Diphtheria in Metro Manila, the Philippines 2006-2017: A Clinical, Molecular, and Spatial Characterization.

BACKGROUND: Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. METHODS: We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). RESULTS: We studied 267 patients (range:12-54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8-50.0%). A higher number of cases and CFR was observed among children <10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types. CONCLUSIONS: Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized.

Epidemiology of a measles epidemic in Vietnam 2008-2010.

BACKGROUND: Vietnam conducted a measles catch-up supplementary immunization activity (SIA) during 2002-2003 that targeted children 9 months-10 years of age, followed by subnational SIAs targeting persons up to 20 years of age during 2004 and 2007-2008. A measles epidemic began among young adults in October 2008 in the northern region, spread nationwide during early 2009, and continued during 2010. METHODS: We reviewed national epidemiologic and laboratory surveillance data. Measles cases were defined and classified according to World Health Organization recommendations. RESULTS: From October 2008 through January 2010, 7948 confirmed measles cases were reported from 60 of 63 provinces, an incidence of 93 cases per million population. Incidence was 328 cases per million population among children age 1-4 years, 318 cases per million population among infants, and 271 cases per million population among persons aged 20-24 years. Few cases were reported among persons 7-17 or >27 years of age. Median age of cases trended downward over time in all regions. CONCLUSIONS: The 2002-2003 measles SIA protected its targeted age group, but this epidemic was not prevented by follow-up subnational SIAs in selected provinces during 2007-2008. Transmission began among young adults and was sustained among children. The outcome of Vietnam's 2010 SIA targeting children only and change in routine schedule may influence elimination strategies for other countries.

Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance.

OBJECTIVES: To describe the results from two years of Japanese encephalitis (JE) sentinel surveillance in Cambodia. METHODS: Sentinel site surveillance for JE in children aged 15 years and under was implemented in Cambodia in mid-2006. It was integrated into the routine meningoencephalitis surveillance system. Six hospitals were selected as sentinel sites. Epidemiological information and diagnostic specimens were collected from each patient presenting with meningoencephalitis. Cerebrospinal fluid and sera were tested for presence of immunoglobulin M antibodies against JE and dengue viruses by an ELISA. Surveillance data from 2006 to 2008 were analysed. RESULTS: Of 586 patients presenting with meningoencephalitis, 110 (19%) were confirmed to have JE. The percentage of confirmed JE cases at individual sentinel sites ranged from 13% to 35% of all meningoencephalitis cases. Mean age was 6.2 years, with 95% of JE cases in children aged 12 years and under. Cases occurred year-round in both 12-month reporting periods. CONCLUSIONS: JE is an important cause of meningoencephalitis in Cambodian children. As JE is a vaccine-preventable disease, an immunization programme could result in a considerable reduction in morbidity and mortality from JE among children in Cambodia.

Molecular characterization of rotavirus diarrhea among children aged under five years in the Philippines, 2013-2015.

With the availability of new and existing rotavirus vaccines, credible and reliable data on burden of rotavirus-associated disease are needed to enable evidence-based decision making regarding the introduction of rotavirus vaccines. The national rotavirus surveillance program in the Philippines, a sentinel-based surveillance, was established in 2012 to determine the proportion of laboratory-confirmed rotavirus cases among children under five years with acute gastroenteritis and to describe the geographic distribution and molecular epidemiology of rotavirus in the country. During 2013 to 2015, rotavirus infection was the cause of acute gastroenteritis among children under five years admitted to hospitals or evaluated in emergency rooms, constituting more than one-third of gastroenteritis hospitalizations at the sentinel site hospitals. The predominant genotype observed was G1P[8]. Although a rotavirus surveillance network has been established, findings suggest the need to strengthen the network in the country and to continue monitoring prevalent rotavirus strains to help identify the possible emergence of new strains.

Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct genotyping of clinical specimens.

OBJECTIVES: This study sought to determine the genotypes of circulating Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct molecular typing of clinical specimens. METHODS: DNA extracts from nasopharyngeal swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter ptxP were also investigated by DNA sequence-based typing. RESULTS: Forty-four DNA extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which are common in developed countries, were the predominant strain types (total 73%). The predominant profile of virulence-associated allelic genes was the combination of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire study period, whereas MT29 strains were only found in 2014-2016. CONCLUSIONS: The B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV) has been continuously used, resembled those observed previously in developed countries where acellular pertussis vaccines are used. Circulating B. pertussis strains in Cambodia were distinct from those in other countries using WCVs.

Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.

Modeling the impact of rubella vaccination in Vietnam.

Supported by GAVI Alliance, measles-rubella vaccination was introduced in Vietnam in 2014, involving a mass campaign among 1-14 year olds and routine immunization of children aged 9 months. We explore the impact on the incidence of Congenital Rubella Syndrome (CRS) during 2013-2050 of this strategy and variants involving women aged 15-35 years. We use an age and sex-structured dynamic transmission model, set up using recently-collected seroprevalence data from Central Vietnam, and also consider different levels of transmission and contact patterns. If the serological profile resembles that in Central Vietnam, the planned vaccination strategy could potentially prevent 125,000 CRS cases by 2050 in Vietnam, despite outbreaks predicted in the meantime. Targeting the initial campaign at 15-35 year old women with or without children aged 9 months-14 years led to sustained reductions in incidence, unless levels of ongoing transmission were medium-high before vaccination started. Assumptions about contact greatly influenced predictions if the initial campaign just targeted 15-35 year old women and/or levels of ongoing transmission were medium-high. Given increased interest in rubella vaccination, resulting from GAVI Alliance funding, the findings are relevant for many countries.

Congenital rubella syndrome (CRS) in Vietnam 2011-2012--CRS epidemic after rubella epidemic in 2010-2011.

BACKGROUND: Rubella is endemic in Vietnam with epidemics occurring every 4-5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system. METHOD: Three national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory. RESULTS: From January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of "fever and rash" during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%). CONCLUSIONS: The newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization.

Thirty years of vaccination in Vietnam: Impact and cost-effectiveness of the national Expanded Programme on Immunization.

INTRODUCTION: Countries like Vietnam transitioning to middle-income status increasingly bear the cost of both existing and new vaccines. However, the impact and cost-effectiveness of the Expanded Programme on Immunization (EPI) as a whole has never been assessed on a country level. METHODS: Data on vaccine-preventable disease incidence and mortality from Vietnam's national surveillance was analysed to estimate the likely impact that vaccination in 1980-2010 may have had. Adjustment for under-reporting was made by examining trends in reported mumps incidence and in case-fatality risks for each disease. The same data were separately analysed using the Lives Saved Tool (LiST) to give an alternative estimate of impact. The financial cost of EPI in 1996-2010 was also estimated from the perspective of service provider. RESULTS: National surveillance data suggests that up to 5.7 million diseases cases and 26,000 deaths may have been prevented by EPI. Analysis using LiST suggests that even more deaths (370,000) may have been prevented by measles and pertussis vaccination alone. The cost-effectiveness of EPI is estimated to be around $1000-$27,000 per death prevented. CONCLUSION: Two separate approaches to assessing EPI impact in Vietnam give different quantitative results but a common conclusion: that EPI has made a substantial impact on mortality and represents good value for money.

A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination.

BACKGROUND: Vietnam has high endemic hepatitis B virus infection with >8% of adults estimated to have chronic infection. Hepatitis B vaccine was first introduced in the national childhood immunization program in 1997 in high-risk areas, expanded nationwide in 2002, and included birth dose vaccination in 2003. This survey aimed to assess the impact of Vietnam's vaccination programme by estimating the prevalence of hepatitis B surface antigen (HBsAg) among children born during 2000-2008. METHODS: This nationally representative cross-sectional survey sampled children based on a stratified three-stage cluster design. Demographic and vaccination data were collected along with a whole blood specimen that was collected and interpreted in the field with a point-of-care HBsAg test. RESULTS: A total of 6,949 children were included in the survey analyses. The overall HBsAg prevalence among surveyed children was 2.70% (95% confidence interval (CI): 2.20-3.30). However, HBsAg prevalence was significantly higher among children born in 2000-2003 (3.64%) compared to children born 2007-2008 (1.64%) (prevalence ratio (PR: 2.22, CI 1.55-3.18)). Among all children included in the survey, unadjusted HBsAg prevalence among children with ≥3 doses of hepatitis B vaccine including a birth dose (1.75%) was significantly lower than among children with ≥3 doses of hepatitis B vaccine but lacked a birth dose (2.98%) (PR: 1.71, CI: 1.00-2.91) and significantly lower than among unvaccinated children (3.47%) (PR: 1.99, CI: 1.15-3.45). Infants receiving hepatitis B vaccine >7 days after birth had significantly higher HBsAg prevalence (3.20%) than those vaccinated 0-1 day after birth (1.52%) (PR: 2.09, CI: 1.27-3.46). CONCLUSION: Childhood chronic HBV infection prevalence has been markedly reduced in Vietnam due to vaccination. Further strengthening of timely birth dose vaccination will be important for reducing chronic HBV infection prevalence of under 5 children to <1%, a national and Western Pacific regional hepatitis B control goal.

Development and evaluation of a loop-mediated isothermal amplification method for rapid diagnosis of Bordetella pertussis infection.

We developed a loop-mediated isothermal amplification (LAMP) method to detect Bordetella pertussis infection. This LAMP assay detected B. pertussis with high sensitivity, but not other Bordetella species. Among nasopharyngeal swab samples from subjects with suspected pertussis, LAMP results showed a high level of agreement with results of conventional PCR. This method is a rapid, sensitive, and specific method for diagnosis of B. pertussis infection even in clinical laboratories with no specific equipment.