283 results on '"Pape JW"'
Search Results
2. Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.
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Walsh, KF, McAulay, K, Lee, MH, Vilbrun, SC, Mathurin, L, Jean Francois, D, Zimmerman, M, Kaya, F, Zhang, N, Saito, K, Ocheretina, O, Savic, R, Dartois, V, Johnson, WD, Pape, JW, Nathan, C, and Fitzgerald, DW
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Orphan Drug ,Tuberculosis ,Lung ,Clinical Research ,Infectious Diseases ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,Female ,Haiti ,Humans ,Male ,Microbial Sensitivity Tests ,Mycobacterium tuberculosis ,Nitro Compounds ,Sputum ,Thiazoles ,Tuberculosis ,Pulmonary ,Young Adult ,tuberculosis ,nitazoxanide ,bactericidal activity ,Microbiology ,Medical Microbiology ,Pharmacology and Pharmaceutical Sciences - Abstract
This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P
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- 2020
3. Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy
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Hoffman, Risa M, Brummel, Sean S, Britto, Paula, Pilotto, Jose H, Masheto, Gaerolwe, Aurpibul, Linda, Joao, Esau, Purswani, Murli U, Buschur, Shelley, Pierre, Marie Flore, Coletti, Anne, Chakhtoura, Nahida, Klingman, Karin L, Currier, Judith S, Losso, M, Machado, E, de Menezes, J, Duarte, G, Sperhacke, R, Pinto, J, Kreitchman, R, Santos, B, Wei, L, Pape, JW, Sanchez, J, Sandoval, E, Chokephaibulkit, K, Achalapong, J, Halue, G, Yuthavisuthi, P, Prommas, S, Bowonwatanuwong, C, Sirisanthana, V, Riddler, S, Kumar, P, Shearer, W, Yogev, R, Scott, G, Spector, S, Cunningham, C, Bamji, M, Cooper, E, Wiznia, A, Hitti, J, Emmanuel, P, Scott, R, Acevedo, M, Nachman, S, Jones, T, Rana, S, Keller, M, Stek, A, Rathore, M, McFarland, E, Puga, A, Agwu, A, Chen, T, Van Dyke, R, Deville, J, Purswani, M, Tebas, P, Flynn, P, and Fischl, M
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Contraception/Reproduction ,Infectious Diseases ,Reproductive health and childbirth ,Abortion ,Spontaneous ,Adult ,Anti-Retroviral Agents ,Female ,HIV Infections ,Humans ,Pregnancy ,Stillbirth ,Young Adult ,HIV/AIDS ,antiretroviral therapy ,pregnancy ,conception ,pregnancy outcomes ,PROMISE (Promoting Maternal and Infant Safety Everywhere) 1077HS Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundAdverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting.MethodsHuman immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/μL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm.ResultsSubsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/μL (IQR, 492-833 cells/μL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]).ConclusionsWomen randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.
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- 2019
4. An Adapted Self-Screening Tool for Peripartum Cardiomyopathy in Haiti. Adapted Self-Screening Tool for PPCM in Haiti
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Rene, C., Faustin, M., Bonhomme, J, Deschamps, M.M., Jean-Gilles, M., Rosenberg, R., Ibrahim, M., McNairy, M., Pape, JW, and Devieux, J.G.
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- 2023
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5. Harnessing Type I IFN immunity against SARS-CoV-2 with early administration of IFN-β
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Vinh, Dc, Abel, L, Bastard, P, Cheng, Mp, Condino-Neto, A, Gregersen, Pk, Haerynck, F, Cicalese, M, Hagin, D, Soler-Palacin, P, Planas, Am, Pujol, A, Notarangelo, Ld, Zhang, Q, H. C., S, Casanova, J, Meyts, I, Aiuti, A, Arkin, Lm, Bolze, A, Charkravorty, S, Christodoulou, J, Colobran, R, Drolet, Ba, Fellay, J, Froidure, Pa, Pape, Jw, Halwani, R, Mogensen, Th, Novelli, G, Resnick, Ib, Sediva, A, Tancevski, I, Turvey, S, Vinh, Donald C, Abel, Laurent, Bastard, Paul, Cheng, Matthew P, Condino-Neto, Antonio, Gregersen, Peter K, Haerynck, Filomeen, Cicalese, Maria-Pia, Hagin, David, Soler-Palacín, Pere, Planas, Anna M, Pujol, Aurora, Notarangelo, Luigi D, Zhang, Qian, Su, Helen C, Casanova, Jean-Laurent, and Meyts, Isabelle
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0301 basic medicine ,2019-20 coronavirus outbreak ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Library science ,Lymphocyte Depletion ,03 medical and health sciences ,0302 clinical medicine ,Political science ,Triple combination ,Immunology and Allergy ,Animals ,Humans ,Integrative biology ,Protein Kinase Inhibitors ,COVID-19 Serotherapy ,Autoantibodies ,B-Lymphocytes ,SARS-CoV-2 ,Vaccination ,Immunization, Passive ,COVID-19 ,Immunoglobulins, Intravenous ,Interferon-beta ,Plasmapheresis ,ESTUDOS DE COORTES ,030104 developmental biology ,Infectious Diseases / Laboratory ,Settore MED/03 ,Interferon Type I ,Clinical and Translational Science Award ,Commentary ,Immunotherapy ,Translational science ,Administration (government) ,030215 immunology - Abstract
D.C.V. is supported by the Fonds de la recherche en sante du Quebec clinician-scientist scholar Junior 2 program. L.D.N. and H.C.S. are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarite pour l’enfance, the SCOR Corporate Foundation for Science, Institut National de la Sante et de la Recherche Medicale (INSERM), and the University of Paris. PB is supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). I.M. is a Senior Clinical Investigator at the Research Foundation – Flanders, and is chair of the CSL Behring Chair of Primary Immunodeficiencies at KU Leuven, by the KU Leuven C1 Grant C16/18/007, by a VIB GC PID Grant, by the FWO Grants G0C8517N, G0B5120N, and G0E8420N, and by the Jeffrey Modell Foundation. This work is supported by ERN-RITA.
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- 2021
6. Dual rapid lateral flow immunoassay fingerstick wholeblood testing for syphilis and HIV infections is acceptable and accurate, Port-au-Prince, Haiti
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Bristow, CC, Severe, L, Pape, JW, Javanbakht, M, Lee, S-J, Comulada, WS, Klausner, JD, Bristow, CC, Severe, L, Pape, JW, Javanbakht, M, Lee, S-J, Comulada, WS, and Klausner, JD
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- 2016
7. P18.03 Rapid training and implementation of the pollock technique, a safe, rapid and effective newborn circumcision procedure, in a low-resource setting
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Kojima, N, primary, Bristow, CC, additional, Pollock, N, additional, Crouse, P, additional, Theodore, H, additional, Bonhomme, J, additional, Gaston, CF, additional, Dévieux, JG, additional, Pape, JW, additional, and Klausner, JD, additional
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- 2015
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8. Successes and challenges of HIV treatment programs in Haiti: aftermath of the earthquake
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Koenig, Serena, primary, Ivers, LC, additional, Pace, S, additional, Destine, R, additional, Leandre, F, additional, Grandpierre, R, additional, Mukherjee, J, additional, Farmer, PE, additional, and Pape, JW, additional
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- 2010
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9. Preliminary findings on cancer incidence in HIV-infected persons from six countries in Central and South America and the Caribbean
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Masys, DR, primary, Fang, F, additional, Ye, I, additional, Fink, V, additional, Gotuzzo, E, additional, Padgett, D, additional, Pape, JW, additional, Cortes, C, additional, Bacon, M, additional, and Schechter, M, additional
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- 2009
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10. The Molecular Epidemiology of a Heterosexual Subtype B HIV Epidemic: the Latest Results from the Caribbean
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Carr, JK, primary, Nadai, Y, additional, Eyzaguirre, L, additional, Charurat, M, additional, Sill, A, additional, Jack, N, additional, Figueroa, P, additional, Pape, JW, additional, Guerrero, E, additional, Cleghorn, F, additional, and Blattner, W, additional
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- 2005
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11. Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa.
