Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial

BACKGROUND:  If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS:  Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS:  Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS:  Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION:  ISRCTN58046240

Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: A systematic review and individual patient data meta-analysis

Background Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92). Interpretation We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted

Household costs and time to treatment for children with severe febrile illness in rural Burkina Faso: the role of rectal artesunate

UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland [Project ID number: Burkina Faso: A80553

Quantifying and valuing community health worker time in improving access to malaria diagnosis and treatment

Background: Community health workers (CHWs) are members of a community who are chosen by their communities as first-line, volunteer health workers. The time they spend providing healthcare and the value of this time are often not evaluated. Our aim was to quantify the time CHWs spent on providing healthcare before and during the implementation of an integrated programme of diagnosis and treatment of febrile illness in three African countries. Methods: In Burkina Faso, Nigeria and Uganda, CHWs were trained to assess and manage febrile patients in keeping with Integrated Management of Childhood Illness recommendations to use rapid diagnostic tests, artemisinin-based combination therapy and rectal artesunate for malaria treatment. All CHWs provided healthcare only to young children usually under 5 years old, and hence daily time allocation of their time to child healthcare was documented for one day (in the high malaria season) before the intervention and at several time points following the implementation of the intervention. Time spent in providing child healthcare was valued in earnings of persons with similar experience. Results: During the high malaria season of the intervention, CHWs spent nearly 50 minutes more in daily healthcare provision (average daily time 30.2 minutes before the intervention versus 79.5 minutes during the intervention; test for difference in means p&lt; 0.01). On average, the daily time spent providing healthcare during the intervention was 55.8 minutes (Burkina Faso), 77.4 minutes (Nigeria) and 72.2 minutes (Uganda). Using the country minimum monthly salary, CHWs time allocated to child healthcare for one year was valued at USD 52 in Burkina Faso, USD 295 in Nigeria and USD 141 in Uganda. Conclusion: CHWs spend up to an hour and a half daily on child healthcare in their communities. These data are informative in designing reward systems to motivate CHWs to continue providing good quality services

Quantifying and Valuing Community Health Worker Time in Improving Access to Malaria Diagnosis and Treatment

This work was supported by the UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland (project ID number A80553 [Burkina Faso]; A80550 [Nigeria]; and A80556 [Uganda]) through funds made available by the European Commission (FP7) for research to improve community access to health interventions in Africa

Impact of improving community-based access to malaria diagnosis and treatment on household costs

Background: Community health workers (CHWs) were trained in Burkina Faso, Nigeria and Uganda to diagnose febrile children using malaria rapid diagnostic tests (RDTs), treat positive malaria cases with artemisinin combination treatment (ACTs) and those who could not take oral medicines with rectal artesunate. We quantified the impact of this intervention on private household costs for childhood febrile illness. Methods: Households with recent febrile illness in a young child in previous two weeks were selected randomly before and during the intervention and data obtained on household costs for the illness episode. Household costs included consultation fees, registration costs, user fees, diagnosis, bed, drugs, food and transport costs. Private household costs per episode before and during the intervention were compared. The intervention’s impact on household costs per episode was calculated and projected to district-wide impacts on household costs. Results: Use of CHW increased from 35% of illness episodes before the intervention to 50% during the intervention (p&lt;0.0001) and total household costs per episode decreased significantly in each country from 4.36 to 1.54 dollars in Burkina Faso, from 3.90 to 2.04 dollars in Nigeria and from 4.46 to 1.42 in dollars Uganda (all p&lt;0.0001). There was no difference in the time used by the child’s caregiver to care for a sick child (59% before intervention vs. 51% during intervention spent 2 days or less). Using the most recent population figures for each study district, we estimate that the intervention could save households a total of 29,965, 254,268 and 303,467 dollars, respectively in the study districts in Burkina Faso, Nigeria and Uganda. Conclusions: Improving access to malaria diagnostics and treatments in malaria endemic areas substantially reduces private household costs. The key challenge is to develop and strengthen community human resources to deliver the intervention, and ensure adequate supplies of commodities and supervision. We demonstrate feasibility and benefit to populations living in difficult circumstances

Impact of improving community-based access to malaria diagnosis and treatment on household costs

Background: Community health workers (CHWs) were trained in Burkina Faso, Nigeria and Uganda to diagnose febrile children using malaria rapid diagnostic tests (RDTs), treat positive malaria cases with artemisinin combination treatment (ACTs) and those who could not take oral medicines with rectal artesunate. We quantified the impact of this intervention on private household costs for childhood febrile illness. Methods: Households with recent febrile illness in a young child in previous two weeks were selected randomly before and during the intervention and data obtained on household costs for the illness episode. Household costs included consultation fees, registration costs, user fees, diagnosis, bed, drugs, food and transport costs. Private household costs per episode before and during the intervention were compared. The intervention’s impact on household costs per episode was calculated and projected to district-wide impacts on household costs. Results: Use of CHW increased from 35% of illness episodes before the intervention to 50% during the intervention (p<0.0001) and total household costs per episode decreased significantly in each country from 4.36 to 1.54 dollars in Burkina Faso, from 3.90 to 2.04 dollars in Nigeria and from 4.46 to 1.42 in dollars Uganda (all p<0.0001). There was no difference in the time used by the child’s caregiver to care for a sick child (59% before intervention vs. 51% during intervention spent 2 days or less). Using the most recent population figures for each study district, we estimate that the intervention could save households a total of 29,965, 254,268 and 303,467 dollars, respectively in the study districts in Burkina Faso, Nigeria and Uganda. Conclusions: Improving access to malaria diagnostics and treatments in malaria endemic areas substantially reduces private household costs. The key challenge is to develop and strengthen community human resources to deliver the intervention, and ensure adequate supplies of commodities and supervision. We demonstrate feasibility and benefit to populations living in difficult circumstances

Can we measure cognitive constructs consistently within and across cultures? Evidence from a test battery in Bangladesh, Ghana, and Tanzania

We developed a test battery for use among children in Bangladesh, Ghana, and Tanzania, assessing general intelligence, executive functioning, and school achievement. The instruments were drawn from previously published materials and tests. The instruments were adapted and translated in a systematic way to meet the needs of the three assessment contexts. The instruments were administered by a total of 43 trained assessors to 786 children in Bangladesh, Ghana, and Tanzania with a mean age of about 13 years (range: 7–18 years). The battery provides a psychometrically solid basis for evaluating intervention studies in multiple settings. Within-group variation was adequate in each group. The expected positive correlations between test performance and age were found and reliability indices yielded adequate values. A confirmatory factor analysis (not including the literacy and numeracy tests) showed a good fit for a model, merging the intelligence and executive tests in a single factor labeled general intelligence. Measurement weights invariance was found, supporting conceptual equivalence across the three country groups, but not supporting full score comparability across the three countries