Modeling the impact of national and regional lockdowns on the 2020 spring wave of COVID-19 in France.

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like "where" and "when" still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increase. However, the public health costs associated with these delays tend to grow with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality, and stress on the healthcare system.

Evaluating the strategies to control SARS-CoV-2 Delta variant spread in New Caledonia, a zero-COVID country until September 2021.

Objectives: New Caledonia, a former zero-COVID country, was confronted with a SARS-CoV-2 Delta variant outbreak in September 2021. We evaluate the relative contribution of vaccination, lockdown, and timing of interventions on healthcare burden. Methods: We developed an age-stratified mathematical model of SARS-CoV-2 transmission and vaccination calibrated for New Caledonia and evaluated three alternative scenarios. Results: High virus transmission early on was estimated, with R0 equal to 6.6 (95% confidence interval [6.4-6.7]). Lockdown reduced R0 by 73% (95% confidence interval [70-76%]). Easing the lockdown increased transmission (39% reduction of the initial R0); but we did not observe an epidemic rebound. This contrasts with the rebound in hospital admissions (+116% total hospital admissions) that would have been expected in the absence of an intensified vaccination campaign (76,220 people or 34% of the eligible population were first-dose vaccinated during 1 month of lockdown). A 15-day earlier lockdown would have led to a significant reduction in the magnitude of the epidemic (-53% total hospital admissions). Conclusion: The success of the response against the Delta variant epidemic in New Caledonia was due to an effective lockdown that provided additional time for people to vaccinate. Earlier lockdown would have greatly mitigated the magnitude of the epidemic.

Household transmission of 2009 pandemic influenza A (H1N1) virus in the United States.

BACKGROUND: As of June 11, 2009, a total of 17,855 probable or confirmed cases of 2009 pandemic influenza A (H1N1) had been reported in the United States. Risk factors for transmission remain largely uncharacterized. We characterize the risk factors and describe the transmission of the virus within households. METHODS: Probable and confirmed cases of infection with the 2009 H1N1 virus in the United States were reported to the Centers for Disease Control and Prevention with the use of a standardized case form. We investigated transmission of infection in 216 households--including 216 index patients and their 600 household contacts--in which the index patient was the first case patient and complete information on symptoms and age was available for all household members. RESULTS: An acute respiratory illness developed in 78 of 600 household contacts (13%). In 156 households (72% of the 216 households), an acute respiratory illness developed in none of the household contacts; in 46 households (21%), illness developed in one contact; and in 14 households (6%), illness developed in more than one contact. The proportion of household contacts in whom acute respiratory illness developed decreased with the size of the household, from 28% in two-member households to 9% in six-member households. Household contacts 18 years of age or younger were twice as susceptible as those 19 to 50 years of age (relative susceptibility, 1.96; Bayesian 95% credible interval, 1.05 to 3.78; P=0.005), and household contacts older than 50 years of age were less susceptible than those who were 19 to 50 years of age (relative susceptibility, 0.17; 95% credible interval, 0.02 to 0.92; P=0.03). Infectivity did not vary with age. The mean time between the onset of symptoms in a case patient and the onset of symptoms in the household contacts infected by that patient was 2.6 days (95% credible interval, 2.2 to 3.5). CONCLUSIONS: The transmissibility of the 2009 H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms in a case patient.

Serial intervals and the temporal distribution of secondary infections within households of 2009 pandemic influenza A (H1N1): implications for influenza control recommendations.

A critical issue during the 2009 influenza A (H1N1) pandemic was determining the appropriate duration of time individuals with influenza-like illness (ILI) should remain isolated to reduce onward transmission while limiting societal disruption. Ideally this is based on knowledge of the relative infectiousness of ill individuals at each point during the course of the infection. Data on 261 clinically apparent pH1N1 infector-infectee pairs in households, from 7 epidemiological studies conducted in the United States early in 2009, were analyzed to estimate the distribution of times from symptom onset in an infector to symptom onset in the household contacts they infect (mean, 2.9 days, not correcting for tertiary transmission). Only 5% of transmission events were estimated to take place >3 days after the onset of clinical symptoms among those ill with pH1N1 virus. These results will inform future recommendations on duration of isolation of individuals with ILI.