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Andernach IE, Nolte C, Pape JW, Muller CP, Andernach, Iris E, Nolte, Claudine, Pape, Jean W, and Muller, Claude P
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In Haiti, >90% of the population descended from African slaves. Of 7,147 Haitian pregnant women sampled, 44% of hepatitis B virus (HBV) infections were caused by genotype A1, which today is found mainly in eastern Africa. Twenty percent belong to a rare subgenotype, A5, which has been found only in the former Bight of Benin, a former primary slave trading post. Haitian A subgenotypes appear to have separated early from the African subgenotypes; the most prevalent genotype and subgenotype in West Africa today (E and A3, respectively) are rare in Haiti. This difference indicates that the dominant subgenotypes in Africa emerged in the general population only after the slave trade and explains the low genetic diversity of genotype E. The high prevalence of HBV genotype E in much of Africa further suggests that HBV hyperendemicity is a recent phenomenon, probably resulting from extensive use of unsafe needles. [ABSTRACT FROM AUTHOR]
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- 2009
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12. A novel approach to directly observed therapy for tuberculosis in an HIV-endemic area.
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Desvarieux M, Hyppolite P, Johnson WD Jr., and Pape JW
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OBJECTIVES: This study evaluated a novel approach to the delivery of directly observed therapy (DOT) for tuberculosis in Haiti. METHODS: A total of 194 patients (152 HIV seropositive, 42 HIV seronegative) received daily unsupervised triple-drug therapy for 4 to 8 weeks, followed by twice-weekly 2-drug therapy for the remainder of the 6-month period. DOT was deferred until initiation of the twice-weekly phase. RESULTS: A total of 169 of 194 patients (87.1%) completed the 6-month course. The program of deferred DOT had an effectiveness of 85%. Overall cost was reduced by approximately 40%. CONCLUSIONS: Flexible approaches to DOT, integrating behavioral knowledge, cost considerations, and practicality may improve completion rates and program effectiveness. [ABSTRACT FROM AUTHOR]
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- 2001
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13. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection.
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Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD Jr., Pape, J W, Jean, S S, Ho, J L, Hafner, A, and Johnson, W D Jr
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Tuberculosis occurring with human immunodeficiency virus (HIV) infection is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid plus vitamin B6 versus vitamin B6 alone in Port-au-Prince, Haiti, to assess the efficacy of isoniazid in preventing active tuberculosis in symptom-free HIV-infected individuals. The effect of prophylaxis on the development of HIV disease, AIDS, and death was also investigated. 118 subjects were assigned treatment with isoniazid plus B6 (n = 58) or B6 alone (n = 60) between 1986 and 1989. The treatment groups were similar at study entry in demographic, clinical, and immunological characteristics. Interim analysis in 1990 revealed no significant difference in tuberculosis outcome measures. Follow-up was continued until 1992, at which time significant protection by isoniazid against the development of tuberculosis was apparent, both for the whole study population and for subjects positive for purified protein derivative of tuberculin (PPD). The incidence of tuberculosis was lower in isoniazid recipients than in patients who received B6 alone (2.2 vs 7.5 per 100 person-years). The relative risk of tuberculosis was 3.4 (95% CI 1.1-10.6) for B6 alone versus isoniazid plus B6 (p < 0.05). Isoniazid also delayed progression to HIV disease and AIDS and death. Thus isoniazid effectively decreases the incidence of tuberculosis and delays the onset of HIV-related disease in symptom-free HIV-seropositive individuals. Isoniazid prophylaxis should be considered for HIV-seropositive, PPD-positive subjects, and may also be appropriate for PPD-negative patients in areas where tuberculosis is highly endemic. [ABSTRACT FROM AUTHOR]
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- 1993
14. Assessing whether consent for a clinical trial is voluntary.
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Horwitz RH, Roberts LW, Seal DW, Joseph P, Maschke KJ, Verdier RI, Nerette S, Pape JW, Fitzgerald DW, Horwitz, Russell H, Roberts, Laura W, Seal, David W, Joseph, Patrice, Maschke, Karen J, Verdier, Rose I, Nerette, Sandy, Pape, Jean W, and Fitzgerald, Daniel W
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- 2013
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15. Provision of treatment in HIV-1 vaccine trials in developing countries.
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Fitzgerald DW, Pape JW, Wasserheit JN, Counts GW, and Corey L
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- 2003
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16. Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals.
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Charles M, Noel F, Leger P, Severe P, Riviere C, Beauharnais CA, Miller E, Rutledge J, Bang H, Shealey W, D'Aquila RT, Gulick RM, Johnson WD Jr., Wright PF, Pape JW, and Fitzgerald DW
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Objective: To assess outcomes after antiretroviral therapy (ART) in adolescents and youth in Haiti, a country with a generalized epidemic of infection with HIV-1.Methods: An assessment was made of survival, plasma HIV-1 ribonucleic acid (RNA) concentrations and HIV-1 drug resistance patterns after 12 months of ART in patients aged 13-25 years who presented to a clinic in Port-au-Prince, Haiti, with AIDS between 1 March 2003 and 31 December 2005. Participants received ART in accordance with WHO guidelines. Kaplan-Meier analysis was used to estimate survival probabilities and their 95% confidence intervals (CI) for the period from ART initiation to death.Findings: Of a total of 146 patients, 96 (66%) were female; the median CD4+ T-cell count at baseline was 129 cells/ml. By Kaplan-Meier analysis, 13% of the patients had died at 12 months, 17% at 24 months and 20% at 36 months. A plasma HIV-1 RNA concentration >/= 50 copies/ml was seen in 40 (51%) of 79 patients 12 months after treatment initiation and was associated with poor ART adherence. Among 29 patients with > 1000 copies/ml at 12 months, resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 23 cases (79%); to both NNRTIs and lamivudine in 21 (72%) cases; and to NNRTIs, lamivudine and other nucleoside reverse transcriptase inhibitors in 10 (35%) cases. One hundred and six participants (73%) reported sexual intercourse without condoms, and 35 of the 96 women (36%) were pregnant during follow-up.Conclusion: Adolescents and youth with AIDS receiving ART are at risk of virologic failure and disease progression and can therefore transmit HIV-1 to sexual partners and infants. Strategies to target the special needs of this age group are urgently needed. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]
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- 2008
17. Antiretroviral therapy in a thousand patients with AIDS in Haiti.
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Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G, George E, Kenel-Pierre S, Wright PF, Gulick R, Johnson WD Jr., Pape JW, and Fitzgerald DW
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- 2005
18. Prevention of mother-to-child transmission of HIV in Haiti.
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Deschamps M, Noel F, Bonhomme J, Dévieux JG, Saint-Jean G, Zhu Y, Wright P, Pape JW, and Malow RM
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Objectives. To describe the effectiveness of a program designed to reduce the rate of motherto- child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. Methods. All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. Results. Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2% (95% CI: 6.14- 12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of followup (x² = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. Conclusions. The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality. [ABSTRACT FROM AUTHOR]
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- 2009
19. Comprehension during informed consent in a less-developed country.
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Fitzgerald DW, Marotte C, Verdier RI, Johnson WD Jr., and Pape JW
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- 2002
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20. COVID-19 lineages in a minimally vaccinated island population: Genomic epidemiology of SARS-CoV-2 in Haiti.
