Spectrum of prevalent cardiovascular diseases in urban Port-au-Prince, Haiti: a population-based cross-sectional study.

Background: Eighty percent of global cardiovascular disease (CVD) is projected to occur in low- and middle -income countries (LMICs), yet local epidemiological data are scarce. We provide the first population-based, adjudicated CVD prevalence estimates in Port-au-Prince, Haiti to describe the spectrum of heart disease and investigate associated risk factors. Methods: Demographic, medical history, clinical, imaging and laboratory data were collected among adults recruited using multistage random sampling from 2019 to 2021. Prevalent CVD (heart failure, stroke, ischemic disease) were adjudicated using epidemiological criteria similar to international cohorts. Multivariable Poisson regressions assessed relationships between risk factors and prevalent CVD. Findings: Among 3003 participants, median age was 40 years, 58.1% were female, 70.2% reported income <1 USD/day, and all identified as Black Haitian. CVD age-adjusted prevalence was 14.7% (95% CI 13.3%, 16.5%), including heart failure (11.9% [95% CI 10.5%, 13.5%]), stroke (2.4% [95% CI 1.9%, 3.3%]), angina (2.1% [95% CI 1.6%, 2.9%]), myocardial infarction (1.0% [95% CI 0.6%, 1.8%]), and transient ischemic attack (0.4% [95% CI 0.2%, 1.0%]). Among participants with heart failure, median age was 57 years and 68.5% of cases were among women. The most common subtype was heart failure with preserved ejection fraction (80.4%). Heart failure was associated with hypertension, obesity, chronic kidney disease, depression, and stress. Interpretation: Early-onset heart failure prevalence is alarmingly high in urban Haiti and challenge modelling assumptions that ischemic heart disease and stroke dominate CVDs in LMICs. These data underscore the importance of local population-based epidemiologic data within LMICs to expedite the selection and implementation of evidence-based cardiovascular health policies targeting each country's spectrum of heart disease. Funding: This study was funded by NIH grants R01HL143788, D43TW011972, and K24HL163393, clinicaltrials.govNCT03892265.

Linkage Case Management and Posthospitalization Outcomes in People With HIV: The Daraja Randomized Clinical Trial.

Importance: Despite the widespread availability of antiretroviral therapy (ART), people with HIV still experience high mortality after hospital admission. Objective: To determine whether a linkage case management intervention (named "Daraja" ["bridge" in Kiswahili]) that was designed to address barriers to HIV care engagement could improve posthospital outcomes. Design, Setting, and Participants: Single-blind, individually randomized clinical trial to evaluate the effectiveness of the Daraja intervention. The study was conducted in 20 hospitals in Northwestern Tanzania. Five hundred people with HIV who were either not treated (ART-naive) or had discontinued ART and were hospitalized for any reason were enrolled between March 2019 and February 2022. Participants were randomly assigned 1:1 to receive either the Daraja intervention or enhanced standard care and were followed up for 12 months through March 2023. Intervention: The Daraja intervention group (n = 250) received up to 5 sessions conducted by a social worker at the hospital, in the home, and in the HIV clinic over a 3-month period. The enhanced standard care group (n = 250) received predischarge HIV counseling and assistance in scheduling an HIV clinic appointment. Main Outcomes and Measures: The primary outcome was all-cause mortality at 12 months after enrollment. Secondary outcomes related to HIV clinic attendance, ART use, and viral load suppression were extracted from HIV medical records. Antiretroviral therapy adherence was self-reported and pharmacy records confirmed perfect adherence. Results: The mean age was 37 (SD, 12) years, 76.8% were female, 35.0% had CD4 cell counts of less than 100/µL, and 80.4% were ART-naive. Intervention fidelity and uptake were high. A total of 85 participants (17.0%) died (43 in the intervention group; 42 in the enhanced standard care group); mortality did not differ by trial group (17.2% with intervention vs 16.8% with standard care; hazard ratio [HR], 1.01; 95% CI, 0.66-1.55; P = .96). The intervention, compared with enhanced standard care, reduced time to HIV clinic linkage (HR, 1.50; 95% CI, 1.24-1.82; P < .001) and ART initiation (HR, 1.56; 95% CI, 1.28-1.89; P < .001). Intervention participants also achieved higher rates of HIV clinic retention (87.4% vs 76.3%; P = .005), ART adherence (81.1% vs 67.6%; P = .002), and HIV viral load suppression (78.6% vs 67.1%; P = .01) at 12 months. The mean cost of the Daraja intervention was about US $22 per participant including startup costs. Conclusions and Relevance: Among hospitalized people with HIV, a linkage case management intervention did not reduce 12-month mortality outcomes. These findings may help inform decisions about the potential role of linkage case management among hospitalized people with HIV. Trial Registration: ClinicalTrials.gov Identifier: NCT03858998.

