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Background: Withania somnifera (L.) Dunal (W. somnifera) is a herb commonly known by its English name as Winter Cherry. Africa is indigenous to many medicinal plants and natural products. However, there is inadequate documentation of medicinal plants, including W. somnifera, in Africa. There is, therefore, a need for a comprehensive compilation of research outcomes of this reviewed plant as used in traditional medicine in different regions of Africa. Methodology: Scientific articles and publications were scooped and sourced from high-impact factor journals and filtered with relevant keywords on W. somnifera. Scientific databases, including GBIF, PubMed, NCBI, Google Scholar, Research Gate, Science Direct, SciFinder, and Web of Science, were accessed to identify the most influential articles and recent breakthroughs published on the contexts of ethnography, ethnomedicinal uses, phytochemistry, pharmacology, and commercialization of W. somnifera. Results: This critical review covers the W. somnifera ethnography, phytochemistry, and ethnomedicinal usage to demonstrate the use of the plant in Africa and elsewhere to prevent or alleviate several pathophysiological conditions, including cardiovascular, neurodegenerative, reproductive impotence, as well as other chronic diseases. Conclusion: W. somnifera is reportedly safe for administration in ethnomedicine as several research outcomes confirmed its safety status. The significance of commercializing this plant in Africa for drug development is herein thoroughly covered to provide the much-needed highlights towards its cultivations economic benefit to Africa. [ABSTRACT FROM AUTHOR]

Background: Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based object detection application named Kankanet to address those two needs. Methodology/Principal findings: A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%). Conclusions/Significance: The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology. [ABSTRACT FROM AUTHOR]

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: In Equatorial Guinea, malaria continues to be one of the main causes of morbidity and mortality among children. The National Therapeutic Guide established artesunate-amodiaquine (ASAQ) as first-line treatment for uncomplicated malaria, but compliance with this treatment is low. The aim of this study was to assess, for the first time, the performance of public healthcare workers in the diagnosis and treatment of uncomplicated malaria, their compliance with first-line Malaria National Therapeutic Guide and the associated factors. Methods: A cross-sectional survey was conducted at the nine public health facilities in the Bata District of Equatorial Guinea to assess the management of uncomplicated malaria in children < 15 years of age. Bivariate and multivariate statistical analyses were used to determine the recommended treatment compliance and related factors. Results: A total of 227 children with uncomplicated malaria were recorded from 9 public health facilities. Most of the treatments prescribed (83.3%) did not follow the first-line treatment recommended for uncomplicated malaria. The diagnosis was established with parasite confirmation in 182 cases (80.2%). After adjustment for other variables, children under 2 months of age, the use of parasite confirmation to the diagnosis of malaria and being familiar with the national therapeutic guide were significantly associated with the prescription of the first-line recommended treatment. Cases attended at the hospital or in a health facility with ASAQ in the pharmacy at the time of the study were also more likely to be prescribed with the recommended treatment, but with non-significant association after adjustment for other variables. Conclusions: This study identified the factors associated with the low compliance with the first-line treatment by the public healthcare facilities of Bata District of Equatorial Guinea. It seems necessary to improve case management of children with uncomplicated malaria; to reinforce the use of Malaria National Therapeutic Guide and to inform about the danger of using artemisinin monotherapy. Furthermore, it is crucial to provide recommended first-line treatment to the pharmacies of all public health facilities to ensure access to this treatment. [ABSTRACT FROM AUTHOR]

