Jennifer A. Downs

Examining the Relationship between Urogenital Schistosomiasis and HIV Infection

Background Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is widespread and causes substantial morbidity on the African continent. The infection has been suggested as an unrecognized risk factor for incident HIV infection. Current guidelines recommend preventive chemotherapy, using praziquantel as a public health tool, to avert morbidity due to schistosomiasis. In individuals of reproductive age, urogenital schistosomiasis remains highly prevalent and, likely, underdiagnosed. This comprehensive literature review was undertaken to examine the evidence for a cause-effect relationship between urogenital schistosomiasis and HIV/AIDS. The review aims to support discussions of urogenital schistosomiasis as a neglected yet urgent public health challenge. Methodology/Principal Findings We conducted a systematic search of the literature including online databases, clinical guidelines, and current medical textbooks. We describe plausible local and systemic mechanisms by which Schistosoma haematobium infection could increase the risk of HIV acquisition in both women and men. We also detail the effects of S. haematobium infection on the progression and transmissibility of HIV in co-infected individuals. We briefly summarize available evidence on the immunomodulatory effects of chronic schistosomiasis and the implications this might have for populations at high risk of both schistosomiasis and HIV. Conclusions/Significance Studies support the hypothesis that urogenital schistosomiasis in women and men constitutes a significant risk factor for HIV acquisition due both to local genital tract and global immunological effects. In those who become HIV-infected, schistosomal co-infection may accelerate HIV disease progression and facilitate viral transmission to sexual partners. Establishing effective prevention strategies using praziquantel, including better definition of treatment age, duration, and frequency of treatment for urogenital schistosomiasis, is an important public health priority. Our findings call attention to this pressing yet neglected public health issue and the potential added benefit of scaling up coverage of schistosomal treatment for populations in whom HIV infection is prevalent.

Urogenital Schistosomiasis in Women of Reproductive Age in Tanzania's Lake Victoria Region

We conducted a community-based study of 457 women aged 18-50 years living in eight rural villages in northwest Tanzania. The prevalence of female urogenital schistosomiasis (FUS) was 5% overall but ranged from 0% to 11%. FUS was associated with human immunodeficiency virus (HIV) infection (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.2-13.5) and younger age (OR = 5.5 and 95% CI = 1.2-26.3 for ages < 25 years and OR = 8.2 and 95% CI = 1.7-38.4 for ages 25-29 years compared with age > 35 years). Overall HIV prevalence was 5.9% but was 17% among women with FUS. We observed significant geographical clustering of schistosomiasis: northern villages near Lake Victoria had more Schistosoma mansoni infections (P < 0.0001), and southern villages farther from the lake had more S. haematobium (P = 0.002). Our data support the postulate that FUS may be a risk factor for HIV infection and may contribute to the extremely high rates of HIV among young women in sub-Saharan Africa.

Association of schistosomiasis and HIV infection in Tanzania

Animal and human studies suggest that Schistosoma mansoni infection may increase risk of human immunodeficiency virus (HIV) acquisition. Therefore, we tested 345 reproductive age women in rural Tanzanian villages near Lake Victoria, where S. mansoni is hyperendemic, for sexually transmitted infections (STIs) and schistosomiasis by circulating anodic antigen (CAA) serum assay. Over one-half (54%) had an active schistosome infection; 6% were HIV-seropositive. By univariate analysis, only schistosome infection predicted HIV infection (odds ratio [OR] = 3.9, 95% confidence interval = [1.3-12.0], P = 0.015) and remained significant using multivariate analysis to control for age, STIs, and distance from the lake (OR = 6.2 [1.7-22.9], P = 0.006). HIV prevalence was higher among women with more intense schistosome infections (P = 0.005), and the median schistosome intensity was higher in HIV-infected than -uninfected women (400 versus 15 pg CAA/mL, P = 0.01). This finding suggests that S. mansoni infection may be a modifiable HIV risk factor that places millions of people worldwide at increased risk of HIV acquisition.

Renal dysfunction among HIV-infected patients starting antiretroviral therapy.

Objective:HIV-related renal dysfunction is associated with high mortality. Data on the prevalence of renal dysfunction among HIV-infected outpatients starting antiretroviral therapy (ART) in sub-Saharan Africa are limited. Recent recommendations to include the nephrotoxic drug tenofovir in first-line ART regimens make clarification of this issue urgent. Methods:We screened for renal dysfunction by measuring serum creatinine, proteinuria, and microalbuminuria in HIV-positive outpatients initiating ART in Mwanza, Tanzania. We excluded patients with pre-existing renal disease, hypertension, diabetes, or hepatitis C virus co-infection. Estimated glomerular filtration rates (eGFRs) were calculated by Cockroft–Gault and Modification of Diet in Renal Disease equations. Results:Only 129 (36%) of 355 enrolled patients had normal eGFRs (grade 0 or 1) above 90 ml/min per 1.73 m2. Grade 2 renal dysfunction (eGFR between 60 and 89 ml/min per 1.73 m2) was present in 137 patients (38.6%), and 87 patients (25%) had grade 3 dysfunction (eGFR between 30 and 59 ml/min per 1.73 m2). Microalbuminuria and proteinuria were detected in 72 and 36% of patients, respectively. Factors predictive of renal dysfunction in multivariate analysis included female sex [odds ratio (OR) 3.0, 95% confidence interval (1.8–5.1), P < 0.0001], BMI less than 18.5 [OR 2.3 (1.3–4.1), P = 0.004], CD4+ T-cell count below 200 cells/&mgr;l [OR 2.3 (1.1–4.8), P = 0.04], and WHO clinical stage II or above [OR 1.6 (1.2–2.3), P = 0.001]. Conclusion:Renal dysfunction was highly prevalent in this population of HIV-positive outpatients initiating first ART in Tanzania. This highlights the critical and underappreciated need to monitor renal function in HIV-positive patients in sub-Saharan Africa, particularly given the increasing use of tenofovir in first-line ART.

Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study

BackgroundCryptococcal meningitis is a leading cause of death among HIV-infected individuals in sub-Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre-emptive treatment. In this study, we describe the impact of screening HIV-positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital.MethodsAll adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV-positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in-hospital mortality were recorded.ResultsOf 333 HIV-infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in-hospital deaths.ConclusionsDespite screening of all HIV-positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high-dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in-hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre-emptive treatment for high-risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed.

Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV-positive outpatients beginning antiretroviral therapy in Mwanza, Tanzania

Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV‐positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre‐emptively. Recently developed point‐of‐care cryptococcal antigen tests may be useful for screening, particularly in resource‐limiting settings, but few studies have assessed their utility.

Hypertension, Kidney Disease, HIV and Antiretroviral therapy among Tanzanian Adults: A Cross-sectional Study.

BackgroundThe epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity.MethodsIn this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher’s exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding.ResultsAmong HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR = 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with hypertension (P <0.001 for trend); among hypertensive participants, 50/76 (65.8%) had microalbuminuria and 20/76 (26.3%) had an estimated glomerular filtration rate (eGFR) <60 versus 33/184 (17.9%) and 16/184 (8.7%) participants with normal blood pressure.ConclusionsHIV-infected adults on ART >2 years had two-fold greater odds of hypertension than HIV-negative controls. HIV-infected adults with hypertension were rarely aware of their diagnosis but often have evidence of kidney disease. Intensive hypertension screening and education are needed in HIV-clinics in sub-Saharan Africa. Further studies should determine if chronic, dysregulated inflammation may accelerate hypertension in this population.

Hypertension-related diseases as a common cause of hospital mortality in Tanzania: a 3-year prospective study.

