Nery Sanchez - Academia.edu (original) (raw)
Papers by Nery Sanchez
medRxiv (Cold Spring Harbor Laboratory), Jun 18, 2022
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
The Journal of Infectious Diseases, Jul 16, 2020
Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent ... more Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent antibody responses. Methods This study examines the relationship between influenza symptoms and serological response. Influenza-positive index cases and household members in Managua, Nicaragua, during 2012–2017 were categorized by symptom status. Results Antibody response was assessed using hemagglutination inhibition assays (HAI). Among 510 cases, 74.5% had ≥4-fold increase in HAI antibodies, and 75.3% had febrile illness. In a logistic regression model, febrile cases had 2.17 times higher odds of a ≥4-fold titer rise compared to asymptomatic cases (95% confidence interval, 1.02–4.64). Conclusions Studies relying on serological assays may not generalize to asymptomatic infections.
Clinical Infectious Diseases, Sep 7, 2022
Background. Children constitute an important component of the influenza burden and community tran... more 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.
Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, ... more 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 l...
Influenza and Other Respiratory Viruses
BackgroundThe current SARS‐CoV‐2 pandemic highlights the need for an increased understanding of c... more BackgroundThe current SARS‐CoV‐2 pandemic highlights the need for an increased understanding of coronavirus epidemiology. In a pediatric cohort in Nicaragua, we evaluate the seasonality and burden of common cold coronavirus (ccCoV) infection and evaluate likelihood of symptoms in reinfections.MethodsChildren presenting with symptoms of respiratory illness were tested for each of the four ccCoVs (NL63, 229E, OC43, and HKU1). Annual blood samples collected before ccCoV infection were tested for antibodies against each ccCoV. Seasonality was evaluated using wavelet and generalized additive model (GAM) analyses, and age–period effects were investigated using a Poisson model. We also evaluate the risk of symptom presentation between primary and secondary infections.ResultsIn our cohort of 2576 children from 2011 to 2016, we observed 595 ccCoV infections and 107 cases of ccCoV‐associated lower respiratory infection (LRI). The overall incidence rate was 61.1 per 1000 person years (95% conf...
The Journal of Infectious Diseases
In their first season of vaccination, young children are recommended 2 doses of influenza vaccine... more In their first season of vaccination, young children are recommended 2 doses of influenza vaccine, but a 2-dose schedule might be difficult to implement in many countries. Within a cohort study of 742 children aged 6 to <24 months in Managua, Nicaragua, this study estimated effectiveness of partial vaccination from 3 to 9 months postvaccination. Vaccine effectiveness was 74% (95% confidence interval [CI], 24%–91%) within 3 months and 55% (95% CI, 10%–77%) within 4 months. There was not significant protection beyond 5 months. Partial vaccination might confer some benefits but should be followed by a second dose.
Background Human Metapneumovirus (hMPV) is an important cause of pediatric respiratory infection.... more 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 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 2011-2016 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 3,509 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 ...
International Journal of Infectious Diseases, 2020
PLOS Neglected Tropical Diseases, 2016
<p>The seroprevalence for each neighborhood was calculated using participants from both the... more <p>The seroprevalence for each neighborhood was calculated using participants from both the pediatric (2–14 years) and ≥15 year-old study populations. Seroprevalence levels were divided into four groups and color-coded, as shown in the legend key.</p
PLOS Neglected Tropical Diseases, 2016
<p>Demographic data of pediatric and ≥15 year-old participants, District II of Managua, Mar... more <p>Demographic data of pediatric and ≥15 year-old participants, District II of Managua, March–June 2015.</p
PLOS Neglected Tropical Diseases, 2016
<p>Prevalence and prevalence ratio of anti-CHIKV antibodies in participants aged 2–14 years... more <p>Prevalence and prevalence ratio of anti-CHIKV antibodies in participants aged 2–14 years, District II of Managua, March–April 2015.</p
Clinical Infectious Diseases
Background Children account for a large portion of global influenza burden and transmission, and ... more 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 ...
In this low-income country setting, ≈16% of household contacts acquired infections from index pat... more In this low-income country setting, ≈16% of household contacts acquired infections from index patients, despite high oseltamivir use.
Background Chikungunya, an arboviral disease, caused massive epidemics in Central and South Ameri... more Background Chikungunya, an arboviral disease, caused massive epidemics in Central and South America in 2014-2016. In a prospective pediatric cohort study, we examined the introduction of chikungunya in a naive population and investigated transmission and clinical characteristics. Methods Children presenting to the study health center with a chikungunya-like illness or undifferentiated fever were tested for chikungunya virus (CHIKV) infection by reverse transcriptase-polymerase chain reaction (RT-PCR) and serological assays. Inapparent CHIKV infections in the intervening year were determined by seroconversion in healthy blood samples collected annually. Results A total of 4353 children participated in the cohort study from March 2014 to February 2016 during the 2 epidemic waves of chikungunya. A total of 539 cases of chikungunya were documented, for an incidence rate of 80.2 cases per 1000 person-years (95% confidence interval [CI]: 73.7, 87.2); and a total of 893 CHIKV infections we...
