Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). METHODS AND FINDINGS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

Disparities in SARS-CoV-2 Infection by Race, Ethnicity, Language, and Social Vulnerability: Evidence from a Citywide Seroprevalence Study in Massachusetts, USA.

OBJECTIVES: Uncovering and addressing disparities in infectious disease outbreaks require a rapid, methodical understanding of local epidemiology. We conducted a seroprevalence study of SARS-CoV-2 infection in Holyoke, Massachusetts, a majority Hispanic city with high levels of socio-economic disadvantage to estimate seroprevalence and identify disparities in SARS-CoV-2 infection. METHODS: We invited 2000 randomly sampled households between 11/5/2020 and 12/31/2020 to complete questionnaires and provide dried blood spots for SARS-CoV-2 antibody testing. We calculated seroprevalence based on the presence of IgG antibodies using a weighted Bayesian procedure that incorporated uncertainty in antibody test sensitivity and specificity and accounted for household clustering. RESULTS: Two hundred eighty households including 472 individuals were enrolled. Three hundred twenty-eight individuals underwent antibody testing. Citywide seroprevalence of SARS-CoV-2 IgG was 13.1% (95% CI 6.9-22.3) compared to 9.8% of the population infected based on publicly reported cases. Seroprevalence was 16.1% (95% CI 6.2-31.8) among Hispanic individuals compared to 9.4% (95% CI 4.6-16.4) among non-Hispanic white individuals. Seroprevalence was higher among Spanish-speaking households (21.9%; 95% CI 8.3-43.9) compared to English-speaking households (10.2%; 95% CI 5.2-18.0) and among individuals in high social vulnerability index (SVI) areas based on the CDC SVI (14.4%; 95% CI 7.1-25.5) compared to low SVI areas (8.2%; 95% CI 3.1-16.9). CONCLUSIONS: The SARS-CoV-2 IgG seroprevalence in a city with high levels of social vulnerability was 13.1% during the pre-vaccination period of the COVID-19 pandemic. Hispanic individuals and individuals in communities characterized by high SVI were at the highest risk of infection. Public health interventions should be designed to ensure that individuals in high social vulnerability communities have access to the tools to combat COVID-19.

A Cross-Sectional Analysis of Self-Reported Needs and Health Service Utilization Among Transgender Women in Lima, Perú.

Purpose: Globally, transgender women (TGW) experience wide-ranging barriers to health and care, with disproportionately high risks of infectious and chronic diseases. Yet, research on transgender populations' access to care in low- and middle-income countries remains limited, focused on human immunodeficiency virus (HIV) infection, and assesses TGW as a homogenous group. We analyzed morbidity and health service uptake patterns among TGW in Lima, Perú, to understand health outreach and service needs to inform targeting and design of community-level interventions. Methods: This cross-sectional study surveyed a convenience sample of 301 TGW in metropolitan Lima during September-October 2020. We report descriptive statistics and bivariable and multivariable regression model results as adjusted prevalence ratios (aPRs). Results: Health coverage and access to care were suboptimal. Less education and older age were positively associated with illness and negatively associated with HIV and tuberculosis (TB) testing. In the first study to quantitatively examine health utilization by gender identity subgroup (i.e., woman, trans or transgender, transsexual, "transformista," "travesti," and other) in Perú, TGW who identified as women were more likely to ever test for HIV (aPR = 1.49, 95% confidence interval [CI]: 1.16-1.91) and use pre-exposure prophylaxis (PrEP) (aPR = 2.36, 95% CI: 1.15-4.80). Both awareness and interest regarding PrEP were low, as was usage among those who were interested in taking PrEP. Conclusion: Public health efforts should be tailored to meet TGW's diverse needs, expand TB testing, bridge the gap between PrEP interest and use, and increase insurance coverage and access to trans-friendly services for improved health.

Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru.

Widely available and reliable testing for SARS-CoV-2 is essential for the public health response to the COVID-19 pandemic. We estimated the diagnostic performance of reverse transcription PCR (RT-PCR) performed on saliva and the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab compared to the reference standard, nasopharyngeal swab (NP) RT-PCR. We enrolled participants living and/or seeking care in health facilities in North Lima, Peru from November 2020 to January 2021. Consenting participants underwent same-day RT-PCR on both saliva and nasopharyngeal swab specimens, antigen testing on a nasopharyngeal swab specimen, pulse oximetry, and standardized symptom assessment. We calculated sensitivity, specificity, and predictive values for the nasopharyngeal antigen and saliva RT-PCR compared to nasopharyngeal RT-PCR. Of 896 participants analyzed, 567 (63.3%) had acute signs/symptoms of COVID-19. The overall sensitivity and specificity of saliva RT-PCR were 85.8% and 98.1%, respectively. Among participants with and without acute signs/symptoms of COVID-19, saliva sensitivity was 87.3% and 37.5%, respectively. Saliva sensitivity was 97.4% and 56.0% among participants with cycle threshold (CT) values of ≤30 and >30 on nasopharyngeal RT-PCR, respectively. The overall sensitivity and specificity of nasopharyngeal antigen were 73.2% and 99.4%, respectively. The sensitivity of the nasopharyngeal antigen test was 75.1% and 12.5% among participants with and without acute signs/symptoms of COVID-19, and 91.2% and 26.7% among participants with CT values of ≤30 and >30 on nasopharyngeal RT-PCR, respectively. Saliva RT-PCR achieved the WHO-recommended threshold of >80% for sensitivity for the detection of SARS-CoV-2, while the SD Biosensor nasopharyngeal antigen test did not. IMPORTANCE In this diagnostic validation study of 896 participants in Peru, saliva reverse transcription PCR (RT-PCR) had >80% sensitivity for the detection of SARS-CoV-2 among all-comers and symptomatic individuals, while the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab had <80% sensitivity, except for participants whose same-day nasopharyngeal RT-PCR results showed cycle threshold values of <30, consistent with a high viral load in the nasopharynx. The specificity was high for both tests. Our results demonstrate that saliva sampling could serve as an alternative noninvasive technique for RT-PCR diagnosis of SARS-CoV-2. The role of nasopharyngeal antigen testing is more limited; when community transmission is low, it may be used for mass screenings among asymptomatic individuals with high testing frequency. Among symptomatic individuals, the nasopharyngeal antigen test may be relied upon for 4 to 8 days after symptom onset, or in those likely to have high viral load, whereupon it showed >80% sensitivity.

Observational stepped-wedge analysis of a community health worker-led intervention for diabetes and hypertension in rural Mexico.

OBJECTIVES: There is emerging interest and data supporting the effectiveness of community health workers (CHWs) in non-communicable diseases (NCDs) in low/middle-income countries (LMICs). This study aimed to determine whether a CHW-led intervention targeting diabetes and hypertension could improve markers of clinical disease control in rural Mexico. DESIGN AND SETTING: A prospective observational stepped-wedge study was conducted across seven communities in rural Chiapas, Mexico from March 2014 to April 2018. PARTICIPANTS: 149 adults with hypertension and/or diabetes. INTERVENTION: This study was conducted in the context of the programmatic roll-out of an accompaniment-based CHW-led intervention designed to complement comprehensive primary care for adults with diabetes and/or hypertension. Implementation occurred sequentially at 3-month intervals with point-of-care data collected at baseline and every 3 months thereafter for 12 months following roll-out in all communities. OUTCOME MEASURES: Primary outcomes were glycated haemoglobin (HbA1c) and systolic blood pressure (SBP), overall and stratified by baseline disease control. We conducted an individual-level analysis using mixed effects regression, adjusting for time, cohort and clustering at the individual and community levels. RESULTS: Among patients with diabetes, the CHW-led intervention was associated with a decrease in HbA1c of 0.35%; however, CIs were wide (95% CI -0.90% to 0.20%). In patients with hypertension, there was a 4.7 mm Hg decrease in SBP (95% CI -8.9 to -0.6). In diabetic patients with HbA1c ≥9%, HbA1c decreased by 0.96% (95% CI -1.69% to -0.23%), and in patients with uncontrolled hypertension, SBP decreased by 10.2 mm Hg (95% CI -17.7 to -2.8). CONCLUSIONS: We found that a CHW-led intervention resulted in clinically meaningful improvement in disease markers for patients with diabetes and hypertension, most apparent among patients with hypertension and patients with uncontrolled disease at baseline. These findings suggest that CHWs can play a valuable role in supporting NCD management in LMICs. TRIAL REGISTRATION NUMBER: NCT02549495.

Outcomes of a primary care mental health implementation program in rural Rwanda: A quasi-experimental implementation-effectiveness study.

INTRODUCTION: To address the know-do gap in the integration of mental health care into primary care in resource-limited settings, a multi-faceted implementation program initially designed to integrate HIV/AIDS care into primary care was adapted for severe mental disorders and epilepsy in Burera District, Rwanda. The Mentoring and Enhanced Supervision at Health Centers (MESH MH) program supported primary care-delivered mental health service delivery scale-up from 6 to 19 government-run health centers over two years. This quasi-experimental study assessed implementation reach, fidelity, and clinical outcomes at health centers supported by MESH MH during the scale up period. METHODS: MESH MH consisted of four strategies to ensure the delivery of the priority care packages at health centers: training; supervision and mentorship; audit and feedback; and systems-based quality improvement (QI). Implementation reach (service use) across the 19 health centers supported by MESH MH during the two year scale-up period was described using routine service data. Implementation fidelity was measured at four select health centers by comparing total clinical supervisory visits and checklists to target goals, and by tracking clinical observation checklist item completion rates over a nine month period. A prospective before and after evaluation measured clinical outcomes in consecutive adults presenting to four select health centers over a nine month period. Primary outcome assessments at baseline, 2 and 6 months included symptoms and functioning, measured by the General Health Questionnaire (GHQ-12) and the World Health Organization Disability Assessment Scale (WHO-DAS Brief), respectively. Secondary outcome assessments included engagement in income generating work and caregiver burden using a quantitative scale adapted to context. RESULTS: A total of 2239 mental health service users completed 15,744 visits during the scale up period. MESH MH facilitated 70% and 76% of supervisory visit and clinical checklist utilization target goals, respectively. Checklist item completion rates significantly improved overall, and for three of five checklist item subgroups examined. 121 of 146 consecutive service users completed outcome measurements six months after entry into care. Scores improved significantly over six months on both the GHQ-12, with median score improving from 26 to 10 (mean within-person change 12.5 [95% CI: 10.9-14.0] p< 0.0001), and the WHO-DAS Brief, with median score improving from 26.5 to 7 (mean within-person change 16.9 [95% CI: 14.9-18.8] p< 0.0001). Over the same period, the percentage of surveyed service users reporting an inability to work decreased significantly (51% to 6% (p < 0.001)), and the proportion of households reporting that a caregiver had left income-generating work decreased significantly (41% to 4% (p < 0.001)). CONCLUSION: MESH MH was associated with high service use, improvements in mental health care delivery by primary care nurses, and significant improvements in clinical symptoms and functional disability of service users receiving care at health centers supported by the program. Multifaceted implementation programs such as MESH MH can reduce the evidence to practice gap for mental health care delivery by nonspecialists in resource-limited settings. The primary limitation of this study is the lack of a control condition, consistent with the implementation science approach of the study. STUDY REGISTRATION: ISRCTN #37231.

Evaluating process and clinical outcomes of a primary care mental health integration project in rural Rwanda: a prospective mixed-methods protocol.

INTRODUCTION: Integrating mental healthcare into primary care can reduce the global burden of mental disorders. Yet data on the effective implementation of real-world task-shared mental health programmes are limited. In 2012, the Rwandan Ministry of Health and the international healthcare organisation Partners in Health collaboratively adapted the Mentoring and Enhanced Supervision at Health Centers (MESH) programme, a successful programme of supported supervision based on task-sharing for HIV/AIDS care, to include care of neuropsychiatric disorders within primary care settings (MESH Mental Health). We propose 1 of the first studies in a rural low-income country to assess the implementation and clinical outcomes of a programme integrating neuropsychiatric care into a public primary care system. METHODS AND ANALYSIS: A mixed-methods evaluation will be conducted. First, we will conduct a quantitative outcomes evaluation using a pretest and post-test design at 4 purposively selected MESH MH participating health centres. At least 112 consecutive adults with schizophrenia, bipolar disorder, depression or epilepsy will be enrolled. Primary outcomes are symptoms and functioning measured at baseline, 8 weeks and 6 months using clinician-administered scales: the General Health Questionnaire and the brief WHO Disability Assessment Scale. We hypothesise that service users will experience at least a 25% improvement in symptoms and functioning from baseline after MESH MH programme participation. To understand any outcome improvements under the intervention, we will evaluate programme processes using (1) quantitative analyses of routine service utilisation data and supervision checklist data and (2) qualitative semistructured interviews with primary care nurses, service users and family members. ETHICS AND DISSEMINATION: This evaluation was approved by the Rwanda National Ethics Committee (Protocol #736/RNEC/2016) and deemed exempt by the Harvard University Institutional Review Board. Results will be submitted for peer-reviewed journal publication, presented at conferences and disseminated to communities served by the programme.

Food Insecurity, Dietary Diversity, and Body Mass Index of HIV-Infected Individuals on Antiretroviral Therapy in Rural Haiti.

Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p < 0.001). Compared with those with little to no food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.

Reliability and construct validity of three health-related self-report scales in HIV-positive adults in rural Rwanda.

Depression, low health-related quality of life, and low perceived social support have been shown to predict poor health outcomes, including HIV-related outcomes. Mental health morbidity and HIV are important public health concerns in Rwanda, where approximately half of the current population is estimated to have survived the genocide and 3% is living with HIV. We examined the reliability and construct validity of the Hopkins Symptom Checklist-15 (HSCL-15), the Medical Outcomes Study HIV Health Survey (MOS-HIV), and the Duke/UNC Functional Social Support Questionnaire (DUFSSQ), which were used to assess depression, health-related quality of life, and perceived social support, respectively, among HIV-infected adults in rural Rwanda. We also studied whether scale reliability differed by gender, literacy status, or antiretroviral therapy (ART) delivery strategy. The Kinyarwanda versions of the HSCL-15, MOS-HIV, and DUFSSQ performed well in the study population. Reliability was favorable (Cronbach's alpha coefficients ≥0.75 or above) for the scales overall and across subgroups of gender, literacy, and mode of ART delivery. The scales also demonstrated good convergent, discriminant, and known-group validity.

Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have emerged as major global health threats. WHO recommends contact investigation in close contacts of patients with MDR and XDR tuberculosis. We aimed to assess the burden of tuberculosis disease in household contacts of such patients. METHODS: We undertook a retrospective cohort study of household contacts of patients treated for MDR or XDR tuberculosis in Lima, Peru, in 1996-2003. The primary outcome was active tuberculosis in household contacts at the time the index patient began MDR tuberculosis treatment and during the 4-year follow-up. We examined whether the occurrence of active tuberculosis in the household contacts differed by resistance pattern of the index patient: either MDR or XDR tuberculosis. FINDINGS: 693 households of index patients with MDR tuberculosis were enrolled in the study. In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4503 household contacts, 117 (2·60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment-there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis-the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis (hazard ratio 1·88, 95% CI 1·10-3·21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance against first-line drugs, of whom 129 (90·9%, 95% CI 85·0-94·6) had MDR tuberculosis. INTERPRETATION: In view of the high risk of disease recorded in household contacts of patients with MDR or XDR tuberculosis, tuberculosis programmes should implement systematic household contact investigations for all patients identified as having MDR or XDR tuberculosis. If shown to have active tuberculosis, these household contacts should be suspected as having MDR tuberculosis until proven otherwise. FUNDING: The Charles H Hood Foundation, the David Rockefeller Center for Latin American Studies at Harvard University, and the Bill & Melinda Gates Foundation.