Protozoan-Viral-Bacterial Co-Infections Alter Galectin Levels and Associated Immunity Mediators in the Female Genital Tract.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log10 unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1ß and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1ß and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1ß and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro, TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1ß, mirroring the clinical findings of mixed TV-BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral-protozoan-bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections.

Factors Influencing Uptake of Rapid HIV and Hepatitis C Screening Among Drug Misusing Adult Emergency Department Patients: Implications for Future HIV/HCV Screening Interventions.

In this randomized, controlled trial among 957 English- or Spanish-speaking drug misusing adult emergency department (ED) patients, we determined if a tailored brief intervention (BI) increased uptake of rapid HIV/HCV screening, and identified factors associated with greater screening uptake. Rapid HIV/HCV screening uptake was greater in the control than the BI arm (45 vs. 38 %; p < 0.04). Screening uptake depended on elapsed study time and which research staff member offered testing. In the control arm, uptake was lowest for those spending <30 or ≥90 min in the study. In the BI arm, screening uptake generally increased over time. Tailored BI content specifically addressing participant HIV/HCV knowledge, HIV/HCV risk behaviors, or need for HIV/HCV screening was not associated with greater screening uptake. These study findings suggested factors that should be considered when designing future ED-based screening initiatives, such as elapsed study time, who offers testing, and the content of interventions.

The spectrum of undiagnosed hepatitis C virus infection in a US HIV clinic.

United States guidelines endorse one-time HCV antibody screening at HIV diagnosis. Rescreening HCV-seronegative patients on a regular basis is still not policy, although HIV-infected persons have reasonably substantial HCV incidence. We evaluated routine risk factor-independent HCV antibody re-testing in a Rhode Island HIV clinic. We instituted annual HCV antibody testing for HCV-seronegative patients who had not been rescreened in a year or more. Testing based on clinical suspicion continued. We conducted a chart review of new antibody-positive cases in the first year of rescreening, July 2006 to June 2007. Of 245 rescreened patients, 11 (4.5%) seroconverted. Five (45%) were female. Median time between last negative and first positive result was 32 months (range 8-98 months). Six (55%) had documented risk factors and 6 (55%) elevated ALT (> 45 IU/L) between antibody tests; none prompted re-testing. One seroconverter died of hepatocellular carcinoma 3.7 years after HCV diagnosis. A twelfth was rescreened for suspected acute HCV based on ALT of 515 IU/L. He had newly detectable HCV RNA then seroconversion, and achieved SVR following 6 months of treatment in the acute phase for genotype 1 infection. Incident HCV is not uncommon among HIV-infected patients in care. Rescreening identified undiagnosed HCV in this population. HCV RNA should be checked promptly in HCV-seronegative persons with ALT elevation. We observed consequences of late diagnosis (hepatocellular carcinoma) and benefits of early diagnosis (cure with treatment of acute HCV). Adding annual rescreening to the Ryan White Program would facilitate earlier identification of undiagnosed HCV and create an instant widespread surveillance system, providing HCV incidence data.

Factors associated with isolated right heart failure in women: a pilot study from western Kenya.

BACKGROUND: Small observational studies have found that isolated right heart failure (IRHF) is prevalent among women of sub-Saharan Africa. Further, several risk factors for the development of IRHF have been identified. However, no similar studies have been conducted in Kenya. OBJECTIVE: We hypothesized that specific environmental exposures and comorbidities were associated with IRHF in women of western Kenya. METHODS: We conducted a case-control study at a referral hospital in western Kenya. Cases were defined as women at least 35 years old with IRHF. Control subjects were similarly aged volunteers without IRHF. Exclusion criteria in both groups included history of tobacco use, tuberculosis, or thromboembolic disease. Participants underwent echocardiography, spirometry, 6-min walk test, rest/exercise oximetry, respiratory health interviews, and human immunodeficiency virus (HIV) testing. Home visits were performed to evaluate kitchen ventilation, fuel use, and cook smoke exposure time, all surrogate measures of indoor air pollution (IAP). A total of 31 cases and 65 control subjects were enrolled. Surrogate measures of indoor air pollution were not associated with IRHF. However, lower forced expiratory volume at 1 s percent predicted (adjusted odds ratio [AOR]: 2.02, 95% confidence interval [CI]: 1.27 to 3.20; p = 0.004), HIV positivity (AOR: 40.4, 95% CI: 3.7 to 441; p < 0.01), and self-report of exposure to occupational dust (AOR: 3.9, 95% CI: 1.14 to 14.2; p = 0.04) were associated with IRHF. In an analysis of subgroups of participants with and without these factors, lower kitchen ventilation was significantly associated with IRHF among participants without airflow limitation (AOR: 2.63 per 0.10 unit lower ventilation, 95% CI: 1.06 to 6.49; p = 0.04), without HIV (AOR: 2.55, 95% CI: 1.21 to 5.37; p = 0.02), and without occupational dust exposure (AOR: 2.37, 95% CI: 1.01 to 5.56; p = 0.05). CONCLUSIONS: In this pilot study among women of western Kenya, lower kitchen ventilation, airflow limitation, HIV, and occupational dust exposure were associated with IRHF, overall or in participant subgroups. Direct or indirect causality requires further study.

Predictors of the initiation of HIV postexposure prophylaxis in Rhode Island emergency departments.

The objective of this study was to elucidate factors that predicted the initiation of HIV postexposure prophylaxis (PEP) for blood or body fluid exposures evaluated at Rhode Island emergency departments (EDs). The study involved a retrospective review of patient visits to all civilian Rhode Island EDs for these exposures from 1995 to mid-2001. Multivariate logistic regression models were created to evaluate predictors of the offering and the acceptance and receipt of HIV PEP from 1996 to 2001. The search identified 3622 patients who sustained a blood or body fluid exposure. Of these, 43.8% were health care workers (HCWs) and 57.2% were not HCWs. Most (52.0%) of the exposures were nonsexual. HIV PEP was offered to 21.0% and accepted and received by 9.4% of all patients. HIV PEP was offered more often after significant exposures, exposures to known HIV-infected sources, when time elapsed after the exposure was shorter, if the patients were HCWs, adults, presented to a teaching hospital, presented during the latter years of the study, or sustained nonsexual exposures. Once offered HIV PEP, patients who were male, adult, sustained a significant exposure, knew the source was HIV infected, sustained a nonsexual exposure, or were HCWs had a greater odds of accepting and receiving HIV PEP. Even when controlling for exposure significance, HIV status, and time elapsed since the exposure, several factors such as gender and type of hospital that are unrelated to the exposure appeared to influence the initiation of HIV PEP. ED providers should ensure that these factors do not inappropriately restrict its initiation.