Publications by authors named "Daniel W Fitzgerald"

108 Publications

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

J Glob Antimicrob Resist 2021 Mar 1;25:60-65. Epub 2021 Mar 1.

Center for Global Health, Weill Cornell Medicine, New York, NY, USA.

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-β-lactamase genes (bla) 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.
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http://dx.doi.org/10.1016/j.jgar.2021.02.016DOI Listing
March 2021

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

Nat Commun 2021 02 18;12(1):1141. Epub 2021 Feb 18.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.

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.
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http://dx.doi.org/10.1038/s41467-021-21475-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892575PMC
February 2021

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

ISME J 2021 Jan 6. Epub 2021 Jan 6.

Center for Global Health, Weill Cornell Medicine, New York, NY, USA.

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.
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http://dx.doi.org/10.1038/s41396-020-00868-9DOI Listing
January 2021

Point-of-care viral load testing among adolescents and youth living with HIV in Haiti: a protocol for a randomised trial to evaluate implementation and effect.

BMJ Open 2020 08 31;10(8):e036147. Epub 2020 Aug 31.

ICAP at Columbia University, Mailman School of Public Health, Columbia University Irving Medical Center, New York, New York, USA.

Introduction: Adolescents living with HIV have poor antiretroviral therapy (ART) adherence and viral suppression outcomes. Viral load (VL) monitoring could reinforce adherence but standard VL testing requires strong laboratory capacity often only available in large central laboratories. Thus, coordinated transport of samples and results between the clinic and laboratory is required, presenting opportunities for delayed or misplaced results. Newly available point-of-care (POC) VL testing systems return test results the same day and could simplify VL monitoring so that adolescents receive test results faster which could strengthen adherence counselling and improve ART adherence and viral suppression.

Methods And Analysis: This non-blinded randomised clinical trial is designed to evaluate the implementation and effectiveness of POC VL testing compared with standard laboratory-based VL testing among adolescents and youth living with HIV in Haiti. A total of 150 participants ages 10-24 who have been on ART for >6 months are randomised 1:1 to intervention or standard arms. Intervention arm participants receive a POC VL test (Cepheid Xpert HIV-1 Viral Load system) with same-day result and immediate ART adherence counselling. Standard care participants receive a laboratory-based VL test (Abbott m2000sp/m2000rt) with the result available 1 month later, at which time they receive ART adherence counselling. VL testing is repeated 6 months later for both arms. The primary objective is to describe the implementation of POC VL testing compared with standard laboratory-based VL testing. The secondary objective is to evaluate the effect of POC VL testing on VL suppression at 6 months and participant comprehension of the correlation between VL and ART adherence.

Ethics And Dissemination: This study is approved by GHESKIO, Weill Cornell Medicine and Columbia University ethics committees. This trial will provide critical data to understand if and how POC VL testing may impact adolescent ART adherence and viral suppression. If effective, POC VL testing could routinely supplement standard laboratory-based VL testing among high-risk populations living with HIV.

Trial Registration Number: NCT03288246.
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http://dx.doi.org/10.1136/bmjopen-2019-036147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462242PMC
August 2020

Urinary biomarkers of mycobacterial load and treatment response in pulmonary tuberculosis.

JCI Insight 2020 09 17;5(18). Epub 2020 Sep 17.

Department of Medicine, and.

BACKGROUNDControl of the tuberculosis (TB) pandemic remains hindered in part by a lack of simple and accurate measures of treatment efficacy, as current gold standard markers rely on sputum-based assays that are slow and challenging to implement. However, previous work identified urinary N1, N12-diacetylspermine (DiAcSpm), neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and mass-to-charge ratio (m/z) 241.0903 as potential biomarkers of active pulmonary TB (ATB). Here, we evaluated their ability to serve as biomarkers of TB treatment response and mycobacterial load.METHODSWe analyzed urine samples prospectively collected from 2 cohorts with ATB. A total of 34 study participants from African countries treated with first-line TB therapy rifampin, isoniazid, pyrazinamide, and ethambutol (HRZE) were followed for 1 year, and 35 participants from Haiti treated with either HRZE or an experimental drug were followed for 14 days. Blinded samples were analyzed by untargeted HPLC-coupled high-resolution TOF-mass spectrometry.RESULTSUrinary levels of all 7 molecules significantly decreased by week 26 of successful treatment (P = 0.01 to P < 0.0001) and positively correlated with sputum mycobacterial load (P < 0.0001). Urinary DiAcSpm levels decreased significantly in participants treated with HRZE as early as 14 days (P < 0.0001) but remained unchanged in cases of ineffective therapy (P = 0.14).CONCLUSIONUrinary DiAcSpm, neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and m/z 241.0903 reductions correlated with successful anti-TB treatment and sputum mycobacterial load. Urinary DiAcSpm levels exhibited reductions capable of differentiating treatment success from failure as early as 2 weeks after the initiation of chemotherapy, advocating its further development as a potentially simple, noninvasive biomarker for assessing treatment response and bacterial load.FUNDINGThis work was supported by the Clinical and Translational Science Center at Weill Cornell College of Medicine (NIH/NCATS 1 UL1 TR002384-02 and KL2TR000458), the Department of Defense (PR170782), the National Institute of Allergy and Infectious Disease grants (NIAID T32AI007613-16, K24 AI098627, and K23 AI131913), the NIH Fogarty International Center grants (R24 TW007988 and TW010062), NIH grant (R01 GM135926), the Abby and Howard P. Milstein Program in Chemical Biology and Translational Medicine, and the Tuberculosis Research Units Networks (TBRU-N, AI111143).
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http://dx.doi.org/10.1172/jci.insight.136301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526545PMC
September 2020

Interventions to Improve Antiretroviral Therapy Adherence Among Adolescents and Youth in Low- and Middle-Income Countries: A Systematic Review 2015-2019.

