Thực trạng chẩn đoán và điều trị lao tiềm ẩn tại 2 tỉnh quảng nam, đà nẵng và kết quả một số giải pháp can thiệp TT TIENG ANH

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEATH HANOI MEDICAL UNIVERSITY LUONG ANH BINH LATENT TUBERCULOSIS INFECTION DIAGNOSIS AND TREATMENT IN QUANG NAM, DANANG AND RESULTS OF PUBLIC HEALTH INTERVENTIONS Specialism : Public Health Code : 62720301 ABSTRACT OF PUBLIC HEALTH THESIS HANOI - 2021 The thesis has been completed at HANOI MEDICAL UNIVERSITY Supervisors: Supervisor 1: Assoc Prof Nguyen Viet Nhung, MD PhD Supervisor 2: Prof Luu Ngoc Hoat, MD PhD Reviewer 1: Reviewer 2: Reviewer 3: The thesis will be present in front of board of university examiner and reviewer lever at on 2021 This thesis can be found at: - National Library - Library of Hanoi Medical University INTRODUCTION According to the World Health Organization (WHO), despite gaining significant achievements in TB control, Tuberculosis (TB) has been still one of the main health problems in the world The 2019 global Tuberculosis Report by WHO estimated that the world has about 10 million new TB cases, 1.7 million people with latent TB infection (LTBI) Vietnam still ranked at 11th out of 30 countries with the highest burden TB and MDR- TB on the world, the rate of LTBI in Vietnam was estimated at about 40% LTBI is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifest active TB The LTBI people have no signs or symptoms of TB but are at risk for active TB disease Several studies have shown that, on average, 5-10% of those infected will develop active TB disease over the course of their life LTBI diagnosis and treatment is the main intervention for global TB control, and is recommended by the WHO, especially for the high-risk groups such as people living with HIV, close contact with TB patients However, in the countries with low and middle - income including Vietnam, expansion of LTBI diagnosis and treatment is a big challenge, one of the main barriers is drop-outs at each step of LTBI management cascade, from identification, diagnosis, medical evaluation, treatment enrolment and completion, which reduced 90% benefits of LTBI management With expectation of improving LTBI management capacity, the study “LTBI diagnosis and treatment in Quang Nam, Danang and results of public health interventions” was conducted with aiming at following objectives: To describe the current situation of screening household contacts with pulmonary TB patients and LTBI treatment in Quang Nam and Danang in 2016 To evaluate results of interventions for household contacts with pulmonary TB patients and LTBI treatment in Quang Nam and Danang in the period July, 2017 to October, 2019 To describe a number of barriers detected during the interventive phase in order to recommend the reasonable solutions to improve LTBI diagnosis and treatment for household contacts New contribution of the thesis: This is the research that designed the public health interventions based on the scientific evidence with aiming at improving LTBI diagnosis, treatment, and contribution on TB prevention among high-risk group, namely, household contacts with TB patients Thesis outline: The thesis consists of 139 pages, in which, includes introduction (2 pages), objectives (1 page), literature review (28 pages), research targets and methods (23 pages), results (47 pages), discussion (35 pages), conclusion and recommendation (3 pages) The thesis includes 32 tables, 12 figures, charts, 78 references, including English and Vietnamese versions CHAPTER LITERATURE REVIEW 1.1 Tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) 1.1.1 General introduction of TB TB is defined as the disease state due to Mycobacterium Tuberculosis TB can affect in any parts of the body, in which, pulmonary TB is the most contagious type (accounted for 80-85%) TB patients have the TB symptoms, number of bacteria in TB patients are more than those in LTBI ones 1.1.2 General introduction of LTBI LTBI is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifest active TB Risk of activating from LTBI to TB: about 10% of those with normal immune system infected TB will develop active TB disease over the course of their life Those with immunodeficiency and TB infection, such as people living with HIV, have much higher risk of developing active TB disease, about 10% per year LTBI diagnosis: There is no gold standard test for direct identification of Mycobacterium Tuberculosis infection in human LTBI people are only diagnosed by immunoassay Currently, LTBI diagnosis depends on the two key tests, namely, Tuberculin Skin Test (TST) and Interferon-Gamma (Interferon-Gamma Release Assays/IGRAs) LTBI treatment: According to the Latent Tuberculosis Infection Update and consolidated guideline for programmatic management, WHO recommended to use Isoniazid monotherapy for 6-9 months, or Rifapentine and Isoniazid weekly for months, or Rifampicin plus Isoniazid daily for 3-4 months, or Rifampicin monotherapy for 3-4 months 1.2 LTBI situation in Vietnam and intervention strategies 1.2.1 TB and LTBI situation in Vietnam TB situation Vietnam is still the country with high TB burden Based on the results of the 2nd TB