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Mavian CN, Tagliamonte MS, Bassett M, Alam M, Cash MN, Hitchings M, Louis R, Riva A, Zainabadi K, Deschamps MM, Liautaud B, Rouzier V, Fitzgerald DW, Pape JW, Morris JG Jr, and Salemi M
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We monitored SARS-CoV-2 variants in Haiti from 2020-2023. Despite Haitian COVID-19 travel restrictions and in the setting of a vaccination rate of 2.7%, the timing and lineage evolution of the Haiti epidemic mirrored what was occurring in the rest of the world. Sources for importation of lineages into Haiti were the United States (US), the Dominican Republic (DR), Europe, and Brazil, with exportation of lineages to the US, DR, Europe, and Asia. Viral load in patients infected by the Delta and Omicron BA.1 were correlated along the phylogenies, suggesting that higher viral loads have facilitated strain transmission and evolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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21. Effectiveness of community-based hypertension management on hypertension in the urban slums of Haiti: A mixed methods study.
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St Sauveur R, Sufra R, Jean Pierre MC, Rouzier V, Preval F, Exantus S, Jean M, Jean J, Forestal GP, Fleurijean O, Mourra N, Ogyu A, Malebranche R, Brisma JP, Deschamps MM, Pape JW, Sundararajan R, McNairy ML, and Yan LD
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- Humans, Female, Male, Haiti epidemiology, Middle Aged, Community Health Services methods, Aged, Blood Pressure physiology, Blood Pressure drug effects, Adult, Blood Pressure Determination methods, Urban Population statistics & numerical data, Hypertension drug therapy, Hypertension epidemiology, Hypertension therapy, Poverty Areas, Community Health Workers organization & administration, Antihypertensive Agents therapeutic use
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Hypertension is a leading contributor to mortality in low-middle income countries including Haiti, yet only 13% achieve blood pressure (BP) control. We evaluated the effectiveness of a community-based hypertension management program delivered by community health workers (CHWs) and physicians among 100 adults with uncontrolled hypertension from the Haiti Cardiovascular Disease Cohort. The 12-month intervention included: community follow-up visits with CHWs (1 month if BP uncontrolled ≥140/90, 3 months otherwise) for BP measurement, lifestyle counseling, medication delivery, and dose adjustments. Primary outcome was mean change in systolic BP from enrollment to 12 months. Secondary outcomes were mean change in diastolic BP, BP control, acceptability, feasibility, and adverse events. We compared outcomes to 100 age, sex, and baseline BP matched controls with standard of care: clinic follow-up visits with physicians every 3 months. We also conducted qualitative interviews with participants and providers. Among 200 adults, median age was 59 years, 59% were female. Baseline mean BP was 154/89 mmHg intervention versus 153/88 mmHg control. At 12 months, the difference in SBP change between groups was -12.8 mmHg (95%CI -6.9, -18.7) and for DBP -7.1 mmHg (95%CI -3.3, -11.0). BP control increased from 0% to 58.1% in intervention, and 28.4% in control group. Four participants reported mild adverse events. In mixed methods analysis, we found community-based delivery addressed multiple participant barriers to care, and task-shifting with strong teamwork enhanced medication adherence. Community-based hypertension management using task-shifting with CHWs and community-based care was acceptable, and effective in reducing SBP, DBP, and increasing BP control., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)
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- 2024
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22. People Living With HIV Have More Intact HIV DNA in Circulating CD4+ T Cells if They Have History of Pulmonary Tuberculosis.
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Juste MAJ, Joseph Y, Lespinasse D, Apollon A, Jamshidi P, Lee MH, Ward M, Brill E, Duffus Y, Chukwukere U, Danesh A, Alberto WC, Fitzgerald DW, Pape JW, Jones RB, and Dupnik K
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Background: A primary barrier to curing HIV is the HIV reservoir. The leading infectious cause of death worldwide for people living with HIV is tuberculosis (TB), but we do not know how TB impacts the HIV reservoir., Methods: Participants in identification and validation cohorts were selected from previously enrolled studies at Groupe Haïtien d'Étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of peripheral blood mononuclear cell (PBMC)-derived CD4+ T cells. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring., Results: In the identification cohort, we found that people living with HIV with a history of active pulmonary TB (n=19) had higher levels of intact provirus than people living with HIV without a history of active TB (n=47) (median 762; IQR, 183-1173 vs 117; IQR, 24-279 intact provirus per million CD4, respectively; P =0.0001). This difference also was seen in the validation cohort (n=31), (median 102; IQR, 0-737 vs 0; IQR, 0-24.5 intact provirus per million CD4, P =0.03) for TB vs no-TB history groups, respectively. The frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of interleukin-1 beta (r=0.524, P = 0.0025) and interleukin-2 (r=0.622, P =0.0002)., Conclusions: People living with HIV with a history of active pulmonary TB have more HIV pro-virus in their circulating CD4+ T cells, even years after TB cure. We need to characterize which CD4+ T cells are harboring intact provirus to consider the impact of T cell-targeting HIV cure interventions for people living in TB-endemic areas., Competing Interests: The authors report no competing financial interests., (Copyright © 2024 Pathogens and Immunity.)
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- 2024
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23. GHESKIO's model of patient care during civil unrest in Haiti.
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Deschamps MM, Bat-Erdene M, Duerr A, and Pape JW
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- Humans, Haiti epidemiology, Patient Care, Delivery of Health Care, HIV Infections epidemiology, HIV Infections prevention & control
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Competing Interests: MMD and JWP are employees of GHESKIO Centers. AD and MB declare no competing interests. We acknowledge the entire staff of GHESKIO for their ongoing work for and dedication to the people of Haiti, especially the important contributions of the following: Genevieve Hilaire, Nadalette Alcenat, Patrice Severe, Vanessa Rouzier, Samuel Pierre, Nancy Dorvil, Yvetot Joseph, Patrice Joseph, Mireille Peck, Rhode Secours, Laurent Daniel Mathurin, Staltz Vilbrun, Bernard Liautaud, Maria Linda Aristomeme, Stanley Cadet, and Reginal Osse. We also acknowledge the collaboration of Delia Pinto-Santini critically reviewing drafts and final article and Siavash Pasalar in preparing the submission.
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- 2024
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24. A Bedaquiline, Pyrazinamide, Levofloxacin, Linezolid, and Clofazimine Second-line Regimen for Tuberculosis Displays Similar Early Bactericidal Activity as the Standard Rifampin-Based First-line Regimen.
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Zainabadi K, Vilbrun SC, Mathurin LD, Walsh KF, Pape JW, Fitzgerald DW, and Lee MH
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- Humans, Adult, Middle Aged, Male, Female, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Rifampin therapeutic use, Rifampin pharmacology, Microbial Sensitivity Tests, Drug Therapy, Combination, Treatment Outcome, Young Adult, Aged, Antitubercular Agents therapeutic use, Antitubercular Agents pharmacology, Antitubercular Agents administration & dosage, Linezolid pharmacology, Linezolid therapeutic use, Clofazimine therapeutic use, Clofazimine pharmacology, Diarylquinolines therapeutic use, Diarylquinolines pharmacology, Pyrazinamide therapeutic use, Mycobacterium tuberculosis drug effects, Levofloxacin pharmacology, Levofloxacin therapeutic use
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Background: In 2018 the World Health Organization recommended a switch to an all oral bedaquiline-based second-line regimen for treatment of drug-resistant tuberculosis (DR-TB). How these new second-line regimens fare in comparison to first-line regimens for treatment of drug-sensitive tuberculosis (DS-TB) is not well known., Methods: In this study, we contemporaneously enrolled subjects with DS-TB (n = 31) or DR-TB (n = 23) 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 2 weeks of therapy as determined by BACTEC MGIT, colony-forming units, and a liquid limiting dilution assay capable of detecting differentially detectable/culturable Mycobacterium tuberculosis. Furthermore, an identical percentage (77.8%) of subjects from the DS-TB and DR-TB cohorts converted to culture negative after 2 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., Competing Interests: Potential conflicts of interest. The authors declare no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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25. Continuity of care during severe civil unrest with a model of community-based HIV care: a retrospective cohort study from Haiti.
