Patients' experience of accessing hepatitis C treatment through the Myanmar national hepatitis C treatment program: a qualitative evaluation.

BACKGROUND: Globally, 56.8 million people are living with hepatitis C and over three-quarters of those reside in low and middle-income countries (LMICs). Barriers and enablers to hepatitis C care among people who inject drugs in high-income countries are well documented. However, there is scant literature describing the patient experience in LMICs. Understanding the barriers and enablers to care from the patient perspective is important to inform service refinements to improve accessibility and acceptability of hepatitis C care. METHODS: We conducted a qualitative evaluation of the patient experience of accessing the national hepatitis C program at eight hospital sites in Myanmar. Semi-structured interviews were conducted with four to five participants per site. Interview data were analysed thematically, with deductive codes from Levesque et al.'s (2013) Framework on patient-centred access to healthcare. RESULTS: Across the eight sites, 38 participants who had completed treatment were interviewed. Barriers to accessing care were mostly related to attending for care and included travel time and costs, multiple appointments, and wait times. Some participants described how they did not receive adequate information on hepatitis C, particularly its transmission routes, and on the level of cirrhosis of their liver and what they were required to do after treatment (i.e. reduce alcohol consumption, liver cirrhosis monitoring). Many participants commented that they had few or no opportunities to ask questions. Provision of treatment at no cost was essential to accessibility, and gratitude for free treatment led to high acceptability of care, even when accessing care was inconvenient. CONCLUSIONS: These findings highlight the importance of streamlining and decentralising health services, adequate human resourcing and training, and affordable treatment in maximising the accessibility and acceptability of hepatitis C care in LMICs. Findings from this work will inform future service delivery refinements for national program and other decentralised programs to improve accessibility and acceptability of hepatitis C care in Myanmar.

Cost-effectiveness of a decentralized, community-based "one-stop-shop" hepatitis C testing and treatment program in Yangon, Myanmar.

Background and Aim: The availability of direct-acting antiviral (DAA) treatment and point-of-care diagnostic testing has made hepatitis C (HCV) elimination possible even in low- and middle-income countries (LMICs); however, testing and treatment costs remain a barrier. We estimated the cost and cost-effectiveness of a decentralized community-based HCV testing and treatment program (CT2) in Myanmar. Methods: Primary cost data included the costs of DAAs, investigations, medical supplies and other consumables, staff salaries, equipment, and overheads. A deterministic cohort-based Markov model was used to estimate the average cost of care, the overall quality-adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) of providing testing and DAA treatment compared with a modeled counterfactual scenario of no testing and no treatment. Results: From 30 January to 30 September 2019, 633 patients were enrolled, of whom 535 were HCV RNA-positive, 489 were treatment eligible, and 488 were treated. Lifetime discounted costs and QALYs of the cohort in the counterfactual no testing and no treatment scenario were estimated to be USD61790 (57 898-66 898) and 6309 (5682-6363) respectively, compared with USD123 248 (122 432-124 101) and 6518 (5894-6671) with the CT2 model of care, giving an ICER of USD294 (192-340) per QALY gained. This "one-stop-shop" model of care has a 90% likelihood of being cost-effective if benchmarked against a willingness to pay of US$300, which is 20% of Myanmar's GDP per capita (2020). Conclusions: The CT2 model of HCV care is cost-effective in Myanmar and should be expanded to meet the National Hepatitis Control Program's 2030 target, alongside increasing the affordability and accessibility of services.

Patients' access to and acceptance of community-based hepatitis C testing and treatment in Myanmar: A mixed-method study.

Hepatitis C (HCV) infection elimination in low- and middle-income countries requires decentralised HCV services to increase testing and linkage to care. The CT2 Study investigated patients' views of access to and acceptance of two community-based HCV care models in Myanmar using a mixed-methods approach. Point-of-care HCV testing and general practitioner-initiated HCV treatment were provided at two community clinics in Yangon, Myanmar-the Burnet Institute's (BI) clinic focused on people who inject drugs (PWID), and the Myanmar Liver Foundation's (MLF) clinic focused on people with liver-related diseases. Study staff administered quantitative questionnaires to 633 participants receiving anti-HCV antibody testing. Purposive sampling was used to recruit 29 participants receiving direct-acting antiviral treatment for qualitative interviews. Among participants completing quantitative questionnaires, almost all reported the clinic location was convenient (447/463, 97%), waiting time was acceptable (455/463, 98%), and HCV antibody and RNA testing methods were acceptable (617/632, 98% and 592/605, 97% respectively). Nearly all participants were satisfied with their clinic's services (444/463, 96%) and preferred same-day test results (589/632, 93%). BI clinic participants were more confident that they understood HCV antibody and RNA results; MLF clinic participants were more comfortable disclosing their risk behaviour to staff and had slightly higher satisfaction with the overall care, privacy and secure storage of their information. In qualitative interviews, participants reported that flexible appointment scheduling, short wait times and rapid return of results increased the clinic's accessibility. The simplified point-of-care testing and treatment procedures and supportive healthcare providers contributed to participants' acceptance of the HCV care model. This decentralised community-based HCV testing and treatment model was highly accessible and acceptable to CT2 participants. Prioritizing patient-centred care, rapid provision of results, flexible appointments and convenient clinic locations can promote accessible and acceptable services which may in turn help accelerate progress in reaching HCV elimination targets.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