Circulating CD4+ T cells in people with HIV and history of pulmonary tuberculosis have more intact HIV DNA.

Background: The primary barrier to curing HIV infection is the pool of intact HIV proviruses integrated into host cell DNA throughout the bodies of people living with HIV (PLHIV), called the HIV reservoir. Reservoir size is impacted by the duration of HIV infection, delay in starting antiretroviral therapy (ART), and breakthrough viremia during ART. The leading infectious cause of death worldwide for PLHIV is TB, but we don't know how TB impacts the HIV reservoir. Methods: We designed a case-control study to compare HIV provirus-containing CD4 in PLHIV with vs. without a history of active TB disease. Study participants in the pilot and confirmatory cohort were enrolled at GHESKIO Centers in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of PBMC-derived CD4 cells. For a subset, Th1 and Th2 cytokines were assayed in plasma. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. Results: In the pilot cohort, we found that PLHIV with history of active pulmonary TB (n=20) had higher intact provirus than PLHIV without history of active TB (n=47) (794 vs 117 copies per million CD4, respectively; p<0.0001). In the confirmatory cohort, the quantity of intact provirus was higher in the TB group (n=13) compared with the non-TB group (n=18) (median 102 vs. 0 intact provirus per million CD4, respectively p=0.03). Additionally, we found that the frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of IL1B (p= 0.0025) and IL2 (p=0.0002). Conclusions: This is the first assessment of HIV provirus using IPDA in a clinical cohort from a resource limited setting, and the finding of larger reservoir in PLHIV with history of TB has significant implications for our understanding of TB-HIV coinfection and HIV cure efforts in TB-endemic settings.

Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption.

Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis, the world's most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.

A bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine second line regimen for tuberculosis displays similar early bactericidal activity as the standard rifampin based first line regimen.

BACKGROUND: In 2018 the World Health Organization (WHO) recommended a switch to an all oral bedaquiline based second line regimen for treatment of drug resistant (DR) tuberculosis (TB). How these new second line regimens fare in comparison to first line regimens for treatment of drug sensitive (DS) tuberculosis is not well known. METHODS: In this study, we contemporaneously enrolled subjects with DS (n = 31) and DR (n = 23) TB and assessed their response to therapy with first-line (rifampin, isoniazid, ethambutol, pyrazinamide) or second-line (bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine) regimens, respectively. RESULTS: We found that the early bactericidal activity of first and second line regimens was similar during the first two weeks of therapy as determined by BACTEC MGIT, colony forming units (CFU), and a liquid limiting dilution (LD) assays capable of detecting differentially detectable/culturable Mtb (DD Mtb). Further, an identical percentage (77.8%) of subjects from the DS and DR cohorts converted to culture negative after two months of therapy. CONCLUSIONS: Despite presenting with more advanced disease at time of treatment, subjects with DR TB receiving an all oral bedaquiline based second line treatment regimen displayed a similar microbiological response to therapy as subjects with DS TB receiving a first-line treatment regimen.

"Mobilizing our leaders": A multi-country qualitative study to increase the representation of women in global health leadership.

