High Burden Countries Research Articles

COVID-19 policies and tuberculosis services in private health sectors of India, Indonesia, and Nigeria

IntroductionThe COVID-19 pandemic created unprecedented challenges in the field of global health. Nigeria, Indonesia and India are three high tuberculosis (TB) burden countries with large private health sectors. Both TB and the private health sector faced challenges in these countries because of COVID-19. This study aimed to compare the COVID-19 control measures and policies in the provision of TB care services and gain insights from policymakers on how the pandemic affected the provision of TB services in the private healthcare sector, how each country adapted, and identify lessons learned for health system preparedness MethodsQualitative, in-depth interviews were conducted among a purposive sample of 11 national and sub-national policymakers in each country. Thematic content analysis was conducted on the data collected using an adapted WHO Health Equity Policy Framework. ResultsResults revealed three policy dimensions under costs, access, and quality. Under healthcare costs, policymakers highlighted resource allocation and diversion of TB resources to COVID response, and increased operational costs for private provider. Under healthcare access, key themes included key themes included reduced TB case detection due to fear of COVID-19, disrupted diagnostic services, and adaptations such as extended medicine supplies and virtual consultations. Under healthcare quality, themes included compromised TB diagnostic accuracy due to similar respiratory symptoms with COVID-19, and strain on laboratory infrastructure due to competing demands from both diseases. Policymakers across the three countries pointed to the need for strengthening private–public partnerships (PPP) for healthcare service delivery and continued private sector investment to facilitate the continuity of TB care within a pandemic context. ConclusionThe results of this study provide an overview of the impact of the pandemic from the perspective of private facilities and policymakers in Nigeria, Indonesia and India, which can inform future policy and ways forward in strengthening PPP for healthcare service delivery in high TB burden countries.

Social and health factors associated with unfavourable treatment outcomes in children and adolescents with drug-sensitive tuberculosis in Brazil: a national retrospective cohort study

Although tuberculosis (TB) poses a significant global health threat to children and adolescents, there is limited information on the factors associated with TB treatment outcomes in this group. This study investigated the social and health factors associated with unfavourable treatment outcomes in children and adolescents with TB in Brazil, a high TB burden country. We conducted a population-based national retrospective cohort study of children (0-9 years) and adolescents (10-17 years) with TB in Brazil notified to the national Sistema de Informação de Agravos de Notificação (Sinan) from Jan 1, 2001, to Dec 31, 2022. Unfavourable treatment outcomes were defined as loss to follow-up, treatment failure, and death. Logistic regression and multinomial models examined the association between social and health factors, unfavourable treatment outcomes overall, and loss to follow-up and death, respectively. A total of 88,270 children and adolescents with TB were included of whom 25,600 (30.6%) had healthcare worker-supervised directly observed therapy (DOT). Of these, 9303 (10.5%) individuals experienced unfavourable TB treatment outcomes. For children, HIV infection (adjusted Odds Ratio 2.4, 95% confidence interval 1.9-3.1) and did not receive DOT (2.3, 1.9-2.7) were associated with unfavourable treatment outcomes. For adolescents, alcohol use (1.6, 1.2-2.0), illicit drug use (4.2, 3.4-5.1), tobacco use (1.6, 1.3-2.1), HIV infection (2.7, 2.2-3.4), and not receiving DOT (2.6, 2.3-2.9) were associated with unfavourable TB treatment outcome. Receiving social protection through government cash transfers protected against death (0.5, 0.3-0.9). In Brazil, TB treatment success rates were comparable to WHO End TB Strategy targets (90%). Substance use, HIV infection, and the absence of supervised treatment were the main factors associated with unfavourable treatment outcomes. Strategies to improve equity of TB treatment outcomes in this vulnerable group, including integrated HIV-TB services, DOT in healthcare facilities or communities, and holistic, person-centred healthcare and social protection, should be evaluated. Department of Health and Social Care (DHSC), the Foreign, Commonwealth & Development Office (FCDO), the Medical Research Council (MRC) and Wellcome, UK.

Digital continuous glucose monitoring systems for patients with HIV-diabetes comorbidity in Ethiopia: a situational analysis

In patients with HIV-diabetes mellitus (DM) comorbidity, invasive blood glucose testing can increase the risk of HIV-related blood contamination and discourage regular glucose monitoring. Digital continuous glucose monitoring (CGM) systems may allow real-time glucose monitoring without the need for blood specimens. However, in high-burden HIV-DM countries, current glucose monitoring practices and their challenges are insufficiently explored to guide digital CGM research and developments. This study sought to explore the lived experiences of patients with HIV-DM comorbidity and their healthcare providers regarding glucose monitoring practices, and their openness to CGM and other digital technologies, to provide formative insights for a planned implementation trial of digital CGM in Ethiopia. A phenomenological qualitative study was conducted among patients with HIV-DM and their providers at the two largest public hospitals in Ethiopia. Both groups were interviewed face-to-face about DM clinic workflows, blood glucose monitoring and self-testing practices, and potential benefits and limitations of digital CGM systems. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically. A total of 37 participants were interviewed, consisting of 18 patients with HIV-DM comorbidity and 19 healthcare providers. Patients had an average (min-max) duration of living with HIV and DM of 14 (8–31) and 6.6 (1–16) years, respectively, with 61% taking insulin—33% alone and 28% alongside oral hypoglycemic agents—and 79% having comorbid hypertension. The thematic analysis identified five main themes: “Diabetes routine clinical care and follow-up”, “Blood glucose monitoring practices”, “Perceptions about digital CGMs”, “Technology adoption”, and “Financial coverage”. Home self-testing was deemed beneficial, but the need for regular follow-ups, result cross-referencing, and glucometer reliability were emphasized. Patients performed fingerstick themselves or with family members, expressing concerns about waste disposal and the risk of HIV transmission. They rely mainly on health insurance for DM care. Patients and providers are happy with the quality of DM services but note a lack of integrated HIV-DM care. Very few providers and patients possessed background information about digital CGMs, and all have not yet utilized them in practice, but expressed keen interest in trying them, representing an important step for upcoming CGM clinical trials in these settings. Given the crucial role of regular glucose testing in managing HIV-DM comorbidity, it is essential to explore testing options that align with patient preferences and minimize the risk of HIV transmission.

Cost-effectiveness of diagnostic technologies for mycobacterium tuberculosis infection in India and Brazil.

The economic value of new skin-based tests and blood-based interferon-γ release assays (IGRAs) for tuberculosis (TB) infection is not yet well-established. This study evaluates the cost and cost-effectiveness in two high-burden countries by comparing:(a) new skin-based tests(Diaskintest and Cy-Tb) with the purified protein derivative (PPD)-tuberculin test (TST);(b) IGRAs (Standard E TB-Feron ELISA (TBF))with approved IGRAs (QuantiFERON-TB Gold Plus (QFT-GP)and TSPOT.TB); and (c) the best performing skin-based test with the best performing IGRA) based on cost effectiveness. In this paper, we developed a decision tree model for India and Brazil from a health system perspective. To quantify the effect of parameter variability and uncertainty, we performed both univariate and probabilistic sensitivity analysis. The study findings reveal that among skin-based tests, the Diaskintest is more cost-effective compared to TST-PPD at 22.6 USD and 41.0 USD per correctly diagnosed case of TB infection for Brazil and India, respectively. For blood-based assays, TSPOT.TB outperforms QFT-GP and TBF due to its lower cost and higher effectiveness. When compared with Diaskintest, TSPOT.TB has an incremental cost of approximately 8 USD and 6 USD for India and Brazil respectively but is more effective. The incremental cost-effectiveness ratio (ICER) was 74 USD and 55 USD for India and Brazil, respectively. In summary, while Diaskintest is potentially cost-saving when compared to TSPOT.TB in these two high-burden TB countries but the TSPOT.TB demonstrates higher effectiveness.

Global maternal health country typologies: A framework to guide policy.

Maternal mortality remains a large challenge in global health. Learning from the experience of similar countries can help to accelerate progress. In this analysis we develop a typology of country groupings for maternal health and provide guidance on how policy implications vary by country typology. We used estimates from the Global Maternal Health (GMatH) microsimulation model, which was empirically calibrated to a range of fertility, process, and mortality indicators and provides estimates for 200 countries and territories. We used the 2022 estimates of the maternal mortality ratio (MMR) and lifetime risk of maternal death (LTR) and used a k-means clustering algorithm to define groups of countries based on these indicators. We estimated the means of other maternal indicators for each group, as well as the mean impact of different policy interventions. We identified 7 groups (A-G) of country typologies with different salient features. High burden countries (A-B) generally have MMRs above 500 and LTRs above 2%, and account for nearly 25% of global maternal deaths. Countries in these groups are estimated to benefit most from improving access to family planning and increasing facility births. Middle burden countries (C-E) generally have MMRs between 100-500 and LTRs between 0.5%-3%. Countries in these groups account for 55% of global maternal deaths and would benefit most from increasing facility births and improving quality of care. Low burden countries (F-G) generally have MMRs below 100 and LTRs below 0.5%, account for 20% of global maternal deaths, and would benefit most from improving access to family planning and community-based interventions and linkages to care. Indicators vary widely across groups, but also within groups, highlighting the importance of considering multiple indicators when assessing progress in maternal health. Policy impacts also differ by country typology, providing policymakers with information to help prioritize interventions.

Diagnostic accuracy of TB screening tests in a prospective multinational cohort: Chest-X-ray with computer-aided detection, Xpert TB host response, and C-reactive protein.

Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. We prospectively screened adults with ≥2 weeks of cough at primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. Participants received chest-X-ray, Cepheid Xpert TB Host Response (Xpert HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech). Chest-X-ray images were processed using CAD4TB v7, a computer-aided detection algorithm. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to maximize specificity at 90% sensitivity. Two-test screening algorithms were considered, using 1) sequential negative serial screening (positive defined as positive on either test) and 2) sequential positive serial screening (positive defined as positive on both tests). Between July 2021 and August 2022, 1,392 participants with presumptive TB had valid index tests and reference standard results, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity at 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Three two-test screening algorithms met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive]. CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. NCT04923958.

Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: An epidemiological analysis of historical data.

Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening. Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing. A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today's high tuberculosis burden countries and with new screening tools and technologies.

Evaluation of Multiplex loop-mediated isothermal amplification assay for the detection of Mycobacterium tuberculosis complex from clinically suspected cases of pulmonary tuberculosis

Tuberculosis (TB) is the second leading cause of death from a single infectious agent worldwide. Bangladesh ranks 7th among the 30 high TB burdened countries in the world. Accurate detection of Mycobacterium tuberculosis complex (MTBC) is challenging for developing countries as most of the resource poor settings are not suitable to perform molecular techniques.The purpose of the study was to compare the multiplex TB-LAMP assay with MTB/NTM qPCR, culture, Z-N staining, and fluorescence microscopy in order to assess the effectiveness of the LAMP assay for detecting cases of pulmonary tuberculosis.This research work was done from March 2022 to February 2023. Fulfilling the inclusion criteria 130 sputum samples were collected. TB-LAMP assay, qPCR, culture in L-J media, Z-N staining and fluorescence microscopy were performed.Out of 130 samples qPCR detected MTBC in 56.92 % cases and TB-LAMP detected 53.85 %. MTBC was detected by culture 46.15 %, by Fluorescence microscopy 40.77 % and Z-N staining 36.92 %. TB-LAMP detected 16.93 % more cases than Z-N staining and 13.08 % more cases than fluorescence microscopy. The sensitivity, specificity, positive, and negative predictive values of multiplex-LAMP assay were 95 %, 81.4 %, 81.4 % and 95 % respectively considering culture as a gold-standard. MTBC negative culture samples (18.57 %) showed positivity by LAMP assay as well as by qPCR. This study detected 7.69 % non-tuberculous mycobacteria (NTM) by qPCR. All NTM positive samples were negative by TB-LAMP.TB-LAMP is an easy to perform, cost-effective, reliable assay with high sensitivity and specificity. World Health Organization recommended TB-LAMP as a rapid molecular test for rapid detection of tuberculosis and as replacement of microscopy in resource poor settings/hard to reach areas. Bangladesh being a high TB burden country it is essential to implement TB-LAMP to achieve End TB Strategy by 2035.

An Assessment on the Application of the Porter Diamond Model Aspects within Tuberculosis Treatment Healthcare Facilities in Nairobi County, Kenya

Strategic management involves formulating and implementing an organization’s vision, mission, and objectives, making decisions on resource allocation, and developing appropriate strategies to achieve set goals. Contemporary strategic management theories provide frameworks and models that guide organizations in these processes. One prominent theory is the Resource-based Theory, particularly the Porter Diamond Theory, which is essential for understanding organizational dynamics, competitive strengths, and strategy development across various sectors, including healthcare. The Porter Diamond Theory posits that an entity's competitiveness is influenced by four interconnected factors: Factor Conditions: These include tangible and intangible resources relevant to the organization. Market Demand Conditions: The nature and scope of market demand that shape industry competitiveness. Related and Supporting Industries: The presence of suppliers, manufacturers, and service providers that enhance organizational capabilities. Industry Strategy, Structure, and Rivalry: The conditions within which institutions are created, organized, and managed, influencing their strategic direction and competitive behavior.Strategic management in healthcare supports quality improvement, monitoring, and evaluation by identifying strategic advantages. It enhances leadership, streamlines management, improves decision-making, and elevates the appeal and efficacy of healthcare organizations and workers. Quality healthcare is crucial for disease prevention and improving life quality. However, strategic management practices specific to healthcare, especially for tuberculosis (TB), remain under-explored. TB is a contagious bacterial infection primarily affecting the lungs, caused by Mycobacterium tuberculosis. It spreads through airborne droplets from coughing, sneezing, or breathing, and can also impact the kidneys, spine, and brain. Symptoms include persistent cough, fever, chest pain, fatigue, night sweats, and loss of appetite. TB is one of the most common infections globally, causing significant morbidity and mortality. In 2019, the World Health Organization estimated 10 million TB cases and 1.2 million deaths. Despite global efforts, about 3.6 million people with TB are missed annually by health systems and do not receive needed care. Kenya is among the 30 high TB burden countries, facing significant challenges from multidrug-resistant TB and TB/HIV co-infection. In 2019, Kenya had over 140,000 TB cases, with Nairobi reporting the highest numbers. The Kenya Country TB prevalence report (2016) indicates that TB in the country is higher than estimated, with about half of those who fall ill annually being missed. Direct research on the application of strategic management practices for TB case finding in Kenya is limited. A study adopting a pragmatic design, which incorporates the collection and analysis of both quantitative and qualitative data, was conducted to explore this issue comprehensively. Between April and June 2024, a total of 406 respondents (81% response rate) from 239 TB treatment sites in Nairobi participated. Additionally, four Focus Group Discussions (FGDs) involving 44 respondents were conducted. The study reveals variations in strategy formulation practices across facilities, with differing frequencies of TB performance review meetings, indicating a need for standardization. Total Quality Management (TQM) faces implementation challenges, including high staff turnover, shortages, frequent staff rotations, and resource constraints like insufficient human resources and frequent stock-outs of diagnostic tools and drugs. The involvement of diverse technical teams in TB case-finding activities reflects a collaborative approach to TB control. Findings suggest a need for further investigation into factors influencing the establishment of strategic management committees and highlight areas for increased investment in infrastructure and capacity-building to enhance TB services' sustainability and effectiveness. Addressing inadequate sanitation facilities and other environmental factors is crucial for improving TB case-finding and public health outcomes. Emphasizing community awareness campaigns and enhancing demand for TB services among key population groups is essential. The Government of Kenya plays a central role in TB service supply, necessitating robust supply chain management and strategic planning to ensure consistent access to essential commodities. Tailored strategies, technological integration, and strategic partnerships are vital for enhancing TB case-finding and overall service delivery. The study reccomends to Implement a standardized schedule for TB performance review meetings across all sub-counties to ensure uniformity and consistency in TB management practices. Increase investment in staff training and retention programs to address TQM challenges and resource constraints, enhancing the effectiveness and sustainability of TB services

A Study to Assess Anti-TB Treatment Compliance, Factors Predictive for Poor Adherence and Perpetual Defaulting among Patient Living with TB in Namuseche Chipata Eastern Province–Zambia

