Detection of Plasmodium falciparum male and female gametocytes and determination of parasite sex ratio in human endemic populations by novel, cheap and robust RTqPCR assays

The presence of Plasmodium falciparum gametocytes in peripheral blood is essential for human to mosquito parasite transmission. The detection of submicroscopic infections with gametocytes and the estimation of the gametocyte sex ratio are crucial to assess the human host potential ability to infect mosquitoes and transmit malaria parasites

Novel Insights Into the Protective Role of Hemoglobin S and C Against Plasmodium falciparum Parasitemia.

Although hemoglobin S (HbS) and hemoglobin C (HbC) are well known to protect against severe Plasmodium falciparum malaria, conclusive evidence on their role against infection has not yet been obtained. Here we show, in 2 populations from Burkina Faso (2007-2008), that HbS is associated with a 70% reduction of harboring P. falciparum parasitemia at the heterozygous state (odds ratio [OR] for AS vs AA, 0.27; 95% confidence interval [CI], .11-.66; P = .004). There is no evidence of protection for HbC in the heterozygous state (OR for AC vs AA, 1.49; 95% CI, .69-3.21; P = .31), whereas protection even higher than that observed with AS is observed in the homozygous and double heterozygous states (OR for CC + SC vs AA, 0.04; 95% CI, .01-.29; P = .002). The abnormal display of parasite-adhesive molecules on the surface of HbS and HbC infected erythrocytes, disrupting the pathogenic process of sequestration, might displace the parasite from the deep to the peripheral circulation, promoting its elimination at the spleen level

High Risk of Severe Anaemia after Chlorproguanil-Dapsone+Artesunate Antimalarial Treatment in Patients with G6PD (A-) Deficiency

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. METHODS: The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. FINDINGS: In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7). CONCLUSIONS: CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary

Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria

A recently proposed mechanism of protection for haemoglobin C (HbC; β6Glu→Lys) links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i) total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS); ii) total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii) total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the β-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria

Genetic epidemiology of susceptibility to malaria: not only academic exercises.

Descriptive genetic epidemiology represents the initial step of a logical procedure of linked and consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development and potential of this pathway is based on complementary interactions of heterogeneus disciplines going from epidemiology (the transmission, the infection, the disease) to vaccinology passing through genetics, pathogenesis, and immunology. Several epidemiological approaches can be applied in the study of the genetic susceptibility to Plasmodium falciparum malaria: intra-ethnic case-control studies comparing genetic candidates of resistance/susceptibility between subjects with different presentation of malaria (from severe disease to asymptomatic infection) and the general healthy population is the classic approach; inter-ethnic comparative analyses among populations with different genetic backgrounds, exposed to the same epidemiological context and showing different susceptibility to the disease is a further, complementary, strategy