Takafira Mduluza

ASSOCIATION BETWEEN GENITAL SCHISTOSOMIASIS AND HIV IN RURAL ZIMBABWEAN WOMEN

Objective:To determine the association between female genital Schistosoma haematobium infection and HIV. Design and methods:A cross-sectional study with a 1-year follow-up. Gynecological and laboratory investigations were performed for S. haematobium and HIV. Sexually transmitted infections, demographic and urogenital history were analysed as confounders. The participants were 527 sexually active, non-pregnant, non-menopausal women between the ages of 20 and 49 years. The setting was a rural Zimbabwean community where S. haematobium related lesions were found in 46% of the women, HIV in 29% and herpes simplex type- 2 (HSV-2) in 65%. Results:In permanent residents (>3 years residency), HIV was found in 41% (29/70) of women with laboratory proven genital schistosomiasis as opposed to 26% HIV positive (96/375) in the schistosomal ova negative group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.2–3.5; P = 0.008. In multivariate analysis S. haematobium infection of the genital mucosa was significantly associated with HIV seropositivity (adjusted OR, 2.9; 95% CI, 1.11–7.5; P = 0.030). All seven women who became HIV positive during the study period (seroincidence 3.1%) had signs of S. haematobium at baseline. In accordance with other studies HIV was significantly associated with HSV-2 (OR, 3.0; 95% CI, 1.7–5.3; P < 0.001), syphilis and human papillomavirus. The highest HIV prevalence (45%) was found in the 25–29 years age group. Conclusion:Women with genital schistosomiasis had an almost three-fold risk of having HIV in this rural Zimbabwean community. Prospective studies are needed to confirm the association.

Praziquantel Treatment of Individuals Exposed to Schistosoma haematobium Enhances Serological Recognition of Defined Parasite Antigens

BACKGROUND Schistosomiasis is a major parasitic disease affecting >200 million people in the developing world, and 400 million people are at risk for infection. This study aimed to identify and compare proteins recognized by serum samples from schistosome-exposed individuals before and after curative praziquantel treatment. METHODS Proteins recognized by pooled serum samples from Schistosoma haematobium-exposed Zimbabweans were determined by 2-dimensional Western blotting and identified by mass spectrometry. RESULTS Serum samples recognized 71 spots, which resolved to 26 different characterized proteins. Eleven of these proteins have not previously been shown to be immunogenic in natural human infection or in experimental models of schistosomiasis, making them novel antigens in the parasite. Pretreatment serum samples recognized 59 spots, which resolved to 21 different identified proteins. Posttreatment serum samples recognized an additional 12 spots, which resolved to 8 different identified proteins. Of these 8 proteins, 3 had putative isoforms recognized before treatment, and 5 (calreticulin, tropomyosin 1, tropomyosin 2, paramyosin, and triose phosphate isomerase) did not. CONCLUSIONS This study is the most comprehensive characterization of S. haematobium antigens to date and describes novel antigens in all schistosome species. Posttreatment results are consistent with praziquantel treatment inducing quantitative and qualitative changes in schistosome-specific antibody responses.

Schistosoma haematobium treatment in 1-5 year old children: safety and efficacy of the antihelminthic drug praziquantel

Background Morbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel (PZQ). Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group. This study investigated the safety and efficacy of PZQ treatment in such children. Methods Zimbabwean children aged 1–5 years (n = 104) were treated with PZQ tablets and side effects were assessed by questionnaire administered to their caregivers within 24 hours of taking PZQ. Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine. The change in infection levels in the children 1–5 years old (n = 100) was compared to that in 6–10 year old children (n = 435). Principal Findings Pre-treatment S. haematobium infection intensity in 1–5 year olds was 14.6 eggs/10 ml urine and prevalence was 21%. Of the 104 children, 3.8% reported side effects within 24 hours of taking PZQ treatment. These were stomach ache, loss of appetite, lethargy and inflammation of the face and body. PZQ treatment significantly reduced schistosome infection levels in 1–5 year olds with an egg reduction rate (ERR) of 99% and cure rate (CR) of 92%. This was comparable to the efficacy of praziquantel in 6–10 year olds where ERR was 96% and CR was 67%. Interpretation/Significance PZQ treatment is as safe and efficacious in children aged 1–5 years as it is in older children aged 6–10 years in whom PZQ is the drug of choice for control of schistosome infections.

The burden of polyparasitism among primary schoolchildren in rural and farming areas in Zimbabwe

A cross-sectional study was conducted in Zimbabwe among 1303 primary schoolchildren from a rural (53.3%) and a commercial farming area (46.7%) to determine the prevalence of co-infection by helminths and Plasmodium falciparum. Urine was examined on three successive days using the filtration method. Two stool specimens were processed using the Kato-Katz method and a third specimen was processed using the sedimentation method. Plasmodium falciparum was diagnosed from thick blood films. The prevalence of Schistosoma haematobium in the rural and farming areas was 66.8% and 52.3%, respectively, and for S. mansoni the prevalence was 12.4% and 22.7%, respectively. Plasmodium falciparum, hookworms, Ascaris lumbricoides and Trichuris trichiura occurred only in the farming area, with a prevalence of 27.9%, 23.7%, 2.1%, 2.3%, respectively. Co-infection and triple infection with schistosomes, P. falciparum and soil-transmitted helminths occurred in the commercial farming area only. Hookworm and S. mansoni infections were associated with P. falciparum malaria (P<0.001, OR=2.48, 95% CI 1.56-3.93 and P=0.005, OR=1.85, 95% CI 1.20-2.87, respectively). Overlap of helminths with malaria is a concern among primary schoolchildren and incorporating helminth control in programmes aiming to control malaria will improve funding and increase the efficiency of control for neglected tropical diseases in identified co-endemic settings.

Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α1,3-galactose

BACKGROUND The carbohydrate epitope galactose-α 1,3-galactose (α-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that α-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). OBJECTIVE We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and α-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. METHODS Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with α-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and α-Gal was analyzed by means of ELISA. RESULTS Among the 47 parasite-infected patients, 85% had IgE antibodies against α-Gal (OD; median, 0.175; range, 0.102-1.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.103-1.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and α-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and α-Gal (P < .001). Among the group with cat allergy, only 5 patients had IgE to α-Gal, and nearly 75% (n = 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kU(A)/L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P < .05) but no correlation between CDE and Fel d 5 and α-Gal. CONCLUSION IgE to α-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/allergy in parasite-infested areas.

Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age

BackgroundThe rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity.MethodsSchistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches.ResultsAge profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other.ConclusionTaken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.

The impact of zinc supplementation on growth and body composition: A randomized, controlled trial among rural Zimbabwean schoolchildren

OBJECTIVES: To assess the effect of zinc supplementation on growth and body composition among schoolchildren.DESIGN: Randomized, double-blind, placebo-controlled trial.SETTING AND SUBJECTS: 313 rural Zimbabwean schoolchildren (144 boys and 169 girls), 11–17 y).INTERVENTIONS: Supplementation with zinc (30 or 50 mg) or placebo on schooldays for 12 months. Due to drought, a food programme was in operation during the last eight months of the study.VARIABLES: Weight, height, upper arm circumference, triceps skinfold thickness, and weight-for-age, height-for-age, weight-for-height, arm muscle-area-for-age and arm fat-area-for-age Z-scores.RESULTS: Significant effects on weight gain (0.51 vs 0.14 kg, P=0.01), weight-for-age Z (−0.08 vs −0.14, P=0.01) and arm muscle area-for-age Z-score (0.10 vs 0.01, P=0.03) were seen over the first three months, whereas no effects were seen over the full 12 months.CONCLUSIONS: Zinc deficiency impairing lean body mass and weight gain was documented. However, the effect of zinc seen over the first three months vanished during the last nine months when the food programme was in operation. Zinc deficiency may have persisted, but another nutrient may have become growth limiting during the last nine months.SPONSORSHIP: Danish International Development Assistance.

Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe

We examined the efficacy of praziquantel against Schistosoma haematobium among primary school children during a school-based deworming programme in the Burma Valley commercial farming area and the Nyamaropa rural areas in Zimbabwe, where the disease is highly endemic. Among 767 individuals infected with S. haematobium, 675 (88.0%) received treatment. Two single oral doses of 40mg/kg praziquantel were given 6 weeks apart. Of the 675 participants, heavy infection intensity was more common in males than females (chi(2)=6.61, P=0.010). Six weeks later, 624 participants (92.4%) were successfully followed up. The overall cure rate was 88.5% and the egg reduction rate was 98.2%. The highest cure rate was among those individuals with light infection. Seventy-two individuals remained infected at 6 weeks post treatment, among which 3 and 69 individuals had heavy and light infection, respectively. Forty-six of these children resolved following a second round of treatment at 6 weeks follow-up. Of the remaining children successfully followed-up, 22 resolved after a third round of treatment 6 months later. A wide range of observed mild and transient side effects were not associated with egg intensity. The parasitological cure rate was not associated with gender or age. Our study demonstrates that praziquantel is efficacious against S. haematobium in Zimbabwe, although low levels of persistent infection warrant further investigation.

Schistosomiasis PCR in Vaginal Lavage as an Indicator of Genital Schistosoma haematobium Infection in Rural Zimbabwean Women

Schistosoma real-time polymerase chain reaction (PCR) is sensitive and specific in urine and stool. We sought to explore the relationship between genital schistosomiasis and the Schistosoma PCR in women. PCR was run on 83 vaginal lavage samples from a rural Zimbabwean population. Women underwent clinical and colposcopic investigations, analyses for sexually transmitted infections, and genital schistosomiasis. Thirty samples were positive for Schistosoma PCR: 12 were strong and 18 were weak positive. Sensitivity (67%) and specificity (83%) were best in women below the age of 25 years. A positive schistosome PCR result was associated with S. haematobium ova in genital tissue, so-called sandy patches, and bleeding. Prevalence determined by PCR were lower and real-time PCR values were weaker in older women. The presence of Schistosoma DNA may be greater in the recent lesions (e.g., in younger women). For diagnosis in rural areas and in large studies, Schistosoma PCR could become a supplement to gynecologic examinations.

Female genital schistosomiasis – a differential diagnosis to sexually transmitted disease: genital itch and vaginal discharge as indicators of genital Schistosoma haematobium morbidity in a cross‐sectional study in endemic rural Zimbabwe

Objective  To examine the association between schistosomiasis and reproductive tract symptoms.