Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer.

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women's empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and women.

La schistosomiase génitale féminine, résultant d'une infection chronique à Schistosoma haematobium (également connue sous le nom de bilharziose), continue d'être largement ignorée par les responsables des politiques de santé nationales et internationales. Si le monde lui accorde son attention en vue de mener une action à grande échelle contre la maladie, c'est surtout pour déterminer s'il s'agit d'un facteur de risque pour la transmission du virus de l'immunodéficience humaine (VIH). Pourtant, la schistosomiase génitale féminine est associée à des douleurs, des saignements et peut engendrer l'hypofertilité, voire la stérilité. Par conséquent, celles qui en souffrent sont souvent stigmatisées, et le problème est courant dans les régions endémiques d'Afrique subsaharienne. Cette maladie doit donc être considérée comme composante à part entière d'une approche globale de la santé et des droits humains pour les femmes et filles africaines, à l'instar du VIH et du cancer du col de l'utérus. Chacune de ces trois maladies fait l'objet d'une intervention préventive ciblée qui a déjà fait ses preuves: le traitement antirétroviral et la prophylaxie pré-exposition pour le VIH; le vaccin contre le papillomavirus humain pour le cancer du col de l'utérus; et l'administration de praziquantel pour la schistosomiase génitale féminine. Le présent document se penche sur la manière d'intégrer la schistosomiase génitale féminine dans la prise en charge du VIH et du cancer du col de l'utérus. Un tel programme fera partie d'un cadre plus vaste consacré aux droits et à la santé sexuelle et reproductive, à l'émancipation des femmes et à la justice sociale en Afrique. Les approches intégrées qui regroupent plusieurs programmes de santé publique permettent d'élargir des perspectives ou de créer des opportunités visant à atteindre un plus grand nombre de filles et de femmes tout au long de leur vie. Nous exposons les grandes lignes d'un programme de recherches pragmatiques et opérationnelles capable d'optimiser la mise en œuvre conjointe d'une série de mesures qui répondent aux besoins spécifiques des filles et des femmes.

Los responsables de formular las políticas sanitarias nacionales y globales siguen ignorando en gran medida la esquistosomiasis genital femenina como consecuencia de la infección crónica por Schistosoma haematobium (conocida comúnmente como bilharziasis). La atención internacional para adoptar medidas de gran alcance contra la enfermedad se centra en determinar si es un factor de riesgo para la transmisión del virus de la inmunodeficiencia humana (VIH). Sin embargo, la propia esquistosomiasis genital femenina está vinculada al dolor, las hemorragias y la infertilidad o subfertilidad, lo que conduce al estigma social, además de ser un problema común para las mujeres de las áreas en donde la esquistosomiasis es endémica en el África subsahariana. Por consiguiente, la enfermedad debe ser reconocida como otro componente de un programa integral de salud y de derechos humanos para las mujeres y las niñas de África, junto con el VIH y el cáncer de cuello uterino. Cada una de estas tres enfermedades tiene una intervención preventiva específica y comprobada: la terapia antirretroviral y la profilaxis previa a la exposición para el VIH; la vacuna contra el virus del papiloma humano para el cáncer de cuello uterino; y el tratamiento con praziquantel para la esquistosomiasis genital femenina. Se analiza cómo el control de la esquistosomiasis genital femenina se puede integrar con la atención del VIH y el cáncer de cuello uterino. Ese programa formará parte de un marco más amplio de salud y de derechos sexuales y reproductivos, de empoderamiento de la mujer y de justicia social en África. Los enfoques integrados que unen múltiples programas de salud pública tienen el potencial de ampliar o crear oportunidades para llegar a más niñas y mujeres a lo largo de sus vidas. Se describe a grandes rasgos un programa de investigación operacional pragmático que tiene el potencial de optimizar la implementación conjunta de una serie de medidas que respondan a las necesidades específicas de las niñas y de las mujeres.

Control of taeniasis and cysticercosis in China.

National surveys suggest that the prevalence of taeniasis has considerably decreased in China, while reported cases indicated T. solium cysticercosis was historically highly endemic in northeastern, central and southwestern China. The high prevalence of taeniasis and cysticercosis there was driven by socio-ecological determinants. Cysticercosis may occur in the central nervous system, spinal cord, subcutaneous muscle, eyes, heart and oral cavity. Neurocysticercosis, the clinically most important type, causes epilepsy, increased intracranial pressure and neuropsychiatric symptoms. New molecular diagnostic techniques have been introduced for high sensitivity and discrimination of Taenia species. Immunological methods remain useful in the diagnosis of cysticercosis, especially neurocysticercosis. The introduction of imaging techniques including computed tomography and magnetic resonance imaging has significantly improved the diagnosis of neurocysticercosis. Recently, a combination of pumpkin seeds and areca nut has been explored against taeniasis, while praziquantel and albendazole are administrated simultaneously against cysticercosis, with promising efficacy and low side-effects. The widespread adoption of deworming protocols and techniques for inspection, management and treatment of pigs as well as improved sewage management has contributed to the significant decrease of taeniasis and cysticercosis in northern China. The positive results of these techniques should now be extended to highly endemic areas in western China to achieve the national elimination target for taeniasis and cysticercosis. Elimination of taeniasis and cysticercosis in China will not only benefit public health within China but also set an important example for less developed countries.