Background: Differentiated antiretroviral therapy (ART) delivery models, in which patients are provided with care relevant to their current status (e.g., newly initiating, stable on treatment, or unstable on treatment) has become an essential part of patient-centered health systems. In 2015, the South African government implemented Chronic Disease Adherence Guidelines (AGLs), which involved five interventions: Fast Track Initiation Counseling for newly initiating patients, Enhanced Adherence Counseling for patients with an unsuppressed viral load, Early Tracing of patients who miss visits, and Adherence Clubs (ACs) and Decentralized Medication Delivery (DMD) for stable patients. We evaluated two of these interventions in 24 South African facilities: ACs, in which patients meet in groups outside usual clinic procedures and receive medication; and DMD, in which patients pick up their medication outside usual pharmacy queues.Methods and Findings: We compared those participating in ACs or receiving DMD at intervention sites to those eligible for ACs or DMD at control sites. Outcomes were retention and sustained viral suppression (<400 copies/mL) 12 months after AC or DMD enrollment (or comparable time for controls). 12 facilities were randomly allocated to intervention and 12 to control arms in four provinces (Gauteng, North West, Limpopo, and KwaZulu Natal). We calculated adjusted risk differences (aRDs) with cluster adjustment using generalized estimating equations (GEEs) using difference in differences (DiD) with patients eligible for ACs/DMD prior to implementation (Jan 1, 2015) for comparison. For DMD, randomization was not preserved, and the analysis was treated as observational. For ACs, 275 intervention and 294 control patients were enrolled; 72% of patients were female, 61% were aged 30-49 years, and median CD4 count at ART initiation was 268 cells/μL. AC patients had higher 1-year retention (89.5% versus 81.6%, aRD: 8.3%; 95% CI: 1.1% to 15.6%) and comparable sustained 1-year viral suppression (<400 copies/mL any time ≤ 18 months) (80.0% versus 79.6%, aRD: 3.8%; 95% CI: -6.9% to 14.4%). Retention associations were apparently stronger for men than women (men RD: 13.1%, 95% CI: 0.3% to 23.5%; women RD: 6.0%, 95% CI: -0.9% to 12.9%). For DMD, 232 intervention and 346 control patients were enrolled; 71% of patients were female, 65% were aged 30-49 years, and median CD4 count at ART initiation was 270 cells/μL. DMD patients had apparently lower retention (81.5% versus 87.2%, aRD: -5.9%; 95% CI: -12.5% to 0.8%) and comparable viral suppression versus standard of care (77.2% versus 74.3%, aRD: -1.0%; 95% CI: -12.2% to 10.1%), though in both cases, our findings were imprecise. We also noted apparently increased viral suppression among men (RD: 11.1%; 95% CI: -3.4% to 25.5%). The main study limitations were missing data and lack of randomization in the DMD analysis.Conclusions: In this study, we found comparable DMD outcomes versus standard of care at facilities, a benefit for retention of patients in care with ACs, and apparent benefits in terms of retention (for AC patients) and sustained viral suppression (for DMD patients) among men. This suggests the importance of alternative service delivery models for men and of community-based strategies to decongest primary healthcare facilities. Because these strategies also reduce patient inconvenience and decongest clinics, comparable outcomes are a potential success. The cost of all five AGL interventions and possible effects on reducing clinic congestion should be investigated.Clinical Trial Registration: NCT02536768. [ABSTRACT FROM AUTHOR]

Introduction: Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa. Aims: We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries. Method: We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries. Results: There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95%CI [1.79–2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95%CI [1.35–2.56] and middle vs. high wealth: OR: 1.42, 95%CI [1.11–1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p<0.001) but not in middle-income countries (p = 0.17). In addition, 26.5% of the patients admitted having stopped their treatment due to financial reasons and this proportion was 4 fold higher in the lowest than highest wealth group (47.8% vs 11.4%) (p<0.001). Conclusion: This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis (LF) elimination as a public health problem requires the interruption of transmission by administration of preventive mass drug administration (MDA) to the eligible population living in endemic districts. Suboptimal MDA coverage leads to persistent parasite transmission with consequential infection, disease and disability, and the need for continuing MDA rounds, requiring considerable investment. Routine coverage reports must be verified in each MDA implementation unit (IU) due to incorrect denominators and numerators used to calculate coverage estimates with administrative data. IU are usually the health districts. Coverage is verified so IU teams can evaluate their outreach and take appropriate action to improve performance. Mozambique and the Democratic Republic of Congo (DRC) have conducted MDA campaigns for LF since 2009 and 2014, respectively. To verify district reports and assess the declared achievement using administrative data of the minimum 80% coverage of eligible people (or 65% of the total population), both countries conducted rapid probability surveys using Lot Quality Assurance Sampling (LQAS)(n = 1102) in 2015 and 2016 in 58 IU in 49 districts. The surveys identified IU with suboptimal coverage, reasons for not residents did not take the medication, place where the medication was received, information sources, and knowledge about diseases prevented by the MDA. LQAS identified four inadequately covered IU triggering district team performance reviews with provincial and national teams and district retreatment. Provincial estimates using probability samples (weighted by populations sizes) were 10 and 17 percentage points lower than reported coverage in DRC and Mozambique. The surveys identified: absence from home during annual MDA rounds as the main reason for low performance and provided valuable information about pre-campaign and campaign activities resulting in improved strategies and continued progress towards elimination of LF and co-endemic Neglected Tropical Diseases. [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]