SARS-CoV-2 transmission across age groups in France and implications for control.

The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups.

A modelling study investigating short and medium-term challenges for COVID-19 vaccination: From prioritisation to the relaxation of measures.

BACKGROUND: The roll-out of COVID-19 vaccines is a multi-faceted challenge whose performance depends on pace of vaccination, vaccine characteristics and heterogeneities in individual risks. METHODS: We developed a mathematical model accounting for the risk of severe disease by age and comorbidity, and transmission dynamics. We compared vaccine prioritisation strategies in the early roll-out stage and quantified the extent to which measures could be relaxed as a function of the vaccine coverage achieved in France. FINDINGS: Prioritizing at-risk individuals reduces morbi-mortality the most if vaccines only reduce severity, but is of less importance if vaccines also substantially reduce infectivity or susceptibility. Age is the most important factor to consider for prioritization; additionally accounting for comorbidities increases the performance of the campaign in a context of scarce resources. Vaccinating 90% of ≥65 y.o. and 70% of 18-64 y.o. before autumn 2021 with a vaccine that reduces severity by 90% and susceptibility by 80%, we find that control measures reducing transmission rates by 15-27% should be maintained to remain below 1000 daily hospital admissions in France with a highly transmissible variant (basic reproduction number R0  = 4). Assuming 90% of ≥65 y.o. are vaccinated, full relaxation of control measures might be achieved with a vaccine coverage of 89-100% in 18-64 y.o or 60-69% of 0-64 y.o. INTERPRETATION: Age and comorbidity-based vaccine prioritization strategies could reduce the burden of the disease. Very high vaccination coverage may be required to completely relax control measures. Vaccination of children, if possible, could lower coverage targets necessary to achieve this objective.

Couple oriented counselling improves male partner involvement in sexual and reproductive health of a couple: Evidence from the ANRS PRENAHTEST randomized trial.

BACKGROUND: Male partner involvement (MPI) has been recognized as a priority area to be strengthened in Prevention of Mother to Child Transmission (PMTCT) of HIV. We explored the impact of Couple Oriented Counselling (COC) in MPI in sexual and reproductive health and associated factors. METHOD: From February 2009 to October 2011, pregnant women were enrolled at their first antenatal care visit (ANC-1) and followed up until 6 months after delivery in the Mother and Child Center of the Chantal Biya Foundation within the randomized prenahtest multicentric trial. The MPI index was defined using sexual and reproductive health behaviour variables by using multiple correspondence analysis followed by mixed classification. Men were considered as highly involved if they had shared their HIV test results with their partner, had discussed on HIV or condom used, had contributed financially to ANC, had accompanied their wife to ANC or had practiced safe sex. Factors associated to MPI were investigated by the logistic model with GEE estimation approach. RESULTS: A total of 484 pregnant women were enrolled. The median age of the women was 27 years (IQR: 23-31) and 55.23% had a gestational age greater than 16 weeks at ANC-1. Among them, HIV prevalence was 11.9% (95% CI: 9.0-15.4). The median duration of the women's relationship with their partner was 84 months (IQR: 48-120). MPI index at 6 months after delivery was significantly greater in the COC group than the classical counselling group (14.8% vs 8,82%; p = 0,043; Fig 1). The partners of the women who participated in the COC were more likely to be involved during follow up than others (aOR = 1.45; 95% CI = 1.00-2.10). Partners with no incoming activity (aOR = 2.90; 95% CI = 1.96-4.29), who did not used violence within the couple (aOR = 1.70; 95% CI = 1.07-2.68), and whose partner came early for ANC-1 (aOR = 1.37; 95% CI = 1.00-1.89) were more likely to be involved than others. CONCLUSION: MPI remains low in stable couples and COC improves partner involvement. Our findings also support the need of strengthening outreach towards "stable" couples and addressing barriers. This could go a long way to improve PMTCT outcomes in Cameroon. TRIAL REGISTRATION: PRENAHTEST, NCT01494961. Registered 15 December 2011-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01494961.

Time lines of infection and disease in human influenza: a review of volunteer challenge studies.

The dynamics of viral shedding and symptoms following influenza virus infection are key factors when considering epidemic control measures. The authors reviewed published studies describing the course of influenza virus infection in placebo-treated and untreated volunteers challenged with wild-type influenza virus. A total of 56 different studies with 1,280 healthy participants were considered. Viral shedding increased sharply between 0.5 and 1 day after challenge and consistently peaked on day 2. The duration of viral shedding averaged over 375 participants was 4.80 days (95% confidence interval: 4.31, 5.29). The frequency of symptomatic infection was 66.9% (95% confidence interval: 58.3, 74.5). Fever was observed in 37.0% of A/H1N1, 40.6% of A/H3N2 (p = 0.86), and 7.5% of B infections (p = 0.001). The total symptoms scores increased on day 1 and peaked on day 3. Systemic symptoms peaked on day 2. No such data exist for children or elderly subjects, but epidemiologic studies suggest that the natural history might differ. The present analysis confirms prior expert opinion on the duration of viral shedding or the frequency of asymptomatic influenza infection, extends prior knowledge on the dynamics of viral shedding and symptoms, and provides original results on the frequency of respiratory symptoms or fever.

Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009.

BACKGROUND: Leptospirosis is an emerging but neglected public health challenge in the Asia/Pacific Region with an annual incidence estimated at 10-100 per 100,000 population. No accurate data, however, are available for at-risk rural Cambodian communities. METHOD: We conducted anonymous, unlinked testing for IgM antibodies to Leptospira spp. on paired sera of Cambodian patients <20 years of age between 2007-2009 collected through active, community-based surveillance for febrile illnesses in a convenience sample of 27 rural and semi-rural villages in four districts of Kampong Cham province, Cambodia. Leptospirosis testing was done on paired serological samples negative for Dengue, Japanese encephalitis and Chikungunya viruses after random selection. Convalescent samples found positive while initial samples were negative were considered as proof of acute infection. We then applied a mathematical model to estimate the risk of fever caused by leptospirosis, dengue or other causes in rural Cambodia. RESULTS: A total of 630 samples are coming from a randomly selected subset of 2358 samples. IgM positive were found on the convalescent serum sample, among which 100 (15.8%) samples were IgM negative on an earlier sample. Seventeen of these 100 seroconversions were confirmed using a Microagglutination Test. We estimated the probability of having a fever due to leptospirosis at 1. 03% (95% Credible Interval CI: 0. 95%-1. 22%) per semester. In comparison, this probability was 2. 61% (95% CI: 2. 55%, 2. 83%) for dengue and 17. 65% (95% CI: 17. 49%, 18. 08%) for other causes. CONCLUSION: Our data from febrile cases aged below 20 years suggest that the burden of leptospirosis is high in rural Cambodian communities. This is especially true during the rainy season, even in the absence of identified epidemics.

Closure of schools during an influenza pandemic.

In response to WHO raising the influenza pandemic alert level from phase five to phase six, health officials around the world are carefully reviewing pandemic mitigation protocols. School closure (also called class dismissal in North America) is a non-pharmaceutical intervention that is commonly suggested for mitigating influenza pandemics. Health officials taking the decision to close schools must weigh the potential health benefits of reducing transmission and thus case numbers against high economic and social costs, difficult ethical issues, and the possible disruption of key services such as health care. Also, if schools are expected to close as a deliberate policy option, or just because of high levels of staff absenteeism, it is important to plan to mitigate the negative features of closure. In this context, there is still debate about if, when, and how school closure policy should be used. In this Review, we take a multidisciplinary and holistic perspective and review the multiple aspects of school closure as a public health policy. Implications for the mitigation of the swine-origin influenza A H1N1 pandemic are also discussed.