Background: In recent years, tropical countries have faced consecutive explosive epidemics of chi... more Background: In recent years, tropical countries have faced consecutive explosive epidemics of chikungunya, Zika, and now COVID-19, each of which have featured large proportions of subclinical infections. Spatial studies of epidemics typically use case-only datasets to estimate incidence rates (cases/total population), often misinterpreting them as infection risks (infections/total population) or disease risks (cases/infected population). Methods: We examined these three measures in a pediatric cohort (N≈3,000) over two chikungunya epidemics and one Zika epidemic and in a household cohort (N=1,793) over one COVID-19 epidemic in Nicaragua. We used generalized additive models, the intra-cluster correlation coefficient, cluster detection analyses, geostatistical models, and spatiotemporal models to characterize the spatial epidemiology of each epidemic and examine the limitations of the case-only incidence rate. Results: Across analyses and all epidemics, case-based incidence rates cons...
Science Translational Medicine
Clinical Infectious Diseases
Background There are few data on the full spectrum of disease caused by severe acute respiratory ... more 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 t...
Science
The Zika pandemic sparked intense interest in whether immune interactions among dengue virus sero... more 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 challen...
Vaccines
More information about influenza in low- and middle-income countries could guide the establishmen... more More information about influenza in low- and middle-income countries could guide the establishment of pediatric influenza vaccine programs. This study (1) characterizes the burden of influenza in infants, and (2) compares signs and symptoms by prior influenza vaccination or influenza illness. Newborns from Managua, Nicaragua, were followed for two years. Data came from primary medical appointments, PCR testing, and parents’ daily symptom diaries. Logistic regression models estimated associations between preceding vaccination or illness and influenza incidence. Linear models compared duration of illness by prior vaccination or influenza illness. Among 833 infants, 31% had PCR-positive influenza, and 28% were vaccinated against influenza. Four (<0.5%) were fully vaccinated. Overall, influenza incidence was 21.0 (95% confidence interval (CI): 18.8, 23.2) per 100 person-years. Incidence was lower among those with prior influenza compared with those without preceding illness or vaccin...
medRxiv (Cold Spring Harbor Laboratory), Jun 18, 2022
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
The Journal of Infectious Diseases, Jul 16, 2020
Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent ... more Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent antibody responses. Methods This study examines the relationship between influenza symptoms and serological response. Influenza-positive index cases and household members in Managua, Nicaragua, during 2012–2017 were categorized by symptom status. Results Antibody response was assessed using hemagglutination inhibition assays (HAI). Among 510 cases, 74.5% had ≥4-fold increase in HAI antibodies, and 75.3% had febrile illness. In a logistic regression model, febrile cases had 2.17 times higher odds of a ≥4-fold titer rise compared to asymptomatic cases (95% confidence interval, 1.02–4.64). Conclusions Studies relying on serological assays may not generalize to asymptomatic infections.
Clinical Infectious Diseases, Sep 7, 2022
Background. Children constitute an important component of the influenza burden and community tran... more 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.
Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, ... more 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 l...
Influenza and Other Respiratory Viruses
BackgroundThe current SARS‐CoV‐2 pandemic highlights the need for an increased understanding of c... more BackgroundThe current SARS‐CoV‐2 pandemic highlights the need for an increased understanding of coronavirus epidemiology. In a pediatric cohort in Nicaragua, we evaluate the seasonality and burden of common cold coronavirus (ccCoV) infection and evaluate likelihood of symptoms in reinfections.MethodsChildren presenting with symptoms of respiratory illness were tested for each of the four ccCoVs (NL63, 229E, OC43, and HKU1). Annual blood samples collected before ccCoV infection were tested for antibodies against each ccCoV. Seasonality was evaluated using wavelet and generalized additive model (GAM) analyses, and age–period effects were investigated using a Poisson model. We also evaluate the risk of symptom presentation between primary and secondary infections.ResultsIn our cohort of 2576 children from 2011 to 2016, we observed 595 ccCoV infections and 107 cases of ccCoV‐associated lower respiratory infection (LRI). The overall incidence rate was 61.1 per 1000 person years (95% conf...
