Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study.

BACKGROUND: Community-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia. METHODS: PCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019. DISCUSSION: Establishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.

Influenza epidemiology and burden of disease in Mongolia, 2013-2014 to 2017-2018.

BACKGROUND: Mongolia is a vast, sparsely populated country in central Asia. Its harsh climate and nomadic lifestyle make the population vulnerable to acute respiratory infections, particularly influenza. Evidence on the morbidity, mortality and socioeconomic impact of influenza in Mongolia is scarce; however, routine surveillance for influenza-like illness (ILI), severe acute respiratory infection (SARI) and laboratory-detected influenza is conducted. This paper describes the epidemiology of influenza and the estimated burden of influenza-associated illness in Mongolia in the five influenza seasons between 2013-2014 and 2017-2018. METHODS: Demographic and laboratory data from 152 sentinel surveillance sites on all patients who met the case definitions of ILI and SARI between October 2013 and May 2018 were extracted and analysed as described in A Manual for Estimating Disease Burden Associated with Seasonal Influenza. RESULTS: The estimated annual influenza-associated ILI and SARI rates, presented as ranges, were 1279-2798 and 81-666 cases per 100 000 population, respectively. Children aged < 5 years accounted for 67% of all ILI cases and 79% of all SARI cases. The annual specimen positivity for influenza was highest (11-30% for ILI and 8-31% for SARI) for children aged 5- < 15 years and children < 2 years old, respectively. The annual mortality rate due to pneumonia and SARI was highest among children aged < 2 years (15.8-54.0 per 100 000 population). Although the incidence of influenza-associated ILI and SARI was lowest for people aged 365 years, the mortality rate due to pneumonia and SARI (1.2-5.1 per 100 000) was higher than that for those aged 15-64 years. CONCLUSION: The estimated influenza-associated ILI and SARI incidence rates are high in Mongolia, and children, especially those aged < 5 years, have the highest influenza-associated burden in Mongolia. These findings provide evidence for decision-makers in Mongolia to consider targeted influenza vaccination, particularly for children.

Little evidence of avian or equine influenza virus infection among a cohort of Mongolian adults with animal exposures, 2010-2011.

Avian (AIV) and equine influenza virus (EIV) have been repeatedly shown to circulate among Mongolia's migrating birds or domestic horses. In 2009, 439 Mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. Sera were drawn upon enrollment and again at 12 and 24 months. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members confirmed to have acute influenza A infections, permitted respiratory swab collections which were studied with rRT-PCR for influenza A. Serologic assays were performed against equine, avian, and human influenza viruses. Over the 2 yrs of follow-up, 100 ILI investigations in the cohort were conducted. Thirty-six ILI cases (36%) were identified as influenza A infections by rRT-PCR; none yielded evidence for AIV or EIV. Serological examination of 12 mo and 24 mo annual sera revealed 37 participants had detectable antibody titers (≥1∶10) against studied viruses during the course of study follow-up: 21 against A/Equine/Mongolia/01/2008(H3N8); 4 against an avian A/Teal/Hong Kong/w3129(H6N1), 11 against an avian-like A/Hong Kong/1073/1999(H9N2), and 1 against an avian A/Migrating duck/Hong Kong/MPD268/2007(H10N4) virus. However, all such titers were <1∶80 and none were statistically associated with avian or horse exposures. A number of subjects had evidence of seroconversion to zoonotic viruses, but the 4-fold titer changes were again not associated with avian or horse exposures. As elevated antibodies against seasonal influenza viruses were high during the study period, it seems likely that cross-reacting antibodies against seasonal human influenza viruses were a cause of the low-level seroreactivity against AIV or EIV. Despite the presence of AIV and EIV circulating among wild birds and horses in Mongolia, there was little evidence of AIV or EIV infection in this prospective study of Mongolians with animal exposures.

Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures.

In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2·1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population-based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine influenza virus strains. Seroreactivity was sparse among participants suggesting little human risk of zoonotic influenza infection.

Influenza transmission in a community during a seasonal influenza A(H3N2) outbreak (2010-2011) in Mongolia: a community-based prospective cohort study.

BACKGROUND: Knowledge of how influenza viruses spread in a community is important for planning and implementation of effective interventions, including social distancing measures. Households and schools are implicated as the major sites for influenza virus transmission. However, the overall picture of community transmission is not well defined during actual outbreaks. We conducted a community-based prospective cohort study to describe the transmission characteristics of influenza in Mongolia. METHODS AND FINDINGS: A total of 5,655 residents in 1,343 households were included in this cohort study. An active search for cases of influenza-like illness (ILI) was performed between October 2010 and April 2011. Data collected during a community outbreak of influenza A(H3N2) were analyzed. Total 282 ILI cases occurred during this period, and 73% of the subjects were aged <15 years. The highest attack rate (20.4%) was in those aged 1-4 years, whereas the attack rate in those aged 5-9 years was 10.8%. Fifty-one secondary cases occurred among 900 household contacts from 43 households (43 index cases), giving an overall crude household secondary attack rate (SAR) of 5.7%. SAR was significantly higher in younger household contacts (relative risk for those aged <1 year: 9.90, 1-4 years: 5.59, and 5-9 years: 6.43). We analyzed the transmission patterns among households and a community and repeated transmissions were detected between households, preschools, and schools. Children aged 1-4 years played an important role in influenza transmission in households and in the community at large. Working-age adults were also a source of influenza in households, whereas elderly cases (aged ≥ 65 years) had no link with household transmission. CONCLUSIONS: Repeated transmissions between households, preschools, and schools were observed during an influenza A(H3N2) outbreak period in Mongolia, where subjects aged 1-4 years played an important role in influenza transmission.

Evaluating influenza disease burden during the 2008-2009 and 2009-2010 influenza seasons in Mongolia.

It is critical to monitor the incidence and clinical characteristics of influenza and its associated hospitalization to understand influenza disease burden. A disease burden study can inform the prioritization of a public health response. However, little is known about the epidemiology and disease burden of influenza in developing countries, including Mongolia. Thus we performed prospective data and sample collection from patients who visited outpatient clinics with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infections (SARI) in two sites of Mongolia, Baganuur District of Ulaanbaatar and Selenghe Province, from 2008 to 2010. In total, we examined 350 ILI cases during the 2008-2009 influenza epidemic period and 1723 ILI cases during the 2009-2010 influenza epidemic period. We observed the highest ILI incidence per 1000 population in the one to four year age group in Baganuur and in the under one year age group in Selenghe during both periods. Thirteen SARI cases were positive for seasonal influenza A(H1N1) during the 2008-2009 season and 17 SARI cases were positive for pandemic influenza A(H1N1) 2009 during the 2009-2010 season. Among these cases, 84.6% and 58.8% were children under five years of age, respectively, during the 2008-2009 and 2009-2010 seasons. Taken together, children, especially children under five years, had higher influenza infection incidence and hospitalization rate in Mongolia. Although mortality impact also should be considered, we believe that our findings can be useful in formulating an influenza control strategy during influenza epidemic periods in Mongolia.

Evaluating influenza disease burden during the 2008–2009 and 2009–2010 influenza seasons in Mongolia

It is critical to monitor the incidence and clinical characteristics of influenza and its associated hospitalization to understand influenza disease burden. A disease burden study can inform the prioritization of a public health response. However, little is known about the epidemiology and disease burden of influenza in developing countries, including Mongolia. Thus we performed prospective data and sample collection from patients who visited outpatient clinics with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infections (SARI) in two sites of Mongolia, Baganuur District of Ulaanbaatar and Selenghe Province, from 2008 to 2010. In total, we examined 350 ILI cases during the 2008–2009 influenza epidemic period and 1723 ILI cases during the 2009–2010 influenza epidemic period. We observed the highest ILI incidence per 1000 population in the one to four year age group in Baganuur and in the under one year age group in Selenghe during both periods. Thirteen SARI cases were positive for seasonal influenza A(H1N1) during the 2008–2009 season and 17 SARI cases were positive for pandemic influenza A(H1N1) 2009 during the 2009–2010 season. Among these cases, 84.6% and 58.8% were children under five years of age, respectively, during the 2008–2009 and 2009–2010 seasons. Taken together, children, especially children under five years, had higher influenza infection incidence and hospitalization rate in Mongolia. Although mortality impact also should be considered, we believe that our findings can be useful in formulating an influenza control strategy during influenza epidemic periods in Mongolia.