World Health Organization Target Research Articles

Quantitative drug susceptibility testing for Mycobacterium tuberculosis using unassembled sequencing data and machine learning.

There remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs. We trained, validated and tested the system on 10,859 isolates from the CRyPTIC dataset. Essential agreement rates (predicted MIC within one doubling dilution of observed MIC) were above 92% for first-line drugs, 91% for fluoroquinolones and aminoglycosides, and 90% for new and repurposed drugs, albeit with a significant drop in performance for the very few phenotypically resistant isolates in the latter group. To further validate the model in the absence of external MIC datasets, we predicted MIC and converted values to binary for an external set of 15,239 isolates with binary phenotypes, and compare their performance against a previously validated mutation catalogue, the expected performance of existing molecular assays, and World Health Organization Target Product Profiles. The sensitivity of the model on the external dataset was greater than 90% for all drugs except ethionamide, clofazimine and linezolid. Specificity was greater than 95% for all drugs except ethambutol, ethionamide, bedaquiline, delamanid and clofazimine. The proposed system can provide quantitative susceptibility phenotyping to help guide antimicrobial therapy, although further data collection and validation are required before machine learning can be used clinically for all drugs.

Hepatitis C: From diagnosis to global virus elimination

Chronic infection with hepatitis C virus (HCV) is a common cause of complications such as liver cirrhosis and hepatocellular carcinoma (HCC). It is one of the most significant infectious diseases worldwide, posing a substantial health burden. Since the introduction of direct-acting antiviral agents (DAAs), the treatment landscape has undergone a revolution. HCV infection is curable, and the treatment is safe and well tolerated. Due to the availability of this effective therapeutic option, the World Health Organization (WHO) set an ambitious goal in 2015 to eliminate Hepatitis C by 2030, a goal that the German government also embraced in 2016. The key tasks involve identifying previously undiagnosed cases and ensuring they receive antiviral treatment. Addressing at-risk populations through specific measures, including micro-elimination projects and population-wide campaigns, is essential to achieving the WHO's target both in Germany and globally.

Bridging Hepatitis C Care Gaps: A Modeling Approach for Achieving the WHO's Targets in Ontario, Canada.

The World Health Organization (WHO) has set hepatitis C (HCV) elimination targets for 2030. Understanding existing gaps in the "HCV care-cascade" is essential for meeting these targets. We aimed to identify the level of service scale-up needed along the "HCV care-cascade" to achieve the WHO's HCV elimination targets in Ontario, Canada. By employing a decision analytic model, we projected the quality-adjusted life years (QALYs) and healthcare costs for individuals with HCV in Ontario. We increased RNA testing and treatment rates to 98%, followed by increasing antibody testing uptake until we achieved the WHO's mortality target (i.e., a 65% reduction in liver-related mortality by 2030 vs. 2015). Without scaling up by 2030, the expected QALYs and costs per person were 9.156 and CAD 48,996, respectively. Improved RNA testing and treatment rates reduced liver-related deaths to 3.3/100,000, a 57% reduction from 2015. Further doubling the antibody testing rates can achieve the WHO's mortality target in 2035, but not in 2030. Compared to the status quo, such program would be cost-effective considering a 50,000 CAD/QALY gained threshold if annual implementation costs stayed under 2.3 M CAD/100,000 people. Doubling the antibody testing rates, along with increased RNA testing and treatment rates, showed promise in meeting the WHO's goals by 2035.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti.

In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization's goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures. To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city. We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software. Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01). Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

How feasible is it to mobilize $31 billion a year for pandemic preparedness and response? An economic growth modelling analysis