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Joseph P, Sun R, Guiteau C, Jean Juste MA, Dorvil N, Vilbrun S, Secours R, Severe K, Raymond P, Cetoute F, Baptiste WJ, Forestal G, Cadet S, Marcelin A, Deschamps MM, McNairy ML, Dua A, Cheung HC, Pape JW, and Koenig SP
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Background: There are limited data on the effectiveness of differentiated service delivery (DSD) for HIV care during sociopolitical turmoil. We assessed outcomes with a DSD model of care that includes patient choice between community-based antiretroviral therapy (ART) centres, home-based ART dispensing, or facility-based care at GHESKIO clinic during a period of severe civil unrest in Port-au-Prince, Haiti., Methods: This retrospective analysis included data on patients with at least one HIV visit at GHESKIO between May 1, 2019, and December 31, 2021. Multivariable logistic regression models were used to assess predictors of attending ≥1 community visit during the study period, and failure to attend timely visits. HIV-1 RNA test results were reported among patients who had been ART for ≥3 months at last visit., Findings: Of the 18,625 patients included in the analysis, 9659 (51.9%) attended at least one community visit. The proportion of community visits ranged from 0.3% (2019) to 44.1% (2021). Predictors of ≥1 community visit included male sex (aOR: 1.13; 95% CI: 1.06, 1.20), secondary education (aOR: 1.07; 95% CI: 1.01, 1.14), income > $USD 1.00/day (aOR: 1.24; 95% CI: 1.14, 1.35), longer duration on ART (aOR: 1.08 per additional year; 95% CI: 1.07, 1.09), and residence in Carrefour/Gressier (p < 0.0001 in comparisons with all other zones). Younger age and shorter time on ART were associated with late visits and loss to follow-up. Among 12,586 patients with an on-time final visit who had been on ART for ≥3 months, 11,131 (88.4%) received a viral load test and 9639 (86.6%) had HIV-1 RNA < 1000 copies/mL., Interpretation: The socio-political situation in Haiti has presented extraordinary challenges to the health care system, but retention and viral suppression rates remain high with a model of community-based HIV care. Additional interventions are needed to improve outcomes for younger patients, and those with shorter time on ART., Funding: No funding., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)
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- 2024
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26. Neighborhood Social Vulnerability and Premature Cardiovascular Disease in Haiti.
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Roberts NLS, Sufra R, Yan LD, St Sauveur R, Inddy J, Macius Y, Théard M, Lee MH, Mourra N, Rasul R, Nash D, Deschamps MM, Safford MM, Pape JW, Rouzier V, and McNairy ML
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- Humans, Haiti epidemiology, Female, Male, Middle Aged, Adult, Prevalence, Neighborhood Characteristics, Cohort Studies, Residence Characteristics statistics & numerical data, Heart Failure epidemiology, Aged, Cardiovascular Diseases epidemiology, Hypertension epidemiology, Social Vulnerability
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Importance: Higher social vulnerability is associated with premature cardiovascular disease (CVD) and mortality but is understudied in low-income countries that have both the highest magnitude of social vulnerability and a growing CVD epidemic., Objective: To evaluate the association between social vulnerability and hypertension, CVD, and CVD subtypes in Haiti as a model for similar low-income countries., Design, Setting, and Participants: This population-based cohort study used enrollment data from adults participating in the Haiti Cardiovascular Disease Cohort Study. Recruitment occurred via multistage random sampling throughout slum and urban neighborhoods in Port-au-Prince, Haiti, from March 2019 to August 2021. Data were analyzed from May 2022 to December 2023., Exposures: A modified Haitian Social Vulnerability Index (SVI-H) was created following the US Centers for Disease Control and Prevention Social Vulnerability Index method. Twelve variables across the domains of socioeconomic status, household characteristics, and social and community context were included. The SVI-H was calculated for each study neighborhood block and then stratified into SVI-H quartiles (quartile 1 was the least vulnerable; quartile 4, the most vulnerable)., Main Outcomes and Measures: Prevalent hypertension and total CVD, defined as heart failure (HF), stroke, transient ischemic attack (TIA), angina, or myocardial infarction (MI). Age-adjusted Poisson regression analysis yielded prevalence ratios (PRs) comparing the prevalence of hypertension, total CVD, and CVD subtypes across SVI-H quartiles., Results: Among 2925 adults (1704 [58.3%] female; mean [SD] age, 41.9 [15.9] years), the prevalence of hypertension was 32.8% (95% CI, 31.1%-34.5%) and the prevalence of CVD was 14.7% (95% CI, 13.5%-16.0%). Hypertension prevalence ranged from 26.2% (95% CI, 23.1%-29.3%) to 38.4% (95% CI, 34.8%-42.0%) between quartiles 1 and 4, while CVD prevalence ranged from 11.1% (95% CI, 8.8%-13.3%) to 19.7% (95% CI, 16.8%-22.6%). SVI-H quartile 4 vs 1 was associated with a greater prevalence of hypertension (PR, 1.17; 95% CI, 1.02-1.34) and CVD (PR, 1.48; 95% CI, 1.16-1.89). Among CVD subtypes, SVI-H was significantly associated with HF (PR, 1.64; 95% CI, 1.23-2.18) but not with combined stroke and TIA or combined angina and MI., Conclusions and Relevance: In urban Haiti, individuals living in neighborhoods with the highest social vulnerability had greater prevalence of hypertension and HF. Understanding CVD disparities in low-income countries is essential for targeting prevention and treatment interventions toward populations at highest risk globally.
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- 2024
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27. Molecular Epidemiology of Isoniazid-resistant M tuberculosis in Port-au-Prince, Haiti.
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Walsh KF, Lee MH, Chaguza C, Pamphile W, Royal G, Escuyer V, Pape JW, Fitzgerald D, Cohen T, and Ocheretina O
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Background: Isoniazid-resistant, rifampin-susceptible tuberculosis (Hr-TB) is associated with poor treatment outcomes and higher rates of acquisition of further drug resistance during treatment. Due to a lack of widespread diagnostics, Hr-TB is frequently undetected and its epidemiology is incompletely understood., Methods: We studied the molecular epidemiology of Hr-TB among all patients diagnosed with culture-positive pulmonary tuberculosis between January 1 and June 30, 2017, at an urban referral tuberculosis clinic in Port-au-Prince, Haiti. Demographic and clinical data were extracted from the electronic medical record. Archived diagnostic Mycobacterium tuberculosis isolates were tested for genotypic and phenotypic isoniazid resistance using the Genotype MTBDR plus assay (Hain, Nehren, Germany) and culture-based testing, respectively. All isoniazid-resistant isolates and a randomly selected subset of isoniazid-susceptible isolates underwent whole-genome sequencing to confirm the presence of mutations associated with isoniazid resistance, to validate use of Genotype MTBDR plus in this population, and to identify potential transmission links between isoniazid-resistant isolates., Results and Conclusions: Among 845 patients with culture-positive pulmonary tuberculosis in Haiti, 65 (7.7%) had Hr-TB based on the Genotype MTBDR plus molecular assay. Age < 20 years was significantly associated with Hr-TB (odds ratio, 2.39; 95% confidence interval, 1.14, 4.70; P = .015). Thirteen (20%) isoniazid-resistant isolates were found in 5 putative transmission clusters based on a single nucleotide polymorphism distance of ≤ 5. No patients in these transmission clusters were members of the same household. Adolescents are at higher risk for Hr-TB. Strains of isoniazid-resistant M tuberculosis are actively circulating in Haiti and transmission is likely occurring in community settings., Competing Interests: Potential conflicts of interest: The authors have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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28. High variance in quantification of Mycobacterium tuberculosis at low bacterial loads and with differentially detectable mycobacteria.
