The effects of genital schistosoma haematobium on human papillomavirus and the development of cervical neoplasia after five years in a Zimbabwean population.

BACKGROUND: High-risk human papillomavirus (HPV) is responsible for cervical cancer and genital Schistosoma haematobium infection has been hypothesized to be an additional co-factor or even an independent risk factor for cervical neoplasia. The present study aimed to investigate the impact of schistosomiasis on HPV persistence and development of cell atypia in a group of rural Zimbabwean women with confirmed high-risk HPV. METHODS: A five-year follow-up was done among women previously included in a study on genital schistosomiasis. Women who had high-risk HPV at baseline were invited after 5 years for examination of cell atypia, genital schistosomiasis, and high-risk HPV. Both vaginal lavage samples (low-cost) and cervix brush samples (high-cost) were obtained for further analysis. RESULTS: Thirty-seven women were re-examined. Genital Schistosoma haematobium of a minimum of five years' duration was associated with the development high-grade squamous intraepithelial neoplasia, but not with persistent high-risk HPV. There was a high concordance between the brush and vaginal lavage (96.3% agreement, kappa 0.93); however, the number of beta-globin negative vaginal lavage samples was unacceptably high. CONCLUSIONS: Findings warrant an exploration in a larger longitudinal study where a vaginal swab should be explored.

The cost of a school based mass treatment of schistosomiasis in Ugu District, KwaZulu Natal, South Africa in 2012.

INTRODUCTION: The Neglected Tropical Diseases Roadmap of the WHO set targets for potential elimination as a "public health problem" for the period 2012-2020 in multiple countries in Africa, with the aim of global elimination of schistosomiasis as a "public health problem" by 2025. AIM: The purpose of the study was to estimate the cost from a provider's perspective of the Department of Health's Schistosomiasis Mass Drug Administration (MDA) in Ugu District, KwaZulu-Natal in 2012, with a view to project the costs for the entire KwaZulu Natal Province. METHODS: A total of 491 public schools and 16 independent schools in Ugu District, a predominantly rural district in KwaZulu-Natal with a total of 218 242 learners, were included in the schistosomiasis control programme. They were randomly selected from schools situated below an altitude of 300 meters, where schistosomiasis is endemic. A retrospective costing study was conducted using the provider's perspective to cost. Cost data were collected by reviewing existing records including financial statements, invoices, receipts, transport log books, equipment inventories, and information from personnel payroll, existing budget, and the staff diaries. RESULTS: A total of 15571 children were treated in 2012, resulting in a total cost of the MDA programme of ZAR 2 137 143 and a unit cost of ZAR 137. The three main cost components were Medication Costs (37%), Human Resources Cost (36%) and Capital items (16%). The total cost for treating all eligible pupils in KwaZulu-Natal will be ZAR 149 031 888. However, should the capital cost be excluded, then the unit cost will be ZAR 112 per patient and this will translate to a total cost of ZAR 121 836 288. CONCLUSIONS: Low coverage exacerbates the cost of the programme and makes a decision to support such a programme difficult. However, a normative costing study based on the integration of the programme within the Department of Health should be conducted.

Detection of Schistosoma DNA in genital specimens and urine: A comparison between five female African study populations originating from S. haematobium and/or S. mansoni endemic areas.

Female Genital Schistosomiasis (FGS) is a neglected disease affecting millions, however challenging to diagnose. This explorative descriptive study compares Schistosoma real-time PCR analysis of cervico-vaginal lavages (CVL) with corresponding urine and stool samples of 933 women from five different previously described study populations. Sampling included 310 women from an S. mansoni endemic region in Mwanza, Tanzania and 112 women from a nearby S. haematobium endemic region. Findings were compared with samples collected from S. haematobium endemic regions in South Africa from 394 women and from 117 women from Madagascar of which 79 were urine pre-selected microscopy positive cases from highly-endemic communities and 38 were urine microscopy negatives from a low-endemic community. As anticipated, urine and stool microscopy and gynecological investigations varied substantially between study populations; however, the same Schistosoma real-time PCR was performed in one reference laboratory. Schistosoma DNA was detected in 13% (120/933) of the CVL, ranging from 3% in the S. mansoni Tanzanian endemic region to 61% in the pre-selected Malagasy urine microscopy positive cases. Detectable Schistosoma DNA in CVL was associated with Schistosoma DNA in urine but not with microscopic detection of eggs in urine or by cytological examination. This study confirmed real-time PCR for the detection of Schistosoma DNA in gynecological samples to be a valuable diagnostic tool to study the distribution of FGS within schistosomiasis endemic areas.

Indicators of anaemia in under-fives with malaria at a hospital in northern Cameroon.

BACKGROUND: Severe malarial anaemia accounts for nearly one million deaths annually in under-fives in Africa. OBJECTIVE: To describe the clinical and social indicators of anaemia in under-fives with malaria seeking healthcare at a hospital in northern Cameroon. METHODS: This cross-sectional study included 91 consecutive patients below the age of 60 months in whom malaria was diagnosed by symptomatic fever and microscopic examination. Patients were clinically investigated and mothers questioned on related clinical and social aspects. RESULTS: Anaemia (haemoglobin less than 110 g/L) was detected in 69 (82%), and a high parasite load (more than 100 Plasmodia per 100 high-power fields) in 24 (26%) of the patients. Clinical findings were associated with the levels of haemoglobin, rather than the parasite load in a single blood slide. Anaemia was found significantly more often in children between the ages of 12 and 23 months and in patients born at home (p = 0.035 and p = 0.048 respectively). Severe anaemia (haemoglobin less than 50 g/L) was found significantly more often in patients who had not been vaccinated (p = 0.008). CONCLUSION: Anaemia is an important health issue in this population. Clinical signs appear to be associated with the haemoglobin status of the patient rather than the parasite load determined in a single blood slide. Recently weaned children and children of mothers with low socio-economic status and who do not usually use the hospital services, may need particular attention in prevention of anaemia. Further studies are required in order to establish cost-effective interventions against anaemia in under-fives in northern Cameroon.

Seasonal variations in Schistosoma haematobium egg excretion in school-age girls in rural KwaZulu-Natal Province, South Africa.

BACKGROUND: A predominant feature of Schistosoma haematobium infection is urinary egg excretion, and microscopic egg detection remains the accepted standard field diagnostic tool. Praziquantel is the drug of choice for schistosomiasis, and the World Health Organization recommends that it should be administered to all children >4 years of age living in schistosomiasis-endemic areas. The frequency of mass drug administration depends on the prevalence rate in the community. Urinary schistosome egg output has a day-to-day and hour-to-hour intrasubject variation. Therefore, it is important to assess possible seasonal variations in egg excretion to improve the planning of drug treatment. OBJECTIVES: To assess the influence of seasonality on urinary schistosome egg excretion in South Africa (SA). METHODS: We performed a prospective cohort study, exploring seasonal variations of S. haematobium egg excretion in 184 girls aged 10 - 12 years from randomly selected schools in a rural area of KwaZulu-Natal Province, SA. The area has a subtropical climate characterised by a cool dry season and a hot humid season. For children, water contact is higher in the latter season. At baseline, 108 girls were examined in the hot season, and 76 in the cold season. In the next year's cold season the untreated patients were re-investigated before treatment. RESULTS: There was a decrease in infection in the group initially tested in the hot season compared with the group tested in the cold season at both time points when adjusted for age and water contact (adjusted odds ratio 3.61 (95% confidence interval 1.14 - 11.44); p=0.03). CONCLUSIONS: This unique study shows that schistosomiasis prevalence determined by microscopy exhibits seasonal variation, with a higher prevalence in the hot rainy season. Precise community prevalence estimations are key in decisions to treat communities. There was significantly lower egg output in the cold season, and sampling in that season may therefore underestimate the prevalence of urinary schistosomiasis. The study indicates that sampling in SA should be done in the hot season.

Correction to: Self-sampling for human papillomavirus testing among rural young women of KwaZulu-Natal, South Africa.

Following publication of the original article [1], one of the authors reported that his name had been spelled incorrectly. It should be Galappaththi-Arachchige, not Galapaththi-Arachchige.

Prevalence of urinary schistosomiasis and HIV in females living in a rural community of Zimbabwe: does age matter?

A cross-sectional study was conducted on 544 women living in Mupfure rural area of Zimbabwe to determine whether infection with urinary schistosomiasis is associated with HIV infection. Schistosoma haematobium infection was examined in urine samples and HIV infection was determined in sera. The prevalence of S. haematobium infection was highest (60%) in women below 20 years of age and declined to 29% in the oldest age group (test for trends, P<0.001). Overall, women infected with urinary schistosomiasis had an HIV prevalence of 33.3%, whilst women without urinary schistosomiasis had an HIV prevalence of 25.6% (chi(2), P=0.053). Women above the age of 35 years and infected with urinary schistosomiasis had a significantly higher HIV prevalence (37.5%) than those without urinary schistosomiasis (16.8%; chi(2), P<0.001).