BackgroundCovid-19 has reinforced health and economic cases for investing in pandemic preparedness and response (PPR). The World Bank and World Health Organization (WHO) propose that low- and middle-income governments and donor countries should invest $31.1 billion each year for PPR. We analyse, based on the projected economic growth of countries between 2022 and 2027, how likely it is that low- and middle-income country governments and donors can mobilize the estimated funding.MethodsWe modelled trends in economic growth to project domestic health spending by low- and middle-income governments and official development assistance (ODA) by donors for years 2022 to 2027. We modelled two scenarios for countries and donors – a constant and an optimistic scenario. Under the constant scenario we assume that countries and donors continue to dedicate the same proportion of their health spending and ODA as a share of gross domestic product (GDP) and gross national income (GNI), respectively, as they did during baseline (the latest year for which data are available). In the optimistic scenario, we assume a yearly increase of 2.5% in health spending as a share of GDP for countries and ODA as a share of GNI for donors.FindingsOur analysis shows that low-income countries would need to invest on average 37%, lower-middle income countries 9%, and upper-middle income countries 1%, of their total health spending on PPR each year under the constant scenario to meet the World Bank WHO targets. Donors would need to allocate on average 8% of their total ODA across all sectors to PPR each year to meet their target.ConclusionsThe World Bank WHO targets for PPR will not be met unless low- and middle-income governments and donors spend a much higher share of their funding on PPR. Even under optimistic growth scenarios, low-income and lower-middle income countries will require increased support from global health donors. The donor target cannot be met using the yearly increase in ODA under any scenario. If the country and donor targets are not met, the highest-impact health security measures need to be prioritized for funding. Alternative sources of PPR financing could include global taxation (e.g., on financial transactions, carbon, or airline flights), cancelling debt, and addressing illicit financial flows. There is also a need for continued work on estimating current PPR costs and funding requirements in order to arrive at more enduring and reliable estimates.

Human Papillomavirus Vaccination by Birth Fiscal Year in Japan

The Ministry of Health, Labour, and Welfare (MHLW) of Japan aggregates human papillomavirus (HPV) vaccination data across Japan for each fiscal year (FY) by age at vaccination. Birth FY (BFY)-specific vaccination coverage remains unknown. To calculate the BFY-specific vaccination coverage for each FY and the cumulative first-dose coverage for each BFY in Japan, to understand the generation-specific vaccination coverage, and to estimate the cumulative first-dose coverage of each BFY that would be achieved by FY 2028 vs World Health Organization (WHO) targets. In this cross-sectional study, MHLW-published national age-specific HPV vaccination numbers and demographic data for female individuals were used to calculate the BFY-specific first-dose coverage for each FY and the BFY-specific cumulative first-dose coverage. It was assumed that the BFYs 2007 to 2012 vaccination coverage in FY 2023 to 2028 would remain the same as the vaccination coverage of the same grade in FY 2022 to estimate the cumulative first-dose coverage that would be achieved by FY 2028. Data analysis was performed from December 2023 to January 2024. Two MHLW policy changes were the government's suspension of proactive recommendation for HPV vaccination in June 2013 and the government's resumption of proactive recommendation for HPV vaccination in April 2022. The primary outcome was generation-specific vaccination coverage among female individuals born in BFYs 1994 to 2010 in FYs 2010 to 2022, calculated using reconfigured published data. In this study of vaccination data for 9 414 620 female individuals, the generation-specific vaccination coverage was 71.96% for the vaccination generation (BFYs 1994-1999), 4.62% for the vaccine-suspension generation (BFYs 2000-2003), 16.16% for the generation that received information individually (BFYs 2004-2009), and 2.83% for the vaccine-resumed generation (BFY 2010). HPV routine vaccination coverage was extremely low in BFYs 2000 to 2010 (0.84%-25.21%) vs BFYs 1994 to 1999 (53.31%-79.47%). The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 plateaued at 43.16%. Even after the resumption of MHLW's proactive recommendations, HPV vaccination coverage has only minimally recovered in Japan. The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 is below the WHO target. These findings reveal that stronger cervical cancer control measures are required, particularly for the vaccine-resumed generation, which will plateau at approximately one-half the WHO target values.

Providers and women’s perspectives on opportunities, challenges and recommendations to improve cervical cancer screening in women living with HIV at Mbarara Regional Referral Hospital: a qualitative study

