Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.

BACKGROUND: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. METHODS: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. RESULTS: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. INTERPRETATION: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.

High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti.

BACKGROUND: In low HIV prevalence settings, understanding the transmission dynamics and the impact of drug resistance is critical to curb down the epidemic. This study aims to explore the prevalence and dynamics of transmission of HIV drug-resistance mutations (DRMs) among key populations in Haiti. SETTINGS: Eligible participants (naive, treated) were selected from 7 key population friendly health care centers in Port-au-Prince, Haiti, from September 2018 to July 2019. METHODS: A total of 119 HIV-1 pol sequences were analyzed from men having sex with men (MSM), female sex workers (FSWs), and their sexual partners. Screening for HIV DRMs was performed using the Stanford University Drug Resistance Database. Phylogenetic and network analyses using HIV-TRACE software were performed to infer putative relationships and shared DRMs. RESULTS: Of the 119 participants, 62.2% were men (74/119), and 75.7% of them (56/74) reported MSM as a main risk factor. The overall DRM prevalence was 58.8% (70/119). A DRM was observed in 37.5% of MSM (21/56), 82.2% of FSWs (37/45), and 66.7% (12/18) among FSWs' clients. In a multivariate model, age and FSWs were significant predictors for DRMs (P = 0.001). Transmission network analysis found 24 of the 119 (20.2%) genetically linked individuals forming 8 clusters. Clustering participants were mostly MSM (15/24; 62.5%). Five clusters (62.5%) had shared DRMs, and K103N and M184V were the main shared mutations. CONCLUSIONS: High prevalence of HIV DRMs was observed among MSM, FSWs, and their clients in Port-au-Prince, Haiti. Network analysis revealed frequent DRM transmission among genetically linked individuals, highlighting the need for appropriate interventions to limit HIV transmission in these high-risk populations.

Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis in men having sex with men in Port-au-Prince, Haiti: a cross-sectional study.

OBJECTIVES: Over the last 15 years, the prevalence of HIV in Haiti has stabilised to around 2.0%. However, key populations remain at higher risk of contracting HIV and other sexually transmitted infections (STIs). The prevalence of HIV is 12.9% among men having sex with men (MSM). There is limited information about the prevalence of other STI in the Haitian population in general and even less among key populations. We assessed the burden of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) and risk factors for infections among MSM in Haiti. METHODS: A cross-sectional study was conducted. MSM were recruited from seven health facilities in Port-au-Prince. All samples were tested by nucleic acid amplification test, using GeneXpert. A survey was administered to the participants to collect socio-demographic, clinical and risk behaviour data. RESULTS: A total of 216 MSM were recruited in the study. The prevalence rates of CT and NG were 11.1% and 16.2%, respectively. CT NG co-infections were found in 10/216 (4.6%) of the participants. There were 39 MSM with rectal STI compared with 17 with genital infections. Participants between 18-24 and 30-34 years old were significantly more likely to be infected with NG than those aged 35 years or older (OR: 22.96, 95% CI: 2.79 to 188.5; OR: 15.1, 95% CI: 1.68 to 135.4, respectively). Participants who never attended school or had some primary education were significantly more likely to be infected with NG than those with secondary education or higher (OR: 3.38, 95% CI: 1.26 to 9.07). People tested negative for HIV were significantly more likely to be infected with CT than people living with HIV/AIDS (OR: 3.91, 95% CI: 1.37 to 11.2). CONCLUSIONS: Periodic risk assessment and testing for STI should be offered in Haiti as part of a comprehensive strategy to improve the sexual health of key populations.

External quality assessment for HIV rapid tests: challenges and opportunities in Haiti.

HIV rapid diagnostic tests (RDTs) are instrumental in scaling-up HIV testing services (HTS) in low-income and middle-income countries (LMICs). HIV misdiagnosis is a growing concern in the era of expanded and decentralised access to HTS. External quality assurance (EQA) programme including proficiency testing (PT) for HIV RDTs is a priority to guarantee the accuracy and reliability of the patients' result. Here we are sharing Haiti's 11 years' experience in implementing HIV RDTs EQA programme to help address some of the challenges faced by other LMICs. HTS is expanding beyond laboratory walls and HIV RDTs are increasingly performed by non-laboratory personnel and closer to the community. EQA programmes for HIV RDTs in Haiti have faced significant challenges. In expanded HTS settings, non-laboratory personnel (nurses, aid-nurses) involved in HIV RDT are usually undertrained and participate poorly in PT programs. In more than half of the lab enrolled in the PT programme in Haiti, the panels are always tested by the most experienced technician, defying the purpose of the program which is to evaluate the performance of the technician performing the test daily. EQA programme in Haiti and other LMICs are usually not tailored to address community HIV testing challenges. With decreased funding and absence of government financial commitment to HIV RDTs EQA programmes, more innovative and cost-efficient strategies are sought to ensure the quality of HIV diagnosis in LMICs. Qualified human resources, continuous training, supervision and community-tailored PT programmes remain key components for the success of HIV RDT quality management.

Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.

INTRODUCTION: Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti. METHODS: Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures. RESULTS: Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]). CONCLUSIONS: This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

Building and Rebuilding: The National Public Health Laboratory Systems and Services Before and After the Earthquake and Cholera Epidemic, Haiti, 2009-2015.

Before the 2010 devastating earthquake and cholera outbreak, Haiti's public health laboratory systems were weak and services were limited. There was no national laboratory strategic plan and only minimal coordination across the laboratory network. Laboratory capacity was further weakened by the destruction of over 25 laboratories and testing sites at the departmental and peripheral levels and the loss of life among the laboratory health-care workers. However, since 2010, tremendous progress has been made in building stronger laboratory infrastructure and training a qualified public health laboratory workforce across the country, allowing for decentralization of access to quality-assured services. Major achievements include development and implementation of a national laboratory strategic plan with a formalized and strengthened laboratory network; introduction of automation of testing to ensure better quality of results and diversify the menu of tests to effectively respond to outbreaks; expansion of molecular testing for tuberculosis, human immunodeficiency virus, malaria, diarrheal and respiratory diseases; establishment of laboratory-based surveillance of epidemic-prone diseases; and improvement of the overall quality of testing. Nonetheless, the progress and gains made remain fragile and require the full ownership and continuous investment from the Haitian government to sustain these successes and achievements.

Implementation of broad screening with Ebola rapid diagnostic tests in Forécariah, Guinea.

BACKGROUND: Laboratory-enhanced surveillance is critical for rapidly detecting the potential re-emergence of Ebola virus disease. Rapid diagnostic tests (RDT) for Ebola antigens could expand diagnostic capacity for Ebola virus disease. OBJECTIVES: The Guinean National Coordination for Ebola Response conducted a pilot implementation to determine the feasibility of broad screening of patients and corpses with the OraQuick® Ebola RDT. METHODS: The implementation team developed protocols and trained healthcare workers to screen patients and corpses in Forécariah prefecture, Guinea, from 15 October to 30 November 2015. Data collected included number of consultations, number of fevers reported or measured, number of tests performed for patients or corpses and results of confirmatory RT-PCR testing. Data on malaria RDT results were collected for comparison. Feedback from Ebola RDT users was collected informally during supervision visits and forums. RESULTS: There were 3738 consultations at the 15 selected healthcare facilities; 74.6% of consultations were for febrile illness. Among 2787 eligible febrile patients, 2633 were tested for malaria and 1628 OraQuick® Ebola RDTs were performed. A total of 322 OraQuick® Ebola RDTs were conducted on corpses. All Ebola tests on eligible patients were negative. CONCLUSIONS: Access to Ebola testing was expanded by the implementation of RDTs in an emergency situation. Feedback from Ebola RDT users and lessons learned will contribute to improving quality for RDT expansion.

Seroprevalence of Herpes Simplex Virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti.

BACKGROUND: Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. METHODS: Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. RESULTS: Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. CONCLUSION: The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

Natriuretic peptide receptor A signaling regulates stem cell recruitment and angiogenesis: a model to study linkage between inflammation and tumorigenesis.

Natriuretic peptide receptor A (NPRA), the signaling receptor for the cardiac hormone, atrial natriuretic peptide (ANP), is expressed abundantly in inflamed/injured tissues and tumors. NPRA deficiency substantially decreases tissue inflammation and inhibits tumor growth. However, the precise mechanism of NPRA function and whether it links inflammation and tumorigenesis remains unknown. Since both injury repair and tumor growth require stem cell recruitment and angiogenesis, we examined the role of NPRA signaling in tumor angiogenesis as a model of tissue injury repair in this study. In in vitro cultures, aortas from NPRA-KO mice show significantly lower angiogenic response compared to wild-type counterparts. The NPRA antagonist that decreases NPRA expression, inhibits lipopolysaccharide-induced angiogenesis. The reduction in angiogenesis correlates with decreased expression of vascular endothelial growth factor and chemokine (C-X-C motif) receptor 4 (CXCR4) implicating a cell recruitment defect. To test whether NPRA regulates migration of cells to tumors, mesenchymal stem cells (MSCs) were administered i.v., and the results showed that MSCs fail to migrate to the tumor microenvironment in NPRA-KO mice. However, coimplanting tumor cells with MSCs increases angiogenesis and tumorigenesis in NPRA-KO mice, in part by promoting expression of CXCR4 and its ligand, stromal cell-derived factor 1α. Taken together, these results demonstrate that NPRA signaling regulates stem cell recruitment and angiogenesis leading to tumor growth. Thus, NPRA signaling provides a key linkage between inflammation and tumorigenesis, and NPRA may be a target for drug development against cancers and tissue injury repair.