prevalence survey in 2017-2018, WHO re-estimated the TB burden in Vietnam Vietnam currently ranked at 11th out of 30 countries with the highest burden TB and MDR- TB on the world Table 1.5: TB burden in Vietnam, 2018 Number Rate (per (1,000 pop.) 100.000 pop.) TB mortality (HIV-) 11 (6,7-15) 11 (7-16) TB incidence, all forms (including HIV +) 174 (111-251) 182 (116-263) TB /HIV+ incidence (3,8-8,6) 6,2 (4-9) Detection rate, all forms (%) 57 (40-90) Multi-drug resistant rate among new TB cases (%) 3,6 (3,4 - 3,8) Multi-drug resistant rate among re-treatment TB cases (%) 17 (17 - 18) Source: Updated country profile Vietnam 2019 - WHO TB burden estimation in Vietnam - 2018 LTBI situation The statistic data of LTBI in Vietnam is quite limited The 1st TB infection and prevalence survey in 2006-2007 showed the infection risk in Vietnam, in general, was 1.67%, in which, the rate in urban area was 2.19%, in mountainous areas was 1.55%, agricultural areas was 1.63%, in the Northern region was 1.57%, Central region was 1.49% and Sourthern region was 2.05% Accordingly, the NTP estimated that more than 40% of Vietnamese population were infected with TB Vietnam also conducted a few researches to estimate the LTBI burden, but were in small scale A cross-sectional study conducted in Ca Mau province showed that the LTBI rate were 36.8%, the positive IGRA rate of the female was lower than that of male (31% vs 44,7%) Also in Ca Mau, another research showed that 25.8% of contacting with new pulmonary TB patients and 40,8% of contacting with MDR-TB patients had the positive Mantoux results 1.2.2 LTBI management program in Vietnam In Vietnam, LTBI managemnet program has started to conduct for the people living with HIV since 2000s Since 2012, the groups provided with LTBI treatment have been expanded for the children less than years or less than 15 years with HIV(+) who closely contacted with pulmonary TB patients Vietnam NTP piloted the Isoniazid monotherapy for the under-5-year children as household contacts with pulmonary TB patients in the provinces of Hanoi, Thai Binh, Hochiminh City and Can Tho Since 2015, the LTBI management for children has been expanded on the whole country In 2015, Ministry of Health issued the Guideline of preventive treatment for people living with HIV and under-5-year children as household contacts with pulmonary TB patients after being confirmation of no TB in order to improve LTBI management for these two groups on the whole country Up to 2017 and then in 2020, the guideline was updated to be align with the WHO recommendation and the NTP situation Accordingly, the high-risk groups of LTBI were expanded, especially focused on the household contacts at all ages with pulmonary TB patients; in addition, short-term regimens of LTBI treatment were added, namely, Rifapentine and Isoniazid weekly for months (3HP), Rifampicin and Isonizid daily for months (3RH) CHAPTER RESEARCH TARGETS AND METHODS 2.1 Research site and time: Research sites: the research was selected to conduct at the 08 district health centers in Danang and Quang Nam by randomization The 04 intervention sites included Tam Ky, Phu Ninh (Quang Nam province), Son Tra, Lien Chieu (Danang) The 04 control sites included Nui Thanh, Thang Binh (Quang Nam), Thanh Khe, Hai Chau (Danang) Research time: years from October 2016 to October 2019 The duration of intervention phase was from July 2017 to October 2019 2.2 Research target - Pulmonary TB patients (index patients) - Household contacts with pulmonary TB patients - Heath workers (NTP staff) at district level 2.3 Research design Objective 1: Cross-sectional descriptive research based on the secondary data related all pulmonary TB patients at the 04 intervention districts and 04 control districts in 2016 Objective 2: A pragmatic randomized controlled trial with community and health system interventions to detect the interventions that increased the results of LTBI screening and treatment Objective 3: Qualitative research to determine the barriers for recommending more reasonable solution 2.4 Research phases Phase 1: Pre-intervention assessment At intervention sites: Conduct baseline assessment at the 04 intervention sites At control sites: Collect the baseline data (2016) from Register of TB patients and Pediatrict TB management books of the NTP Phase 2: Development of interventions The interventions were developed based on the interview results for relevant groups (pulmonary TB patients, household contacts, health workers) and analysis of baseline indicators Phase 3: Implementation of interventions On the basis of Phase result, researchers conducted the public health interventions at the 04 intervention districts in order to increase LTBI patients with prevention treatment The interventions included: a) Training: Trainees were provincial and district health workers Training methods were primary training and continuous training via supportive supervision missions b) Communication and education for pulmonary TB patients and household contacts with LTBI accepted the LTBI treatment: designed and printed leaflets, folded sheets, posters related to LTBI, direct counselling between NTP health workers and