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Walsh KF, Lee MH, Zainabadi K, Vilbrun SC, Jean Juste MA, Joseph Y, Royal G, Saito K, McAulay K, Pape JW, and Fitzgerald D
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- Humans, Prospective Studies, Male, Adult, Female, Mycobacterium tuberculosis drug effects, Bacterial Load methods
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We examined the correlation between three different methods of Mycobacterium tuberculosis quantification: time to positivity (TTP), log
10 CFU, and an assay to detect differentially detectable M. tuberculosis (DD Mtb) from three different prospective studies. Participants with DD Mtb have significantly more variation in the CFU/TTP correlation than participants with no DD Mtb ( P < 0.001). This may impact the design of early bactericidal activity studies that use TTP as the primary outcome., Competing Interests: The authors declare no conflict of interest.- Published
- 2024
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29. Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification Among Patients With Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-income Countries.
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Dupnik K, Rivera VR, Dorvil N, Duffus Y, Akbarnejad H, Gao Y, Liu J, Apollon A, Dumont E, Riviere C, Severe P, Lavoile K, Duran Mendicuti MA, Pierre S, Rouzier V, Walsh KF, Byrne AL, Joseph P, Cremieux PY, Pape JW, and Koenig SP
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Background: The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population., Methods: In this baseline analysis of 498 adults (>18 years) with TB symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP as a continuous variable using generalized linear models., Results: Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4% and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART and 0.8% to 5.0% would have untreated TB at ART initiation., Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results., Competing Interests: Potential conflicts of interest. All authors report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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30. Predictors of Clinical Outcomes among People with HIV and Tuberculosis Symptoms after Rapid Treatment Initiation in Haiti.
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Richterman A, Dorvil N, Rivera V, Bang H, Severe P, Lavoile K, Pierre S, Apollon A, Dumond E, Pierre Louis Forestal G, Rouzier V, Joseph P, Cremieux PY, Pape JW, and Koenig SP
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Introduction: Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation., Methods: We conducted a secondary analysis of a randomized controlled trial of two rapid treatment initiation strategies for people with treatment-naïve HIV and tuberculosis symptoms at an urban clinic in Haiti. We used logistic regression models to assess associations between baseline characteristics and (1) retention in care at 48 weeks, (2) HIV viral load suppression at 48 weeks (among participants who underwent viral load testing), and (3) all-cause mortality., Results: 500 participants were enrolled in the study 11/2017-1/2020. Eighty-eight (18%) participants were diagnosed with tuberculosis, and ART was started in 494 (99%). After adjustment, less than secondary education (adjusted odds ratio [AOR] 0.21, 95% CI 0.10-0.46), dolutegravir initiation (AOR 2.57, 95% CI 1.22-5.43), age (AOR 1.42 per 10-year increase, 95% CI 1.01-1.99), and tuberculosis diagnosis (AOR 3.92, 95% CI 1.36-11.28) were significantly associated with retention. Age (AOR 1.36, 95% CI 1.05-1.75), dolutegravir initiation (AOR 1.75, 95% CI 1.07-2.85), and tuberculosis diagnosis (AOR 0.50, 95% CI 0.28-0.89) were associated with viral suppression. Higher CD4 cell count at enrollment (unadjusted odds ratio [OR] 0.69, 95% CI 0.55-0.87) and anemia (OR 4.86, 95% CI 1.71-13.81) were associated with mortality., Conclusions: We identified sociodemographic, treatment-related, clinical, and laboratory-based predictors of clinical outcomes. These characteristics may serve as markers of sub-populations that could benefit from additional interventions to support treatment success after rapid treatment initiation., Competing Interests: All authors declare no conflicts of interest.
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- 2024
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31. Spectrum of prevalent cardiovascular diseases in urban Port-au-Prince, Haiti: a population-based cross-sectional study.
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Yan LD, Sufra R, St Sauveur R, Jean-Pierre MC, Apollon A, Malebranche R, Théard M, Pierre G, Dévieux J, Lau J, Mourra N, Roberts NLS, Rasul R, Nash D, Pirmohamed AM, Devereux RB, Lee MH, Kwan GF, Safford MM, Adrien L, Alfred JP, Deschamps M, Severe P, Fitzgerald DW, Pape JW, Rouzier V, and McNairy ML
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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., Competing Interests: RS, RSS, MJP, YM, AA, JD, MHL, MMS, MD, PS, JWP, VR, MLM report a grant R01HL143788. RS, RSS, JWP, MLM report a grant D43TW011972. MLM reports a grant K24HL163393. DWF reports grants K24AI098627, D43TW011826, U19AI162568, P30AI168433. JD reports grant R34MH133481. DN reports grants U01AI096299, R01MH125735, P30MH043520, R01MH117793, R34MH126809, R01AI179420, R21AI147933, RF1MH132360, R21AI177008, COVID research grant from Pfizer, and has received consulting fees from Gilead and Abbvie. GFK reports grants K23HL140133, and R21TW012165. MMS reports grant R01HL165452. JWP reports grants UM1AI069421 and D43TW011295., (© 2024 The Author(s).)
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- 2024
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32. Circulating CD4+ T cells in people with HIV and history of pulmonary tuberculosis have more intact HIV DNA.
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Juste MAJ, Joseph Y, Lespinasse D, Apollon A, Jamshidi P, Lee MH, Ward M, Brill E, Duffus Y, Chukwukere U, Danesh A, Alberto WC, Fitzgerald DW, Pape JW, Jones RB, and Dupnik K
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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., Competing Interests: Conflict of interest statement: The authors have declared that no conflict of interest exists.
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- 2024
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33. Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification among Patients with Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-Income Countries.
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Dupnik K, Rivera VR, Dorvil N, Akbarnejad H, Gao Y, Liu J, Apollon A, Dumond E, Riviere C, Severe P, Lavoile K, Duran Mendicuti MA, Pierre S, Rouzier V, Walsh KF, Byrne AL, Joseph P, Cremieux PY, Pape JW, and Koenig SP
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Article Summary: We assessed the association between C-reactive protein (CRP) and Mycobacterium tuberculosis (TB) diagnosis in symptomatic patients at HIV diagnosis. We found that CRP concentrations can improve tuberculosis risk stratification, facilitating decision making about whether (specific) tuberculosis testing is indicated before antiretroviral therapy initiation., Background: The World Health Organization recommends initiating same-day ART while tuberculosis testing is underway for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve tuberculosis risk stratification in this population., Methods: In this baseline analysis of 498 adults (>18 years) with tuberculosis symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP (≥3 mg/dL) using generalized linear models., Results: Eighty-seven (17.5%) patients were diagnosed with baseline TB. The median CRP was 33.0 mg/L (IQR: 5.1, 85.5) in those with TB, and 2.6 mg/L (IQR: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4%, and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART, and 0.8% to 5.0% would have untreated TB at ART initiation., Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3-fold to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.
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- 2023
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34. Ancestral Origin and Dissemination Dynamics of Reemerging Toxigenic Vibrio cholerae, Haiti.
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Mavian CN, Tagliamonte MS, Alam MT, Sakib SN, Cash MN, Moir M, Jimenez JP, Riva A, Nelson EJ, Cato ET, Ajayakumar J, Louis R, Curtis A, De Rochars VMB, Rouzier V, Pape JW, de Oliveira T, Morris JG Jr, Salemi M, and Ali A
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- Humans, Haiti epidemiology, Bayes Theorem, Disease Outbreaks, Vibrio cholerae genetics, Cholera epidemiology
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The 2010 cholera epidemic in Haiti was thought to have ended in 2019, and the Prime Minister of Haiti declared the country cholera-free in February 2022. On September 25, 2022, cholera cases were again identified in Port-au-Prince. We compared genomic data from 42 clinical Vibrio cholerae strains from 2022 with data from 327 other strains from Haiti and 1,824 strains collected worldwide. The 2022 isolates were homogeneous and closely related to clinical and environmental strains circulating in Haiti during 2012-2019. Bayesian hypothesis testing indicated that the 2022 clinical isolates shared their most recent common ancestor with an environmental lineage circulating in Haiti in July 2018. Our findings strongly suggest that toxigenic V. cholerae O1 can persist for years in aquatic environmental reservoirs and ignite new outbreaks. These results highlight the urgent need for improved public health infrastructure and possible periodic vaccination campaigns to maintain population immunity against V. cholerae.
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- 2023
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35. Threatening the Global AIDS Response - Obstacles to PEPFAR's Reauthorization.
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Abdool Karim SS, Barre-Sinoussi F, Varmus HE, Serwadda D, Bukusi E, M'boup S, Kamarulzaman A, Swaminathan S, and Pape JW
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- Humans, HIV Infections drug therapy, HIV Infections prevention & control, International Cooperation, United States, Government Programs legislation & jurisprudence, Federal Government, International Health Regulations, Acquired Immunodeficiency Syndrome drug therapy, Acquired Immunodeficiency Syndrome prevention & control
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- 2023
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36. Successful outcomes for patients with drug-resistant tuberculosis despite civil unrest and COVID-19 in Haiti.
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Vilbrun SC, Souroutzidis A, Walsh KF, Ellis J, Guiteau C, Delva S, Joissaint G, Joseph P, Pape JW, and Koenig SP
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Globally, treatment outcomes for people with multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB) are sub-optimal, with MDR/RR-TB programs further weakened due to the COVID-19 pandemic, and in Haiti, by severe civil unrest. We assessed the impact of these disruptions on treatment outcomes at GHESKIO, in Port-au-Prince, Haiti. We conducted a retrospective analysis including all adults (age ≥18 years) who initiated MDR/RR-TB treatment at GHESKIO from 2010 to 2020. We assessed predictors of poor treatment outcome using multivariable logistic regression, adjusting for baseline characteristics and year of treatment. 453 patients initiated treatment for MDR/RR-TB at GHESKIO. Median age was 31 (IQR: 25, 40), 233 (51.4%) were male, and 100 (22.1%) were living with HIV. Three hundred sixty-nine patients (81.5%) achieved cure, 42 (9.3%) died, 40 (8.8%) were lost to follow-up and 2 (<1%) failed treatment. HIV status was associated with poor treatment outcome (aRR: 1.65 (95% CI: 1.09, 2.48)) but there was no difference by year of treatment initiation. Outcomes for patients with MDR/RR-TB remained outstanding, even during the COVID-19 pandemic and severe civil unrest in Haiti. We attribute this resilience in care to the adaptability of program staff and provision of economic and psychosocial support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vilbrun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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37. Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.
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Dorvil N, Rivera VR, Riviere C, Berman R, Severe P, Bang H, Lavoile K, Devieux JG, Faustin M, Saintyl G, Mendicuti MD, Pierre S, Apollon A, Dumond E, Forestal GPL, Rouzier V, Marcelin A, McNairy ML, Walsh KF, Dupnik K, Reif LK, Byrne AL, Bousleiman S, Orvis E, Joseph P, Cremieux PY, Pape JW, and Koenig SP
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- Adult, Humans, Haiti epidemiology, RNA, Anti-HIV Agents therapeutic use, HIV Infections complications, HIV Infections diagnosis, HIV Infections drug therapy, Tuberculosis complications, Tuberculosis diagnosis, Tuberculosis drug therapy
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Background: Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population., Methods and Findings: We conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA <200 copies/mL, with intention to treat (ITT) analysis. From November 6, 2017 to January 16, 2020, 500 participants were randomized (250/group); the final study visit occurred on March 1, 2021. Baseline TB was diagnosed in 40 (16.0%) in the standard and 48 (19.2%) in the same-day group; all initiated TB treatment. In the standard group, 245 (98.0%) initiated ART at median of 9 days; 6 (2.4%) died, 15 (6.0%) missed the 48-week visit, and 229 (91.6%) attended the 48-week visit. Among all who were randomized, 220 (88.0%) received 48-week HIV-1 RNA testing; 168 had <200 copies/mL (among randomized: 67.2%; among tested: 76.4%). In the same-day group, 249 (99.6%) initiated ART at median of 0 days; 9 (3.6%) died, 23 (9.2%) missed the 48-week visit, and 218 (87.2%) attended the 48-week visit. Among all who were randomized, 211 (84.4%) received 48-week HIV-1 RNA; 152 had <200 copies/mL (among randomized: 60.8%; among tested: 72.0%). There was no difference between groups in the primary outcome (60.8% versus 67.2%; risk difference: -0.06; 95% CI [-0.15, 0.02]; p = 0.14). Two new grade 3 or 4 events were reported per group; none were judged to be related to the intervention. The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain., Conclusions: In patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes., Trial Registration: This study is registered with ClinicalTrials.gov NCT03154320., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dorvil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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38. Prevalence and Severity of Chronic Kidney Disease in Haiti.
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Roberts NLS, Pierre JL, Rouzier V, Sufra R, St-Preux S, Yan LD, Metz M, Clermont A, Apollon A, Sabwa S, Deschamps MM, Kingery JR, Peck R, Fitzgerald D, Pape JW, Tummalapalli SL, and McNairy ML
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- Adult, Humans, Female, Male, Haiti epidemiology, Prevalence, Creatinine, Nutrition Surveys, Longitudinal Studies, Cross-Sectional Studies, Glomerular Filtration Rate, Risk Factors, Albumins, Albuminuria urine, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic epidemiology, Renal Insufficiency, Chronic complications, Diabetes Mellitus epidemiology, Hypertension epidemiology, Hypertension complications
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Background: CKD is a major cause of morbidity and mortality in lower-income countries. However, population-based studies characterizing the epidemiology of CKD in these settings are lacking. The study objective was to describe the epidemiology of CKD in a population-based cohort in urban Haiti, including estimates of the prevalence by CKD stage, the magnitude of associated factors with CKD, and the proportion on guideline-recommended treatment., Methods: We assessed the prevalence of CKD and associated risk factors in the population-based Haiti Cardiovascular Disease Cohort. We analyzed cross-sectional data from 2424 adults who completed a clinical examination, risk factor surveys, and laboratory measurements for serum creatinine, urinary albumin, and urinary creatinine. We compared our results with US estimates from the National Health and Nutrition Examination Survey. CKD was defined as either a reduced eGFR <60 ml/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥30 mg/g according to the Kidney Disease Improving Global Outcomes guidelines. Multivariable logistic regression identified associated factors with CKD., Results: The mean age was 42 years, 57% of participants were female, and 69% lived in extreme poverty on ≤1 US dollar per day. The age-standardized prevalence of CKD was 14% (95% confidence interval [CI], 12% to 15%). The age-standardized prevalence of reduced eGFR and elevated urinary albumin-to-creatinine ratio was 3% (95% CI, 2% to 4%) and 11% (95% CI, 10% to 13%), respectively. Diabetes (adjusted odds ratio, 4.1; 95% CI, 2.7 to 6.2) and hypertension (adjusted odds ratio, 2.9; 95% CI, 2.0 to 4.2) were significantly associated with CKD. Only 12% of participants with CKD and albuminuria were on guideline-recommended agents, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers., Conclusions: In a large population-based cohort of Haitian adults, CKD was highly associated with both diabetes and hypertension. The proportion of participants with CKD on treatment was low, underscoring the need for strengthening clinical management and nephrology care health infrastructure in Haiti., Clinical Trial Registry Name and Registration Number: A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti, NCT03892265 ., (Copyright © 2023 by the American Society of Nephrology.)
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- 2023
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39. In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.
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Hooli S, King C, McCollum ED, Colbourn T, Lufesi N, Mwansambo C, Gregory CJ, Thamthitiwat S, Cutland C, Madhi SA, Nunes MC, Gessner BD, Hazir T, Mathew JL, Addo-Yobo E, Chisaka N, Hassan M, Hibberd PL, Jeena P, Lozano JM, MacLeod WB, Patel A, Thea DM, Nguyen NTV, Zaman SM, Ruvinsky RO, Lucero M, Kartasasmita CB, Turner C, Asghar R, Banajeh S, Iqbal I, Maulen-Radovan I, Mino-Leon G, Saha SK, Santosham M, Singhi S, Awasthi S, Bavdekar A, Chou M, Nymadawa P, Pape JW, Paranhos-Baccala G, Picot VS, Rakoto-Andrianarivelo M, Rouzier V, Russomando G, Sylla M, Vanhems P, Wang J, Basnet S, Strand TA, Neuman MI, Arroyo LM, Echavarria M, Bhatnagar S, Wadhwa N, Lodha R, Aneja S, Gentile A, Chadha M, Hirve S, O'Grady KF, Clara AW, Rees CA, Campbell H, Nair H, Falconer J, Williams LJ, Horne M, Qazi SA, and Nisar YB
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- Child, Humans, Female, Infant, Child, Preschool, Hospital Mortality, Oximetry, World Health Organization, Risk Assessment, Pneumonia diagnosis, Malnutrition
- Abstract
Objectives: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors., Methods: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors., Results: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32)., Conclusion: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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40. High Dietary Sodium, Measured Using Spot Urine Samples, is Associated with Higher Blood Pressure among Young Adults in Haiti.
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Clermont A, Rouzier V, Pierre JL, Sufra R, Dade E, Preval F, St-Preux S, Deschamps MM, Apollon A, Dupnik K, Metz M, Duffus Y, Sabwa S, Yan LD, Lee MH, Palmer LG, Gerber LM, Pecker MS, Mann SJ, Safford MM, Fitzgerald DW, Pape JW, and McNairy ML
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- Humans, Female, Young Adult, Aged, Adolescent, Adult, Middle Aged, Aged, 80 and over, Male, Sodium Chloride, Dietary, Haiti, Blood Pressure, Sodium urine, Sodium, Dietary, Cardiovascular Diseases complications, Hypertension epidemiology
- Abstract
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., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)
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- 2023
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41. Population-Based Epidemiology of Heart Failure in a Low-Income Country: The Haiti Cardiovascular Disease Cohort.
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Kingery JR, Roberts NL, Lookens Pierre J, Sufra R, Dade E, Rouzier V, Malebranche R, Theard M, Goyal P, Pirmohamed A, Yan LD, Hee Lee M, Nash D, Metz M, Peck RN, Safford MM, Fitzgerald D, Deschamps MM, Pape JW, and McNairy M
- Subjects
- Adult, Humans, Female, Middle Aged, Male, Stroke Volume, Haiti, Risk Factors, Cardiovascular Diseases, Heart Failure
- Abstract
Background: Cardiovascular disease disproportionately affects persons living in low- and middle-income countries and heart failure (HF) is thought to be a leading cause. Population-based studies characterizing the epidemiology of HF in these settings are lacking. We describe the age-standardized prevalence, survival, subtypes, risk factors, and 1-year mortality of HF in the population-based Haiti Cardiovascular Disease Cohort., Methods: Participants were recruited using multistage cluster-area random sampling in Port-au-Prince, Haiti. A total of 2981 completed standardized history and exam, laboratory measures, and cardiac imaging. Clinical HF was defined by Framingham criteria. Kaplan-Meier and Cox proportional hazard regression assessed mortality among participants with and without HF; logistic regression identified associated factors., Results: Among all participants, the median age was 40 years (interquartile range, 27-55), and 58.2% were female. Median follow-up was 15.4 months (interquartile range, 9-22). The age-standardized HF prevalence was 3.2% (93/2981 [95% CI, 2.6-3.9]). The average age of participants with HF was 57 years (interquartile range, 45-65), and 67.7% were female. The first significant increase in HF prevalence occurred between 30 to 39 and 40 to 49 years (1.1% versus 3.7%, P =0.003). HF with preserved ejection fraction was the most common HF subtype (71.0%). Age (adjusted odds ratio, 1.36 [1.12-1.66] per 10-year increase), hypertension (2.14 [1.26-3.66]), obesity (3.35 [95% CI, 1.99-5.62]), poverty (2.10 [1.18-3.72]), and renal dysfunction (5.42 [2.94-9.98]) were associated with HF. One-year HF mortality was 6.6% versus 0.8% (hazard ratio, 7.7 [95% CI, 2.9-20.6]; P <0.0001)., Conclusions: The age-standardized prevalence of HF in this low-income setting was alarmingly high at 3.2%-5-fold higher than modeling estimates for low- and middle-income countries. Adults with HF were two decades younger and 7.7× more likely to die at 1 year compared with those in the community without HF. Further research characterizing the population burden of HF in low- and middle-income countries can guide resource allocation and development of pragmatic HF prevention and treatment interventions, ultimately reducing global cardiovascular disease health disparities., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03892265.
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- 2023
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42. Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.
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Martin H, Falconer J, Addo-Yobo E, Aneja S, Arroyo LM, Asghar R, Awasthi S, Banajeh S, Bari A, Basnet S, Bavdekar A, Bhandari N, Bhatnagar S, Bhutta ZA, Brooks A, Chadha M, Chisaka N, Chou M, Clara AW, Colbourn T, Cutland C, D'Acremont V, Echavarria M, Gentile A, Gessner B, Gregory CJ, Hazir T, Hibberd PL, Hirve S, Hooli S, Iqbal I, Jeena P, Kartasasmita CB, King C, Libster R, Lodha R, Lozano JM, Lucero M, Lufesi N, MacLeod WB, Madhi SA, Mathew JL, Maulen-Radovan I, McCollum ED, Mino G, Mwansambo C, Neuman MI, Nguyen NTV, Nunes MC, Nymadawa P, O'Grady KF, Pape JW, Paranhos-Baccala G, Patel A, Picot VS, Rakoto-Andrianarivelo M, Rasmussen Z, Rouzier V, Russomando G, Ruvinsky RO, Sadruddin S, Saha SK, Santosham M, Singhi S, Soofi S, Strand TA, Sylla M, Thamthitiwat S, Thea DM, Turner C, Vanhems P, Wadhwa N, Wang J, Zaman SM, Campbell H, Nair H, Qazi SA, and Nisar YB
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- Male, Child, Humans, Infant, Infant, Newborn, Child, Preschool, Female, Case Management, World Health Organization, Algorithms, Research, Pneumonia drug therapy
- Abstract
Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines., Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set., Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males., Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: YBN is staff member of the World Health Organization., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)
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- 2022
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43. Transcriptional Biomarkers of Differentially Detectable Mycobacterium tuberculosis in Patient Sputum.