Background: Drug resistant-tuberculosis is a growing burden on the South African health care budget. In response the National Department of Health implemented two important strategies in 2011; universal access to drug-sensitivity testing for rifampicin with Xpert MTB/RIF as the first-line diagnostic test for TB; and decentralization of treatment for RR/MDR-TB to improve access and reduce costs of treatment. Objective: Estimate the costs by treatment outcome of decentralized care for rifampicin and multi-drug resistant tuberculosis under routine conditions. The study was set at an outpatient drug resistant-tuberculosis treatment facility at a public academic hospital in Johannesburg, South Africa. During the study period 18–24 month long course treatment was offered for rifampicin-resistant and multi-drug-resistant tuberculosis. Methods: Data are from a prospective observational cohort study. Costs of treatment were estimated from the provider perspective using bottom-up micro-costing. Costs were estimated as patient-level resource use multiplied by the unit cost of the resource. Clinic visits, drugs, laboratory tests, and total days hospitalized were collected from patients' medical records. Staff time was estimated through a time and motion study. A successful treatment outcome was defined as cure or completion of the regimen. Results: We enrolled 124 patients with 52% having a successful outcome. The average total cost/patient for all patients was $3,430 and $4,530 for successfully treated patients. The largest contributors to total cost across all outcomes were drugs (43%) and staff (28%). The average cost to achieve a successful outcome including all patients who started treatment ("production cost") in the cohort is $6,684. Conclusions: Decentralized, outpatient RR/MDR-TB care under South Africa's 2011 strategy costs 74% less per patient than the previous strategy of inpatient care. The treatment cost of RR/MDR-TB is primarily driven by drug and staff costs, which are in turn dependant on treatment length. [ABSTRACT FROM AUTHOR]

Background: A single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without Wuchereria bancrofti infection in West Africa. Methods: In this open-label cohort study, treatment-naïve microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Côte d’Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants’ infection status. Findings: There was no difference in AUC0-inf or Cmax between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, P<0.001) and scrotal pain/swelling in males (6 of 20 versus 0 of 12, P = 0.025) were more frequent in infected than uninfected participants. All LF positive participants were amicrofilaremic at 7 days post-treatment and 27 of 31 (87%) remained amicrofilaremic 12 months after treatment. Conclusions: Moderate to heavy W. bancrofti infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing W. bancrofti Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: The annual number of surgical operations performed is increasing throughout the world. With this rise in the number of surgeries performed, so too, the challenge of effectively managing postoperative pain. In Africa, there are scanty data available that make use of multi-center data to characterize the quality of postoperative pain management. In this study using a longitudinal data, we have attempted to characterize the quality of postoperative pain management; among patients scheduled for major elective orthopedic, gynecologic and general surgery. Methods: This prospective longitudinal study evaluated the quality of postoperative pain management in patients undergoing elective general, gynecologic, and orthopedic surgery. We quantified the prevalence of moderate to severe postoperative pain with the International Pain Outcome Questionnaire and the corresponding adequacy of treatment with the pain management index. At four time points after surgery, we estimated pain severity, its physical and emotional interference, and patient satisfaction. Results: Moderate to severe postoperative pain was present in 88.2% of patients, and pain was inadequately treated in 58.4% of these patients. Chronic pain (β = 0.346, 95% CI: 0.212, 0.480) predicted patients’ worst pain intensity. Gender was not associated with the worst pain intensity or percentage of time spent in severe pain. Patient’s pain intensity did not predicted the level of satisfaction. Conclusions: The prevalence of moderate to severe postoperative pain and its functional interference is high in Ethiopian patients. The treatment provided to patients is inadequate and not in line with international recommendations and standards. [ABSTRACT FROM AUTHOR]

Objective: To assess the existing knowledge and skills relating to Emergency Obstetrics Care (EMOC) among health providers in eight referral maternity hospitals in Nigeria. Study design: A cross-sectional study of skilled health providers (doctors, nurses and midwives) working in the hospitals during the period. Setting: Six general hospitals (4 in the south and 2 in the north), and two teaching hospitals (both in the Northern part) of the country. Population: All skilled providers offering EMOC services in the hospitals during the study. Methods: A pre-tested self-administered questionnaire was used to obtain information relating to socio-demographic characteristics, the respondents’ knowledge and skills in offering specific EMOC services (as compared to standard World Health Organization recommendations), and their confidence in transferring the skills to mid-level providers. Data were analyzed with univariate, bivariate, binary and multinomial logistic regression analyses. Main outcome measures: knowledge and skills in EMOC services by hospital and overall. Results: A total of 341 health providers (148 doctors and 193 nurses/midwives) participated in the study. Averagely, the providers scored less than 46% in a composite EMOC knowledge score, with doctors scoring considerable higher than the nurses/midwives. Similarly, doctors scored higher than nurses/midwives in the self-reporting of confidence in carrying out specific EMOC functions. Health providers that scored higher in knowledge were significantly more likely to report confidence in performing specific EMOC functions as compared to those with lower scores. The self-reporting of confidence in transferring clinical skills was also higher in those with higher EMOC knowledge scores. Conclusion: The knowledge and reported skills on EMOC by health providers in referral facilities in Nigeria was lower than average. We conclude that the in-service training and re-training of health providers should be included in national policy and programs that address maternal mortality prevention in referral facilities in the country. Trial registration: Nigeria Clinical Trials Registry . [ABSTRACT FROM AUTHOR]

