Genotyping and macrolide-resistant mutation of Bordetella pertussis in East and South-East Asia.

OBJECTIVES: Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and macrolide resistance of circulating B. pertussis in East and Southeast Asia using genetic analyses. METHODS: A total of 302 DNA extracts from clinical specimens and isolates from 2010 to 2020 were analyzed: 145 from Vietnam, 76 from Cambodia, 48 from Taiwan, and 33 from Japan. Genotypes were determined by multilocus variable-number tandem-repeat analysis (MLVA). Macrolide-resistant A2047G mutation in B. pertussis 23S rRNA was investigated using the duplex Cycleave real-time polymerase chain reaction (PCR) assay. Whole-genome sequencing was performed on two MRBP isolates that were identified for the first time in Taiwan. RESULTS: Overall, 286 DNA extracts (95%) generated a complete MLVA genotype and 283 DNA extracts (94%) yielded a complete result for the A2047G mutation analysis. The A2047G mutation was detected in 18 DNA extracts: fourteen from Vietnam, one from Cambodia, two from Taiwan, and one from Japan. Most of them (78%) showed the genotypes MT104 and MT195, which have previously been reported in Chinese MRBP isolates. Further, the Taiwanese MRBP isolates were classified into the MT104 clade of Chinese MRBP isolates. CONCLUSION: After MRBP emerged and spread in mainland China, it may have spread to East and Southeast Asia in the 2010s. Continued surveillance targeting the A2047G mutation of MRBP is needed to prevent further spread of this emerging pathogen.

Integrated approach for triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis is highly effective and cost-effective: an economic evaluation.

BACKGROUND: The Regional Framework for Triple Elimination of Mother-to-Child Transmission (EMTCT) of HIV, Hepatitis B (HBV) and Syphilis in Asia and the Pacific 2018-30 was endorsed by the Regional Committee of WHO Western Pacific in October 2017, proposing an integrated and coordinated approach to achieve elimination in an efficient, coordinated and sustainable manner. This study aims to assess the population impacts and cost-effectiveness of this integrated approach in the Cambodian context. METHODS: Based on existing frameworks for the EMTCT for each individual infection, an integrated framework that combines infection prevention procedures with routine antenatal care was constructed. Using decision tree analyses, population impacts, cost-effectiveness and the potential reduction in required resources of the integrated approach as a result of resource pooling and improvements in service coverage and coordination, were evaluated. The tool was assessed using simulated epidemiological data from Cambodia. RESULTS: The current prevention programme for 370,000 Cambodian pregnant women was estimated at USD$2.3 ($2.0-$2.5) million per year, including the duration of pregnancy and up to 18 months after delivery. A model estimate of current MTCT rates in Cambodia was 6.6% (6.2-7.1%) for HIV, 14.1% (13.1-15.2%) for HBV and 9.4% (9.0-9.8%) for syphilis. Integrating HIV and syphilis prevention into the existing antenatal care framework will reduce the total time required to provide this integrated care by 19% for health care workers and by 32% for pregnant women, resulting in a net saving of $380,000 per year for the EMTCT programme. This integrated approach reduces HIV and HBV MTCT to 6.1% (5.7-6.5%) and 13.0% (12.1-14.0%), respectively, and substantially reduces syphilis MCTC to 4.6% (4.3-5.0%). Further introduction of either antiviral treatment for pregnant women with high viral load of HBV, or hepatitis B immunoglobulin (HBIG) to exposed newborns, will increase the total cost of EMTCT to $4.4 ($3.6-$5.2) million and $3.3 ($2.7-$4.0) million per year, respectively, but substantially reduce HBV MTCT to 3.5% (3.2-3.8%) and 5.0% (4.6-5.5%), respectively. Combining both antiviral and HBIG treatments will further reduce HBV MTCT to 3.4% (3.1-3.7%) at an increased total cost of EMTCT of $4.5 ($3.7-$5.4) million per year. All these HBV intervention scenarios are highly cost-effective ($64-$114 per disability-adjusted life years averted) when the life benefits of these prevention measures are considered. CONCLUSIONS: The integrated approach, using antenatal, perinatal and postnatal care as a platform in Cambodia for triple EMTCT of HIV, HBV and syphilis, is highly cost-effective and efficient.

Pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children: Seven years of active surveillance, 2010-2016.

BACKGROUND: Each year, approximately 1,066 Cambodian children under five years old die of diarrhea, and 51% of these deaths are due to rotavirus gastroenteritis. Quantifying childhood hospitalizations caused by severe rotavirus infections is also important in demonstrating disease burden caused by this virus. The objective of this study is to update and confirm the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children using seven years of continuous active, prospective surveillance from 2010 to 2016. We also characterize the circulating rotavirus genotypic strains during this period. METHODS: Active surveillance for rotavirus gastroenteritis was conducted from January 2010 through December 2016 at a national hospital in Phnom Penh, Cambodia. Children <60 months of age who were hospitalized for acute gastroenteritis (AGE) were consented and enrolled. Information on gender, age, clinical characteristics, and month of onset were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus antigen, and genotyping was performed on rotavirus test-positive specimens to characterize predominant rotavirus strains during the surveillance period. RESULTS: Of 7007 children enrolled with AGE and having specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The majority of rotavirus hospitalizations occurred in children younger than two years old (92%). Year-round rotavirus transmission was observed, with seasonal peaks during the cooler, dry months between November and May. Genotypic trends in rotavirus were observed over the surveillance period; the predominant rotavirus strains changed from G1P[8] (2010-2012), to G2P[4] (2013-2014), the emergence of genotype G8P[8] in 2015, and G3P[8] in 2016. CONCLUSIONS: Rotavirus is the leading cause of severe acute gastroenteritis hospitalizations in Cambodian children under five years old, with 50% of such hospitalizations attributable to rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2 years of age. Changes in the predominant rotavirus strains occurred over time among these unvaccinated children. This information is important to understand and prioritize the current potential impacts upon child health that could be achieved through the introduction of rotavirus vaccines in Cambodia.

Immunization against Viral Hepatitis B: Lessons Learnt from Kingdom of Cambodia.

An account of immunization against hepatitis B virus in Cambodia is given. How to cite this article: Sreng B, Vichit O, Vuthikol Y, Aun C, Samnang C. Immunization against Viral Hepatitis B: Lessons Learnt from Kingdom of Cambodia. Euroasian J Hepato-Gastroenterol 2017;7(1):43-47.

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.

Viral Hepatitis in Cambodia: Past, Present, and Future.

The prevalence of viral hepatitis represents Cambodia as 1 of the highest endemic countries in the world. But the prevalence of viral hepatitis B among 5-year-olds is on a decreasing trend due to the effect of nationwide vaccination against hepatitis B. There are key interventions to address viral hepatitis by the Cambodian Ministry of Health. There are so far no comprehensive national guidelines for the prevention, care, and treatment of viral hepatitis. In 2014, the coverage of hepatitis B vaccine at birth and HepB3 vaccine was very high, at 87 and 97% respectively. Other interventions include the screening of viral hepatitis B and C among blood donors; the enhancement of infection prevention and control at health facilities; the program for People Who Use Drugs (PWUDs) and People Who Inject Drugs (PWIDs); control and prevention of HIV/AIDS and sexually transmitted diseases (STDs); and improved sanitation, clean water, and food safety. The diagnosis of viral hepatitis B and C could be made only at the national and provincial referral hospitals and there are no specific antiviral therapies for people who are infected with hepatitis B and C. HOW TO CITE THIS ARTICLE: Sreng B, Sophal C, Srun S, Samnang C, Huot E. Viral Hepatitis in Cambodia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):45-48.

Disability from Japanese encephalitis in Cambodia and Viet Nam.

