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.

Immunogenicity, safety, and reactogenicity of a half- versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial.

Background: COVID-19 vaccine booster doses restore vaccine effectiveness lost from waning immunity and emerging variants. Fractional dosing may improve COVID-19 booster acceptability and uptake and will reduce the per-dose cost of COVID-19 booster programmes. We sought to quantify the immunogenicity, reactogenicity, and safety of a half-dose BNT162b2 (Pfizer-BioNTech) booster relative to the standard formulation. Methods: This randomised, controlled, non-inferiority trial recruited adults in Mongolia primed with a two-dose homologous ChAdOx1 nCov-19 (Oxford-AstraZeneca, n = 129 participants), BBIBP-CorV (Sinopharm (Beijing), n = 399), or Gam-COVID-Vac (Gamaleya, n = 70) schedule. Participants were randomised (1:1) to receive a 15 µg (half-dose) or 30 µg (full-dose) BNT162b2 booster. Participants and study staff assessing reactogenicity were blinded up to day 28. Co-primary endpoints were Wuhan-Hu-1 anti-spike S1 IgG seroresponse 28 days post-boosting and reactogenicity within 7 days of boosting. The non-inferiority margin for the absolute difference in seroresponse was -10%. Differences in seroresponse were estimated from logistic regression with marginal standardisation. Geometric mean ratios of IgG were also estimated. ClinicalTrials.gov Identifier: NCT05265065. Findings: Between May 27th and September 30th, 2022, 601 participants were randomized to full-dose BNT162b2 (n = 300) or half-dose (n = 301). 598 were included in safety analyses, and 587 in immunological analyses. The frequency of grade 3-4 reactions was similar between arms (half-dose: 4/299 [1.3%]; full-dose: 6/299 [2.0%]). Across all severity grades, half-dose recipients reported fewer local and systemic reactions (60% versus 72% and 25% versus 32%, respectively). Seroresponse was 84.7% (250/295) and 86.6% (253/292) in the half-dose and full-dose arms, respectively (Difference: -2.8%; 95% CI -7.7, 2.1). Geometric mean IgG titres were similar in those receiving full and half-dose boosters for the ChAdOx1 and BBIBP-CorV primed groups, but lower in the half-dose arm in Gam-COVID-Vac-primed participants (GMR: 0.71; 95% CI 0.54, 0.93). Interpretation: Half-dose BNT162b2 boosting elicited an immune response that was non-inferior to a full-dose, with fewer reactions, in adults primed with ChAdOx1 nCov-19 or BBIBP-CorV. Half-dose boosting may not be suitable in adults primed with Gam-COVID-Vac. Half-dose BNT162b2 boosting may be considered in populations primed with ChAdOx1 nCov-19 or BBIBP-CorV. Funding: Coalition for Epidemic Preparedness Innovations (CEPI).

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis.

Background: Few studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. Methods: We conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015-February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. Findings: The average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62.81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisation in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. Interpretation: We did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

RBD-specific antibody response after two doses of different SARS-CoV-2 vaccines during the mass vaccination campaign in Mongolia.

