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In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

SummaryDeterminations of in vitro proliferative and secretory activities of peripheral blood cells are used widely for research in clinical immunology but, to our knowledge, have not been evaluated as to their power to reflect in vivo activities quantitatively. Here, we addressed this question by quantitatively correlating the in vitro secretion of interleukin (IL)-5 by peripheral blood cells to the in vivo activity of IL-5 as reflected by peripheral-blood eosinophil counts. Studying 458 humans exposed to transmission of the nematode Onchocerca volvulus, IL-5 was measured in the supernatants of 0·02-ml whole-blood cells cultured in the presence of O. volvulus extract or mitogen. O. volvulus-reactive IL-5 secretion was correlated significantly to blood eosinophilia in a quantitative manner explaining 15·1% (95% CI 8·3–19·9%) of the variability of eosinophil counts. Interestingly, correlations were obtained only if parasite counts were included in the calculation using multiple regression analysis. The results show that in vitro assays of minute amounts of blood lymphocytes may quantitatively reflect activities of the entire lymphocyte population in vivo.

Most cases of α-thalassemia result from large deletions at the α-globin locus (1). The α-globin gene cluster contains a tandem array of 2 nearly identical α-globin genes ( HBA ; Fig. 1A⇓ ) (2). The α-thalassemias are characterized by deletions that inactivate both α-globin genes of a given chromosome, whereas in α+-thalassemias, one gene remains functional. The most widespread α+-thalassemias are those designated −α3.7 and −α4.2, according to the lengths of the deleted fragments (3). The α+-thalassemias cannot be diagnosed on clinical grounds, and routine laboratory tests fail, except in the perinatal period, when transient expression of hemoglobin (Hb) Barts may be found (4). Diagnostic assays are also important for genetic counseling because, when occurring in compound heterozygosity with α-thalassemia, α+-thalassemia causes Hb H disease with a thalassemia intermedia phenotype (5). The classic method to diagnose α-thalassemias is the laborious and expensive Southern blot hybridization. Alternative assays include qualitative gap-PCRs (3)(6), which depend on the generation of long PCR products, which is not consistently reproducible (3) in the GC-rich sequences of the α-globin gene cluster. In addition, gap-PCRs require the use of deletion-type–specific primers, which limits their sensitivities to distinct variants. Moreover, as for any PCR-based, allele-specific method, they carry the risk that alleles may be amplified from minimal contaminants, such as maternal DNA in prenatal diagnostics or fetal DNA circulating in maternal blood (7)(8)(9). Quantitative PCR has been proposed to avoid these problems (9). Because of limited sensitivity, however, real-time PCR approaches have been successful only for the diagnosis of α-thalassemias (9)(10)(11). We studied a group of 122 individuals from the Ashanti Region of Ghana, West Africa, which has a moderate prevalence of −α3.7-thalassemia. …

A randomized double blind study was performed to evaluate the tolerance and the acceptance of mefloquine alone (Lariam) compared to a combined drug regimen consisting of mefloquine, sulfadoxine and pyrimethamine (MSP; Fansimef) in the prophylaxis of malaria. 175 Europeans travelling to different malaria endemic areas received either mefloquine alone (250 mg/week) or its combination with sulfadoxine (500 mg/week) plus pyrimethamine (25 mg/week). One person taking mefloquine and two taking MSP discontinued the drug intake because of moderate clinical side effects. Mild and moderate adverse clinical reactions predominantly concerning the gastro-intestinal tract and the autonomous nervous system were reported with a significantly higher occurrence in the MSP group. With both prophylactic regimens, reversibly elevated liver enzyme activities (glutamate oxalate transaminase and glutamate pyruvate transaminase [GPT]) were observed after prophylaxis. The increase of GPT serum activity correlated significantly with relatively high GPT levels before prophylaxis in both groups. This finding suggests a limited use of both regimens in cases of liver dysfunction. One case of mefloquine-resistant Plasmodium falciparum malaria was observed from West Africa; this patient was cured by a standard regimen of chloroquine.