AIDS Behav 2020 Oct;24(10):2797-2810

Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.

Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: [1] included participants ages 10-24 years; [2] assessed the efficacy of an intervention to improve ART adherence; [3] reported an ART adherence measurement or viral load; [4] conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study's evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research.
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http://dx.doi.org/10.1007/s10461-020-02822-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223708PMC
October 2020

Psychological distress among a population-representative sample of residents of four slum neighborhoods in Port-au-Prince, Haiti.

J Affect Disord 2020 02 23;263:241-245. Epub 2019 Nov 23.

Institute of Implementation Science in Population Health, City University of New York, New York, NY 10027, USA; Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: Almost one billion people live in slum environments across low- and middle-income countries. Little is known about the mental health status of slum residents or its associations with living conditions.

Methods: A cross-sectional, population-representative survey was conducted among 892 adults in four slum communities in Port-au-Prince. Psychological distress was assessed with the Kessler Psychological Distress Scale (K-6). Log-binomial regression modeled the association of sociodemographic variables, living conditions, and material hardship and severe psychological distress [SPD].

Results: Eighty-six percent of adults reported psychological distress (24% severe and 62% moderate). Reliance on an outdoor drinking water source (versus bottled water) and a pit toilet (versus a flush toilet) were marginally positively associated with SPD (adjusted prevalence ratio [aPR]=1.42, 95% confidence interval [CI]: 1.00-2.02 and aPR=1.74, 95% CI: 0.96-3.15, respectively). The prevalence of SPD was higher among women (versus men, aPR=1.66, 95% CI: 1.26-2.19), residents who had foregone healthcare to afford food (versus those who had never done so, aPR=1.60, 95% CI: 1.16-2.45), and persons who drank alcohol at least twice a week (versus monthly or less, aPR=1.73, 95% CI: 1.22-2.45).

Limitations: Data were cross-sectional and lacked information on potential risk factors such as exposure to trauma.

Conclusions: Psychological distress was highly prevalent and associated with poor living conditions. Prospective studies on the mechanisms through which slum living conditions are associated with psychological distress are needed. Research should also assess the feasibility and acceptability of implementation strategies to increase access to mental health screening and treatment for slum residents.
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http://dx.doi.org/10.1016/j.jad.2019.11.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989354PMC
February 2020

High Burden of Non-communicable Diseases among a Young Slum Population in Haiti.

J Urban Health 2019 12;96(6):797-812

Center for Global Health, Weill Cornell Medicine, New York, NY, USA.

The objective of this study was to characterize the demographics and population health of four slum communities in Port-au-Prince, Haiti, including population density and the burden of communicable and non-communicable diseases. Four urban slums were surveyed using a population-representative design between July and October 2016. A multistage cluster area random sampling process was used to identify households and individuals for the survey. Household surveys included rosters of residents, household characteristics, adult and child deaths in the past year, child health, and healthcare access and utilization. Individual surveys of two randomly sampled adults from each household included sociodemographic data, maternal health, and adult health. Additionally, blood pressure, height, weight, and psychological distress were measured by study staff. Data were weighted for complex survey design and non-response. A total of 525 households and 894 individuals completed the survey (96% household and 90% individual response rate, respectively). The estimated population density was 58,000 persons/km. Across slums, 55% of all residents were female, and 38% were adolescents and youth 10-24 years. Among adults, 58% were female with median age 29 years (22-38). The most common adult illnesses were severe psychological distress (24%), hypertension (20%), history of physical injury/trauma (10%), asthma (7%), history of cholera (4%), and history of tuberculosis (3%). Ten percent of adults had obesity (BMI > 30 kg/m), and 7% currently smoked. The most common under-5 diseases during the last 3 months were respiratory and gastrointestinal illnesses (50% and 28%, respectively). One-third of households reported needing medical care for a child in the past year but not being able to access it, largely due to financial constraints. Unique features of these slums are a population structure dominated by adolescents and youth, a high proportion of females, and a high burden of non-communicable diseases including hypertension and psychological distress. Screening, diagnostic, and disease management interventions are urgently needed to protect and promote improved population health outcomes in these slum communities.
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http://dx.doi.org/10.1007/s11524-019-00368-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904710PMC
December 2019

Hypertension prevalence and risk factors among residents of four slum communities: population-representative findings from Port-au-Prince, Haiti.

J Hypertens 2019 04;37(4):685-695

Institute of Implementation Science in Population Health.

Objectives: The aim of this study was to estimate the prevalence of hypertension and its risk factors among adults in four slum communities in Port-au-Prince.

Methods: Cluster area random sampling was used to select adults for a health and demographic survey, including anthropometric measurements. Hypertension was defined as SBP at least 140 mmHg and/or DBP at least 90 mmHg, or current hypertension treatment, and was age-standardized to WHO world population. Correlates of hypertension were tested using sex-stratified logistic regression.

Results: Overall, 20.3% of adults had hypertension (28.5% age-standardized), including 22.3% of men and 18.9% of women. Three percent of participants reported current hypertension treatment, and 49.5% of them had their hypertension controlled. Overweight/obesity (BMI ≥25) was the most common risk factor (20.6% among men, 48.5% among women), while smoking was less common (11.8 and 3.9%, respectively). Increasing age and hypertension prevalence in immediate surroundings were associated with greater odds of hypertension. Among men, having in-migrated in the 3 years prior (versus ≥3 years) was also associated with hypertension [adjusted odds ratio (aOR)=3.32, 95% confidence interval (95% CI): 1.79-6.17], as was overweight and obesity (aOR = 1.90, 95% CI: 1.09-3.33, and aOR = 5.73, 95% CI: 2.49-13.19, respectively) and nonreceipt of needed medical care in the preceding 6 months (aOR = 2.82, 95% CI: 1.35-5.88) among women.

