Prevalence and clinical relevance of helminth and tuberculosis co-infecion in children under five years of age in Tanzania

Background: About 1.5 billion people are infected with helminth infection. The World Health Organization (WHO) estimates one third of the world population to have latent tuberculosis infection (LTBI) following exposure to an individual with smear-positive pulmonary tuberculosis (TB). Geographical distribution of these diseases and others such as human immunodeficiency virus (HIV) infection overlaps significantly in settings with inadequate sanitation, overcrowding and low socioeconomic status. Children less than five years of age (under-five) experience the highest burden of infectious disease that significantly contributes to their morbidity and mortality. Helminthiases and tuberculosis (TB) are among diseases affecting this population. Once inside the host, helminth parasites impair immune response against other infectious agents such as Mycobacterium tuberculosis. Helminth also negatively impact nutritional status. They compete for nutrients with their host or cause malabsorption. Consequently, the host will experience loss of appetite, reduction of nutritional intake and nutritional deficiency due to increase in the body demand for micronutrients. However, sometimes micronutrient deficiency occurs in developing countries due to marginal diets.
To tackle helminthiases, Tanzania adopted the WHO initiative to integrate preventive chemotherapy into its neglected tropical diseases control program, which also covers helminthiasis since 2009. The WHO also recommends Isoniazid Preventive Therapy (IPT) in children under-five to prevent progression of TB infection to active TB disease following exposure. To date, there are no universal guidelines for preventive chemotherapy for various helminth infections in children under-five; the focus is school-aged children and adults.
Objectives: The overall goal of this PhD thesis was to assess the interplay of helminth and tuberculosis co-infection and its impact on clinical outcomes, nutritional status, growth and cognitive development among children under-five with and without documented exposure to infectious smear-positive adult pulmonary TB case in Temeke District, Dar es Salaam, Tanzania. 
The specific objectives of the thesis were; First, to determine the prevalence and intensity of helminth infections in children under-five with and without documented TB exposure in their households, and identify risk factors related to helminth infection; Second, to assess the prevalence of latent TB infection and determine its associated factors among children under-five comparing children with and without known TB exposure in their households (measured by Interferon gamma release assays (IGRAs) using QuantiFERON-TB Gold (QFT)). Last, to assess the association of helminth and M. tuberculosis infection and their impact on growth development (measured by WHO Z-scores), micronutrients status and cognitive function among children under-five exposed and unexposed to individuals with smear-positive pulmonary TB.
Methods: The field work for this PhD study was carried out in Temeke District, in Dar es Salaam Tanzania between October 2015 and September 2016. We combined cross-sectional and longitudinal study designs to meet our objectives. We prospectively enrolled children aged 6-59 months from households with at least an adult with smear-positive pulmonary TB, controls were recruited from households without a known TB case. We used a cross-sectional design to assess the prevalence of helminth infection and its risk factors (Objective 1). A longitudinal study design was used to evaluate the prevalence of LTBI and its associated factors after six months of follow-up comparing children with and without known TB exposure (Objective 2). To meet our third objective, we used a longitudinal study design to assess the association of helminth and M. tuberculosis coinfection and their impact on child growth development, micronutrients status and cognitive function. We enrolled 310 children aged 6-59 months and collected sociodemographic, socioeconomic and clinical data. We collected blood to screen for malaria, HIV, TB and analyze for micronutrients and inflammatory markers; stool and urine to screen for helminths and induced sputum samples to screen TB.
Results: The prevalence of helminth infection, particularly Schistosoma mansoni, was high. This high prevalence was not associated with commonly reported risk factors such as age, sex and socioeconomic
status. We report high prevalence of anemia among our study population. Overall, eight in twelve children were found to be anemic. The prevalence of anemia was higher among helminth infected children than their peers; nine out of twelve children with helminth infection were anemic.
TB screening showed equal proportion of LTBI among under-fives with and without documented exposure to infectious TB case. A small proportion of children developed active TB disease in the six month of study observation. Uptake of IPT has not reached the WHO target of 90%. About 8 in eleven children eligible for preventive therapy were reported to have been started on medication.
We found vitamin A deficiency to be prevalent; four out of twelve children were deficient. The prevalence of anemia was four times that of serum ferritin deficiency. There was no increase in serum ferritin and soluble transferrin receptor levels at the end of six-month study observation. We observed improvement of cognitive function that we could associate with better nutrition and deworming.
Conclusions: Tanzania was able to reach the millennium development goal of reducing child mortality attributing disease preventive interventions and improved social economic status. Yet the prevalence of infections that significantly contribute to under-five morbidity and mortality remains high especially in urban settings where there is better access to health services. Our findings call for further action to develop integrated guidelines to intervene the high prevalence of S. mansoni infection, latent TB infection due to non-household transmission, micronutrient deficiency and reduced cognitive function in under-fives. It is likely that, interventions such as micronutrient supplementation and deworming reduce helminth burden and anemia prevalence consequently improving children’s development and cognition. In order to avoid lifelong consequences, interventions should aim at the first 1,000 days of life for optimal outcome.