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.

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.

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.

Age- and sex-related differences in antibody responses against Schistosoma mansoni soluble egg antigen in a cohort of school children in Ethiopia.

Acquired immunity is believed to be the main factor in the age-related differences in prevalence and intensity of Schistosoma infections. We studied antibody responses against S. mansoni soluble egg antigen (SEA) by ELISA in children before treatment, 5 weeks and one year after treatment. After screening for S. mansoni infection, positive children were treated with praziquantel (40 mg per kg body weight). Infection rate was significantly higher in boys younger than 12 years than in girls in the same age group. Levels of all antibody isotypes, except IgG1 (before treatment) or IgA (one year after treatment), were higher in children older or equal to 12 years than in those younger. The difference between age groups was significant for IgE, IgM, IgG3 and IgG4 (before treatment) and IgE (one year after treatment). Similarly, all antibody isotypes, except IgE, before treatment were higher in boys than in girls. At 5 weeks after treatment, IgG, IgE and IgG1 showed an increasing tendency, whereas IgM and IgG3 tended to decrease. One year after treatment, significant decreases were observed in IgG, IgG1 and IgG4 and a significant increase in IgG2 levels. The study presents further evidence for the difference in acquired immunity between younger and older children, and between boys and girls. The study also suggests that praziquantel differentially affects antibody responses against S. mansoni SEA.

Praziquantel side effects and efficacy related to Schistosoma mansoni egg loads and morbidity in primary school children in north-east Ethiopia.

A total of 611 Schistosoma mansoni infected primary school children from three schools in north-east Ethiopia were treated with praziquantel at 40 mg/kg body weight in a single dose. Pre-treatment, 40.4% had no presenting symptoms and 30-40% had nausea, abdominal cramps and/or bloody-mucoid diarrhoea. None of the pre-treatment symptoms was related to nutritional status, intensity of S. mansoni egg excretion, or to the presence of other concomitant intestinal parasitic infections. During the first 4-6 h post-treatment observation period, 90 (14.7%) children self-presented with severe gastro-intestinal symptoms. Children who self-presented with severe symptoms had a higher mean age and mean S. mansoni egg excretion compared with children who did not self-present. The following day a total of 529 (86.6%) children, including all who self-presented during the first 4-6 h post-treatment, reported for clinical check-up and were subjected to a structured questionnaire interview on symptoms they had experienced over the time lapse following treatment. Among these, 91.5% reported one or more treatment related symptoms which were at times severe. Abdominal cramps (86.9%), diarrhoea with blood and/or mucus (49.5%), dizziness (31.2%) and vomiting (24.9%) were the most common treatment related symptoms. Skin rash with oedema were observed in four cases. Among treatment related symptoms, the combination of abdominal cramps with vomiting, bloody diarrhoea, vomiting alone and general weakness were significantly higher among the malnourished. A proportion of these symptoms increased with increasing categories of S. mansoni egg excretion before and after adjusting for nutritional status and concurrent intestinal parasitic infections. Overall, the cure rate of praziquantel, among 541 children who had stool examination 5 weeks after treatment was 83.2% and this rate decreased with increasing pre-treatment egg counts. In conclusion, most of the treatment related symptoms were mild. However, some of the objective symptoms were at times severe and may reduce drug compliance in primary health care based population chemotherapy.

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.

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.

Mezlocillin treatment of septicemia in general hospitals.

Gramnegative septicemia in 23 patients from different Norwegian departments of general medicine or surgery was treated with mezlocillin. Most of the patients were old, and 14 patients were considered compromised due to underlying disease. In the majority of cases the septicemia originated from urinary tract infections. Uneventful recovery was accomplished in 16 patients (70%) and another 5 cases improved. In 2 patients no clinical effects were observed within 3 days of treatment. Apart from diarrhoea in 5 of the cases, no side-effects occurred. Mezlocillin proved to be a safe and efficient drug for the treatment of gramnegative septicemias of the type that is most commonly encountered in Norwegian general hospitals.