The SARS-CoV-2 vaccination campaign began in February 2021 and achieved a high rate of 62.7% of the total population fully vaccinated by August 16, 2021, in Mongolia. We aimed to assess the initial protective antibody production after two doses of a variety of types of SARS-CoV-2 vaccines in the Mongolian pre-vaccine antibody-naïve adult population. This prospective study was conducted from March-April to July-August of 2021. All participants received one of the four government-proposed COVID-19 vaccines including Pfizer/BioNTech (BNT162b2), AstraZeneca (ChAdOx1-S), Sinopharm (BBIBP-CorV), and Sputnik V (Gam-COVID-Vac). Before receiving the first shot, anti-SARS-CoV-2 S-RBD human IgG titers were measured in all participants (n = 1833), and titers were measured 21-28 days after the second shot in a subset of participants (n = 831). We found an overall average protective antibody response of 84.8% (705 of 831 vaccinated) in 21-28 days after two doses of the four types of COVID-19 vaccines. Seropositivity and titer of protective antibodies produced after two shots of vaccine were associated with the vaccine types, age, and residence of vaccinees. Seropositivity rate varied significantly between vaccine types, 80.0% (28 of 35) for AstraZeneca ChAdOx1-S; 97.0% (193 of 199) for Pfizer BNT162b2; 80.7% (474 of 587) for Sinopharm BBIBP-CorV, and 100.0% (10 of 10) for Sputnik V Gam-COVID-Vac, respectively. Immunocompromised vaccinees with increased risk for developing severe COVID-19 disease had received the Pfizer vaccine and demonstrated a high rate of seropositivity. A high geometric mean titer (GMT) was found in vaccinees who received BNT162b2, while vaccinees who received ChAdOx1-S, Sputnik V, and BBIBP-CorV showed a lower GMT. In summary, we observed first stages of the immunization campaign against COVID-19 in Mongolia have been completed successfully, with a high immunogenicity level achieved among the population with an increased risk for developing severe illness.

Molecular epidemiology of SARS-CoV-2 in Mongolia, first experience with nanopore sequencing in lower- and middle-income countries setting.

BACKGROUND: Coronavirus disease (COVID-19) has had a significant impact globally, and extensive genomic research has been conducted on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage patterns and its variants. Mongolia's effective response resulted in low prevalence until vaccinations became available. However, due to the lack of systematically collected data and absence of whole genome sequencing capabilities, we conducted a two-stepped, nationally representative molecular epidemiologic study of SARS-CoV-2 in Mongolia for 2020 and 2021. METHODS: We used retrospective analysis of stored biological samples from November 2020 to October 2021 and a variant-specific real-time reverse transcription polymerase chain reaction (RT-PCR) test to detect SARS-CoV-2 variants, followed by whole genome sequencing by Nanopore technology. Samples were retrieved from different sites and stored at -70°C deep freezer, and tests were performed on samples with cycle threshold <30. RESULTS: Out of 4879 nucleic acid tests, 799 whole genome sequencing had been carried out. Among the stored samples of earlier local transmission, we found the 20B (B.1.1.46) variant predominated in the earlier local transmission period. A slower introduction and circulation of alpha and delta variants were observed compared to global dynamics in 2020 and 2021. Beta or Gamma variants were not detected between November 2020 and September 2021 in Mongolia. CONCLUSIONS: SARS-CoV-2 variants of concerns including alpha and delta were delayed in circulation potentially due to public health stringencies in Mongolia. We are sharing our initial experience with whole genome sequencing of SARS-CoV-2 from Mongolia, where sequencing data is sparse.

Antibody responses to mRNA versus non-mRNA COVID vaccines among the Mongolian population.

Background: A nationwide vaccination program against coronavirus disease 2019 (COVID-19) was started in Mongolia 4 months after the first local transmission, which occurred in November 2020. Previous studies have reported that two doses of COVID-19 vaccine result in increased antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A study was conducted in Mongolia 2 weeks after the second vaccine dose. In the present study, the serum levels of antibodies of individuals 6 months after natural SARS-CoV-2 infection were compared with those of individuals who had not been infected or had been infected but had received two doses of vaccine, including BNT162b2, ChAdOx1 n-CoV-19, Gam-COVID-Vac, and BBIBP-CorV, which were used for COVID-19 in Mongolia. Methods: Of the 450 participants in this study, 237 (52.66%) were female and 213 (47.33%) were male. Four hundred people with or without SARS-CoV-2 infection who received two doses of 4 different COVID-19 vaccine participated in the vaccine groups and vaccine plus SARS-CoV-2 infection groups (50 in each group) and 50 individuals previously infected with SARS-CoV-2 participated in the unvaccinated group. Total antibody against SARS-CoV-2 infection, anti-SARS-CoV-2 N and S protein human IgG, and antibody inhibiting RBD-ACE2 binding were tested. Results: In the BNT162b2 vaccine group, total antibody against SARS-CoV-2 remained constant until 6 months, while the other vaccine groups showed a significant decrease, as compared to the unvaccinated group. The level of anti-SARS-CoV-2 S-RBD protein IgG was significantly increased in the ChAdOx1 n-CoV-19, Gam-COVID-Vac, and BNT162b2 vaccines groups as compared to the unvaccinated group. Participants in the BNT162b2 vaccine group had higher ACE2 inhibition efficiency compared to the other vaccine groups as well as the unvaccinated group. Conclusions: The BNT162b2 vaccine showed the highest level of antibody against SARS-CoV-2, followed by the BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 n-CoV-19 vaccines. The level of antibodies was increased in people infected with SARS-CoV-2 after vaccination, as compared to uninfected but vaccinated individuals.

