Longitudinal analysis of post-acute chikungunya-associated arthralgia in children and adults: A prospective cohort study in Managua, Nicaragua (2014-2018).

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 years old [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 consecutive 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 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 subsequent interim/chronic phases. Thus, 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

Odds of progressing to chronic chikungunya-associated arthralgia after an initial presentation with only acute or interim chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).

Odds of progressing to chronic chikungunya-associated arthralgia after an initial presentation with only acute or interim chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).</p

Reported polyarthralgia beyond the acute phase of chikungunya associated-arthralgia by body part and age in year in Managua, Nicaragua (2014–2018).

Cluster dendrogram depicting the relationship between occurrence of polyarthralgia across the different body parts, with the y-axis representing the underlying cluster distance calculated using the Manhattan distance method. The cophenetic distance correlation coefficient is 0.95; the higher the cophenetic distance correlation coefficient is, the more appropriately the dendrogram represents a hierarchical structure present in the original data (A). Age trends of the prevalence of arthralgia among clustered body groups (B) and individual body parts (C), including the 95% confidence intervals, visualized using shading corresponding to each respective color group and depicted using a generalized additive model.</p

Density plot of participants stratified by age range in years in Managua, Nicaragua (2014–2018).

The percent of participants in this study across age are depicted using an age-density plot. Colors correspond to the age-ranges defined within the study (0–4, 5–9, 10–15, and 16+ years old). (TIF)</p

Prevalence of post-acute polyarthralgia by age and body part in Managua, Nicaragua (2014–2018).

Prevalence of post-acute polyarthralgia by age and body part in Managua, Nicaragua (2014–2018).</p

Hazards for chikungunya-associated arthralgia >10 days post-fever onset in Managua, Nicaragua (2014–2018).

Hazards for chikungunya-associated arthralgia >10 days post-fever onset in Managua, Nicaragua (2014–2018).</p

Risk factors for acute chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).

Risk factors for acute chikungunya-associated arthralgia in Managua, Nicaragua (2014–2018).</p

Prevalence of reports of arthralgia in the acute and post-acute phase in Managua, Nicaragua (2014–2018).

Prevalence of reports of arthralgia in the acute and post-acute phase in Managua, Nicaragua (2014–2018).</p

Kaplan-Meier plot showing the proportion of participants reporting arthralgia over time in years in Managua, Nicaragua (2014–2018).

A Kaplan-Meier graph plotting the proportion of participants not reporting arthralgia (y-axis) against days since fever onset (x-axis). Ticks correspond to censoring events. Panels show the distribution of participants beginning 10 days post-fever onset and ending at the last reported data point based on the exclusion criteria (< 625 days post-fever onset), stratified by age range (A) and sex (B). The p-values were calculated using the log-rank test.</p

Questionnaire for the Retrospective and Prospective Study of Clinical, Virological, and Immunological Characteristics of Chikungunya Cases in Nicaragua.

Questionnaire for the Retrospective and Prospective Study of Clinical, Virological, and Immunological Characteristics of Chikungunya Cases in Nicaragua.</p