Gaps in Hepatitis B Vaccination Completion and Sero-Protection for People Who Inject Drugs in Hpakant, Myanmar, 2015–2018

Hepatitis B vaccination (HBV) is recommended for high-risk groups, such as people who inject drugs (PWIDs). As part of a harm reduction program by a non-governmental organization, hepatitis B screening, vaccination and antibody (HBAb) testing after completion of the vaccination schedule were offered to PWIDS in Myanmar. We determined the proportions of HBV non-completion and sero-unprotection among PWIDs enrolled in the program and their association with socio-demographic and clinical characteristics. We conducted a descriptive study based on routine program data in five selected clinics in Hpakant Township, Myanmar. PWIDs who were Hepatitis B antigen negative at screening during January 2015–December 2018 were included. Among 5386 participants eligible for HBV, 9% refused vaccination. Among those who accepted vaccination (n = 3177 individuals), 65% completed vaccination. Of those tested for HBsAb (n = 2202), 30% were sero-unprotected. Young-adults (aged 18–44 years) and migrant workers had a higher risk of incomplete vaccination. However, participants who used methadone had a lower risk of incomplete vaccination. Migrant workers had higher risk of not returning for HBsAb testing and HIV-positive participants had a higher risk of being HBV sero-unprotected. Efforts to increase HBV vaccination in PWIDs for young adults and clients during methadone and anti-retroviral services should be prioritized.


Introduction
In South-East Asia there were an estimated 39 million people living with chronic hepatitis B viral infection in 2015 [1]. Among adults, ongoing HBV transmission occurs primarily among incompletely immunized clients with behavioural risks for HBV transmission including individuals with multiple sex partners, people who inject drugs (PWIDs), men who have sex with men and household contacts and sex partners of persons with chronic HBV infection. Hepatitis B vaccination is an effective measure to prevent HBV infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure and death [2].
In Myanmar, the prevalence of viral hepatitis in the general population was 10%−12% in 2013, and viral hepatitis places a heavy burden on the health care system because of the costs of treatment of In the AHRN Program, PWIDs receive health education about hepatitis and are offered a referral for HBV treatment. If clients are HBV negative during screening (HBV antigen test), they are started on an accelerated vaccination schedule at days 0, 7 and 21 [8]. The vaccine dosage for HBV is 20 µg for HIV negative and 40 µg for HIV positive clients. Antibodies for hepatitis B are tested two months after the third vaccination. AHRN provides free medical care support to all clients enrolled in the program. An incentive of 2000 Kyats (1.4 USD) is given to PWIDs after completion of the third dose vaccination.
The clinic nurse offers PWID clients HIV counseling and testing, and hepatitis B screening. If they are hepatitis B negative, the clinic nurse asks them whether they are willing to receive the vaccination, which is then administered.

Study Site and Population
Five clinics (Hpakant, Seik Mu, Lone Khin, Tamakhan and Selzin) in the Hpakant Township were selected for the study. These sites were chosen based on a high number of PWIDs and study feasibility. We included all PWID clients who were eligible to receive hepatitis B vaccination (HBV antigen-negative), enrolled in the program between 1 January 2015 and 31 December 2018 in the five study sites. Clients who were hepatitis B antigen positive during screening, and those who had been previously vaccinated were excluded. The DIAQUICK HBs Ab Dipstick, a rapid chromatographic lateral flow immunoassay for the qualitative detection of antibody to HBs antigen in serum or plasma, was used as the marker of immunity to HBV [11].

Data Variables, Sources of Date and Data Collection
The variables included the project site, client identification number, type of client, date and result of HBsAg, HBV vaccination accepted or not, HIV status, gender, age, risk group (PWIDs only, PWID who used methadone, PWID who were commercial sex workers), date of first, second, third doses, dosage and HBV antibody results that were recorded in the AHRN program electronic database. They were extracted and reviewed with the program officer to ensure completeness and quality of the data. A vaccination card is started and clients are given an appointment for the next vaccination and checked the completion of vaccination card and gave the next date appointment. The clinic nurse entered this information into a paper-based format. Then, the data assistant entered it into the access based software and checked the data for monthly reporting in the study clinic.

Data Analysis and Statistics
Data was exported into EpiData analysis software (version 2.2.2.183) and STATA (version 11, StataCorp, College Station, TX, USA) for data analysis. Continuous variables such as age were described as median and interquartile ranges (IQR). Categorical variables such as gender (male/female), vaccination completion (yes/no) and sero-protection (yes/no) were described as frequencies and proportions. Unadjusted risk ratios (RR) and adjusted risk ratios (aRR) were calculated for the association of select socio-demographic and clinical factors (age group, gender, project site, educational levels, occupation, risk group and HIV status) with outcome variables (HBV vaccination refusal, vaccination incompletion, those who did not return for HBV antibody testing and HBV sero-un-protection). Confidence intervals (CI) of 95% and a p-value < 0.05 were considered significant.

Characteristics of Participants According to HBV Vaccination Refusal
The socio-demographic and clinical characteristics of PWIDs eligible for HBV vaccination (i.e., those who were HBsAg negative on screening) are described in Table 1. The majority (89%) were aged between 18 and 44 years and were males (98%). About 34% were residents of Seng Taung followed by Lone Khin (29%). 55% had completed high school, and the most frequent occupation was being a farmer (45%). About 27% of PWIDs also used methadone and 39% had HIV infection. PWIDs

Characteristics of Participants According to HBV Vaccination Refusal
The socio-demographic and clinical characteristics of PWIDs eligible for HBV vaccination (i.e., those who were HBsAg negative on screening) are described in Table 1. The majority (89%) were aged between 18 and 44 years and were males (98%). About 34% were residents of Seng Taung followed by Lone Khin (29%). 55% had completed high school, and the most frequent occupation was being a farmer (45%). About 27% of PWIDs also used methadone and 39% had HIV infection. PWIDs with residence in Hpakant (aRR: 2.  1-0.3)). Among those who accepted vaccination, 22% received only one vaccine dose, 13% received two doses and 65% three doses (complete vaccination). , ** row percentage, refused vaccination: a person who did not want to take three doses vaccination due of the high cost of transportation, 1 drug dealer: a person who sells illicit drugs, 2 jade broker: a person who buys and sells a green precious stone and jewelry, migrant worker: a person who lives away from their town or village of origin, mining worker: a person who works in the mining areas, N = number of case, aRR = adjusted risk ratio, CI = confidence interval.  4-2.3)) had a higher risk of not returning for HBs Ab while PWIDs from Tamakhan (aRR (95%CI): 0.6 (0.5-0.9)) had a lower risk compared to those who lived in Selzin. Among all recorded occupations, migrant workers (aRR (95%CI): 1.3 (1.0-1.6)) had a higher risk of not coming for HBs Ab testing. Among participants with completed vaccination in which HBsAb test was done, factors associated with sero un-protection are shown in Table 3. HIV positive participants had a higher risk of being HBV sero-unprotected compared to the ones with HIV negative status [aRR (95%CI): 1.8 (1.6-2.2)]. * Row percentage, refused vaccination: a person who did not want to take three doses vaccination due of the high cost of transportation, 1 drug dealer: a person who sells illicit drugs, 2 jade broker: a person who buys and sells a green precious stone and jewellery, migrant worker: a person who lives away from their town or village of origin, mining worker: a person who works in the mining areas, N = number of case, aRR = adjusted risk ratio, CI = confidence interval.

Discussion
In our study, one third of PWIDs did not complete the hepatitis B vaccination schedule. Among those who completed the vaccination and had their Hepatitis B Antibody performed, almost one third were sero-unprotected. However, the fact that two-thirds of PWIDs clients completed hepatitis B vaccination demonstrated the performance of our harm reduction program for PWIDs. It compares favorably with hepatitis B vaccination programs elsewhere: 52% completion rates in UK [12], 47%, 31% and 27% in different US settings [13] and 59.2% of PWIDs who had received a first dose in Sweden [14].
We found several socio-demographic and clinical characteristics associated with incomplete vaccination and sero-un-protection. We present them separately to tackle each of the findings relevance for programmatic reorientations.
In the AHRN program, HIV and HBV screening were offered at the same place on the same day, which may have helped PWIDs receive information about both HIV and HBV. However, one-tenth of PWIDs refused HIV testing, which may underestimate the proportion of HIV in the study population.
Our study reported clients with HIV infection to be more likely HBV sero-unprotected. This indicates that despite the higher vaccination dose used in HIV positive PWIDs, we need to continue our efforts to offer and comply with the second series of three doses, as mentioned in the literature [15].
More than one-third of young and middle-aged adults (aged 18-44 years) failed to complete the HBV vaccination. This finding is in line with a recent study in London that mentioned that PWIDs in a similar age group were less likely to complete vaccination [12]. Considering that this age group is economically active and may incur a loss of wages, they may have more trouble coming for multiple visits to complete vaccination. Though the program provides monetary incentives after completion of the third dose, additional transport reimbursements on the day of the first and second doses might motivate clients to return for vaccination. It has been recognized that adults with high-risk behaviours, such as PWIDs, are the second most urgent group to be prioritized for complete vaccination after infants [16], thus this group needs attention.
Migrant workers are known for being lost to follow up in vaccination programs [17]. Our study found that a significant proportion of migrant workers did not return for HBV antibody testing after completion of vaccination. To address this, programs must devise strategies to establish a referral link to other program sites or government healthcare centers for migrant workers, near their places of work. Catch-up vaccination drives using mobile vans that visit jade mining sites would help to complete vaccination schedules.
In our study, PWIDs who were using methadone had a higher proportion of vaccination completion. More than half of PWIDs using methadone were HIV-infected, and they received ART services in the same clinic. We suggest that, as methadone users were coming to the clinic often to receive methadone and ART services, they were more likely to complete the vaccination schedule [18]. Methadone users could be great advocates for HBV vaccination and inform their networks to avail the services of the clinic.
The study had the following strengths. HBV vaccination services were evaluated for PWIDs in the routine program of AHRN in Myanmar and thus reflect the on-the-ground realities. Our study population was high risk for HBV and difficult to reach, and therefore the study created a unique opportunity to access those clients through AHRN services. The program activities of HBsAg screening, consent for vaccination, vaccination provision, HBsAb testing and data entry were performed by trained staff. Vaccination cards were checked by the nurse on the day of antibody testing to confirm vaccination completion [19].
Our study had three main limitations. It was based on secondary data, so there could be errors and omissions, though the data supervisor in the program ensured the quality of data. The study included only clients of the AHRN services, thus the results of the study may not be generalizable to all PWIDs in Myanmar. PWIDs attending AHRN may have different attitudes and adherence behaviours towards health services than other PWIDs not attending. Approximately one-tenth of PWIDs refused to do an HIV test, so the proportions of HBV sero-non-protection in HIV positive PWIDs may be under-estimated.

Conclusions
In a harm-reduction program for PWIDs in Myanmar, we demonstrated that two-thirds of clients completed the three injection vaccination schedule, and of those, 70% showed sero-conversion. However, one-third of the most numerous and economically active group of 18−44-year-old age group failed to complete the vaccination schedule. As well, migrant workers had a poorer completion rate and HIV clients had a lower sero-conversion rate despite a higher dose of vaccine. We recommend HBV programs in this setting should focus on young adults and migrant workers as priorities for completion of vaccination. Methadone users receiving HIV services may also be a good resource in recruiting clients for hepatitis B vaccination.