Access to needles and syringes and methadone maintenance therapy among people who inject drugs in Yangon, Myanmar: a qualitative study.

BACKGROUND: Access to sterile needles, syringes and methadone maintenance therapy (MMT) is critical to reduce the prevalence of bloodborne virus infections among people who inject drugs (PWID). We aimed to explore the experiences of PWID with respect to accessing needles/syringes services and MMT in Yangon, Myanmar. METHODS: Burnet Institute implemented a community-based hepatitis C testing and treatment (CT2) program for PWID with on-site needles and syringes distribution. Separate from CT2, MMT was available at two government-run sites in Yangon. We conducted in-depth interviews with 15 PWID who received hepatitis C care in this program. Interviews were transcribed verbatim and translated into English. Thematic data analysis was performed using NVivo12 software. RESULTS: Self-reported changes to needles/syringes sharing behaviour after hepatitis C education in the CT2 program and commencement of treatment were observed. One third of participants reported they became aware of the risks of sharing and reusing needles/syringes, and consequently refrained from sharing after the CT2 program. Inadequate availability of NSPs, cost of needles/syringes, and issues maintaining privacy when accessing needles/syringes emerged as key barriers to accessibility of needles/syringes. Participants described difficulties in accessing free needles/syringes. They were not aware of other free needles/syringes services at the time of the interview. Purchasing needles/syringes from pharmacies had privacy and confidentiality concerns. Structural barriers to accessibility of MMT were identified for both MMT sites in Yangon. Of the two MMT sites in Yangon, participants reported that the Ywarthargyi center had strict eligibility criteria for take-home methadone and transportation issues as it was located in the outskirt of the town. The Thingyangyun center was in a more convenient location, but only offered daily observed doses and had a long waiting time which was burdensome for some employed participants. CONCLUSION: Expansion of free needles/syringes services and adaptations of MMT to consider the needs and individual preferences of PWID will improve their access to these services and would likely reduce injecting related harms.

Feasibility of decentralised, task-shifted hepatitis C testing and treatment services in urban Myanmar: implications for scale-up.

OBJECTIVES: To assess the feasibility considerations for a decentralised, one-stop-shop model of care implemented in Yangon, Myanmar. SETTING: Two primary care level clinics in urban Yangon, Myanmar. DESIGN: This is a feasibility study of a highly effective care model. Using Intervention Complexity Framework by Gericke et al, we collated and analysed programmatic data and evaluation data to outline key project implementation requirements and experiences. PARTICIPANTS: Programmatic data were collected from clinical records, GeneXpert device test and maintenance reports, national guidelines, product and device instructions and site monitoring visit reports. Healthcare providers involved in delivering care model contributed interview data. RESULTS: The main feasibility considerations are appropriate storage for test kits and treatments (in response to temperature and humidity requirements), installation of a continuous stable electricity supply for the GeneXpert device, air-conditioning for the laboratory room hosting GeneXpert, access to a laboratory for pretreatment assessments and clear referral pathways for specialist consultation when required. Lessons from our project implementation experiences included the extensive time requirements for patient education, the importance of regular error monitoring and stock storage reviews and that flexible appointment scheduling and robust reminder system likely contributed to high retention in care. CONCLUSIONS: Detailed documentation and dissemination of feasibility requirements and implementation considerations is vital to assist others to successfully implement a similar model of care elsewhere. We provide 10 recommendations for successful implementation. TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov NCT03939013 on May 6, 2019. This manuscript presents post-results data on feasibility.

Operational experiences associated with the implementation of near point-of-care early infant diagnosis of HIV in Myanmar: a qualitative study.

