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Introduction The rise of antimicrobial resistance represents a critical threat to global health, exacerbated by the excessive and inappropriate dispensing and use of antimicrobial drugs, notably antibiotics, which specifically target bacterial infections. The surge in antibiotic consumption globally is particularly concerning in low-income and middle-income countries (LMICs), where informal healthcare providers (IPs) play a vital role in the healthcare landscape. Often the initial point of contact for healthcare-seeking individuals, IPs play a crucial role in delivering primary care services in these regions. Despite the prevalent dispensing of antibiotics by IPs in many LMICs, as highlighted by existing research, there remains a gap in the comprehensive synthesis of antibiotic dispensing practices and the influencing factors among IPs. Hence, this scoping review seeks to map and consolidate the literature regarding antibiotic dispensing and its drivers among IPs in LMICs.Methods and analysis This review will follow the Joanna Briggs Institute guideline for scoping review. A comprehensive search across nine electronic databases (MEDLINE, EMBASE, SCOPUS, Global Health, CINAHL, Web of Science, LILACS, AJOL and IMSEAR) will be performed, supplemented by manual searches of reference lists of eligible publications. The search strategy will impose no constraints on study design, methodology, publication date or language. The study selection process will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The findings on antibiotic dispensing and its patterns will be synthesised and reported descriptively using tables, visuals and a narrative summary. Additionally, factors influencing antibiotic dispensing will be elucidated through both inductive and deductive content analysis methods.Ethics and dissemination Ethical approval is not required for scoping reviews. The findings will be disseminated through peer-reviewed publications and presentations at relevant conferences.

Abstract Background Indonesia has the second highest incidence of tuberculosis in the world. While 74% of people with tuberculosis in Indonesia first accessed the private health sector when seeking care for their symptoms, only 18% of tuberculosis notifications originate in the private sector. Little is known about the impact of the COVID-19 pandemic on the private sector. Using unannounced standardized patient visits to private providers, we aimed to measure quality of tuberculosis care during the COVID-19 pandemic. Methods A cross-sectional study was conducted using standardized patients in Bandung City, West Java, Indonesia. Ten standardized patients completed 292 visits with private providers between 9 July 2021 and 21 January 2022, wherein standardized patients presented a presumptive tuberculosis case. Results were compared to standardized patients surveys conducted in the same geographical area before the onset of COVID-19. Results Overall, 35% (95% confidence interval (CI): 29.2–40.4%) of visits were managed correctly according to national tuberculosis guidelines. There were no significant differences in the clinical management of presumptive tuberculosis patients before and during the COVID-19 pandemic, apart from an increase in temperature checks (adjusted odds ratio (aOR): 8.05, 95% CI: 2.96–21.9, p

Summary: Background: The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at high risk for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown. Methods: Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression. Findings: DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9–62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5–17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78–0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76–1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92–1.25), although treatment success was higher in the incarcerated population (OR [incarcerated vs. not incarcerated, pre-COVID]: 1.52, 95% CI: 1.39–1.67). Interpretation: Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons. Funding: Canadian Institutes of Health Research (Funding Reference Number: 179418) .

The COVID-19 pandemic is thought to have undone years' worth of progress in the fight against tuberculosis (TB). For instance, in Indonesia, a high TB burden country, TB case notifications decreased by 14% and treatment coverage decreased by 47% during COVID-19. We sought to better understand the impact of COVID-19 on TB case detection using two cross-sectional surveys conducted before (2018) and after the onset of the pandemic (2021). These surveys allowed us to quantify the delays that individuals with TB who eventually received treatment at private providers faced while trying to access care for their illness, their journey to obtain a diagnosis, the encounters individuals had with healthcare providers before a TB diagnosis, and the factors associated with patient delay and the total number of provider encounters. We found some worsening of care seeking pathways on multiple dimensions. Median patient delay increased from 28 days (IQR: 10, 31) to 32 days (IQR: 14, 90) and the median number of encounters increased from 5 (IQR: 4, 8) to 7 (IQR: 5, 10), but doctor and treatment delays remained relatively unchanged. Employed individuals experienced shorter delays compared to unemployed individuals (adjusted medians: -20.13, CI -39.14, -1.12) while individuals whose initial consult was in the private hospitals experienced less encounters compared to those visiting public providers, private primary care providers, and informal providers (-4.29 encounters, CI -6.76, -1.81). Patients who visited the healthcare providers >6 times experienced longer total delay compared to those with less than 6 visits (adjusted medians: 59.40, 95% CI: 35.04, 83.77). Our findings suggest the need to ramp up awareness programs to reduce patient delay and strengthen private provide engagement in the country, particularly in the primary care sector.

Background Pre-COVID-19, individuals with tuberculosis (TB) in Nigeria were often underdiagnosed and untreated. TB services were mostly in the public sector with only 15% of new cases in 2019 reported from the private sector. Reports highlighted challenges in accessing care in the private sector, which accounted for 67% of all initial care-seeking. Our study examined patients’ health seeking pathways for TB in Nigeria’s private sector and explored any changes to care pathways during COVID-19.Methods We conducted 180 cross-sectional surveys and 20 in-depth interviews with individuals having chest symptoms attending 18 high-volume private clinics and hospitals in Kano and Lagos States. Questions focused on sociodemographic characteristics, health-seeking behaviour, and pathways to care during the COVID-19 pandemic. All surveys and interviews were conducted in May 2021.Results Most participants were male (111/180), with an average age of 37. Half (96/180) sought healthcare within a week of symptoms, while few (20/180) waited over 2 months. Individuals testing positive for TB had more health-seeking delays, and those testing negative for TB had more provider delays. On average, participants visited two providers in Kano and 1.69 in Lagos, with 61 of 180 in Kano and 48 of 180 in Lagos visiting other providers before the recruitment facility. Private providers were the initial encounters for most participants (60/180 in Kano, 83/180 in Lagos). Most respondents (164/180) experienced short-lived pandemic-related restrictions, affecting access to transportation, and closed facilities.Conclusions This study showed a few challenges in accessing TB care, necessitating continued investment in healthcare infrastructure and resources, particularly in the private sector. Understanding the different care pathways and delays in care provides opportunities for targeted interventions to improve deployment of services closer to where patients first seek care.

Abstract Background Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB). Methods We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays. Results A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI − 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54–4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82–53.37) and treatment initiation delay by 45.32 days (95% CI 30.27–60.37) in comparison to any culture DST methods. Conclusions Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.

The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs—Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam—to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services.

Zimmer et al. discuss the importance of cough assessment in clinical management of tuberculosis (TB). They describe how acoustic epidemiology, which uses recording devices and artificial intelligence to detect, record and analyze cough, can be used in TB control and individual patient management.

Abstract Background Evaluating the accuracy of extrapulmonary tuberculosis (TB) tests is challenging due to lack of a gold standard. Latent class analysis (LCA), a statistical modeling approach, can adjust for reference tests’ imperfect accuracies to produce less biased test accuracy estimates than those produced by commonly used methods like composite reference standards (CRSs). Our objective is to illustrate how Bayesian LCA can address the problem of an unavailable gold standard and demonstrate how it compares to using CRSs for extrapulmonary TB tests. Methods We re-analyzed a dataset of presumptive extrapulmonary TB cases in New Delhi, India, for three forms of extrapulmonary TB. Results were available for culture, smear microscopy, Xpert MTB/RIF, and a non-microbiological test, cytopathology/histopathology, or adenosine deaminase (ADA). A diagram was used to define assumed relationships between observed tests and underlying latent variables in the Bayesian LCA with input from an inter-disciplinary team. We compared the results to estimates obtained from a sequence of CRSs defined by increasing numbers of positive reference tests necessary for positive disease status. Results Data were available from 298, 388, and 230 individuals with presumptive TB lymphadenitis, meningitis, and pleuritis, respectively. Using Bayesian LCA, estimates were obtained for accuracy of all tests and for extrapulmonary TB prevalence. Xpert sensitivity neared that of culture for TB lymphadenitis and meningitis but was lower for TB pleuritis, and specificities of all microbiological tests approached 100%. Non-microbiological tests’ sensitivities were high, but specificities were only moderate, preventing disease rule-in. CRSs’ only provided estimates of Xpert and these varied widely per CRS definition. Accuracy of the CRSs also varied by definition, and no CRS was 100% accurate. Conclusion Unlike CRSs, Bayesian LCA takes into account known information about test performance resulting in accuracy estimates that are easier to interpret. LCA should receive greater consideration for evaluating extrapulmonary TB diagnostic tests.

As the first point of care for many healthcare seekers, private pharmacies play an important role in tuberculosis (TB) care. However, previous studies in India have showed that private pharmacies commonly dispense symptomatic treatments and broad-spectrum antibiotics over-the-counter (OTC), rather than referring patients for TB testing. Such inappropriate management by pharmacies can delaye TB diagnosis. We assessed medical advice and OTC drug dispensing practices of pharmacists for standardized patients presenting with classic symptoms of pulmonary TB (case 1) and for those with sputum smear positive pulmonary TB (case 2), and examined how practices have changed over time in an urban Indian site. We examined how and whether private pharmacies improved practices for TB in 2019 compared to a baseline study conducted in 2015 in the city of Patna, using the same survey sampling techniques and study staff. The proportion of patient-pharmacist interactions that resulted in correct or ideal management, as well as the proportion of interactions resulting in antibiotic, quinolone, and corticosteroid are presented, with standard errors clustered at the provider level. To assess the difference in case management and the use of drugs across the two cases by round, a difference in difference (DiD) model was employed. A total of 936 SP interactions were completed over both rounds of survey. Our results indicate that across both rounds of data collection, 331 of 936 (35%; 95% CI: 32-38%) of interactions were correctly managed. At baseline, 215 of 500 (43%; 95% CI: 39-47%) of interactions were correctly managed whereas 116 of 436 (27%; 95% CI: 23-31%) were correctly managed in the second round of data collection. Ideal management, where in addition to a referral, patients were not prescribed any potentially harmful medications, was seen in 275 of 936 (29%; 95% CI: 27-32%) of interactions overall, with 194 of 500 (39%; 95% CI: 35-43%) of interactions at baseline and 81 of 436 (19%; 95% CI: 15-22%) in round 2. No private pharmacy dispensed anti-TB medications without a prescription. On average, the difference in correct case management between case 1 vs. case 2 dropped by 20 percent points from baseline to the second round of data collection. Similarly, ideal case management decreased by 26 percentage points between rounds. This is in contrast with the dispensation of medicines, which had the opposite effect between rounds; the difference in dispensation of quinolones between case 1 and case 2 increased by 14 percentage points, as did corticosteroids by 9 percentage points, antibiotics by 25 percentage points and medicines generally by 30 percentage points. Our standardised patient study provides valuable insights into how private pharmacies in an Indian city changed their management of patients with TB symptoms or with confirmed TB over a 5-year period. We saw that overall, private pharmacy performance has weakened over time. However, no OTC dispensation of anti-TB medications occurred in either survey round. As the first point of contact for many care seekers, continued and sustained efforts to engage with Indian private pharmacies should be prioritized.

Nigeria has the second largest share of undiagnosed TB cases in the world and a large private health sector estimated to be the point of initial care-seeking for 67% of TB patients. There is evidence that COVID-19 restrictions disrupted private healthcare provision, but insufficient data on how private healthcare provision changed as a result of the pandemic. We conducted qualitative interviews and a survey to assess the impact of the pandemic, and government response on private healthcare provision, and the disruptions providers experienced, particularly for TB services. Using mixed methods, we targeted policymakers, and a network of clinical facilities, laboratories, community pharmacies, and medicine vendors in Kano and Lagos, Nigeria. We interviewed 11 policymakers, surveyed participants in 2,412 private facilities. Most (n = 1,676, 70%) facilities remained open during the initial lockdown period, and most (n = 1,667, 69%) offered TB screening. TB notifications dipped during the lockdown periods but quickly recovered. Clinical facilities reported disruptions in availability of medical supplies, staff, required renovations, patient volume and income. Few private providers (n = 119, 11% in Kano; n = 323, 25% in Lagos) offered any COVID-19 screening up to the time of the survey, as these were only available in designated facilities. These findings aligned with the interviews as policymakers reported a gradual return to pre-COVID services after initial disruptions and diversion of resources to the pandemic response. Our results show that COVID-19 and control measures had a temporary impact on private sector TB care. Although some facilities saw decreases in TB notifications, private facilities continued to provide care for individuals with TB who otherwise might have been unable to seek care in the public sector. Our findings highlight resilience in the private sector as they recovered fairly quickly from pandemic-related disruptions, and the important role private providers can play in supporting TB control efforts.

Efficacy and safety data on quadrivalent influenza vaccines (QIVs) for immunization of Indian children are scarce. This phase 3, registration study evaluated the immunogenicity, safety, and tolerability of a QIV in Indian children aged 6–35 months (Group 1) and 3–17 y (Group 2). Subjects received one or two doses (0.5 mL each) of the study vaccine based on their priming status. Immunogenicity (post-vaccination geometric mean fold increase in hemagglutination inhibition [HI] titers and proportion of patients with seroprotection and seroconversion against the four influenza strains), unsolicited adverse events (AEs), and tolerability were analyzed. Among 118 subjects enrolled in each group, the geometric mean(standard deviation) fold increase in HI titers against A(H3N2), A(H1N1), B(Victoria), and B(Yamagata) strains were 31.7(5.33), 10.5(6.06), 4.1(5.70), and 8.6(5.34) in Group 1 and 14.0(4.37), 9.2(4.26), 14.3(6.73), and 14.4(5.41) in Group 2, respectively. Seroprotection was achieved by 91.2%, 83.3%, 41.2%, and 68.4% subjects in Group 1 and 100%, 95.8%, 73.7%, and 89.8% subjects in Group 2, respectively. Seroconversion was achieved by 87.7%, 66.7%, 41.2%, and 64.9% subjects in Group 1 and 89.0%, 78.8%, 69.5%, and 75.4% subjects in Group 2, respectively. Vaccination site pain and fever were the most common local and systemic reactions, respectively. Systemic reactions were more frequent in Group 1 (16.9% vs 7.6%). Most subjects (>90%) did not experience inconvenience within 7 d of vaccination;

Background There are few rigorous studies comparing quality of tuberculosis (TB) care in public versus private sectors.Methods We used standardised patients (SPs) to measure technical quality and patient experience in a sample of private and public facilities in Mumbai.Results SPs presented a ‘classic, suspected TB’ scenario and a ‘recurrence or drug-resistance’ scenario. In the private sector, SPs completed 643 interactions. In the public sector, 164 interactions. Outcomes included indicators of correct management, medication use and client experience. Public providers used microbiological testing (typically, microscopy) more frequently, in 123 of 164 (75%; 95% CI 68% to 81%) vs 223 of 644 interactions (35%; 95% CI 31% to 38%) in the private sector. Private providers were more likely to order chest X-rays, in 556 of 639 interactions (86%; 95% CI 84% to 89%). According to national TB guidelines, we found higher proportions of correct management in the public sector (75% vs 35%; (adjusted) difference 35 percentage points (pp); 95% CI 25 to 46). If X-rays were considered acceptable for the first case but drug-susceptibility testing was required for the second case, the private sector correctly managed a slightly higher proportion of interactions (67% vs 51%; adjusted difference 16 pp; 95% CI 7 to 25). Broad-spectrum antibiotics were used in 76% (95% CI 66% to 84%) of the interactions in public hospitals, and 61% (95% CI 58% to 65%) in private facilities. Costs in the private clinics averaged rupees INR 512 (95% CI 485 to 539); public facilities charged INR 10. Private providers spent more time with patients (4.4 min vs 2.4 min; adjusted difference 2.0 min; 95% CI 1.2 to 2.9) and asked a greater share of relevant questions (29% vs 43%; adjusted difference 13.7 pp; 95% CI 8.2 to 19.3).Conclusions While the public providers did a better job of adhering to national TB guidelines (especially microbiological testing) and offered less expensive care, private sector providers did better on client experience.

Background: India’s dominant private healthcare sector is the destination for 60–85% of initial tuberculosis care-seeking. The COVID-19 pandemic in India drastically affected TB case notifications in the first half of 2020. In this survey, we assessed the impact of the first wave of COVID-19 in India on private providers, and changes they adopted in their practice due to the pandemic. Methods: The Joint Effort for Elimination of TB (JEET) is a nationwide Global Fund project implemented across 406 districts in 23 states to extend quality TB services to patients seeking care in private sector. We conducted a rapid survey of 11% (2,750) of active providers engaged under JEET’s intense Patient Provider Support Agency (PPSA) model across 15 Indian states in Q1 (February–March) of 2021. Providers were contacted in person or telephonically, and consenting participants were interviewed using a web-based survey tool. Responses from participants were elicited on their practice before COVID-19, during the 2020 lockdowns (March–April 2020) and currently (Q1 2021). Data were adjusted for survey design and non-response, and results were summarised using descriptive statistics and logistic regression. Results: Of the 2,750 providers sampled, 2,011 consented and were surveyed (73 % response). Nearly 50 % were between 30 and 45 years of age, and 51 % were from Uttar Pradesh, Maharashtra and Gujarat. Seventy percent of providers reported reduced daily out-patient numbers in Q1 2021 compared to pre-COVID times. During the lockdown, 898 (40 %) of providers said their facilities were closed, while 323 (11 %) offered limited services including teleconsultation. In Q1 2021, 88 % of provider facilities were fully open, with 10 % providing adjusted services, and 4 % using teleconsultation. Only 2 % remained completely closed. Majority of the providers (92 %) reported not experiencing any delays in TB testing in Q1 2021 compared to pre-COVID times. Only 6 % reported raising costs at their clinic, mostly to cover personal protective equipment (PPE) and other infection control measures, although 60–90 % implemented various infection control measures. Thirty-three percent of TB providers were ordering COVID-19 testing, in addition to TB testing.To adapt, 82% of survey providers implemented social distancing and increased timing between appointments and 83% started conducting temperature checks, with variation by state and provider type, while 89% adopted additional sanitation measures in their facilities. Furthermore, 62% of providers started using PPE, and 13% made physical changes (air filters, isolation of patient areas) to their clinic to prevent infection. Seventy percent of providers stated that infection control measures could decrease TB transmission. Conclusion: Although COVID-19 restrictions resulted in significant declines in patient turn-out at private facilities, our analysis showed that most providers were open and costs for TB care remained mostly the same in Q1 2021. As result of the COVID-19 pandemic, several positive strategies have been adapted by the private sector TB care providers. Since the subsequent COVID-19 waves were more severe or widespread, additional work is needed to assess the impact of the pandemic on the private health sector.

Currently, the diagnosis of tuberculosis (TB) is mainly based on the comprehensive consideration of the patient's symptoms and signs, laboratory examinations and chest radiography (CXR). CXR plays a pivotal role to support the early diagnosis of TB, especially when used for TB screening and differential diagnosis. However, high cost of CXR hardware and shortage of certified radiologists poses a major challenge for CXR application in TB screening in resource limited settings. The latest development of artificial intelligence (AI) combined with the accumulation of a large number of medical images provides new opportunities for the establishment of computer-aided detection (CAD) systems in the medical applications, especially in the era of deep learning (DL) technology. Several CAD solutions are now commercially available and there is growing evidence demonstrate their value in imaging diagnosis. Recently, WHO published a rapid communication which stated that CAD may be used as an alternative to human reader interpretation of plain digital CXRs for screening and triage of TB.

Background & objectives: In India, the burden of Plasmodium vivax malaria has been projected to be highest in some areas. This study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate (AM) 37.5 mg and piperaquine phosphate 187.5 mg (PQP) dispersible tablets and (not with) chloroquine in the treatment of uncomplicated vivax malaria in pediatric patients. Methods: This multicentric, open-label trial was carried out at 12 sites in India. A total of 164 patients aged 6 months to 12 years with P. vivax malaria were randomized in a ratio of 2:1 to AM-PQP (111 patients) or chloroquine (53 patients) arms. The duration of follow up was 42 days. Results: At 72 hours, the proportion of a parasitaemic and afebrile patients was 100% in both treatment arms in per protocol (PP) population, and 98.2% and 100% [95% CI: -1.8 (-6.33 to 5.08)] in AM-PQP and chloroquine arms, respectively, in intent to treat (ITT) population. The efficacy and safety of AM-PQP was found to be comparable to chloroquine in the treatment of uncomplicated P. vivax malaria in pediatric patients. Overall, the cure rate at Day 28 and 42 was >95% for both AM-PQP or CQ. The commonly reported clinical adverse event was vomiting. No patient was discontinued for any QTc abnormality. Interpretation & conclusion: The efficacy and safety of FDC of arterolane maleate and piperaquine phosphate was found to be comparable to chloroquine for treatment of uncomplicated P. vivax malaria in pediatric patients.

Global health research is mired by inequities, some of which are linked to current approaches to research funding. The role of funders and donors in achieving greater equity in global health research needs to be clearly defined. Imbalances of power and resources between high income countries (HICs) and low- and middle-income countries (LMICs) is such that many funding approaches do not centre the role of LMIC researchers in shaping global health research priorities and agenda. Relative to need, there is also disparity in financial investment by LMIC governments in health research. These imbalances put at a disadvantage LMIC health professionals and researchers who are at forefront of global health practice. Whilst many LMICs do not have the means (due to geopolitical, historical, and economic reasons) for direct investment, if those with means were to invest more of their own funds in health research, it may help LMICs become more self-sufficient and shift some of the power imbalances. Funders and donors in HICs should address inequities in their approach to research funding and proactively identify mechanisms that assure greater equity-including via direct funding to LMIC researchers and direct funding to build local LMIC-based, led, and run knowledge infrastructures. To collectively shape a new approach to global health research funding, it is essential that funders and donors are part of the conversation. This article provides a way to bring funders and donors into the conversation on equity in global health research.

With the Covid-19 pandemic and the introduction of the WHO's Essential Diagnostics List (EDL), increasing global attention is focused on the crucial role of diagnostics in achieving universal health coverage. To create national EDLs and to aid health system planning, it is vital to understand the most common conditions with which people present at primary care health facilities. We undertook a systematic review of the most common reasons for primary care visits in low- and middle-income countries. Six databases were searched for articles published between January 2009 and December 2019, with the search updated on MEDLINE to January 2021. Data on the most common patient reasons for encounter (RFEs) and provider diagnoses were collected. 17 of 22,279 screened articles were included. Most studies used unvalidated diagnostic classification systems or presented provider diagnosis data grouped by organ system, rather than presenting specific diagnoses. No studies included data from low-income countries. Only four studies (from Brazil, India, Nigeria and South Africa) using the ICPC-2 classification system contained RFE and provider diagnosis data and could be pooled. The top five RFEs from the four studies were headache, fever, back or low back symptom, cough and pain general/multiple sites. The top five diagnoses were uncomplicated hypertension, upper respiratory tract infection, type 2 diabetes, malaria and health maintenance/prevention. No psychological symptoms were among the top 10 pooled RFEs. There was more variation in top diagnoses between studies than top RFEs, showing the importance of creating location-specific lists of essential diagnostics for primary care. Future studies should aim to sample primary care facilities from across their country of study and use ICPC-3 to report both patient RFEs and provider diagnoses.

The BCG vaccine is a widely given vaccine against tuberculosis (TB), yet studies on effectiveness have shown considerable heterogeneity; as a result, BCG vaccine policies vary greatly across the globe and change across geography, and with time and disease burden. The recently updated third BCG World Atlas (www.bcgatlas.org) is a publicly available online database with information on BCG practices across 194 countries. This helpful resource has been used for over 10 years to support clinicians, TB researchers and TB vaccine development worldwide. Here, we summarise main findings from the third BCG Atlas’ most recent update which included additional data collected around BCG strain type, vaccine stockouts and associated changes. Longitudinal analysis enables evaluation of changes in TB incidence over time, a method becoming more common in legislation interventions. A large number of countries in the BCG Atlas (156/194 countries) maintain universal neonatal BCG vaccination, of which 51 are considered low TB burden countries. We demonstrate the majority of countries who changed their national policy moved to targeted vaccination for high-risk groups, were in Europe and also had significant decreases in TB incidence both before and after policy change. Globally, the most common BCG strain continues to be the Danish strain, despite its worldwide manufacturing interruption in 2015. Substantial variation and disproportionality exists in which regions were most affected by stockouts between 2009 and 2019. Tracking and understanding the reasoning behind changes to national BCG practices and their impact on TB burden is critical for decision makers as they contemplate how to include BCG vaccination in future immunisation guidelines in low and high TB burden countries.

The COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019. This is due in large part to the efforts of intermediary agencies, which aggregate demand from private providers. The COVID-19 pandemic has put these gains at risk over the past year. In this rapid assessment, representatives of 15 intermediary agencies from seven countries that are considered the highest priority for PPM in TB care (the Big Seven) share their views on the impact of COVID-19 on their programs, the private providers operating under their PPM schemes, and their private TB clients.All intermediaries reported a drop in TB testing and notifications, and the closure of some private practices. While travel restrictions and the fear of contracting COVID-19 were the main contributing factors, there were also unanticipated expenses for private providers, which were transferred to patients via increased prices. Intermediaries also had their routine activities disrupted and had to shift tasks and budgets to meet the new needs. However, the intermediaries and their partners rapidly adapted, including an increased use of digital tools, patient-centric services, and ancillary support for private providers.Despite many setbacks, the COVID-19 pandemic has underlined the importance of effective private sector engagement. The robust approach to fight COVID-19 has shown the possibilities for ending TB with a similar approach, augmented by the digital revolution around treatment and diagnostics and the push to decentralize health services.

BackgroundSuboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).Methods and findingsIn this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon.ConclusionsDCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment.Trial registrationclinicaltrials.gov NCT03519425.

BackgroundWe assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred.Methods and findingsWe performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches.ConclusionsA significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Rates of depression in youth are continuing to increase at a steady rate, yet these youth often do not receive mental health services (Bertha & Balázs, 2013; Thomas et al., 2011). Schools are an ideal setting to connect youth to mental health services; however, many barriers exist with respect to schools having adequate resources and access to the appropriate levels of services (Duong et al., 2021; Owens & Peltier, 2002). Schools may collaborate with local community providers with available resources to address these gaps. The current article describes the pilot of a school-based mental health promotion program intended to reduce depression in youth by promoting access to care through referrals to community providers. Data were collected, via self-report measures, every 3 months for 12 months from students from three middle and high schools in North Texas. The students (N = 88) enrolled in this program experienced significant reductions in their depression symptoms at the end of 12 months. This program highlights the importance of school-community partnerships to promote access to care to address mental health concerns. The results from our pilot study demonstrate the feasibility and the potential of school-based programs in improving the mental health of youth in schools through community partnership.

Abstract Background India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). Methods We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. Results Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] − $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. Conclusions Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.

BACKGROUND: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. OBJECTIVES: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. METHODS: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. RESULTS: Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. CONCLUSIONS: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Background South Africa has high burdens of tuberculosis (TB) and TB-HIV, yet the quality of patient care in the private sector is unknown. We describe quality of TB and TB-HIV care among private general practitioners (GPs) in two South African cities using standardised patients (SPs).Methods Sixteen SPs presented one of three cases during unannounced visits to private GPs in selected high-TB burden communities in Durban and Cape Town: case 1, typical TB symptoms, HIV-positive; case 2, TB-specified laboratory report, HIV-negative and case 3, history of incomplete TB treatment, HIV-positive. Clinical practices were recorded in standardised exit interviews. Ideal management was defined as relevant testing or public sector referral for any reason. The difference between knowledge and practice (know-do gap) was assessed through case 1 vignettes among 25% of GPs. Factors associated with ideal management were assessed using bivariate logistic regression.Results 511 SP visits were completed with 212 GPs. Respectively, TB and HIV were ideally managed in 43% (95% CI 36% to 50%) and 41% (95% CI 34% to 48%) of case 1, 85% (95% CI 78% to 90%) and 61% (95% CI 73% to 86%) of case 2 and 69% (95% CI 61% to 76%) and 80% (95% CI 52% to 68%) of case 3 presentations. HIV status was queried in 35% (95% CI 31% to 39%) of visits, least with case 1 (24%, 95% CI 18% to 30%). The difference between knowledge and practice was 80% versus 43% for TB and 55% versus 37% for HIV, resulting in know-do gaps of 37% (95% CI 19% to 55%) and 18% (95% CI −1% to 38%), respectively. Ideal TB management was associated with longer visit time (OR=1.1, 95% CI 1.1 to 1.2), female GPs (3.2, 95% CI 2.0 to 5.1), basic symptom inquiry (2.0, 95% CI 1.7 to 2.3), HIV-status inquiry (OR=11.2, 95% CI 6.4 to 19.6), fewer medications dispensed (OR=0.6, 95% CI 0.5 to 0.7) and Cape Town (OR=2.2, 95% CI 1.5 to 3.1). Similar associations were observed for HIV.Conclusions Private providers ideally managed TB more often when a diagnosis or history of TB was implied or provided. Management of HIV in the context of TB was less than optimal.

Seye Abimbola and co-authors argue for a transformation in global health research and practice in the post-COVID-19 world.

BackgroundA key component of the WHO End TB Strategy is quality of care, for which case fatality is a critical marker. Half of India's nearly 3 million TB patients are treated in the highly unregulated private sector, yet little is known about the outcomes of these patients. Using a retrospective cohort design, we estimated the case fatality ratio (CFR) and rate of recurrent TB among patients managed in the private healthcare sector in Patna, India.MethodsWorld Health Partners' Private Provider Interface Agencies (PPIA) pilot project in Patna has treated 89,906 private sector TB patients since 2013. A random sample of 4,000 patients treated from 2014 to 2016 were surveyed in 2018 for case fatality and recurrent TB. CFR is defined as the proportion of patients who die during the period of interest. Treatment CFRs, post-treatment CFRs and rates of recurrent TB were estimated. Predictors for fatality and recurrence were identified using Cox proportional hazards modelling. Survey non-response was adjusted for using inverse probability selection weighting.ResultsThe survey response rate was 56.0%. The weighted average follow-up times were 8.7 months in the treatment phase and 26.4 months in the post-treatment phase. Unobserved patients were more likely to have less than one month of treatment adherence (32.0% vs. 13.5%) and were more likely to live in rural Patna (21.9% vs. 15.0%). The adjusted treatment phase CFR was 7.27% (5.97%, 8.49%) and at 24 months post-treatment was 3.32% (2.36%, 4.42%). The adjusted 24 month post-treatment phase recurrent TB rate was 3.56% (2.54%, 4.79%).ConclusionsOur cohort study provides critical estimates of TB patient outcomes in the Indian private sector, and accounts for selection bias. Patients in the private sector in Patna experienced a moderate treatment CFR but rates of recurrent TB and post-treatment fatality were low.

The advent of affordable, portable ultrasound devices has led to increasing interest in the use of point-of-care ultrasound (POCUS) for the detection of pulmonary TB (PTB). We undertook a systematic review of the diagnostic accuracy of POCUS for PTB. Five databases were searched for articles published between January 2010 and June 2020. Risk of bias was assessed using QUADAS-2. Data on sensitivity and specificity of individual lung ultrasound findings were collected, with variable reference standards including PCR and sputum smear microscopy. Six of 3,919 reviewed articles were included: five in adults and one in children, with a total sample size of 564. Studies had high risk of bias in many domains. In adults, subpleural nodule and lung consolidation were the lung ultrasound findings with the highest sensitivities, ranging from 72.5% to 100.0% and 46.7% to 80.4%, respectively. Only one study reported specificity data. Variability in sensitivity may be due to variable reference standards or may imply operator dependence. There is insufficient evidence to judge the diagnostic accuracy of POCUS for PTB. There is also no consensus on the optimal protocols for acquiring and analysing POCUS images for PTB. New studies which minimise potential sources of bias are required to further assess the diagnostic accuracy of POCUS for PTB.