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Weekly Digest: At least 6 months of immune memory for COVID-19; Household transmission of SARS-CoV-2; Harmonizing regulatory approval for antibiotics in children; Post-exposure TB vaccine could avert RR-TB cases and deaths.

COVID-19

Immune memory for COVID-19 lasts at least six months. Researchers at Rockefeller University conducted a prospective cohort study to assess levels of antibodies in 87 COVID-19 patients. The study showed that IgM and IgG anti-SARS-CoV-2 antibody titres decreased significantly between 1.3 and 6.2 months post-infection, while IgA was less affected. Furthermore, the neutralizing activity in plasma decreased by fivefold, while the number of RBD-specific memory B cells remained unchanged. Intestinal biopsies of asymptomatic patients four months post-infection revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in seven out of fourteen volunteers, implying that the immune system may continue to be stimulated post-infection. The observation that memory B cell responses persisted and continued to evolve 6 months post-infection suggests that individuals infected with SARS-CoV-2 could mount a rapid and effective response to the virus upon re-exposure. [Nature]

Household transmission of SARS-CoV-2. Researchers conducted a retrospective observational study in Wuhan revealing that within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Infants aged 0–1 year were significantly more likely to be infected than children aged 2–5 years (odds ratio [OR] 2.20, 95% CI 1.40–3.44) and children aged 6–12 years (1.53, 1.01–2.34). Children and adolescents were more likely to infect others than adults aged 60 years or older (1.58, 1.28–1.95). Pre-symptomatic cases were more infectious (1·42, 1·30–1·55), and individuals with asymptomatic infection were less infectious than symptomatic cases (0.21, 0.14–0.31). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases and 63% among secondary cases. These findings have implications for devising interventions to block household transmission of SARS-CoV-2. [The Lancet Infectious Diseases]

Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study. The use of face masks effectively reduces the risk of SARS-CoV-2 transmission; however, there is little research on its effectiveness at a population level. Researchers implemented a web-based survey on mask-wearing behavior across the United States and analysed more than 370,000 responses. Ultimately, they found that a higher rate of self-reported mask usage was correlated with an increased odds of transmission control. In other words, areas, where more people chose to wear masks were more likely to control the transmission of SARS-CoV-2. Although this finding represents a promising result for mask usage, the challenge of translating government mandates into community behavior, especially in the US, remains. (The Lancet)

 Factors associated with adherence to COVID-19 prevention measures in the Democratic Republic of the Congo (DRC): results of an online survey. The majority of African countries continue to be relatively resilient to COVID-19 without a clear explanation of why. While it is safe to assume a degree of undercounting of cases due to limited testing capacity, healthcare facilities still do not report an overwhelming number of respiratory illnesses and deaths. Researchers conducted an online survey to investigate compliance with COVID-19 prevention guidelines by adults in 22 provinces of the Democratic Republic of Congo. Of 3268 participants, 54.7% reported no mask-wearing, 41.7% reported non-adherence to physical distancing, and 15.3% reported non-regular handwashing. Among the characteristics associated with poor adherence were lower education level, living with other people at home, being jobless/students, living with a partner, and not being a healthcare worker. The authors concluded that urgent action is needed to close the gap on disparities in measure implementation across the country and that future research should investigate transmission dynamics in countries that, despite a considerable degree of non-adherence with COVID-19 preventions measures, are experiencing a lower burden than countries in Europe and the Americas. (BMJ Open)

 

Drug Resistance and Global Health

Harmonizing regulatory approval for antibiotics in children. Emerging antibiotic resistance and multidrug-resistant infections represent a threat to children’s health worldwide; however, very few paediatric trials for new antibiotics have been done to determine the optimal treatment in children. While the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) both accept that efficacy can be extrapolated from adult studies, the FDA continues to require a de-novo generation of primary safety data in children and that recruitment of children in these trials can only be on the clinical indication for which the agent is licensed in adults. Contrary to the FDA, the EMA accepts that both efficacy and safety can be extrapolated from adult studies for well-established classes of antibiotics and that children can be recruited into pharmacokinetic studies with any relevant clinical infection. The discrepancies in these regulating bodies’ policies come with substantial increases in cost, complexity, and time to drug development. There is currently a delay of around a decade between the time antibiotics are licensed for use in adults and the time they are licensed in children, warranting global efforts and collaboration to address the threat of MDR in children. [The Lancet]

A small molecule interacts with pMAC-derived hydroperoxide reductase and enhances the activity of aminoglycosides. The global threat of antimicrobial resistance necessitates new medications to combat drug-resistant pathogens. Gram-negative pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, are resistant to nearly all commonly used antibiotics, requiring clinicians to prescribe stronger antibiotics, which can cause negative side effects and lead to more resistance. In this study, scientists used whole cell-based screening to identify antibacterial agents against A. baumannii. They discovered a small molecule named 6D1 that suppressed the growth of A. baumannii. Additionally, 61D enhanced the antibacterial activity of the aminoglycosides kanamycin and gentamicin against K. pneumoniae. [Nature: The Journal of Antibiotics]

Post-exposure TB vaccine could avert 10% of cases and 14% of deaths from rifampicin-resistant TB. Researchers performed mathematical modeling of TB transmission dynamics with a post-exposure vaccine rollout in 30 countries with high rifampicin-resistant TB (RR-TB) burden. The study revealed that a post-exposure TB vaccine could avert 10% (95% CI: 9.7 to 11%) of RR-TB cases and 7.3% (6.6 to 8.1%) of deaths over 2020–2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. Further, this impact would increase to 14% (12 to 16%) and 31% (29 to 33%), respectively, when combined with RR-TB diagnosis and treatment improvements. A post-exposure TB vaccine could have important implications for antibiotic use and the global control of RR-TB, especially if implemented with other measures related to RR-TB management. [Nature] 

HPV vaccination could reduce the incidence of oropharyngeal cancer and improve the quality of life among men and women in Texas. Researchers modelled the demographic dynamics and transmission of human papillomavirus (HPV) and oropharyngeal cancer progression (OPC) in the U.S. state of Texas. The study revealed that compared with the current vaccination program, increasing vaccine uptake rates by 50% in males and females would decrease the cumulative cases by 4403 (within 100 years), reduce the incidence rates of OPC, and improve the quality-adjusted life-years (QALYs), among males and females. The incremental cost-effectiveness ratio of this strategy was $94,518 per QALY gained. The researchers concluded that this strategy was cost-effective and could provide tremendous public health benefits in Texas. [Nature]

Conference equity in global health: a systematic review of factors impacting LMIC representation at global health conferences. To date, stakeholders from low- and middle-income countries (LMICs) have been under-represented at Global Health conferences. This systematic review aimed to identify facilitators and barriers to conference attendance by representatives from LMIC. Researchers screened 8765 articles, of which 46 met inclusion criteria. Only 4 percent of the 112 conferences (254,601 attendees) described were hosted in LMICs, and 39 percent of the 98,302 attendees who disclosed affiliation were from LMICs. Barriers included high travel costs, visa restrictions, and lower acceptance rates. These factors can be mitigated by hosting conferences in visa-friendly countries, providing travel scholarships, and developing mentorship programs. Facilitating representation of stakeholders from LMIC at conferences is crucial in making Global Health a more equitable field. [BMJ Global Health]

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