Field evaluation of a coproantigen detection test for fascioliasis diagnosis and surveillance in human hyperendemic areas of Andean countries.

BACKGROUND: Emergence of human fascioliasis prompted a worldwide control initiative including a pilot study in a few countries. Two hyperendemic areas were chosen: Huacullani, Northern Altiplano, Bolivia, representing the Altiplanic transmission pattern with high prevalences and intensities; Cajamarca valley, Peru, representing the valley pattern with high prevalences but low intensities. Coprological sample collection, transport and study procedures were analyzed to improve individual diagnosis and subsequent treatments and surveillance activities. Therefore, a coproantigen-detection technique (MM3-COPRO ELISA) was evaluated, using classical techniques for egg detection for comparison. METHODOLOGY AND FINDINGS: A total of 436 and 362 stool samples from schoolchildren of Huacullani and Cajamarca, respectively, were used. Positive samples from Huacullani were 24.77% using the MM3-COPRO technique, and 21.56% using Kato-Katz. Positive samples from Cajamarca were 11.05% using MM3-COPRO, and 5.24% using rapid sedimentation and Kato-Katz. In Huacullani, using Kato-Katz as gold standard, sensitivity and specificity were 94.68% and 98.48%, respectively, and using Kato-Katz and COPRO-ELISA test together, they were 95.68% and 100%. In Cajamarca, using rapid sedimentation and Kato-Katz together, results were 94.73% and 93.58%, and using rapid sedimentation, Kato-Katz and copro-ELISA together, they were 97.56% and 100%, respectively. There was no correlation between coproantigen detection by optical density (OD) and infection intensity by eggs per gram of feces (epg) in Cajamarca low burden cases (<400 epg), nor in Huacullani high burden cases (≥ 400 epg), although there was in Huacullani low burden cases (<400 epg). Six cases of egg emission appeared negative by MM3-COPRO, including one with a high egg count (1248 epg). CONCLUSIONS: The coproantigen-detection test allows for high sensitivity and specificity, fast large mass screening capacity, detection in the chronic phase, early detection of treatment failure or reinfection in post-treated subjects, and usefulness in surveillance programs. However, this technique falls short when evaluating the fluke burden on its own.

Administration of triclabendazole is safe and effective in controlling fascioliasis in an endemic community of the Bolivian Altiplano.

BACKGROUND: The Bolivian northern Altiplano is characterized by a high prevalence of Fasciola hepatica infection. In order to assess the feasibility, safety and efficacy of large-scale administration of triclabendazole as an appropriate public health measure to control morbidity associated with fascioliasis, a pilot intervention was implemented in 2008. MATERIALS AND METHODS: Schoolchildren from an endemic community were screened for fascioliasis and treated with a single administration of triclabendazole (10 mg/kg). Interviews to assess the occurrence of adverse events were conducted on treatment day, one week later, and one month after treatment. Further parasitological screenings were performed three months after treatment and again two months later (following a further treatment) in order to evaluate the efficacy of the intervention. RESULTS: Ninety infected children were administered triclabendazole. Adverse events were infrequent and mild. No serious adverse events were reported. Observed cure rates were 77.8% after one treatment and 97.8% after two treatments, while egg reduction rates ranged between 74% and 90.3% after one treatment, and between 84.2% and 99.9% after two treatments. The proportion of high-intensity infections (≥ 400 epg) decreased from 7.8% to 1.1% after one treatment and to 0% after two treatments. CONCLUSION: Administration of triclabendazole is a feasible, safe and efficacious public health intervention in an endemic community in the Bolivian Altiplano, suggesting that preventive chemotherapy can be applied to control of fascioliasis. Further investigations are needed to define the most appropriate frequency of treatment.

Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: identifying best practices to roll out programs at national scale.

In 2006 the U.S. Agency for International Development (USAID) established the Neglected Tropical Disease (NTD) Control Program to support national governments in developing successful, cost-efficient NTD programs that integrate disease-specific programs into coordinated national initiatives, in accord with the World Health Organization recommendations. A 3-stage "roll-out package" has been developed for effectively integrating and scaling up such programs to full-national scale. Stage-1 lays the groundwork-identifying NTD leadership within the Ministry of Health, conducting a national Situation Analysis, formulating a multiyear Plan of Action, and undertaking a funding gap analysis. Stage-2 focuses on scaling up the integrated NTD program-convening national stakeholder meetings, developing annual work plans, carrying out disease mapping, and establishing monitoring and evaluation activities. Stage-3 aims at ensuring effective management-identifying clear roles and responsibilities for partners, and creating a central coordinating mechanism. Assessment and reassessment of these complex NTD programs that target literally billions of people are essential to establish "best practice" strategies for long-term public health success.

Preventive Chemotherapy and Transmission Control (PCT) databank: a tool for planning, implementation and monitoring of integrated preventive chemotherapy for control of neglected tropical diseases.

The integration of vertical control programmes of neglected tropical diseases (NTDs) aims to contain operational cost, simplify the application of the control measures and further extend the coverage of interventions. The Preventive Chemotherapy and Transmission Control (PCT) databank was established by the WHO to facilitate access and sharing of information from national programmes with stakeholders involved in NTD control. The PCT databank contains compilations of historical and current information on disease-specific epidemiological situations, the geographical overlapping of NTDs and progress of control activities in all the NTD-endemic countries. A summary of country-specific epidemiological maps and the progress of control activities are available from the online PCT databank and the Country Profiles. Annual progress of preventive chemotherapy interventions targeting specific NTDs is reported in the Weekly Epidemiological Record (WER) published annually for each disease targeted. In this paper, the method of data collection and compilation used to establish the PCT databank is explained and the key features of the online PCT databank, the Country Profiles and WER are presented.

Preventive chemotherapy and the fight against neglected tropical diseases.

Preventive chemotherapy is the public health strategy recommended by the WHO against a set of neglected tropical diseases that includes four groups of helminth infections (lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis) and one chlamydial (trachoma) infection. This article presents the characteristics of preventive chemotherapy interventions directed against each disease targeted by this strategy and provides an update on the status of their implementation worldwide.

Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study.

BACKGROUND: Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. METHODOLOGY/PRINCIPAL FINDINGS: Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. CONCLUSIONS/SIGNIFICANCE: Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.

An analysis of the impact of the Schistosomiasis Control Programme in Brazil

The impact of the Schistosomiasis Control Programme (PCE) in Brazil was analyzed, covering the period 1976 to 2003, using the following indicators: percentage of Schistosoma mansoni carriers detected among the population examined in the coproscopic surveys (PPS): mortality rate for schistosomiasis, per 100,000 inhabitants (TME): hospitalization rate for schistosomiasis, per 100,000 inhabitants (TIE): average age of deaths caused by schistosomiasis (IMOE). There was a 38.5 percent reduction in the PPS after the introduction of the PCE, attributed to the treatment of carriers. Even in hyper-endemic municipalities, such as Conde and Cuitegí, in the state of Paraíba, the PPS fell more than 50 percent after the first year of treatment. The parasitic burden of the carriers also decreased in the two municipalities. The TME was reduced by 63.4 percent and the TIE by 77.3 percent. The mortality rate was highest among the 50-and-above age group. The country×s IMOE rose 32.3 percent. The IMOE was seen to be much lower in the state of Minas Gerais, where the PCE was only initiated in 1983, with very limited coverage.

Control of Taenia solium cysticercosis/taeniosis.

Cysticercosis is emerging as a serious public health and agricultural problem in many poorer countries of Latin America, Africa, and Asia. Caused by the pork tapeworm, Taenia solium, this zoonotic disease forms larval cysts in humans and pigs that can lead to epilepsy and death in humans, reduces the market value of pigs and makes pork unsafe to eat. It occurs where pigs range freely, sanitation is poor, and meat inspection is absent or inadequate, and is thus strongly associated with poverty and smallholder farming. Although theoretically easy to control and declared eradicable cysticercosis remains neglected in most endemic countries due to lack of information and awareness about the extent of the problem, suitable diagnostic and management capacity, and appropriate prevention and control strategies. Human neurocysticercosis occurs when the larval cysts develop in the brain. It is considered to be the most common parasitic infection of the human nervous system and the most frequent preventable cause of epilepsy in the developing world. Thus far the infection has not been eliminated from any region by a specific program, and no national control programs are yet in place. We consider the tools available for combating cysticercosis and suggest simple packages of interventions, which can be conducted utilizing existing services and structures in the endemic countries to provide appropriate and sustainable control of the disease.

An analysis of the impact of the Schistosomiasis Control Programme in Brazil.

