Improving community coverage of Japanese encephalitis vaccination: lessons learned from a mass campaign in Battambang Province, Cambodia.

A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products' live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere.

An evaluation of adverse events following an immunization campaign with the live, attenuated SA14-14-2 Japanese encephalitis vaccine in Cambodia.

INTRODUCTION: Japanese encephalitis (JE) virus is the most common cause of vaccine-preventable encephalitis in Asia. The SA14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products has been shown to be safe and effective in clinical trials and childhood routine immunization programs. However, there are few published reports describing results of surveillance for adverse events following immunization (AEFI) when the vaccine is used in mass campaigns. We describe the results of AEFI surveillance following a 2013 vaccination campaign among almost 310,000 children aged 9 months-12 years in Battambang Province, Cambodia. METHODS: Routine AEFI surveillance was strengthened by staff training and supplemented by active hospital surveillance. An AEFI was defined as any sign, symptom, or disease temporally associated (i.e., within 4 weeks) with receipt of the vaccine, irrespective of whether it was considered related to immunization. Data were collected on standardized forms and causality assessments were conducted for serious AEFI. RESULTS: Passive and active surveillance detected 28 AEFI for an overall incidence of 9.0 AEFI per 100,000 doses administered. The most frequent events were vasovagal episodes (n = 7, 25%) and rash (n = 6, 21%), and most other events were common childhood conditions such as fever and vomiting. Three AEFI were classified as serious, including one hypersensitivity reaction and two meningoencephalitis cases. Of these, the hypersensitivity event was the only serious AEFI classified as being consistent with a causal association to immunization. CONCLUSIONS: Most reported adverse events were conditions that commonly occur after other childhood vaccinations or independently of vaccination, and in the context of careful monitoring for serious AEFI only one serious event consistent with a causal association with immunization was identified. These results support the good safety profile of the SA14-14-2 JE vaccine, and provide reassuring data as the vaccine's use expands.

The current situation of health services for hydatidiform mole in Cambodia.

AIM: Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. METHODS: A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. RESULTS: A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n = 29), provincial hospitals (n = 42), district hospitals (n = 20), health centers (n = 6), and others (n = 29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. CONCLUSIONS: The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

The cooperation between professional societies contributes to the capacity building and system development for prevention and control of cancer in low- and middle-income countries: the practice of Cervical Cancer Prevention and Control Project in Cambodia.

Globally, an estimated 570,000 women are newly diagnosed with cervical cancer, and 311,000 women die every year, with approximately 90% of the cases occurring in low- and middle-income countries (LMICs). Cervical cancer is the most common cancer in women in Cambodia, with age-standard incidence rate of 13.5/100,000 and mortality rate of 10.1/100,000. This paper introduces the educational and managerial interventions of Cambodia Cervical Cancer Project 2015-2018 by two professional societies of Cambodia and Japan. It can be categorized into three phases: health education and screening; diagnosis and treatment of precancerous lesions; and pathology service. Human papillomavirus test-based cancer screening and treatment of precancerous lesions were successfully initiated. Key factors contributed to optimal outcomes are partnership between two professional societies with strong commitment, and a comprehensive and stepwise quality-focused approach. A complementary role and joint society initiatives is a novel approach and substantial in sustainability for developing a system of cervical cancer management. This effort might serve as a good example how professional societies can contribute to capacity building and system development for prevention and control of cancer in LMICs.

Assessment of vaccine wastage rates, missed opportunities, and related knowledge, attitudes and practices during introduction of a second dose of measles-containing vaccine into Cambodia's national immunization program.

INTRODUCTION: Missed opportunities for vaccination (MOV) can result in inadequate protection against disease. Although healthcare provider reluctance to open multi-dose, lyophilized vaccine vials (particularly the measles-containing vaccine [MCV]) for every eligible child due to concerns about wasting vaccine is a known reason for MOV, little is known about providers' related attitudes and practices. METHODS: In 100 randomly selected health facilities and 24 districts of Cambodia, we surveyed healthcare providers and their district supervisors regarding routine vaccine administration and wastage knowledge and practices, and child caregivers (five per facility) regarding MOV. Vaccine stock management data covering six months were reviewed to calculate facility and district level wastage rates and vaccine usage patterns for six vaccines, including a recently introduced second dose of MCV (MCV2). RESULTS: Response rates were 100/100 (100%) among facility staff, 48/48 (100%) among district staff, and 436/500 (87%) among caregivers. Mean facility-level wastage rates varied from 4% for single-dose diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine to 60% for 10-dose MCV; district-level wastage rates for all vaccines were 0%. Some vaccines had lower wastage rates in large facilities compared to small facilities. The mean MCV wastage rate was the same before and immediately after MCV2 introduction. Providers reported waiting for a mean of two children prior to opening an MCV vial, and 71% of providers reported offering MCV vaccination less frequently during scheduled vaccination sessions than other vaccines. Less than 5% of caregivers reported that their child had been turned away for vaccination, most frequently (65%) for MCV. DISCUSSION: Although the MCV wastage rate in our study was in line with national targets, providers reported waiting for more than one child before opening an MCV vial, contrary to vaccine management guidelines. Future research should explore the causal links between provider practices related to vaccine wastage and their impact on vaccination coverage.

