Clinical predictors of severe malarial anaemia in a holoendemic Plasmodium falciparum transmission area

Abstract

SUMMARYSevere malarial anaemia (SMA) is a common complication of Plasmodium falciparum infections, resulting in mortality rates that may exceed 30% in paediatric populations residing in holoendemic transmission areas. One strategy for reducing the morbidity and mortality associated with SMA is to identify clinical predictors that can be readily recognized by caregivers for prompt therapeutic interventions. To determine clinical predictors of SMA, Kenyan children (3-36 mos., n=671) presenting with acute illness at a rural hospital in Siaya District were recruited. Demographic, clinical, laboratory and haematological parameters were measured upon enrolment. Since HIV-1 and bacteraemia promote reduced haemoglobin (Hb) concentrations, children with these infections were excluded from the analyses. Children with P. falciparum mono-infections (n=355) were stratified into three groups: uncomplicated malaria (Hb≥11.0 g/dL); non-SMA (6.0≤Hb<10.9), and SMA (Hb<6.0 g/dL). SMA was characterized by a younger age, monocytosis, thrombocytopaenia, reticulocytosis, reduced erythropoiesis, elevated pigment-containing monocytes (PCM), respiratory distress, conjunctival and palmar pallor, splenomegaly, signs of malnutrition, and protracted fever and emesis. Logistic regression analysis demonstrated that age, reticulocyte count, presence of PCM and conjunctival and palmar pallor were significant predictors of SMA. Recognition of these clinical signs in children residing in resource-poor settings may help guide the identification and management of SMA.

Determinants of mortality in Nigerian children with severe anaemia

“…Features such as tachypnoea, tachycardia, hepatomegaly, gallop rhythm, lethargy and grunting, which are characteristic of heart failure in anaemic children, are thought to arise from lactic acidosis. 4,13 Consistent with previous studies, 12,13 high-density parasitaemia was neither significantly related nor a predictor of death from severe anaemia. A study on the clinical predictors of severe malaria anaemia in a holo-endemic P. falciparum transmission area found that children with uncomplicated malaria had more peripheral parasitaemia, geomean parasitaemia and proportion of high-density parasitaemia than those with severe anaemia.…”

“…A study on the clinical predictors of severe malaria anaemia in a holo-endemic P. falciparum transmission area found that children with uncomplicated malaria had more peripheral parasitaemia, geomean parasitaemia and proportion of high-density parasitaemia than those with severe anaemia. 13 Our findings therefore support the hypothesis that immune response to P. falciparum rather than the cumulative parasite burden may be the primary factor responsible for the development and promotion of severe malaria anaemia in holo-endemic regions. 13 Of our patients, 26% had bacteraemia and 55.2% of those who died had bacteraemia.…”

“…13 Our findings therefore support the hypothesis that immune response to P. falciparum rather than the cumulative parasite burden may be the primary factor responsible for the development and promotion of severe malaria anaemia in holo-endemic regions. 13 Of our patients, 26% had bacteraemia and 55.2% of those who died had bacteraemia. Hence, in Africa, where bacterial infections such as staphylococcal and Salmonella infections are prevalent, 14 the use of antibiotics for severely anaemic children may be justified, especially where blood culture facilities are not readily available.…”

“…1,13 Respiratory distress (presence of fast breathing, chest in-drawing, grunting and flaring of nostrils) increases case fatality rates of severely anaemic children 10 times. 13 This may result from lower oxygen concentration and metabolic acidosis commonly seen in such children. In this study, hypoxaemia (SaO 2 <90%) and metabolic acidosis were also significantly related to death.…”

CD4 T-cell expression of IFN-γ and IL-17 in pediatric malarial anemia

“…Therefore to test this hypothesis, we characterized the ex vivo ability of peripheral lymphocytes and CD4+ T-cell sub-populations to produce IFN-γ and IL-17 in acutely infected children presenting with non-SMA and SMA. In agreement with previous reports, children presenting with SMA had leukocytosis [56, 57]. In addition, our observation of elevated levels of lymphocytes expressing IFN-γ in children with SMA and memory-like CD4+ T-cells expressing IL-17 in children with non-SMA, suggests in vivo induction of these cells as has been reported in animal models [43, 58–60].…”