Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

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 .

Increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

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.

Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population.

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.

AIDS and optic neuritis in a rhesus monkey infected with the R5 clade C SHIV-1157ipd3N4.

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.

Impact of intense, longitudinal retreatment with praziquantel on cure rates of schistosomiasis mansoni in a cohort of occupationally exposed adults in western Kenya.

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.

Immunoregulation and World Health Assembly resolution 54.19: why does treatment control morbidity?

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.