Patricia D. Ndhlovu

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.

A review of female genital schistosomiasis.

In a review of the studies on genital schistosomiasis, the cervix, the Fallopian tubes, and the vagina are the most common gynaecological sites to harbour Schistosoma haematobium. Lesions are caused by host responses to dead or viable schistosomiasis eggs and may render women with genital schistosomiasis susceptible to HIV. The typical genital changes, such as sandy patches and pathological blood vessels may make women susceptible to super-infection, cause contact bleeding, decreased fertility, abortions, discharge and bleeding. Further research is needed to find simple, low-tech diagnostic methods, treatment for chronic lesions, and to explore the preventive effects of mass drug administration on symptoms, sandy patches, HPV and the HIV epidemic.

A comparison of humoral responses to Schistosoma haematobium in areas with low and high levels of infection

Antibody responses to Schistosoma haematobium of 280 Zimbabweans were studied in two areas of differing infection levels. 133 of the subjects came from a low infection area with a prevalence of 33.8% and geometric mean infection intensity of 0.8 eggs per 10 ml of urine, while 147 of the subjects came from a high infection area with a prevalence of 62.7% and geometric mean intensity of 3.2 eggs per 10 ml of urine. Both the age‐prevalence and age‐intensity curves exhibited a peak shift. IgA, IgE, IgG, IgG1, IgG2, IgG3, IgG4, and IgM antibody levels against soluble egg antigen (SEA) and whole worm homogenate (WWH) were assayed by ELISA. Females produced significantly more anti‐SEA IgG1, IgG4, IgM, anti‐WWH IgE and IgG1. People from the high infection area produced significantly more anti‐SEA IgE, IgG3 and anti‐WWH IgG3 and significantly lower levels of anti‐SEA IgA, IgM and anti‐WWH IgM when the effects of infection intensity, sex and age had been allowed for. The age profiles of anti‐SEA IgA, IgG and anti‐WWH IgA and IgM reflected current levels of infection while anti‐WWH IgG1, IgG2 and anti‐SEA IgG1 evolved more slowly with age, and anti‐WWH IgE rose with age in both areas. Some antibody responses, anti‐SEA/WWH IgM, anti‐SEA IgG1 and possibly anti‐SEA/WWH IgA showed different age profiles in the two areas, with changes in antibody levels occurring at a younger age in the high infection area suggesting that immune responses are evolving more rapidly in residents of this area. This result clearly demonstrates that antibody levels are not a function of age alone.

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.

Age‐related antibody profiles in Schistosoma haematobium infections in a rural community in Zimbabwe

Antibody responses to soluble Schistosoma haematobium egg (SEA) and worm (SWA) antigens in a rural Zimbabwean study population were examined by ELISA. One hundred and sixteen S. haematobium infected and 124 non‐infected individuals representing individuals greater than five years old, were included. Non‐endemic control sera were obtained from a schistosomiasis non‐endemic part of Zimbabwe and from Norwegian blood donors. A possible association between IgE antibody responses and resistance to S. haematobium infection was indicated by a negative correlation between IgE anti‐SEA levels and intensity of S. haematobium infection, and by a positive correlation between IgE responses to SEA and SWA and age. Similarly, an association between IgA and anti‐SWA and resistance to S. haematobium was suggested by a negative correlation to intensity of infection and a positive correlation with age. A probably association between IgM and IgG4 with susceptibility to S. haematobium infection was described; intensity of S. haematobium infection correlated positively with IgG, IgG4 and IgM responses to SEA and with IgG4 and IgM responses to SWA, also age correlated negatively with IgG4 and IgM responses to SEA and with IgG4 responses to SWA. These findings support the concept of IgG4 and IgM as blocking antibodies. Significant positive correlations between antibody responses to SEA and SWA suggests cross‐reactivity between eggs and adult worms. In addition, the recognition by IgE and IgG4 of the same schistosomulum antigens in immunoblotting suggests competition for the same antigens.

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.

