Impact of HIV self-testing for oral pre-exposure prophylaxis scale-up on drug resistance and HIV outcomes in western Kenya: a modelling study.

BACKGROUND: Community-based oral pre-exposure prophylaxis (PrEP) provision has the potential to expand PrEP coverage. HIV self-testing can facilitate PrEP community-based delivery but might have lower sensitivity than facility-based HIV testing, potentially leading to inappropriate PrEP use among people with HIV and subsequent development of drug resistance. We aimed to evaluate the impact of HIV self-testing use for PrEP scale-up. METHODS: We parameterised an agent-based network model, EMOD-HIV, to simulate generic tenofovir disoproxil fumarate and emtricitabine PrEP scale-up in western Kenya using four testing scenarios: provider-administered nucleic acid testing, provider-administered rapid diagnostic tests detecting antibodies, blood-based HIV self-testing, or oral fluid HIV self-testing. Scenarios were compared with a no PrEP counterfactual. Individuals aged 18-49 years with one or more heterosexual partners who screened HIV-negative were eligible for PrEP. We assessed the cost and health impact of rapid PrEP scale-up with high coverage over 20 years, and the budget impact over 5 years, using various HIV testing modalities. FINDINGS: PrEP coverage of 29% was projected to avert approximately 54% of HIV infections and 17% of HIV-related deaths among adults aged 18-49 years over 20 years; health impacts were similar across HIV testing modalities used to deliver PrEP. The percentage of HIV infections with PrEP-associated nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was 0·6% (95% uncertainty intervals 0·4-0·9) in the blood HIV self-testing scenario and 0·8% (0·6-1·0) in the oral HIV self-testing scenario, compared with 0·3% (0·2-0·3) in the antibody rapid diagnostic testing scenario and 0·2% (0·1-0·2) in the nucleic acid testing scenario. Accounting for background NRTI resistance, we found similarly low proportions of drug resistance across scenarios. The budget impact of implementing PrEP using HIV self-testing and provider-administered rapid diagnostic tests were similar, while nucleic acid testing was approximately 50% more costly. INTERPRETATION: Scaling up PrEP using HIV self-testing has similar health impacts, costs, and low risk of drug resistance as provider-administered rapid diagnostic tests. Policy makers should consider leveraging HIV self-testing to expand PrEP access among those at HIV risk. FUNDING: The Bill and Melinda Gates Foundation.

Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Cost of childhood RSV management and cost-effectiveness of RSV interventions: a systematic review from a low- and middle-income country perspective.

BACKGROUND: Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a shortacting monoclonal antibody (mAb), palivizumab (PVZ) that is expensive and intensive to administer, making it poorly suited for low-resource settings. Currently, new longer acting RSV mAbs and maternal vaccines are emerging from late-stage clinical development with promising clinical effectiveness. However, evidence of economic value and affordability must also be considered if these interventions are to be globally accessible. This systematic review's objective was to summarise existing evidence on the cost-of-illness (COI) and cost-effectiveness of RSV prevention interventions in LMICs. METHODS: We conducted a systematic literature review using the Embase, MEDLINE, and Global Index Medicus databases for publications between Jan 2000 and Jan 2022. Two categories of studies in LMICs were targeted: cost-of-illness (COI) of RSV episodes and cost-effectiveness analyses (CEA) of RSV preventive interventions including maternal vaccines and long-acting mAbs. Of the 491 articles reviewed, 19 met the inclusion criteria. RESULTS: COI estimates varied widely: for severe RSV, the cost per episode ranged from $92 to $4114. CEA results also varied-e.g. evaluations of long-acting mAbs found ICERs from $462/DALY averted to $2971/DALY averted. Study assumptions of input parameters varied substantially and their results often had wide confidence intervals. CONCLUSIONS: RSV represents a substantial disease burden; however, evidence of economic burden is limited. Knowledge gaps remain regarding the economic value of new technologies specifically in LMICs. Further research is needed to understand the economic burden of childhood RSV in LMICs and reduce uncertainty about the relative value of anticipated RSV prevention interventions. Most CEA studies evaluated palivizumab with fewer analyses of interventions in development that may be more accessible for LMICs.