The impact of the Schistosomiasis Control Programme (PCE) in Brazil was analyzed, covering the period 1976 to 2003, using the following indicators: percentage of Schistosoma mansoni carriers detected among the population examined in the coproscopic surveys (PPS): mortality rate for schistosomiasis, per 100,000 inhabitants (TME): hospitalization rate for schistosomiasis, per 100,000 inhabitants (TIE): average age of deaths caused by schistosomiasis (IMOE). There was a 38.5% reduction in the PPS after the introduction of the PCE, attributed to the treatment of carriers. Even in hyper-endemic municipalities, such as Conde and Cuitegí, in the state of Paraíba, the PPS fell more than 50% after the first year of treatment. The parasitic burden of the carriers also decreased in the two municipalities. The TME was reduced by 63.4% and the TIE by 77.3%. The mortality rate was highest among the 50-and-above age group. The country's IMOE rose 32.3%. The IMOE was seen to be much lower in the state of Minas Gerais, where the PCE was only initiated in 1983, with very limited coverage.

Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households.

This trial investigated the anti-schistosomal activity of mirazid in comparison with that of praziquantel in Schistosoma mansoni-infected Egyptian patients. The sample population was composed of 1,131 individuals (459 school children and 672 household members). Screening for S. mansoni was conducted using the standard Kato Katz technique. Four slides from a single stool sample were examined before treatment, and four slides per sample from stool samples obtained on three consecutive days were examined post-treatment. All positive eligible subjects were randomly assigned into two groups, the first received mirazid at a dose of 300 mg/day for three consecutive days, and the second received praziquantel at a single dose of 40 mg/kg. All treated subjects were examined 4-6 weeks post-treatment. Mirazid showed low cure rates of 9.1% and 8.9% in S. mansoni-infected school children and household members, respectively, compared with cure rates of 62.5% and 79.7%, respectively, in those treated with praziquantel. Therefore, we do not recommend mirazid as an agent to control schistosomiasis.

Determination of ED50 values for praziquantel in praziquantel-resistant and -susceptible Schistosoma mansoni isolates.

The dose of praziquantel required to kill 50% of adult worms in vivo (i.e. the ED50) was estimated for nine different isolates of Schistosoma mansoni in infected mice. Four of the isolates were selected because they had not knowingly been in contact with the drug (i.e. they were putatively praziquantel-susceptible). Five putatively praziquantel-resistant isolates were chosen because they had been selectively bred for drug-resistance in the laboratory and/or had previously been shown to be relatively resistant to praziquantel in the field. The work was performed in three laboratories in different countries using pre-agreed and comparable experimental protocols. All four praziquantel-susceptible isolates had ED50s estimated to be <100 mg/kg (mean=70+/-7 SD; median=68), while all five putatively praziquantel-resistant isolates had estimated ED50s >100 mg/kg (mean=209+/-48 SD; median=192). Thus, the five praziquantel-resistant isolates, including two that had been subjected to drug pressure during more than 20 passages in mice, had drug ED50s that were approximately three times as great as those of the praziquantel-susceptible isolates. Two of the five isolates in the putatively resistant group had previously been passaged 15 or more times in mice without administration of drug-pressure, but had ED50s consistent with the other three isolates in the group, indicating that the trait of praziquantel-resistance did not necessarily impair biological fitness during laboratory passage. The protocols used here to estimate the praziquantel ED50s of S. mansoni isolates should be useful for establishing and monitoring the drug susceptibility/resistance profiles of parasite isolates freshly obtained from endemic areas, particularly those in which increased usage of the drug is likely to occur.

The control of human (neuro)cysticercosis: which way forward?

Taenia solium cysticercosis, and its public health and economic consequences, appears to be a growing problem in poor areas of Africa, Asia and Latin America where people eat pork and traditional pig husbandry is practiced (and expanding). Its burden is counted in terms of human disease (mainly neurocysticercosis related epilepsy) and economic losses, in a context of both commercial and traditional subsistence pig farming. Although substantial fragmentary information seems to be available from local settings, national and global burdens due to T. solium cysticercosis are still to be comprehensively assessed. With regard to control, several strategies have been checked out at a small or medium scale and have proven to be successful. Yet, no intervention programmes have been implemented so far at the national level with proven success. Although T. solium cysticercosis is considered to be a potentially eradicable disease, there is no evidence yet that it is feasible and recommendable to envisage this within a reasonable time frame. However, it appears realistic to aim for the rapid definition of a simple package of interventions, which can routinely be carried out by existing services and structures, and will give an optimal, long-term return in terms of burden relief. Also, a number of international initiatives and opportunities currently exist in which a more pro-active attitude towards the control of T. solium cysticercosis can be integrated and promoted. Commitment of both national and local authorities to control the disease needs to be convincingly solicited and, as for most zoonotic diseases, an interdisciplinary approach is essential.