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 LD50 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 LD50 obtained shows that C. orbiculata may be safe in or nontoxic to mice

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

Pharmacological evaluation of some central nervous system effects of Cotyledon Orbiculata

Magister Pharmaceuticae - MPharmThe use of traditional medicine through the use of medicinal plants in Africa and especially in South Africa has long been considered an important characteristic of people's daily lives and socio-cultural heritage. Cotyledon Orbiculata is among the medicinal plants that are used by South African traditional practitioners for the treatment of epilepsy and painful conditions such as corns, warts, toothache, earache, boils and various other ailments. However, the claim of therapeutic successes of medicinal plants by traditional medicine practitioners are hardly subjected to scientific scrutiny. This study therefore, investigated the anti-epileptic property of Cotyledon Orbiculata by studying the effects of the methanol extract of the plant against chemically induced seizures by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid in mice. The study also investigated the analgestic effects of Cotyledon Orbiculata by studying the effect of the plant extract on pain induced by acetic acid and hot plate thermal stimulation.South Afric

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

Pharmacovigilance of mass drug administration for the control of schistosomiasis and soil transmitted helminths in Rwanda

Preventive chemotherapy (PC) is a WHO recommended core interventional measure or a strategy to prevent, control and eliminate STH and schistosomiasis as public health burden by 2030. Though preventable and treatable, they are still endemic in Rwanda and continue to cause significant mortality and morbidity. This prompted us to conduct a cross-sectional study to assess the prevalence, intensity, and correlates of STH after a decade of PC. In addition, an active safety surveillance study to identify the incidence, type, severity, and risk factors for AEs following MDA of praziquantel (PZQ) and albendazole co-administration was conducted. We further assessed the effectiveness of both 400 mg single-dose albendazole against STH infections and single-dose PZQ 40 mg/kg body weight against schistosomiasis, administered to SAC during MDA campaign respectively. Lastly, the effect of pharmacogenetic variations on PZQ plasma concentrations and safety outcomes was equally investigated. Firstly, in paper I, we screened and assessed for STH prevalence amongst 4998 SAC between 5 to 15 years old from four selected districts alongside Lake Kivu in the western province of Rwanda. An overall 77.7% prevalence of STH irrespective of several rounds of mass albendazole PC was reported. T. trichiura was found to be the most common STH species with 66.8%, followed by A. lumbricoides with 49.9%, and lastly hookworms with 1.9%. The prevalence of single, double, and triple parasite co-infection was 48.6%, 50.3%, and 1.1%, respectively. The study findings revealed that male sex, district, stunting, and schistosomiasis co-infection were significant predictors of STH infections. Subsequently, in paper II, an active safety surveillance study was conducted and enrolled a total of 8037 SAC (5-15 years old). AEs were actively monitored on days 1, 2 and 7-post- MDA to identify and categorize AEs following mass administration of PZQ and albendazole. During the study, a total of 3196 AEs were reported by 1658 SAC and respectively, 91.3%, 8.4%, and 0.3% of the AEs were mild, moderate, and severe. The reported AEs mostly resolved within 3 days after drug administration and during the active safety monitoring, headache (21%), dizziness (15.2 %), nausea (12.8%) and stomach pain (12.2%) were the most reported AEs. 20.6% of SAC experienced at least one type of AE and this was significantly higher in SAC with pre-MDA clinical Events (27.5%) compared to those without (18.7%) clinical events. In this paper, it was further observed that being a female, older age, having pre-MDA events, types of food taken before MDA and taking two or more PZQ tablets were significantly associated with AEs. In paper III, a total of 1526 SAC were enrolled in a cross-sectional efficacy surveillance study to assess the effectiveness of single-dose albendazole (400 mg) against STH infections. Drug efficacy follow-up was performed 21 days post-MDA treatment in accordance with the WHO guidelines. Thereafter, we observed that cure rate (CR) and egg reduction rate (ERR) for hookworms (CR = 96.7%, ERR = 97.4%) was above the recommended WHO threshold and for A. lumbricoides (CR = 95.1%, ERR = 94.6%) at borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). We further observed a low efficacy rate for T. trichiura with CR (17.6%) and ERR (40.3%) respectively as opposed to the recommended WHO threshold of ≥ 50%. Exhibiting moderate -heavy infection intensity and STH parasite co-infections were found to be risk factors of CR and ERR against T. trichiura. 400 mg single-dose albendazole used in mass deworming campaigns was found to be effective for the treatment of hookworms and A. lumbricoides but not effective for T. trichiura infections. In paper IV, efficacy surveillance of PZQ 40 mg/kg body weight following MDA was conducted and 265 SAC infected with intestinal schistosomiasis were enrolled in the study. our findings indicated that PZQ used in MDA is effective in treating light and moderate infection intensities of S. mansoni infection. CR and ERR were revealed to be 97.9% and 97.0% respectively way higher compared with the WHO recommended efficacy threshold. Among 173 cases of light infection intensity for intestinal schistosomiasis, 98. 3% (170) of SAC got healed or cured whereas 1.7% (3) were not cured post-MDA. 93.3% of the 15(8%) SAC who had moderate infection intensities were cured and 6.7% were not post-MDA. The findings indicated no significant association between CR, Pre-MDA treatment and post-MDA infection intensities. In this paper therefore, PZQ exhibited high efficacy potential and reduced morbidities correlated to light and moderate infection intensities. It is evident to say that single dose PZQ 40 mg/kg is still efficacious against intestinal schistosomiasis infections. Finally in paper V, the effect of pharmacogenetics variations on PZQ plasma concentrations and safety outcomes amongst 462 Rwandan SAC who were given the single dose PZQ co-administered with albendazole during MDA was investigated. Genotyping for common functional variant alleles CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3) and CYP2J2*7 were performed from the collected whole blood samples. Our findings showed that, CYP2C19 and CYP2C9 were associated with plasma PZQ concentrations and cis- and trans-4-OH-PZQ metabolic rations (MRs) respectively. It was equally observed that, CYP2C9 genotype was associated with a decreased trans-4-OH-PZQ MR and a closer association with PZQ and cis-4-OHPZQ/PZQ MR. CYP3A4 genotype was reported to be in association with Cis-4-OHPZQ/PZQ MR, but not with the parent drug and Trans-4-OH-PZQ/PZQ metabolites. our findings further demonstrated relevance of plasma PZQ exposure and its MRs for MDAassociated AEs. We observed no meaningful relationship between the CYP3A4, CYP3A5, CYP2C9, CYP2C19 and CYP2J2 genotypes and MDA-associated AEs. On the other hand, SAC who experienced AEs had a significantly lower mean cis-4-OH-PZQ MR in comparison with those who did not experienced AEs. In conclusion, irrespective of several rounds of mass albendazole, the prevalence of STH remains high with T. trichiura being reported to be the most common specie. Evidently, T. trichiura indicated no response to the preventive chemotherapeutic interventions. Active safety surveillance of mass PZQ co-administered with albendazole revealed that one in five SAC who participated in the study experienced transient- mild to moderate AEs and some reported fewer severe AEs cases post- MDA. Similarly, single-dose PZQ is reported to still be effective against intestinal schistosomiasis. Both preventive chemotherapeutic drugs used in MDA were reported to be safe. CYP2C19 and CYP2C9 were associated with plasma PZQ concentrations and cis- and trans-4-OH-PZQ MR. CYP2C9 genotype was reported to associate with a decreased trans-4-OH-PZQ MR and a closer association with PZQ and cis-4-OH- PZQ/PZQ MR. Equally, CYP3A4 genotype was found to be in association with Cis-4-OH-PZQ/PZQ MR and no significant correlation between CYP3A4, CYP3A5, CYP2C9, CYP2C19 and CYP2J2 genotypes and MDA-associated AEs

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

Abstract 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 <i>Schistosoma mansoni</i> 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

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

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