Introduction of New Dengue Virus Lineages of Multiple Serotypes after COVID-19 Pandemic, Nicaragua, 2022.

Major dengue epidemics throughout Nicaragua's history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

Effects on household income and earnings from chronic kidney disease of non-traditional origins: PREP project findings from Chichigalpa, Nicaragua.

OBJECTIVE: Our purpose with this study is to examine the socioeconomic outcomes associated with chronic kidney disease not related to well-known risk factors (CKDnt) in four communities in Chichigalpa, Nicaragua that are home to a substantial number of sugarcane workers. METHODS: We employed a cluster-based systematic sampling design to identify differences in outcomes between those households affected directly by CKDnt and those that are not. RESULTS: Overall, we find that approximately one-third of households surveyed had a household member diagnosed with CKDnt. 86% of CKDnt households reported that the head of the household had been without work for the last 6 months or more, compared with 53% of non-CKDnt households. Non-CKDnt households took in more than double the earnings income on average than CKDnt households ($C52 835 and $C3120, respectively). Nonetheless, on average, CKDnt households' total income exceeded that of non-CKDnt households due to Nicaragua's national Instituto Nicaraguense de Seguridad Social Social Security payments to CKDnt households, suggestive of a substantial economic burden on the state resulting from the disease. Households headed by widows or widowers who are widowed as a result of CKDnt demonstrate distinct deficits in total income when compared with either non-widowed households or to households widowed by causes other than CKDnt. CONCLUSIONS: Despite strong similarities in terms of demographic characteristics and despite residing in the same communities with similar access to the available resources, households experiencing CKDnt exhibit distinct and statistically significant differences in important socioeconomic outcomes when compared to non-CKDnt households.

Primary exposure to Zika virus is linked with increased risk of symptomatic dengue virus infection with serotypes 2, 3, and 4, but not 1.

Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on preexisting antibodies and infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) is associated with increased risk of DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by DENV1-4 in a pediatric Nicaraguan cohort. Of 3412 participants in 2022, 10.6% experienced dengue cases caused by DENV1 (n = 139), DENV4 (n = 133), DENV3 (n = 54), DENV2 (n = 9), or an undetermined serotype (n = 39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since last infection, and year, and repeat measurements were used to predict disease risk. Compared with flavivirus-naïve participants, primary ZIKV infection was associated with increased risk of disease caused by DENV4 (relative risk = 2.62, 95% confidence interval: 1.48 to 4.63) and DENV3 (2.90, 1.34 to 6.27), but not DENV1 infection. Primary DENV infection or DENV followed by ZIKV infection was also associated with increased risk of DENV4 disease. We reanalyzed 19 years of cohort data and demonstrated that prior flavivirus immunity and antibody titer had distinct associations with disease risk depending on incoming serotype. We thus find that prior ZIKV infection, like prior DENV infection, is associated with increased risk of disease with certain DENV serotypes. Cross-reactivity among flaviviruses should be considered when assessing vaccine safety and efficacy.

Association Between Acute Kidney Injury Hospital Visits and Environmental Heat Stress at a Nicaraguan Sugarcane Plantation.

BACKGROUND: Mesoamerican sugarcane cutters are at a high risk of chronic kidney disease of non-traditional origin, a disease likely linked to heat-related acute kidney injury (AKI). Studies in general populations have described a positive association between high environmental temperatures and clinically assessed kidney outcomes, but there are no studies in occupational settings. METHOD: We accessed routine records of clinically diagnosed AKI (AKI-CD) and wet bulb globe temperatures (WBGT) at a large Nicaraguan sugarcane plantation and modeled the relationship between these using negative binomial regression. A rest-shade-hydration intervention was gradually enhanced during the study period, and efforts were made to increase the referral of workers with suspected AKI to healthcare. RESULTS: Each 1°C WBGT was associated with an 18% (95% confidence interval [CI]: [4, 33%]) higher AKI-CD rate on the same day and a 14% (95% CI [-5, 37%]) higher rate over a week. AKI-CD rates and severity, and time between symptoms onset and diagnosis decreased during the study period, that is, with increasing rest-shade-hydration intervention. Symptoms and biochemical signs of systemic inflammation were common among AKI-CD cases. DISCUSSION: Occupational heat stress, resulting from heavy work in environmental heat, was associated with a higher rate of clinically diagnosed AKI in a population at risk of CKDnt. Promoting rest-shade-hydration may have contributed to reducing AKI rates during the study period. Occupational health and safety personnel have key roles to play in enforcing rest, shade, and hydration practices, referring workers with suspected AKI to healthcare as well as collecting and analyzing the data needed to support workplace heat stress interventions.

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.

Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua.

Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.

Enduring association between irritable bowel syndrome and war trauma during the Nicaragua civil war period: A population-based study.

BACKGROUND: Psychosocial and physical trauma are known risk factors for irritable bowel syndrome (IBS), including in war veterans, whereas war exposure in civilians is unclear. Nicaragua experienced two wars, 1970-1990: The Sandinistas Revolution (1970s) and The Contra War (1980s). Our aim was to investigate the role of exposure to war trauma in the subsequent development of IBS in the context of an established health surveillance system (11000 households). AIM: To investigate in a civilian population the relationship between exposure to war trauma and events and the subsequent development of IBS in the context of an established public health and demographic surveillance system in western Nicaragua. METHODS: We conducted a nested population-based, cross-sectional study focused on functional gastrointestinal disorders based on Rome II criteria. 1617 adults were randomly selected. The Spanish Rome II Modular Questionnaire and Harvard Trauma Questionnaire were validated in Nicaragua. War exposure was assessed with 10 measures of direct and indirect war trauma and post-war effects. Multiple exposures were defined by ≥ 3 measures. RESULTS: The prevalence of IBS was 15.2% [Female (F) 17.1%, Male (M) 12.0%], war exposure 19.3% (F 9.3%, M 36.7%), and post-traumatic stress disorder (PTSD) 5.6% (F 6.4%, M 4.3%). Significant associations with IBS in the civilian population were observed (adjusted by gender, age, socioeconomic status, education): physical and psychological abuse [adjusted odds ratio (aOR): 2.25; 95% confidence interval: 1.1-4.5], witnessed execution (aOR: 2.4; 1.1-5.2), family member death (aOR: 2.2; 1.2-4.2), and multiple exposures (aOR: 2.7; 1.4-5.1). PTSD was independently associated with IBS (aOR: 2.6; 1.2-5.7). CONCLUSION: An enduring association was observed in the Nicaragua civilian population between specific civil war-related events and subsequent IBS. Civilian populations in regions with extended armed conflict may warrant provider education and targeted interventions for patients.

Kidney disease characteristics, prevalence, and risk factors in León, Nicaragua: a population-based study.

BACKGROUND: CKD of unknown etiology (CKDu) disproportionately affects young people in Central America who lack traditional CKD risk factors (diabetes and hypertension) and has instead been variably linked to heat stress, occupational and environmental exposures, nephrotoxic medications, and/or genetic susceptibility. This study aimed to estimate the prevalence of CKD and identify risk factors for traditional CKD and CKDu in Nicaragua. METHODS: Surveys and assessment for CKD markers in urine and serum were performed in 15-59 year olds in households of the León municipality of Nicaragua. The survey included questions on demographics, health behaviors, occupation, and medical history. Participants with CKD were subdivided into traditional CKD and suspected CKDu based on history of diabetes, hypertension, or other specified conditions. A multinomial logistic regression model was used to identify factors associated with traditional CKD and suspected CKDu, compared to the non-CKD reference group. RESULTS: In 1795 study participants, CKD prevalence was 8.6%. Prevalence in males was twofold higher than females (12% vs 6%). Of those with CKD, 35% had suspected CKDu. Both traditional CKD and CKDu were associated with male sex and increasing age. Traditional CKD was associated with a family history of CKD, history of urinary tract infections, and lower socioeconomic status, while CKDu was associated with drinking well water and a lower body mass index. CONCLUSIONS: Both traditional CKD and CKDu are significant burdens in this region. Our study supports previous hypotheses of CKDu etiology and emphasizes the importance of CKD screening.

Phylodynamics of dengue virus 2 in Nicaragua leading up to the 2019 epidemic reveals a role for lineage turnover.

BACKGROUND: Dengue is a mosquito-borne viral disease posing a significant threat to public health. Dengue virus (DENV) evolution is often characterized by lineage turnover, which, along with ecological and immunological factors, has been linked to changes in dengue phenotype affecting epidemic dynamics. Utilizing epidemiologic and virologic data from long-term population-based studies (the Nicaraguan Pediatric Dengue Cohort Study and Nicaraguan Dengue Hospital-based Study), we describe a lineage turnover of DENV serotype 2 (DENV-2) prior to a large dengue epidemic in 2019. Prior to this epidemic, Nicaragua had experienced relatively low levels of DENV transmission from 2014 to 2019, a period dominated by chikungunya in 2014/15 and Zika in 2016. RESULTS: Our phylogenetic analyses confirmed that all Nicaraguan DENV-2 isolates from 2018 to 2019 formed their own clade within the Nicaraguan lineage of the Asian/American genotype. The emergence of the new DENV-2 lineage reflects a replacement of the formerly dominant clade presiding from 2005 to 2009, a lineage turnover marked by several shared derived amino acid substitutions throughout the genome. To elucidate evolutionary drivers of lineage turnover, we performed selection pressure analysis and reconstructed the demographic history of DENV-2. We found evidence of adaptive evolution by natural selection at the codon level as well as in branch formation. CONCLUSIONS: The timing of its emergence, along with a statistical signal of adaptive evolution and distinctive amino acid substitutions, the latest in the NS5 gene, suggest that this lineage may have increased fitness relative to the prior dominant DENV-2 strains. This may have contributed to the intensity of the 2019 DENV-2 epidemic, in addition to previously identified immunological factors associated with pre-existing Zika virus immunity.

Visual findings in children exposed to Zika in utero in Nicaragua.

Knowledge regarding the frequency of ocular abnormalities and abnormal visual function in children exposed to Zika virus (ZIKV) in utero but born without congenital Zika syndrome (CZS) is limited. We hypothesized that children exposed to ZIKV in utero born without CZS may have visual impairments in early childhood. We performed ophthalmic examination between 16 and 21 months of age and neurodevelopment assessment at 24 months of age with the Mullen Scales of Early Learning test (MSEL) on children enrolled in a cohort born to women pregnant during and shortly after the ZIKV epidemic in Nicaragua (2016-2017). ZIKV exposure status was defined based on maternal and infant serological testing. Visual impairment was defined as abnormal if the child had an abnormal ophthalmic exam and/or low visual reception score in the MSEL assessment. Of 124 children included in the analysis, 24 (19.4%) were classified as ZIKV-exposed and 100 (80.6%) unexposed according to maternal or cord blood serology. Ophthalmic examination showed that visual acuity did not differ significantly between groups, thus, 17.4% of ZIKV-exposed and 5.2% of unexposed had abnormal visual function (p = 0.07) and 12.5% of the ZIKV-exposed and 2% of the unexposed had abnormal contrast testing (p = 0.05). Low MSEL visual reception score was 3.2-fold higher in ZIKV-exposed than unexposed children, but not statistically significant (OR 3.2, CI: 0.8-14.0; p = 0.10). Visual impairment (a composite measure of visual function or low MESL visual reception score) was present in more ZIKV-exposed than in unexposed children (OR 3.7, CI: 1.2, 11.0; p = 0.02). However, the limited sample size warrants future investigations to fully assess the impact of in utero ZIKV exposure on ocular structures and visual function in early childhood, even in apparently healthy children.

Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018.

BACKGROUND: Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS: A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS: Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION: The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.

Antibody Immunity to Zika Virus among Young Children in a Flavivirus-Endemic Area in Nicaragua.

Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6-9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.

Infection-Induced Immunity Is Associated With Protection Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Decreased Infectivity.

BACKGROUND: The impact of infection-induced immunity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has not been well established. Here we estimate the effects of prior infection induced immunity in adults and children on SARS-CoV-2 transmission in households. METHODS: We conducted a household cohort study from March 2020-November 2022 in Managua, Nicaragua; following a housheold SARS-CoV-2 infection, household members are closely monitored for infection. We estimate the association of time period, age, symptoms, and prior infection with secondary attack risk. RESULTS: Overall, transmission occurred in 70.2% of households, 40.9% of household contacts were infected, and the secondary attack risk ranged from 8.1% to 13.9% depending on the time period. Symptomatic infected individuals were more infectious (rate ratio [RR] 21.2, 95% confidence interval [CI]: 7.4-60.7) and participants with a prior infection were half as likely to be infected compared to naïve individuals (RR 0.52, 95% CI:.38-.70). In models stratified by age, prior infection was associated with decreased infectivity in adults and adolescents (secondary attack risk [SAR] 12.3, 95% CI: 10.3, 14.8 vs 17.5, 95% CI: 14.8, 20.7). However, although young children were less likely to transmit, neither prior infection nor symptom presentation was associated with infectivity. During the Omicron era, infection-induced immunity remained protective against infection. CONCLUSIONS: Infection-induced immunity is associated with decreased infectivity for adults and adolescents. Although young children are less infectious, prior infection and asymptomatic presentation did not reduce their infectivity as was seen in adults. As SARS-CoV-2 transitions to endemicity, children may become more important in transmission dynamics.

Stressful life events among women living homeless in Nicaragua, a low-income country.

Nicaragua is one of the lowest income countries in Latin America, where there is a shortage of data on women living homeless. This paper analyses the types, timing and perceived causality of stressful life events (SLE) suffered both during childhood and adolescence and throughout life by women living homeless (n = 30). A structured interview was used to collect the data. Findings showed that women living homeless in Nicaragua suffered a very high number of SLEs, and that these were extremely severe and from very early ages. Most of the SLEs took place before the women became homeless. The SLEs suffered by the women interviewed in Nicaragua were largely similar to those seen in women living homeless in other cultural contexts with higher incomes, although it should be noted that those interviewed in Nicaragua had suffered a higher number of SLE during their childhood and adolescence. The women interviewed mainly attributed finding themselves homeless to having suffered SLEs in the family environment. The suffering of multiple and severe SLEs, largely leading to living in socioeconomically disadvantaged situations, seem to present a significant vulnerability factor both for becoming homeless and remaining homeless over time.

School Hearing Screening With a Portable, Tablet-Based, Noise-Attenuating Audiometric Headset in Rural Nicaragua.

OBJECTIVE: To investigate the utility and effectiveness of a noise-attenuating, tablet-based mobile health system combined with asynchronous telehealth evaluations for screening rural Nicaraguan schoolchildren for hearing loss. STUDY DESIGN: Prospective population-based survey. SETTING: Rural Nicaraguan communities. PATIENTS: There were 3,398 school children 7 to 9 years of age. INTERVENTIONS: Diagnostic automated and manual audiometry, detailed asynchronous telehealth evaluations. MAIN OUTCOME MEASURES: Referral rates, ambient noise levels, and audiometric results as well as hearing loss prevalence, types, and risk factors. RESULTS: Despite high ambient noise levels during screening (46.7 dBA), no effect of noise on referral rates on automated audiometry or confirmatory manual audiometry in those who failed automated testing was seen. The overall audiometric referral rate was 2.6%. Idiopathic sensorineural hearing loss (SNHL) and cerumen impaction were the most common types of hearing loss in this population with an estimated prevalence of hearing loss (all types) of 18.3 per 1,000 children. SNHL was associated with both drug exposure during pregnancy (p = 0.04) and pesticide exposure in the home (p = 0.03). CONCLUSION: Hearing screening using a tablet-based, noise-attenuating wireless headset audiometer is feasible and effective in rural low-resource environments with moderately elevated ambient noise levels. The referral rate with noise-attenuating headsets was much lower than that previous reports on this population. In addition, manual audiometry resulted in much lower referral rates than automated audiometry. The confirmed hearing loss rate in this study is comparable to reports from other low-income countries that use some form of noise attenuation during screening. Pesticide exposure and drug exposure during pregnancy are potential causes of SNHL in this population.

Pediatric burden and seasonality of human metapneumovirus over 5 years in Managua, Nicaragua.

BACKGROUND: Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children. METHODS: NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via real-time reverse-transcription polymerase chain reaction (RT-PCR). We used classical additive decomposition analysis to assess the temporal trends, and generalized growth models (GGMs) were used to estimate effective reproduction numbers. RESULTS: From 2011 to 2016, there were 564 hMPV symptomatic infections, yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3509 acute lower respiratory infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (rate ratio 5.5 95% CI 4.1, 7.4 p < 0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were detected reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011 to 2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4). CONCLUSIONS: Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.