Longitudinal Analysis of the Burden of Post-Acute Chikungunya-Associated Arthralgia in Children and Adults: A Prospective Cohort Study in Managua, Nicaragua (2014-2019).

Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, but occasionally manifesting chronically. Little is known about differences in chikungunya-associated arthralgia comparing children to adults over time. To characterize long-term chikungunya-associated arthralgia, we recruited 770 patients (105 0-4 year olds [y/o], 200 5-9 y/o, 307 10-15 y/o, and 158 16+ y/o) with symptomatic chikungunya virus infections in Managua, Nicaragua, during two chikungunya epidemics (2014-2015). Participants were assessed at ~15 days and 1, 3, 6, 12, and 18 months post-fever onset. Following clinical guidelines, we defined participants by their last reported instance of arthralgia as acute (≤10 days post-fever onset), interim (>10 and <90 days), or chronic (≥90 days) cases. We observed a high prevalence of arthralgia (80-95%) across all ages over the study period. Overall, the odds of acute arthralgia increased in an age-dependent manner, with the lowest odds of arthralgia in the 0-4 y/o group (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.14-0.51) and the highest odds of arthralgia in the 16+ y/o participants (OR: 4.91, 95% CI: 1.42-30.95) relative to 10-15 y/o participants. Females had a higher odds of acute arthralgia than males (OR: 1.63, 95% CI: 1.01-2.65) across all ages. We found that 23-36% of pediatric and 53% of adult participants reported an instance of post-acute arthralgia. Children exhibited the highest prevalence of post-acute polyarthralgia in their legs, followed by the hands and torso - a pattern not seen among adult participants. Further, we observed pediatric chikungunya presenting in two distinct phases: the acute phase and the associated interim and chronic phases. Differences in the presentation of arthralgia were observed across age, sex, and disease phase in this longitudinal chikungunya cohort. Our results elucidate the long-term burden of chikungunya-associated arthralgia among pediatric and adult populations.

Homotypic protection against influenza in a pediatric cohort in Managua, Nicaragua.

The period of protection from repeat infection following symptomatic influenza is not well established due to limited availability of longitudinal data. Using data from a pediatric cohort in Managua, Nicaragua, we examine the effects of natural influenza virus infection on subsequent infection with the same influenza virus subtype/lineage across multiple seasons, totaling 2,170 RT-PCR-confirmed symptomatic influenza infections. Logistic regression models assessed whether infection in the prior influenza season protected against homologous reinfection. We sequenced viruses from 2011-2019 identifying dominant clades and measuring antigenic distances between hemagglutinin clades. We observe homotypic protection from repeat infection in children infected with influenza A/H1N1pdm (OR 0.12, CI 0.02-0.88), A/H3N2 (OR 0.41, CI 0.24-0.73), and B/Victoria (OR 0.00, CI 0.00-0.14), but not with B/Yamagata viruses (OR 0.60, CI 0.09-2.10). Overall, protection wanes as time or antigenic distance increases. Individuals infected with one subtype or lineage of influenza virus have significantly lower odds of homologous reinfection for the following one to two years; after two years this protection wanes. This protection is demonstrated across multiple seasons, subtypes, and lineages among children.

Clinical Spectrum of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Protection From Symptomatic Reinfection.

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.