Importation trends in antibiotics for veterinary use in Rwanda: A retrospective study between 2019 and 2021.

Estimating antibiotic consumption in animals is fundamental to guiding decision-making and research on controlling the emergence and spread of antibiotic-resistant bacteria in humans, animals, and the environment. This study aimed to establish importation trends of antibiotics for veterinary use in Rwanda between 2019 and 2021. Data was collected from the Rwanda Food and Drugs Authority's database. Quantities of imported antibiotic active ingredients were computed using the information extracted from the issued import licenses. These quantities were subsequently adjusted per animal biomass. In total, 35,291.4 kg of antibiotics were imported into Rwanda between 2019 and 2021, with an annual mean of 11,763.8 ± 1,486.9 kg. The adjustment of imported quantities of antibiotics per animal biomass revealed that 29.1 mg/kg, 24.3 mg/kg, and 30.3 mg/kg were imported in 2019, 2020, and 2021 respectively. A slight but not statistically significant decline in antibiotic importation was noted in 2020 (p-value = 0.547). Most of the imported antibiotics were indicated to be used in food-producing animals (35,253.8 kg or 99.9% of the imported antibiotics). Tetracyclines (17,768.6 kg or 50.3%), followed by sulfonamides (7,865.0 kg or 22.3%) and aminoglycosides (4,071.1 kg or 11.5%), were the most imported antibiotics over the studied period. It was noted that 78.9% of the imported antibiotics were categorized as highly important antimicrobials for human medicine. This study established a generalized overview of the importation of antibiotics for veterinary use in Rwanda. These results can serve as guidance for the control of antibiotic misuse. They can be used to make a correlation between antibiotic importation, antibiotic consumption, and the occurrence of antibiotic resistance in the country.

Labor markets for health supply chain management in Rwanda: a qualitative study of stakeholder perspectives.

BACKGROUND: Effective supply chains for health products require an adequate, skilled workforce for supply chain management (SCM). Rwanda faces challenges in human resources for SCM, including limited capacity for SCM at different levels. Understanding of the factors influencing the supply of and demand for SCM professionals in Rwanda is necessary to ensure the labor market contains an adequate workforce. This study identifies the perspectives of key stakeholders in the supply chain management sector about the factors influencing the supply of and demand for SCM professionals. METHODS: Data were collected in semi-structured group and one-on-one interviews with 39 key stakeholders involved in the supply chain management labor market between March and April 2019. Interviewees were categorized according to their role in the labor market as system actors, functional actors involved in the supply of SCM workers, and functional actors involved in the demand for SCM workers. Interviewees were asked open-ended questions about factors influencing the demand for and the supply of SCM workers, and recommendations for improvement. Interviews were analyzed thematically. One validation focus group was held and the results were also reviewed by the Ministry of Health in Rwanda. RESULTS: Stakeholders agreed that skills mismatch between SCM workers' skills and the competencies jobs require impacts the supply of workers. A lack of career structure for SCM, lack of professional definitions for health supply chain management, and SCM curricula that do not match the needs of the workplace contribute to this gap. The demand for SCM professionals is poorly defined in terms of the numbers of professionals needed and the skills workers require. Financial limitations hinder demand for health SCM professionals. CONCLUSIONS: This study adds to the understanding of factors influencing the SCM labor market in Rwanda by documenting perspectives from government ministries, professional organizations, universities, and employers from SCM organizations. Improving the SCM labor market in Rwanda and the availability of the skilled cadres required for the effective management of health supply chains in Rwanda requires a coordinated effort by the Ministry of Health in Rwanda, private SCM companies, professional associations, education sector, and policy makers.

Efficacy of Single-Dose Praziquantel for the Treatment of Schistosoma mansoni Infections among School Children in Rwanda.

Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against S. mansoni infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for S. mansoni infection using the Kato-Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for S. mansoni infection were 97.9% (95% CI = 94.6-99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0-99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate S. mansoni infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children.

Efficacy of Single-Dose Albendazole for the Treatment of Soil-Transmitted Helminthic Infections among School Children in Rwanda-A Prospective Cohort Study.

Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province of Rwanda, where STH prevalence remains high despite the implementation of preventive chemotherapy for over a decade. Two weeks before the scheduled MDA, 4998 school children (5-15 years old) were screened for STH infections (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and 1526 children who tested positive for at least one type of STH parasite were enrolled and received single-dose albendazole (400 mg) through MDA. A follow-up stool exam was performed at three weeks post-treatment using Kato-Katz. Efficacy was assessed by cure rate (CR), defined as the proportion of children who became egg-free, and egg reduction rates (ERRs) at three weeks post-treatment. The CR and ERR for hookworms (CR = 96.7%, ERR = 97.4%) was above, and for Ascaris lumbricoides (CR = 95.1%, ERR = 94.6%) was borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). However, the CR and ERR for T. trichiura (CR = 17.6% ERR = 40.3%) were below the WHO threshold for efficacy (CR and ERR ≥ 50%). Having moderate-to-heavy infection intensity and coinfection with another type of STH parasites were independent risk factors for lower CR and ERR against Trichirus trichiura (p < 0.001). Single-dose albendazole used in the MDA program is efficacious for the treatment and control for hookworms and Ascaris lumbricoides infections but not effective for Trichirus trichiura. An alternative treatment regimen is urgently needed to prevent, control, and eliminate STH as a public health problem.

Effect of pharmacogenetic variations on praziquantel plasma concentration and safety outcomes among school children in Rwanda.

School-based mass drug administration (MDA) of Praziquantel (PZQ) is the global intervention strategy for elimination of schistosomiasis. Genetic variations in drug metabolizing enzymes and transporter proteins influences drug exposure and treatment outcomes, but data on PZQ pharmacokinetics and safety outcomes are scarce. We investigated the effect of pharmacogenetics variations on PZQ plasma concentrations and safety outcomes among 462 Rwandan schoolchildren who received single dose PZQ and albendazole in MDA. Genotyping for common functional variant alleles CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3) and CYP2J2*7 were done. Plasma concentration of PZQ, cis-4-OH-PZQ and trans-4-OH-PZQ were measured using LC/MS/MS. Active safety monitoring was done on days 1, 2, and 7 post-MDA. CYP2C9 and CYP2C19 genotypes were significantly associated with PZQ plasma concentrations and its cis- and trans-4-OH-PZQ/PZQ metabolic ratios (MR). CYP2C9*2 and CYP2C9*3 carriers had significantly higher PZQ concentration (p = 0.02), lower trans-4-OH-PZQ/PZQ (p < 0.001), and cis-4-OH-PZQ/PZQ (p = 0.02) MR. CYP2C19 (*2, *3) carriers had significantly higher plasma PZQ concentration than CYP2C19 *1/*1 and CYP2C19 *17 carriers (*1/*17 or *17/*17) (p < 0.001). CYP3A4 was significantly associated with cis-4-OH-PZQ MR (p = 0.04). Lower cis-4-OH-PZQ/PZQ MR (p < 0.0001) was a predictor of MDA-associated adverse events, but no significant association with genotypes were found. In conclusion, CYP2C9 and CYP2C19 genotypes significantly influence the plasma PZQ concentration and its MR. Lower cis-4-OH-PZQ/PZQ MR is significant predictor of adverse events following MDA.

Safety of Praziquantel and Albendazole Coadministration for the Control and Elimination of Schistosomiasis and Soil-Transmitted Helminths Among Children in Rwanda: An Active Surveillance Study.