BACKGROUND: Timely diagnosis and early initiation of life-saving antiretroviral therapy are critical factors in preventing mortality among HIV-infected infants. However, resource-limited settings experience numerous challenges associated with centralised laboratory-based testing, including low rates of testing, complex sample referral pathways and unacceptably long turnaround times for results. Point-of-care (POC) HIV testing for HIV-exposed infants can enable same-day communication of results and early treatment initiation for HIV-infected infants. However, complex operational issues and service integration can limit utility and must be well understood prior to implementation. We explored and documented the challenges and enabling factors in implementing the POC Xpert® HIV-1 Qual test (Cepheid, Sunnyvale, CA, USA) for early infant diagnosis (EID) as part of routine services in four public hospitals in Myanmar. METHODS: This sub-study was part of a randomised controlled stepped-wedge trial (Australian and New Zealand Clinical Trials Registry, number 12616000734460) designed to investigate the impact of POC testing for EID in Myanmar and Papua New Guinea. Infants recruited during the intervention phase underwent POC testing at the participating hospitals as part of routine care. Semi-structured interviews with 23 caregivers, 12 healthcare providers and 10 key informants were used to explore experiences of POC-EID testing. The research team and hospital staff documented and discussed implementation challenges throughout the study. RESULTS: Overall, caregivers and healthcare workers were satisfied with the short turnaround time of the POC test. Occasional delays in POC testing were mostly attributable to late receipt of samples by laboratory technicians and communication constraints among healthcare staff. Hospital staff valued technical assistance from the research group and the National Health Laboratory. Despite staff shortages and infrastructure challenges such as unreliable electricity supply and cramped space, healthcare workers and caregivers found the implementation of the POC test to be feasible at pilot sites. CONCLUSIONS: As plans for national scale-up evolve, there needs to be a continual focus on staff training, communication pathways and infrastructure. Other models of care, such as allowing non-laboratory-trained personnel to perform POC testing, and cost effectiveness should also be evaluated.

Hepatitis C elimination in Myanmar: Modelling the impact, cost, cost-effectiveness and economic benefits.

BACKGROUND: Myanmar has set national hepatitis C (HCV) targets to achieve 50% of people diagnosed and 50% treated by 2030. The WHO has additional targets of reducing incidence by 80% and mortality by 65% by 2030. We aimed to estimate the impact, cost, cost-effectiveness and net economic benefit of achieving these targets. METHODS: Mathematical models of HCV transmission, disease progression and the care cascade were calibrated to 15 administrative regions of Myanmar. Cost data were collected from a community testing and treatment program in Yangon. Three scenarios were projected for 2020-2030: (1) baseline (current levels of testing/treatment); and testing/treatment scaled up sufficiently to reach (2) the national strategy targets; and (3) the WHO targets. FINDINGS: Without treatment scale-up, 333,000 new HCV infections and 97,000 HCV-related deaths were estimated to occur in Myanmar 2020-2030, with HCV costing a total $100 million in direct costs (testing, treatment, disease management) and $10.4 billion in lost productivity. In the model, treating 55,000 people each year was sufficient to reach the national strategy targets and prevented a cumulative 40,000 new infections (12%) and 25,000 HCV-related deaths (25%) 2020-2030. This was estimated to cost a total $189 million in direct costs ($243 per DALY averted compared to no treatment scale-up), but only $9.8 billion in lost productivity, making it cost-saving from a societal perspective by 2024 with an estimated net economic benefit of $553 million by 2030. Reaching the WHO targets required further treatment scale-up and additional direct costs but resulted in greater longer-term benefits. INTERPRETATION: Current levels of HCV testing and treatment in Myanmar are insufficient to reach the national strategy targets. Scaling up HCV testing and treatment in Myanmar to reach the national strategy targets is estimated to generate significant health and economic benefits. FUNDING: Gilead Sciences.

Outcomes of the CT2 study: A 'one-stop-shop' for community-based hepatitis C testing and treatment in Yangon, Myanmar.

BACKGROUND: With the advent of low-cost generic direct-acting antivirals (DAA), hepatitis C (HCV) elimination is now achievable even in low-/middle-income settings. We assessed the feasibility and effectiveness of a simplified clinical pathway using point-of-care diagnostic testing and non-specialist-led care in a decentralized, community-based setting. METHODS: This feasibility study was conducted at two sites in Yangon, Myanmar: one for people who inject drugs (PWID), and the other for people with liver disease. Participants underwent on-site rapid anti-HCV testing and HCV RNA testing using GeneXpert(R) . General practitioners determined whether participants started DAA therapy immediately or required specialist evaluation. Primary outcome measures were progression through the HCV care cascade, including uptake of RNA testing and treatment, and treatment outcomes. FINDINGS: All 633 participants underwent anti-HCV testing; 606 (96%) were anti-HCV positive and had HCV RNA testing. Of 606 tested, 535 (88%) were RNA positive and had pre-treatment assessments; 30 (6%) completed specialist evaluation. Of 535 RNA positive participants, 489 (91%) were eligible to initiate DAAs, 477 (98%) completed DAA therapy and 421 achieved SVR12 (92%; 421/456). Outcomes were similar by site: PWID site: 91% [146/161], and liver disease site: 93% [275/295]). Compensated cirrhotic patients were treated in the community; they achieved an SVR12 of 83% (19/23). Median time from RNA test to DAA initiation was 3 days (IQR 2-5). CONCLUSIONS: Delivering a simplified, non-specialist-led HCV treatment pathway in a decentralized community setting was feasible in Yangon, Myanmar; retention in care and treatment success rates were very high. This care model could be integral in scaling up HCV services in Myanmar and other low- and middle-income settings.

Caregiver experience and perceived acceptability of a novel near point-of-care early infant HIV diagnostic test among caregivers enrolled in the PMTCT program, Myanmar: A qualitative study.

BACKGROUND: The majority of HIV infection among children occurs through mother-to-child transmission. HIV exposed infants are recommended to have virological testing at birth or 4-6 weeks of age but challenges with centralized laboratory-based testing in Myanmar result in low testing rates and delays in result communication and treatment initiation. Decentralized point-of-care (POC) testing when integrated in prevention of mother-to-child transmission of HIV (PMTCT) services, can be an alternative to increase coverage of early infant diagnosis (EID) and timely engagement in HIV treatment and care. AIM: This paper aims to explore experiences of caregivers of HIV-exposed infants enrolled in the PMTCT program in Myanmar and the perceived acceptability of point-of-care EID testing compared to conventional centralised laboratory-based testing. METHODS: This is a sub-study of the cluster randomised controlled stepped-wedge trial (Trial registration number: ACTRN12616000734460) that assessed the impact of near POC EID testing using Xpert HIV-1 Qual assay in four public hospitals in Myanmar. Caregivers of infants who were enrolled in the intervention phase of the main study, had been tested with both Xpert and standard of care tests and had received the results were eligible for this qualitative study. Semi-structured interviews were conducted with 23 caregivers. Interviews were audio recorded, transcribed verbatim and translated into English. Thematic data analysis was undertaken using NVivo 12 Software (QSR International). RESULTS: The majority of caregivers were satisfied with the quality of care provided by PMTCT services. However, they encountered social and financial access barriers to attend the PMTCT clinic regularly. Mothers had concerns about community stigma from the disclosure of their HIV status and the potential consequences for their infants. While medical care at the PMTCT clinics was free, caregivers sometimes experienced financial difficulties associated with out-of-pocket expenses for childbirth and transportation. Some caregivers had to choose not to attend work (impacting their income) or the adult antiretroviral clinic in order to attend the paediatric PMTCT clinic appointment. The acceptability of the Xpert testing process was high among the caregiver participants and more than half received the Xpert result on the same day as testing. Short turnaround time of the near POC EID testing enabled the caregivers to find out their infants' HIV status quicker, thereby shortening the stressful waiting time for results. CONCLUSION: Our study identified important access challenges facing caregivers of HIV exposed infants and high acceptability of near POC EID testing. Improving the retention rate in the PMTCT and EID programs necessitates careful attention of program managers and policy makers to these challenges, and POC EID represents a potential solution.

Decentralized, Community-Based Hepatitis C Point-of-Care Testing and Direct-Acting Antiviral Treatment for People Who Inject Drugs and the General Population in Myanmar: Protocol for a Feasibility Study.

BACKGROUND: The advent of direct-acting antivirals (DAAs) and point-of-care (POC) testing platforms for hepatitis C allow for the decentralization of care to primary care settings. In many countries, access to DAAs is generally limited to tertiary hospitals, with limited published research documenting decentralized models of care in low-and middle-income settings. OBJECTIVE: This study aims to assess the feasibility, acceptability, effectiveness, and cost-effectiveness of decentralized community-based POC testing and DAA therapy for hepatitis C among people who inject drugs and the general population in Yangon, Myanmar. METHODS: Rapid diagnostic tests for anti-hepatitis C antibodies were carried out on-site and, if reactive, were followed by POC GeneXpert hepatitis C RNA polymerase chain reaction tests. External laboratory blood tests to exclude other major health issues were undertaken. Results were given to participants at their next appointment, with the participants commencing DAA therapy that day if a specialist review was not required. Standard clinical data were collected, and the participants completed behavioral questionnaires. The primary outcome measures are the proportion of participants receiving GeneXpert hepatitis C RNA test, the proportion of participants commencing DAA therapy, the proportion of participants completing DAA therapy, and the proportion of participants achieving sustained virological response 12 weeks after completing DAA therapy. RESULTS: Recruitment was completed on September 30, 2019. Monitoring visits and treatment outcome visits are scheduled to continue until June 2020. CONCLUSIONS: This feasibility study in Myanmar contributes to the evidence gap for community-based hepatitis C care in low- and middle-income settings. Evidence from this study will inform the scale-up of hepatitis C treatment programs in Myanmar and globally.

Biological and molecular characteristics of Mycobacterium tuberculosis clinical isolates with low-level resistance to isoniazid in Japan.

We reevaluated the BACTEC MGIT 960 antimicrobial susceptibility testing system (MGIT 960 AST) by using 1,112 isolates of Mycobacterium tuberculosis. When the results of MGIT 960 AST were compared with that of the proportion method using Ogawa medium (Ogawa PM), discrepant results were obtained for 30 strains with isoniazid, all resistant by MGIT 960 AST but susceptible by Ogawa PM. For 93% of the strains that produced discrepant results, the MIC was 0.4 or 0.8 microg/ml, showing resistance by the proportion method using Middlebrook agar plates. Furthermore, it was also established by analyses of the katG and inhA genes that strains resistant only by MGIT 960 AST have a low level of isoniazid (INH) resistance, indicating that MGIT 960 AST is a reliable method. Ninety-six strains were resistant to 0.1 microg/ml INH by MGIT 960 AST. When they were divided into three groups, Low-S (susceptible at 0.2 microg/ml), Low-R (resistant at 0.2 microg/ml), and High-R (resistant at 1.0 microg/ml), by Ogawa PM, 43.3% of the Low-S strains had mutations in the promoter region of inhA and no mutations were detected in katG codon 315, while 61.7% of the High-R strains had katG codon 315 mutations or a gross deletion of katG. These results suggest that mutations in inhA are associated with low-level resistance to INH and katG codon 315 mutations are associated with high-level resistance to INH. In addition, the analyses demonstrated some relationship of mutations in the inhA gene with ethionamide resistance for the Low-S strains, but not for the High-R strains.

Mental health and psychosocial aspects of disaster preparedness in Myanmar.

Myanmar as a country in South-East Asia is vulnerable to disasters including storms, floods, fire, earth fall, earthquakes, depending on the geographical nature and climate of the area. The National Health Committee (NHC) of Myanmar has formed under it an Emergency Healthcare Committee. After the Asian tsunami, the Ministry of Health (MoH) formed the National Disaster Preparedness and Response Committee which developed the National Guidelines for Disasters Preparedness and Response. The experience of dealing with the tsunami has shown that psychosocial support to the affected community not only reduces its psychological distress but can also facilitate physical rehabilitation. Thus mental health and psychosocial aspects have been included in disaster preparedness and management plans of the MoH.

Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA and induction of apoptotic cell death.

Curcumin, a well-known antioxidant in a principal ingredient of turmeric, acted as a prooxidant causing a copper-dependent DNA damage and the induction of apoptosis. Treatment of DNA from plasmid pBR322 and calf thymus with curcumin plus copper ion caused strand scission and the formation of 8-hydroxy-2(')-deoxyguanosine in DNA. Addition of catalase protected DNA from the curcumin-dependent injuries, indicating that hydroxyl radical may participate in the DNA damage. Flow cytometry analysis showed that curcumin caused an apoptotic cell death of HL60 cells in a dose- and time-dependent manner. Curcumin-mediated apoptosis was closely related to the increase in intracellular reactive oxygen species. On the contrary, capsaicinoids, which have a ortho-methoxy phenolic structure without beta-diketone in the side chain, did not produce 8-hydroxy-2(')-deoxyguanosine. Capsaicin further did not induce apoptosis of HL60 cells, but rather protected cells from prooxidant-induced apoptosis. Curcumin can generate reactive oxygen species as a prooxidant in the presence of transition metals in cells, resulting in DNA injuries and apoptotic cell death. The prooxidant action of curcumin may be related to the conjugated beta-diketone structure of this compound.