The Journal of Infectious Diseases
In their first season of vaccination, young children are recommended 2 doses of influenza vaccine... more In their first season of vaccination, young children are recommended 2 doses of influenza vaccine, but a 2-dose schedule might be difficult to implement in many countries. Within a cohort study of 742 children aged 6 to <24 months in Managua, Nicaragua, this study estimated effectiveness of partial vaccination from 3 to 9 months postvaccination. Vaccine effectiveness was 74% (95% confidence interval [CI], 24%–91%) within 3 months and 55% (95% CI, 10%–77%) within 4 months. There was not significant protection beyond 5 months. Partial vaccination might confer some benefits but should be followed by a second dose.
Background Human Metapneumovirus (hMPV) is an important cause of pediatric respiratory infection.... more 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 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 2011-2016 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 3,509 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 ...
International Journal of Infectious Diseases, 2020
PLOS Neglected Tropical Diseases, 2016
<p>The seroprevalence for each neighborhood was calculated using participants from both the... more <p>The seroprevalence for each neighborhood was calculated using participants from both the pediatric (2–14 years) and ≥15 year-old study populations. Seroprevalence levels were divided into four groups and color-coded, as shown in the legend key.</p
PLOS Neglected Tropical Diseases, 2016
<p>Demographic data of pediatric and ≥15 year-old participants, District II of Managua, Mar... more <p>Demographic data of pediatric and ≥15 year-old participants, District II of Managua, March–June 2015.</p
PLOS Neglected Tropical Diseases, 2016
<p>Prevalence and prevalence ratio of anti-CHIKV antibodies in participants aged 2–14 years... more <p>Prevalence and prevalence ratio of anti-CHIKV antibodies in participants aged 2–14 years, District II of Managua, March–April 2015.</p
Clinical Infectious Diseases
Background Children account for a large portion of global influenza burden and transmission, and ... more 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 ...
In this low-income country setting, ≈16% of household contacts acquired infections from index pat... more In this low-income country setting, ≈16% of household contacts acquired infections from index patients, despite high oseltamivir use.
Background Chikungunya, an arboviral disease, caused massive epidemics in Central and South Ameri... more Background Chikungunya, an arboviral disease, caused massive epidemics in Central and South America in 2014-2016. In a prospective pediatric cohort study, we examined the introduction of chikungunya in a naive population and investigated transmission and clinical characteristics. Methods Children presenting to the study health center with a chikungunya-like illness or undifferentiated fever were tested for chikungunya virus (CHIKV) infection by reverse transcriptase-polymerase chain reaction (RT-PCR) and serological assays. Inapparent CHIKV infections in the intervening year were determined by seroconversion in healthy blood samples collected annually. Results A total of 4353 children participated in the cohort study from March 2014 to February 2016 during the 2 epidemic waves of chikungunya. A total of 539 cases of chikungunya were documented, for an incidence rate of 80.2 cases per 1000 person-years (95% confidence interval [CI]: 73.7, 87.2); and a total of 893 CHIKV infections we...
Background: In recent years, tropical countries have faced consecutive explosive epidemics of chi... more Background: In recent years, tropical countries have faced consecutive explosive epidemics of chikungunya, Zika, and now COVID-19, each of which have featured large proportions of subclinical infections. Spatial studies of epidemics typically use case-only datasets to estimate incidence rates (cases/total population), often misinterpreting them as infection risks (infections/total population) or disease risks (cases/infected population). Methods: We examined these three measures in a pediatric cohort (N≈3,000) over two chikungunya epidemics and one Zika epidemic and in a household cohort (N=1,793) over one COVID-19 epidemic in Nicaragua. We used generalized additive models, the intra-cluster correlation coefficient, cluster detection analyses, geostatistical models, and spatiotemporal models to characterize the spatial epidemiology of each epidemic and examine the limitations of the case-only incidence rate. Results: Across analyses and all epidemics, case-based incidence rates cons...
Science Translational Medicine
Clinical Infectious Diseases
Background There are few data on the full spectrum of disease caused by severe acute respiratory ... more 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 t...
Science
The Zika pandemic sparked intense interest in whether immune interactions among dengue virus sero... more 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 challen...
Vaccines
More information about influenza in low- and middle-income countries could guide the establishmen... more More information about influenza in low- and middle-income countries could guide the establishment of pediatric influenza vaccine programs. This study (1) characterizes the burden of influenza in infants, and (2) compares signs and symptoms by prior influenza vaccination or influenza illness. Newborns from Managua, Nicaragua, were followed for two years. Data came from primary medical appointments, PCR testing, and parents’ daily symptom diaries. Logistic regression models estimated associations between preceding vaccination or illness and influenza incidence. Linear models compared duration of illness by prior vaccination or influenza illness. Among 833 infants, 31% had PCR-positive influenza, and 28% were vaccinated against influenza. Four (<0.5%) were fully vaccinated. Overall, influenza incidence was 21.0 (95% confidence interval (CI): 18.8, 23.2) per 100 person-years. Incidence was lower among those with prior influenza compared with those without preceding illness or vaccin...