Background of the Study: Tuberculosis (TB) is the ninth leading cause of death worldwide. According to WHO at least 1.5 million people each year succumb to TB, thus making it the world's top infectious killer as well as the leading cause from a single infectious agent, ranking above HIV/AIDS. Zambia is one of the top 30 high TB burden countries. People with active TB can infect 5– 15 other people through close contact over the course of a year. TB patients with compromised immune systems, such as people living with HIV, malnutrition or diabetes, or people who use tobacco, have a higher risk of falling ill. Without proper treatment, 45% of HIV-negative people with TB on average and nearly all HIV-positive people with TB will die. Defaulting on TB medication is a major barrier to both local and global TB control. Defaulting increases, the risk of drug resistance, treatment failure, relapse and death, and may prolong infectiousness. Poor adherence to treatment means that patients remain infectious for longer and are more likely to relapse or succumb to tuberculosis. The rate of anti-TB treatment compliance, adherence and perpetual defaulting TB treatment was and is still high during the intensive phase of treatment. Most people who are called “lost to follow up” don’t have adequate information as to why they should continue and finish their TB medication.  Methodology: A qualitative, phenomenological cross-sectional research design was used. Namuseche Prison Clinic and surrounding compounds of Chipata Township in Eastern Province Zambia. A total of 141 participants was recruited through purposive sampling. In-depth interviews were conducted. The SPSS package version 23 was applied to conduct quantitative analysis. The proposal was approved by the Chreso University Ethics Clearance Committee and National Health Research Authority. Researcher ensured confidentially and voluntary participation with informed consent.  Results: The age of the respondents in this study ranged from 18 years to 50 years. Knowledge on TB related questions was very high in this study and stood at 87.3%. TB treatment default was found in 34 (32.7%) respondents and was associated with distance to the facility and transport costs, feeling unwell and the drug side effects.  Conclusion: TB treatment default was found in 34 (32.7%) respondents and was associated with distance to the facility and transport costs, feeling unwell and the drug side effects.

UNSEEN TUBERCULOSIS: STUDY AMONG INPATIENTS OF A TERTIARY CARE HOSPITAL OF NORTH KARNATAKA

Objective: Tuberculosis (TB) remains a significant global health challenge, particularly in high-burden countries like India. However, high proportion of people never diagnosed or treated. Delayed diagnosis poses a significant threat to hospital inpatients, health-care workers, and medical trainees. Hence, systematic screening of high-risk groups, including hospital inpatients, has been recommended as a strategy to identify TB. Using signs and symptoms as an independent screening tool remains a global challenge for its relatively low accuracy. However, it could still be of value when it was used in a specific target population like inpatients of hospital. Hence, this study is aimed to determine the proportion of presumptive and active TB cases among inpatients. Methods: A hospital-based cross-sectional study was conducted among inpatients above 18 years of age admitted in non-emergency wards admitted during March to April 2023 at ESIC Hospital in Kalaburagi. A pre-existing TB diagnosis and patients admitted to critical care units were excluded. The convenient sampling method was used to recruit participants. Data were collected through using a pre-designed, semi-structured questionnaire. The patients who presented with one of the four symptoms for screening had undergone investigations such as cartridge-based nucleic acid amplification test, chest X-ray, and sputum microscopy to confirm the diagnosis, and the findings were recorded as proportion. Results: Out of 1363 inpatients, 35 (2.5%) patients had classified as presumptive TB case. Out of 35, 3 (8.57%) were found to be actual TB cases. All patients who had positive results for TB were young patients and belonged to low socioeconomic class. Two of three were rifampicin-sensitive TB cases. Conclusion: Timely screening of the patient’s is of utmost importance to avoid further spread of TB infection among inpatients. The higher prevalence of actual TB cases in younger adults needs further exploration.

Clinical characteristics and mortality of tuberculosis among adults living with HIV/AIDS: A single center, retrospective cohort study in Thailand.

Tuberculosis (TB) among people living with HIV/AIDS (PLWHA) contributes substantially to morbidity and mortality, particularly in high TB burden countries. Our objective is to investigate the clinical characteristics and mortality rates associated with TB among adult PLWHA over a 10-year period at an urban HIV clinic situated in a high TB burden country. A retrospective cohort study was conducted in 2022. The primary endpoints were clinical characteristics and mortality rate of TB, determined as per 100 person-years among adult PLWHA, presented with a 95% confidence interval. Univariable and multivariable Cox proportional regression analyses were performed to determine risk factors for TB mortality. From January 2012-December 2022, 155 PLWHA receiving a diagnosis of TB were enrolled. The median age was 29 (26.5-48.5) years, and the median CD4 + T cell count was 141 (41.8-252.8) cells/µL, with 60.0% of patients with TB manifesting as disseminated infection. The most involved organs were pulmonary (89.7%), lymph nodes (39.4%) and pleura (14.8%). The treatment outcomes exhibited success in 63.2% of cases, relapse in 5.2%, loss to follow up in 17.4% and death in 14.2%. The overall mortality rate was 18.8 per 100 person-years. Multivariable analyses showed significant factors affecting mortality, including lymph node involvement (adjusted HR 3.5; 95% CI 1.1-10.8) and thrombocytopenia (adjusted HR 74.2; 95% CI 10.0-551.4). TB in PLWHA, commonly presenting as disseminated infection, contributes to high mortality. Lymph node involvement and thrombocytopenia are significant factors contributing to mortality. Tuberculosis preventive treatment should be considered for improved prevention strategies among PLWHA, particularly in high TB burden countries.

5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial

WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. The Bill & Melinda Gates Foundation.

Further analysis of tuberculosis in eight high-burden countries based on the Global Burden of Disease Study 2021 data

BackgroundsMost significant findings from the Global Tuberculosis (TB) Report 2023 indicate that India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo (DRC) collectively contribute to approximately two-thirds of global TB cases. This study aims to provide crucial data-driven insights and references to improve TB control measures through a comprehensive analysis of these eight high-burden countries.MethodsThe eight high-burden TB countries analyzed in this study include India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the DRC. Age-standardized incidence rates (ASIR) of TB were derived from the Global Burden of Diseases Study 2021 data. Temporal trends were analyzed using Joinpoint regression. An age-period-cohort model was applied to examine the risk ratios (RR) of TB across diverse age groups, periods, and birth cohorts. A Bayesian age-period-cohort framework was employed to predict the ASIR of TB by 2030.ResultsThe study found that the Philippines (average annual percentage change = 3.1%, P < 0.001) exhibited an upward trend from 1990 to 2021. In India, the Philippines, Pakistan, and Bangladesh, the RR of TB incidence exceeded 1 after individuals reached 25 years old. Notably, the RR has shown a consistent upward trend since 2001, peaking during the period of 2017–2021 with an estimated RR of 1.5 (P < 0.001) in the Philippines. Similarly, the highest RR was observed during the period of 2017–2021 reaching 1.1 (P < 0.001) in the DRC. In the Philippines, the markedly increasing RR values for TB have been observed among individuals born after 1997–2001. Projections suggest that the ASIR of TB is expected to follow a continued upward trajectory, with an estimated rate of 392.9 per 100,000 by 2030 in the Philippines; India and Indonesia are projected to achieve less than 20.0% of the target set by the World Health Organization (WHO).ConclusionsAmong the eight high-burden countries, the Philippines, India and Indonesia are diverging from the goals set by the WHO, and the risk of TB in the Philippines and the DRC shows a trend toward affecting younger populations, which suggests that the management strategies for TB patients need to be further strengthened.Graphical

Estimates of Potential Demand for Measles and Rubella Microarray Patches.

Global measles vaccine coverage has stagnated at approximately 85% for over a decade. By simplifying vaccine logistics and administration, the measles and rubella microarray patch (MR-MAP) may improve coverage. Clinical trials have demonstrated similar safety and immunogenicity in 9-month-old infants for MR-MAPs compared with syringe-and-needle vaccination. To aid commercialization, we present estimates of MR-MAP demand. We created a spreadsheet-based tool to estimate demand for MR-MAPs using data from 180 WHO countries during 2000-2016. Five immunization scenarios were analyzed: (1a) Supplementary Immunization Activities (SIAs) in Gavi, the Vaccine Alliance (Gavi)-eligible countries and (1b) WHO countries where preventive SIAs are routinely conducted; (2) SIAs and outbreak response immunization in all WHO countries; (3) routine immunization (RI) and SIAs in six high-burden measles countries (the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, and Pakistan); (4) RI and SIAs in six high-burden countries and Gavi-eligible countries; and (5) hard-to-reach populations. MR-MAP demand varied greatly across scenarios. Forecasts for 2025-2034 estimate from 137 million doses in hard-to-reach populations (scenario 5) to 2.587 billion doses for RI and SIAs in six high-burden countries and Gavi-eligible countries (scenario 4). When policymakers and manufacturers assess MR-MAP demand, they may consider multiple scenarios to allow for a complete consideration of potential markets and public health needs.

Health and economic impacts of Vaccae vaccination incorporating active case finding in India and South Africa: a modelling study

IntroductionTuberculosis (TB) is a major global health issue, particularly, in India and South Africa. We aim to evaluate the potential of the new TB vaccine, Vaccae, to enhance TB control...

Design and implementation of a Type-2 hybrid, prospective randomized trial of opioid agonist therapies integration into primary care clinics in Ukraine

IntroductionUkraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). MethodsA randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) – standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. Preliminary resultsAmong the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. ConclusionPWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

The intersection of TB and health financing: defining needs and opportunities

TB is an airborne public health threat, so the reponse to TB has been defined mainly through the lens of vertical, public-sector national TB programs (NTPs). However, TB exists within a broader health systems and health financing context. Here, we examine the intersection between the particular needs of TB programs and the broader health financing landscape. This includes the strategies needed to finance both the clinical and public health aspects of the TB response. In high-burden countries, the resource mobilization and strategic purchasing approaches described here will be critical if we are to maximize the reach and impact of the TB response.

Genetic diversity, variation and recombination among the human papillomaviruses (HPVs) genomes isolated in China: a comparative genomic and phylogenetic analysis

ABSTRACT Human papillomaviruses (HPVs) are widespread, sexually transmitted group of viruses that infect most individuals at some stage, causing genital warts and cancers. They are members of the Papillomaviridae family, which contains about 400 HPV types. China is among the high HPV burden countries with reported infections of multiple HPV types, accounting for 17.3% of global deaths and 18.2% of global new cases. Thus, understanding the genetic variation and geographic diversity characteristics of HPVs isolated in China is critical for global HPV prevention strategies. Thus, we analyzed the available HPV genome sequences isolated in China that grouped into two categories (alpha- and gamma-papillomaviruses) based on full-length genomes. The most common were HPV-16, −6, −58, and −52 respectively. In addition, four of the novel strains isolated in China, e.g. TG550, JDFY01, CH2, and L55 clustered with the HPV-mSK 159, 244, 201, and 200 respectively. Our phylogeographic network analysis indicated that the L55, TG550, and CH2 are genetically identical to the mSK 200, 046, and 201 respectively, while JDFY01 appeared separately, connected to the mSK-040 following five mutational steps. Also, we found ten recombination events among HPV-6/11 types within their E1, E2, E7, L1/L2 proteins, and Long Control Region ORFs. We achieved the consensus amino acid sequences of HPV proteins and found a conserved stretch of amino acids within E5A of all HPVs circulating in China. These findings offer valued insights into the genetic relationships, distribution, and evolution of the HPVs in China that may assist in adapting effective HPV preventive measures.

Using the Lives Saved Tool to inform global nutrition advocacy.

The global nutrition community has been interested in investigating investment strategies that could be used to promote an increased focus and investment in nutrition programming in low- and middle-income countries. The Lives Saved Tool (LiST) was used to evaluate lives saved and the costs of nutrition interventions in nine high-burden countries. In this case study, we detail the analyses that were conducted with LiST and how the results were packaged to develop Nourish the Future - a five-year proposal for the US government to scale up lifesaving malnutrition interventions. Scaling up a proposed package of critical nutrition interventions including micronutrient supplementation for pregnant women, breastfeeding support, Vitamin A supplementation for children, and treatments for moderate and severe acute malnutrition is an effective and cost-effective way to avert millions of child deaths and stillbirths. This is one of the few case studies that outlines how a nutrition modeling tool (in this case LiST) was used to engage in a prioritisation exercise to inform a US-based advocacy ask. We share reflections and provide practical insights into user motivation and preferences for existing and future modeling tool developers. This case study also emphasises how integral evidence translation and strategic advocacy are to ensure the use of the modeling results.