INTRODUCTION: Women play an essential role in health care delivery, and it is vital that they have equal representation in health leadership for equity, innovation, and the strengthening of health systems globally. Yet women remain vastly underrepresented in global health leadership positions, providing a clear example of the deeply rooted power imbalances that are central to the calls to decolonize global health. We conducted a multi-country study in Haiti, Tanzania, India, and the USA to examine gender-based challenges to career advancement for women in the global health workforce. Quantitative data on the type and prevalence of gender-based challenges has been previously reported. In this study, we analyze qualitative data collected through focus group discussions and in-depth interviews to understand women's experiences of gender-based obstacles to career advancement, their perceptions of underlying drivers, and perspectives on effective solutions. Guided by an adaptation of the Social Action Theory, we conducted focus group discussions and in-depth interviews with women at 4 major academic centers for clinical care and research in Haiti, India, Tanzania, and the United States. In total, 85 women participated in focus groups and 15 also participated in in-depth interviews. Discussions and interviews were conducted in the local language, by an experienced local facilitator unaffiliated with the participating institution, between 2017 and 2018. Discussions were recorded, transcribed, and translated. Data were analyzed by interpretive phenomenological methods for emergent themes. Three transcendent themes on gender-based challenges were identified: 1) cultural power imbalance, referring to the prevailing norms and engrained assumptions that women are less capable than men and that women's primary responsibility should be to their families; 2) institutional power imbalance, referring to the systematic gender bias upheld by existing leadership and power structures, and ranging from exclusion from career development opportunities to sexual harassment and assault; and 3) restricted agency, referring to women's limited ability to change their circumstances because of unequal cultural and institutional structures. Participants also described local, actionable solutions to address these barriers. These included: 1) formal reporting systems for sexual harassment and assault; 2) peer support and mentorship; and 3) accessible leadership training and mandatory gender equity training. Participants proposed feasible strategies to address gender-based challenges that could improve women's retention in health careers and foster their rise to leadership. Increasing the representation of women in global health leadership positions responds directly to efforts to decolonize global health and is integral to strengthening health systems and improving health outcomes for women and children worldwide.

High Dietary Sodium, Measured Using Spot Urine Samples, is Associated with Higher Blood Pressure among Young Adults in Haiti.

Background: Hypertension (HTN) is the leading cardiovascular disease (CVD) risk factor in Haiti and is likely driven by poverty-related social and dietary factors. Salt consumption in Haiti is hypothesized to be high but has never been rigorously quantified. Methods: We used spot urine samples from a subset of participants in the population-based Haiti Cardiovascular Disease Cohort to estimate population mean daily sodium intake. We compared three previously validated formulas for estimating dietary sodium intake using urine sodium, urine creatinine, age, sex, height, and weight. We explored the association between dietary sodium intake and blood pressure, stratified by age group. Results: A total of 1,240 participants had spot urine samples. Median age was 38 years (range 18-93), and 48% were female. The mean dietary sodium intake was 3.5-5.0 g/day across the three estimation methods, with 94.2%-97.9% of participants consuming above the World Health Organization (WHO) recommended maximum of 2 g/day of sodium. Among young adults aged 18-29, increasing salt intake from the lowest quartile of consumption (<3.73 g/day) to the highest quartile (>5.88 g/day) was associated with a mean 8.71 mmHg higher systolic blood pressure (SBP) (95% confidence interval: 3.35, 14.07; p = 0.001). An association was not seen in older age groups. Among participants under age 40, those with SBP ≥120 mmHg consumed 0.5 g/day more sodium than those with SBP <120 mmHg (95% confidence interval: 0.08, 0.69; p = 0.012). Conclusions: Nine out of 10 Haitian adults in our study population consumed more than the WHO recommended maximum for daily sodium intake. In young adults, higher sodium consumption was associated with higher SBP. This represents an inflection point for increased HTN risk early in the life course and points to dietary salt intake as a potential modifiable risk factor for primordial and primary CVD prevention in young adults.

Extreme Food Insecurity and Malnutrition in Haiti: Findings from a Population-Based Cohort in Port-au-Prince, Haiti.

Haiti is one of the most food-insecure (FIS) nations in the world, with increasing rates of overweight and obesity. This study aimed to characterize FIS among households in urban Haiti and assess the relationship between FIS and body mass index (BMI) using enrollment data from the Haiti Cardiovascular Disease Cohort Study. FIS was characterized as no/low, moderate/high, and extreme based on the Household Food Security Scale. Multinomial logistic generalized estimating equations were used to evaluate the association between FIS categories and BMI, with obesity defined as BMI ≥ 30 kg/m2. Among 2972 participants, the prevalence of moderate/high FIS was 40.1% and extreme FIS was 43.7%. Those with extreme FIS had higher median age (41 vs. 38 years) and were less educated (secondary education: 11.6% vs. 20.3%) compared to those with no/low FIS. Although all FIS categories had high obesity prevalence, those with extreme FIS compared to no/low FIS (15.3% vs. 21.6%) had the lowest prevalence. Multivariable models showed an inverse relationship between FIS and obesity: moderate/high FIS (OR: 0.77, 95% CI: 0.56, 1.08) and extreme FIS (OR: 0.58, 95% CI: 0.42, 0.81) versus no/low FIS were associated with lower adjusted odds of obesity. We found high prevalence of extreme FIS in urban Haiti in a transitioning nutrition setting. The inverse relationship between extreme FIS and obesity needs to be further studied to reduce both FIS and obesity in this population.

Transcriptional Biomarkers of Differentially Detectable Mycobacterium tuberculosis in Patient Sputum.

Certain populations of Mycobacterium tuberculosis go undetected by standard diagnostics but can be enumerated using limiting dilution assays. These differentially detectable M. tuberculosis (DD M. tuberculosis) populations may have relevance for persistence due to their drug tolerance. It is unclear how well DD M. tuberculosis from patients is modeled by a recently developed in vitro model in which M. tuberculosis starved in phosphate-buffered saline is incubated with rifampin to produce DD M. tuberculosis (the PBS-RIF model). This study attempted to answer this question. We selected 14 genes that displayed differential expression in the PBS-RIF model and evaluated their expression in patient sputa containing various proportions of DD M. tuberculosis. The expression of 12/14 genes correlated with the relative abundance of DD M. tuberculosis in patient sputa. Culture filtrate (CF), which promotes recovery of DD M. tuberculosis from certain patient sputa, improved these correlations in most cases. The gene whose reduced expression relative to M. tuberculosis 16S rRNA showed the greatest association with the presence and relative abundance of DD M. tuberculosis in patient sputa, icl1, was recently shown to play a functional role in restraining DD M. tuberculosis formation in the PBS-RIF model. Expression of icl1, combined with two additional DD M. tuberculosis-related genes, showed strong performance for predicting the presence or absence of DD M. tuberculosis in patient sputa (receiver operating characteristic [ROC] area under the curve [AUC] = 0.88). Thus, the in vitro DD M. tuberculosis model developed by Saito et al. (K. Saito, T. Warrier, S. Somersan-Karakaya, L. Kaminski, et al., Proc Natl Acad Sci U S A 114:E4832-E4840, 2017, https://doi.org/10.1073/pnas.1705385114) bears a resemblance to DD M. tuberculosis found in tuberculosis (TB) patients, and DD M. tuberculosis transcriptional profiles may be useful for monitoring DD M. tuberculosis populations in patient sputum. IMPORTANCE Differentially detectable M. tuberculosis (DD M. tuberculosis), which is detectable by limiting dilution assays but not by CFU, is present and enriched for in TB patient sputum after initiation of first-line therapy. These cryptic cells may play a role in disease persistence due to their phenotypic tolerance to anti-TB drugs. A recently developed in vitro model of DD M. tuberculosis (the PBS-RIF model) has expanded our understanding of these cells, though how well it translates to DD M. tuberculosis in patients is currently unknown. To answer this question, we selected 14 genes that displayed differential expression in the PBS-RIF model and evaluated their expression in TB patient sputa. We found that 12/14 of these genes showed a similar expression profile in patient sputa that correlated with the relative abundance of DD M. tuberculosis. Further, the expression of three of these genes showed strong performance for predicting the presence or absence of DD M. tuberculosis in patient sputa. The use of DD M. tuberculosis transcriptional profiles may allow for easier monitoring of DD M. tuberculosis populations in patient sputum in comparison to limiting dilution assays.

An optimized method for purifying, detecting and quantifying Mycobacterium tuberculosis RNA from sputum for monitoring treatment response in TB patients.

Diagnostics that more accurately detect and quantify viable Mycobacterium tuberculosis (Mtb) in the sputum of patients undergoing therapy are needed. Current culture- and molecular-based tests have shown limited efficacy for monitoring treatment response in TB patients, either due to the presence of viable sub-populations of Mtb which fail to grow under standard culture conditions (termed differentially detectable/culturable Mtb, DD Mtb) or the prolonged half-life of Mtb DNA in sputum. Here, we report an optimized RNA-based method for detecting and quantifying viable Mtb from patient sputum during the course of therapy. We first empirically derived a novel RNA extraction protocol from sputum that improves recovery of Mtb RNA while almost completely eliminating contamination from Mtb DNA and host nucleic acids. Next, we identified five Mtb 16S rRNA primer sets with varying limits of detection that were capable of distinguishing between live versus dead H37Rv Mtb. This combined protocol was then tested on sputa from a longitudinal cohort of patients receiving therapy for drug sensitive (DS) or drug resistant (DR) TB with first-line or second-line regimens, respectively. Results were compared with that of culture, including CFU, BACTEC MGIT, and a limiting dilution assay capable of detecting DD Mtb. The five 16S rRNA primer sets positively identified nearly all (range 94-100%) culture positive sputa, and a portion (19-37%) of culture negative sputa. In comparison, ten highly expressed Mtb mRNAs showed positivity in 72-86% of culture positive sputa, and in 0-13% of culture negative sputa. Two of the five 16S rRNA primer sets were able to positively identify 100% of culture positive sputa, and when tested on culture negative sputa from the DS cohort at 2 months post-initiation of therapy, identified 40% of samples as positive; a percentage that is in line with expected treatment failure rates when first-line therapy is discontinued early. These two primer sets also detected 16S rRNA in 13-20% of sputa at 6 months post-initiation of therapy in the DR cohort. Cycle threshold values for 16S rRNA showed a strong correlation with Mtb numbers as determined by culture (R > 0.87), including as Mtb numbers declined during the course of treatment with first-line and second-line regimens. The optimized molecular assay outlined here may have utility for monitoring treatment response in TB patients.