Conclusion: Hypertension prevalence was high across the age spectrum, in addition to substantial levels of overweight/obesity and unmet healthcare needs. It is important to better understand the possible effects of intraurban migration and environmental risk factors on hypertension and ensure that the benefits of increasingly cost-effective prevention and treatment programmes extend to slum residents.
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http://dx.doi.org/10.1097/HJH.0000000000001966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680636PMC
April 2019

Female global health leadership: data-driven approaches to close the gender gap.

Lancet 2019 02;393(10171):521-523

Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Bugando Medical Centre and Catholic University of Health and Allied Sciences, Mwanza, Tanzania.

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http://dx.doi.org/10.1016/S0140-6736(19)30203-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391058PMC
February 2019

Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment.

mBio 2018 11 20;9(6). Epub 2018 Nov 20.

Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA

Recent reports indicate that the sputum of 80% or more of treatment-naive subjects with tuberculosis recruited in England or South Africa contained more viable cells detected by limiting dilution (LD) in liquid culture than detected as CFU. Efforts to generate such differentially detectable (DD) populations have been difficult to reproduce, and the LD assay is prone to artifact. Here, we applied a stringent version of the LD assay to sputum from 33 treatment-naive, HIV-negative Haitian subjects with drug-sensitive tuberculosis (TB) and to a second sputum sample after two weeks of standard treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 13 of these subjects. Twenty-one percent had statistically defined levels of DD in their pretreatment sputum at an average proportional excess over CFU of 3-fold. Sixty-nine percent of those who received HRZE had statistically defined levels of DD in their sputum, and of these, the mean proportionate excess over CFU was 7.9-fold. Thus, DD is detectable in pretreatment sputum from a significant proportion of subjects in the Western Hemisphere, and certain drugs or drug regimens, while reducing CFU, may at the same time increase the proportional representation of DD among the surviving bacilli. Monitoring DD may improve our ability to predict the efficacy of efforts to shorten treatment. Measurement of the reduction in CFU in sputum of patients with TB up to 2 weeks after the initiation of treatment is the gateway test for a new TB treatment. Reports have suggested that CFU assays fail to detect the majority of viable cells in sputum samples from the majority of patients when the number of is estimated by limiting dilution (LD). In an effort to avoid potential methodologic confounders, we applied a modified version of the LD assay in a study of a geographically distinct population. We confirmed that differentially detectable (DD) is often found before treatment, albeit at lower proportionate levels than in earlier reports. Strikingly, the prevalence and proportionate representation of DD increased during standard treatment. Sublethal exposure to certain antibiotics may help generate DD cells or enrich their representation among the surviving bacteria, and this may contribute to the need for prolonged treatment with those agents in order to achieve durable cures.
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http://dx.doi.org/10.1128/mBio.02192-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247085PMC
November 2018

Mucosal-associated invariant and γδ T cell subsets respond to initial Mycobacterium tuberculosis infection.

JCI Insight 2018 10 4;3(19). Epub 2018 Oct 4.

Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.

Innate immune responses that control early Mtb infection are poorly understood, but understanding these responses may inform vaccination and immunotherapy strategies. Innate T cells that respond to conserved bacterial ligands such as mucosal-associated invariant T (MAIT) and γδ T cells are prime candidates to mediate these early innate responses but have not been examined in subjects who have been recently exposed to Mtb. We recruited a cohort living in the same household with an active tuberculosis (TB) case and examined the abundance and functional phenotypes of 3 innate T cell populations reactive to M. tuberculosis: γδ T, invariant NK T (iNKT), and MAIT cells. Both MAIT and γδ T cells from subjects with Mtb exposure display ex vivo phenotypes consistent with recent activation. However, both MAIT and γδ T cell subsets have distinct response profiles, with CD4+ MAIT and γδ T cells accumulating after infection. Examination of exposed but uninfected contacts demonstrates that resistance to initial infection is accompanied by robust MAIT cell CD25 expression and granzyme B production coupled with a depressed CD69 and IFNγ response. Finally, we demonstrate that MAIT cell abundance and function correlate with the abundance of specific gut microbes, suggesting that responses to initial infection may be modulated by the intestinal microbiome.
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http://dx.doi.org/10.1172/jci.insight.121899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237486PMC
October 2018

Integrating hypertension services at an HIV clinic in Port-au-Prince, Haiti: A report from the field.

J Clin Hypertens (Greenwich) 2018 10 26;20(10):1485-1492. Epub 2018 Sep 26.

Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York City, New York.

HIV-positive adults with hypertension have increased risk of mortality but HIV clinics often do not provide hypertension care. The authors integrated hypertension management into existing HIV services at a large clinic in Haiti. Of 1729 documented HIV-positive adults presenting for care at the GHESKIO HIV clinic between March and July 2016, 551 screened positive for hypertension, with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. A convenience sample of 100 patients from this group received integrated hypertension and HIV care for 6 months. At time of identification, patients were screened for proteinuria and initiated on antihypertensive medication. Hypertension and HIV visits coincided; medications were free. Outcomes were retention in care and change in blood pressure over 6 months. Average blood pressure over 6 months was described using linear mixed-effects model. Of 100 HIV-positive adults with hypertension referred for integrated care, three were ineligible due to comorbidities. Among 97 participants, 82% (N = 80) remained in care at 6 months from time of positive hypertension identification. 96% (N = 93) were on antiretroviral therapy with median CD4+ count of 442 cells/µL (IQR 257-640). Estimated average blood pressure over 6 months decreased from systolic 160 mmHg (CI 156, 165) to 146 mmHg (CI 141, 150), P-value <0.0001, and diastolic 105 mmHg (CI 102, 108) to 93 mmHg (CI 89, 96), P-value <0.0001. HIV and hypertension management were successfully integrated at a HIV clinic in Haiti. Integrated management is essential to combat the growing burden of cardiovascular disease among HIV-positive adults.
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http://dx.doi.org/10.1111/jch.13392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186190PMC
October 2018

Predicting death and lost to follow-up among adults initiating antiretroviral therapy in resource-limited settings: Derivation and external validation of a risk score in Haiti.

