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Background: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. Methods: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. Principal findings and conclusions: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: Self-medication is the use of any drug or medication to treat an illness or ailment without the supervision of a licensed medical doctor/health care providers. Self-medication practice in Eastern Ethiopia is quite common. However, there is little information with regard to magnitude and associated factors. The objective of this study was to assess the magnitude of self-medication practice and associated factors among adult community members of Jigjiga town, Eastern Ethiopia. Methods: A community based cross-sectional study was conducted from June 27- July 12, 2017. Multistage sampling method was used and the number of kebeles and Sub-kebeles were selected using simple random sampling technique. Finally, sampled households in the Sub-kebeles were selected using systematic random sampling. Data were collected using face to face interview with 547 adult (≥18 years) participants. It was entered and cleaned using EPI-Data version 3.02 and exported to Statistical Package for Social Science (SPSS) Version 23 for further analysis. Bi-variable and multivariable logistic regression models were carried out to identify factors associated with the self-medication. Result: The magnitude of self-medication was found to be 37.5% (95% CI: (33.6%–41.7%). Educational status of secondary school [(AOR = 0.46; 95% CI: (0.22–0.98)], high income [(AOR = 3.00; 95% CI: (1.77–5.06)], advised by neighbors, friends or relatives to take drug for their complaint [(AOR = 2.59; 95% CI: (1.62–4.14)], used old prescription /past experience to bought drugs [(AOR = 12.19; 95% CI: (6.65–22.35)], follow advertisements of drugs by television [(AOR = 0.21; 95% CI: (0.05–0.85)], and perception about Hospital drugs (clinics, health centers and hospitals) do not work [(AOR = 2.36; 95% CI: (1.39–3.99)] were significantly associated with self-medication. Conclusion: High income, advice by neighbors, friends or relatives to take drug for their complaint, old prescription/past experience use to bought drugs, and perception of hospital drugs do not work was positively associated with self-medication. Therefore, health education should be given to the community on the importance of hospital drugs (clinics, health centers and hospitals) to shift their perception. [ABSTRACT FROM AUTHOR]

Background: Medicines regulatory harmonization has been recommended as one way to improve access to quality-assured medicines in low- and middle-income countries. The rationale is that by lowering barriers to entry more manufacturers will be enticed to enter the market, while the capacity at the national medicines regulatory authorities is strengthened. The African Medicines Regulatory Harmonization Initiative, agreed in 2009, is developing regional platforms with harmonized regulatory procedures for the registration of medicines. The first region to implement medicines regulatory harmonization was the East African Community (EAC). The harmonization was based on the existing EAC Free Trade Agreement, which officially launched the free movement of goods and services in 2010. Methods and findings: In this study we conducted semi-structured interviews and performed document reviews. The main target group for our interviews was pharmaceutical companies. We interviewed 18 companies, including 64% of the total companies who had experienced the EAC joint product assessment procedure, and two EAC-based national medicines regulatory authorities. We found that generally pharmaceutical companies are supportive of the African-based MRH efforts and appreciative of the progress being achieved. However, many companies are now hesitant to use the joint product assessment procedure until efficiency improvements are made. Common frustrations were the length of time to receive the actual marketing authorization; unexpectedly higher quality standards than national procedures; and challenges in getting all EAC countries to recognize EAC approvals. Smaller, less attractive markets have not yet become more attractive from a corporate perspective, and there is no free trade of pharmaceuticals in the EAC region. Conclusions: Pharmaceutical companies agree that medicines regulatory harmonization is the way forward. However, regulatory medicines harmonization must actually result in quicker access to the harmonized markets for quality-assured medicines. At this time, improvements are required to the current EAC processes to meet the vision of harmonization. [ABSTRACT FROM AUTHOR]

Despite the high success rates of preformed metal crowns (PMCs) in children no randomized clinical trials compare methods of placement and none describe its use in Africa. Our aim was to compare survival and cost-effectiveness of PMCs placed by conventional techniques (CT) and biological Hall techniques (HT) using a prospective randomized control trial in a general dental practice from Khartoum. One hundred and nine and 103 PMCs were placed in randomly selected children (5-8years) with 1–2 carious primary molars using HT and CT respectively and followed for 2 years. Socioeconomic status, periodontal health, occlusion, anxiety, and procedure time were compared using student t-test. Kaplan–Meier survival rates and incremental cost effectiveness ratio (ICER) were compared between CT and HT. CT and HT groups were similar for age, gender, socio-economic status. Survival rates were high (over 90%) for both study arms and not statistically different (p>0.05). Anxiety scores were significantly higher in CT arm after 12 months compared to HT (p<0.001). Clinically, gingival and plaque indices were similar between groups (p>0.05) but occlusions were raised in nearly all subjects in the HT arm (p<0.05). Periodontal health improved, and occlusions adjusted over time in both arms. There were 3 (2.7%) and 6 (5.8%) minor failures, 7 (6.4%) and 6 (5.8%) major failures in HT and CT arms respectively. Mean procedure time was lower in HT (9.1 min) than CT (33.9 min); p<0.001. Mean PMC cost was US$2.45 and US$7.81 for HT and CT respectively. The ICER was US$136.56 more for each PMC placed by CT per life year. We show that PMCs have high survival outcomes in disadvantaged populations similar to results from developed countries. As HT can be carried out by less experienced dental operators and therapists, this biological approach provides a promising cost-effective option to manage caries in developing countries with limited resources. Trial registration: The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: [ABSTRACT FROM AUTHOR]

Background: Patients experiencing adverse drug events (ADE) in many developing countries are in the best position to report these events to the authorities but need to be empowered to do so. Systematic evaluation of community engagement and patient support especially in rural areas would provide evidence for a program to monitor potential harm from medicines. The aim of this study was to assess the effects of a community dialogue and sensitization (CDS) program on the knowledge, attitude and practises of community members for reporting ADE. Methods: This an uncontrolled before-after study was conducted in two eastern Ugandan districts between September 2016 and August 2017 Results: After implementation of the community dialogue and sensitization (CDS) program, there was an overall 20% (95% CI:16% to 25%) increase in knowledge about ADE in the community compared to before the program began. Awareness levels increased by 50% (95% CI: 37% to 63%) among those with little or no education and by41% (95% CI: 31% to 52%) among young people (15–24 years). Furthermore, 5% (95% CI: 3% to 7%) more respondents recognized the need for reporting ADEs compared to before the program. Finally, there was a significant increase of 115% (95% CI:137% to 217%) in respondent recognition and reporting of ADEs compared to the beginning of the CDS program. Overall, this community found the CDS program acceptable and proposed aspects that could be improved for future use. Conclusion: Our evaluation showed that the CDS program increased knowledge and improved attitudes by catalyzing discussions among community members and healthcare professionals on health issues and monitoring safety of medicines compared to before the program. Successful implementation of the program depends on holistic health systems strengthening and adaptation to the community’s way of life. [ABSTRACT FROM AUTHOR]

The scientific and ethical importance of including women of reproductive age in biomedical research is widely acknowledged. Concerns about preventing fetal exposure to research interventions have motivated requirements for contraception among reproductive aged women in biomedical studies–often irrespective of risks and benefits or a woman’s actual potential for pregnancy, raising important questions about when such requirements are appropriate. The perspectives of women themselves on these issues are largely unexplored. We conducted 140 interviews, 70 in the U.S. and 70 in Malawi, with women either living with or at-risk for HIV, exploring their views about the practice of requiring contraception in clinical trials. A majority of women interviewed from both countries indicated overall support for the practice, with seven themes characterizing advantages and disadvantages raised: reproductive control, health effects, prevention of fetal harm, burden on women, deferral to authority, autonomy regarding enrollment and birth control method, and relationship concerns. While women in the US frequently raised prevention of fetal harm as a key advantage, many other positives noted by women in both countries were related to contraception use in general, not specific to a trial context. With regard to disadvantages, U.S. women tended to focus on biomedical risks such as side effects and impact on fertility, whereas Malawian women focused on the social risks of contraception requirements, including violations of trust in marital relations and suspicions of potential infidelity. Given the potential benefits and burdens highlighted, contraception in research should be sensitive to actual fetal risk assessments; directed where justified at optimizing effective pregnancy prevention; responsive to women’s reproductive preferences; and made available as an ancillary benefit even where risk thresholds do not justify requirement–in order to facilitate trials that are both ethical and robustly oriented around the interests and lives of women who will participate in them. [ABSTRACT FROM AUTHOR]

Robert W. Snow discusses the importance of empirical evidence, such as that provided in the trial published this week by Milligan and colleagues, in guiding malaria control in Africa. [ABSTRACT FROM AUTHOR]

Background: Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria in African children. Methods: We used paediatric safety data from a multi-site, multi-country clinical study conducted in seven African countries (Burkina Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique). Each site compared three out of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) or chlorproguanil/dapsone and artesunate (CD+A). We examine two pharmacovigilance signal detection methods, namely proportional reporting ratio and Bayesian Confidence Propagation Neural Network on the clinical safety dataset. Results: Among the 4,116 children (6–59 months old) enrolled and followed up for 28 days post treatment, a total of 6,238 adverse events were reported resulting into 346 drug-event combinations. Nine signals were generated both by proportional reporting ratio and Bayesian Confidence Propagation Neural Network. A review of the manufacturer package leaflets, an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD) and further by therapeutic area experts reduced the number of signals to five. The ranking of some drug-adverse reaction pairs on the basis of their signal index differed between the two methods. Conclusions: Our two data mining methods were equally able to generate suspected signals using the pooled safety data from a phase IIIb/IV clinical trial. This analysis demonstrated the possibility of utilising clinical studies safety data for key pharmacovigilance activities like signal detection and evaluation. This approach can be applied to complement the spontaneous reporting systems which are limited by under reporting. [ABSTRACT FROM AUTHOR]

Background: Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted. Experimental approach: A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski’s “Rule of Five” has been used to evaluate likely oral availability of the samples. Results: A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the “Rule of Five”. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed. Conclusions and implications: The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns. [ABSTRACT FROM AUTHOR]