Introduction: The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods: Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results: The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion: This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the performance of the use of fixed-dose combination (FDC) TB drugs when used under programmatic settings in high TB-endemic countries. We evaluated the efficacy and safety of FDC versus loose formulation (LF) TB treatment regimens for treatment of pulmonary TB (PTB) in the context of actual medical practice in prevailing conditions within programmatic settings in five sites in two high TB-burden African countries. Methods: A two-arm, single-blind, randomized clinical trial comparing FDCs with separate LFs involving 1000 adults newly diagnosed with culture positive PTB was conducted at five sites in two African countries between 2007 and 2011. Participants were randomized to receive daily treatment with anti-TB drugs given as either FDC or separate LFs for 24 weeks (intensive phase– 8 weeks of isoniazid, rifampicin, ethambutol and pyrazinamide; continuation phase– 16 weeks of rifampicin and isoniazid). Primary outcome measures were microbiological cure and safety at the end of six months’ treatment; pre-specified non-inferiority margin for difference in cure rate was 4%. The primary efficacy analysis was based on the modified intent to treat (mITT) cohort comprising all randomized patients with a positive baseline culture result for TB and who received at least one dose of study treatment. Patients missing end of treatment culture results were considered failures. Further analyses were done in which mITT patients without an end of treatment (EOT) culture were excluded in a complete case analysis (mITTcc) and a per protocol cohort analysis defined as mITTcc patients who received at least 95% of their intended doses and had an EOT culture result. Results: In the mITT analysis, the cure rate in the FDC group was 86.7% (398/459) and in the LF group 85.2% (396/465) (difference 1.5-% (90% confidence interval (CI) (-2.2%– 5.3%)). Per Protocol analysis showed similar results: FDC 98.9% (359/363) versus LF 96.9% (345/356), (difference 2.0% (90% CI: 0.1%– 3.8%)). The two arms showed no significant differences in terms of safety, early culture conversion and patient adherence to treatment. Interpretation: The comparison of the two drug regimens satisfied the pre-specified non-inferiority criterion. Our results support the WHO recommendations for the use of FDC in the context of actual medical practice within health services in high TB-endemic countries. Trial Registration: ISRCTN Registry [ABSTRACT FROM AUTHOR]

Objectives: There is an urgent need to develop a safe, effective, orally active, and inexpensive therapy for African trypanosomiasis due to the drawbacks of current drugs. Selective tubulin inhibitors have the potential to be promising drug candidates for the treatment of this disease, which is based on the tubulin protein structural difference between mammalian and trypanosome cells. We propose to identify novel tubulin inhibitors from a compound library developed based on the lead compounds that selectively target trypanosomiasis. Methods: We used Trypanosoma brucei brucei as the parasite model, and human normal kidney cells and mouse microphage cells as the host model. Growth rates of both trypanosomes and mammalian cells were determined as a means to screen compounds that selectively inhibit the proliferation of parasites. Furthermore, we examined the cell cycle profile of the parasite and compared tubulin polymerization dynamics before and after the treatment using identified compounds. Last, in vivo anti-parasite activities of these compounds were determined in T. brucei-infected mice. Results: Three compounds were selected that are 100 fold more effective against the growth of T. brucei cells than mammalian cells. These compounds caused cell cycle progression defects in T. brucei cells. Western analyses indicated that these compounds decreased tubulin polymerization in T. brucei cells. The in vivo investigation revealed that these compounds, when admitted orally, inhibited T. brucei cell proliferation in mouse blood. However, they were not potent enough to clear up the infection completely. Conclusions: These compounds are promising lead compounds as orally active agents for drug development of anti-trypanosome agents. A more detail structure activity relationship (SAR) was summarized that will be used to guide future lead optimization to improve the selectivity and potency of the current compounds. [ABSTRACT FROM AUTHOR]