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Background Approximately 15–25% of depressed patients suffer from difficult-to-treat depression (DTD). Patients with DTD require a thorough examination to avoid the oversight of treatable (psychiatric/somatic) comorbidities or (pseudo-)resistance to antidepressant drugs (ADs). Polymorphisms of the cytochrome P450 (CYP) enzymes 2D6 and 2C19, which play a major role in the metabolism of ADs, may contribute to resistance to ADs. Patients with DTD might benefit from electroconvulsive therapy (ECT). Methods We enrolled 109 patients with DTD and 29 untreated depressed controls (UDC). We assessed risk phenotypes, comorbidities, and treatment, including ECT. We also performed pharmacokinetic analyses of CYP2D6 and CYP2C19. Results DTD patients significantly more often suffered from comorbid psychiatric diseases, especially ICD-10: F40-F48 (DTD:40.4%, UDC:17.2%, OR 11.87, p =0.011) than UDC patients. DTD patients receiving ECT were more likely to achieve remission (37.7% vs. 11.8%, OR=3.96, p =0.023). Treatment with ADs did not differ between remitters and non-remitters. No significant differences were observed in the distribution of CYP2D6 and CYP2C19 variants between both groups. Conclusion Patients with DTD appear to experience comorbid neurotic stress and somatoform disorders (ICD-10: F40 – F48) more frequently. Therefore, a comprehensive differential diagnosis is crucial when patients do not respond sufficiently to antidepressant medication. Genotyping CYP2D6 and CYP2C19 should be considered. [ABSTRACT FROM AUTHOR]

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 Children constitute an important component of the influenza burden and community transmission, but the frequency of asymptomatic infection and post-influenza sequelae at the community level is poorly understood. Methods Two community-based prospective cohort studies (2011–2020, 2017–2020) and 1 case-ascertained study (2012–2017) were conducted in Managua, Nicaragua. Non-immunocompromised children aged 0–14 years with ≥1 influenza infections, determined by polymerase chain reaction and hemagglutination inhibition assay, were included. Results A total of 1272 influenza infections occurred in the household-based portion of the study. Influenza infection was asymptomatic in 84 (6.6%) infections, and the asymptomatic fraction increased with age (1.7%, 3.5%, and 9.1% for ages 0–1, 2–4, and 5–14, respectively; P <.001). Of asymptomatic children, 43 (51.2%) shed virus, compared to 1099 (92.5%) symptomatic children (P <.001). Also, 2140 cases of influenza occurred in the primary care portion of the study. Sequelae of influenza were rare, with the most common being pneumonia (52, 2.4%) and acute otitis media (71, 3.3%). A/H1N1 had higher age-adjusted odds of acute otitis media (odds ratio [OR] 1.99, 95% confidence interval [CI]: 1.14–3.48; P =.015) and hospitalization (OR 3.73, 95% CI: 1.68–8.67; P =.002) than A/H3N2. B/Victoria had higher age-adjusted odds of pneumonia (OR 10.99, 95% CI: 1.34–90.28; P =.026) than B/Yamagata. Conclusions Asymptomatic influenza infection is much less common in children than adults, although viral shedding still occurs in asymptomatic children. Post-influenza sequelae are rare in children in the community setting, and virus strain may be important in understanding the risk of sequelae. [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]