PLoS One 2018 29;13(8):e0201945. Epub 2018 Aug 29.

Division of General Internal Medicine, Weill Cornell Medicine, New York, United States of America.

Background: Over 18 million adults have initiated life-saving antiretroviral therapy (ART) in resource-poor settings; however, mortality and lost-to-follow-up rates continue to be high among patients in their first year after treatment start. Clinical decision tools are needed to identify patients at high risk for poor outcomes in order to provide individualized risk assessment and intervention. This study aimed to develop and externally validate risk prediction tools that estimate the probability of dying or of being lost to follow-up (LTF) during the year after starting ART.

Methods: We used a derivation cohort of 7,031 adults age 15-70 years initiating ART from 2007 to 2013 at 6 clinics in Haiti; 242 (3.5%) had documented death and 1,521 (21.6%) were LTF at 1 year after starting ART. The following routinely collected data were used as predictors in two logistic regression models (one to predict death and another to predict LTF): age, gender, weight, CD4 count, WHO Stage, and diagnosis of tuberculosis (TB). The validation cohort consisted of 1,835 adults initiating ART at a different HIV clinic in Haiti during 2012. We assessed model discrimination by measuring the C-statistic, and measured model calibration by how closely the predicted probabilities approximated actual probabilities of the two outcomes. We derived a nomogram and a point-based risk score from the predictive models.

Findings: The model predicting death within the year after starting ART had a C-statistic of 0.75 (95% CI 0.74 to 0.81). There was no evidence for significant overfitting and the predictions were well calibrated. The strongest predictors of 1-year mortality were male gender, low weight, low CD4 count, advanced WHO stage, and the absence of TB. In the validation cohort, the C-statistic was 0.69 (95% CI 0.59 to 0.77). A point-based risk score for death had a C-statistic 0.73 (95% CI 0.69 to 0.76) and categorizes patients as low risk (<2% risk of death), average risk (3-4%), and high-risk (8-10%) and very high-risk (14-19%) with likelihood ratios to be used in settings where the baseline risk is different from our study population. The model predicting LTF did not discriminate well (C-statistic 0.59).

Conclusions: A simple risk-score using routinely collected data can predict 1-year mortality after ART initiation for HIV-positive adults in Haiti. However, predicting lost to follow-up using routinely collected data was not as successful. The next step is to assess whether use of this risk score can identify patients who need tailored services to reduce mortality in resource-poor settings such as Haiti.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201945PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114504PMC
January 2019

Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis.

EBioMedicine 2018 May 22;31:157-165. Epub 2018 Apr 22.

Department of Medicine, Weill Cornell Medicine, New York, NY, United States; Center for Global Health, Weill Cornell Medicine, New York, NY, United States. Electronic address:

Background: Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics.

Methods: We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry.

Results: We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease.

Conclusion: Urinary levels of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB.

Funding: This study was funded by Weill Cornell Medicine, the National Institute of Allergy and Infectious Diseases, the Clinical and Translational Science Center at Weill Cornell, the NIH Fogarty International Center grants, and the NIH Tuberculosis Research Unit (Tri-I TBRU).
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http://dx.doi.org/10.1016/j.ebiom.2018.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013777PMC
May 2018

Blood pressure and mortality in a prospective cohort of HIV-infected adults in Port-au-Prince, Haiti.

J Hypertens 2018 07;36(7):1533-1539

Weill Cornell Medicine, Department of Medicine, New York, New York, USA.

Objective: The objective of this study was to determine how baseline blood pressure and incident hypertension related to antiretroviral therapy (ART) initiation, HIV-related inflammation and mortality in HIV-infected adults in a low-income country.

Methods: We conducted long-term follow-up of HIV-infected adults who had participated in a trial of early vs. delayed initiation of ART in Port-au-Prince, Haiti. Between 2005 and 2008, 816 HIV-infected adults were randomized to early (N = 408) vs. delayed ART (when CD4 cell count <200 cells/μl or AIDS-defining condition; N = 408). Blood pressure was measured every 3 months. Hypertension was diagnosed according to the Joint National Committee (JNC-7) guidelines. Biomarkers of inflammation and coagulation were measured from banked enrolment plasma samples. Survival analyses were performed using Stata 14.

Results: The median age at enrolment was 39 years. The median follow-up time was 7.3 years. The hypertension incidence rate was 3.41 per 100 person-years, and was similar in early and delayed ART groups. In multivariable models, independent predictors of incident hypertension were older age, higher BMI and plasma interleukin (IL)-6 levels (adjusted hazard ratio, aHR = 1.23, P < 0.001). Systolic pressure more than 140 mmHg at enrolment was associated with increased mortality (aHR = 2.47, P = 0.03) as was systolic pressure less than 90 mmHg (aHR = 2.25, P = 0.04). Prevalent and incident hypertension were also significantly associated with mortality.