BackgroundCervical cancer screening uptake remains low despite being a critical prevention method for adult women living with HIV(WLHIV). These women experience greater incidence and persistence of high-risk human papillomavirus (HPV) and severe outcomes, including cervical cancer comorbidity and death.ObjectiveWe explored the opportunities, challenges, and recommendations of clinical care providers and WLHIV to improve cervical cancer screening uptake among WLHIV in Southwestern Uganda.MethodsIn a cross-sectional qualitative study from January to June 2021 at Mbarara Regional Referral Hospital, we interviewed six key informant clinical care providers and held four focus group discussions with women living with HIV. Data was coded using Atlas ti software and analysed using thematic inductive analysis.ResultsThe participants identified several prevailing opportunities for cervical cancer screening, including skilled clinical care workers, public awareness for demand creation, optimized clinic flow, provider-led referrals, and peer-led information sharing that ease clinic navigation and shorten participant throughput. However, challenges occurred due to standalone services resulting in double queuing, longer clinic visit hours, missed chances for screening alongside unsupported lower health facilities leading to crowding at the referral hospital, and inadequate patient privacy measures leading to shame and stigma and the misconception that cervical cancer is incurable. Integrating HPV-DNA testing in HIV services was perceived with ambivalence; some participants worried about the quality of sample collection, while others valued the privacy it offered. Optimising self-collected DNA testing and sufficient counselling were recommended to improve cervical cancer screening uptake.ConclusionOpportunities for cervical cancer screening included trained clinical care professionals, increased public awareness, improved clinic flow, provider referrals, and peer education. Challenges, such as unsupported lower-level health facilities, misconceptions, inadequate patient privacy, and uncertainty about integrating HPV-DNA screening into HIV services, were cited. Adequate counselling and self-sample collection were recommended to foster screening. Our findings may guide healthcare programs integrating cervical cancer screening into HIV clinics to reach the 70% World Health Organisation targets by 2030.

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London. Evidence before this study: Blood RNA biomarker signatures and CRP measurements have emerged as potential triage tests for TB, but evidence is mostly limited to their performance in pulmonary TB. Microbiological diagnosis of extrapulmonary TB (EPTB) is made challenging by the need for invasive sampling to obtain tissue from the site of disease. This is compounded by lower sensitivity of confirmatory molecular tests for EPTB compared to their performance in pulmonary disease. We performed a systematic review of diagnostic accuracy studies of blood RNA biomarkers or CRP measurements for EPTB, which could mitigate the need for site-of-disease sampling for the diagnosis of TB. We searched PubMed up to 1 st August 2023, using the following criteria: "extrapulmonary [title/abstract] AND tuberculosis [title/abstract] AND biomarker [title/abstract]". Although extrapulmonary TB was included in several studies, none focused specifically on EPTB or included an adequate number of EPTB cases to provide precise estimates of test accuracy. Added value of this study: To the best of our knowledge, we report the first diagnostic accuracy study of blood RNA biomarkers and CRP for TB among people with EPTB syndromes. We examined the performance of seven previously identified blood RNA biomarkers as triage tests for TB lymphadenitis and TB pericarditis compared to a microbiology reference standard among people referred to hospital for invasive sampling in a high TB and HIV prevalence setting. Multiple blood RNA biomarkers showed comparable diagnostic accuracy to that previously reported for pulmonary TB in both EPTB disease cohorts, irrespective of HIV status. All seven blood RNA biomarkers showed superior diagnostic accuracy to CRP for both lymphadenitis and pericarditis, but failed to meet the combined >90% sensitivity and >70% specificity recommended for a blood-based diagnostic triage test by WHO. Nonetheless, in decision curve analysis, an approach of using the best performing blood RNA biomarker to trigger confirmatory microbiological testing showed superior clinical utility in clinical services seeking to reduce the number needed to test (using invasive confirmatory testing) to less than 4 for each EPTB case detected. If acceptable to undertake invasive testing in more than 4 people for each true case detected, then a test-all approach will provide greater net benefit in this TB/HIV hyperendemic setting.Implications of all the available evidence: Blood RNA biomarkers show some potential as diagnostic triage tests for TB lymphadenitis and TB pericarditis, but do not provide the level of accuracy for blood-based triage tests recommended by WHO for community-based tests. CRP has inferior diagnostic accuracy to blood RNA biomarkers and cannot be recommended for diagnostic triage among people with EPTB syndromes referred for invasive sampling.

