Vaccine Development Should Be Polytheistic, Not Monotheistic.

Vaccines based on mRNA technology have been tremendously successful, but their properties are not necessarily ideal for all pathogens. There is a risk that concentration on that technology alone for new vaccine development will ignore older technologies that have properties giving broader and more persistent protection.

IgG Seroconversion and Pathophysiology in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

Laboratory Evaluation and Field Testing of Dengue NS1 and IgM/IgG Rapid Diagnostic Tests in an Epidemic Context in Senegal.

In Senegal, the burden of dengue is increasing and expanding. As case management and traditional diagnostic techniques can be difficult to implement, rapid diagnostic tests (RDTs) deployed at point of care are ideal for investigating active outbreaks. The aim of this study was to evaluate the diagnostic performance of the Dengue NS1 and Dengue IgM/IgG RDTs on the serum/plasma samples in a laboratory setting and in the field. During laboratory evaluation, performance of the NS1 RDT was assessed using NS1 ELISA as the gold standard. Sensitivity and specificity were 88% [75-95%] and 100% [97-100%], respectively. Performance of the IgM/IG RDT was assessed using the IgM Antibody Capture (MAC) ELISA, indirect IgG, and PRNT as gold standards. The IgM and IgG test lines respectively displayed sensitivities of 94% [83-99%] and 70% [59-79%] and specificities of 91% [84-95%] and 91% [79-98%]. In the field, the Dengue NS1 RDT sensitivity and specificity was 82% [60-95%] and 75% [53-90%], respectively. The IgM and IgG test lines displayed sensitivities of 86% [42-100%] and 78% [64-88%], specificities of 85% [76-92%] and 55% [36-73%], respectively. These results demonstrate that RDTs are ideal for use in a context of high prevalence or outbreak setting and can be implemented in the absence of a confirmatory test for acute and convalescent patients.

Prevalence of neutralising antibodies against SARS-CoV-2 in acute infection and convalescence: A systematic review and meta-analysis.

BACKGROUND: Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates. METHODOLOGY/PRINCIPAL FINDINGS: This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5-86.9) using the titre cut off >1:20 and 83.9% (82.2-85.6), 70.2% (68.1-72.5) and 54.2% (52.0-56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0-89.2], >1:160, 74.4% [67.5-79.7]) than those with mild presentation (56.7% [49.9-62.9] and 44.1% [37.3-50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9-39.2] and 10.0% [3.7-20.1], respectively). IgG and neutralising antibody levels correlated poorly. CONCLUSIONS/SIGNIFICANCE: 85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.

Self-sampling of capillary blood for SARS-CoV-2 serology.

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty eight out of thirty nine participants were able to self-collect an adequate sample of capillary blood (≥ 50 µl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen's kappa coefficient of > 0.88 (near-perfect agreement, 95% CI 0.738-1.000). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

Campylobacter bacteremia in London: A 44-year single-center study.

PURPOSE: Campylobacter species are a well-recognized but rare cause of bloodstream infection. METHODS: Here we reviewed 41 cases of Campylobacter bloodstream infection occurring at a single center in London over 44years, comprising 0.2% of all recorded episodes during this time period. RESULTS: Patients had a mean age of 46years and, contrasting with previous reports, nearly 50% of our patients did not have significant comorbidities. Ciprofloxacin resistance increased over the study period with 35% of isolates overall being resistant compared with only 3% exhibiting macrolide resistance. Despite a minority of patients receiving appropriate empirical antibiotic therapy, overall mortality was only 7%. CONCLUSION: Campylobacter bacteremia remains a rare but significant cause of morbidity with a low associated mortality. Underlying immunosuppressive conditions are common but by no means universal. In our setting, macrolides would be favored as empirical agents to treat suspected Campylobacter enteritis, including cases with associated bacteremia.

Global funding trends for malaria research in sub-Saharan Africa: a systematic analysis.

BACKGROUND: Total domestic and international funding for malaria is inadequate to achieve WHO global targets in burden reduction by 2030. We describe the trends of investments in malaria-related research in sub-Saharan Africa and compare investment with national disease burden to identify areas of funding strength and potentially neglected populations. We also considered funding for malaria control. METHODS: Research funding data related to malaria for 1997-2013 were sourced from existing datasets, from 13 major public and philanthropic global health funders, and from funding databases. Investments (reported in US$) were considered by geographical area and compared with data on parasite prevalence and populations at risk in sub-Saharan Africa. 45 sub-Saharan African countries were ranked by amount of research funding received. FINDINGS: We found 333 research awards totalling US$814·4 million. Public health research covered $308·1 million (37·8%) and clinical trials covered $275·2 million (33·8%). Tanzania ($107·8 million [13·2%]), Uganda ($97·9 million [12·0%]), and Kenya ($92·9 million [11·4%]) received the highest sum of research investment and the most research awards. Malawi, Tanzania, and Uganda remained highly ranked after adjusting for national gross domestic product. Countries with a reasonably high malaria burden that received little research investment or funding for malaria control included Central African Republic (ranked 40th) and Sierra Leone (ranked 35th). Congo (Brazzaville) and Guinea had reasonably high malaria mortality, yet Congo (Brazzaville) ranked 38th and Guinea ranked 25th, thus receiving little investment. INTERPRETATION: Some countries receive reasonably large investments in malaria-related research (Tanzania, Kenya, Uganda), whereas others receive little or no investments (Sierra Leone, Central African Republic). Research investments are typically highest in countries where funding for malaria control is also high. Investment strategies should consider more equitable research and operational investments across countries to include currently neglected and susceptible populations. FUNDING: Royal Society of Tropical Medicine and Hygiene and Bill & Melinda Gates Foundation.