Objective: Hypertension is believed to be an increasingly common driver of the epidemic of noncommunicable diseases (NCDs) in sub-Saharan Africa, but prospective data are scarce. The objective of this prospective study was to determine the contribution of hypertension to deaths, admissions, and hospital days at a Tanzanian zonal hospital. Methods: Between 2009 and 2011, diagnoses were recorded for all medical admissions together with age, sex, length of hospitalization and in-hospital mortality. Results: Among 11 045 consecutive admissions, NCDs accounted for nearly half of all deaths, admissions, and hospital days. Among NCDs, hypertension-related diseases were the most common and accounted for 314 (33.9%) of the total NCD deaths, 1611 (29.9%) of the NCD admissions, and 12 837 (27.8%) NCD hospital days. Stroke (167 deaths) was the leading cause of hypertension-related death. Hypertension was the leading cause of death in patients over the age of 50 years and 57% of hypertension-related deaths occurred in patients less than 65 years old. Conclusion: NCDs account for half of all deaths, admissions and hospital days at our Tanzanian hospital and hypertension-related diseases were the most common NCD. Hypertension accounted for 34% of NCD deaths and 15% of all deaths. Hypertension was the second most common cause of death overall and the leading cause of death in patients more than 50 years old. More than half of hypertension-related deaths occurred before retirement age. These findings have important implications for public health and medical education in sub-Saharan Africa, wherein hypertension and related diseases have not traditionally been given a high priority.

Cryptococcal meningitis management in Tanzania with strict schedule of serial lumber punctures using intravenous tubing sets: an operational research study.

Background:Cryptococcal meningitis (CM) has a mortality rate of ∼70% among HIV-infected adults in low-income countries. Controlling intracranial pressure (ICP) is essential in CM, but it is difficult in low-income countries because manometers and practical ICP management protocols are lacking. Methods:As part of a continuous quality improvement project, our Tanzanian hospital initiated a new protocol for ICP management for CM. All adult inpatients with CM are included in a prospective patient registry. At the time of analysis, this registry included data from 2 years before the initiation of this new ICP management protocol and for a 9-month period after. ICP was measured at baseline and at days 3, 7, and 14 by both manometer and intravenous (IV) tubing set. All patients were given IV fluconazole according to Tanzanian treatment guidelines and were followed until 30 days after admission. Results:Among adult inpatients with CM, 32 of 35 patients (91%) had elevated ICP on admission. Cerebrospinal fluid pressure measurements using the improvised IV tubing set demonstrated excellent agreement (r2 = 0.96) with manometer measurements. Compared with historical controls, the new ICP management protocol was associated with a significant reduction in 30-day mortality (16/35 [46%] vs. 48/64 [75%] in historical controls; hazard ratio = 2.1 [95% CI: 1.1 to 3.8]; P = 0.018]. Conclusions:Increased ICP is almost universal among HIV-infected adults admitted with CM in Tanzania. Intensive ICP management with a strict schedule of serial lumbar punctures reduced in-hospital mortality compared with historical controls. ICP measurement with IV tubing sets may be a good alternative in resource-limited health facilities where manometers are not available.

Increasing Women in Leadership in Global Health

Globally, women experience a disproportionate burden of disease and death due to inequities in access to basic health care, nutrition, and education. In the face of this disparity, it is striking that leadership in the field of global health is highly skewed towards men and that global health organizations neglect the issue of gender equality in their own leadership. Randomized trials demonstrate that women in leadership positions in governmental organizations implement different policies than men and that these policies are more supportive of women and children. Other studies show that proactive interventions to increase the proportion of women in leadership positions within businesses or government can be successful. Therefore, the authors assert that increasing female leadership in global health is both feasible and a fundamental step towards addressing the problem of women’s health. In this Perspective, the authors contrast the high proportion of young female trainees who are interested in academic global health early in their careers with the low numbers of women successfully rising to global health leadership roles. The authors subsequently explore reasons for female attrition from the field of global health and offer practical strategies for closing the gender gap in global health leadership. The authors propose solutions aimed to promote female leaders from both resource-wealthy and resource-poor countries, including leadership training grants, mentorship from female leaders in global professions, strengthening health education in resource-poor countries, research-enabling grants, and altering institutional policies to support women choosing a global health career path.