The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

Unexpectedly, cross-reactive antibodies are stable or rise after primary dengue and Zika virus infection and wane slowly after secondary infection.

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 Background Obesity has been shown to increase the risk of severe outcomes and death for influenza virus infections. However, we don’t understand the influence of obesity on susceptibility to infection or on non-severe 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 use logistic regression models. Results Between 2015 and 2018, a total of 335 index cases with influenza A and 1,506 of their household contacts were enrolled. Obesity was associated with increased susceptibility to symptomatic H1N1pdm infection among adults (OR: 2.10, 95%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: 0.62-2.34). Body Mass Index (BMI) was also linearly associated with increased susceptibility to symptomatic H1N1pdm infection, primarily among middle aged and older adult 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.

Background Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. Methods We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0-14 years from 2011-2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness (IMCI) guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian non-linear survival model to estimate pneumonia hazard following influenza. Results Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR]: 2.7, 95% CI: 1.9, 3.9). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR: 3.7, 95% CI: 2.0, 6.9), followed by influenza B, and A(H3N2). Participants’ odds of pneumonia following influenza were not constant, showing distinct peaks 0-6 days (mOR: 8.3, 95% CI: 4.8, 14.5) and 14-20 (mOR: 2.5, 95% CI: 1.1, 5.5) days post influenza infection. Conclusions Influenza is a significant driver of both primary and secondary pneumonia among children. Distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.