A cohort of Japanese encephalitis (JE) survivors in Cambodia and Viet Nam were assessed at least 4 months after hospital discharge in order to understand the extent of disability after JE. We used a simple assessment tool which focuses on the impact on daily life. In total, 64 disability assessments were conducted: 38 in Cambodia and 26 in Viet Nam. In Cambodia, 4 (11%) children had severe sequelae, suggesting the children would likely be dependent, 15 (39%) had moderate sequelae and 17 (45%) had mild sequelae. In Viet Nam, two (8%) persons had severe sequelae, five (19%) had moderate sequelae and eight (31%) had mild sequelae. In many JE-endemic areas there are no multi-disciplinary teams with sophisticated equipment to assess patients after JE disease. This assessment tool can assist with patient management and generate data to support the need for programmes to prevent disease and improve outcomes for survivors.

A cost-effectiveness analysis of Japanese encephalitis vaccine in Cambodia.

This study aimed to evaluate the cost and effectiveness of introducing a live, attenuated vaccine (SA 14-14-2) against Japanese encephalitis (JE) into the immunization program. The study demonstrated that SA 14-14-2 immunization is cost-effective in controlling JE in Cambodia compared to no vaccination. Averting one disability-adjusted life year, from a societal perspective, through the introduction of SA 14-14-2 through routine immunization, or a combination of routine immunization plus a campaign targeting children 1-5 or 1-10 years of age, costs US$22, US$34 and US$53, respectively. Sensitivity analyses confirmed that there was a high probability of SA 14-14-2 immunization being cost-effective under conditions of uncertainty.

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.

The rationale for integrated childhood meningoencephalitis surveillance: a case study from Cambodia.

PROBLEM: Recent progress in vaccine availability and affordability has raised prospects for reducing death and disability from neurological infections in children. In many Asian countries, however, the epidemiology and public health burden of neurological diseases such as Japanese encephalitis and bacterial meningitis are poorly understood. APPROACH: A sentinel surveillance system for Japanese encephalitis was developed and embedded within the routine meningoencephalitis syndromic surveillance system in Cambodia in 2006. The sentinel surveillance system was designed so surveillance and laboratory testing for other etiologies of neurological infection could be incorporated. LOCAL SETTING: The Communicable Disease Control department of the Ministry of Health in Cambodia worked with partners to establish the sentinel surveillance system. RELEVANT CHANGES: The sentinel surveillance system has provided important information on the disease burden of Japanese encephalitis in Cambodia and is now providing a platform for expansion to incorporate laboratory testing for other vaccine-preventable neurological infections in children. LESSONS LEARNED: Sentinel surveillance systems, when linked to syndromic reporting systems, can characterize the epidemiology of meningoencephalitis and identify the proportion of hospital-based neurological infection in children that is vaccine preventable. Integrated systems enable consistency in data collection, analysis and information dissemination, and they enhance the capacity of public health managers to provide more credible and integrated information to policy-makers. This will assist decision-making about the potential role of immunization in reducing the incidence of childhood neurological infections.

Evaluation of immunization knowledge, practices, and service-delivery in the private sector in Cambodia.

A study of private-sector immunization services was undertaken to assess scope of practice and quality of care and to identify opportunities for the development of models of collaboration between the public and the private health sector. A questionnaire survey was conducted with health providers at 127 private facilities; clinical practices were directly observed; and a policy forum was held for government representatives, private healthcare providers, and international partners. In terms of prevalence of private-sector provision of immunization services, 93% of the private inpatient clinics surveyed provided immunization services. The private sector demonstrated a lack of quality of care and management in terms of health workers' knowledge of immunization schedules, waste and vaccine management practices, and exchange of health information with the public sector. Policy and operational guidelines are required for private-sector immunization practices that address critical subject areas, such as setting of standards, capacity-building, public-sector monitoring, and exchange of health information between the public and the private sector. Such public/private collaborations will keep pace with the trends towards the development of private-sector provision of health services in developing countries.