GENETIC VARIATIONS IN SCHISTOSOMA HAEMATOBIUM, DISEASE SEVERITY AND DRUG RESISTANCE/RE-INFECTION IN THE PRU DISTRICT OF GHANA

ABSTRACT Background: Schistosomiasis is a neglected tropical disease caused by the genus Schistosoma. It has a worldwide distribution with more cases occurring in Africa. Urogenital schistosomiasis caused by Schistosoma haematobium is prevalent in several places within Ghana, particularly in areas where there are large water bodies. Persistent infection of S. haematobium leads to cytological changes of urothelial cells which in turn could lead to the development of bladder cancer. The persistence of this infection can be as a result of multiple re-infection or therapeutic failure to the drug of choice, Praziquantel (PZQ), and this has been reported in places like Egypt and Mali, but not much have been reported about the trends in Ghana. Genetic variation in schistosomes might influence disease severity and development of drug resistance; therefore, there is the need to investigate the situation in the Pru district of Ghana. General Aim: The aim of this study was to investigate possible genetic variations in S. haematobium, assess disease severity and drug resistance/re-infection in the Pru district of Ghana which had over 50% prevalence in the year 2010, as reported by the world health organization. Methodology: This was a longitudinal study involving baseline and follow-up sampling among basic school children living in schistosomiasis endemic communities, within the Pru district of the Brong Ahafo Region of Ghana. Urine samples were collected at baseline with consent/assent from the parents or guardians/children, and examined for S. haematobium ova by microscopy. Egg count and viability test (modified hatchability technique and vital stains) were used for assessment of resistance/re-infection, while urine cytology was used for disease severity. Children with positive S. haematobium eggs were treated with a single oral dose (40mg/kg) of PZQ after which egg count, viability test as well as cytological analyses were repeated weekly for comparison with baseline. Disease severity was assessed by identification of cytological changes (squamous cell metaplasia, inflammation and hyperkeratosis) in both baseline and post treatment urine samples. Molecular analysis involved PCR amplifications and visualization (on agarose gel) of chromosomal gene (ITS2), for confirmation of S. haematobium and the detection of possible genetic variants in the mitochondrial genes (NAD1 and COX1). Results: A low prevalence (6.5%) of S. haematobium infection was observed in this study with a re-infection rate of 19.2%, but no drug resistance was detected after complementing results from egg count and viability tests. Cytological abnormalities such as squamous cell metaplasia, hyperkeratosis and inflammation were found with most of the S. haematobium samples, which reduced with the weekly follow up examinations. Disease severity recorded in the current study was 26.7%. All the cases identified by microscopy got amplified with S. haematobium species specific DNA marker (ITS2), however, some were found to vary in their ability to express the mitochondrial genes; NAD1, and or COX1. Conclusion: Severe form of S. haematobium disease has been observed in the Pru District of Ghana with re-infection recorded among the study participants as well as variants of the mitochondrial genes, but no records of PZQ resistance. This finding will therefore add to knowledge on genetic variations in S. haematobium, disease severity and drug resistance or reinfection in Ghana. Similar studies at other locations in Ghana are therefore recommended.