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The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4 + T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4 + T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4 + T cells. Children with complicated malaria had higher frequencies of CTLA-4 + or PD-1 + CD4 + T cells than children with uncomplicated malaria. Conversely, children with uncomplicated malaria showed a higher proportion of CD4 + T cells expressing CD39 and Granzyme B, compared to children with complicated malaria. In contrast, asymptomatically infected children expressed only low levels of co-inhibitory molecules. Thus, different CD4 + T cell phenotypes are associated with complicated versus uncomplicated malaria, suggesting a two-sided role of CD4 + T cells in malaria pathogenesis and protection. Deciphering the signals that shape the CD4 + T cell phenotype in malaria will be important for new treatment and immunization strategies.

Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106-135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC 50 -value of 35 μg/ml (95% confidence interval: 33 μg/ml-37 μg/ml), which is three to eight times lower than the IC 50 -values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.

This study was designed to investigate the prevalence and type of sexual dysfunction (SD) in healthy sexually active Ghanaian men of fertile age. Sexual functioning was determined in 300 healthy Ghanaian men with the Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire leaving in Kumasi metropolis, between December 2009 and April 2010. All men had a steady heterosexual relationship for at least 2 years before enrollment in the study. Of the 300 men selected, 255 (85%) completed the survey; the overall prevalence of SD in these subjects was 66%. The most prevalent areas of difficulty were infrequency (70.2%), premature ejaculation (64.7%), dissatisfaction with sexual acts (61.2%), impotency (59.6%), nonsensuality (59.2%), noncommunication (56.9%) and avoidance (49.0%). There were positive correlation between SD, impotence, dissatisfaction and age. The prevalence rate of SD in Ghanaian men is high and related to age.