Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads

World Viral Hepatitis Day in Burkina Faso, 2020: awareness, prevention and hepatitis B vaccine to achieve the WHO eradication goal by 2030

Running title: Hepatitis B vaccine coverage in Ouagadougou, Burkina Faso Burkina Faso is located in a region where hepatitis B is endemic with low vaccination coverage. The aim of this study was to evaluate the vaccine coverage during Hepatitis B screening campaign organized by "SOS Hepatitis Burkina"in Ouagadougou in July 2020. A rapid HBsAg detection test (Abon Biopharma Guangzhou, Co., Ltd. China; sensitivity > 99.0%; specificity, 96.8%) was performed on 252 individuals who voluntarily agreed to participate in the study. This study was approved by the Institutional Ethics Committee of the Centre de recherche Biomoleculaire Pietro Annigoni (CERBA).We included 252 participants aged 2 to 77 years (mean age 31.77±14.07 and 29.67±13.71 for males and females, respectively). The prevalence of HBsAg was 18.25% (46/252) and was slightly high in the age groups 21-30 years (23.71%) and 31-40 years (23.73%). Out of 252 participants, 25 HBV-negative participants were vaccinated, giving a vaccination rate of 9.92%.This study reports a high prevalence of HBV infection in Burkina Faso with low vaccination coverage. The study suggests that more attention should be paid to HBV prevention in Burkina Fas

Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants

BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naïve, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14 weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48 weeks of age. HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log(10) IU/ml compared to ≥8 log(10) IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver