Recent developments in antimalarial drug discovery.

Although malaria remains a big burden to many countries that it threatens their socio-economic stability, particularly in the countries where malaria is endemic, there have been great efforts to eradicate this disease with both successes and failures. For example, there has been a great improvement in malaria prevention and treatment methods with a net reduction in infection and mortality rates. However, the disease remains a global threat in terms of the number of people affected because it is one of the infectious diseases that has the highest prevalence rate, especially in Africa where the deadly Plasmodium falciparum is still widely spread. Methods to fight malaria are being diversified, including the use of mosquito nets, the target candidate profiles (TCPs) and target product profiles (TPPs) of medicine for malarial venture (MMV) strategy, the search for newer and potent drugs that could reverse chloroquine resistance, and the use of adjuvants such as rosiglitazone and sevuparin. Although these adjuvants have no antiplasmodial activity, they can help to alleviate the effects which result from plasmodium invasion such as cytoadherence. The list of new antimalarial drugs under development is long, including the out of ordinary new drugs MMV048, CDRI-97/78 and INE963 from South Africa, India and Novartis, respectively.

Factors that affect vaccines availability in public health facilities in Nairobi City County: a cross-sectional study.

INTRODUCTION: over 1.5 million children die from vaccine-preventable diseases yearly. To avert these deaths and improve their livelihood, vaccine availability is important. The study assessed the availability of the vaccine, injection accessories and the associated factors in public health facilities in Nairobi City County and provided valuable data to contribute to improving healthcare infrastructure, stock management and vaccine distribution. METHODS: a descriptive cross-sectional study was conducted in 68 randomly selected public health facilities at Nairobi City County in Kenya. Data was collected using a researcher-administered structured questionnaire and more information abstracted from the Vaccines management tools. The analysis was carried out using STATA version 14. RESULTS: most facilities had experienced vaccines and accessories stock out at the time of the study and in the preceding twelve months. The most affected vaccines were tetanus (88%), measles-rubella (81%) and oral polio (79%). The causes of stockouts were rationing (82%), unavailability at the depot (93%), lack of transport (55%) and poor forecasting (50%). The majority (91%) of the facilities used the public transport system and only 1% had reliable government utility vehicles for delivery of vaccines and other logistics. Those near the vaccine depots preferred walking. CONCLUSION: the public health facilities in Nairobi City County experienced frequent stockouts of vaccines and accessories thereby exposing the residents to vaccine-preventable diseases.

Quality of oxytocin and misoprostol in health facilities of Rwanda.

Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2-8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2-121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5-48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities.

Prices, availability and affordability of medicines in Rwanda.

BACKGROUND: Access to affordable and good quality medicines is a key to meeting Sustainable Development Goal No. 3 by the year 2030. Prices, availability and affordability of essential medicines have been studied in many developing countries, but no such information has been published about Rwanda yet. This study aimed at providing data on prices, availability and affordability of medicines in different health facilities of Rwanda. METHODS: A survey was carried out on availability, prices and affordability of 18 medicines in Kigali City and five districts of Rwanda. 44 health facilities were surveyed, including public and faith-based hospitals, public and faith-based health centers and private pharmacies. The standardized methodology developed by WHO and Health Action International (HAI) was used to collect and analyze the data. FINDINGS: Prices for generic medicines in public and faith-based health facilities were remarkably low, with median price ratios (MPRs) of 1.0 in comparison to the international procurement prices published by Management Sciences for Health. In private pharmacies, prices were twice as high (MPR = 1.99 for generics). Availability of medicines fell short of the of 80% target set by WHO, but was better than reported from many other developing countries. Availability of medicines was highest in the private sector (71.3%) and slightly lower in the faith-based (62.8%) and public (59.6%) sectors. The government procurement agency was found to work efficiently, achieving prices 30% below the international procurement price given in the International Medical Product Price Guide. Affordability of medicines was better in the public and faith-based sectors than in the private sector. CONCLUSION: In Rwanda, medicines are affordable but poorly available in both the public and the faith-based sectors. Further improvements of the availability of medicines in the public and the faith-based health facilities represent the most important key to increase accessibility and affordability of medicines in Rwanda.

Stability of Oxytocin Preparations in Malawi and Rwanda: Stabilizing Effect of Chlorobutanol.

