Childhood Mortality During and After Hospitalization in Western Kenya: Effect of Malaria Treatment Regimens

Abstract

Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Increasingly, the contribution of P. falciparum-associated severe anemia to pediatric mortality is being recognized while the impact of chloroquine resistance on mortality has not been evaluated. To address the issues of pediatric mortality, causes of death among hospitalized children less than five years of age in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were conducted to determine the child's clinical status posthospitalization. Of the 1,223 children admitted to Siaya District Hospital from March to September 1991, 293 (24%) were severely anemic (hemoglobin level < 5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144 (13%) occurred out-of-hospital within eight weeks after admission; 32% of all deaths were associated with malaria. Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days). The risk of dying was associated with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.

Antimalarial drug resistance and combination chemotherapy

“…Ultimately, with high levels of resistance, there is no clinical or parasitological response at all to treatment (¢gure 1). In high-transmission areas an increasing prevalence of anaemia may be the ¢rst sign of worsening drug resistance (Bloland et al 1998;Zucker et al 1996). As host factors also contribute signi¢cantly to the therapeutic response in malaria, there tends to be a poor correlation between in vitro and in vivo antimalarial drug susceptibility responses.…”

Blood transfusions for severe malaria-related anemia in Africa: a decision analysis.

“…We identified eight prospective hospital-based studies conducted in African settings that had reported mortality rates associated with severe malarial anemia between 1990 and 1997 6,7,16,18,19,[26][27][28] (Table 1). The average risk of mortality was 12%, but the heterogeneity was significant (P Ͻ 0.001, by chi-square test).…”

“…21,33 Furthermore, the mortality risk may vary depending on several clinical characteristics, such as respiratory distress, impaired consciousness, age, hemoglobin level, parasite density, and comorbidity. 7,[16][17][18][19][20][21][22] Transfusion was not beneficial when the patient's risk of mortality without a transfusion was Ͻ 5%. Because most deaths among severely anemic children tend to occur within 12 hr of admission, it is important to identify those patients at high risk timely to allow for early intervention.…”

“…This may be reasonable since most of the risk factors overlap (e.g., impaired consciousness and respiratory distress). 16 Third, we assumed that the pa- Lackritz, 1992 7 Brewster, 1993 18 Craighead, 1993 26 Holzer 6 Marsh, 1995 16 Zucker, 1996 19 Newton, 1997 28 Total Model quantification. Probabilities of the occurrence of the different events in the decision analysis were based on published studies as identified with a MEDLINE search.…”

“…12,15 The mortality from severe anemia is known to be higher with more intense P. falciparum transmission patterns and patient characteristics such as younger age, lower hemoglobin level, and presence of respiratory distress or impaired consciousness. 7,[16][17][18][19][20][21][22] A survival benefit of transfusion was found in an observational study in western Kenya, 7 but the effectiveness of transfusions has unfortunately not been studied in randomized controlled trials.…”