1,721,614 research outputs found
FIGURE 2 in RANDOM SPATIAL DISTRIBUTION OF SCHISTOSOMA MANSONI AND HOOKWORM INFECTIONS AMONG SCHOOL CHILDREN WITHIN A SINGLE VILLAGE
FIGURE 2. Spatial distribution of different infection intensity levels of hookworm among school children living in the village of Fagnampleu, western Côte d'Ivoire.Published as part of Utzinger, Jürg, Müller, Ivo, Vounatsou, Penelope, Singer, Burton H., N'Goran, Eliézer K. & Tanner, Marcel, 2003, RANDOM SPATIAL DISTRIBUTION OF SCHISTOSOMA MANSONI AND HOOKWORM INFECTIONS AMONG SCHOOL CHILDREN WITHIN A SINGLE VILLAGE, pp. 686-692 in Journal of Parasitology 89 (4) on page 690, DOI: 10.1645/ge-75r, http://zenodo.org/record/767889
Rights incorporated : integrating human rights impact assessment into global business practices
Background: In 2011, the United Nations (UN) Human Rights Council unanimously endorsed a protocol dictating the role of multinational corporations towards human rights. What resulted, the UN Guiding Principles on Business and Human Rights, set forth a framework for corporations to proactively “respect” human rights. The responsibility to respect was reasoned to include: (i) policy statements; (ii) the conduct of “human rights due diligence,” to know and demonstrate that companies understand and manage their human rights impacts; and (iii) processes for hearing and addressing human rights-related grievances from affected people. This framework was embraced by the business, government and civil society communities, but it did not include detailed guidance on how it could be implemented.
Objectives: Four specific objectives were pursued in this PhD thesis: (i) to develop and advance tools and methods for human rights due diligence and, specifically, human rights impact assessment (HRIA) with the intention that these tools can be readily adapted to a variety of industries and contexts; (ii) to validate these tools at investment projects around the globe; (iii) to draw from existing environmental, social and health impact assessments and build on best practices while avoiding redundancy with environmental, social and health impact assessments; and (iv) to synthesise the experiences of HRIA practitioners, find commonalities and consider next steps.
Research partnership: These doctoral studies were carried out through a public-private partnership between the Swiss Tropical and Public Health Institute (Swiss TPH), NewFields LLC and NomoGaia. NewFields is an international consulting firm with long-standing expertise in health impact assessment (HIA) in developing countries. NomoGaia is a global human rights think tank dedicated to making human rights due diligence a core practice for multinational corporations. Fieldwork for NomoGaia’s assessment served as a platform for the present research, while learnings from consulting work with NewFields clients informed the candidate’s understanding of issues.
Methods: This PhD thesis entailed fieldwork primarily at four investment projects in low- and middle-income countries in Africa, Southeast Asia and Central America. Analysis was also informed by additional field experience through work with NewFields and NomoGaia. At each project location, HRIA tools were employed, modified, consolidated and validated. Follow-up monitoring at several locations contributed methodological developments for longitudinal “surveillance-response” approaches to HRIA.
Results: The culmination of fieldwork and desk-based analysis has resulted in a comprehensive depiction of HRIA in practice. The chapters that follow, as both published and working papers on HRIA, describe how HRIA can be conducted, and how its implementation can affect corporate behaviours. Each assessment conducted and analysed identified corporate impacts and risks not identified in other assessment. Each also documented positive changes in corporate behaviour over time. A key finding was the importance of longitudinal assessment, using initial HRIA as a benchmark for ongoing, periodic analysis of changing contexts and impacts. Because neither companies nor human rights exist in a vacuum, companies must be nimble and responsive to changes. By assessing the Kayelekera uranium mine repeatedly over five years, we identified contextual risks associated with HIV transmission that posed minimal threat during initial assessment but became significant as contextual conditions deteriorated. At the Uchindile plantation in Tanzania, we found that major improvements in housing and working conditions were limited to specific dormitories, making clear the necessity of broad assessment across operations. This was particularly relevant with regard to health, where improved access to care for one population was presented as a positive, but assessment found that decreased access to medical care for others outweighed those gains.
Conclusions/significance: The systematic HRIA approach that evolved over the three years of this PhD and the four preceding years of preliminary fieldwork represents a vital first step in the establishment of HRIA as a valuable corporate tool. Evidence-based, transparent, dialectic, responsive and holistic HRIA is increasingly seen as an appropriate approach to identifying and managing corporate human rights risks. Going forward, companies will need to embrace transparency to further validate HRIA and to demonstrate that affected rightsholders are entitled to know the human rights risks they face and to have a say in how they are managed. Governments can support this effort by mandating that companies conduct and publish HRIA for capital intensive projects planned within their jurisdiction
Health risk assessment along wastewater recovery and reuse systems in Kampala, Uganda and Hanoi, Vietnam
Background: Reuse and recovery of wastewater in agriculture and aquaculture has gained traction in the new millennium. In view of continued population growth, increasing scarcity of freshwater and other natural resources, the demand to boost food production and efforts to enhance wastewater reuse will increase in the years to come. Indeed, wastewater reuse and the recovery of water, nutrients and energy can generate promising business opportunities and support livelihoods in poor communities, particularly in urban and peri-urban areas of low- and middle-income countries (LMICs). Contact with untreated wastewater is associated with microbial and chemical hazards and thus might negatively affect human health. Standardised, quality-controlled methods to assess and manage health risks are available, such as those described in the World Health Organization (WHO) guidelines for the safe use of wastewater, excreta and greywater. However, the practicability and uptake of these methods have proved difficult in LMICs. There is a paucity of context-specific, quality-based environmental pollution data, epidemiological data and accurate disease burden estimates for highly dynamic environments along wastewater recovery and reuse systems in major urban settings, especially in Africa, Asia and Latin America. Moreover, discharge thresholds and health-based targets need to be reviewed to match the realities of LMICs.
Objectives: This PhD thesis aims to generate evidence of health risks among people living and working along wastewater and faecal sludge management and reuse systems in Kampala, Uganda, a low-income African city, and in Hanoi, Vietnam, a lower-middle-income Asian city. By comparing relevant conditions in these two systems, the thesis seeks to: (i) generate evidence on microbial and chemical contamination and treatment capacities along wastewater management systems; (ii) assess prevalence and risk factors of intestinal parasitic infections in different population groups exposed to wastewater and faecal sludge; (iii) estimate the burden of gastrointestinal infections due to the exposure to wastewater; and (iv) discuss and compare risk assessment approaches and their potential for application along wastewater recovery reuse systems in selected LMICs.
Research partnership: This PhD thesis is embedded in the “Resource Recovery and Reuse” (RRR) project, funded by the Swiss Agency for Development and Cooperation (SDC). Our main partner in this collaborating endeavour is WHO, while other international partners include the International Water Management Institute, the International Centre for Water Management Services, and the Department of Water and Sanitation in Developing Countries, Swiss Federal Institute of Aquatic Science and Technology. In Uganda, we closely work with the Makerere School of Public Health, the Vector Control Division of the Ministry of Health and the National Water and Sewerage Corporation. In Hanoi, our main partner is the Center for Public Health and Ecosystem Research at Hanoi School of Public Health. Moreover, we closely work with the Department of Parasitology at the National Institute of Malaria, Parasitology and Entomology, the National Institute of Hygiene and Epidemiology, and the National Institute of Veterinary Research.
Methods: Two accordant case studies were carried out along the major wastewater recovery and reuse systems in Kampala (along the Nakivubo channel) between September and December 2013 and in Hanoi (along the To Lich River) between April and June 2014. A methodological triangulation was performed, including (i) an environmental assessment; (ii) a cross-sectional survey; and (iii) a quantitative microbial risk assessment (QMRA). In brief, the environmental assessment entailed different standard analyses to observe the variance of microbial contamination (thermotolerant coliforms (TTC), Escherichia coli, Salmonella spp. and helminths (e.g. Ascaris and hookworm eggs) in water at critical control points over a period of two months. In addition, in Kampala, a range of physico-chemical parameters and heavy metal contamination in sediment, soil and plants were measured. Cross-sectional parasitological surveys were conducted to assess intestinal parasitic infections in different population groups (aged ≥18 years) exposed to wastewater and faecal sludge such as sanitation workers, urban farmers and community members living in proximity to wastewater channels. Moreover, comparison groups without exposure to wastewater were included. Stool samples were subjected to the Kato-Katz and formalin-ether concentration methods for the diagnosis of helminth and intestinal protozoa infections. A questionnaire was administered to all participants to identify self-reported signs and symptoms and risk factors for intestinal parasite infections. The QMRA methodology was applied to different scenarios of exposure to wastewater (e.g. farming, flooding of living area, living in informal communities and swimming). Pathogenic strains of norovirus, rotavirus, Campylobacter spp., pathogenic E. coli, pathogenic Salmonella spp., Cryptosporidium spp. and Ascaris lumbricoides were used to estimate annual incidence of gastrointestinal illness and the resulting disease burden.
