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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 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.

IntroductionChildren 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.MethodsAn 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.ResultsReferral 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).ConclusionsThe 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 numberNCT03568344; ClinicalTrials.gov.

IntroductionCommunity 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.MethodsAn 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.ResultsOf 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%, pConclusionsHealth 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.

BackgroundAppropriate clinical management of severe malaria is critical to avert morbidity and death. Recommended treatment consists of an injectable antimalarial followed by a full course of oral artemisinin-based combination therapy (ACT). Children who cannot access prompt parenteral treatment should be administered a single dose of rectal artesunate (RAS) and promptly referred to an appropriate facility for further care. This study aimed to assess compliance with the treatment recommendation in children under 5 years diagnosed with severe malaria and admitted to referral facilities in 3 high-burden sub-Saharan African countries.Methods and FindingsThis study accompanied the implementation of RAS as a pre-referral treatment in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children under 5 who were admitted at a referral health facility (RHF) with a diagnosis of severe malaria were included. Type and dosage of antimalarial treatment at RHFs was assessed for children referred from a community-based provider and those directly attending the RHF. We used multivariable regression models to assess factors associated with administration of compliant treatment.RHF data of 7,983 children was analysed for compliance with regards to antimalarials, a subsample of 3,449 children was assessed in more detail for schedule and dosage compliance and method of ACT provision. Overall, 42.0% (3,356/7,983) of admitted children were administered full treatment consisting of a parenteral antimalarial and an ACT, with large variation among study countries (2.7% in Nigeria, 44.5% in Uganda and 50.3% in DRC). Children receiving RAS from a community-based provider were more likely to be administered compliant post-referral medication at RHFs in DRC (adjusted odds ratio (aOR)=2.19, 95% CI 1.60-2.99), but less likely in Uganda (aOR = 0.43, 95% CI 0.19-0.96). Use of injectable antimalarials was very high in all three countries (99.2% (1,344/1,355) in Uganda, 98.1% (413/421) in Nigeria and 94.4% (1,580/1,673) in DRC), with most children receiving the recommended minimum of three doses (99.0% (1,331/1,344) in Uganda, 95.5% (1,509/1,580) in DRC and 92.0% (380/413) in Nigeria). Rather than being administered in the RHF, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349), while this was rarely done in DRC (0.8%, 14/1,669) where inpatient administration was more common.ConclusionsDirectly observed treatment with both a parenteral antimalarial and an ACT was rare and variable between countries, bearing a high risk for incomplete parasite clearance and disease recrudescence. Parenteral artesunate not followed up with a full course of oral ACT constitutes an artemisinin monotherapy and may favour the selection or development of resistant parasites. Stricter health worker compliance with the WHO severe malaria treatment guidelines is therefore needed to effectively manage this disease and further reduce child mortality.

BackgroundTo prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, higher-level facilities offering parenteral antimalarials are often difficult to access. A randomised controlled trial found pre-referral rectal artesunate (RAS) to reduce death and disability in children who delay arriving at a referral facility. This study examined the effectiveness of pre-referral RAS treatment in established community-based health care systems.MethodsAn observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo, Nigeria and Uganda. Children < 5 years presenting to a community-based health provider with a positive malaria test and signs of severe malaria were 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.FindingsPost-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; 865/6286 patients were sick at follow-up. In all countries, the CFR was higher after RAS-roll-out (6.7 vs. 6.6% in DRC, 16.1 vs. 4.2% in Nigeria, 0.7 vs. 0.3% in Uganda). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR = 3.31, 95% CI 1.43-7.65 and aOR = 2.42, 95% CI 1.25-4.70, respectively). In Uganda, RAS users were less likely to be dead or sick at follow-up (aOR = 0.61, 95% CI 0.46-0.80). Post-referral parenteral antimalarials were protective in all countries; however, the effect of ACT administration was inconsistent.InterpretationRAS pre-referral treatment had no beneficial effect on child survival in three highly malaria endemic settings. RAS is unlikely to reduce malaria deaths unless health system shortfalls such as referral and post-referral treatment are addressed.