Search

Background: Female genital schistosomiasis (FGS) affects up to 56 million women in sub-Saharan Africa and may increase risk of HIV infection. Methods: To assess the association of schistosomiasis with HIV infection, peer-reviewed literature published until 31 December 2018 was examined and a pooled estimate for the odds ratio was generated using Bayesian random effects models. Results: Of the 364 abstracts that were identified, 26 were included in the summary. Eight reported odds ratios of the association between schistosomiasis and HIV; one reported a transmission hazard ratio of 1.8 (95% CI, 1.2–2.6) among women and 1.4 (95% CI, 1.0–1.9) among men; 11 described the prevalence of schistosomiasis among HIV-positive people (range, 1.5–36.6%); and six reported the prevalence of HIV among people with schistosomiasis (range, 5.8–57.3%). Six studies were selected for quantitative analysis. The pooled estimate for the odds ratio of HIV among people with schistosomiasis was 2.3 (95% CI, 1.2–4.3). Conclusions: A significant association of schistosomiasis with HIV was found. However, a specific summary estimate for FGS could not be generated. A research agenda was provided to determine the effect of FGS on HIV infection. The WHO’s policy on mass drug administration for schistosomiasis may prevent HIV.

Parasitologic surveys of young adults in college and university settings are not commonly done, even in areas known to be endemic for schistosomiasis and soil-transmitted helminths. We have done a survey of 291 students and staff at the Kisumu National Polytechnic in Kisumu, Kenya, using the stool microscopy Kato-Katz (KK) method and the urine point-of-care circulating cathodic antigen (POC-CCA) test. Based on three stools/two KK slides each, in the 208 participants for whom three consecutive stools were obtained, Schistosoma mansoni prevalence was 17.8%. When all 291 individuals were analyzed based on the first stool, as done by the national neglected tropical disease (NTD) program, and one urine POC-CCA assay (n = 276), the prevalence was 13.7% by KK and 23.2% by POC-CCA. Based on three stools, 2.5% of 208 participants had heavy S. mansoni infections (≥400 eggs/gram feces), with heavy S. mansoni infections making up 13.5% of the S. mansoni cases. The prevalence of the soil-transmitted helminths (STH: Ascaris lumbricoides, Trichuris trichiura and hookworm) by three stools was 1.4%, 3.1%, and 4.1%, respectively, and by the first stool was 1.4%, 2.4% and 1.4%, respectively. This prevalence and intensity of infection with S. mansoni in a college setting warrants mass drug administration with praziquantel. This population of young adults is ‘in school’ and is both approachable and worthy of inclusion in national schistosomiasis control and elimination programs.

The stated goal of the World Health Organization’s program on schistosomiasis is paraphrased as follows: to control morbidity and eliminate transmission where feasible. Switching from a goal of controlling morbidity to interrupting transmission may well be currently feasible in some countries in the Caribbean, some areas in South America, northern Africa, and selected endemic areas in sub-Saharan Africa where there have been improvements in sanitation and access to clean water. However, in most of sub-Saharan Africa, where programmatic interventions still consist solely of annual mass drug administration, such a switch in strategies remains premature. There is a continued need for operational research on how best to reduce transmission to a point where interruption of transmission may be achievable. The level of infection at which it is feasible to transition from control to elimination must also be defined. In parallel, there is also a need to develop and evaluate approaches for achieving and validating elimination. There are currently neither evidence-based methods nor tools for breaking transmission or verifying that it has been accomplished. The basis for these statements stems from numerous studies that will be reviewed and summarized in this article; many, but not all of which were undertaken as part of SCORE, the Schistosomiasis Consortium for Operational Research and Evaluation.

OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3–45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15–44 within household; OR 3.2 95% CI 1.7–6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53–0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70–0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar.

After recreational exposure to river water in Uganda, 12 (17%) of 69 persons had evidence of schistosome infection. Eighteen percent self-medicated with praziquantel prophylaxis immediately after exposure, which was not appropriate. Travelers to schistosomiasis-endemic areas should consult a travel medicine physician.

Background: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies., Methods: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years., Results: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory., Conclusions: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis., Trial Registration: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Background: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood., Methods: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy., Results: Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test)., Conclusions: C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Mass drug administration with praziquantel is the mainstay of programs for the control of schistosomiasis morbidity. However, there is a growing recognition that treatment alone will not be sufficient for eventually effecting elimination and that additional measures will be required to interrupt transmission. In the absence of a safe and an effective vaccine for human schistosomiasis, the strategies to reduce infection levels will necessarily involve some interventions that affect the water-related stages of the schistosome life cycle: by reducing exposure to infectious water, by moderating availability of the intermediate snail host, or by decreasing contamination of water with egg-containing excreta. While much research on the importance of water on schistosomiasis has been performed, advances in these areas have perhaps languished with the ready availability of a cost-effective treatment. As some endemic areas near a shift to an elimination goal, a better understanding of water-based interventions that can be used alone or in concert with treatment will be needed. Reinvigoration of laboratory, field, and human behavioral aspects of this research now will ensure that the appropriate strategies are available by the time their implementation becomes necessary.

A Chinese rhesus macaque infected with the pathogenic CCR5-tropic clade C simian-human immunodeficiency virus, SHIV-1157ipd3N4, had persistent viremia, depletion of CD4(+) T cells to <200 cells/μl, opportunistic infections, coagulopathy, and gradual development of bilateral blindness. MRI revealed marked thickening of both optic nerves. Histopathological evaluation showed diffuse cellular infiltration at necropsy and a focus of SHIV-infected cells. This is the first report of CNS pathology following chronic infection with an obligate R5 SHIV., (© 2010 John Wiley & Sons A/S.)

Objective: To determine the prevalence and incidence of trichomoniasis, risk factors for infection, and the prevalence of metronidazole and tinidazole-resistant Trichomonas vaginalis (T. vaginalis) in female adolescents., Methods: Nonpregnant, HIV-seronegative, sexually active females (13-19 years) visiting an inner city public primary care clinic were tested for T. vaginalis by wet mount and culture, and interviewed about risk-taking behavior every 6 months. Infected patients were treated with a 2 g oral dose of metronidazole. Isolates from positive T. vaginalis cultures were tested for in vitro resistance to metronidazole and tinidazole., Results: Among 467 study participants, 67 (14.4%; 95% confidence interval, 11.3-17.5) were diagnosed with trichomoniasis at first T. vaginalis culture. Significant risk factors for T. vaginalis infection were having an older sex partner and concurrent Neisseria gonorrhoeae infection. The incidence was 22.1 cases per 100 person-years. Among 42 participants who had a prevalent infection and returned for followup, 13 (31.0%) had at least 1 more episode of trichomoniasis. Resistance testing was completed for 78 isolates: 37 at first visit and 41 during follow-up. One (2.7%; 95% confidence interval, 0.07-14.2) of the 37 first-visit isolates was moderately resistant to metronidazole (minimal lethal concentration = 200 microg/mL). Of the 41 follow-up visit isolates, 1 was moderately resistant to metronidazole and 2 had borderline resistance (minimal lethal concentration = 50 microg/mL). The prevalence of tinidazole resistance was 0% (0.0%-9.5%)., Conclusion: The study population had high prevalence and incidence of trichomoniasis. The prevalence of antibiotic-resistant T. vaginalis among female adolescents was low.

Objective: To investigate trends in the efficacy of praziquantel (PZQ) suggestive of the emergence of drug resistance against Schistosoma mansoni infection after 12.5 years of intense, repeated use in a small geographic area along the shores of Lake Victoria., Methods: As part of a longitudinal study, 178 men occupationally exposed to schistosomes were repeatedly tested for S. mansoni infection at 4- to 6-week intervals and treated with PZQ at each reinfection. We compared cure rates by year of study and examined factors associated with cure failure in a multivariate logistic regression model., Results: Overall, the cure rate after a single dose of PZQ was 66%, ranging annually from 36% to 82%. In multivariate analysis, failure to cure after 1 PZQ dose was significantly associated with high intensity of infection and having fewer previous exposures to dying worms. Even after adjustment for these factors, treatments administered in 2006 were significantly more likely to result in cure failures than treatments administered in 2004, the year in which PZQ efficacy was highest. While cure rates varied over the course of 12 years, there was no consistent downward trend towards decreased efficacy over time. In years for which malacological data were available, periods of low PZQ efficacy coincide with high rates of S. mansoni infection in nearby snail populations., Conclusion: We did not find a pattern of cure failures consistent with development of clinical resistance to PZQ in our intensely treated cohort.

World Health Assembly resolution 54.19, passed in May, 2001, declares the intent of the World Health Organization member States to implement a combined strategy for the control of morbidity caused by schistosomiasis and soil-transmitted helminths. Among other things, the resolution urges ministries to treat all clinical cases and groups at high risk of morbidity such as children, women and those exposed occupationally. The policy is predicated on the evidence that morbidity due to these infections can be controlled by periodic treatment with appropriate chemotherapeutic, anti-helminthic drugs. While it is true that annual or biannual praziquantel treatment for schistosomiasis decreases morbidity, we now question how treatment leads to this beneficial effect. It is clear that treatment kills worms, but we propose that this is only a part of how it leads to reduced morbidity in areas of ongoing transmission and reinfection. By killing worms, we postulate that treatment also effects immunologic changes to the normal host/parasite relationship, and the resulting immune responses lead to both increased resistance (protection against reinfection), and increased immunoregulatory mechanisms that control morbidity upon subsequent reinfections. If the effects of treatment contribute to morbidity control in these ways, a better understanding of how this occurs may allow optimization of these effects of treatment through appropriate periodic treatment regimens, resulting in less reinfection and better morbidity control when reinfection does occur.