Results: The environmental assessment revealed high concentrations of bacteria along the major wastewater channels in Kampala and Hanoi (e.g. between 105 and 107 colony forming unit (CFU) per 100 mL). In Kampala, along the Nakivubo channel, the concentration of TTC, biological oxygen demand5 (BOD5), chemical oxygen demand (COD) and total suspended solids (TSS) were 2- to 3-fold higher, when compared with data reported in 2008. Moreover, contamination of bacteria measured in water of the Nakivubo wetland, where urban farming takes place, was above national discharge standards and WHO’s tolerable safety limits for unrestricted irrigation. In Hanoi, the To Lich River water used in wastewater-fed agriculture fields in peri-urban areas showed (beside applied treatment in retention ponds) mean contamination with total coliforms (TC), E. coli and Salmonella spp. of 1.3 × 107, 1.1 × 106 CFU/100 mL and 108 most probable number (MPN)/100 mL, respectively. These values are 110-fold above the Vietnam discharge limits for agriculture reuse and even 260-fold above WHO’s tolerable safety limits for unrestricted irrigation. In both cities, the issue of faecal sludge collection is challenged by the provision of formal and adequate collection services, disposal and reuse solutions. Moreover, industrial pollution is a major issue, while registration and the source control of industries and effluents is lacking, leading to elevated concentration of various heavy metals in the environment.
The cross-sectional survey in Kampala included 915 individuals and revealed that the highest point-prevalence of intestinal parasite infections was found among urban farmers (75.9%), whereas the lowest point-prevalence was found among workers collecting faecal sludge (35.8%). Hookworm was the predominant helminth species (27.8%). Trichuris trichiura, Schistosoma mansoni, A. lumbricoides, and Entamoeba histolytica/E. dispar showed prevalence rates of 15% and above among urban farmers. For all investigated parasite infections, we found significantly higher odds for urban farmers than for the other groups (adjusted odds ratios ranging between 1.6 and 12.9). In Hanoi, the cross-sectional survey included 681 individuals and showed lower point-prevalence rates of intestinal parasite infections than in Kampala. The highest point-prevalence rate of parasitic infection was found among rural farmers (30.2%), with hookworm and T. trichiura being the predominant helminth species (24.8% and 5.4%, respectively). For intestinal parasite infections, we found significantly higher odds for rural farmers than for other groups (adjusted odds ratios 5.8, 95% confidence interval 2.5 to 13.7).
For Kampala, the QMRA estimated an annual disease burden across all 18,204 exposed people of 304,3 disability-adjusted life years (DALYs). Disease burden per person per year (pppy) was highest among urban farmers, sanitation workers and children in slum communities (0.073, 0.040 and 0.017 DALYs, respectively). For Hanoi, QMRA estimated an annual disease burden across 7,125 exposed people of 62.7 DALYs. Disease burden pppy was highest in urban farmers (0.0122 DALYs pppy), followed by sanitation workers (0.006 DALYs pppy) and rural farmers (0.0004 DALYs pppy).
Conclusions: The findings from this 3-year PhD thesis make an important contribution for a deeper understanding of the nexus of urban wastewater recovery and reuse systems, wastewater pollution and their implications for public health in the context of a major East African and Southeast Asian city. In both cities, and besides considerable differences in applied infrastructures, wastewater treatment capacities are insufficient for reducing the levels of microbial and chemical contamination to tolerable levels that would allow for safe reuse in agriculture. Major health risks were observed along both wastewater recovery and reuse systems. Children living in informal communities in Kampala are at very high risk of gastrointestinal diseases, especially due to rotavirus, and pathogenic E. coli and Salmonella spp. Epidemiological survey estimates revealed that urban farmers using wastewater were especially vulnerable for schistosomiasis and soil-transmitted helminthiasis in Kampala, whereas the high risk for urban farmers in Hanoi was only evident by means of QMRA. Indeed, for urban farmers, QMRA estimates were as high as 0.073 and 0.011 DALYs pppy in Kampala and Hanoi, respectively. These estimates are several thousand-fold above the revised WHO health-based targets and 7 and 6 times higher than the estimates made by the Global Burden of Disease study 2010 for an average Ugandan and Vietnamese, respectively. It is argued that the current health-based targets should be set according to local reference levels (e.g. to estimates made by the Global Burden of Disease study 2010). Promoting sanitation safety planning while combining evidence generated from environmental surveys, epidemiological surveys and QMRA can contribute to the understanding of existing systems and hazards along critical control points to better evaluate further investments in infrastructure and coordinate actions to protect public health. Considering the increasing attention to wastewater in the framework of the sustainable development goals (SDGs), more integrated studies using sanitation safety planning approaches are needed to generate sufficient understanding of reuse situations in rapidly changing urban contexts to minimise detrimental health effects and maximise gains from the recovered water, nutrients and energy in urban areas of LMICs
Diagnosis, epidemiology and control of soil-transmitted helminth infection in Zanzibar, Tanzania
Hintergrund: Durch Bodenkontakt übertragene parasitische Würmer infizieren vor allem arme Bevölkerungsgruppen in tropischen und subtropischen Ländern, die einen geringen hygienischen Standard haben. Intestinale Würmer werden übertragen indem Fäkalien, die Wurmeier enthalten, in den Boden gelangen und von dort an Nahrung oder Händen klebend in den Mund geraten und geschluckt werden. Bei manchen Wurmarten können auch die in der Erde lebenden Larven in die menschliche Haut eindringen und von dort in den Körper und Darm wandern. Die globale Belastung, die durch die intestinalen Würmer verursacht wird, wird auf 39 Millionen jährlich verlorene disability adjusted life years (DALYs) geschätzt. Kinder und schwangere Frauen haben das höchste Erkrankungsrisiko. Die Weltgesundheitsorganisation (WHO) vertritt die Strategie einer breiten und wiederholten Entwurmung von Schulkindern zur Bekämpfung der von intestinalen Wurminfektionen verursachten Erkrankungen. Die Weltgesundheitsversammlung setzte im Mai 2001 zum Ziel, dass eine flächendeckende Entwurmung von mindestens 75% aller Schulkinder, die ein Infektionsrisiko haben, bis im Jahr 2010 erreicht werden soll. In Sansibar, Tansania, wurden durch Bodenkontakt übertragene intestinale Würmer bereits in den 90er Jahren als Gesundheitsproblem erkannt, weil 85% der untersuchten Bevölkerung mit mindestens einer Art, Ascaris lumbricoides, Hakenwurm (Ancylostoma duodenale und Necator americanus) und Trichuris trichiura, infiziert war. Infektionen mit Strongyloides stercoralis, der am wenigsten Beachtung findenden Art der intestinalen Würmer, traten bei 40% der untersuchten Schulkinder aus dem ländlichen Sansibar auf. In Sansibar wurden 1994 und 2001 nationale Wurmkontrollprogramme vom Gesundheitsministerium etabliert. Seither werden Schulkindern und andere Risikogruppen jährlich entwurmt. Dabei wurde eine Behandlungsdichte von 80% erreicht.
Ziel: Das allumfassende Ziel dieser Dissertation war die Vertiefung unseres Verständnisses der Epidemiologie und Kontrolle von durch Bodenkontakt übertragene Wurminfektionen in Sansibar. Die drei folgenden bestimmten Ziele sollten untersucht werden. Erstens sollten unterschiedliche diagnostische Methoden für die Diagnose von intestinalen Wurminfektionen verglichen und evaluiert werden. Zweitens sollten die Epidemiologie und Risikofaktoren für durch Bodenkontakt übertragene Würmer, einschließlich S. stercoralis, in Gebieten von Unguja, Sansibar, die sich in ihrer Umwelt und ihrem Sozioökonomischen Status unterscheiden, untersucht werden. Drittens sollte die Langzeitwirkung von Antiwurm-Behandlungen auf das Vorkommen und die Intensität der Wurminfektionen festgestellt werden. Hierbei sollte auch die Wirkkraft und Sicherheit von Albendazole und Mebendazole, einzeln oder in Kombination mit Ivermectin gegen T. trichiura und andere Würmer verabreicht, ermittelt werden.
Methoden: Die Feldarbeit für diese Dissertation gliederte sich in drei Teile. Im Jahr 2007 wurde eine Querschnittsstudie in fünf Koranschulen und in fünf Grundschulen in den sechs Distrikten von Unguja durchgeführt und 336 Kinder untersucht. Diese Studie diente der Untersuchung der epidemiologischen Begebenheiten von Wurminfektionen in Sansibar. Ebenfalls in diesem Jahr wurde eine Querschnittsstudie mit 401 Kindern aus den Grundschulen in Chaani und Kinyasini durchgeführt. Die parasitologischen Ergebnisse wurden mit Daten aus dem Jahr 1994 verglichen, die in den gleichen Schulen erhoben worden waren. Es wurden mehrere Stuhlproben über mehrere Tage hinweg von jedem der Kinder gesammelt. Die Kato-Katz Methode wurde zur Diagnose von A. lumbricoides, Hakenwurm und T. trichiura benutzt. Die Koga Agarplatten Methode diente zur Auffindung von Hakenwürmern und S. stercoralis und die Baermann Methode zur Diagnose von S. stercoralis Infektionen. Zusätzlich wurden Stuhlproben in einer Natriumazetat-Essigsäure-Formalinlösung (SAF) konserviert und in Italien mit der FLOTAC Methode untersucht. Die Sensitivität der einzelnen Methoden und Methodenkombinationen wurde verglichen.
Im Jahr 2008 wurde eine Querschnittsstudie in einer ländlichen und einer vorstädtischen Gemeinde mit 658 Personen im Alter von 5-100 Jahren durchgeführt. Neben der Diagnose von intestinalen Würmern mit den dargelegten Methoden wurden auch Urinproben auf Schistosoma haematobium Infektionen untersucht. Blutproben wurden auf Blutarmut und Antikörper gegen Wurminfektionen analysiert und die Teilnehmer wurden in einem Fragebogen-Interview über Verhaltensrisiken und Erkrankungen, die in Zusammenhang mit intestinalen Wurminfektionen stehen könnten, befragt. Die epidemiologische Situation in beiden Gebieten wurde verglichen und in Kontext mit den Wurmkontrollaktivitäten in Sansibar gesetzt.
Im Jahr 2009 wurde eine randomisierte kontrollierte Studie durchgeführt um die Wirkung von Monotherapien mit der von Kombinationstherapien zu vergleichen. Im Rahmen der Studie wurden 1240 Kinder aus den Grundschulen von Kinyasini und Kilombero auf Wurminfektionen untersucht. Die Kinder, die mit T. trichiura infiziert waren (n=610), wurden vier Behandlungsgruppen zugeteilt. Zur Diagnose wurden vier Kato-Katz Untersuchungen vor und 3-5 Wochen nach der Behandlung durchgeführt. Die Ergebnisse wurden mit denen der FLOTAC Methode verglichen.
Ergebnisse: Nach mehreren Jahren Wurmkontrollaktivitäten in Sansibar sind immer noch viele Menschen in Unguja mit durch Erdkontakt übertragenen intenstinalen Würmern infiziert. Die Prävalenz liegt zwischen 22% im urbanen Distrikt und 70% im Nord A Distrikt. Da die Intensität der Infektionen aber bei den meisten Menschen niedrig ist, sind die Infektionen schwierig zu diagnostizieren. Die Sensitivität der koprologischen Methoden kann (i) durch eine strikte Befolgung der WHO Laborhilfen (Bench aids für die Kato-Katz Methode), (ii) durch die Untersuchung mehrerer Stuhlpropen pro Person, (iii) durch mehrere Untersuchungen einer Stuhlprobe pro Person und (iv) durch die Kombination von verschiedenen Methoden verbessert werden. Die FLOTAC Methode diagnostiziert A. lumbricoides (~80%) und T. trichiura (~90%) Infektionen mit einer hohen Sensitivität. Die Methode muss aber noch weiter evaluiert und standardisiert werden, um Hakenwürmer verlässlich zu diagnostizieren. Das Potenzial der Methode auch in Entwicklungsländern angewendet zu werden und ihre Brauchbarkeit für Medikamentenstudien muss noch weiter untersucht werden. In Unguja kommen intestinale Wurminfektionen am häufigsten im Nord A Distrikt vor. Infektionen mit mehreren Wurmarten auf einmal treten besonders häufig in Kindern aus ländlichen Gegenden auf. Blutarmut kommt ebenfalls häufig vor, war aber in unserer Studie nicht mit intestinalen Wurminfektionen verbunden. Die Risikofaktoren für Wurminfektionen sind von dem Untersuchungsgebiet und der Wurmart abhängig und schließen neben demographischen Faktoren auch den Verzehr von rohem Gemüse oder Salat, das Nicht-Händewaschen nach dem Stuhlgang und eine vorangegangene Reise ein. T. trichiura ist die dominierende Art in Unguja und die höchsten Prävalenzen wurden in der Kilombero Grundschule gefunden (71%). Im Gegensatz zu Hakenwurm (-77%) und A. lumbricoides (-71%) ging die Prävalenz von T. trichiura (-48%) in den vergangenen Jahren weniger stark zurück. Die Ursache hierfür liegt wahrscheinlich in der schlechten Wirkungskraft von Albendazol (Heilungsrate (CR): 10%; Eireduktionsrate (ERR): 40%) und Mebendazol (CR: 19%; ERR: 67%), den Medikamenten, die normalerweise in Schulentwurmungsprogrammen gegen T. trichiura und andere intestinale Wurminfektionen verwendet werden. Der Zusatz von Ivermectin konnte die Wirkungskraft von vor allem Mebendazol (CR: 55%; ERR: 97%), aber auch von Albendazol (CR: 38%; ERR: 91%) gegen T. trichiura verbessern. Alle Medikamente und deren Kombinationen waren sehr wirkungsvoll gegen A. lumbricoides (ERR: >99%). Die Wirkungskraft von Albendazol (CR: 59%; ERR: 94%) gegen Hakenwürmer war sehr viel besser als die von Mebendazol (CR: 35%; ERR: 78%), aber der Zusatz von Ivermectin verbesserte den Behandlungserfolg nicht. Alle Nebenwirkungen waren mild und gingen innerhalb von 48 Stunden zurück und es gab keinen Unterschied zwischen den vier Behandlungsschemen. Die Heilungsraten, die mit FLOTAC gemessen wurden, waren für alle drei Wurmarten niedriger als die Ergebnisse, die mit der Kato-Katz Methode erhalten wurden.
Schlussfolgerung: Die Wurmkontrollprogramme in Sansibar haben die Prävalenz und Intensitäten von durch Erdkontakt übertragenen intestinalen Würmern und die damit in Zusammenhang stehenden Erkrankungen erfolgreich verringert. Eine geringere Armutsrate und ein damit einhergehender verbesserter Zugang zu sanitären Einrichtungen der Haushalte haben sicherlich ebenfalls dazu beigetragen, die Infektionsrate zu verringern. Die Kontrollprogramme von durch Erdkontakt übertragenen intestinalen Wurminfektionen in Unguja können nun die Prävalenz- und Übertragungseinschränkung in Angriff nehmen, müssen aber für einen nachhaltigen Fortschritt einige Massnahmen überarbeiten. Die abwechselnde Anwendung von Albendazol und Mebendazol sollte in Erwägung gezogen werden, um sowohl Hakenwurm als auch T. trichiura Infektionen effektiver einzudämmen. Damit T. trichiura erfolgreicher behandelt werden kann, und um zusätzlich auch S. stercoralis und Ektoparasiten zu erreichen, sollten Albendazol und Mebendazol mit Ivermectin kombiniert werden, wann immer es für Patienten in Frage kommt. Da Neuinfektionen durch Medikamentenanwendung alleine nicht verhindert werden können, und da T. trichiura Infektionen, die den Grossteil in Unguja ausmachen, nur ungenügend mit den vorhandenen Medikamenten geheilt werden, ist eine Verbesserung der Hygiene und der sanitären Einrichtungen unabdingbar, um die Wurminfektionen in Sansibar und in anderen endemischen Gebieten der Erde weiter einzudämmen. Eine ansprechende und einleuchtende Gesundheitserziehung und Kommunikation sollte weithin angewandt werden, um die Einstellung der Bevölkerung zu Verbesserungen im Sanitärwesen (Latrinenbau, Abwasserentsorgung und Zugang zu sauberem Wasser) zu fördern und ihre angemessene Nutzung zu gewährleisten. Nur ein verbreiteter Konsens und Wunsch nach besseren sanitären Einrichtungen auf lokaler Ebene, im Einklang mit von Regierungs- und Nichtregierungsorganisationen geförderten Armutsbekämpfungsmassnahmen wird letztendlich die Ausrottung von durch Bodenkontakt übertragenen intestinalen Würmern in Sansibar und in anderen Regionen der Welt ermöglichen
Enhancing control of schistosomiasis in Niger : assessing morbidity in preschool-aged children, praziquantel treatment efficacy and cost implication for control
Background: Schistosomiasis, accounted among the neglected tropical diseases (NTDs), represents a major public health problem, particularly in Africa, where more than 95% of all the cases of the world are currently concentrated. The health consequences of Schistosoma infection are considerable. Apart from the known long-term complications of a chronic infection (e.g. portal hypertension, kidney failure, bladder cancer and sterility), schistosomiasis is a debilitating disease leading to anaemia, malnutrition, chronic abdominal and pelvic pain, and diarrhoea.
