How will country-based mitigation measures influence the course of the COVID-19 epidemic?

Male circumcision for HIV prevention in young men in Kisumu, Kenya : a randomised controlled trial. Commentary

LEARNING The objectives of BIOS 781 are to present: OBJECTIVES: 1. basic population and quantitative genetic principles, including classical genetics, chromosomal theory of inheritance, and meiotic recombination 2. an exposure to QTL mapping methods of complex quantitative traits and linkage methods to detect co-segregation with disease 3. methods for assessing marker-disease linkage disequilibrium, including case-control approaches 4. methods for genome-wide association and stratification control.

Genetic Data Analysis

This report updates the 2020-21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021-22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4).The 2021-22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021-22 season are expected to be quadrivalent. Second, the composition of 2021-22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture-based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021-22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information.

/pdf/prevention-and-control-of-seasonal-influenza-with-vaccines-1dg9rw8cby.pdf

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season.

Background
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.

Objectives
Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010).

Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms.

Data collection and analysis
Two review authors independently assessed trial quality and extracted data.

Main results
We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barre Syndrome per million vaccinations. The harms evidence base is limited.

Authors' conclusions
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING:
This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.

Vaccines for preventing influenza in healthy adults

Attitudes Towards Circumcision Among Chinese Men

Objective We aimed to describe the theoretical basis and the potential applications of the test-negative design for estimating influenza vaccination effectiveness in sentinel influenza surveillance. Introduction The test-negative design is a variation of the case-control study, in which patients are enrolled in outpatient clinics (and/or hospitals) based on a clinical case definition such as influenza-like illness (ILI). Patients are then tested for influenza virus, and VE is estimated from the odds ratio comparing the odds of vaccination among patients testing positive for influenza versus those testing negative, adjusting for potential confounding factors. The design leverages existing disease surveillance networks and as a result, studies using it are increasingly being reported. Methods We sought to examine the theoretical basis for this design using causal analysis including directed acyclic graphs. We reviewed studies that used this design and examined the study populations and settings, the methodologic choices including analytic approaches, and the estimates of influenza VE provided. We conducted simulation studies to examine specific potential biases. Results We show how studies using this design can avoid or minimize bias, and where bias may be introduced with particular study design variations. A purported advantage of the test-negative design is to minimise selection bias by health-care seeking behaviour and we demonstrate why residual bias may occur. Another purported advantage of the test-negative design is minimization of misclassification of the exposure; however we show how this source of bias may persist and how exposure misclassification may be a greater cause for concern not dealt with by the study design. In our review, we found great variation in estimates, but consistency between interim and final VE estimates from the same locations, and consistency between VE estimates from inpatient and outpatient studies in the same locations, age groups and years. One outstanding issue is the potential bias due to non-collapsibility. Conclusions Our work provides a starting point for further consideration of the validity of the test-negative design, which is an efficient approach for routine monitoring of influenza VE that can be implemented in existing surveillance systems without substantial additional resources. Harmonization of analytic approaches may improve the potential for pooling VE estimates.

/pdf/the-test-negative-design-for-estimating-influenza-24jpldt8g5.pdf

The test-negative design for estimating influenza vaccination effectiveness

For over a decade virtually all A(H3N2) influenza viruses have been resistant to the adamantane class of antivirals. However, during the 2017 influenza season in Australia, 15/461 (3.3%) adamantane-sensitive A(H3N2) viruses encoding serine at residue 31 of the M2 protein were detected, more than the total number identified globally during the last 6 years. A return to wide circulation of adamantane-sensitive A(H3N2) viruses would revive the option of using these drugs for treatment and prophylaxis.

/pdf/detection-of-adamantane-sensitive-influenza-a-h3n2-viruses-4zq8wiz95i.pdf

Detection of adamantane-sensitive influenza A(H3N2) viruses in Australia, 2017: a cause for hope?

Background The Northern Territory (NT) of Australia has a mix of climates, sparsely distributed population and a large proportion of the populace are Indigenous Australians, and influenza is known to have a disproportionate impact upon this group. Understanding the epidemiology of influenza in this region would inform public health strategies. Objectives To assess if there are consistent patterns in characteristics of influenza outbreaks in the NT. Methods Laboratory confirmed influenza cases in the NT are notified to the NT Centre for Disease Control. We conducted analyses on notified cases from 2007-2016 to determine incidence rates (by age group, Indigenous status and area), seasonality of cases and spatial distribution of influenza types. Notified cases were linked to laboratory datasets to update information on influenza type or subtype RESULTS: The disparity in Indigenous and non-Indigenous notification rates varied by age group, with rate ratios for Indigenous versus non-Indigenous ranging from 1.58 (95% CI:1.39, 1.80) for ages 15-24 to 5.56 (95% CI: 4.71, 6.57) for ages 55-64. The disparity between Indigenous and non-Indigenous notification rates appeared higher in the Central Australia region. Indigenous versus non-Indigenous hospitalisation and mortality rate ratios were 6.51 (95% CI: 5.91, 7.18) and 5.46 (95% CI: 2.40, 12.71) respectively. Inter-seasonal peaks during February and March occurred in 2011, 2013 and 2014, and were due to influenza activity in the tropical north of the NT. Conclusions Our results highlight the importance of influenza vaccination across all age groups for Indigenous Australians. An early vaccination campaign targeted against outbreaks in February-March would be best focused on the tropical north.

Sheena G. Sullivan

Papers

Attitudes Towards Circumcision Among Chinese Men

The test-negative design for estimating influenza vaccination effectiveness

Detection of adamantane-sensitive influenza A(H3N2) viruses in Australia, 2017: a cause for hope?

Epidemiological trends in notified influenza cases in Australia's Northern Territory, 2007-2016.

Uptake, barriers and correlates of influenza vaccination among people who inject drugs in Australia.