Blaise Genton

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.

BACKGROUND: Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species. METHODS AND FINDINGS: This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%-6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%-13.2%) for P. falciparum, 8.8% (7.1%-10.7%) for P. vivax, and 17.3% (11.7%-24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001). CONCLUSION: P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden, and especially severe disease, in areas where P. falciparum and P. vivax coexist.

BACKGROUND: As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children. METHODS: We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. CONCLUSIONS: These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.).