Epidemiology of pneumonia in hospitalized adults ≥18 years old in four districts of Ulaanbaatar, Mongolia, 2015-2019.

Background: Community-acquired pneumonia is a leading cause of morbidity and mortality among children and adults worldwide. Adult pneumonia surveillance remains limited in many low- and middle-income settings, resulting in the disease burden being largely unknown. Methods: A retrospective cohort study was conducted by reviewing medical charts for respiratory admissions at four district hospitals in Ulaanbaatar during January 2015-February 2019. Characteristics of community-acquired pneumonia cases were summarized by disease severity and age. To explore factors associated with severe pneumonia, we ran univariable and age-adjusted logistic regression models. Incidence rates were calculated using population denominators. Results: In total, 4290 respiratory admissions met the case definition for clinical pneumonia, including 430 admissions of severe pneumonia. The highest proportion of severe pneumonia admissions occurred in adults >65 years (37.4%). After adjusting for age, there were increased odds of severe pneumonia in males (adjusted odds ratio [aOR]: 1.63; 95% confidence interval [CI]: 1.33-2.00) and those with ≥1 underlying medical condition (aOR: 1.46; 95% CI: 1.14-1.87). The incidence of hospitalized pneumonia in adults ≥18 years increased from 13.49 (95% CI: 12.58-14.44) in 2015 to 17.65 (95% CI: 16.63-18.71) in 2018 per 10,000 population. The incidence of severe pneumonia was highest in adults >65 years, ranging from 9.29 (95% CI: 6.17-13.43) in 2015 to 12.69 (95% CI: 9.22-17.04) in 2018 per 10,000 population. Interpretations: Vaccination and other strategies to reduce the risk of pneumonia, particularly among older adults and those with underlying medical conditions, should be prioritized. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

Sex-adjusted approach to baseline variables demonstrated some improved predictive capabilities for disease severity and survival in patients with Coronavirus Disease 19.

INTRODUCTION: The study was focused on comparing crude and sex-adjusted hazard ratio calculated by the baseline variables which may have contributed to the severity of the disease course and fatal outcomes in Coronavirus Disease-19 (COVID-19) patients. METHOD: The study enrolled 150 eligible adult patients with confirmed SARS-CoV-2 infection. There were 61 (40.7%) male patients, and 89 (59.3%) female patients. Baseline information of patients was collected from patient medical records and surveys that the patients had completed on admission to the hospital. RESULTS: Considerable number of baseline variables stratified according to disease severity and outcomes showed different optimal cut-points (OCP) in men and women. Sex-adjusted baseline data categories such as age; BMI; systolic and diastolic blood pressure; peripheral RBC and platelet counts; haematocrit; percentage of neutrophils, lymphocytes, monocytes, and their ratio; percentage of eosinophils; titre of plasma IL-6, IL-8, IL-10, and IL-17; and CXCL10; and ratio of pro- and anti-inflammatory cytokines demonstrated significant impacts on the development of the severe stage and fatal outcomes by the mean hazard ratio in the Kaplan-Meier and Cox regression models. CONCLUSION: This study confirmed some improved predictive capabilities of the sex-adjusted approach in the analysis of the baseline predictive variables for severity and outcome of the COVID-19.