Conclusion: In a large prospective study of HIV-infected adults, we found a high incidence of hypertension associated with HIV-related inflammation. Baseline hypertension conferred a more than two-fold increased risk of death. Among HIV-infected adults in low-income countries, hypertension should be considered a serious threat to long-term survival.
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http://dx.doi.org/10.1097/HJH.0000000000001723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976542PMC
July 2018

Genotypic drug resistance using whole-genome sequencing of Mycobacterium tuberculosis clinical isolates from North-western Tanzania.

Tuberculosis (Edinb) 2018 03 21;109:97-101. Epub 2018 Feb 21.

Center for Global Health, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA.

Background: Drug resistant Tuberculosis (TB) is considered a global public health threat. Whole-genome sequencing (WGS) is a new technology for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles and genotypes for epidemiologic surveillance. Therefore, we used WGS to determine genotypic drug resistance profiles and genetic diversity of drug resistant Mycobacterium tuberculosis isolates from Mwanza, North-western Tanzania.

Methods: A cross-sectional study was conducted at the Bugando Medical Center (BMC) from September 2014 to June 2015. Consecutively, smear-positive newly diagnosed TB patients aged ≥18 years were enrolled. Sputum samples were cultured on Löwenstein-Jensen (LJ) slants. Mycobacterial genomic DNA was extracted for WGS to determine drug resistant mutations for first and second line drugs as well as the spoligotypes.

Results: A total of 78 newly diagnosed patients with pulmonary TB with a median age of 37 [IQR: 30-46] years were enrolled. Of these, 57.8% (45/74) were males and 34.6% (27/78) were HIV positive. Mycobacterium tuberculosis genomic DNA for WGS was obtained from isolates in 74 (94.9%) patients. Of the 74 isolates, six (8.1%) isolates harbored mutations for resistance to at least one drug. The resistance to the drugs was isoniazid 3/74 (4.1%), rifampicin mono-resistant 2/74 (2.7%), ethambutol 2/74 (2.7%) and streptomycin 1/74 (1.4%). None was isoniazid mono-resistant. Of the 74 only one (1.4%) patient had MDR-TB. The resistance to ethionamide, the second line drug, was detected in one patient (1.4%). None was resistant to pyrazinamide, fluoroquinolones, kanamycin, amikacin, or capreomycin. The mutations detected were mabA-inhA promoter region C(-15)T and katG Ser513Thr for isoniazid; rpoB His526Leu and rpoB Ser531Leu for rifampicin; embB Met306Val and embB Met306Ile for ethambutol; rpsL Lys43Arg for streptomycin; and mabA-inhA promoter region C(-15)T for ethionamide. The spoligotypes of the drug resistant Mycobacterium tuberculosis were distinct to all six isolates and belonged to T1, T2, T3-ETH, CAS1-DELHI, EAI5 and LAM11-ZWE lineages.

Conclusion: The genetic drug resistance profile of Mycobacterium tuberculosis isolates from North-western Tanzania comprises of the common previously reported mutations. The prevalence of resistance to first and second line drugs including MDR-TB is low. Six drug resistant strains exhibited different spoligotypes, suggesting limited transmission of drug resistant strains in the region.
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http://dx.doi.org/10.1016/j.tube.2018.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912878PMC
March 2018

Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study.

PLoS Negl Trop Dis 2017 Sep 25;11(9):e0005968. Epub 2017 Sep 25.

Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America.

Background: Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion.

Methodology/principal Findings: We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants' consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2-6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3-1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9-4.6] log10 copies/mL versus 3.7 [3.2-4.3], p = 0.017.

Conclusions/significance: We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.
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http://dx.doi.org/10.1371/journal.pntd.0005968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629028PMC
September 2017

Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed.

Sci Rep 2017 09 7;7(1):10767. Epub 2017 Sep 7.

Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Mycobacterium tuberculosis, the cause of Tuberculosis (TB), infects one third of the world's population and causes substantial mortality worldwide. In its shortest format, treatment of TB requires six months of multidrug therapy with a mixture of broad spectrum and mycobacterial specific antibiotics, and treatment of multidrug resistant TB is longer. The widespread use of this regimen makes this one of the largest exposures of humans to antimicrobials, yet the effects of TB treatment on intestinal microbiome composition and long-term stability are unknown. We compared the microbiome composition, assessed by both 16S rDNA and metagenomic DNA sequencing, of TB cases during antimycobacterial treatment and following cure by 6 months of antibiotics. TB treatment does not perturb overall diversity, but nonetheless dramatically depletes multiple immunologically significant commensal bacteria. The microbiomic perturbation of TB therapy can persist for at least 1.2 years, indicating that the effects of TB treatment are long lasting. These results demonstrate that TB treatment has dramatic effects on the intestinal microbiome and highlight unexpected durable consequences of treatment for the world's most common infection on human ecology.
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http://dx.doi.org/10.1038/s41598-017-10346-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589918PMC
September 2017

Active Tuberculosis Case Finding in Haiti.

Am J Trop Med Hyg 2017 Aug 19;97(2):433-435. Epub 2017 Jul 19.

Weill Cornell Medical College, New York, New York.

In 2010, Haiti suffered from a devastating earthquake; data on the impact on the tuberculosis (TB) epidemic are limited. From January to June 2013, we conducted active case finding at the household level in a slum in Port-au-Prince. Community health workers identified individuals with cough ≥ 2 weeks, and referred them for evaluation. Contact tracing was conducted for patients with active TB. Of an estimated 7,500 residents screened, 394 (5%) had cough and were tested for TB. One hundred (25%) were diagnosed with active TB; 53 (53%) were smear positive. Ninety of these TB index cases provided 317 contacts, and 44 (14%) were diagnosed with active TB; 17 (39%) were smear positive. Overall, 144 TB cases were detected in 6 months (1,920/100,000; national estimate 200/100,000). We found a high burden of undiagnosed TB in Port-au-Prince 3 years after the earthquake. Further assessment of the burden of TB is indicated.
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http://dx.doi.org/10.4269/ajtmh.16-0674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544073PMC
August 2017

Outcomes after antiretroviral therapy during the expansion of HIV services in Haiti.

PLoS One 2017 24;12(4):e0175521. Epub 2017 Apr 24.

Center for Global Health, Weill Cornell Medical College, New York, New York, United States of America.

Background: We report patient outcomes after antiretroviral therapy (ART) initiation in a network of HIV facilities in Haiti, including temporal trends and differences across clinics, during the expansion of HIV services in the country.

Methods: We assessed outcomes at 12 months after ART initiation (baseline) using routinely collected data on adults (≥15 years) in 11 HIV facilities from July 2007-December 2013. Outcomes include death (ascertained from medical records), lost to follow-up (LTF) defined as no visit > 365 days from ART initiation, and retention defined as being alive and attending care ≥ 365 days from ART initiation. Outcomes were compared across calendar year of ART initiation and across facilities. Risk factors for death and LTF were assessed using Cox proportional hazards and competing risk regression models.

Results: Cumulatively, 9,718 adults initiated ART with median age 37 years (IQR 30-46). Median CD4 count was 254 cells/uL (IQR 139-350). Twelve months after ART initiation, 4.4% (95% CI 4.0-4.8) of patients died, 21.7% (95% CI 20.9-22.6) were LTF, and 73.9% (95% CI 73.0-74.8) were retained in care. Twelve-month mortality decreased from 13.8% among adults who started ART in 2007 to 4.4% in 2013 (p<0.001). Twelve-month LTF after ART start was 29.2% in 2007, 18.7% in 2008, and increased to 30.1% in 2013 (p<0.001). Overall, twelve-month retention after ART start did not change over time but varied widely across facilities from 61.1% to 86.5%.

Conclusion: Expansion of HIV services across Haiti has been successful with increasing numbers of patients initiating ART and decreasing twelve-month mortality rates. However, overall retention has not improved, despite differences across facilities, suggesting additional strategies to improve engagement in care are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175521PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402937PMC
September 2017

Live with the Disease Like You Used to Before You Knew You Were Infected: A Qualitative Study Among 10-Year Survivors Living with HIV in Haiti.

AIDS Patient Care STDS 2017 Mar;31(3):145-151

4 Brooklyn Health Disparities Center, SUNY Downstate Medical Center , New York, New York.

In 2003, the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), a nonprofit organization, began administering antiretroviral therapy (ART) to its patients. This practice transformed HIV from a fatal disease to a more manageable chronic condition. However, relatively few studies focus on the experiences of survivors. This study provided a unique opportunity to interview patients who survived at least 10 years after being treated with ART at GHESKIO. The goal of the study was to elicit from patients their perspectives on what enabled them to survive with AIDS. Grounded Theory, a qualitative research method was used to guide data collection, coding, and analysis. Individual interviews were conducted, audio-taped, transcribed and analyzed in Creole, and translated into English. Data saturation was reached at 25 participants. Of which, 64% were women, the mean age was 49, range of 43-55 years, 24% were married, 44% had not completed elementary school, and 72% had no income, the remaining participants had incomes ranging from $1000 to $5000 annually. Qualitative analysis resulted in 681 codes, which were grouped into six categories: being spiritually grounded, having supportive interactions with providers, caring for children, setting personal goals, persevering and living life as usual, and maintaining strict medication adherence practices. The overarching theory was that having a reason to live despite one's circumstances and living life as usual enabled one to survive. Having a strong spiritual foundation coupled with supportive family and providers motivated participants to live and adhere to their ART. As the number of patients who are living longer with HIV in Haiti increases, results from this study will be important in helping tailor interventions that enhance their overall quality of life.
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http://dx.doi.org/10.1089/apc.2016.0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359685PMC
March 2017

Educating religious leaders to promote uptake of male circumcision in Tanzania: a cluster randomised trial.

Lancet 2017 03 15;389(10074):1124-1132. Epub 2017 Feb 15.

Center for Global Health, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Background: Male circumcision is being widely deployed as an HIV prevention strategy in countries with high HIV incidence, but its uptake in sub-Saharan Africa has been below targets. We did a study to establish whether educating religious leaders about male circumcision would increase uptake in their village.

Methods: In this cluster randomised trial in northwest Tanzania, eligible villages were paired by proximity (<60 km) and the time that a free male circumcision outreach campaign from the Tanzanian Ministry of Health became available in their village. All villages received the standard male circumcision outreach activities provided by the Ministry of Health. Within the village pairs, villages were randomly assigned by coin toss to receive either additional education for Christian church leaders on scientific, religious, and cultural aspects of male circumcision (intervention group), or standard outreach only (control group). Church leaders or their congregations were not masked to random assignment. The educational intervention consisted of a 1-day seminar co-taught by a Tanzanian pastor and a Tanzanian clinician who worked with the Ministry of Health, and meetings with the study team every 2 weeks thereafter, for the duration of the circumcision campaign. The primary outcome was the proportion of male individuals in a village who were circumcised during the campaign, using an intention-to-treat analysis that included all men in the village. This trial is registered with ClinicalTrials.gov, number NCT 02167776.

Findings: Between June 15, 2014, and Dec 10, 2015, we provided education for church leaders in eight intervention villages and compared the outcomes with those in eight control villages. In the intervention villages, 52·8% (30 889 of 58 536) of men were circumcised compared with 29·5% (25 484 of 86 492) of men in the eight control villages (odds ratio 3·2 [95% CI, 1·4-7·3]; p=0·006).

Interpretation: Education of religious leaders had a substantial effect on uptake of male circumcision, and should be considered as part of male circumcision programmes in other sub-Saharan African countries. This study was conducted in one region in Tanzania; however, we believe that our intervention is generalisable. We equipped church leaders with knowledge and tools, and ultimately each leader established the most culturally-appropriate way to promote male circumcision. Therefore, we think that the process of working through religious leaders can serve as an innovative model to promote healthy behaviour, leading to HIV prevention and other clinically relevant outcomes, in a variety of settings.

Funding: Bill & Melinda Gates Foundation, National Institutes of Health, and the Mulago Foundation.
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http://dx.doi.org/10.1016/S0140-6736(16)32055-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364327PMC
March 2017

Schistosomiasis and Human Immunodeficiency Virus in Men in Tanzania.

Am J Trop Med Hyg 2017 Apr 6;96(4):856-862. Epub 2017 Feb 6.

Department of Medicine, Center for Global Health, Weill Cornell Medicine, New York, New York.

AbstractSchistosomiasis is a parasitic worm infection that affects over 260 million individuals worldwide. Women with schistosome infections have been demonstrated to have a 4-fold increase in the odds of human immunodeficiency virus (HIV) infection compared with women without schistosome infections. A relationship between schistosome and HIV infections has not been clearly defined in men. Among 674 men aged 18-50 years living in rural Tanzania, we identified 429 (63.6%) who had a schistosome infection as defined by serum positivity for schistosome circulating anodic antigen, visualization of parasite eggs in urine or stool, or both. HIV infection was identified in 38 (5.6%). The odds of HIV infection was 1.3 [95% confidence interval = 0.6-2.5] ( = 0.53) among men with any schistosome infection ( or ), and it was 1.4 [0.6-3.3] ( = 0.43) among men with infection. Men with infection were significantly more likely to report the symptom of hemospermia than men without infection. We conclude that schistosome infections appear to have little to no association with HIV infection in men.
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http://dx.doi.org/10.4269/ajtmh.16-0897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392632PMC
April 2017

Linkage to Primary Care and Survival After Hospital Discharge for HIV-Infected Adults in Tanzania: A Prospective Cohort Study.

J Acquir Immune Defic Syndr 2016 Dec;73(5):522-530

*Department of Medicine, Weill Bugando School of Medicine, Mwanza, Tanzania; †Department of Medicine, Bugando Medical Centre, Mwanza, Tanzania; ‡Center for Global Health, Weill Cornell Medical College, New York, NY; §University of California, San Francisco, San Francisco, CA; ‖Department of Medicine, University of Dodoma School of Medicine, Dodoma, Tanzania; ¶Weill Cornell Medical College-Qatar, Doha, Qatar; and #Office of the Director General, Bugando Medical Center, Mwanza, Tanzania.

Introduction: Little is known about outcomes after hospitalization for HIV-infected adults in sub-Saharan Africa. We determined 12-month, posthospital mortality rates in HIV-infected vs. uninfected adults and predictors of mortality.

Methods: In this prospective cohort study, we enrolled adults admitted to the medical wards of a public hospital in northwestern Tanzania. We conducted standardized questionnaires, physical examinations, and basic laboratory analyses including HIV testing. Participants or proxies were called at 1, 3, 6, and 12 months to determine outcomes. Predictors of in-hospital and posthospital mortality were determined using logistic regression. Cox regression models were used to analyze mortality incidence and associated factors. To confirm our findings, we studied adults admitted to another government hospital.

Results: We enrolled 637 consecutive adult medical inpatients: 38/143 (26.6%) of the HIV-infected adults died in hospital vs. 104/494 (21.1%) of the HIV-uninfected adults. Twelve-month outcomes were determined for 98/105 (93.3%) vs. 352/390 (90.3%) discharged adults, respectively. Posthospital mortality was 53/105 (50.5%) for HIV-infected adults vs. 126/390 (32.3%) for HIV-uninfected adults (adjusted P = 0.006). The 66/105 (62.9%) HIV-infected adults who attended clinic within 1 month after discharge had significantly lower mortality than the other HIV-infected adults [adjusted hazards ratio = 0.17 (0.07-0.39), P < 0.001]. Adults admitted to a nearby government hospital had similar high rates of posthospital mortality.

Conclusions: Posthospital mortality is disturbingly high among HIV-infected adult inpatients in Tanzania. The posthospital period may offer a window of opportunity to improve survival in this population. Interventions are urgently needed and should focus on increasing posthospital linkage to primary HIV care.
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http://dx.doi.org/10.1097/QAI.000000000001107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129656PMC
December 2016

Clinical Features of Human Immunodeficiency Virus-Infected Patients Presenting with Cholera in Port-au-Prince, Haiti.

Am J Trop Med Hyg 2016 Nov 22;95(5):999-1003. Epub 2016 Aug 22.

Center for Global Health, Weill Cornell Medical College, New York, New York.

Human immunodeficiency virus (HIV) infection has been postulated to alter the natural history of cholera, including increased susceptibility to infection, severity of illness, and chronic carriage of Vibrio cholerae Haiti has a generalized HIV epidemic with an adult HIV prevalence of 1.9% and recently suffered a cholera epidemic. We conducted a prospective study at the cholera treatment center (CTC) of GHESKIO in Haiti to characterize the coinfection. Adults admitted at the CTC for acute diarrhea were invited to participate in the study. Vital signs, frequency, and volume of stools and/or vomiting were monitored, and single-dose doxycycline was administered. After counseling, participants were screened for HIV by enzyme-linked immunosorbent assay and for cholera by culture. Of 729 adults admitted to the CTC, 99 (13.6%) had HIV infection, and 457 (63%) had culture-confirmed cholera. HIV prevalence was three times higher in patients without cholera (23%, 63/272) than in those with culture-confirmed cholera (7.9%, 36/457). HIV prevalence in patients with culture-confirmed cholera (7.9%) was four times higher than the adult prevalence in Port-au-Prince (1.9%). Of the 36 HIV-infected patients with cholera, 25 (69%) had moderate/severe dehydration versus 302/421 (72%) in the HIV negative. Of 30 HIV-infected patients with weekly stool cultures performed after discharge, 29 (97%) were negative at week 1. Of 50 HIV-negative patients with weekly stool cultures, 49 (98%) were negative at week 1. In countries with endemic HIV infection, clinicians should consider screening patients presenting with suspected cholera for HIV coinfection.
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http://dx.doi.org/10.4269/ajtmh.16-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094251PMC
November 2016

No more neglect of helminths and HIV.

Lancet 2016 Oct 3;388(10054):1857-1859. Epub 2016 Aug 3.

Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

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http://dx.doi.org/10.1016/S0140-6736(16)31253-3DOI Listing
October 2016

Community-Based HIV and Health Testing for High-Risk Adolescents and Youth.

AIDS Patient Care STDS 2016 08;30(8):371-8

1 Department of Medicine, Center for Global Health, Weill Cornell Medical College , New York, New York.

Adolescents account for 40% of new HIV infections, and HIV testing strategies to increase uptake of testing are needed. A community-based adolescent and youth HIV and health testing campaign was conducted in seven slum neighborhoods of Port-au-Prince, Haiti, from December 2014 to September 2015. Community health workers provided community sensitization and recruited 10- to 24-year-olds to test for HIV, syphilis, gonorrhea/chlamydia, and to screen for tuberculosis (TB) and pregnancy. HIV-infected individuals were escorted to the GHESKIO HIV clinic for same-day enrollment in care. Among 3425 individuals eligible for testing, 3348 (98%) accepted an HIV test. HIV prevalence was 2.65% (n = 89). Median age was 19 [interquartile range (IQR) 17-20]; 73% were female. HIV prevalence was 0.6-7.4% across slum neighborhoods. All HIV-infected individuals enrolled in care the same day as testing; median CD4 was 529 cells/μL [IQR 363-761]. Syphilis prevalence was 2.60% (65/2536) and gonorrhea/chlamydia prevalence was 6.25% (96/1536). Among 168 (5%) individuals who reported TB symptoms, 7.7% (13/168) had microbiologically confirmed disease. One hundred twenty-nine females (5% of all females) were pregnant. This community-based testing campaign identified an adolescent and youth population with an HIV prevalence six times higher than the estimated national adolescent HIV prevalence (0.4%) in Haiti, including perinatally infected adolescents. This type of community-based campaign for HIV testing within a package of services can serve as a model for other resource-poor settings to identify high-risk adolescents and youth, and curb the global HIV epidemic among adolescents.
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http://dx.doi.org/10.1089/apc.2016.0102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991570PMC
August 2016

Impact of a youth-friendly HIV clinic: 10 years of adolescent outcomes in Port-au-Prince, Haiti.

J Int AIDS Soc 2016 4;19(1):20859. Epub 2016 Jul 4.

Center for Global Health, Weill Cornell Medical College, New York, NY, USA.

Introduction: Adolescents account for over 40% of new HIV infections in Haiti. This analysis compares outcomes among HIV-positive adolescents before and after implementation of an adolescent HIV clinic in Port-au-Prince, Haiti.

Methods: We conducted a cohort study using programmatic data among HIV-positive adolescents aged 13 to 19. Data from 41,218 adolescents who were HIV tested from January 2003 to December 2012 were included. Outcomes across the HIV care cascade were assessed before and after implementation of an adolescent clinic (2009), including HIV testing, enrolment in care, assessment for antiretroviral therapy (ART) eligibility, ART initiation and 12-month retention. Pre-ART outcomes were assessed 12 months after HIV testing. Factors associated with pre-ART and ART attrition were identified through multivariable competing risk and Cox proportional hazards regression modelling.

Results: Cumulatively, 1672 (4.1%) adolescents tested HIV positive (80% female, median age 16 years). Retention by cascade step comparing pre- and post-clinic included the following: 86% versus 87% of patients enrolled in care, 61% versus 79% were assessed for ART eligibility, 85% versus 92% initiated ART and 68% versus 66% were retained 12 months after ART initiation. Pre-ART attrition decreased from 61% pre-clinic to 50% post-clinic (p<0.001). Pre-ART attrition was associated with being female (sub-distributional hazard ratio (sHR): 1.59; CI: 1.31-1.93), syphilis diagnosis (sHR: 1.47; CI: 1.16-1.85) and slum residence (sHR: 0.84; CI: 0.72-0.97). ART attrition was associated with syphilis diagnosis (hazard ratio (HR): 2.23; CI: 1.35-3.68) and CD4 <50 cells/µL (HR: 1.88; CI: 1.15-3.06).

Conclusions: Implementation of a youth-friendly adolescent clinic improved retention in HIV care among adolescents, particularly in the assessment of ART eligibility and ART initiation. Additional interventions are needed to improve retention among pre-ART patients and support long-term retention among ART patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933795PMC
http://dx.doi.org/10.7448/IAS.19.1.20859DOI Listing
July 2017