Safety and immunogenicity of an Ad26.ZEBOV booster vaccine in Human Immunodeficiency Virus positive (HIV+) adults previously vaccinated with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against Ebola: A single-arm, open-label Phase II clinical trial in Kenya and Uganda

BACKGROUND: People living with HIV constitute an important part of the population in regions at risk of Ebola virus disease outbreaks. The two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen induces strong immune responses in HIV-positive (HIV+) adults but the durability of this response is unknown. It is also unclear whether this regimen can establish immune memory to enable an anamnestic response upon re-exposure to antigen. METHODS: This paper describes an open-label, phase 2 trial, conducted in Kenya and Uganda, of Ad26.ZEBOV booster vaccination in HIV+ participants who had previously received the Ad26.ZEBOV, MVA-BN-Filo primary regimen. HIV+ adults with well-controlled infection and on highly active antiretroviral therapy were enrolled, vaccinated with booster, and followed for 28 days. The primary objectives were to assess Ad26.ZEBOV booster safety and antibody responses against the Ebola virus glycoprotein using the Filovirus Animal Non-Clinical Group ELISA. RESULTS: The Ad26.ZEBOV booster was well-tolerated in HIV+ adults with mostly mild to moderate symptoms. No major safety concerns or serious adverse events were reported. Four and a half years after the primary regimen, 24/26 (92 %) participants were still classified as responders, with a pre-booster antibody geometric mean concentration (GMC) of 726 ELISA units (EU)/mL (95 %CI 447-1179). Seven days after the booster, the GMC increased 54-fold to 38,965 EU/mL (95 %CI 23532-64522). Twenty-one days after the booster, the GMC increased 176-fold to 127,959 EU/mL (95 %CI 93872-174422). The responder rate at both post-booster time points was 100 %. CONCLUSIONS: The Ad26.ZEBOV booster is safe and highly immunogenic in HIV+ adults with well-controlled infection. The Ad26.ZEBOV, MVA-BN-Filo regimen can generate long-term immune memory persisting for at least 4·5 years, resulting in a robust anamnestic response. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR202102747294430). CLINICALTRIALS: gov (NCT05064956)

Mode of birth in subsequent pregnancy when first birth was vacuum extraction or second stage cesarean section at a tertiary referral hospital in Uganda

Abstract Introduction The trends of increasing use of cesarean section (CS) with a decrease in assisted vaginal birth (vacuum extraction or forceps) is a major concern in health care systems all over the world, particularly in low-resource settings. Studies show that a first birth by CS is associated with an increased risk of repeat CS in subsequent births. In addition, CS compared to assisted vaginal birth (AVB), attracts higher health service costs. Resource-constrained countries have low rates of AVB compared to high-income countries. The aim of this study was to compare mode of birth in the subsequent pregnancy among women who previously gave birth by vacuum extraction or second stage CS in their first pregnancy at Mulago National Referral Hospital, Uganda. Methods This was a retrospective cohort study that involved interviews of 81 mothers who had a vacuum extraction or second stage CS in their first pregnancy at Mulago hospital between November 2014 to July 2015. Mode of birth in the subsequent pregnancy was compared using Chi-2 square test and a Fisher’s exact test with a 0.05 level of statistical significance. Results Higher rates of vaginal birth were achieved among women who had a vacuum extraction (78.4%) compared to those who had a second stage CS in their first pregnancy (38.6%), p < 0.001. Conclusions and recommendations Vacuum extraction increases a woman’s chance of having a subsequent spontaneous vaginal birth compared to second stage CS. Health professionals need to continue to offer choice of vacuum extraction in the second stage of labor among laboring women that fulfill its indication. This will help curb the up-surging rates of CS

Anti-HIV Ermiasolides from Croton megalocarpus.

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5β-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5β,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5β-Hydroxy-8H-β-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5β-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC50 = 0.002 µg/mL. On the other hand, 5β-Hydroxy-8H-β-eudesm-7(11)-en-12,8-olide (3) and 5β,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC50 = 0.04 µg/mL and 69.5% at IC50 = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease

In vitro anti-HIV and cytotoxic effects of pure compounds isolated from Croton macrostachyus Hochst. Ex Delile.

is an important plant in traditional African medicine, widely utilized to treat a variety of diseases. In Kenya, HIV-infected patients use leaf and root decoctions of the plant as a cure for cough, back pain, bleeding, skin diseases, warts, pneumonia, and wounds. This study aimed to evaluate the anti-HIV activities and cytotoxic effects of extracts and chemical constituents isolated from In our previous study we demonstrated that the hexane, CH Cl , ethyl acetate and methanol soluble fractions of a 1:1 CH Cl /MeOH crude extracts of the leaves and stem bark of exhibited potent anti-HIV activities against HIV-1 with IC values ranging from 0.02–8.1 μg/mL and cytotoxicity effects against MT-4 cells ranging from IC = 0.58–174 μg/mL Hence, hexane soluble extract of 1:1 CH Cl /MeOH crude extract of the leaves of that was more potent against HIV-1 at IC = 0.02 μg/mL was subjected to column chromatography leading to the isolation of 2-methoxy benzyl benzoate (1), lupenone (2), lupeol acetate (3), betulin (4), lupeol (5), sitosterol (6) and stigmasterol (7). Lupenone (2), lupeol acetate (3) and betulin (4) exhibited anti-HIV-1 inhibition at IC = 4.7 nM, 4.3 and 4.5 μg/mL respectively. The results obtained from this study support the potential of as a source of anti-HIV constituents

Malaria is a cause of iron deficiency in African children

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%

Malaria is a cause of iron deficiency in African children.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n?=?7,453), but not among individuals living in malaria-free areas (n?=?3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%