Integration of Multiplex Bead Assays for Parasitic Diseases into a National, Population-Based Serosurvey of Women 15-39 Years of Age in Cambodia.

Collection of surveillance data is essential for monitoring and evaluation of public health programs. Integrated collection of household-based health data, now routinely carried out in many countries through demographic health surveys and multiple indicator surveys, provides critical measures of progress in health delivery. In contrast, biomarker surveys typically focus on single or related measures of malaria infection, HIV status, vaccination coverage, or immunity status for vaccine-preventable diseases (VPD). Here we describe an integrated biomarker survey based on use of a multiplex bead assay (MBA) to simultaneously measure antibody responses to multiple parasitic diseases of public health importance as part of a VPD serological survey in Cambodia. A nationally-representative cluster-based survey was used to collect serum samples from women of child-bearing age. Samples were tested by MBA for immunoglobulin G antibodies recognizing recombinant antigens from Plasmodium falciparum and P. vivax, Wuchereria bancrofti, Toxoplasma gondii, Taenia solium, and Strongyloides stercoralis. Serologic IgG antibody results were useful both for generating national prevalence estimates for the parasitic diseases of interest and for confirming the highly focal distributions of some of these infections. Integrated surveys offer an opportunity to systematically assess the status of multiple public health programs and measure progress toward Millennium Development Goals.

Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012.

To monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. Multistage cluster sampling was used to select 2,154 women aged 15 to 39 years. Tetanus toxoid antibodies in serum samples were measured by gold-standard double-antigen enzyme-linked immunosorbent assay (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations of ≥0.01 IU/ml by DAE or the equivalent for MBA were considered seroprotective. Estimated tetanus seroprotection was 88% (95% confidence interval [CI], 86 to 89%); 64% (95% CI, 61 to 67%) of women had antibody levels of ≥1.0 IU/ml. Seroprotection was significantly lower (P < 0.001) among women aged 15 to 19 years (63%) and 20 to 24 years (87%) than among those aged ≥25 years (96%), among nulliparous women than among parous women (71 versus 97%), and among those living in the western region than among those living in other regions (82 versus 89%). The MBA showed high sensitivity (99% [95% CI, 98 to 99%]) and specificity (92% [95% CI, 88 to 95%]) compared with DAE. Findings were compatible with MNTE in Cambodia (≥80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE.

Prevalence of chronic hepatitis B virus infection after implementation of a hepatitis B vaccination program among children in three provinces in Cambodia.

BACKGROUND: Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B surface antigen (HBsAg) prevalence of 9%. By 2005, a hepatitis B vaccination program was implemented to decrease infection rates in children. We conducted a serosurvey to evaluate the impact of the vaccination program in 2011. METHODS: A cross-sectional two-stage cluster survey was conducted to estimate HBsAg prevalence among children born from 2006 to 2007 in three provinces: Phnom Penh (urban), Kratie (rural), and Ratanakiri (remote). Demographic data, as well as written or oral vaccination history were collected. Children were tested for HBsAg. Factors associated with undervaccination and HBsAg positivity were modeled. RESULTS: Coverage of timely hepatitis B vaccine birth dose (administered at ≤ 24 h) was 55% in Phnom Penh, 36% in Kratie, and 22% in Ratanakiri. Coverage with ≥ 3 hepatitis B vaccine doses (HepB3) was 91% in Phnom Penh, 82% in Kratie, and 64% in Ratanakiri. When compared with children who were born in health facilities with a skilled birth attendant (SBA), children born at home without a SBA were more likely not to have received a timely BD (adjusted relative risk [aRR]=1.94; 95% CI=1.75-2.15) as were children born at home with an SBA (aRR=1.54; 95% CI=1.32-1.80). The proportion of children who tested positive for HBsAg was 0.33% in Phnom Penh, 1.41% in Kratie, and 3.45% in Ratanakiri. In all three provinces, children who received their first dose after 7 days of life and children who never received hepatitis B vaccine had the highest HBsAg prevalence. CONCLUSIONS: Progress has been made in Cambodia in decreasing the burden of chronic HBV infection among children. Improvements in vaccination coverage will further decrease the burden of disease.

Using data to guide policy: next steps for preventing perinatal hepatitis B virus transmission in Cambodia.