INTRODUCTION: School-based preventive chemotherapy (Deworming) with praziquantel and albendazole to control and eliminate schistosomiasis and soil-transmitted helminths as public health problems is recommended by the World Health Organization (WHO). Safety monitoring during mass drug administration (MDA) is imperative but data from sub-Saharan Africa are scarce. OBJECTIVE: The aim of this active safety surveillance study was to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass administration of praziquantel and albendazole. METHODS: Overall, 8037 school children aged 5-15 years in Rwanda were enrolled. Baseline sociodemographic, medical history and any pre-existing clinical symptoms were recorded. Participants received a single dose of praziquantel and albendazole during MDA. AEs were actively monitored on days 1, 2, and 7 post MDA. RESULTS: Overall, 3196 AEs were reported by 1658 children; 91.3%, 8.4%, and 0.3% of the AEs were mild, moderate, and severe, respectively, and most resolved within 3 days. Headache (21%), dizziness or fainting (15.2 %), nausea (12.8%) and stomach pain (12.2%) were the most common AEs. The overall cumulative incidence of experiencing at least one type of AE was 20.6% (95% confidence interval [CI] 19.7-21.5%), being significantly higher (p < 0.001) in children with pre-MDA clinical events (27.5%, 95% CI 25.4-29.6%) than those without (18.7%, 95% CI 17.7-19.7%). Females, older age, having pre-MDA events, types of food taken before MDA and taking two or more praziquantel tablets were significant predictors of AEs. CONCLUSIONS: Praziquantel and albendazole MDA is safe and well-tolerated; however, one in five children experience transient mild to moderate, and in few cases severe, AEs. The incidence of AEs varies significantly between sex and age groups. Pharmacovigilance in the MDA program is recommended for timely detection and management of AEs.

Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania.

Monitoring the safety of medicines used in public health programs (PHPs), including the neglected tropical diseases (NTD) program, is a WHO recommendation, and requires a well-established and robust pharmacovigilance system. The objective of this study was to assess the pharmacovigilance systems within the NTD programs in Ethiopia, Kenya, Rwanda, and Tanzania. The East African Community Harmonized Pharmacovigilance Indicators tool for PHPs was used to interview the staff of the national NTD programs. Data on four components, (i) systems, structures, and stakeholder coordination; (ii) data management and signal generation; (iii) risk assessment and evaluation; and (iv) risk management and communication, were collected and analyzed. The NTD programs in the four countries had a strategic master plan, with pharmacovigilance components and mechanisms to disseminate pharmacovigilance information. However, zero individual case safety reports were received in the last 12 months (2017/2018). There was either limited or no collaboration between the NTD programs and their respective national pharmacovigilance centers. None of the NTD programs had a specific budget for pharmacovigilance. The NTD program in all four countries had some safety monitoring elements. However, key elements, such as the reporting of adverse events, collaboration with national pharmacovigilance centers, and budget for pharmacovigilance activity, were limited/missing.

Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda.

Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5-15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda.

Eight years of the East African Community Medicines Regulatory Harmonization initiative: Implementation, progress, and lessons learned.

Jane H. Mashingia and colleagues reveal the progress made to date for the East African Community Medicines Regulatory Harmonization initiative.

Optimizing the East African Community's Medicines Regulatory Harmonization initiative in 2020-2022: A Roadmap for the Future.

Margareth Ndomondo-Sigonda outlines future challenges for the East African Medicines Regulatory Harmonization initiative.

Coming together to improve access to medicines: The genesis of the East African Community's Medicines Regulatory Harmonization initiative.

Hiiti Sillo and colleagues reveal how the East African Community's Medicines Regulatory Harmonization initiative improves access to important medicines in Africa.

Antinociceptive and Anti-Inflammatory Activities of Leaf Methanol Extract of Cotyledon orbiculata L. (Crassulaceae).

Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100-400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10 mg/kg, i.p.) significantly delayed the reaction time of mice to the thermal stimulation produced with hot plate. Leaf methanol extract of C. orbiculata (50-400 mg/kg, i.p.) significantly attenuated the carrageenan-induced rat paw oedema. Indomethacin (10 mg/kg, p.o.) also significantly attenuated the carrageenan-induced rat paw oedema. The LD(50) value obtained for the plant species was greater than 4000 mg/kg (p.o.). The data obtained indicate that C. orbiculata has antinociceptive and anti-inflammatory activities, justifying the folklore use of the plant species by traditional medicine practitioners in the treatment of painful and inflammatory conditions. The relatively high LD(50) obtained shows that C. orbiculata may be safe in or nontoxic to mice.