Effects of parasitic infections on clinical outcomes, self-rated quality of life and physical fitness in Côte d'Ivoire

Background: Hundreds of millions of people in the developing world are at risk of parasitic diseases, such as malaria and neglected tropical diseases (NTDs). Health implications due to these diseases are manifold. Typical clinical manifestations from infection with Plasmodium spp. include anaemia and splenomegaly associated with erythrocyte death and splenic sequestration, respectively. Intestinal parasitic infections, such as helminth (e.g. soil-transmitted helminthiasis and schistosomiasis) and intestinal protozoa infections (e.g. amoebiasis and giardiasis) are rarely fatal, but cause long-term chronic morbidity. This may include anaemia and other nutritional deficiencies leading to impaired physical growth and cognitive development in children and reduced work capacity in adults. Concurrent infection with several of these parasites – polyparasitism – is the norm rather than the exception in countries like Côte d’Ivoire. To date, most research on parasitic disease-related morbidity, however, focused on single species infections. A deeper understanding of multiple species parasite infections and related morbidity is crucial for disease control and the reduction of the burden due to these (co-)infections. Goal and specific objectives: The overarching goal of this Ph.D. thesis was to deepen our understanding of multiple species parasite infections and its implications for morbidity at local and regional levels in Côte d’Ivoire. The specific objectives pursued can be summarised as follows. First, to elucidate the epidemiology of single and multiple species infections with Plasmodium and intestinal parasites and to investigate associations and interactions between these parasitic infections among all members of entire communities and among children from public schools across Côte d'Ivoire. Second, to identify potential interrelations between parasite species and the implications of these infections on clinical and self-reported morbidity among different age groups. Third, to assess health-related quality of life among school-aged children harbouring parasitic infections and to determine age- and context-specific disability weights. Fourth, to determine clinical status, physical fitness and cognitive functioning in school-aged children and to analyse the relationships with parasitic infections and the effect of repeated deworming on these health status measures. Methods: The field work for this Ph.D. was split into three parts. Between July and September 2011, cross-sectional community-based surveys were conducted in nine settlements situated in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d’Ivoire and in a hamlet of Azaguié town, located in the Agnéby-Tiassa region of south Côte d’Ivoire. Participants of the rural communities were asked to provide single urine, stool and finger-prick blood samples, which were examined for infection with Plasmodium, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa. The Kato-Katz method was employed for the diagnosis of S. mansoni and soil-transmitted helminths, the urine filtration technique for S. haematobium, the formalin-ether concentration for intestinal protozoa, and microscopy of Giemsa-stained thick and blood films and rapid diagnostic testing (RDT) for Plasmodium. All participants additionally underwent clinical examination involving haemoglobin and anthropometric measurements to assess anaemia and nutritional status, palpation to determine liver and spleen enlargement and administration of an anamnestic questionnaire to record self-reported morbidity. Household heads were subjected to questionnaire interviews assessing local knowledge, attitude, practice and beliefs (KAPB) of parasitic diseases and information pertaining to the household’s socioeconomic status. From November 2011 to February 2012 a national cross-sectional study was implemented in 94 schools across Côte d’Ivoire. In each school, approximately 60 children were subjected to parasitological examination for Plasmodium, intestinal helminth (i.e. S. mansoni and soil-transmitted helminths) and S. haematobium infection. The same diagnostic approaches mentioned before were used, with the exception of S. haematobium, where reagent strips were applied to detect microhaematuria as a proxy for infection. Similar to the community-based surveys clinical examination for assessment of anaemia, nutritional status, splenomegaly and hepatomegaly was conducted. Children responded to a questionnaire on household asset ownership, self-reported morbidity and health-related quality of life (HrQoL). A 5-month prospective intervention study, involving two rounds of deworming at month 0 and 2 targetting schistosomiasis and soil-transmitted helminthiasis, was implemented in a school in Niablé in the eastern part of Côte d’Ivoire. Infections with Plasmodium, Schistosoma, soil-transmitted helminths and intestinal protozoa were determined using the same methods as in the community-based surveys. Children’s clinical status, physical fitness and cognitive performance were determined at baseline (December 2012) and in a 5-month follow-up (May 2013). Results: The rate of polyparasitism was high and peaked in school-aged children. Young children were mainly affected by Plasmodium infection, whilst helminth infections were more common among school-aged children and young adults. Intestinal parasitic infections were significantly associated with poor hygiene behaviour and practice of open defecation besides several sociodemographic determinants. Clinical morbidity mainly affected children and the national cross-sectional school-based survey revealed that every third child was anaemic or malnourished. Plasmodium infection showed strong associations with clinical manifestations, i.e. anaemia, splenomegaly and fever. Helminth infections were associated with self-reported morbidity pertaining to gastro-intestinal symptoms. Of note, Plasmodium and helminth infections showed significant interactions on clinical manifestations, i.e. anaemia and pallor indicating a protective effect in co-infected individuals. The questionnaire survey on HrQoL revealed a disability weight of 0.01 for anaemia in school-aged children, whilst no difference in HrQoL measures could be identified between Plasmodium and helminth-infected and non-infected children. Health status rating further depended on socioeconomic status with generally lower HrQoL among the poorest. Plasmodium-S. mansoni co-infection was related with better physical fitness, whilst haematological and nutritional deficiencies negatively impacted on children’s physical performance. Repeated deworming showed only limited benefits on clinical status, physical fitness and cognitive functioning among school-aged children in a high-transmission malaria setting. Conclusions: Parasitic diseases remain of major public health relevance in Côte d’Ivoire and their continued transmission is governed by social-ecological systems and behavioural determinants. Our findings call for concerted efforts of established disease control programmes and implementation of integrated approaches to enhance the impact on prevalence and disease-related morbidity. The most urgent actions to be taken include the universal coverage with long-lasting insecticidal nets (LLINs) for malaria prevention, improved access to effective treatment, safe water and improved sanitation and awareness raising through setting-specific health education programmes among the affected populations. The studies conducted in the frame of this Ph.D. programme provide an extensive evidence-base determining the extent and characterising health implications due to multiple species parasite infections with an emphasis on malaria, schistosomiasis and soil-transmitted helminthiasis at local and national level. Hence, the findings reported here contribute to the planning of targeted integrative control strategies