Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the microvascular endothelium is believed to be a key factor in the development of cerebral malaria. Erythrocyte rosette formation has been correlated with malaria severity in studies from east and west Africa. We cultured fresh isolates from Malawian children with severe (n = 76) or uncomplicated (n = 79) malaria to pigmented trophozoite stage and examined rosette formation and adherence to CD36, intercellular adhesion molecule-1 (ICAM-1), chondroitin sulfate A (CSA), and thrombomodulin (TM). Most (126 of 148) isolates bound to CD36, and 76 of 136 bound to ICAM-1. Fewer bound to CSA (40 of 148) or TM (23 of 148). After controlling for parasitemia, there was an inverse association between binding to CD36 (P = 0.004) or ICAM-1 (P = 0.001) and disease severity. Parasites from children with severe malaria anemia bound least to CD36, whereas ICAM-1 binding was lowest in children with cerebral malaria. There was no difference in rosette formation between any of the groups. In Malawian children, there was no evidence of a positive association between adherence to any of the receptors examined and disease severity. The negative association found raises the possibility that adherence to certain receptors could instead be an indicator of a less pathogenic infection.

Usefulness of clinical case-definitions in guiding therapy for African children with malaria or pneumonia.

The World Health Organisation has developed disease-specific clinical case-definitions to guide management of children with fever or cough, the cardinal signs of malaria and pneumonia. To assess the usefulness of the case-definitions and to investigate their interaction, we studied children with fever or cough brought to a hospital in Lilongwe, Malawi. For all children, a thick blood smear was examined for Plasmodium falciparum parasites. Chest radiography was done only for children with parasitaemia and those who satisfied the clinical case-definition for pneumonia; others were assumed to have normal chest radiographs. Of 1599 enrolled children, 566 (35%) had parasitaemia and 116 had radiographic evidence of pneumonia; 43 had both pneumonia and parasitaemia. Of the 471 children who met the clinical definition for pneumonia, 449 (95%) also met the malaria clinical definition. Among children with radiographic evidence of pneumonia, the clinical definition for malaria was not predictive of parasitaemia (sensitivity 93%, specificity 5%). Whether malaria parasitaemia was present or absent, the pneumonia clinical definition distinguished children with and without radiographic evidence of pneumonia (sensitivity and specificity > 60%). Children who satisfied the pneumonia clinical definition were more likely to have radiographic evidence of pneumonia (odds ratio 10.4, 95% confidence interval 5.2-20.7), parasitaemia (1.6, 1.2-2.2), or both at the same time (4.2, 2.1-8.4) than were children who did not meet the definition. Children who satisfy the malaria and pneumonia clinical definitions need treatment for both disorders. Scarce diagnostic methods, especially microscopy, are needed for more specific treatment of children with fever and cough.

PIP: The WHO has developed disease-specific clinical case definitions to guide the management of children with fever and cough, the cardinal signs of malaria and pneumonia. To assess the usefulness of these case definitions and to investigate their interaction, the authors studied children with fever or cough who were brought to Lilongwe, Malawi. For all children, a thick blood smear was examined for Plasmodium falciparum parasites. Chest radiography was done only for children with parasitemia and those who satisfied the clinical case definition for pneumonia; others were assumed to have normal chest radiographs. Of 1599 enrolled children, 566 (35%) had parasitemia; 43 had both parasitemia and pneumonia. Of the 471 children who met the clinical definition for pneumonia, 449 (95%) also met the clinical definition for malaria. Among children with radiographic evidence of pneumonia, the clinical definition for malaria was not predictive of parasitemia (sensitivity 93%, specificity 5%. Whether malaria parasitemia was present or not, the pneumonia clinical definition distinguished children with and without radiographic evidence of pneumonia (sensitivity and specificity 60%). Children who satisfied the pneumonia clinical definition were more likely to have radiographic evidence of pneumonia (odds ration 10.4, 95% confidence interval 5.2-20.7), parasitemia (1.6, 1.2-2.2), or both at the same time (4.2, 2.1-8.4) than were children who did not meet the definition. Children who satisfy both clinical definitions need treatment for both disorders. Scarce diagnostic methods, especially microscopy, are necessary for more specific treatment of children with fever and cough.

Cotrimoxazole for childhood febrile illness in malaria-endemic regions

The efficacy of co-trimaxozole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia; 37 percent of whom also met clinical criteria for acute respiratory tract infection; were treated with 20 mg/kg co-trimaxozole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and syptoms were rapidly abolished and improvement was maintained during the follow-up 14 days. Co-trimaxozole may be an effecitve single treatment for febrile illness in young children in areas where malaria is endemic; resources are few; and diagnosis must rely on clinical findings alone

Co-trimoxazole for childhood febrile illness in malaria-endemic regions.

The efficacy of co-trimoxazole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mg/kg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone.