Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia.

Objectives: Limited data indicate a beneficial effect of pneumococcal conjugate vaccines (PCVs) on respiratory syncytial virus (RSV) and influenza infections in young children. We evaluated the impact of 13-valent PCV (PCV13) introduction on the incidence of severe lower respiratory tract infections (LRTIs) associated with RSV or influenza in hospitalized children. Methods: Our study was restricted to children aged <2 years with arterial oxygen saturation <93% and children with radiologically confirmed pneumonia nested in a pneumonia surveillance project in four districts of Ulaanbaatar city, Mongolia. We tested nasopharyngeal swabs collected on admission for RSV and influenza using quantitative reverse transcription-polymerase chain reaction. The impact of PCV13 on the incidence of LRTI outcomes associated with RSV or with influenza for the period April 2015-March 2020 was estimated. Incidence rate ratios comparing pre- and post-vaccine periods were estimated for each outcome for each district using negative binomial models and for all districts combined with a mixed-effects negative binomial model. Adjusted models accounted for seasonality. Sensitivity analyses were conducted to assess the robustness of our findings. Results: Among 5577 tested cases, the adjusted incidence rate ratios showed a trend toward a reduction in RSV-associated outcomes: all LRTIs (0.77, 95% confidence interval [CI] 0.44-1.36), severe LRTIs (0.88, 95% CI 0.48-1.62), very severe LRTIs (0.76, 95% CI 0.42-1.38), and radiologically confirmed pneumonia (0.66, 95% CI 0.32-1.38) but inconsistent trends in outcomes associated with influenza. Conclusions: No significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction.

Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

The potential cost-effectiveness of HPV vaccination among girls in Mongolia.

Introduction: Cervical cancer is a leading cause of cancer among women in Mongolia with an age-standardized incidence rate of 23.5 per 100,000. HPV vaccination has not been introduced nationally and Gavi co-financing support is not available in Mongolia. Extended Gavi pricing for HPV vaccine may be available from vaccine manufacturers for a number of years. To inform introduction decision-making, we evaluated the potential cost-effectiveness of HPV vaccination among girls and young women in Mongolia. Methods: We used UNIVAC (version 1.4), a static decision model, to evaluate the health and economic outcomes of single-cohort vaccination among females from the government perspective compared to no vaccination. We modeled vaccine introduction over 10 birth cohorts starting in 2022 comparing quadrivalent or bivalent vaccine selection and vaccine pricing variations. We used locally-specific data for cancer incidence, mortality, treatment and costs. Model outcomes included cancer cases, hospitalizations, deaths, disability-adjusted life years (DALY), and costs presented in 2018 USD. Incremental costs and health outcomes were discounted at 3% and aggregated into an Incremental Cost-Effectiveness Ratio (ICER). Results: The base-case scenario of HPV vaccination among 9 year-old girls was projected to avert 5,692 cervical cancer cases, 3,240 deaths, and 11,886 DALYs and incur $2.4-3.1M more costs compared to no vaccination. At prices of ($4.50-$4.60/dose), we estimated an ICER of $166-$265/DALY averted among 9-year-olds. When price per dose was increased to reported mean vaccine purchase price for non-Gavi LMICs ($14.17/dose), the ICER ranged from $556-820/DALY averted. Conclusion: HPV vaccination among girls is highly likely to be a cost-effective investment in Mongolia compared to no vaccination with projected ICERs less than 20% of the 2018 GDP per capita of $3,735.

Epidemiology of pneumonia in the pre-pneumococcal conjugate vaccine era in children 2-59 months of age, in Ulaanbaatar, Mongolia, 2015-2016.

BACKGROUND: Respiratory diseases, including pneumonia, are the second largest cause of under-five mortality in Mongolia and the most common cause of childhood hospitalization. However information regarding the contribution of Streptococcus pneumoniae to pneumonia causation in Mongolia is limited. We aimed to describe the epidemiology of hospitalized children aged 2-59 months with pneumonia, enrolled into a surveillance program in the period prior to pneumococcal conjugate vaccine (PCV) introduction, in Mongolia. METHODS: An expanded pneumonia surveillance program enrolled children, who met the surveillance case definition, at participating hospitals, between April 2015 and May 2016. Cumulative incidence rates were calculated by district for all pneumonia endpoints using district specific denominators from the Mongolian Health Department census for 2016. Socio-economic and disease-associated factors were compared between districts using chi-squared tests. RESULTS: A total of 4318 eligible children with pneumonia were enrolled over the 14 month period. Overall the incidence for all-cause pneumonia in children aged 12-59 months was 31.8 per 1000 population; children aged 2-11 months had an almost four-fold higher incidence than children aged 12-59 months. Differences were found between districts with regards to housing type, fuel used for cooking, hospital admission practices and the proportions of severe and primary endpoint pneumonia. DISCUSSION: This study shows a high burden of pneumonia in children aged 2-59 months in Mongolia prior to PCV introduction. Rates differed somewhat by district and age group and were influenced by a number of socio-economic factors. It will be important to consider these differences and risk factors when assessing the impact of PCV introduction.

Pneumococcal carriage in children in Ulaanbaatar, Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Nasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia. METHODS: We conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5-8 weeks old) and 989 children eligible for vaccination (12-23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray. FINDINGS: One year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12-23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39-0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30-1.85]), compared with the pre-PCV period. In 5-8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33-0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83-1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed. CONCLUSION: This study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring.

Increase in Infant Measles Deaths During a Nationwide Measles Outbreak-Mongolia, 2015-2016.

BACKGROUND: Surveillance data from a large measles outbreak in Mongolia suggested increased case fatality ratio (CFR) in the second of 2 waves. To confirm the increase in CFR and identify risk factors for measles death, we enhanced mortality ascertainment and conducted a case-control study among infants hospitalized for measles. METHODS: We linked national vital records with surveillance data of clinically or laboratory-confirmed infant (aged <12 months) measles cases with rash onset during March-September 2015 (wave 1) and October 2015-June 2016 (wave 2). We abstracted medical charts of 95 fatal cases and 273 nonfatal cases hospitalized for measles, matched by age and sex. We calculated adjusted matched odds ratios (amORs) and 95% confidence intervals (CIs) for risk factors. RESULTS: Infant measles deaths increased from 3 among 2224 cases (CFR: 0.13%) in wave 1 to 113 among 4884 cases (CFR: 2.31%) in wave 2 (P < .001). Inpatient admission, 7-21 days before measles rash onset, for pneumonia or influenza (amOR: 4.5; CI, 2.6-8.0), but not other diagnoses, was significantly associated with death. DISCUSSION: Measles infection among children hospitalized with respiratory infections likely increased deaths due to measles during wave 2. Preventing measles virus nosocomial transmission likely decreases measles mortality.

Projected impact, cost-effectiveness, and budget implications of rotavirus vaccination in Mongolia.

INTRODUCTION: Rotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country's limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction. METHODS: The analysis examines the use of the two-dose vaccine ROTARIX®, and three-dose vaccines ROTAVAC® and RotaTeq® compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis. RESULTS: Rotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10 years. Averted visits and hospitalizations represent US$2.4 million in health care costs saved by the government. The vaccination program cost ranges from $6 to $11 million depending on vaccine choice. From the governmental perspective, ICER ranged from $412 to $1050 and from $77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty. CONCLUSION: Introduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia's per capita GDP. From an economic standpoint, ROTAVAC® is the least costly and most cost-effective product choice.

Hospital-based surveillance for rotavirus diarrhea in Ulaanbaatar, Mongolia, April 2009 through March 2016.

BACKGROUND: Diarrheal disease is one of the leading causes of illness and death in young children in the world, especially the developing countries. Diarrheal disease results in about half a million childhood death per year, ranking second among all causes worldwide. Diarrheal disease due to rotavirus infection is currently the most common cause of severe diarrhea in infants and young children worldwide. Rotavirus immunization of infants is a safe and effective public health intervention for rotavirus infection control and expected to lead to a reduction of childhood morbidity and mortality. METHODS: We conducted hospital-based surveillance at two representative hospitals in Mongolia to estimate the burden of hospitalizations for rotavirus diarrhea among children aged <5 years and to describe strain distribution patterns during 6-year study period. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay (EIA). Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS: Between April 2009 and March 2016, among 7076 eligible children with diarrhea 6078 patients were enrolled nationally. Forty-six percent (2794/6078) of EIA a specimens were positive for rotavirus. Ninety-three percent (5649/6078) of hospitalizations for diarrhea involved children less than 2 years. No deaths were recorded due to rotavirus diarrhea. The most common genotype was G3P [8] (47.7%) followed by G9P [6] (14.4%), G2P [4] (12%), and G9P [8] (7.1%). CONCLUSIONS: This study found a relatively high prevalence of severe rotavirus-associated diarrhea disease in Mongolia and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program. Continued surveillance is crucial and pre-vaccine introduction rotavirus genotype patterns in Mongolia are valuable and can be followed post-introduction to assess vaccine impact.

Use of a Diagonal Approach to Health System Strengthening and Measles Elimination after a Large Nationwide Outbreak in Mongolia.

Measles is a highly transmissible infectious disease that causes serious illness and death worldwide. Efforts to eliminate measles through achieving high immunization coverage, well-performing surveillance systems, and rapid and effective outbreak response mechanisms while strategically engaging and strengthening health systems have been termed a diagonal approach. In March 2015, a large nationwide measles epidemic occurred in Mongolia, 1 year after verification of measles elimination in this country. A multidisciplinary team conducted an outbreak investigation that included a broad health system assessment, organized around the Global Health Security Agenda framework of Prevent-Detect-Respond, to provide recommendations for evidence-based interventions to interrupt the epidemic and strengthen the overall health system to prevent future outbreaks of measles and other epidemic-prone infectious threats. This investigation demonstrated the value of evaluating elements of the broader health system in investigating measles outbreaks and the need for using a diagonal approach to achieving sustainable measles elimination.