pulmonary TB patients, household contacts and TB suspects c) Household contact investigation: name, age, gender, address, phone d) Coordination of one-stop service: (i) Mantoux test, (ii) read Mantoux test, (iii) clinical examination, chest X-ray, other tests to exclude active TB and confirme LTBI, (iv) specify LTBI treatment regimen At this intervention, researchers intervented to re-arrange the health services and health units where provided LTBI screening, diagnosis and treatment so that TB patients and their household contacts felt easy to approach e) Supply of Tuberculin and drugs: Tuberculin and consumables for Mantoux test, drugs for LTBI treatment f) Incentives for health workers: test fee and incentives when household contacts completed all steps of LTBI management cascade g) Cash support for household contact: support transportation fee for household contacts who visited the health facilities to conduct the screening tests h) Monitoring and reporting: Health workers recorded the results of household contact management, screening and LTBI treatment in the Register of household contact monitoring In the control sites, the LTBI management continued to conduct all current interventions approved by the NTP, including investigation of household contacts among the under-5-year children and under-15-year people with HIV positive, TB diagnosis in according to NTP guideline, LTBI treatment by Isoniazid monotherapy for 6-9 months, recording and reporting Phase 4: Post-intervention assessment Assessing results of intervention programs at the 04 intervention sites and the 04 control sites in Quang Nam and Danang through the following indicators: - Number of household contacts with pulmonary TB patients determined - Rate of household contacts provided with TB and LTBI screening - Rate of household contacts with screening completion - Rate of LTBI patients detected among household contacts - Rate of LTBI patients enrolled with LTBI treatment - Rate of LTBI treatment completed treatment course 2.5 Sampling size and technique Sample size for Objective 1: Collected secondary data related to all pulmonary TB patients and their household contacts in 2016 In the results, at the intervention sites, collected the secondary data of 99 household contacts with pulmonary TB patients in 2016, and number of household contacts collected the data in the control sites were 122 Sample size for Objective 2: Applied two-proportion comparison sampling methods to estimate the sample size at 1,300 household contacts In the results, the total of household contacts determined were 1,623, in which, 1,089 agreed to attend the screening, and the fact number to join the screening were 1,064 Sample size for Objective 3: The researchers selected the purposive sample size for in-depth interviews as follows: 04 pulmonary TB patients, new or relapse (index patients), 04 household contacts (adults) who visited health facilities for screening, 04 parents for under-5-year household contacts, 04 health workers involving in TB control activities) As a result, the total of indepth interviews conducted was 24 2.6 Data management and analysis Qualitative information was analyzed by topic Quantitative data were analyzed by STATA 14.0 CHAPTER RESEARCH RESULTS 3.1 Specific Objective 1: To describe the current situation of screening household contacts with pulmonary TB patients and LTBI treatment in Quang Nam and Danang in 2016 The cascade of care in LTBI diagnosis and treatment (cascade) included steps, namely, (1) household contacts identified, (2) household contacts visited for screening, (3) household contact completed the screening, (4) household contacts eligible for medical evaluation, (5) household contact started medical evaluation, (6) household contacts completed medical evaluation, (7) household contacts recommended for LTBI treatment, (8) household contacts accepted and started LTBI treatment, and (9) household contacts completed treatment The procedure of LTBI diagnosis and treatment at this time was incomprehensive when compared with the 9-step cascade Table 3.4 LTBI management among household contacts in 2016 by intervention and control sites Contents Index patients Estimated contacts Contacts joined the screening (no Mantoux test) Contacts started LTBI treatment Intervention sites Cumulative Number rate (%) 402 1206 100,0% Control sites Cumulative Number rate (%) 492 1476 100,0% pvalue 0,006 138 11,4% 122 8,3% 0,6% 0,6% 0,564 There was no significant difference between the intervention sites and control sites for the children screened (11.4% vs 8.3%), and children treated LTBI (0.6%) 3.2 Specific Objective 2: To evaluate results of interventions for household contacts with pulmonary TB patients and LTBI treatment in Quang Nam and Danang in the period July 2017 to October 2019 3.2.1 General information for research targets The results showed that 524 pulmonary TB patients (index patients) enrolled in the research, in which, 451 household contacts (86.1%) were identified The proportion of index patients from whom health workers could not identify their household contacts was significantly higher in Quang Nam than in Danang (27.6% vs 4.0%, p