The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe ...courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.
The study design of this clinical trial was based on findings from a phase 2a controlled human malaria infection (CHMI) study assessing vaccine efficacy in adults,2 and from a study evaluating the ...effect of a change in the vaccine regimen on the quality of antibody responses.3 The phase 2a CHMI studies in malaria-naive adults showed that a regimen containing a delayed third or fourth fractional dose, or both, of RTS,S confers numerically increased protection against malaria compared with the standard RTS,S regimens upon challenge. ...although Samuels and colleagues aimed to show a meaningful difference between the regimens containing the fractionated doses compared with the standard regimen, statistically there was no difference in efficacy between the different regimens in the CHMI studies or in the current trial in African children. The real immune response history of children cannot be easily assessed with simple antibody measurements but is rather more complex.4 CHMI is done by direct venous inoculation of 3200 purified,5 cryopreserved, fully infectious Plasmodium falciparum sporozoites and has become a gold standard for assessing vaccine candidates, drugs, and naturally acquired immunity.
Abstract
Background
Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment and use of impregnated bed nets, ...we developed a malaria vaccine candidate with the aim of reducing sequestration of asexual “blood-stage” parasites in the placenta, the major virulence mechanism.
Methods
The vaccine candidate PAMVAC is based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive volunteers were immunized with 3 intramuscular injections of 20 μg (n = 9) or 50 μg (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given every 4 weeks. Volunteers were observed for 6 months following last immunization.
Results
All PAMVAC formulations were safe and well tolerated. A total of 262 adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly related to the vaccine. No serious AEs occurred. Distribution and severity of AEs were similar in all arms. PAMVAC was immunogenic in all participants. PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to CSA in a standardized functional assay.
Conclusions
PAMVAC formulated with Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced functionally active antibodies. Next, PAMVAC will be assessed in women before first pregnancies in an endemic area.
Clinical Trials Registration
EudraCT 2015-001827-21; ClinicalTrials.gov NCT02647489.
The pregnancy-associated malaria-vaccine candidate PAMVAC is safe and well tolerated with all three tested formulations and induces functional binding-inhibitory antibodies. The vaccine with glucopyranosyl lipid adjuvant (GLA) in stable emulsion is superior to Alhydrogel and a GLA/QS21 liposomal formulation.
We read with interest the publication on malaria treatment by Obonyo et al. (Malaria J 21:30, 2022). This commentary questions the methodology, especially the chosen time points of treatment outcome ...measures.
Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype ...of OBI infections in Nigerian blood donors.
Serum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced.
Of the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001).
High incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk.
Influenza in Africa Yazdanbakhsh, Maria; Kremsner, Peter G
PLoS medicine,
12/2009, Volume:
6, Issue:
12
Journal Article
Peer reviewed
Open access
Maria Yazdanbakhsh and Peter Kremsner argue that there needs to be better awareness, surveillance, and clinical management of common febrile diseases in Africa, especially influenza.
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has ...raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.
A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 13.0%) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio RR, 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 4.6% in the SP group and 88/2,737 3.2% in the MQ group; RR, 0.70 95% CI 0.51-0.96; p=0.03) and anemia at delivery (609/1,380 44.1% in the SP group and 1,110/2743 40.5% in the MQ group; RR, 0.92 95% CI 0.85-0.99; p=0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year PYAR in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 95% CI 0.52-0.88; p=0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 0.78-0.95; p=0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.
Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary.
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