. Duration of stay in the camp exceeding 3 years (adjusted PR = 2.63; 95% CI (1.73-4.00)) and history of receiving home-based education on hand hygiene (adjusted PR = 9.44; 95% CI (1.40-63.86)) were independent predictors of access to a functional handwashing facility. Conclusion: Access to functional handwashing facilities among the refugee households was low. Our findings highlight the need for more and continued handwashing promotional programs, most especially among newly arrived refugees in the camp.

Application of one health approach in training at Makerere University: experiences from the one health workforce project in Uganda.

The interconnections of humans, domestic animals, wildlife and the environment have increasingly become complex, requiring innovative and collaborative approaches (One Health approach) for addressing global health challenges. One Health is a multidisciplinary and multi-sectoral collaborative approach to human, animal, plant and environmental health. The role of academia in training professionals oriented in One Health is critical in building a global workforce capable of enhancing synergies of various sectors in improving health. Makerere University, Uganda has implemented pre-service capacity building initiatives aimed to foster One Health competencies among students who are future practitioners. In addition to incorporating the One Health concept in didactic curricula, Student One Health Innovation Clubs, undergraduate field placements in 11 demonstration sites, graduate fellowships, small grants to support research and innovations, and cross-college collaborative training approaches have greatly aided the assimilation of One Health into the fabric of university offerings. Partnerships with government ministries, private sector and international agencies were initiated to benefit the students, as well as chart a path for experiential learning and in-service offerings in the future. One major challenge, however, has been the tendency to focus on infectious diseases, especially zoonoses, with less consideration of other health issues. The opportunity for improvement, nonetheless, lies in the increasing emerging and re-emerging health concerns including epidemics, environmental pollution and related challenges which justify the need for countries and institutions to focus on building and strengthening multidisciplinary health systems.