Experiences and perspectives regarding human papillomavirus self-sampling in sub-Saharan Africa: A systematic review of qualitative evidence

IntroductionCervical cancer screening coverage remains low in sub-Saharan Africa (SSA) due to limited access and low uptake of available services by women. The use of HPV-based self-sampling intervention for cervical cancer screening has the potential to increase screening coverage in the region. This study aimed to analyse qualitative evidence on the experiences and perspectives of women, healthcare workers, and policymakers regarding HPV self-sampling. MethodsWe reviewed qualitative studies from January 2011 to March 2023 in PubMed, Scopus, Medline Ovid, Cochrane, and WEB of Science databases for articles with qualitative data on HPV self-sampling from different countries in SSA. The socio-ecological model was used to guide data analysis and the study findings. ResultsThirteen qualitative studies were included for analysis, and they revealed themes under the intrapersonal, interpersonal, community, and health systems constructs of the Socio-ecological model. Intrapersonal themes included the acceptability of self-sampling, self-efficacy, and the perceived value of self-sampling. The interpersonal construct had themes such as women's spousal relationships, peer support, and the health worker's relationship with the women. The community construct had two themes: social stigma and misinformation, and the influence of cultural norms and religion. Finally, the health systems construct had themes such as the setting for self-sampling, follow-up availability of treatment services and education and awareness. ConclusionThis study highlights the factors influencing the acceptability and uptake of an HPV-based self-sampling intervention for cervical cancer screening in SSA. Considering these findings when designing interventions in SSA is crucial to ensure acceptance and demand among end-users. Self-sampling interventions offer the potential to reach many unscreened women and increase cervical cancer screening coverage in SSA, which is an essential strategy towards achieving the World Health Organisation's cervical cancer elimination targets by the close of the century.

Provision of cervical cancer services for women living with HIV, Uganda.

To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49years in Uganda, and to analyse the programme data. The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

Transcriptomic signatures of progression to TB disease among close contacts in Brazil.

Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB, so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. Close contacts (≥4 hours exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically-confirmed or clinically-diagnosed pulmonary or extra-pulmonary TB disease through 24 months of follow-up was symptom-triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative PCR. Prognostic performance for incident TB was tested using receiver operating characteristic curve (ROC) analysis at 6, 9, 12, and 24 months of follow-up. Between June 2015 and June 2019, 1,854 close contacts were enrolled; Twenty-five progressed to incident TB, of whom 13 had microbiologically-confirmed disease. Baseline transcriptomic signature scores were measured in 1,789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile (TPP) for a prognostic test through 6 months; three (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the TPP threshold through 12 or more months of follow-up. Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts, to target preventive therapy administration.

Estimating potentially preventable ambient PM2.5-attributable adult deaths by improving air quality in Nepal

Air pollution is an important global environmental health risk factor, with many Asian countries experiencing alarming levels in recent decades. Nepal, a South Asian country, has been facing severe degradation in air quality in recent years, where data are scarce on the health impact of air pollution, especially at sub-national levels. In this study, we investigated ambient fine particulate matter (PM2.5)-attributable adult (≥25 years) premature mortality in Nepal, analyzed its long-term trend, and estimated potentially preventable adult mortality under different improved air quality scenarios defined using the World Health Organization's (WHO) interim targets (IT) and the air quality goal (AQG). Leveraging an open-source high-resolution PM2.5 dataset and an age-specific population dataset, we employed the Global Exposure Mortality Model to estimate mean and 95% confidence intervals of PM2.5-attributable adult mortality using Monte Carlo simulations. We estimated the country-level NCD + LRI (non-communicable diseases and lower respiratory infections) adult deaths attributable to PM2.5 exposure as 48881 (95% CI: 37175−61470), and the PM2.5-attributable NCD + LRI adult mortality rate as 267 (95% CI: 203−335) per 100000 in 2019. The adult mortality burden consistently increased during 2000–2019. Moreover, improving air quality to the WHO ITs and AQG could prevent an estimated 9690 (95% CI: 7698−11812) to 39419 (95% CI: 30311−49277) premature adult deaths across the country in 2019. Our findings suggest that the adult mortality burden due to air pollution in Nepal is substantial, which offers an opportunity to prevent a considerable number of premature adult deaths by mitigating air pollution in the country.

Factors associated with malaria vaccine uptake in Nsanje district, Malawi

BackgroundMalaria remains a significant global health burden affecting millions of people, children under 5 years and pregnant women being most vulnerable. In 2019, the World Health Organization (WHO) endorsed the introduction of RTS,S/AS01 malaria vaccine as Phase IV implementation evaluation in three countries: Malawi, Kenya and Ghana. Acceptability and factors influencing vaccination coverage in implementing areas is relatively unknown. In Malawi, only 60% of children were fully immunized with malaria vaccine in Nsanje district in 2021, which is below 80% WHO target. This study aimed at exploring factors influencing uptake of malaria vaccine and identify approaches to increase vaccination.MethodsIn a cross-sectional study conducted in April–May, 2023, 410 mothers/caregivers with children aged 24–36 months were selected by stratified random sampling and interviewed using a structured questionnaire. Vaccination data was collected from health passports, for those without health passports, data was collected using recall history. Regression analyses were used to test association between independent variables and full uptake of malaria vaccine.ResultsUptake of malaria vaccine was 90.5% for dose 1, but reduced to 87.6%, 69.5% and 41.2% for dose 2, 3, and 4 respectively. Children of caregivers with secondary or upper education and those who attended antenatal clinic four times or more had increased odds of full uptake of malaria vaccine [OR: 2.43, 95%CI 1.08–6.51 and OR: 1.89, 95%CI 1.18–3.02], respectively. Children who ever suffered side-effects following immunization and those who travelled long distances to reach the vaccination centre had reduced odds of full uptake of malaria vaccine [OR: 0.35, 95%CI 0.06–0.25 and OR: 0.30, 95%CI 0.03–0.39] respectively. Only 17% (n = 65) of mothers/caregivers knew the correct schedule for vaccination and 38.5% (n = 158) knew the correct number of doses a child was to receive.ConclusionOnly RTS,S dose 1 and 2 uptake met WHO coverage targets. Mothers/caregivers had low level of information regarding malaria vaccine, especially on numbers of doses to be received and dosing schedule. The primary modifiable factor influencing vaccine uptake was mother/caregiver knowledge about the vaccine. Thus, to increase the uptake Nsanje District Health Directorate should strengthen communities’ education about malaria vaccine. Programmes to strengthen mother/caregiver knowledge should be included in scale-up of the vaccine in Malawi and across sub-Saharan Africa.

Target product profiles: leprosy diagnostics.

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.

Attitude and predictors of exclusive breastfeeding practice among mothers attending under-five welfare clinics in a rural community in Southwestern Nigeria.

Much previous research on exclusive breastfeeding has focused on urban and semi-urban communities, while there is still a paucity of data from rural areas. We assessed the attitude and practice of exclusive breastfeeding and its predictors among mothers attending the under-five welfare clinics in a rural community. A cross-sectional study was conducted among consecutively recruited 217 mothers attending the three health facilities under-five welfare clinics in Ido-Ekiti, Southwest, Nigeria. Information was collected with a semi-structured interviewer-administered questionnaire adapted from previously published research works. Descriptive and inferential statistics were carried out using IBM SPSS Statistics for Windows, Version 26.0. More than half of the mothers, 117(53.9%) were ≥30 years old, and 191(88.0%) were married. Almost all, 216 (99.5%) attended an ante-natal clinic; however, 174(80.2%) delivered in the health facility. The respondent's mean ± SD exclusive breastfeeding attitudinal score was 29.94 ± 2.14 (maximum obtainable score was 36), and the proportion of mothers that practiced exclusive breastfeeding was 40.6%. Married mothers were more likely to practice exclusive breastfeeding than their unmarried counterparts (AOR:6.324, 95%CI:1.809-22.114). The common reasons for not practicing exclusive breastfeeding were work schedule 57(26.3%), cultural beliefs and the need to introduce herbal medicine 32(14.7%), and insufficient breast milk 30(13.8%). This study revealed a good disposition with a suboptimal practice towards exclusive breastfeeding. Also, being married was a positive predictor of exclusive breastfeeding. Therefore, we recommend policies that will improve exclusive breastfeeding among mothers in rural areas, especially those targeting the unmarried, to achieve the World Health Organization's target.

Assessment of Prevelance and Determinants of Exclusive Breastfeeding among Mothers with Infants Aged under Six Months in Wadajir District, Banadir Region, Somalia

Introduction: The Sustainable Development Goals (SDGs) that include ending hunger and improving nutrition, preventing child mortality, and lowering the risk of non-communicable diseases, and promoting cognitive development and education are among the many that breastfeeding is essential to achieving including SDG 2, ending hunger and improving nutrition; SDG 3, preventing child mortality. By 2025, the World Health Organization's (WHO) global nutrition targets to increase at least 50% of infants under six months old to exclusively breastfeed (EBF).&#x0D; Objective: To assess knowledge, determinants and measure prevalence of exclusive breastfeeding among infants aged below six months in Wadajir district, Banadir region- Somalia.&#x0D; Methodology: A hospital-based cross-sectional study design was applied. Systematic sampling method was used to include mothers with infants aged less than 6 months in search of healthcare in Wadajir health center-mother and child health clinic. Study period was August to September 2023. Close ended structured questionnaire was used to collect data. Data was entered into SPSS, multiple analysis was used to correlate independent variables like cultural barriers, maternal barriers, policy barriers, health system barriers with dependent variable of exclusive breastfeeding.&#x0D; Results: The study population comprised 353 mothers; about 65% were aged 25 to 35 years and 76% of them were housewives. The study established that 65% of mothers in Wadajir district who visited the health facility during study period were practicing exclusive breastfeeding for the first six months. On Knowledge, More than half (59%) of the mothers were not aware of the duration of EBF and there was a correlation between EBF and mother education level (P=0.213). there was no relationship between maternal determinants of EBF and low rates of EBF. There was statistically significant correlation (P=0.199) between EBF and the number of pregnancies. Because of having frequent and close pregnancy outweigh EBF and overall breastfeeding, and infant care.&#x0D; Conclusion: There is poor knowledge on exclusive breastfeeding among mothers in Wadajir district, Somalia. Maternal education, the number of children, the place of delivery, and the educational attainment were all found to be related to exclusive breastfeeding.

Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers.

BACKGROUNDNovel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections.METHODSWe applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modeling and network correlation analyses identified 118 differentially expressed proteins, significant through 3 complementary analytical pipelines. Candidate biomarkers were subsequently analyzed in 2 validation cohorts of differing ethnicity using antibody-based proximity extension assays.RESULTSTB-specific host biomarkers were confirmed. A 6-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14, and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts.CONCLUSIONThis biomarker panel exceeds the World Health Organization Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.FUNDINGMedical Research Council (MRC) (MR/R001065/1, MR/S024220/1, MR/P023754/1, and MR/W025728/1); the MRC and the UK Foreign Commonwealth and Development Office; the UK National Institute for Health Research (NIHR); the Wellcome Trust (094000, 203135, and CC2112); Starter Grant for Clinical Lecturers (Academy of Medical Sciences UK); the British Infection Association; the Program for Advanced Research Capacities for AIDS in Peru at Universidad Peruana Cayetano Heredia (D43TW00976301) from the Fogarty International Center at the US NIH; the UK Technology Strategy Board/Innovate UK (101556); the Francis Crick Institute, which receives funding from UKRI-MRC (CC2112); Cancer Research UK (CC2112); and the NIHR Biomedical Research Centre of Imperial College NHS.

Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

The potential role of artificial intelligence in the clinical management of Hansen's disease (leprosy).

Missed and delayed diagnoses of Hansen's disease (HD) are making the battle against it even more complex, increasing its transmission and significantly impacting those affected and their families. This strains public health systems and raises the risk of lifelong impairments and disabilities. Worryingly, the three countries most affected by HD witnessed a growth in new cases in 2022, jeopardizing the World Health Organization's targets to interrupt transmission. Artificial intelligence (AI) can help address these challenges by offering the potential for rapid case detection, customized treatment, and solutions for accessibility challenges-especially in regions with a shortage of trained healthcare professionals. This perspective article explores how AI can significantly impact the clinical management of HD, focusing on therapeutic strategies. AI can help classify cases, ensure multidrug therapy compliance, monitor geographical treatment coverage, and detect adverse drug reactions and antimicrobial resistance. In addition, AI can assist in the early detection of nerve damage, which aids in disability prevention and planning rehabilitation. Incorporating AI into mental health counseling is also a promising contribution to combating the stigma associated with HD. By revolutionizing therapeutic approaches, AI offers a holistic solution to reduce the burden of HD and improve patient outcomes.