Paediatrics (RCH) - Research Publications

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    Epidemiology of pneumonia in hospitalized adults ≥18 years old in four districts of Ulaanbaatar, Mongolia, 2015-2019.
    Fagerli, K ; Ulziibayar, M ; Suuri, B ; Luvsantseren, D ; Narangerel, D ; Batsaikhan, P ; Tsolmon, B ; Gessner, BD ; Dunne, EM ; Grobler, AC ; Nguyen, CD ; Mungun, T ; Mulholland, EK ; von Mollendorf, C (Elsevier BV, 2023-01)
    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).
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    Aetiology of childhood pneumonia in low-and middle-income countries in the era of vaccination: a systematic review
    von Mollendorf, C ; Berger, D ; Gwee, A ; Duke, T ; Graham, SM ; Russell, FM ; Mulholland, EK (INT SOC GLOBAL HEALTH, 2022)
    BACKGROUND: This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries. METHODS: We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830]. RESULTS: We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis. CONCLUSIONS: Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.
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    Exploring the Possible Cause of the Dramatic Increase in Measles Mortality During the 2015-2016 Mongolian Outbreak
    Do, LAH ; Tsedenbal, N ; von Mollendorf, C ; Mungun, T ; Bardach, D ; Mulholland, K (OXFORD UNIV PRESS INC, 2021-10-01)
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    Direct and indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with pneumonia from formal and informal settlements in Mongolia: an observational study
    Chan, J ; Mungun, T ; Batsaixan, P ; Ulziibayar, M ; Suuri, B ; Otgonbayar, D ; Luvsantseren, D ; Nguyen, CD ; Narangarel, D ; Dunne, EM ; Fox, K ; Hinds, J ; Nation, ML ; Pell, CL ; Mulholland, EK ; Satzke, C ; von Mollendorf, C ; Russell, FM (ELSEVIER, 2021-10)
    BACKGROUND: Within Ulaanbaatar, Mongolia, risk factors for pneumonia are concentrated among children living in informal settlements comprised of temporary shelters (gers). We used pneumococcal carriage surveillance among children from formal and informal settlements hospitalised with pneumonia to evaluate the direct and indirect effects of 13-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) pneumococcal carriage following a phased introduction of PCV13. METHODS: We enrolled and collected nasopharyngeal swabs from children 2-59 months of age presenting to hospital. Pneumococci were detected using lytA qPCR and serotyped using microarray on a random monthly selection of swabs between November 2015 and March 2019 from two districts in Ulaanbaatar. PCV13 status was determined using written records. We quantified the associations between individual PCV13 status (direct effects) and district-level PCV13 coverage (indirect effects) and VT carriage using generalised estimating equations and explored interactions by settlement type. FINDINGS: A total of 1 292 swabs from 6 046 participants were tested for pneumococci. Receipt of PCV13 and increasing PCV13 coverage independently reduced the risk of VT carriage. For each percent increase in PCV13 coverage, the adjusted odds of VT carriage decreased by 1•0% (OR 95% CI 0•983-0•996; p=0•001), with a predicted decrease in VT carriage rate from 29•1% to 13•1% as coverage reached 100%. There was a trend towards a slower decline within informal settlements (p=0•100). Adjusted PCV13 vaccine effectiveness against VT carriage was 39•1% (95% CI 11•4-58•1%, p=0•009). INTERPRETATION: Substantial indirect effects were observed following PCV13 introduction, including among children living within informal settlements. FUNDING: Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance.
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    Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned
    La Vincente, SF ; von Mollendorf, C ; Ulziibayar, M ; Satzke, C ; Dashtseren, L ; Fox, KK ; Dunne, EM ; Nguyen, CD ; de Campo, J ; de Campo, M ; Thomson, H ; Surenkhand, G ; Demberelsuren, S ; Bujinlkham, S ; Do, LAH ; Narangerel, D ; Cherian, T ; Mungun, T ; Mulholland, EK (BMC, 2019-03-21)
    BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.
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    Epidemiology of pneumonia in the pre-pneumococcal conjugate vaccine era in children 2-59 months of age, in Ulaanbaatar, Mongolia, 2015-2016
    von Mollendorf, C ; La Vincente, S ; Ulziibayar, M ; Suuri, B ; Luvsantseren, D ; Narangerel, D ; de Campo, J ; de Campo, M ; Nguyen, C ; Demberelsuren, S ; Mungun, T ; Mulholland, EK ; Sekaran, SD (PUBLIC LIBRARY SCIENCE, 2019-09-11)
    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.
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    HPV genoprevalence and HPV knowledge in young women in Mongolia, five years following a pilot 4vHPV vaccination campaign
    Batmunkh, T ; von Mollendorf, C ; Tulgaa, K ; Surenjav, U ; Dalmau, MT ; Namjil, N ; Tsedevdamba, B ; Tsegmed, S ; Enkhmaa, J ; Garland, SM ; Mulholland, K (ELSEVIER, 2019-12)
    BACKGROUND: In a 2012 pilot, 9111 Mongolian girls aged 11-17 years received three doses of the quadrivalent (4vHPV) vaccine, Gardasil®. This is the first study to measure early vaccine effectiveness and assess knowledge and attitudes of young women in Mongolia in relation to the human papillomavirus (HPV), the vaccine and cervical cancer. METHODS: A cohort of women vaccinated in 2012 (n = 726) and an unvaccinated cohort (n = 790) provided self-administered vaginal swabs for detection of high-risk HPV genotypes 16, 18/45, 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, 68 five years following vaccination. Participant knowledge and attitudes were assessed through a questionnaire. RESULTS: A total of 1882 questionnaires and 1516 self-administered vaginal swabs were analyzed. The prevalence of any HRHPV was 39.5% among both cohorts. The prevalence of vaccine-targeted HPV types was significantly lower in the vaccinated cohort than unvaccinated: 4.8% and 17.2% respectively. The 4vHPV was shown to be protective against HRHPV 16, 18/45 with 75% vaccine effectiveness. Participant knowledge was low. CONCLUSIONS: This study demonstrates that the 4vHPV is associated with reduced vaccine-targeted HPV detection rates in young Mongolian women. The questionnaire results highlight a need for awareness-raising initiatives in Mongolia on HPV, the vaccine and cervical cancer.
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    Impact of the change in WHO's severe pneumonia case definition on hospitalized pneumonia epidemiology: case studies from six countries
    Russell, FM ; Reyburn, R ; Chan, J ; Tuivaga, E ; Lim, R ; Lai, J ; Hoang, MTV ; Choummanivong, M ; Sychareun, V ; Dung, KTK ; de Campo, M ; Enarson, P ; Graham, S ; La Vincente, S ; Mungan, T ; von Mollendorf, C ; Mackenzie, G ; Mulholland, K (WORLD HEALTH ORGANIZATION, 2019-06)
    OBJECTIVE: To quantify the impact of the change in definition of severe pneumonia on documented pneumonia burden. METHODS: We reviewed existing data acquired during observational hospitalized pneumonia studies, before the introduction of the pneumococcal conjugate vaccine, in infants aged 2-23 months from Fiji, Gambia, Lao People's Democratic Republic, Malawi, Mongolia and Viet Nam. We used clinical data to calculate the percentage of all-cause pneumonia hospitalizations with severe pneumonia, and with primary end-point consolidation, according to both the 2005 or 2013 World Health Organization (WHO) definitions. Where population data were available, we also calculated the incidence of severe pneumonia hospitalizations according to the different definitions. FINDINGS: At six of the seven sites, the percentages of all-cause pneumonia hospitalizations due to severe pneumonia were significantly less (P < 0.001) according to the 2013 WHO definition compared with the 2005 definition. However, the percentage of severe pneumonia hospitalizations, according to the two definitions of severe pneumonia, with primary end-point consolidation varied little within each site. The annual incidences of severe pneumonia hospitalizations per 100 000 infants were significantly less (all P < 0.001) according to the 2013 definition compared with the 2005 definition, ranging from a difference of -301.0 (95% confidence interval, CI: -405.2 to -196.8) in Fiji to -3242.6 (95% CI: -3695.2 to -2789.9) in the Gambia. CONCLUSION: The revision of WHO's definition of severe pneumonia affects pneumonia epidemiology, and hence the interpretation of any pneumonia intervention impact evaluation.