Self-sampling for human papillomavirus testing among rural young women of KwaZulu-Natal, South Africa.

BACKGROUND: Cervical cancer is a major problem in women and it is important to find a suitable and acceptable screening method, especially among young in low-resource areas for future human papillomavirus (HPV) vaccine follow-up investigations. The study sought to test the acceptability of self-sampling as well as the suitability of the specimen collecting devices. METHODS: Ninety-eight young women from rural KwaZulu-Natal were enrolled between March and July 2014. Collected genital specimens were transferred to colour indicator cards for HPV detection. Participants answered a questionnaire where they described their experiences with self-sampling. Samples were tested for high-risk HPV using GP5/6+ PCR. RESULTS: Of the enrolled participants, 91 answered questionnaires and indicated that self-sampling was preferred by 51/91 (56%) women while 40/91 (44%) indicated preference for sampling by a doctor (p = 0.023). The majority, 64% were comfortable using a swab, 22% preferred a brush while 11% were comfortable with both devices. Of the 98 self-sampled specimens 61 were negative for HPV in both specimens while 37 were HPV-positive in either brush or swab. Of the 37, 26 (70%) were HPV-positive in both brush and swab (kappa = 0.743) and 11 (30%) were discordant. CONCLUSIONS: Self-sampling was acceptable to the majority of participants in this rural area. The Dacron swab was the preferred device, and can be used in combination with colour indicator cards for comfortable self-sampling, easy storage and transport of specimens plus detection.

Schistosomiasis in women: manifestations in the upper reproductive tract.

Female genital schistosomiasis (FGS) is a neglected disease entity which may give rise to considerable suffering among women of child-bearing age in areas where schistosomiasis (especially due to Schistosoma haematobium) is prevalent. The close relation between the vessels in genital organs and the urinary bladder enables the parasite to easily change location to virtually any organs in the female pelvic area. Symptoms concur with the anatomical location of worm pairs and their ova. Lesions of the lower female genital tract can easily be investigated by cytology, histology or direct demonstration of eggs in scrapings or biopsies whereas schistosomiasis of the upper genital tract is clinically indecipherable and less accessible for examination. In the literature there are references to FGS as a cause of infertility, complications of pregnancy, menstrual disorders, problems related to sexual intercourse, diagnostic similarities to STDs and cancer, unspecified complaints related to blood loss, chronic abdominal pain, social segregation and related psychological problems. The diagnosis of female upper genital schistosomiasis is difficult and the authors point out possible diagnostic procedures which might be helpful for further understanding of this complex entity.

Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi.

A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.

Urine reagent strips for diagnosis of schistosomiasis haematobium in women of fertile age.

Hematuria, proteinuria and leukocyturia were semiquantitatively assessed by reagent strips in single morning urine of women of fertile age visiting the outpatient department of the Mangochi district hospital, Malawi. This was part of a diagnostic approach to female genital schistosomiasis (FGS). In 51 women ova of Schistosoma haematobium were detected in urine by a filtration technique. In 33 of these women ova were also present in genital tissue as demonstrated by microscopic examination of biopsies. In 209 women no ova were found in the single urine filtered. There were significantly higher scores for hematuria, proteinuria and leukocyturia as well as of the combined reagent strip index (RSI) in egg-excreting than in egg-negative women. The sensitivity of a single hematuria, proteinuria and leukocyturia reading was 98, 84 and 73%, respectively. However, the respective specificity was only 24, 22 and 23%. The best prediction of urinary schistosomiasis was achieved by a +2 score for hematuria, of which the sensitivity was 94% and the specificity was 61%. The high false-positive rates can probably be explained by contamination of urine by vaginal secretion. Moreover, cases of schistosomiasis have probably been overlooked because only a single morning urine sample was examined. The total absence of hematuria, proteinuria and leukocyturia, however, may be used to rule out heavy infections in community surveys. There was no difference in reagent strip scores between women with genital and urinary schistosomiasis as compared with those with urinary tract lesions alone. Thus urine analysis reagent strip readings do not help to discriminate between S. haematobium infected women with and without FGS.

Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.

Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.

Female genital schistosomiasis (FGS): relationship between gynecological and histopathological findings.

Schistosomiasis of the lower female reproductive tract manifests itself in a broad spectrum of clinical features. However, clinical and histopathological findings have never been studied in a synoptic manner. Based on the assumption that any type of pathology present in the female reproductive tract is the expression of a complex pathophysiological reaction towards eggs sequestered in the genital tissues, we decided to analyze colposcopic and histopathological findings in a comprehensive manner. Thirty-three women in Malawi with urinary and genital schistosomiasis were examined parasitologically and gynecologically. A thorough colposcopic examination with photodocumentation was performed and biopsies were taken from the cervix, the vagina and/or the vulva for histological sectioning and immunohistochemistry. The predominant colposcopic findings were sandy patches on the cervical surface similar to those seen in the bladder and polypous/papillomatous tumors with irregular surface on the vaginal wall and in the vulvar area. The histopathological sections of sandy-patch-like lesions demonstrated only a small cellular reaction around S. haematobium eggs in various stages of disintegration. In contrast, in the case of polyps the histology revealed a more pronounced immunological reaction characterized by a heavy cellular infiltrate. One case of invasive squamous cell carcinoma of the cervix was diagnosed. We conclude that colposcopy is a useful tool in the detection of FGS related pathology in the lower female reproductive tract and that the synoptic assessment of surface and of corresponding histological sections helped to understand the pathophysiology of S. haematobium associated disease in genital tissue.

Reversibility of lower reproductive tract abnormalities in women with Schistosoma haematobium infection after treatment with praziquantel--an interim report.

Little is known whether and to what extent antiparasitic treatment cures female genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women with FGS nine were re-examined at two to nine weeks after they had been treated with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of the urinary tract and to a lesser extent of genital pathology subsided in most patients. Schistosoma haematobium ova were no longer detectable in urine of any of the patients post-treatment. Efficiency of chemotherapy against adult worms was confirmed by the disappearance of circulating anodic antigen (CAA) in serum. Sandy patches showed resolution in two of four cases after chemotherapy. Papillomata due to schistosomiasis alone improved, but persisted in mixed infection with human papilloma virus (HPV) or when HPV was the only underlying cause. In one patient ulcera could not be related with certainty to schistosomiasis at admission, but resolved after treatment with parziquantel. Leukoplakia (two cases) was not influenced by chemotherapy, or even increased during follow-up, regardless of whether ova had been detected or not. Although the follow-up period was rather short, time intervals were not standardized, and a relatively small number of patients was investigated, it could be shown that genital pathology due to sequestered S. haematobium ova is, at least partially, reversible already two to nine weeks after killing the adult worms by praziquantel. This is paralleled by a normalization of inflammatory immune responses detectable in histological sections and vaginal lavage.

Assessment of eosinophil cationic protein as a possible diagnostic marker for female genital schistosomiasis in women living in a Schistosoma haematobium endemic area.

Eosinophil cationic protein (ECP) levels were measured in vaginal lavage extracts from 518 Zimbabwean reproductive women, age range 15-49 years, to assess the potential use of ECP as a diagnostic marker for female genital schistosomiasis (FGS). One hundred and fifty women had confirmed FGS status. These included 77 (cases) women who had ova in genital tissue and 73 (controls) women who had no ova in genital tissue. Participants were examined at baseline, 3 and 15 months post-treatment with praziquantel. ECP levels were determined using the enzyme linked immunosorbent assay (ECP-ELISA). ECP levels from 18 Norwegian women were used to calculate the diagnostic values of the test. FGS was diagnosed from the study population using genital biopsy and smears. Women were also diagnosed for urinary schistosomiasis using the urine filtration technique. The prevalence of urinary schistosomiasis was 39 % at baseline and this declined to 8% and 6% at 3 and 15 month post-treatment surveys, respectively. There was a higher mean ECP level in women with FGS, 889.3 ng/mL (95% CI: 457.0-1327.5) compared to the endemic control group, 359.1 ng/mL (95%, CI: 227.3-490.9), P = 0.027. Mean ECP levels declined at 3 months following treatment of infected individuals. There was no correlation between ECP levels and tissue ova density, and urine egg intensity. The sensitivity, specificity, positive and negative predictive values for the ECP-ELISA test were 35%, 80%, 65% and 53%, respectively. Our results indicate that FGS causes an inflammatory immune response that increases ECP levels in genital fluid. Treatment of schistosomiasis results in a regression of pathology and a decline in ECP levels. However, other factors such as allergy and microbial infection could also be responsible for increased ECP levels in genital mucosa. These conditions will affect the validity of the test in diagnosis of FGS.