Estimated blood pressure trajectories and hypertension patterns among pregnant women living with HIV, Haiti, 2007-2017.

Hypertension in pregnancy is a key driver of mortality and morbidity among Haitian women. HIV infection and treatment may worsen hypertension and increase cardiovascular disease risk. The authors examined blood pressure and hypertension patterns among 1965 women (2306 pregnancies ending in live births) in a prevention of maternal-to-child transmission (PMTCT) program in Port-au-Prince, Haiti, between 2007 and 2017. Hypertension was defined as blood pressure ≥140/90 mm Hg on two consecutive visits. Latent class analysis assessed trajectories of mean arterial pressure (MAP) and multinomial ordinal logistic regression examined factors associated with higher trajectories. Between 2007-2009 and 2013-2016, hypertension at PMTCT entry increased from 1.3% to 3.8% (p = .005), while incidence at any time during PMTCT follow-up increased from 5.0 to 16.1 per 100 person-years (p < .001). Hypertension detected ≤20 weeks and > 20 weeks of gestation (possible gestational hypertension) increased from 1.1% to 3.5% (p = .003) and from 2.3% to 6.9% (p < .001), respectively. Five MAP trajectories ranged from low-stable to high-increasing. In multivariable analysis controlling for history of antiretroviral therapy, age, parity, and weight, program entry in more recent years was associated with greater odds of higher MAP trajectory (adjusted odds ratio for 2013-2016 vs. 2007-2009 = 3.1, 95% confidence interval: 1.7-5.6). The increasing prevalence and incidence of hypertension highlight a need for screening and management prior to PMTCT entry and during follow-up. In a population with limited access to chronic disease care, and where many deliveries occur outside of a clinical setting, the period of PMTCT follow-up represents an opportunity to diagnose and initiate management of preexisting and pregnancy-related hypertension.

Single-Cell Transcriptional Profiling Reveals Signatures of Helper, Effector, and Regulatory MAIT Cells during Homeostasis and Activation.

Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant TCR, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of over 76,000 human MAIT cells during early and prolonged Ag-specific activation with the MR1 ligand 5-OP-RU and nonspecific TCR stimulation. We show that MAIT cells span a broad range of homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4+ or CD8+ coexpression. During early activation, MAIT cells rapidly adopt a cytotoxic phenotype characterized by high expression of GZMB, IFNG and TNF In contrast, prolonged stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. We further demonstrate a FOXP3 expressing MAIT cell subset that phenotypically resembles conventional regulatory T cells. Moreover, scRNAseq-defined MAIT cell subpopulations were also detected in individuals recently exposed to Mycobacterium tuberculosis, confirming their presence during human infection. To our knowledge, our study provides the first comprehensive atlas of human MAIT cells in activation conditions and defines substantial functional heterogeneity, suggesting complex roles in health and disease.

Dietary Risk Factors for Cardiovascular Disease among Low-Income Haitian Adults: Findings from a Population-Based Cohort.

Poor diets are responsible for a large burden of noncommunicable disease (NCD). The prevalence of modifiable dietary risk factors is rising in lower-income countries such as Haiti, along with increasing urbanization and shifts to diets high in sugar, salt, and fat. We describe self-reported dietary patterns (intake of fruits, vegetables, fried food, sugar-sweetened beverages, and added salt and oil) among a population-based cohort of low-income adults in Port-au-Prince and assess for associated sociodemographic factors (age, sex, income, education, body mass index). Among 2989 participants, the median age was 40 years, and 58.0% were women. Less than 1% met the World Health Organization recommendation of at least five servings/day of fruits and vegetables. Participants consumed fried food on average 1.6 days/week and sugar-sweetened beverages on average 4.7 days/week; young males of low socioeconomic status were the most likely to consume these dietary risk factors. The vast majority of participants reported usually or often consuming salt (87.1%) and oil (86.5%) added to their meals eaten at home. Our findings underscore the need for public health campaigns, particularly those targeting young males and household cooks preparing family meals at home, to improve dietary patterns in Haiti in order to address the growing NCD burden.

High Lead Exposure Associated With Higher Blood Pressure in Haiti: a Warning Sign for Low-Income Countries.

Cardiovascular disease is the leading cause of death in lower-income countries including Haiti. Environmental lead exposure is associated with high blood pressure and cardiovascular mortality in high-income countries but has not been systematically measured and evaluated as a potential modifiable cardiovascular risk factor in lower-income countries where 6.5 billion people reside. We hypothesized lead exposure is high in urban Haiti and associated with higher blood pressure levels. Blood lead levels were measured in 2504 participants ≥18 years enrolled in a longitudinal population-based cohort study in Port-au-Prince. Lead screening was conducted using LeadCare II (detection limit ≥3.3 µg/dL). Levels below detection were imputed by dividing the level of detection by √2. Associations between lead (quartiles) and systolic blood pressure and diastolic blood pressure were assessed, adjusting for age, sex, obesity, smoking, alcohol, physical activity, income, and antihypertensive medication use. The median age of participants was 40 years and 60.1% were female. The geometric mean blood lead level was 4.73µg/dL, 71.1% had a detectable lead level and 42.3% had a blood lead level ≥5 µg/dL. After multivariable adjustment, lead levels in quartile four (≥6.5 µg/dL) compared with quartile 1 (<3.4 µg/dL) were associated with 2.42 mm Hg (95% CI, 0.36-4.49) higher systolic blood pressure and 1.96 mm Hg (95% CI, 0.56-3.37) higher diastolic blood pressure. In conclusion, widespread environmental lead exposure is evident in urban Haiti, with higher lead levels associated with higher systolic and diastolic blood pressure. Lead is a current and potentially modifiable pollutant in lower-income countries that warrants urgent public health remediation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892265.

Point-of-care viral load testing among adolescents and young adults living with HIV in Haiti: a randomized control trial.

HIV viral load (VL) monitoring can reinforce antiretroviral therapy (ART) adherence. Standard VL testing requires high laboratory capacity and coordination between clinic and laboratory which can delay results. A randomized trial comparing point-of-care (POC) VL testing to standard VL testing among 150 adolescents and young adults, ages 10-24 years, living with HIV in Haiti determined if POC VL testing could return faster results and improve ART adherence and viral suppression. Participants received a POC VL test with same-day result (POC arm) or a standard VL test with result given 1 month later (SOC arm). POC arm participants were more likely to receive a test result within 6 weeks than SOC arm participants (94.7% vs. 80.1%; p1000 copies/ml and low self-reported ART adherence was stronger in the POC arm (OR: 6.57; 95%CI: 2.12-25.21) than the SOC arm (OR: 2.62; 95%CI: 0.97-7.44) suggesting more accurate self-report in the POC arm. POC VL testing was effectively implemented in this low-resource setting with faster results and is a pragmatic intervention that may enable clinicians to identify those with high VL to provide enhanced counseling or regimen changes sooner.Trial registration: ClinicalTrials.gov identifier: NCT03288246.

Rapid Emergence and Spread of Severe Acute Respiratory Syndrome Coronavirus 2 Gamma (P.1) Variant in Haiti.

After an initial wave of coronavirus disease 2019 (COVID-19) in Haiti in summer 2020 (primarily lineage B.1), seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) was ~40%. Variant P.1 (gamma) was introduced in February 2021, with an initially limited introduction followed by exponential local dissemination within this unvaccinated population with prior exposure to earlier SARS-CoV-2 lineages.

Characterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.

Standard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. tuberculosis cells that are unable to grow either on solid medium or in liquid medium unless the medium has been extensively diluted. Because these bacteria can be detected in liquid medium after limiting dilution, they have been termed differentially culturable or differentially detectable M. tuberculosis (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 1 to 2 weeks has been shown to increase the representation of DD-Mtb in the sputum of drug-sensitive (DS) tuberculosis (TB) patients. However, little is known about DD-Mtb after longer periods of treatment with HRZE or in patients with drug-resistant (DR) TB who receive second-line therapies. Here, we measured the proportion of DD-Mtb cells in the sputum of 47 subjects, 29 with DS TB and 18 with DR TB, before initiation of treatment and at 2 weeks and 2 months thereafter. Prior to treatment, DD-Mtb cells represented the majority of M. tuberculosis cells in the sputum of 21% of subjects with DS TB, and this proportion rose to 65% after 2 weeks of treatment with first-line drugs. In subjects with DR TB, DD-Mtb cells were found in the sputum of 29% of subjects prior to treatment initiation, and this proportion remained steady at 31% after 2 weeks of treatment with second-line drugs. By 2 months, DD-Mtb cells were detected in the sputum of only 2/15 (13.3%) subjects with DS TB and in 0/15 of subjects with DR TB. One of the DS subjects whose sputum was positive for DD-Mtb at month 2 later experienced treatment failure.

Multidrug-resistant Pseudomonas aeruginosa in healthcare facilities in Port-au-Prince, Haiti.

OBJECTIVES: Pseudomonas aeruginosa is a leading cause of opportunistic infections worldwide, particularly in healthcare settings, and frequently demonstrates resistance to commonly prescribed antimicrobials. Carbapenem resistance is prevalent worldwide, however there are currently limited data available from Haiti. The aim of this study was to characterise and document this phenotype in Port-au-Prince, Haiti, to further inform the need for appropriate infection control, empirical treatment guidelines and laboratory screening measures, both in Haiti and globally. METHODS: A total of 50 P. aeruginosa isolates were characterised by multilocus sequence typing (MLST) and antimicrobial susceptibility testing, of which 8 isolates were also subjected to whole-genome sequencing (WGS) to identify potential genetic correlations of phenotypic resistance. RESULTS: By MLST, 23 sequence types (STs) were identified, including 13 new STs. Nineteen isolates belonged to a single, previously characterised ST (ST654), all of which demonstrated a multidrug-resistant phenotype, including resistance to meropenem, imipenem and ceftazidime; two isolates were also resistant to colistin. WGS revealed the presence of genes encoding several previously characterised resistance determinants in ST654; notably ACC(6')-Ib3-cr and GES-7. Metallo-ß-lactamase genes (blaVIM-5) were also detected in three isolates. CONCLUSION: These findings confirm that drug-resistant clones of P. aeruginosa are present in Haiti, supporting the need for appropriate screening and control measures and confirming that drug-resistant micro-organisms pose a global threat. Further investigations are required to guide appropriate antimicrobial prescribing in this region.

Gastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis.

The composition of the gastrointestinal microbiota influences systemic immune responses, but how this affects infectious disease pathogenesis and antibiotic therapy outcome is poorly understood. This question is rarely examined in humans due to the difficulty in dissociating the immunologic effects of antibiotic-induced pathogen clearance and microbiome alteration. Here, we analyze data from two longitudinal studies of tuberculosis (TB) therapy (35 and 20 individuals) and a cross sectional study from 55 healthy controls, in which we collected fecal samples (for microbiome analysis), sputum (for determination of Mycobacterium tuberculosis (Mtb) bacterial load), and peripheral blood (for transcriptomic analysis). We decouple microbiome effects from pathogen sterilization by comparing standard TB therapy with an experimental TB treatment that did not reduce Mtb bacterial load. Random forest regression to the microbiome-transcriptome-sputum data from the two longitudinal datasets reveals that renormalization of the TB inflammatory state is associated with Mtb pathogen clearance, increased abundance of Clusters IV and XIVa Clostridia, and decreased abundance of Bacilli and Proteobacteria. We find similar associations when applying machine learning to peripheral gene expression and microbiota profiling in the independent cohort of healthy individuals. Our findings indicate that antibiotic-induced reduction in pathogen burden and changes in the microbiome are independently associated with treatment-induced changes of the inflammatory response of active TB, and the response to antibiotic therapy may be a combined effect of pathogen killing and microbiome driven immunomodulation.

Cervicovaginal bacterial communities in reproductive-aged Tanzanian women with Schistosoma mansoni, Schistosoma haematobium, or without schistosome infection.

Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection.