TOLL-LIKE RECEPTOR 2 TLR 2 LEVEL SHOWING GENDER-INDEPENDENT EFFECTS IN MALARIA PEDIATRIC INFECTIONS

ABSTRACT

     This research project was carried out to determine the effect of Toll-like Receptor 2 (TLR2) levels in malaria infection of pediatrics. Using Enzyme-linked immunosorbent assay technique (ELISA), samples consisting of 18 malaria pediatric patients were used for this research. TLR2 levels were significantly higher in male pediatric patients than the female pediatric patients. Results shows that the mean serum concentration of TLR2 level in male pediatric patients was 894.34gn/ml and the standard deviation was 1175.40ng/ml while mean serum concentration of TLR2 levels in female pediatric patients was 404.5ng/ml and the standard deviation was 586.60ng/ml. Also the mean serum concentration of TLR2 for the total infected pediatric patients was 704.63ng/ml and the Standard deviation was 1017.25ng/ml.  Statistics shows that there was significant difference in the concentration between the age groups. Also, student t-test shows that there was no significant difference in TLR2 levels between malaria infected male and female pediatric patient as well as the total infected pediatric patient (p = 0.05). Therefore, TLR2 levels have no gender association with pediatric malaria infection.

CHAPTER ONE
1.1 INTRODUCTION
Malaria is a major cause of illness and death especially among children under 5 years and pregnant women. It is estimated that more than one million children living in Africa especially in remote areas with poor access to health services die annually from direct and indirect effects of malaria. Fatally affected children often die within less than 72hrs after developing the symptoms. In Nigeria, malaria consistently ranks among the five most common causes of death in children (WHO, 2010). Children under 5 years of age are one of most vulnerable groups affected by malaria, accounting for a large portion of the estimated 445,000 malaria deaths around the world (WHO, 2010). In high transmission areas, partial immunity to the disease is acquired during childhood. In such settings, the majority of malarial disease and particularly severe disease with rapid progression to death occurs in young children without acquired immunity. Severe anaemia, hypoglycemia and cerebral malaria are features of severe malaria more commonly seen in children than in adults. The vast majority of malaria-related deaths are due to infection with Plasmodium falciparum and Plasmodium vivax causes severe febrile illness but is rarely fatal. Following repeated exposure to infection, people living in malaria endemic areas gradually acquire mechanisms to limit the inflammatory response to the parasite that causes the acute febrile symptoms (clinical immunity) as well as mechanisms to kill parasites or inhibit parasite replication (antiparasite immunity). Children, who have yet to develop protective immune mechanisms are thus at greater risk of clinical malaria, severe disease and death than adults (Sam-Agudu et al., 2010). However, researchers reveal that cerebral malaria is a common manifestation of severe malaria that typically occurs in children who have already acquired a significant degree of antimalarial immunity as evidenced by lower mean parasite densities and resistance to severe anaemia (Sam-Agudu et al., 2010).
However, no reported study has been carried out in the Nigerian population to determine the association of Toll-like Receptor2 (TLR2) level with malaria infection. The Toll-Like Receptors (TLRs) are a family of pathogen recognition receptors that recognize Pathogen-Associated Molecular Patterns (PAMPs). This initial detection of pathogens plays a central role in the activation of the innate immune system and the generation of an appropriate immune response to infection. To date, ten TLRs in humans (TLR1-10) and twelve TLRs in mice (TLR1-9, 11-13) have been identified, where each TLR binds to specific ligands (Janeway and Medzhitov, 2002). TLR1-2, TLR4-6 and TLR10 are found on the cell surface and interact with extracellular ligands whereas TLR3 and TLR7-9 are found in endosomes and interact with intracellular ligands. Although TLR-induced responses to malaria have been described, the TLR-mediated contribution to malaria-associated pathogenesis has been difficult to determine and is a continued area of intense research.

1.2 OBJECTIVES OF THE STUDY
The overall aim of this work is to determine the effect of toll-like receptor 2 levels in malaria infection of pediatrics.
The objectives of this project study are to:
test the subjects to confirm malaria infection
measure the level of Immune mediator protein (TLR2), to determine its association with malaria infection in children.

1.3 RATIONALE/ JUSTIFICATION FOR STUDY
Toll-like receptors (TLRs) are key pattern-recognition receptors of the innate immune system, hence its effects in malaria infection is largely unknown. No study has been reported on the effect of Toll-like receptor 2 (TLR2) level in malaria infection of children in Nigeria.
This research is to access the effect of the Toll-like receptor 2 (TLR2) level in malaria infection of pediatrics in the sample population from Calabar, Cross River State. This immune protein (TLR2) would be identified by enzyme-linked immunosorbent Assay (ELISA) kit which is specifically designed to identify this protein and its level would be estimated by colorimetry / ELISA plate reader.
The measurement of the level of this immune response protein would be carried out using plasma from the blood samples of patients.