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ASSESSMENT OF THE ROLE OF MALARIA IN THE AETIOLOGY

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CHAPTER ONE

INTRODUCTION AND LITERATURE REVIEW

1.1   INTRODUCTION

1.1.1  Background History of Malaria

The term malaria originated from Italian: meaning bad air and the disease was called ague or mesh fever due to its association with swamps in humid regions of the world (Cheesbrough, 1999). It is an ancient disease that has plagued humans throughout history (Joy et al., 2003).  It is a term used for acute or chronic infection caused in man or other vertebrates such as mice and donkeys. Malaria remains one of the most pressing health problems in the world with an estimated 300-500 million cases annually of which 90% occurs in Africa (Tarimo et al.,1998). It is the most important infection of great global public health concern and by far the world’s most important tropical parasitic disease that kills more people than any other communicable disease except tuberculosis(Yah et al., 2005). According to WHO (2000) about 500 million people are affected by malaria at any time and approximately 2 million of them mostly children die each year (Raven and Johnson, 2002; Onyesome and Onyemakonor, 2011).

The global malaria situation continues to show no real improvement. Downward trends in the number of reported cases are maintained in some countries but are counter balanced by increasing trends in others.  According to WHO (1987), there has been very little change in the geographical distribution of malarious areas but within countries, areas of rural economic exploitation have become foci for intense malaria transmission. The malaria situation in sub-Saharan Africa is grim and the disease constitutes a leading cause of poverty in the region (Wenceslaus, 2000). This is because African region has the greatest number of people exposed to stable malaria transmission and the greatest burden of malaria morbidity and mortality in the world (WHO, 1996; Snow et al., 1999). The problems associated with malaria treatment in Africa and drug resistance also increase the rates of severe illness and death substantially (Peter et al., 2000).

Although accurate figures are difficult to come by, it is estimated that in Africa alone malaria is responsible for one million death of infants and young children each year (Angyo et al., 1996). With regards to morbidity, people in areas of high endemicity usually go through several attacks every year. Each attack may last about 5 to 15 days often incapacitating the victim. In highly endemic areas, most cases of severe malaria occur among children aged six months and five years with the highest mortality in those between one and three years of age.  Another risk group in endemic areas are pregnant women who become susceptible to severe infection due to diminished cellular and humoral immunity during pregnancy (Anorlu et al.,2001; Okwa, 2003; Adefioye et al., 2007; Uneke, 2008). This is because pregnancy is usually accompanied by physiological and immunological changes that modify both resistance to infection and the pathogenesis of the disease. 

The four species of the parasite that infect man are Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Plasmodium falciparum and P. vivax are the most common in the tropics but mixed infection with two or more of the Plasmodium species is common. Blood stage cycle of Plasmodium falciparum is responsible for most cases of malaria and for the most severe, often fatal forms of the disease. It has varied modes of presentation with occasional life threatening complications. It is said to be complicated when any one or more of the clinical features such as cerebral malaria, jaundice, renal failure, pulmonary oedema, hypoglycemia, circulatory collapse, spontaneous bleeding, repeated generalized convulsion and acidosis are manifested (Bag et al.,1994). Severe falciparum malaria remains an important cause of mortality in the tropical world with an annual mortality of 1-2.7 million people and a mortality rate as high as 15-30%, despite effective anti-malarial treatment (WHO, 1990; 1993 and 2013). It is also found to be deeply entrenched in tropical Africa and highly endemic in sub-Saharan Africa.

Plasmodium vivax is the commonest species in South America and Asia while P. malariae and P. ovale typically cause a relatively benign infections and rarely occur in these areas. Malaria infection may be acquired wherever there are human hosts carrying the parasites and a sufficiency of suitable Anopheles mosquitoes together with conditions of temperature and humidity which favour the development of the parasite in the mosquitoes. Plasmodium has strategies for interacting with human immune system in the following ways.

Antigenic variation in malaria parasiteA defined splenic dependent regulation of parasite genes in coding structural proteins and adhesive molecules on the erythrocyte surfaces that are involved in their adherence to the endothelium.Low immunogenicity of conserved parasite peptides that are targets of antibodies able to interfere with parasite survival.

Malaria affects almost all organ systems (e.g lungs, liver, spleen, brain and kidney). Clinically, significant renal involvement is associated with infections by Plasmodium falciparum and Plasmodium malariae. Cases of malaria associated renal impairment have been reported from different parts of the malaria endemic countries (Mishra et al.;2003, Sharma et al.; 2004; Ogbadoyi and Gabi, 2007). Such impairments most of the time lead to nephrotic syndrome or nephrosis. Nephrotic syndrome is a group of symptoms caused by the excretion of large amount of protein in the urine (>3g of protein /day) due to kidney impairment or glomerula disorder. It occurs at any age and is characterized by such symptoms as high levels of protein and high levels of cholesterol and lipids in the blood, retention of fluid in the tissues (oedema) and appearance of fat in the urine. Its causes may include the disease that cause glomerulonephritis (kidney inflammation), systemic diseases such as diabetes or disease of unknown origin which causes a form of the syndrome known as idiopathic nephrotic syndrome. Nephrotic syndrome progresses to kidney failure over several years. Such chronic infection can also be associated with an increased incidence of vascular disease due to the high fat levels in the blood. The most common renal lesion of malaria is acute renal failure due to acute tubular necrosis. This is seen in about1% of all P. falciparum infected patients and its incidence rises to as high as 60% in patients having heavy parasitaemia (Rajapurka, 1994). The severity of malaria-induced renal impairment in a particular area is largely a function of the disease prevalence and other aetiological factors prevailing in the area. Infection with P. falciparum produces only acute manifestations which range from asymptomatic urinary abnormalities and mild electrolyte disturbances. The contribution of falciparum malaria to the total admission with acute renal failure depends to a large extent on the prevalence of disease, referral pattern and other aetiological factors present in the area under study (Barsoum, 2000).

The two major renal syndromes associated with malaria are chronic and progressive glomerulopathy that are usually associated with complicated quartian malaria associated with falciparum malaria. Chronic malarial nephropathy affects children usually 4 to 8 years old and presents as a steroid- resistant nephritic syndrome. Its characteristic histopathologic lesion is mesangio-cappillary glumerulonephritis with subendothelial immune complex deposites containing IgG, C3 and malarial antigens. This proceeds to renal failure even after successful eradication of the infection. It is much more frequent in non-immune population where 25 to 30% cases are reported.  

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