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

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

LUONG ANH BINH

LATENT TUBERCULOSIS INFECTION

DIAGNOSIS AND TREATMENT

IN QUANG NAM, DANANG AND RESULTS

OF PUBLIC HEALTH INTERVENTIONS

Specialism : Public Health

ABSTRACT OF PUBLIC HEALTH THESIS

HANOI - 2021

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:

1 To describe the current situation of screening household contacts with pulmonary TB patients and LTBI treatment in Quang Nam and Danang in 2016

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 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, 4 charts, 78 references, including English and Vietnamese versions

CHAPTER 1 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 3 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

TB burden estimation in Vietnam - 2018 Number

(1,000 pop.)

Rate (per 100.000 pop.)

Multi-drug resistant rate among re-treatment TB cases (%) 17 (17 - 18)

Source: Updated country profile Vietnam 2019 - WHO

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 5 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 4 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 3 months (3HP), Rifampicin and Isonizid daily for 3 months (3RH)

CHAPTER 2 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: 3 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 2 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 in-depth 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 3 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 9 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

Intervention sites Control sites

value Number

p-Cumulative rate (%) Number

Cumulative rate (%)

Contacts joined the

screening (no Mantoux

0,006 Contacts started LTBI

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<0.001)

Table 3.8: Characteristic of household contacts (N=1,089) Characteristic Total Danang Quang Nam p-value

3.2.2 Cascade of care in LTBI mangement among household contacts with the index patients

Cascade of care in LTBI management at the intervention sites by step was showed as follows

Table 3.10 Cascade of care in LTBI mangement among household

contacts with the index patients (by step)

Step 1 Household contacts identified wanted to join the screening (n=1623)

Contents Total Danang Quang Nam p-value

Step 6 Household contacts completed medical evaluation (n=776)

Table 3.12 Household contacts’ results of screening and medical evaluation

The step of medical evaluation detected 27 active TB patients, accounted for 3.5% (27/766), in which, 40.7% at group <5 years (11/27) The number of TB patients detected was the highest at Son Tra, accounted for 81.4% (22/27), other districts detected very few TB patients, namely, Tam Ky and Phu Ninh detected 1 TB patient per district, Lien Chieu detected 3 TB patients

Figure 3.1: Proportion of household contacts attending each step of

the cascade of care in LTBI management

The proportion of dropouts was the highest at the step 2 (visited health facilities for screening), followed by the step 4 (eligible for medical evaluation) and the step 7 (recommended for LTBI treatment)

Table 3.15 Household contacts recommended for LTBI treatment

and started treatment by age group

Household contacts recommended for LTBI treatment (n=548)

with the lowest acceptance was less than 5 years (73.6%)

Table 3.14 Treatment outcome of LTBI cases

of side-effect Transfer Defaulted

Table 3.18 Cascade of care in LTBI mangement among household contacts

with the index patients by province

Household contacts identified wanted to join the screening (n=1623)

Comparing the data among the 04 intervention districts, the proportion of household contacts participating in each step of the cascade was the most stably high when compared with other 3 remaining districts, followed by Son Tra