PREVALENCE AND SEVERITY OF HYPOGLYCAEMIA AND LACTIC ACIDOSIS IN CHILDREN DIAGNOSED WITH PLASMODIUM FALCIPARUM MALARIA

ABSTRACT

The prevalence and severity of hypoglycaemia and lactic acidosis in Nigerian children diagnosed with Plasmodium falciparum malaria were determined in 100 outpatient children aged 3-144 months (12 years). The children were grouped into 2 categories: 3-59 month old and 60-144 month old. The results obtained indicated that out of the 100 children recruited into this study, seventy-five (75%) were infected while twenty-five (25%) were uninfected with Plasmodium falciparum malaria. On the basis of age group, higher incidence of malaria was recorded in children under 5 years of age with prevalence rate of 85.3%, while those above 5 years had low prevalence rate of 14.7%. The mean blood glucose concentration of malaria-infected children below 5 years (3.80 ± 0.73 mmol/l) was lower than  that  of  malaria-infected  children  above  5  years  (4.21  ±  1.34  mmol/l);  however,  the  difference  was  not significant (p>0.05). Comparatively, the mean glucose concentrations of the corresponding uninfected subjects were4.10 ± 0.87 and 4.26 ± 0.51 mmol/l respectively. The mean blood lactate concentration of children below 5 years of age (2.59 ± 1.63 mmol/l ) was significantly (p<0.05) higher than those above 5 years (2.30 ± 1.75 mmol/l). The mean values  for both  groups were also  above  the  normal  range  of 1.0 –  2.0 mmol/l while  the  mean  haemoglobin concentration of malaria-infected children below 5 years (16.11 ± 2.24 g/dl) was slightly lower than that of malaria-infected children above 5 years (16.36 ± 2.64g/dl) though not significant (p> 0.05). The prevalence rates of 14.7% were recorded for both hypoglycaemia and lactic acidosis in malaria-infected subjects while 16.0% was recorded for anaemia. There was no significant correlation between blood lactate concentration and blood glucose concentration (r= 0.032, p=0.751) but there was significant positive correlation between haemoglobin level and glucose concentration (r=0.401, p=0.0001). The results suggest that the risk of hypoglycaemia, lactic acidosis and anaemia is higher in younger children, particularly among those below five years of age and also confirmed the knowledge that malaria is a major cause of hospital visits by children.

CHAPTER ONE

INTRODUCTION

Plasmodium falciparum is the most common cause of severe and life-threatening malaria, which causes over

2 million deaths every year (Bruneel et al., 2003; Njuguna and Newton, 2004). In Africa, a vast majority of these deaths occur in children under five years of age (WHO, 2012). Lactic acidosis complicates 35% of severe childhood malaria (Krishna et al., 1994) and hypoglycaemia is present in 20% of children with cerebral malaria (Newton and Krishna, 1998). Both acidosis and hypoglycaemia commonly coexist but each is considered separately as a cause of fatality in children and adults due to severe complicated malaria. Hypoglycaemia is known to be an independent risk factor for death in both severe malaria (Gray et al., 1985; Molyneux et al., 1989) and other severe childhood infections in the tropics (Kawo et al., 1990). Despite its importance, its pathogenesis is not well understood (English et al., 1998). Hypoglycaemia is associated with a poor prognosis in severe malaria (krishna et al, 1994).

In African children with malaria, impairment in hepatic gluconeogenesis in the presence of adequate levels of precursors (glycerol) has been considered the most likely mechanism (White et al., 1987). Irreversible coma may quickly develop if the condition is not effectively treated. Hyperlactataemia is often associated with a poor outcome in severe malaria in African children (Krishna et al, 1994). The pathophysiology of metabolic acidosis is complex. The direct contribution of P. falciparum to the final lactate concentration, through anaerobic glycolysis in the parasite itself, is likely to be small (Vander et al., 1990). More significantly, an inadequate supply of oxygen to tissues may follow from severe anaemia and provoke a metabolic shift within host cells to anaerobic glucose metabolism and increased lactic acid production. In addition, the flow of blood through the microcirculation may be impeded by adherence of infected erythrocytes to the endothelium of post-capillary venules and/or increased rigidity of uninfected cells (Dondrop et al., 1997). Lactate may not in itself be sufficient to cause acidaemia but the inhibition of oxidative metabolism in the context of an ongoing inflammatory response will cause protons (H+) to accumulate and eventually lead to metabolic acidosis (English et al.,1997). These pathophysiological pathways suggest that the syndrome of lactic acidosis may be associated with the total parasite burden during acute infection.

Acute malaria is estimated to cause 225 million cases of ill health per year, resulting in over one million deaths per year, most of which occur in sub-Saharan Africa (World Malaria Report, 2010; Murray et al., 2012). Malaria is particularly virulent among children, constituting one of the principal causes of child morbidity as well as mortality in

sub-Saharan Africa (WHO, 2000). Exposure to the malaria parasite not only results in bouts of high fevers among children, but also increases the risk of malnutrition and anaemia among children under five (Ehrhardt et al., 2006).

1.1 Malaria

Malaria is world’s most widespread infection. According to the World Malaria Report 2011, malaria is prevalent in 106 countries of the tropical and semitropical world, with 35 countries in central Africa bearing the highest burden of cases and deaths (World Malaria Report, 2011). Compared to a century earlier, the area of malaria risk has reduced from 53% to 27% of the Earth’s land surface and the number of countries exposed to some level of malaria risk has fallen from 140 to 106 (Hay et al., 2004; Uk Aid, 2010; World Malaria Report, 2011). In 2007, 2.37 billion people were estimated as being at risk of Plasmodium falciparum malaria worldwide, with 26% located in the World Health Organization Regional Office for Africa (WHO/AFRO) region compared to 62% in the combined South- East Asia and Western Pacific Regional Offices (SEARO/WPRO) regions (Uk Aid, 2010). Of this total population at risk, about 42% or almost 1 billion people lived under extremely low malaria risk (Uk Aid, 2010).

Of the five Plasmodia species that infect human beings (P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi), P. falciparum and P. vivax cause the significant majority of malaria infections. P. falciparum, which causes most of the severe cases and deaths, is generally found in tropical regions, such as sub-Saharan Africa and Southeast Asia, as well as in the Western Pacific and in countries sharing the Amazon rainforest. P. vivax is common in most of Asia (especially Southeast Asia) and the Eastern Mediterranean, and in most endemic countries of the Americas.

Estimates of the annual incidence of malaria vary widely. According to the estimates of The World Malaria Report, 2011, there were 216 million episodes of malaria in 2010, of which approximately 81%, or 174 million cases, were in the African Region (World Malaria Report, 2011), about 91% being due to P. falciparum (World Malaria Report, 2011). But the actual number of cases may be much more and the number of confirmed cases reported by national malaria control programmes was only 11% of the estimated number of cases (World Malaria Report, 2011). Hay et al have estimated the number of clinical cases of P.falciparum malaria in 2007 at 451 million (95% credible interval 349-552) (Hay et al., 2010; Uk Aid, 2010). According to the estimates of The World Malaria Report, 2011, the vast majority of cases (81%) were in the African Region followed by the South-East Asia (13%) and Eastern Mediterranean Regions (5%) (World Malaria Report, 2011). Nineteen countries in Africa – Rwanda, Angola, Zambia, Guinea, Chad, Mali, Malawi, Cameroon, Niger, Burkina Faso, Côte d’Ivoire, Ghana, Mozambique, Uganda, Kenya, United Republic of Tanzania, Ethiopia, Democratic Republic of the Congo (DRC) and Nigeria – accounted for 90% of

all WHO estimated cases in 2006 (Uk Aid, 2010). Hay et al reported that more than half of all estimated P. falciparum

clinical cases occurred in Nigeria, the DRC, Myanmar (Burma) and India (Uk Aid, 2010; Hay et al., 2010).

1.1.1   World Malaria Report

Malaria is a preventable and treatable mosquito-borne disease, whose main victims are children under five years  of  age  in  Africa.  The  World  Malaria  Report  2012  summarizes  data  received  from  104  malaria-endemic countries and territories for 2011. Ninety-nine of these countries had on-going malaria transmission.

According to the World Malaria Report, 2011, there were 655,000 malaria deaths worldwide in 2010, compared to 781,000 in 2009 (WHO, 2000; World Malaria Report, 2011). It has been estimated that 91% of deaths in 2010 were in the African Region, followed by the South-East Asia (6%) and Eastern Mediterranean Regions (3%) (World Malaria Report, 2011). About 86% of deaths globally were in children under 5 years of age (World Malaria Report,

2011). Of the 35 countries that accounted globally for approximately 98% of malaria deaths, 30 were located in sub- Saharan Africa, with four countries (Nigeria, Democratic Republic of the Congo, Uganda and Ethiopia) alone accounting for approximately 50% of deaths on the continent as shown in Fig. 1 (World Malaria Report, 2011). However, a recent systematic analysis by Murray et al has estimated that the global malaria deaths increased from 995,000 in 1980 to a peak of 1,817,000 in 2004, decreasing to 1,238,000 (929,000 — 1,685,000) in 2010 (almost double  of the  WHO estimate  for the  same  year)  (Murray  et al., 2012).  This  study  estimated  more  deaths  in individuals aged 5 years or older than has been estimated in previous studies: 435,000 (307,000 — 658,000) deaths in Africa and 89,000 (33,000 — 177,000) deaths outside of Africa in 2010 (Murray et al., 2012).

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