Childhood Tuberculosis in Mongolia: Trends and Estimates, 2010-2030.

Mongolia was listed among the 30 countries with a high tuberculosis burden in 2021. Approximately 10-11% of the tuberculosis cases are of children, which is higher than the global average (6.0%). As children are a vulnerable population, it is important to understand the current situation and prioritize the development of tuberculosis prevention strategies. However, only few studies have addressed childhood tuberculosis in Mongolia. Therefore, we aimed to describe the characteristics of childhood tuberculosis and to show its trends and estimates in Mongolia. We performed descriptive and trend analyses on secondary data from the National Center for Communicable Diseases from 2010 to 2020. A total of 4,242 childhood tuberculosis cases, compiled from nine districts of the capital city and 21 provinces, were analyzed. We found that tuberculosis occurred more frequently in school-age children, and 71.8% of the all cases were an extrapulmonary tuberculosis. Trend analysis revealed that childhood tuberculosis continuously increased with fluctuations from 2018 onwards. The central region, including the capital city of Ulaanbaatar, is the most tuberculosis-burdened. Childhood tuberculosis is estimated to increase in the central region and decrease in the others from 2021 to 2030. Our findings showed that the national childhood tuberculosis trend is increasing, although there are differences in the pattern between regions. Further studies are needed to identify the determinant factors of regional differences, and age-specific public health interventions, such as scale-up screening and preventive treatment, are in demand in high-prevalence areas.

The effect of soluble E-selectin on tumor progression and metastasis.

BACKGROUND: Distant metastasis resulting from vascular dissemination of cancer cells is the primary cause of mortality from breast cancer. We have previously reported that E-selectin expression on the endothelial cell surface mediates shear-resistant adhesion and migration of circulating cancer cells via interaction with CD44. As a result of shedding, soluble E-selectin (sE-selectin) from the activated endothelium is present in the serum. In this study, we aimed to understand the role of sE-selectin in tumor progression and metastasis. METHODS: We investigated the effect of sE-selectin on shear-resistant adhesion and migration of metastatic breast cancer cells and leukocytes in vitro and in vivo. RESULTS: We found that sE-selectin promoted migration and shear-resistant adhesion of CD44(+) (/high) breast cancer cell lines (MDA-MB-231 and MDA-MB-468) to non-activated human microvessel endothelial cells (ES-HMVECs), but not of CD44(-/low) breast cancer cell lines (MCF-7 and T-47D). This endothelial E-selectin independent, sE-selectin-mediated shear-resistant adhesion was also observed in a leukocyte cell line (HL-60) as well as human peripheral blood mononuclear cells (PBMCs). Additionally, the incubation of MDA-MB-231 cells with sE-selectin triggered FAK phosphorylation and shear-resistant adhesion of sE-selectin-treated cells resulted in increased endothelial permeabilization. However, CD44 knockdown in MDA-MB-231 and HL-60 cells resulted in a significant reduction of sE-selectin-mediated shear-resistant adhesion to non-activated HMVECs, suggesting the involvement of CD44/FAK. Moreover, functional blockade of ICAM-1 in non-activated HMVECs resulted in a marked reduction of sE-selectin-mediated shear-resistant adhesion. Finally, the pre-incubation of CD44(+) 4 T1 murine breast cancer cells with sE-selectin augmented infiltration into the lung in E-selectin K/O mice and infusion of human PBMCs pre-incubated with sE-selectin stimulated MDA-MB-231 xenografted breast tumor growth in NSG mice. CONCLUSIONS: Our data suggest that circulating sE-selectin stimulates a broad range of circulating cells via CD44 and mediates pleiotropic effects that promote migration and shear-resistant adhesion in an endothelial E-selectin independent fashion, in turn accelerating tissue infiltration of leukocytes and cancer cells.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice.

The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100µg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500µg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions.