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Background Children account for a large portion of global influenza burden and transmission, and a better understanding of influenza in children is needed to improve prevention and control strategies. Methods To examine the incidence and transmission of influenza we conducted a prospective community-based study of children aged 0–14 years in Managua, Nicaragua, between 2011 and 2019. Participants were provided with medical care through study physicians and symptomatic influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). Wavelet analyses were used to examine seasonality. Generalized growth models (GGMs) were used to estimate effective reproduction numbers. Results From 2011 to 2019, 3016 children participated, with an average of ∼1800 participants per year and median follow-up time of 5 years per child, and 48.3% of the cohort in 2019 had been enrolled their entire lives. The overall incidence rates per 100 person-years were 14.5 symptomatic influenza cases (95% confidence interval [CI]: 13.9–15.1) and 1.0 influenza-associated acute lower respiratory infection (ALRI) case (95% CI:.8–1.1). Symptomatic influenza incidence peaked at age 9–11 months. Infants born during peak influenza circulation had lower incidence in the first year of their lives. The mean effective reproduction number was 1.2 (range 1.02–1.49), and we observed significant annual patterns for influenza and influenza A, and a 2.5-year period for influenza B. Conclusions This study provides important information for understanding influenza epidemiology and informing influenza vaccine policy. These results will aid in informing strategies to reduce the burden of influenza. [ABSTRACT FROM AUTHOR]

Background: Much of the world's population has been infected with SARS‐CoV‐2. Thus, immunity from prior infection will play a critical role in future SARS‐CoV‐2 transmission. We investigated the impact of infection‐induced immunity on viral shedding duration and viral load. Methods: We conducted a household cohort study in Managua, Nicaragua, with an embedded transmission study that closely monitors participants regardless of symptoms. Real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity, respectively. Blood samples were collected twice annually and surrounding household intensive monitoring periods. We used accelerated failure time models to compare shedding times. Participants vaccinated ≥14 days prior to infection were excluded from primary analyses. Results: There were 600 RT‐PCR‐confirmed SARS‐CoV‐2 infections in unvaccinated participants between May 1, 2020, and March 10, 2022, with prior ELISA data. Prior infection was associated with 48% shorter shedding times (event time ratio [ETR] 0.52, 95% CI: 0.39–0.69, mean shedding: 13.7 vs. 26.4 days). A fourfold higher anti‐SARS‐CoV‐2 spike titer was associated with 17% shorter shedding (ETR 0.83, 95% CI: 0.78–0.90). Similarly, maximum viral loads (lowest cycle threshold [CT]) were lower for previously infected individuals (mean CT 29.8 vs. 28.0, p = 4.02 × 10−3), for adults and children ≥10 years, but not for children 0–9 years; there was little difference in CT levels for previously infected versus naïve adults aged above 60 years. Conclusions: Prior infection‐induced immunity was associated with shorter viral shedding and lower viral loads, which may be important in the transition from pandemic to endemicity. [ABSTRACT FROM AUTHOR]

Background There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings. Methods We followed 2338 people in Managua, Nicaragua, aged <94 years from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay. Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection. Results There was a large epidemic that peaked between March and August 2020. In total, 129 RT-PCR–positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% confidence interval [CI], 4.4–6.3). Seroprevalence was 56.7% (95% CI, 53.5%–60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were 2 deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2–seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic reinfection (95% CI, 51.1%–99.2%). Conclusions This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic reinfection. [ABSTRACT FROM AUTHOR]

Background Obesity has been shown to increase the risk of severe outcomes and death for influenza virus infections. However, we do not understand the influence of obesity on susceptibility to infection or on nonsevere influenza outcomes. Methods We performed a case-ascertained, community-based study of influenza transmission within households in Nicaragua. To investigate whether obesity increases the likelihood of influenza infection and symptomatic infection we used logistic regression models. Results Between 2015 and 2018, a total of 335 index cases with influenza A and 1506 of their household contacts were enrolled. Obesity was associated with increased susceptibility to symptomatic H1N1pdm infection among adults (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.08–4.06) but not children, and this association increased with age. Among adults with H1N1pdm infection, obesity was associated with increased likelihood of symptoms (OR, 3.91; 95% CI, 1.55–9.87). For middle-aged and older adults with obesity there was also a slight increase in susceptibility to any H1N1pdm infection (OR, 1.20; 95% CI,.62–2.34). Body mass index (BMI) was also linearly associated with increased susceptibility to symptomatic H1N1pdm infection, primarily among middle-aged and older women (5-unit BMI increase OR, 1.40; 95% CI, 1.00–1.97). Obesity was not associated with increased H3N2 susceptibility or associated symptoms. Conclusions We found that, among adults, obesity is associated with susceptibility to H1N1pdm infection and with symptoms associated with H1N1pdm infection, but not with susceptibility to H3N2 infection or associated symptoms. These findings will help target prevention efforts and therapeutics to this high-risk population. [ABSTRACT FROM AUTHOR]

Background Influenza causes a substantial burden worldwide, and current seasonal influenza vaccine has suboptimal effectiveness. To develop better, more broadly protective vaccines, a more thorough understanding is needed of how antibodies that target the influenza virus surface antigens, hemagglutinin (HA) (including head and stalk regions) and neuraminidase (NA), impact influenza illness and virus transmission. Methods We used a case-ascertained, community-based study of household influenza virus transmission set in Managua, Nicaragua. Using data from 170 reverse transcriptase–polymerase chain reaction (RT-PCR)–confirmed influenza virus A(H1N1)pdm infections and 45 household members with serologically confirmed infection, we examined the association of pre-existing NA, hemagglutination inhibiting, and HA stalk antibody levels and influenza viral shedding and disease duration using accelerated failure time models. Results Among RT-PCR–confirmed infections in adults, pre-existing anti-NA antibody levels ≥40 were associated with a 69% (95% confidence interval [CI], 34–85%) shortened shedding duration (mean, 1.0 vs 3.2 days). Neuraminidase antibody levels ≥80 were associated with further shortened shedding and significantly shortened symptom duration (influenza-like illness, 82%; 95% CI, 39–95%). Among RT-PCR–confirmed infections in children, hemagglutination inhibition titers ≥1:20 were associated with a 32% (95% CI, 13–47%) shortened shedding duration (mean, 3.9 vs 6.0 days). Conclusions Our results suggest that anti-NA antibodies play a large role in reducing influenza illness duration in adults and may impact transmission, most clearly among adults. Neuraminidase should be considered as an additional target in next-generation influenza virus vaccine development. We found that antibodies against neuraminidase were associated with significantly shortened viral shedding, and among adults they were also associated with shortened symptom duration. These results support neuraminidase as a potential target of next-generation influenza virus vaccines. [ABSTRACT FROM AUTHOR]

Immune responses against neuraminidase (NA) are of great interest for developing more robust influenza vaccines, but the role of anti-NA antibodies on influenza infectivity has not been established. We conducted household transmission studies in Managua, Nicaragua to examine the impact of anti-NA antibodies on influenza A/H3N2 susceptibility and infectivity. Analyzing these data with mathematical models capturing household transmission dynamics and their drivers, we estimated that having higher preexisting antibody levels against the hemagglutinin (HA) head, HA stalk, and NA was associated with reduced susceptibility to infection (relative susceptibility 0.67, 95% Credible Interval [CrI] 0.50-0.92 for HA head; 0.59, 95% CrI 0.42-0.82 for HA stalk; and 0.56, 95% CrI 0.40-0.77 for NA). Only anti-NA antibodies were associated with reduced infectivity (relative infectivity 0.36, 95% CrI 0.23-0.55). These benefits from anti-NA immunity were observed even among individuals with preexisting anti-HA immunity. These results suggest that influenza vaccines designed to elicit NA immunity in addition to hemagglutinin immunity may not only contribute to protection against infection but reduce infectivity of vaccinated individuals upon infection.