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Zainabadi K, Saito K, Mishra S, Walsh KF, Mathurin LD, Vilbrun SC, Ocheretina O, Pape JW, Fitzgerald DW, Nathan CF, and Lee MH
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- Humans, Sputum microbiology, RNA, Ribosomal, 16S, Antitubercular Agents therapeutic use, Rifampin therapeutic use, Sensitivity and Specificity, Mycobacterium tuberculosis genetics, Tuberculosis microbiology
- Abstract
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.
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- 2022
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44. Extreme Food Insecurity and Malnutrition in Haiti: Findings from a Population-Based Cohort in Port-au-Prince, Haiti.
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Rasul R, Rouzier V, Sufra R, Yan LD, Joseph I, Mourra N, Sabwa S, Deschamps MM, Fitzgerald DW, Pape JW, Nash D, and McNairy ML
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- Humans, Cohort Studies, Haiti epidemiology, Food Insecurity, Obesity epidemiology, Food Supply, Malnutrition epidemiology
- Abstract
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/m
2 . 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.- Published
- 2022
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45. An optimized method for purifying, detecting and quantifying Mycobacterium tuberculosis RNA from sputum for monitoring treatment response in TB patients.
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Zainabadi K, Lee MH, Walsh KF, Vilbrun SC, Mathurin LD, Ocheretina O, Pape JW, and Fitzgerald DW
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- Humans, RNA, Ribosomal, 16S genetics, Sensitivity and Specificity, Sputum microbiology, Mycobacterium tuberculosis genetics, Tuberculosis, Lymph Node, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary microbiology
- Abstract
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., (© 2022. The Author(s).)
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- 2022
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46. High prevalence of obesity among women in urban Haiti: Findings from a population-based cohort.
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Dade E, Metz M, Pierre JL, Rouzier V, Sufra R, Fox E, Preval F, St-Preux S, Zephir JR 2nd, Ariste W, Rasul R, Sabwa S, Roberts N, Deschamps MM, Severe P, Fitzgerald D, Pape JW, Yan LD, and McNairy ML
- Subjects
- Male, Humans, Female, Adult, Prevalence, Cohort Studies, Haiti epidemiology, Obesity, Abdominal complications, Obesity, Abdominal epidemiology, Obesity epidemiology
- Abstract
Introduction: Obesity is associated with increased risk of non-communicable diseases and death and is increasing rapidly in low- and middle-income countries, including Haiti. There is limited population-based data on body mass index (BMI) and waist circumference (WC) and associated risk factors in Haiti. This study describes BMI and WC, and factors associated with obesity using a population-based cohort from Port-au-Prince., Methods: Baseline sociodemographic and clinical data were collected from participants in the Haiti CVD Cohort Study between March 2019 and August 2021. Weight was categorized by BMI (kg/m
2 ) with obesity defined as ≥30 kg/m2 . Abdominal obesity was defined using WC cutoffs of ≥80 cm for women and ≥94 cm for men based on WHO guidelines. Sociodemographic and behavioral risk factors, including age, sex, educational attainment, income, smoking status, physical activity, fat/oil use, daily fruit/vegetable consumption, and frequency of fried food intake were assessed for their association with obesity using a Poisson multivariable regression., Results: Among 2,966 participants, median age was 41 years (IQR: 28-55) and 57.6% were women. Median BMI was 24.0 kg/m2 (IQR: 20.9-28.1) and 508 (17.1%) participants were obese. Women represented 89.2% of the population with BMI ≥30 kg/m2 . A total of 1,167 (68.3%) women had WC ≥80 cm and 144 (11.4%) men had WC ≥94 cm. BMI ≥30 kg/m2 was significantly more prevalent among women than men [PR 5.7; 95% CI: (4.3-7.6)], those 40-49 years compared to 18-29 years [PR 3.3; 95% CI: (2.4-4.6)], and those with income >10 USD per day compared to ≤1 USD [PR 1.3; 95% CI: (1.0-1.6)]. There were no significant associations with other health and behavioral risk factors., Discussion: In Haiti, women have an alarming 6-fold higher obesity prevalence compared to men (26.5 vs. 4.3%) and 89.2% of participants with obesity were women. Abdominal obesity was high, at 44.3%. Haiti faces a paradox of an ongoing national food insecurity crises and a burgeoning obesity epidemic. Individual, social, and environmental drivers of obesity, especially among women, need to be identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dade, Metz, Pierre, Rouzier, Sufra, Fox, Preval, St-Preux, Zephir, Ariste, Rasul, Sabwa, Roberts, Deschamps, Severe, Fitzgerald, Pape, Yan and McNairy.)- Published
- 2022
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47. Time to Culture Conversion of Bedaquiline and High-Dose Isoniazid for Drug-Resistant Tuberculosis.
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Walsh KF, Vilbrun SC, Souroutzidis A, Ellis J, Delva S, Joissaint G, Dupnik KM, Joseph P, Pape JW, and Koenig SP
- Abstract
Patients with multidrug-resistant tuberculosis who received regimens containing high-dose isoniazid (INH
HD ) had similar time to culture conversion and treatment outcomes as patients who received regimens with bedaquiline. INHHD is an inexpensive and safe medication that may contribute additive efficacy in combination regimens., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)- Published
- 2022
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48. Spatial Video and EpiExplorer: A Field Strategy to Contextualize Enteric Disease Risk in Slum Environments.
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Ajayakumar J, Curtis AJ, Rouzier V, Pape JW, Bempah S, Alam MT, Alam MM, Rashid MH, Ali A, and Morris JG Jr
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- Geographic Information Systems, Hygiene, Sanitation, Communications Media, Poverty Areas
- Abstract
Disease risk associated with contaminated water, poor sanitation, and hygiene in informal settlement environments is conceptually well understood. From an analytical perspective, collecting data at a suitably fine scale spatial and temporal granularity is challenging. Novel mobile methodologies, such as spatial video (SV), can complement more traditional epidemiological field work to address this gap. However, this work then poses additional challenges in terms of analytical visualizations that can be used to both understand sub-neighborhood patterns of risk, and even provide an early warning system. In this paper, we use bespoke spatial programming to create a framework for flexible, fine-scale exploratory investigations of simultaneously-collected water quality and environmental surveys in three different informal settlements of Port-au-Prince, Haiti. We dynamically mine these spatio-temporal epidemiological and environmental data to provide insights not easily achievable using more traditional spatial software, such as Geographic Information System (GIS). The results include sub-neighborhood maps of localized risk that vary monthly. Most interestingly, some of these epidemiological variations might have previously been erroneously explained because of proximate environmental factors and/or meteorological conditions.
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- 2022
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49. Rapid Emergence and Spread of Severe Acute Respiratory Syndrome Coronavirus 2 Gamma (P.1) Variant in Haiti.
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Tagliamonte MS, Mavian C, Zainabadi K, Cash MN, Lednicky JA, Magalis BR, Riva A, Deschamps MM, Liautaud B, Rouzier V, Fitzgerald DW, Pape JW, Morris JG, and Salemi M
- Subjects
- COVID-19 Testing, Haiti epidemiology, Humans, COVID-19, SARS-CoV-2 genetics
- Abstract
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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2022
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50. Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.
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Crabtree-Ramirez B, Jenkins CA, Shepherd BE, Jayathilake K, Veloso VG, Carriquiry G, Gotuzzo E, Cortes CP, Padgett D, McGowan C, Sierra-Madero J, Koenig S, Pape JW, and Sterling TR
- Subjects
- Adult, Antitubercular Agents therapeutic use, Brazil, Cohort Studies, Humans, Isoniazid therapeutic use, HIV Infections epidemiology, Tuberculosis complications, Tuberculosis drug therapy
- Abstract
Background: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described., Methods: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation., Results: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20)., Conclusions: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America., (© 2022. The Author(s).)
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- 2022
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