Time Utilization Among Immunization Clinics Using an Electronic Immunization Registry (Part 2): Time and Motion Study of Modified User Workflows.

BACKGROUND: Digital health interventions have the potential to improve the provision of health care services through digitized data collection and management. Low- and middle-income countries are beginning to introduce electronic immunization registries (EIRs) into their routine immunization services to better capture and store childhood vaccination information. Especially in Africa, where 25% of children remain unimmunized or underimmunized, technologies that can help identify children due for a vaccination are particularly important for improving vaccination coverage. However, an improved understanding of the effectiveness of these systems is needed to develop and deploy sustainable EIRs in low- and middle-income countries. OBJECTIVE: We conducted an interventional pretest-posttest design study that sought to improve time efficiency through workflow modifications in Kenyan immunization clinics. Our aim was to describe how activity times differed after introducing workflow modifications that could potentially reduce the time needed to perform routine data entry activities. Our intent was to demonstrate changes in efficiency when moving from the existing dual-data entry workflow to a future paperless workflow by health facility size and experience length of health care workers (HCWs). METHODS: We tested how 3 workflow modifications would affect time utilization among HCWs using the EIR at the point of care compared with baseline immunization clinic workflows. Our outcome of interest was the time taken to complete individual activities and a patient's total time in the clinic where we compared the time spent during the baseline workflow with that during the modified workflow. We used a standardized tool to observe and document the immunization clinic workflow. To estimate differences in time utilization, we used bivariate analyses and fit multivariate linear mixed-effects models. RESULTS: Our study found that for HCWs using an EIR, the introduction of modified workflows decreased the amount of time needed to provide services to children seen in the immunization clinic. With a baseline mean time of 10 minutes spent per child, this decreased by about 3 minutes when the preparation modification was introduced and almost 5 minutes for the paperless and combined modifications. Results pertaining to the EIR's performance and ability to connect to the internet were particularly insightful about potential causes of delays. CONCLUSIONS: We were able to conduct a concise clinical simulation exercise by introducing modified workflows and estimating their impact on time utilization in immunization clinics using an EIR. We found that the paperless workflow provided the largest time savings when delivering services, although this was threatened by poor EIR performance and internet connectivity. This study demonstrated that not only should digital health interventions be built and adapted for particular use cases but existing user workflows also need to adapt to new technology.

Integration of a Digital Health Intervention Into Immunization Clinic Workflows in Kenya: Qualitative, Realist Evaluation of Technology Usability.

BACKGROUND: In an effort to increase vaccination coverage in low-resource settings, digital tools have been introduced to better track immunization records, improve data management practices, and provide improved access to vaccination coverage data for decision-making. Despite the potential of these electronic systems to improve the provision of health services, few digital health interventions have been institutionalized at scale in low- and middle-income countries. OBJECTIVE: In this paper, we aimed to describe how health care workers in Kenya had integrated an electronic immunization registry into their immunization clinic workflows and to use these findings to inform the development of a refined program theory on the registry's usability. METHODS: Informed by realist methodology, we developed a program theory to explain usability of the electronic immunization registry. We designed a qualitative study based on our theory to describe the barriers and facilitators influencing data entry and use. Qualitative data were collected through semistructured interviews with users and workflow observations of immunization clinic sessions. Our findings were summarized by context-mechanism-outcome relationships formed after analyzing our key themes across interviews and workflow observations. Using these relationships, we were able to identify common rules for future implementers. RESULTS: Across the 12 facilities included in our study, 19 health care workers were interviewed, and 58 workflow sessions were observed. The common rules developed from our qualitative findings are as follows: rule 1-ensure that the users complete training to build familiarity with the system, understand the value of the system and data, and know where to find support; rule 2-confirm that the system captures all data needed for users to provide routine health care services and is easy to navigate; rule 3-identify work-arounds for poor network, system performance, and too few staff or resources; and rule 4-make users aware of expected changes to their workflow, and how these changes might differ over time and by facility size or number of patients. Upon study completion, we revised the program theory to reflect the importance of the goals and workflows of electronic immunization registries aligning with reality. CONCLUSIONS: We created a deeper understanding of the underlying mechanisms for usability of the registry. We found that the electronic immunization registry had high acceptability among users; however, there were numerous barriers to using the system, even under ideal conditions, causing a misalignment between the system and the reality of the users' workflows and their environment. Human-centered design and human-factors methods can assist during pilot stages to better align systems with users' needs and again after scale-up to ensure that interventions are suitable for all user settings.

Usability and Acceptability of Electronic Immunization Registry Data Entry Workflows From the Health Care Worker Perspective in Siaya, Kenya (Part 3): Pre-Post Study.

BACKGROUND: Digital health tools such as electronic immunization registries (EIRs) have the potential to improve patient care and alleviate the challenges that arise from the use of paper-based clinic records for reporting. To address some of these challenges, the Kenya Ministry of Health and the International Training and Education Center for Health Kenya implemented an EIR system in 161 immunizing clinics in Siaya County between 2018 and 2019. The successful implementation of digital health tools depends on many factors, one of which is alignment between the technology and the context in which it is used. One important aspect of that implementation context is the perceptions of the health care workers (HCWs) using the EIR. OBJECTIVE: This study aimed to evaluate HCWs' perceptions of the usability and acceptability of multiple clinic workflows using the new EIR. METHODS: We performed a mixed methods pre-post study using semistructured interviews with HCWs at 6 facilities in Siaya County, Kenya. We interviewed HCWs at each facility 4 times: at baseline and once after the implementation of 3 different workflow modifications (n=24 interviews). The baseline state was dual data entry with paper records and the EIR. We then implemented 3 workflow modifications for 1 full day each: fully paperless data entry, preparation of an appointment diary before patient visits for the day, and a combination of the 2 workflows. We compared ratings and themes across interviews after each of the 4 workflows to understand the changes in the usability and acceptability of the EIR. RESULTS: HCWs considered the EIR clinic workflows to be usable and acceptable. Of the modified workflows, HCWs perceived the fully paperless workflow most favorably. In all workflows, HCWs' perceived benefits included ease of clinical decision-making using the EIR, reduced mental burden of data entry when using the EIR, and ease of identification of errors. Perceived barriers to the workflow included contextual challenges such as staffing shortages and lack of network connectivity, EIR platform challenges such as errors in saving records and missing fields, and workflow challenges such as the dual data entry burden of using paper and digital tools simultaneously. CONCLUSIONS: Fully paperless EIR implementation shows great promise from a workflow acceptability standpoint, contingent upon the presence of supporting contextual clinic factors and the resolution of system performance and design challenges. Rather than trying to identify a singular best workflow, future efforts should provide adequate flexibility for HCWs to implement the new system in their unique clinic context. Future EIR implementation stands to benefit from continued monitoring of EIR adoption acceptability during implementation, both for Siaya's program and for other efforts around the globe, as digital health interventions become more widely used.

Pharmacy deserts and COVID-19 risk at the census tract level in the State of Washington.

Community pharmacies are a crucial component of healthcare infrastructure, including for COVID-19 pandemic prevention services like testing and vaccination. Communities that are "pharmacy deserts," experience healthcare inequities. However, little research has characterized where these communities are, making it difficult for local leaders to prioritize resources for them. This study identifies pharmacy deserts at the census tract level in Washington state for the first time and explores their association with COVID-19 risk. Out of 1,441 tracts, 127 were pharmacy deserts, comprising approximately 454,000 adults, or 8% of the state's adult population. Among those tracts identified as pharmacy deserts, 67% were considered high risk for COVID-19. Solutions are needed to expand equitable access to pharmacy services in these communities. The methods and data presented herein provide healthcare leaders with information to address this pharmacy access gap in Washington and could be similarly applied to other settings. Three categories of policy changes could address health inequities found in our study: 1) improve financial incentives for pharmacists to practice in underserved areas, 2) prevent pharmacy closures, and 3) deploy innovative care delivery methods such as telehealth services.

Point Prevalence Survey of Antibiotic Use across 13 Hospitals in Uganda.

Standardized monitoring of antibiotic use underpins the effective implementation of antimicrobial stewardship interventions in combatting antimicrobial resistance (AMR). To date, few studies have assessed antibiotic use in hospitals in Uganda to identify gaps that require intervention. This study applied the World Health Organization's standardized point prevalence survey methodology to assess antibiotic use in 13 public and private not-for-profit hospitals across the country. Data for 1077 patients and 1387 prescriptions were collected between December 2020 and April 2021 and analyzed to understand the characteristics of antibiotic use and the prevalence of the types of antibiotics to assess compliance with Uganda Clinical Guidelines; and classify antibiotics according to the WHO Access, Watch, and Reserve classification. This study found that 74% of patients were on one or more antibiotics. Compliance with Uganda Clinical Guidelines was low (30%); Watch-classified antibiotics were used to a high degree (44% of prescriptions), mainly driven by the wide use of ceftriaxone, which was the most frequently used antibiotic (37% of prescriptions). The results of this study identify key areas for the improvement of antimicrobial stewardship in Uganda and are important benchmarks for future evaluations.

Price, quality, and market dynamics of malaria rapid diagnostic tests: analysis of Global Fund 2009-2018 data.

BACKGROUND: Rapid diagnostic tests (RDTs) for malaria are a vital part of global malaria control. Over the past decade, RDT prices have declined, and quality has improved. However, the relationship between price and product quality and their larger implications on the market have yet to be characterized. This analysis used purchase data from the Global Fund together with product quality data from the World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) Malaria RDT Product Testing Programme to understand three unanswered questions: (1) Has the market share by quality of RDTs in the Global Fund's procurement orders changed over time? (2) What is the relationship between unit price and RDT quality? (3) Has the market for RDTs financed by the Global Fund become more concentrated over time? METHODS: Data from 10,075 procurement transactions in the Global Fund's database, which includes year, product, volume, and price, was merged with product quality data from all eight rounds of the WHO-FIND programme, which evaluated 227 unique RDT products. To describe trends in market share by quality level of RDT, descriptive statistics were used to analyse trends in market share from 2009 to 2018. A generalized linear regression model was then applied to characterize the relationship between price and panel detection score (PDS), adjusting for order volume, year purchased, product type, and manufacturer. Third, a Herfindahl-Hirschman Index (HHI) score was calculated to characterize the degree of market concentration. RESULTS: Lower-quality RDTs have lost market share between 2009 and 2018, as have the highest-quality RDTs. No statistically significant relationship between price per test and PDS was found when adjusting for order volume, product type, and year of purchase. The HHI was 3,570, indicating a highly concentrated market. CONCLUSIONS: Advancements in RDT affordability, quality, and access over the past decade risk stagnation if health of the RDT market as a whole is neglected. These results suggest that from 2009 to 2018, this market was highly concentrated and that quality was not a distinguishing feature between RDTs. This information adds to previous reports noting concerns about the long-term sustainability of this market. Further research is needed to understand the causes and implications of these trends.

Developing a Concept of Operations Template to Guide Collaborative Disaster Research Response Between Academic Public Health and Public Health Agencies.

Research conducted in the context of a disaster or public health emergency is essential to improve knowledge about its short- and long-term health consequences, as well as the implementation and effectiveness of response and recovery strategies. Integrated approaches to conducting Disaster Research Response (DR2) can answer scientific questions, while also providing attendant value for operational response and recovery. Here, we propose a Concept of Operations (CONOPS) template to guide the collaborative development and implementation of DR2 among academic public health and public health agencies, informed by previous literature, semi-structured interviews with disaster researchers from academic public health across the United States, and discussion groups with public health practitioners. The proposed CONOPS outlines actionable strategies to address DR2 issues before, during, and after disasters for public health scholars and practitioners who seek to operationalize or enhance their DR2 programs. Additional financial and human resources will be necessary to promote widespread implementation of collaborative DR2 programs.

Antimicrobial use across six referral hospitals in Tanzania: a point prevalence survey.

OBJECTIVE: To delineate the prevalence and factors associated with antimicrobial use across six referral hospitals in Tanzania using WHO point prevalence survey (PPS) methodology to inform hospital-specific antimicrobial stewardship programmes. DESIGN: Cross-sectional analytical study. SETTING: Six referral hospitals in Tanzania. PARTICIPANTS: Patients irrespective of age and gender (n=948) admitted in the six referral hospital wards before 8:00 hours on each day of the survey were included in December 2019. Using the WHO PPS methodology, data on hospitals, wards, patients, antibiotics, and indications for antibiotics were collected. OUTCOME MEASURES: We analysed the prevalence of antibiotic use by referral hospital, ward, indication and patient characteristics as the main outcomes. We also described adherence to the Tanzania Standard Treatment Guidelines (STG) and WHO's AWaRe categorisation of antibiotics. RESULTS: Approximately 62.3% of inpatients were prescribed antibiotics, predominantly from the Access group of antibiotics (ceftriaxone, metronidazole or ampicillin-cloxacillin). The overall adherence of antibiotic prescriptions to the Tanzania STG was high (84.0%), with the exception of Sekou Toure Regional Referral Hospital (68.0%) and Maweni Regional Referral Hospital (57.8%). The most common indication for antibiotic prescriptions was community-acquired infections (39.8%). Children less than 2 years of age (OR 1.73, 95% CI 1.02 to 2.92, p=0.039); admission to surgical wards (OR 4.90, 95% CI 2.87 to 8.36, p <0.001); and admission to paediatric wards (OR 3.93, 95% CI 2.16 to 7.15, p <0.001) were associated with increased odds of antibiotic use. Only 2 of 591 patients were prescribed antibiotics based on culture and antimicrobial susceptibility testing results. CONCLUSIONS: Empirical use of antibiotics is common, and the Access group of antibiotics is predominantly prescribed in children less than 2 years and patients admitted to surgical and paediatric wards. Lack of utilisation of antimicrobial susceptibility testing services in these hospitals requires urgent interventions. Routine monitoring of antibiotic use is recommended to be part of antibiotic stewardship programmes in Tanzania.

National Consumption of Antimicrobials in Tanzania: 2017-2019.

Objective: Surveillance of antimicrobial consumption is essential to the national action plan for antimicrobial resistance (AMR) as stipulated in the Global Action Plan on AMR and the Tanzanian National Action Plan on AMR. Given the paucity of antimicrobial consumption data in sub-Saharan Africa region, the objective of this study was to measure antimicrobial consumption in Tanzania. Methods: From 2017 to 2019, data on all antimicrobials imported into Tanzania were obtained from the Tanzania Medicines and Medical Devices Authority Data, augmented with purchasing data from the Medical Stores Department and data from local manufacturers. Data were collected and analyzed in accordance with the World Health Organization Anatomical Therapeutic Chemical and defined daily doses (DDD) methodology. Results: The average DDD per 1,000 inhabitants per day (DDD/1,000/D) for all antimicrobials was 80.8 ± 39.35. The DDD/1,000/D declined from 136.41 in 2017 to 54.98 in 2018 and 51.02 in 2019. Doxycycline, amoxicillin, and trimethoprim-sulfamethoxazole were the most frequently consumed antibiotics during these years, accounting for 20.01, 16.75, and 12.42 DDD/1,000/D, respectively. The majority of antimicrobial consumption in Tanzania occurred in the private sector, with the proportion of private-sector antibiotic consumption increasing annually from 2017 to 2019. Based on AWaRe classification >90% of antimicrobial consumption was Access class medications, with Watch and Reserve class medications accounting for <10% and <1%, respectively. Conclusion: The private sector use of antimicrobials is significantly increasing and should be carefully monitored in accordance with national policies. Future work is necessary to increase reporting of antimicrobial consumption patterns in sub-Saharan Africa.