In 2001, the World Health Assembly (WHA) adopted resolution 54.19, which urged member states to regularly treat at least 75% and up to 100% of all school-aged children at risk of schistosomiasis and other high-risk groups. Moreover, in 2006, the World Health Organization (WHO) launched the “preventive chemotherapy” (PCT) strategy, which relies on the regular administration of anthelminthic drugs to at-risk populations in an integrated manner. Following these international calls for action against NTDs, several African countries, including Niger, launched national control programmes based on PCT with support from partners.
The aims of the present PhD thesis in epidemiology were (i) to assess the morbidity of schistosomiasis in infants and preschool-aged children currently not included in PCT; (ii) to evaluate praziquantel (PZQ) efficacy using different treatment schemes, including a detailed analysis of cost; and (iii) to enhance the control of schistosomiasis and other NTDs in Niger.
Methods and principal finding: First, achievements and remaining challenges of schistosomiasis and soil-transmitted helminthiasis (STH) control in three countries of West Africa (i.e. Burkina Faso, Mali and Niger) that benefited from support of the Schistosomiasis Control Initiative (SCI) have been analysed. In the first 3 years of the control programmes, nearly 13.5 million doses of PZQ have been administrated against schistosomiasis and albendazole against STH with coverage rates varying between 67% and 94%. The PZQ treatments have resulted in a reduction of the prevalence and intensity of Schistosoma infection in sentinel cohorts that were set up to monitor and evaluate the national control programmes. Key challenges these national control programmes are currently facing include the ability to maintain the reduction in morbidity achieved so far and ensuring sustainability.
Second, we assessed morbidity due to schistosomiasis in infants and preschool-aged children who are currently not included in PCT according to WHO guidelines, including risk factors for infection in early childhood. We carried out a cross-sectional epidemiological survey in two villages in Niger: Falmado that is endemic for Schistosoma haematobium only, and Diambala that is a mixed S. haematobium-S. mansoni focus. A total of 282 children were examined (149 girls, 133 boys; average age, 2.6 years) and 224 mothers (average age, 30.1 years). For S. haematobium diagnosis, two urine samples obtained over consecutive days were subjected to a standard filtration method, while the diagnosis of S. mansoni was based on a single stool sample using duplicate Kato-Katz thick smears. Additionally, in Diambala, a pre-tested questionnaire was administered to mothers, which recorded demographic data, recent treatment history with anthelminthic drugs, household sanitation and water supply and bathing practices for their children. Prevalence of egg-patent S. haematobium infection among young children and their mothers was, respectively, 51% and 56% in Falmado, and 61% and 72% in Diambala. The prevalence of S. mansoni infection in Diambala was 44% among children and 52% in mothers. Mixed egg-patent infections of S. haematobium and S. mansoni were revealed in 29% of the children and 37% of the mothers. Results from the questionnaire survey showed that 70% of the children were accompanied by their mothers to schistosomiasis transmission sites before reaching their first birthday, and that three-quarter of the mothers used water directly drawn from the irrigation canals to wash their children.
Third, we evaluated the efficacy and safety of two closely spaced doses of PZQ against S. haematobium and S. mansoni in school-aged children, and characterised re-infection patterns over a 1-year period. The study was carried out in five villages in western Niger: Falmado, Seberi, Diambala, Namarigoungou and Libore. Parasitological examinations consisted of triplicate urine filtrations and triplicate Kato-Katz thick smears at each visit. Two 40 mg/kg oral doses of PZQ were administered 3 weeks apart. Follow-up visits were conducted 6 weeks, 6 months and 12 months after the first dose of PZQ. Adverse events were monitored within 4 hours after dosing by the survey team and 24 hours after treatment using a questionnaire. Our final study cohort comprised 877 children who were infected with either S. haematobium, or S. mansoni, or both species concurrently and received both doses of PZQ. At baseline, the geometric mean (GM) infection intensity of S. haematobium ranged from 3.6 (Diambala) to 30.3 eggs/10 ml of urine (Falmado). The GM infection intensity of S. mansoni ranged from 86.7 (Diambala) to 151.4 eggs/gram of stool (EPG) (Namarigoungou). Adverse events were reported by 33% and 1.5% of the children after the first and second dose of PZQ, respectively. We found cure rates in S. haematobium-infected children 3 weeks after the second dose of PZQ ranging between 49% (Falmado) and 98% (Namarigoungou) and high egg reduction rates (92-100%). Regarding S. mansoni, only moderate cure and egg reduction rates were found (52-59% in Diambala, 55-60% in Namarigoungou).
Fourth, in order to generate additional evidence regarding the safety and efficacy of PZQ for schistosomiasis in infants and preschool-aged children, we pursued a drug efficacy trial using PZQ syrup (Epiquantel®) in children aged below 72 months. The study was carried out between May and August 2010 in three villages. Overall, 243 children infected with S. haematobium and/or S. mansoni were treated with PZQ syrup at a dose of 40 mg/kg after they had received a meal of millet porridge. Children were observed during 4 hours post-treatment and a questionnaire was administered to the mothers the following day to determine adverse events. Follow-up visits consisting of three urine filtrations and triplicate Kato-Katz thick smears were conducted 3 and 6 weeks post-treatment. The proportion of children having presented early adverse events during the 4-hour period post-treatment was 33% and the proportion of adverse events occurring within 24 hours after treatment was 6.2%. No serious adverse events were recorded. The most frequent symptoms were abdominal pains (31%), bloody diarrhoea (16.2%) and sleepiness (15.3%). Before treatment, 165 children were infected with S. haematobium among whom 87% presented a light infection (1-49 eggs/10 ml of urine) and 13% a heavy infection (?50 eggs/10 ml of urine). The overall cure rate against S. haematobium was 86% and 95% after 3 and 6 weeks post-treatment, respectively. Three and 6 months after treatment, the GM egg reduction rate for S. haematobium was 69% and 71%, respectively. With regard to S. mansoni, 96 infected children, were treated with PZQ. Among them, 39% had moderated to heavy infection intensities (?100 EPG). Observed cure rates were 75% and 50%, respectively, 3 and 6 weeks after treatment. The respective GM egg reduction rates were 67% and 19%.
Fifth, in order to help countries in finding viable strategies that are financially acceptable to sustain schistosomiasis control activities, we conducted a cost-effectiveness study comparing a school-based and a community-based mass drug administration strategy for schistosomiasis and STH control in Niger. In 2006, we undertook a survey in four districts to estimate the economic cost per district, per treatment and per Schistosoma infection averted. The study compared the costs of treatment at start-up and in a subsequent year and identified the allocation of costs by activity, input and organization. The total economic cost of the programme, including programme-specific expenditures, national and local government costs and international technical support and programme co-ordination in four study districts, over a 2-year period, was US\$ 456,718, which translates to an economic cost per treatment of US\$ 0.58. The full economic delivery cost of school-based treatment in 2005/2006 was US\$ 0.76, while a somewhat lower cost was observed for community distribution (US\$ 0.46). If only costs to the programme were included, the respective figures were US\$ 0.47 and US\$ 0.41. In the study district over a 2-year period, the average cost per Schistosoma infection averted was US\$ 0.76 for children with one treatment and the cost was US\$ 6.7 for adults.
Conclusion: Sustainability of schistosomiasis and STH control programmes in sub-Saharan Africa remains a grand challenge. Integration with other existing health interventions, particularly those targeting NTDs and strengthening of health systems is a way to ensure continued distribution of anthelminthic drugs and other interventions. At an average cost per treatment of US\$ 0.58, control could be handled by the countries.
A substantive proportion of preschool-aged children had egg-patent Schistosoma infection, inclusive of co-infection with S. haematobium and S. mansoni. Hence, in highly endemic areas, more attention should be paid on preschool-aged children and women of childbearing age, so that they can benefit from PCT, thus, increasing effective coverage of those infected. PZQ syrup is well tolerated in infants and preschool-aged children. The cure and eggs reduction rates were high against S. haematobium infection, but additional studies are warranted to determine the efficacy against S. mansoni.
In school-aged children, PZQ given in two closely spaced doses is efficacious against S. haematobium. However, low egg reduction rate observed against S. mansoni raises concern about mounting PZQ tolerance. ---------- Zusammenfassung:
Hintergrund: Schistosomiasis ist eine vernachlässigte tropische Krankheit, welche ein bedeutendes Problem für die öffentliche Gesundheit darstellt, vor allem in Afrika, wo aktuell mehr als 95% aller weltweit auftretenden Fälle konzentriert sind. Die gesundheitlichen Auswirkungen der Schistosomiasis sind beträchtlich. Abgesehen von den bekannten Langzeit Komplikationen einer chronischen Infektion (wie Pfortaderhochdruck, Leberversagen, Blasenkrebs und Unfruchtbarkeit) ist Schistosomiasis eine kräftezehrende Erkrankung welche zu Anämie, Mangelernährung, chronischen Unterleibsschmerzen sowie Diarrhö führen kann.
Im Mai 2001 wurde an der ‘‘World Health Assembly“ (WHA) die Resolution Nummer 54.19 ins Leben gerufen. Diese Resolution hält Mitgliederstaaten dazu an regelmässig mindestens 75% und bis 100% aller Kinder im Schulalter, welche dem Risiko einer Schistosomen Infektion ausgesetzt sind, sowie andere Gruppen mit hohem Risiko, regelmässig mit Praziquantel zu behandeln. Desweiteren führte die Weltgesundheitsorganisation (WHO) eine Strategie der „präventiven Chemotherapie“ (PCT) ein, welche sich auf eine regelmässige, integrative Verabreichung von Entwurmungsmitteln stützt. Diesen internationalen Aufrufen für die Bekämpfung der Schistosomiasis und anderer vernachlässigter Tropenkrankheiten folgend, lancierten einige afrikanische Länder, einschliesslich Niger, mit Hilfe von Partnern, PCT-basierte, nationale Kontrollprogramme.
Die Ziele dieser Dissertation in Epidemiologie waren (i) die Morbidität durch Schistosomiasis in Klein- und Vorschulkindern, welche derzeit nicht in die PCT Strategie eingeschlossen sind, zu ermessen; (ii) die Wirksamkeit und Verträglichkeit von Praziquantel bei verschiedenen Behandlungsschemata zu evaluieren, einschliesslich einer detaillierten Kostenanalyse; und (iii) die Kontrolle der Schistosomiasis und anderer vernachlässigter Tropenkrankheiten in Niger zu stärken.
Methoden und wichtigste Ergebnisse: Zuerst wurden die bisherigen Leistungen und verbleibenden Herausforderungen der Schistosomiasis und der vom Boden-übertragenen Wurminfektionen in drei Ländern Westafrikas (nämlich Burkina Faso, Mali und Niger), welche von der Unterstützung der “Schistosomiasis Control Initiative“ (SCI) profitierten, analysiert. In den ersten drei Jahren des Kontrollprogramms wurden annähernd 13.5 Millionen Dosen Praziquantel gegen Schistosomiasis, und Alendazole gegen von Boden-übertragenen Wurminfektionen verabreicht mit einer Deckungsrate zwischen 67% und 94%. Die Praziquantel Behandlungen führten zu einer Reduktion der Prävalenz und Intensität von Schistosomen Infektionen in den Beobachtungskohorten welche zur Überwachung und Bewertung der nationalen Kontrollprogramme etabliert worden waren. Die Schlüsselherausvorderungen welchen diese nationalen Kontrollprogramme derzeit gegenüber stehen, sind das Vermögen, diesen Rückgang der Morbidität welcher bisher erreicht wurde beizubehalten sowie die Sicherung der Nachhaltigkeit.
Zweitens ermassen wir die Morbidität von Schistosomiasis in Klein- und Vorschulkindern, welche zur Zeit nicht in der PCT wie von der WHO empfohlen eingeschlossen sind, einschliesslich der Risikofaktoren einer Infektion in der frühen Kindheit. Wir führten eine Querschnittsstudie in zwei Dörfern in Niger durch: Falmado welches endemisch nur für Schistosoma haematobium ist und Diambala welches ein Brennpunkt sowohl für S. haematobium wie auch S. mansoni ist. Insgesamt wurden 282 Kinder (149 Mädchen, 133 Jungen; durchschnittliches Alter: 2.6 Jahre) und 224 Mütter (durchschnittliches Alter: 30.1 Jahre) untersucht. Für die Diagnose von S. haematobium wurden zwei Urinproben an zwei aufeinanderfolgenden Tagen mit der Standard Filtrationsmethode untersucht, während die Diagnose von S. mansoni auf der Untersuchung einer einzelnen Stuhlprobe mittels zweier Kato-Katz Ausstriche beruhte. Desweiteren wurden vorgetestete Fragebögen, welche demographische Daten, kürzliche Behandlungsgeschichten mit Entwurmungsmitteln, die sanitäre Situation des Haushalts und Wasserversorgung sowie Badepraktiken für die Kinder aufnahmen, mit den Müttern in Diambala durchgeführt. Die Prävalenz von Ei-patenten S. haematobium Infektionen bei jungen Kindern und deren Mütter war 51% und 56% in Falmado, sowie 61% und 72% und Diambala. Die Prävalenz von S. mansoni in Diambala war 44% unter den Kindern und 72% unter den Müttern. Gemischte, Ei-patente Infektionen von S. haematobium und S. mansoni zeigten sich in 29% der Kinder und 37% der Mütter. Die Auswertung der Fragebogenstudie zeigte, dass 70% aller Kinder von ihren Müttern zu Schistosomiasis Übertragungsstellen begleitet wurden, bevor sie ein Jahr alt waren und dass drei-Viertel der Mütter Wasser welches sie direkt aus den Bewässerungskanälen bezogen benutzten um ihre Kinder zu waschen.
Drittens evaluierten wir die Wirksamkeit und Sicherheit zweier eng aufeinanderfolgender Dosen Praziquantel gegen S. haematobium und S. mansoni bei Kindern im Schulalter und charaktisierten die Re-infektionsmuster über einen Zeitraum von einem Jahr. Die Studie wurde in den folgenden fünf Dörfern im Westen Nigers durchgeführt: Falmado, Seberi, Diambala, Namarigoungou und Libore. Parasitologische Untersuchungen bestanden aus drei Urinfiltrationen und drei Kato-Katz Ausstrichen bei jedem Besuch. Zwei 40 mg/kg Praziquantel Dosen wurden in einem Abstand von drei Wochen verabreicht. Folgebesuche wurden 6 Wochen, 6 Monate und 12 Monate nach der ersten Praziquantel Dosis durchgeführt. Nebenwirkungen wurden während vier Stunden nach der Medikamentenverabreichung vom Studienteam, und 24 Stunden danach mittels eines Fragebogens überwacht. Unsere letztendliche Studienkohorte bestand aus 877 Kindern die entweder mit S. haematobium oder S. mansoni oder mit beiden parasitären Wurmarten zugleich infiziert waren und beide Dosen Praziquantel erhalten hatten. Bei der Basisstudie reichte der geometrische Mittelwert (GM) der Infektionsintensität von S. haematobium von 3.6 (Diambala) bis 30.3 Eier pro 10 ml Urin (Falmado). Der GM der Infektionsintensität von S. mansoni reichte von 86.7 (Diambala) bis 151.4 Eier pro Gramm Stuhl (EPG) (Namarigoungou). Nebenwirkungen wurden bei 33% bzw. 1.5% der Kinder nach der ersten bzw. zweiten Dosis Praziquantel berichtet. Wir fanden Heilungsraten zwischen 49% (Falmado) und 98% (Namarigoungou) sowie hohe Ei Reduktionsraten (92-100%) bei S. haematobium-infizierten Kindern drei Wochen nach Verabreichung der zweiten Praziquantel Dosis. Für S. mansoni wurden lediglich mittelmässige Heilungs- und Ei Reduktionsraten gefunden (52-59% in Diambala, 55-60% in Namarigoungou).
Viertens führten wir, um weitere Befunde bezüglich der Verträglichkeit und Wirksamkeit von Praziquantel gegen Schistosomiasis bei Klein- und Vorschulkindern zu erhalten, eine Wirksamkeitsstudie mit einem Praziquantel Sirup (Epiquantel® ) bei Kindern mit einem Alter von bis zu 72 Monaten durch. Die Studie wurde zwischen Mai und August 2010 in drei Dörfern in Niger durchgeführt. Insgesamt wurden 243 Kinder welche mit S. haematobium und/oder S. mansoni infiziert waren, mit einer Dosis von 40 mg/kg des Praziquantel Sirups behandelt, nachdem ihnen eine Mahlzeit aus Hirsebrei verabreicht worden war. Nach der Behandlung wurden die Kinder über 4 Stunden beobachtet und am darauffolgenden Tag ein Fragebogen mit den Müttern durchgeführt um Nebenwirkungen zu ermitteln. Folgeuntersuchungen bestehend aus 3 Urinfiltrationen und 3 Kato-Katz Ausstrichen wurden 3 und 6 Wochen nach der Behandlung durchgeführt. Der Anteil Kinder, der frühe Nebenwirkungen während der ersten 4 Stunden nach Behandlung zeigte, lag bei 33% und der Anteil Nebenwirkungen welche innerhalb von 4-24 Stunden nach der Behandlung auftraten bei 6.1%. Es wurden keine ernsten Nebenwirkungen berichtet. Die am häufigsten auftretenden Symptome waren Unterleibsschmerzen (31%) sowie blutiger Durchfall und Schläfrigkeit (16%). Vor der Behandlung waren 166 Kinder mit S. haematobium infiziert, von welchen 87% eine leichte Infektion (1-49 Eier pro 10 ml Urin) und 13% eine schwere Infektion (?50 Eier pro 10 ml Urin) aufwiesen. Die Heilungsrate für S. haematobium betrug im Gesamten 86% drei Wochen, bzw. 95% sechs Wochen nach Behandlung. Der GM der Ei Reduktionsrate für S. haematobium betrug 71% drei, bzw. 77% sechs Wochen nach Behandlung. Gegen S. mansoni wurden 96 infizierte Kinder mit Praziquantel behandelt. Unter diesen hatten 39% eine mittlere bis schwere Infektion (?100 EPG). Die beobachtete Heilungsrate lag bei 75% drei, bzw. 50% sechs Wochen nach Behandlung. Die entsprechenden GM der Ei Reduktionsraten waren 67% und 19%.
Fünftens, um den Ländern dabei zu helfen durchführbare Strategien dafür zu finden die Schistosomiasis Kontrollstrategien langfristig zu gewährleisten, führten wir eine Kosteneffizienzstudie durch in welcher wir eine schulbasierte mit einer gemeindebasierten Massenbehandlungsstrategie gegen die Schistosomiasis und von Boden-übertragener Wurminfektionen verglichen. Unsere Studie wurde im Jahr 2006 durchgeführt in vier Distrikten von Niger um die wirtschaftlichen Kosten pro Distrikt, pro Behandlung und pro abgewendeter Schistosomen Infektion abzuschätzen. In der Studie wurden die Behandlungskosten beim Start und im darauffolgenden Jahr verglichen und die Kostenverteilung auf die Aktivitäten, den Einsatz und die Organisation identifiziert. Die gesamten wirtschaftlichen Kosten des Programms, einschliesslich programmspezifischer Ausgaben, nationaler und lokaler Regierungskosten und internationaler technischer Unterstützung sowie Programmkoordination von vier Distrikten betrugen 456,718 US\$ über einen Zeitraum von zwei Jahren, was einem Kostenpunkt von 0.58 US\$ pro Behandlung entspricht. Die vollen wirtschaftlichen Kosten für eine schulbasierte Behandlung in Jahr 2005/2006 betrugen 0.76 US\$ während für die gemeindebasierte Behandlung etwas niedrigere Kosten beobachtet wurden (0.46 US\$). Wenn man für die jeweiligen Grafiken ausschliesslich die Kosten des Programms berücksichtigt, handelt es sich um 0.47 US\$ bzw. 0.41US\$. Die durchschnittlichen Kosten pro abgewandter Schistosomen Infektion im Studiengebiet über den Zeitraum von zwei Jahren betrugen 0.76 US\$ für Kinder mit einer Behandlung und 6.7 US\$ für Erwachsene.
Schlussfolgerungen: Die Nachhaltigkeit von Kontrollprogrammen gegen die Schistosomiasis und anderer vernachlässigter Tropenkrankeiten in Subsahara-Afrika bleibt eine gewaltige Herausforderung. Die Eingliederung in andere Gesundheitsinterventionen, vor allem jener welche auf vernachlässigte Tropenkrankheiten und die Stärkung von Gesundheitssystemen abzielen, stellt einen Weg dar, um die kontinuierliche Verteilung von Entwurmungsmedikamenten und anderer Interventionen sicher zu stellen. Wir spekulieren, dass die durchschnittlichen Kosten von 0.58 US\$ pro Behandlung von den Ländern gehandhabt werden können.
Ein bedeutender Anteil Vorschulkinder hatte eine Ei-patente Schistosomen Infektion, inklusive Co-Infektion zwischen S. haematobium und S. mansoni. Daher sollte in hochendemischen Gebieten Vorschulkindern und Frauen im gebährfähigen Alter mehr Aufmerksamkeit geschenkt werden, damit sie von der PCT profitieren und so die effektive Abdeckung der Infizierten erhöht wird. Praziquantel Sirup wird von Klein- und Vorschulkindern gut vertragen. Gute Heilungsraten und hohe Ei Reduktionsraten wurden bei der S. haematobium gefunden, doch weitere Studien sind angebracht um die Wirksamkeit gegen S. mansoni zu bestimmen.
Bei Kindern im Schulalter ist Praziquantel in zwei eng beieinanderliegenden Dosen verabreicht, wirksam gegen S. haematobium. Jedoch erweckt die niedrige Ei
Assessment of Psychosocial Problems and Risky Sexual Behaviours of Ethiopian Youth Migrants in Switzerland
Epidemiology and burden of soil-transmitted helminth infections among school-aged Bulang children in Yunnan province, People's Republic of China
Background: The three most common soil-transmitted helminths are Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Collectively, they infect around 1 billion people and put approximately 5 billion people at risk of infection worldwide. Strongyloides stercoralis is a less common soil-transmitted helminth than the species mentioned above, but still significant from a public health perspective. The global prevalence of S. stercoralis is estimated to be 30-100 million. Populations most affected by these parasitic worms are often impoverished, living on less than US$ 2 per day, and have poor sanitation facilities and hygiene habits. Despite the low prevalence levels of soil-transmitted helminth infections observed on a national level in the People’s Republic of China (P.R. China), hotspots of these infections, particularly within ethnic minority groups residing in rural areas, still exist.
Single-species infections with the common soil-transmitted helminths can cause symptoms ranging from abdominal pain to anaemia, and impaired development of cognitive abilities. For S. stercoralis infections, symptoms such as severe abdominal pain and blood in the stool have been reported. Due to the chronic and subtle nature of most morbidities commonly associated with soil-transmitted helminthiasis, it is difficult to assess the true burden due to these infections.
Objectives: The goal guiding this Ph.D. project was to deepen the understanding of the epidemiology and burden of soil-transmitted helminthiasis among school-aged children from the Bulang ethnic minority group in P.R. China. The following objectives were pursued: (i) to evaluate the feasibility of deploying different tools for the assessment of physical fitness in soil-transmitted helminth-endemic settings; (ii) to monitor changes in physical fitness, strength and anthropometric measurements over a six-month period among treated children and their untreated peers; (iii) to predict and visualize the change in physical fitness of school-aged children due to soil-transmitted helminth infections over a 1-month period across P.R. China; (iv) to assess the efficacy of triple-dose albendazole and study soil-transmitted helminth re-infection patterns after deworming; and (v) to estimate the odds of re-infection with soil-transmitted helminths for different natural nutritional statuses and types of nutritional supplementation.
Methods: For the field studies, parasitological examination of stool samples was performed. The Kato-Katz technique was used to identify the eggs of A. lumbricoides, hookworm, T. trichiura and other helminths, while the Baermann technique was used to identify the larvae of S. stercoralis. In addition, each stool sample was visually inspected for Taenia spp. proglottids. Physical fitness was estimated with the 20-m shuttle run test and physical strength was assessed with the grip strength and standing broad jump tests. Anthropometric measurements, including body height and weight and sum of skinfolds, and haemoglobin level were also recorded. Physical fitness and strength scores, anthropometric measurements, and haemoglobin level were expressed as means, and compared among children of distinct soil-transmitted helminth infection status and intensity. For the prediction and visualization exercise, the change in physical fitness over 1 month across P.R. China was predicted over a smooth surface of soil-transmitted helminth risk. Maps, with lower and upper boundaries of the predicted values as well as population-adjusted estimates, were further created. Finally, for the systematic review, the odds of re-infection with soil-transmitted helminths for different natural nutritional statuses and types of nutritional supplementation were estimated and qualitative content analysis was conducted for all studies included in the review.
Results: In a cross-sectional survey, the maximum aerobic capacity in 1 min of exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.9 ml kg-1 min-1 lower than that of their non-infected counterparts (P=0.01). Until exhaustion, T. trichiura-infected children had completed six 20-m laps less (P<0.01). No significant association between anthropometric indicators and infection with any soil-transmitted helminth species could be established.
In a randomised controlled trial, which investigated the effects of triple-dose albendazole on physical fitness of school-aged children, baseline prevalences of T. trichiura, A. lumbricoides, hookworm, and S. stercoralis were 94.5%, 93.3%, 61.3%, and 3.1% respectively, with more than half harboring triple-species infections. During the course of the trial, rapid re-infection with A. lumbricoides was observed and low cure rate was achieved with T. trichiura infections. Children receiving triple-dose albendazole scored slightly higher values in physical fitness and strength scores, anthropometric measurements, and haemoglobin level than placebo recipients, but the difference lacked statistical significance. The increase in VO2 max estimate from baseline was 1.6 ml kg-1 min-1 (P=0.02) less and the increase in the number of 20-m laps completed from baseline was five 20-m laps (P=0.04) less for T. trichiura-infected children compared to their non-infected peers. In addition, children with low infection intensity of T. trichiura and hookworm had consistently more increase in the VO2 max estimate from baseline than their peers with high infection intensity of all soil-transmitted helminths (range: 1.9-2.1 ml kg-1 min-1; all P <0.05).
In the systematic review, multi-micronutrients seemed to have the clearest effect with regards to lowering re-infection rates and intensity of soil-transmitted helminths, whereas consumption of zinc or vitamin A alone might have a negative impact on these two outcomes measures. With regards to the natural nutrition status of the host, the general trend observed was that individuals with poor nutrition status suffered higher re-infection rates and intensities when compared to their well-nourished peers. Overall, only fifteen studies met our inclusion criteria and majority of them were of low quality.
Conclusions/significance: The negative associations observed between T. trichiura infections and physical fitness among school-aged Bulang children in Yunnan suggests that the current burden estimate of soil-transmitted helminth infections, in particular T. trichiura infections, might be underestimated and there are still subtle and hidden morbidities to be quantified. A paradigm shift is needed to further understand the burden of soil-transmitted helminth infections as the presence of co-infections and co-morbidities add layers of complexity to the task. Finally, the epidemiological findings on soil-transmitted helminthiasis from this thesis highlight that a national soil-transmitted helminth control programme is overdue and urgently needed as P.R. China further develops into a global powerhouse. With many of their rural communities starting to have their hands on the first rung of the development ladder, P.R. China seems to be in a good position to set a leading example on how to control and eliminate soil-transmitted helminthiasis, and possibly other neglected tropical diseases, for developing countries around the world
Systems epidemiology of snail-borne diseases : from methodological to social-ecological considerations in the fight towards elimination
Background: Snail-borne trematode infections, including schistosomiasis and fascioliasis, affect an estimated 250 million and 2.4 million people worldwide, respectively. Health implications range from asymptomatic infections to severe morbidity, developmental and cognitive impairment, thus affecting the current and later life of infected individuals. Nonetheless, snail-borne trematodiasis in general, and fascioliasis in particular, remain among the most neglected of the neglected tropical diseases. The occurrence of these parasitic liver- and blood-fluke infections depend on a myriad of interrelating factors comprising a complex system of disease and health. A key feature pertains to the availability of suitable aquatic snail intermediate hosts from the family of the Lymnaeidae (for schistosomiasis) and Planorbidae (for fascioliasis). The distribution of these intermediate host snails, in turn, depends on ecological and environmental factors of their habitats, whereas these habitats are shaped by humans. The construction of dams, for example, extends the suitable habitats for intermediate host snail species and has been implicated with the spread and intensification of schistosomiasis. Furthermore, socio-economic and cultural factors as well as behaviour largely determine the extent of risky water contact including direct and indirect consumption and thus govern the risk of becoming infected with Schistosoma and Fasciola. Prevailing habits and social believes as well as knowledge and education likewise influence water contact patterns and health seeking behaviour. Individual immunology plays a role in acquiring infections and subsequent development of the disease for individuals exposed to these fluke infections. The nature of the interrelations in snail-borne trematode infections are complex and widespread. In order to eliminate snail-borne trematodiasis, especially schistosomiasis, efforts in the domains from innovation to application need to be increased covering all aspects of the whole system.
Goal and specific objectives: The overarching goal of this PhD thesis was to obtain a systems overview of schistosomiasis and – to some extend – fascioliasis in the northern area of Côte d’Ivoire, placing particular emphasis of disease prevalence, social-ecological systems and methodological considerations. Specific objectives include: (i) to evaluate and improve currently existing tools for the assessment of infection within the communities ranging from household sampling to the validation of two rapid-diagnostic test within the setting; (ii) to elucidate prevailing water contact pattern and underlying reasons thereof alongside other factors leading to an increased risk of acquiring snail-borne trematodiasis for the local communities in northern Côte d’Ivoire; and (iii) to assess the distribution and ecological determinants of aquatic snail species serving as intermediate hosts for schistosomiasis and fascioliasis and relating it to the prevalence of infections within the human communities using these water sources.
Methods: A literature review was performed to identify suitable household sampling methods for situations where sampling frames are not available. Identified and newly proposed sampling methods were simulated over 250 iterations to identify features or the resulting samplings and assessing the amount of oversampling, systematic household exclusion as well as clustering.
For the studies involving fieldwork, a total of forty villages were randomly selected for participation. The study protocols received clearance from the ethics committees of Basel (EKBB, reference no. 64/13) and the national ethics committee in Côte d’Ivoire (reference no. 32-MSLS/CNERdkn). In Chad, research authorization including ethical approval was granted by the
District, regional and local authorities, village chiefs, study participants and parents/guardians of individuals aged below 18 years were informed about the purpose, procedures and potential risks and benefits of the study. Written informed consent was obtained from all participants and the parents/guardians of minors. Parasitological examinations as well as questionnaire surveys, focus group discussions and direct observations were performed within the villages, nearby Peulh settlements and surrounding water bodies. Parasitological examinations included reagent strip testing with Hemastix®, (Bayer Diagnostics; Basingstoke, United Kingdom), urine filtration of 10 ml of urine, double Kato-Katz of a single stool sample, Baerman filtration and the point-of-care circulating cathodic antigen test. Snails and water parameters were collected from water sites indicated by the communities as the ones most frequently accessed by the population.
Results: Our literature review revealed 21 methods for household sampling and/or the creation or update of sampling frames. Some methods describe variations of cluster sampling, some aiming at the creation/obtaining or improving of existing sampling frames and some pertaining to achieve sampling in the absence of a sampling frame. Three methods pertained to sampling with rather strict requirements in surveys. A preliminary computer simulation of several existing and newly proposed spatial methods for household sampling revealed that all sampling methods based on a spatial approach oversampled houses around the starting point. Additionally many also systematically excluded certain households. One newly proposed method which employs the simple to implement use of a pouch of numbered paper lots is an adaption of the method from the extended programme of immunization (EPI). Equally sized and shaped paper lots containing numbers ranging from 1 to 20 are put into the pouch. An additional 21st lot is included, indicating that a new walking direction will have to be chosen randomly by spinning a bottle. This method delivered the best sample in the simulations, whereas several methods developed to improve the original EPI methods actually had worse outcomes compared to the original EPI method. A decision frame for choosing an adequate household sampling method for researchers and other individuals conducting surveys is proposed in the respective chapter.
The prevalence of schistosomiasis in the Tchologo region of northern Côte d’Ivoire was very low; Infections with S. haematobium and S. mansoni infections were found in 2.2% and 1.0%, respectively. No human Fasciola infection was found. With a prevalence of 13%, microhaematuria, as assessed with reagent strips, far surpassed the prevalence of S. haematobium determined with urine filtration in the study region. Our literature review revealed that in many published surveys, microhaematuria-positive test results that were not linked to positive urine filtration results occurred irrespective of the underlying S. haematobium prevalence assessed by urine filtration. These findings indicate either the occurrence of alternative causes for blood in urine in endemic settings or the gross underestimation of the true prevalence of S. haematobium in various settings.
All individuals in our study villages had access to, and were using, safe water sources. Nevertheless, accessing and consuming unsafe water was very common and occurred in most instances during work on the fields or at the side of the road where it was unfeasible to transport needed quantities of drinking water and/or where water from the dams, rivers and small water collections was needed for the work. Additionally we could show that 38% of direct physical contact with unsafe water resulted from the fact that people who otherwise reported to only use safe water sources had to cross open water and thus increase the risk of acquiring schistosomiasis, albeit adequate water supply and sanitation facilities.
Intermediate host snail species were present in the study area, with fascioliasis intermediate host snails from the family of the Lymnaeidae occurring mostly in the northern part of the region, whereas Schistosoma mansoni transmitting Biomphalaria snails occurred mostly in the southern region, while Bulinus (intermediate host of S. haematobium) were ubiquitous. Human and animal presence at the water sites strongly correlated with snail occurrence.
Conclusions: The adoption of a systemic approach for the control and elimination of snail-borne trematodiases can be very helpful, as it allows inclusion and consideration of a myriad of factors, ranging from methodological to social-ecological issues. Furthermore, researchers and intervention programmes could benefit from an even greater collaboration between different scientific fields, including but not limited to epidemiology, parasitology, sociology, anthropology and social psychology. Indeed, understanding the factors which make humans act in a certain desired or undesired way can play a major role in the success of control or elimination efforts. Most notably, the largest potential benefit could arise from working together with social marketers and drawing upon their years of experience in adequately identifying and analysing target populations and designing ways to tailor implement and communicate public health programmes/messages in a way that maximises community interest and incentives to adopt and sustain the programmes
System-level metabolic effects of trematode infections in rodent models
Background: Trematode infections impose a great burden on the developing world by impairing life quality, productivity and life span of an individual. The prerequisite for efficient treatment and control of the diseases is the use of a quick and sensitive diagnostic tool which could replace the multi-diagnostic approach that is still used. The metabolic profiling approach implies the use of spectroscopic tools such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) on potentially interesting biofluids and tissues, and is coupled with multivariate mathematical data modelling. It has been applied to many different field of research, such as biochemistry, medical sciences, drug pathway discovery, non-communicable diseases, nutrition and psychological disorders, and has been established as an efficient method for biomarker recovery and pathway deciphering. There is growing interest in metabolic profiling in systems biology. The first attempt to bring together metabolic profiling with the epidemiology of neglected tropical diseases was in mid-2002, when urine samples were obtained from more than 500 individuals in a rural Western part of Côte d’Ivoire. However, it was impossible to extract any meaningful information with regard to specific parasitic infection. The high degree of metabolic variation of the studied population in terms of age, genetic and nutritional background and the fact that the majority of individuals harboured three or more parasites concurrently might explain this observation.
My thesis outline was put forward once the metabolic profiles of selected parasitic infections in suitable rodent models, namely Schistosoma mansoni and Trypanosoma brucei brucei in the mouse, and Schistosoma japonicum in the hamster, were established as an alternative to directly exploring human populations in order to ascertain if characteristic biomarkers of infection could be found for single host-parasite scenarios. The success of these experimental investigations encouraged further studies, including the extension of metabolic profiling to other host-parasite models, in order to gain insight into specificity of biomarkers and to reveal the diagnostic potential of this metabolic profiling approach.
Goal and objectives: The overarching goal of this Ph.D. project was to deepen our understanding of trematode-induced metabolic changes in selected rodent models, and to critically assess the potential of a metabolic profiling approach applied to biofluids and tissue samples for biomarker recovery that may contain diagnostic and prognostic properties.
The specific objectives were (i) to optimise faecal sample preparation for subsequent 1H NMR spectroscopy, and to assess metabolic variation in faecal samples with regard to species (i.e. human, rat and mouse), gender and age, (ii) to assess longitudinally the biochemical changes
in urine, plasma and faecal water of E. caproni-infected mice, and to compare the diagnostic capacity of different biofluids collected from infected and uninfected control mice, (iii) to gain information about E. caproni-induced changes in selected tissue samples e.g. (liver, kidney, spleen, ileum, jejunum and colon) of infected mice and correlate identified biomarkers with the previously extracted markers in the biofluids, which might reveal infection-related systems level changes (iv) to evaluate the remote and direct impact of three different trematodes (E. caproni, F. hepatica, S. mansoni) on the rodent host neural metabolic composition.
Findings: Comparing the diagnostic templates, all three biofluids showed interesting deviations between uninfected control and E. caproni-infected mice. Urine and plasma were considered as most suitable biofluids due to the large number of potential biomarkers
identified and because faecal water showed high fluctuations in the metabolic concentrations over time and a high degree of variation from one animal to another which was significantly higher than in urine and plasma. More detailed metabonomic investigations were performed
with E. caproni to assess systems impact on the mouse host. Resulting changes in the metabolic profiles of biofluids and tissue samples were correlated with each other, and revealed new insights into the biological pathomechanisms of this trematode, e.g. impact on gut microbial species and a trematode-induced imbalance of the transporter system in the gut. Whereas E. caproni did not induce any biochemical changes in the neural profile, rats infected with F. hepatica, and mice infected with S. mansoni showed strong deviations from uninfected control animals. F. hepatica-induced changes in the rat brain nucleotide metabolism was correlated to certain cytokine levels, e.g. IFN-γ, IL-5 and IL-13, and was consistent with modulation of the immune mechanisms.This finding provides a rationale for deeper analysis into the interaction of parasitic worms with the central nervous system of the host organism
Relating health benefits of water, sanitation, and hygiene services with the context of urban informal settlements: lessons from Côte d'Ivoire and Kenya
This thesis is inscribed in the recent efforts to reconnect urban planning and public health. It focused on the context of sub-Saharan African cities, for they offer invaluable lessons regarding environmental health determinants and potential solutions to address rapidly growing urban areas characterized by a high prevalence of "informal" settlements. A major concern is that living environments in these areas often exacerbate the risk of several diseases. We addressed these health inequities from a spatial perspective, investigating how material deprivations that typically affect informal settlements and shape their built environment relate to the effectiveness of water, sanitation, and hygiene (WASH) services in these vulnerable settings. Diarrhea was the health outcome of interest, as it is directly related to the quality and accessibility of such services. Moreover, it remains among the leading causes of death worldwide, especially in sub-Saharan Africa.
The overarching goal of this study was to understand, in the context of informal settlements in two African countries, how the performance of different WASH facilities (measured by the occurrence of diarrhea and continuity of access to such services) related to the place where they were inserted. Hence, the thesis contextualized WASH facilities by looking beyond the single object, under the hypothesis that their sole availability is not enough to prevent diarrhea in informal settlements, as certain characteristics of their built environments are, per se, risk factors, and affect the accessibility to WASH facilities.
Multi-level analyses were conducted at: (i) a broader geographic scale based on secondary datasets; and (ii) a local geographic scale based on primary datasets. In this way, the study critically confronted observations of large-scale analyses (resulting from low-resolution, aggregated data) to more detailed observations (resulting from high-resolution, primary data collected at the individual level). The study focused on sites in Côte d'Ivoire and Kenya, two countries affected by significant challenges regarding the expansion of WASH services in low-income urban areas and by a high burden of diarrheal diseases.
We obtained secondary data from 9686 households in Côte d'Ivoire, and primary data from 1147 households in Nairobi, and 567 in Abidjan. The results suggest that the accessibility and health benefits of WASH facilities in informal settlements are interrelated with the form and composition of the built environment at different scales, from the single housing conditions to the spatial configurations of the neighborhood. Ultimately, this study provides empirical knowledge suggesting that "unconventional" WASH solutions already implemented in informal settlements might be viable alternatives to expand, in the short term, the coverage of these essential services. Also, the study highlights the need to consider the built environment as a potential risk factor for diarrhea, as well as a key parameter to determine the most suitable WASH facility type. More generally, the findings contribute to advancements toward SDGs 3 (good health and well-being), 6 (clean water and sanitation), and 11 (sustainable cities and communities).CEA
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