Preparing healthcare facilities in sub-Saharan Africa for future outbreaks: insights from a multi-country digital self-assessment of COVID-19 preparedness.

BACKGROUND: Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running. METHODS: Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected. RESULTS: Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks. CONCLUSIONS: A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Effect of a multifaceted intervention to improve clinical quality of care through stepwise certification (SafeCare) in health-care facilities in Tanzania: a cluster-randomised controlled trial.

BACKGROUND: Quality of care is consistently shown to be inadequate in health-care settings in many low-income and middle-income countries, including in private facilities, which are rapidly growing in number but often do not have effective quality stewardship mechanisms. The SafeCare programme aims to address this gap in quality of care, using a standards-based approach adapted to low-resource settings, involving assessments, mentoring, training, and access to loans, to improve clinical quality and facility business performance. We assessed the effect of the SafeCare programme on quality of patient care in faith-based and private for-profit facilities in Tanzania. METHODS: In this cluster-randomised controlled trial, health facilities were eligible if they were dispensaries, health centres, or hospitals in the faith-based or private for-profit sectors in Tanzania. We randomly assigned facilities (1:1) using computer-generated stratified randomisation to receive the full SafeCare package (intervention) or an assessment only (control). Implementing staff and participants were masked to outcome measurement and the primary outcomes were measured by fieldworkers who had no knowledge of the study group allocation. The primary outcomes were health worker compliance with infection prevention and control (IPC) practices as measured by observation of provider-patient interactions, and correct case management of undercover standardised patients at endline (after a minimum of 18 months). Analyses were by modified intention to treat. The trial is registered with ISRCTN, ISRCTN93644888. FINDINGS: Between March 7 and Nov 30, 2016, we enrolled and randomly assigned 237 health facilities to the intervention (n=118) or control (n=119). Nine facilities (seven intervention facilities and two control facilities) closed during the trial and were not included in the analysis. We observed 29 608 IPC indications in 5425 provider-patient interactions between Feb 7 and April 5, 2018. Health facilities received visits from 909 standardised patients between May 3 and June 12, 2018. Intervention facilities had a 4·4 percentage point (95% CI 0·9-7·7; p=0.015) higher mean SafeCare standards assessment score at endline than control facilities. However, there was no evidence of a difference in clinical quality between intervention and control groups at endline. Compliance with IPC practices was observed in 8181 (56·9%) of 14 366 indications in intervention facilities and 8336 (54·7%) of 15 242 indications in control facilities (absolute difference 2·2 percentage points, 95% CI -0·2 to -4·7; p=0·071). Correct management occurred in 120 (27·0%) of 444 standardised patients in the intervention group and in 136 (29·2%) of 465 in the control group (absolute difference -2·8 percentage points, 95% CI -8·6 to -3·1; p=0·36). INTERPRETATION: SafeCare did not improve clinical quality as assessed by compliance with IPC practices and correct case management. The absence of effect on clinical quality could reflect a combination of insufficient intervention intensity, insufficient links between structural quality and care processes, scarcity of resources for quality improvement, and inadequate financial and regulatory incentives for improvement. FUNDING: UK Health Systems Research Initiative (Medical Research Council, Economic and Social Research Council, UK Department for International Development, Global Challenges Research Fund, and Wellcome Trust).

Infection prevention and control compliance in Tanzanian outpatient facilities: a cross-sectional study with implications for the control of COVID-19.

BACKGROUND: As coronavirus disease 2019 (COVID-19) spreads, weak health systems must not become a vehicle for transmission through poor infection prevention and control practices. We assessed the compliance of health workers with infection prevention and control practices relevant to COVID-19 in outpatient settings in Tanzania, before the pandemic. METHODS: This study was based on a secondary analysis of cross-sectional data collected as part of a randomised controlled trial in private for-profit dispensaries and health centres and in faith-based dispensaries, health centres, and hospitals, in 18 regions. We observed provider-patient interactions in outpatient consultation rooms, laboratories, and dressing rooms, and categorised infection prevention and control practices into four domains: hand hygiene, glove use, disinfection of reusable equipment, and waste management. We calculated compliance as the proportion of indications (infection risks) in which a health worker performed a correct action, and examined associations between compliance and health worker and facility characteristics using multilevel mixed-effects logistic regression models. FINDINGS: Between Feb 7 and April 5, 2018, we visited 228 health facilities, and observed at least one infection prevention and control indication in 220 facilities (118 [54%] dispensaries, 66 [30%] health centres, and 36 [16%] hospitals). 18 710 indications were observed across 734 health workers (49 [7%] medical doctors, 214 [29%] assistant medical officers or clinical officers, 106 [14%] nurses or midwives, 126 [17%] clinical assistants, and 238 [32%] laboratory technicians or assistants). Compliance was 6·9% for hand hygiene (n=8655 indications), 74·8% for glove use (n=4915), 4·8% for disinfection of reusable equipment (n=841), and 43·3% for waste management (n=4299). Facility location was not associated with compliance in any of the infection prevention and control domains. Facility level and ownership were also not significantly associated with compliance, except for waste management. For hand hygiene, nurses and midwives (odds ratio 5·80 [95% CI 3·91-8·61]) and nursing and medical assistants (2·65 [1·67-4·20]) significantly outperformed the reference category of assistant medical officers or clinical officers. For glove use, nurses and midwives (10·06 [6·68-15·13]) and nursing and medical assistants (5·93 [4·05-8·71]) also significantly outperformed the reference category. Laboratory technicians performed significantly better in glove use (11·95 [8·98-15·89]), but significantly worse in hand hygiene (0·27 [0·17-0·43]) and waste management (0·25 [0·14-0·44] than the reference category. Health worker age was negatively associated with correct glove use and female health workers were more likely to comply with hand hygiene. INTERPRETATION: Health worker infection prevention and control compliance, particularly for hand hygiene and disinfection, was inadequate in these outpatient settings. Improvements in provision of supplies and health worker behaviours are urgently needed in the face of the current pandemic. FUNDING: UK Medical Research Council, Economic and Social Research Council, Department for International Development, Global Challenges Research Fund, Wellcome Trust.

Reforms: a quest for efficiency or an opportunity for vested interests'? A case study of pharmaceutical policy reforms in Tanzania.

BACKGROUND: Regulation of the pharmaceutical sector is a challenging task for most governments in the developing countries. In Tanzania, this task falls under the Food and Drugs Authority and the Pharmacy Council. In 2010, the Pharmacy Council spearheaded policy reforms in the pharmaceutical sector aimed at taking over the control of the regulation of the business of pharmacy from the Tanzania Food and Drugs Authority. This study provides a critical analysis of these reforms. METHODS: The study employed a qualitative case-study design. Data was collected through in-depth interviews, focus group discussions and document reviews. Data was analyzed thematically using a policy triangle framework. The analysis was done manually. RESULTS: The reforms adopted an incremental model of public policy-making and the process was characterized by lobbying for political support, negotiations and bargaining between the interest groups. These negotiations were largely centred on vested interests and not on the impact of the reforms on the efficiency of pharmaceutical regulations in the country. Stakeholders from the micro and meso levels were minimally involved in the policy reforms. CONCLUSION: Recent pharmaceutical regulation reforms in Tanzania were overshadowed by vested interests, displacing a critical analysis of optimal policy options that have the potential to increase efficiency in the regulation of the business of pharmacy. Politics influenced decision-making at different levels of the reform process.

Acceptability of vaginal film, soft-gel capsule, and tablet as potential microbicide delivery methods among African women.

BACKGROUND: Vaginal microbicides are in development for the prevention of HIV transmission to women via sexual intercourse. Acceptability of the microbicide delivery method in the targeted population is important to product adherence and, therefore, product effectiveness. It is anticipated that multiple delivery methods will be required to satisfy personal preferences among future microbicide users. METHODS: A total of 526 sexually active women aged 18-30 years participated in a consumer product preference study in Burkina Faso, Tanzania, and Zambia. Screened women who had given consent were instructed to use each of the three products (placebo formulations of a vaginal tablet, film, and soft-gel capsule) once daily for 7 consecutive days for a total of 21 days. Women were interviewed about their impressions of the product at the completion of each 7-day trial period. RESULTS: Over 80% of women reported they liked using each dosage form, and over 85% said they would definitely use it. The film and soft-gel capsule were chosen significantly more often than the tablet as the preferred dosage form (39% and 37% vs. 25%, respectively) mainly because of faster dissolving time and easier insertion. Women in Burkina Faso and Tanzania preferred the soft-gel capsule (42%-46%), whereas Zambian women preferred the film (51%). Age, socioeconomic status, and marital status did not significantly affect product preference. CONCLUSIONS: All three dosage forms were acceptable to the women surveyed. Preferred dosage forms varied by country. These data suggest that the availability of microbicides in multiple dosage forms may increase acceptability, adherence, and, therefore, effectiveness.

TLC for pharmaceutical analysis in resource limited countries.

This review article discusses the sustainability and robust advantages of planar chromatography that are critical to the successful performance of product quality assessments in resource limited areas including field applications. Because of the robustness and ease of use, the training required for successful performance of the high performance thin layer chromatography (HPTLC) assessments is much lower than that of other technologies with comparable reproducibility such as high performance liquid chromatography (HPLC). Some of the successful applications of planar chromatography in resource limited countries are presented. It should be noted that these planar chromatographic technologies have much lower plate counts and therefore separation power than column technologies such as HPLC and gas liquid chromatography (GLC). However in finished pharmaceutical products there are generally few active ingredients which are assessed making the HPTLC adequate for these analyses. In addition at this time there is a much wider array of detection technologies available for HPLC and GLC.

An interlaboratory investigation on the use of high-performance thin layer chromatography to perform assays of lamivudine-zidovudine, metronidazole, nevirapine, and quinine composite samples.

Two laboratories extensively investigated the use of HPTLC to perform assays on lamivudine-zidovudine, metronidazole, nevirapine, and quinine composite samples. To minimize the effects of differences in analysts' technique, the laboratories conducted the study with automatic sample application devices in conjunction with variable-wavelength scanning densitometers to evaluate the plates. The HPTLC procedures used relatively innocuous, inexpensive, and readily available chromatography solvents used in the Kenyon or the Global Pharma Health Fund Minilabs TLC methods. The use of automatic sample applications in conjunction with variable- wavelength scanning densitometry demonstrated an average repeatability or within-laboratory RSD of 1.90%, with 73% less than 2% and 97% at 2.60% or less, and an average reproducibility or among-laboratory RSD of 2.74%.

The use of Minilabs to improve the testing capacity of regulatory authorities in resource limited settings: Tanzanian experience.

The Tanzania Food and Drugs Authority piloted the use of Minilab kits, a thin-layer-chromatographic based drug quality testing technique, in a two-tier quality assurance program. The program is intended to improve testing capacity with timely screening of the quality of medicines as they enter the market. After 1 week training of inspectors on Minilab screening techniques, they were stationed at key Ports-of-Entry (POE) to screen the quality of imported medicines. In addition, three non-Ports-of-Entry centres were established to screen samples collected during Post-Marketing-Surveillance. Standard operating procedures (SOPs) were developed to structure and standardize the implementation process. Over 1200 samples were tested using the Minilab outside the central quality control laboratory (QCL), almost doubling the previous testing capacity. The program contributed to increased regulatory reach and visibility of the Authority throughout the country, serving as a deterrent against entry of substandard medicines into market. The use of Minilab for quality screening was inexpensive and provided a high sample throughput. However, it suffers from the limitation that it can reliably detect only grossly substandard or wrong drug samples and therefore, it should not be used as an independent testing resource but in conjunction with a full-service quality control laboratory capable of auditing reported substandard results.

Proficiency testing as a tool to assess the performance of visual TLC quantitation estimates.

The use of rapid and inexpensive nonlaboratory-based screening tests for drug quality assessments is recommended as a component of a drug quality assurance program in poor resource settings. We have established routine Minilab test procedures to screen product quality and a proficiency testing program to determine the competency of the inspectors and reliability of results. Samples for the proficiency testing were prepared by pulverizing a standard reference tablet of the appropriate drug and making serial dilutions with starch to obtain concentrations of 0, 40, and 100%. The samples, which were labeled only with the drug name and an identifying letter, were given to inspectors for quality screening using Minilab procedures. In round 1 of the proficiency test, only 3 of 28 substandard samples were correctly identified. Round 2 of the proficiency test, which was administered after a performance qualification test for the analytical method, showed much improvement: 19 of 27 substandard drugs were correctly identified, while 5 out of 9 inspectors made the correct inference on the quality of 45 samples. However, in both rounds, 2 inspectors failed to identify substandard samples, indicating that their technical competencies need to be improved for the reliability of the results. Although the thin-layer chromatography screening methods provide a rapid means for drug quality assessment, they need to be put in the hands of competent users. The inclusion of a proficiency test in the screening program provides a measure of determining competency of the personnel and reliability of the results.

Liquid chromatographic-mass spectrometric assay for simultaneous pyrimethamine and sulfadoxine determination in human plasma samples.

We present a liquid chromatographic-mass spectrometric assay for the simultaneous determination of sulfadoxine and pyrimethamine in human plasma samples. Sample clean-up was achieved by adding acetonitrile for protein precipitation. Gradient elution in only 10 min resulted in high throughput capability. Tandem mass spectrometric detection in multiple reaction monitoring was used for quantification. The developed analytical approach was successfully validated and was applied in the pharmacokinetic evaluation of the bioavailability between two sulfadoxine/pyrimethamine formulations available on the Eastern African market, using a cross-over design.

In vitro evaluation of the quality of essential drugs on the Tanzanian market.

We evaluated the in vitro availability and its stability under simulated tropical conditions of various formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro availability (dissolution) and its stability under simulated tropical conditions were determined using methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All formulations passed the pharmacopoeia requirements for the drug content. However, seven formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated stability test under simulated tropical conditions (75% RH/40 degrees C) for 6 months. The study has demonstrated the presence on the Tanzanian market of essential drug formulations that met potency requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand storage under simulated tropical conditions.