BACKGROUND: Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinatal HBV transmission should be prioritized in health facilities by providing hepatitis B vaccination to all infants within 24 h of birth (timely birth dose coverage). METHODS: Teams assessed birth dose policy, practices and coverage in hospitals and health facilities in 10 provinces in Cambodia. RESULTS: Fifty-one sites were assessed. Median (interquartile range) timely birth dose coverage was 66% (48-92%); coverage was 88% (range=60-96%) in facilities vaccinating on-site and 48% (range=20-52%) in those referring off-site (p<0.0001). Overall, 5 (29%) of 16 hospitals that referred vaccination off-site did not tell mothers vaccination should take place within 24 h of birth, and 6 (35%) discharged mothers when no vaccination services were available for infants to receive the birth dose. CONCLUSIONS: Newborns can miss a time-sensitive opportunity to be protected against perinatal HBV infection when they are referred for vaccination off-site rather than being vaccinated in the delivery facility. These data support the case to strengthen policies and practices to provide hepatitis B birth dose vaccination in the delivery facility.

The social determinants of health and health service access: an in depth study in four poor communities in Phnom Penh Cambodia.

BACKGROUND: Increasing urbanization and population density, and persisting inequities in health outcomes across socioeconomic groupings have raised concerns internationally regarding the health of the urban poor. These concerns are also evident in Cambodia, which prompted the design of a study to identify and describe the main barriers to access to health services by the poor in the capital city, Phnom Penh. SOURCES AND METHODS: Main sources of data were through a household survey, followed by in-depth qualitative interviews with mothers, local authorities and health centre workers in four very poor communities in Phnom Penh. MAIN FINDINGS: Despite low incomes and education levels, the study communities have moderate levels of access to services for curative and preventive care. However, qualitative findings demonstrate that households contextualize poor health and health access in terms of their daily living conditions, particularly in relation to environmental conditions and social insecurity. The interactions of low education, poor living conditions and high food costs in the context of low and irregular incomes reinforce a pattern of "living from moment to moment" and results in a cycle of disadvantage and ill health in these communities. There were three main factors that put poor communities at a health disadvantage; these are the everyday living conditions of communities, social and economic inequality and the extent to which a society assesses and acts on inequities in their health care access. CONCLUSIONS: In order to improve access to health and health services for the urban poor, expansion of public health functions and capacities will be required, including building partnerships between health providers, municipal authorities and civil society.

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.

Results from nationwide hepatitis B serosurvey in Cambodia using simple and rapid laboratory test: implications for National Immunization Program.

Chronic liver infection and cancer in the western Pacific region is disproportionate to the population globally. This study provides the first nationwide estimates of hepatitis B surface antigen (HBsAg) seroprevalence in Cambodia among children five year of age. Using a simple and rapid test for HBsAg and multi-stage stratified cluster sampling design, we estimated HBsAg seroprevalence to be 3.5% (95% confidence interval = 2.4-4.8%) among five-year old children. Triangulating the results with other studies, we demonstrate the importance of interrupting perinatal transmission and one-time catch-up vaccination of older children born before nationwide introduction of vaccination for effective hepatitis B control in Cambodia and for reaching the disease control goal of less than 2% chronic infection rates among children > or = 5 years of age. The results demonstrate the feasibility of conducting nationwide serosurveys using simple and rapid tests to evaluate the impact of hepatitis B vaccination programs in lieu of standard enzyme-linked immunosorbent assays.

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.

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.

Financial sustainability planning for immunization services in Cambodia.

The expanded programme of immunization was established in Cambodia in 1986. In 2002, 67% of eligible children were immunized, despite significant health sector and macro-economic financial constraints. A financial sustainability planning process for immunization was introduced in 2002, in order to mobilize national and international resources in support of the achievement of child health objectives. The aim of this paper is to outline this process, describe its early impact as an advocacy tool and recommend additional strategies for mobilizing additional resources for health. The methods of financial sustainability planning are described, including the advocacy strategies that were applied. Analysis of financial sustainability planning results indicates rising programme costs associated with new vaccine introduction and new technologies. Despite this, the national programme has demonstrated important early successes in using financial sustainability planning to advocate for increased mobilization of national and international sources of funding for immunization. The national immunization programme nevertheless faces formidable system and financial challenges in the coming years associated with rising costs, potentially diminishing sources of international assistance, and the developing role of sub-national authorities in programme management and financing.

Key issues relating to decentralization at the provincial level of health management in Cambodia.

The following study was conducted as part of a review of management systems at a Provincial Health Department (Kampong Cham Province) and a National Health Programme (National Immunization Program) in 2002-2003 in Cambodia. The aim of this paper is to identify, analyse and recommend those management system factors that are critical to the success of health management performance, with a particular focus on provincial management. The review has identified critical success factors associated with health management performance at the sub-national level that include a stronger role for effective human resource management in health sector reform, elevation of the status of planning in senior level management, and the development of a more comprehensive and transparent finance system. These success factors will position the provincial level of health management to respond more effectively to the reform challenges of administrative de-concentration and political decentralization that are currently underway across a range of government sectors in Cambodia.