Exposure, infection and immune responses to Schistosoma haematobium in young children

Behavioural, parasitological and immunological data were obtained from 48 children up to 6 years old, resident in a Schistosoma haematobium endemic area in Zimbabwe. The children averaged more than 1 contact with infective water bodies every 3 days and all showed immunological evidence of exposure (an anti-cercarial and/or anti-egg antibody response). IgM was the dominant isotype and appeared in the youngest children, followed by IgA, IgE and IgG3. However, only 38 children showed evidence of infection (an anti-egg response or eggs in urine) and only 14 were excreting eggs. The best estimates from these data are that less than 1 in 100 contacts results in infection and less than 1 in 1000 result in egg output. This suggests that there may be substantial attrition of invading cercaria even in naïve individuals.

Iron haptoglobin phenotype and HIV-1 viral load: a cross-sectional study among pregnant Zimbabwean women.

Background: Viral load is a determinant of HIV‐1 progression and transmission. Iron status and the phenotype of haptoglobin, a heme‐binding acute phase reactant, may be determinants of viral load. We aimed to describe the effect of iron status, haptoglobin phenotype (Hp), and other predictors on HIV‐1 viral load. Methods: Based on a cross‐sectional study among 1669 antenatal care attenders (22‐35 weeks) in Zimbabwe, 526 (31.5%) were found to be HIV infected. The role of season, age, gravidity, gestational age, malaria parasitemia, Hp, and elevated serum &agr;1‐antichymotrypsin (ACT) as well as serum ferritin, folate, retinol, and &bgr;‐carotene on HIV viral load among the 526 HIV‐infected women was assessed using multiple linear regression analysis. Results: The distribution of Hp 1‐1 (32%), Hp 2‐1 (48%), and Hp 2‐2 (20%) was not different from that of 53 uninfected women. Mean viral load was 3.85 log10 (95% CI: 3.77‐3.93) genome equivalents (geq)/mL, ranging from 3.77 (95% CI: 3.64‐3.90) geq/mL in women with Hp 1‐1 to 4.05 (95% CI: 3.81‐4.21) geq/mL in women with Hp 2‐2. With elevated serum ACT controlled for, women with Hp 2‐2 had viral loads twice (95% CI: 1.4‐4.0, p = .002) that of women with Hp 1‐1, whereas those with serum ferritin <6 &mgr;g/L had viral loads less than one third (95% CI: 0.13‐0.53, p = .013) that of women with serum ferritin >24 &mgr;g/L. Viral loads were also higher in women enrolled in the early rainy season compared with the dry season, in gravidae 4+ compared with gravidae 1 through 3, and in those with moderately elevated compared with low serum &agr;1‐antichymotrypsin, but neither age, gestational age, serum folate, serum retinol, nor serum &bgr;‐carotene were predictors. Conclusion: Storage iron, Hp 2‐2, and elevated ACT are independent positive predictors of HIV‐1 viral load. The positive relationship between serum ferritin and viral load was not the result of an acute phase response or iron accumulation with advanced HIV infection. A possible detrimental role of iron in HIV infection would have serious public health implications.

Epidemiological assessment of Schistosoma haematobium-induced kidney and bladder pathology in rural Zimbabwe

Clinical outcome of Schistosoma haematobium infection may vary significantly, ranging from mild symptoms to severe damage of urinary tract organs. This present study was undertaken to assess the relationship of a number of epidemiological and parasitological parameters with disease outcome in children from rural Zimbabwe. We surveyed 551 primary school students from three schools in the Chikwaka Communal Lands for schistosomiasis; 59.7% were infected with S. haematobium. Ultrasound examination of 189 of the infected students revealed that 50% had pathological changes of their bladder and 36% had abnormal pyelon dilation of at least one of their kidneys. Intensity of infection, certain water contact behaviours, male gender, proteinuria, and self-perceived haematuria were associated with increased bladder damage. Strenuous playing was negatively associated with pathology, especially for those with the highest grade of bladder damage. Kidney pathology was significantly linked with fatigue and pain upon urination and was more prevalent in students from schools closest to the major river systems. Our findings suggest that pathology due to urinary schistosomiasis is widespread and symptomatic in this population. The associations with bladder and kidney pathology can be used to predict disease severity and may be useful in targeting treatment to those most at risk.