Oxytocin is used for the prevention and treatment of postpartum hemorrhage, the leading cause of maternal mortality in low- and middle-income countries. Because of the high instability of oxytocin, most products are labeled for storage at 2-8°C. Some other products are on the market which are labeled for non-refrigerated storage, but independent evaluations of their stability hardly exist. In the present study, seven brands (nine batches) of oxytocin were purchased from wholesalers and medical stores in Malawi and Rwanda and investigated by accelerated stability testing according to the ICH/WHO guidelines. Two oxytocin brands approved by a stringent regulatory authority (SRA) or by the WHO Prequalification of Medicines program and purchased in Europe were used as comparison. All investigated brands which were either produced in countries with SRAs, or were WHO-prequalified products, were labeled for storage at 2-8°C, and all of them passed stability testing with very good results. Even exposure to 25°C or 30°C for several months hardly affected their oxytocin content. However, two other investigated brands were labeled for non-refrigerated storage, and both of them had been produced in countries without SRAs. These two preparations showed not higher but lower stability than the brands labeled for storage at 2-8°C, and, for both of them, noncompliance with pharmacopoeial specifications was found after accelerated stability testing. At 40°C, and in forced degradation studies at 80°C, chlorobutanol showed a remarkable stabilizing effect on oxytocin, which may deserve further investigation. The results of the present study support the policy "Buy Quality Oxytocin, Keep It Cool."

A rapid and selective HPLC-UV method for the quantitation of efavirenz in plasma from patients on concurrent HIV/AIDS and tuberculosis treatments.

Owing to heterogeneity in therapeutic response, efavirenz is of research and clinical interest. There is a need to quantitate it using noncostly and selective methods. A method for efavirenz quantitation in plasma containing HIV and tuberculosis drugs was developed. Chromatographic separation was carried out using a C18 column. The mobile phase consisted of 0.1% formic acid and acetonitrile, and was pumped at a flow rate of 0.3 mL/min. Efavirenz and ritonavir (internal standard) were monitored at 247 nm. Plasma proteins were precipitated by centrifugation. The analysis time was 6 min. The response was linear (r = 0.9997). The accuracy ranged between 98 and 115% (intraday) and between 99 and 117% (interday). The precision ranged from 1.670 to 4.087% (intraday) and from 3.447 to 13.347% (interday). Recovery ranged from 98 to 132%. Stability ranged between 99 and 123%. The selectivity was proven by analysis of drugs used for the management of HIV/AIDS and tuberculosis. Plasma sample analysis showed an efavirenz retention time of 5.57 min and a peak plasma concentration of 2.4 µg/mL occurring at 2 h. This method is rapid and selective, and thus suitable for monitoring efavirenz in patients with HIV/AIDS alone or co-infected with tuberculosis in a less resourced setting.

Evaluation of medication adherence methods in the treatment of malaria in Rwandan infants.

OBJECTIVES: To compare three methods for evaluating treatment adherence in a 7-day controlled treatment period for malaria in children in Rwanda. METHODS: Fifty-six children (< 5 years) with malaria were recruited at the University Hospital of Butare, Rwanda. Patients were treated with quinine sulfate, taste-masked, pellets during seven days: three days in hospital (in-patient) followed by a four-day out-patient period. Three methods to evaluate medication adherence among patients were compared: manual pill count of returned tablets, patient self-report and electronic pill-box monitoring. These pill-boxes were equipped with a microchip registering date and time of every opening. Medication adherence was defined as the proportion of prescribed doses taken. The inter-dose intervals were analysed as well. RESULTS: Medication adherence data were available for 54 of the 56 patients. Manual pill count and patient self-report yielded a medication adherence of 100% for the in- and out-patient treatment periods. Based on electronic pill-box monitoring, medication adherence during the seven-day treatment period was 90.5 +/- 8.3%. Based on electronic pill-box monitoring inpatient medication adherence (99.3 +/- 2.7%) was markedly higher (p < 0.03) than out-patient adherence (82.7 +/- 14.7%), showing a clear difference between health workers' and consumers' medication adherence. CONCLUSION: Health workers' medication adherence was good. However, a significant lower medication adherence was observed for consumers' adherence in the outpatient setting. This was only detected by electronic pill-box monitoring. Therefore, this latter method is more accurate than the two other methods used in this study.