TREATMENT OUTCOMES OF PATIENTS UNDER RNTCP DOTS IN KOLLAM DISTRICT, KERALA Dr Shibu Vijayan Dissertation submitted in partial fulfillment of the requirements for the award of the degree of Master of Public Health Achutha Menon Center for Health Science Studies Sree Chitra Tirunal Institute for Medical Sciences & Technology Trivandrum October 2007
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TREATMENT OUTCOMES OF PATIENTS UNDER RNTCP
DOTS IN KOLLAM DISTRICT, KERALA
Dr Shibu Vijayan
Dissertation submitted in partial fulfillment of the requirements for the
award of the degree of Master of Public Health
Achutha Menon Center for Health Science Studies Sree Chitra Tirunal Institute for Medical Sciences & Technology
Trivandrum
October 2007
l .
Declaration
I hereby certify that the work embodied in this dissertation titled 'Treatment
Outcomes of Patients under RNTCP DOTS in Kollam District, Kerala' is the result
of original research and has not been submitted in any form for another
degree/diploma at any university or other institution of higher education.
v ?;
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Trivandrum Dr Shibb Vijayan
October 2007
~
Acknowledgements
The most important part of this study could only be covered by the co-operation of respondents and the health staff especially the staff in RNTCP. Their hospitality, and the many hours spent together with them, made this work an outstanding experience which has deeply impressed me. I would like to thank all the respondents of the study.
I am extremely obliged to my guide Dr Manju Nair, Scientist C, AMCHSS, and it was a piece of good luck to have her as my mentor.
I am also indebted to Dr.Biju Soman, Assistant Professor, AMCHSS, Dr. Srinivasan, Kerala State WHO-RNTCP consultant, and Dr. Hemachandran, WHO consultant, PPMDOTS, Kerala for their cooperation in conceptualization of the research and preparation of study tools and sharing data.
I extend my heartfelt thanks to Dr. Jayasanker former District TB Officer, Kollam, Dr Neetha District TB Officer Kollam and Dr Sabeena second MO Kollam for their fabulous support offered to me for conducting the study. I am also thanking the RNTCP staff in Kollam district who helped me without any incentive to materialize this thesis.
I would like to thank all Medical Officers, TB control for arranging the staff for helping me in my data collection.
I would like to thank Dr. K. Mohandas, Director, Dr K R Thankappan, Professor and head, AMCHSS, and all my teachers including Dr. K Sundari Ravindran, Honorary Professor, Dr. V Raman Kutty, Professor, Dr. Mala Ramanathan, Additional Professor, Dr. P Sankara Sarma, Additional Professor and Dr. Richard A Cash, Visiting Professor, Harvard School of Public Health for their constructive criticisms and suggestions during the progress of the research and up until completion. I am also grateful to Mr. Sundar Jayasingh, Assistant Registrar, for his support in helping me through all the administrative procedures. Last, but not least, I do remember my family back in Kollam who have shared in my zest and supported me silently.
Certificate
Certified that the dissertation titled 'Treatment Outcomes of Patients under
RNTCP DOTS in Kollam District, Kerala' is a bonafide record of original research
work undertaken by Dr Shibu Vijayan, in partial fulfillment of the requirements for
the award of the Master of Public Health degree under my guidance and
supervision.
Guide~-Dr Manju Nair R Scientist C Achutha Menon Center for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum. October 2007
iii
Chapter List of abbreviations Abstract Introduction-! 1.1 1.2 1.2.1 1.2.2 1.2.3 1.2.4
Background 3 Literature review 4 Evolution of Tuberculosis control strategy.,. Global scenario 4 DOTS strategy 4 Evolution of Tuberculosis control strategy in India 6 Revised National Tuberculosis Control Programme (RNTCP) 7 DOTS Regimen 7 Impact of DOTS strategy in India 8 Factors affecting the treatment outcomes of Tuberculosis 9 Relapse 17 Rationale for the study 18 Objectives 19 Research Questions 19
Study type Study setting Sample size Sample selection procedures Definition of study variables Data collection Data collection methods Data entry and Analysis Ethical considerations
Characteristics of the cohort Age and Sex wise distribution of the cohort Initial smear status Outcome at the end of DOTS treatment Survey findings Characteristics of the sample Educational status Employment status Marital status House hold characteristics Type ofhouse Place of residence Socioeconomic status Smoking status
20 20 20 20 20 21 22 22 22
25 25 25 26 27 27 28 28 28 28 29 29 29 29
3.2.10 Smokeless tobacco use 30 3.2.11 Alcohol use 31 3.2.12 History of exposure to tuberculosis 31 3.2.13 Knowledge and perception about Tuberculosis and
Its treatment 31 3.2.14 History of previous Anti tuberculosis drugs 32 3.2.15 Facility first sought by patient for diagnosis 32 3.2.16 DOTS and its components 32 3.2.17 Profile of DOT centre 33 3.2.18 Intake of drugs 33 3.2.19 Treatment components 34 3.2.20 Duration of treatment 34 3.2.21 Adverse effects of drugs 34 3.2.22 Confidentiality and stigma 35 3.2.23 Co morbidities 35 3.2.24 Treatment outcome 18 months after completion
of treatment 36 3.2.25 Relapse 37 3.2.26 Death 37 3.2.27 Defaulters 37 3.2.28 Failure 37 3.2.29 Patients with unsupervised drug intake 37 3.2.30 Chest symptomatics 37 3.3 Factors affecting the outcome 38 3.3.1 Age group and outcome after the treatment (7 months) 38 3.3.2 Sex differential among treatment outcome 38 3.3.3 Pre treatment smear status and outcome. 39 3.3.4 Use of alcohol and treatment outcome 39 3.3.5 DOTS centre and type of drug intake 40 3.3.6 Diabetes and treatment outcomes 40 3.3.7 Type of DOTS centre and outcome 40 3.3.8 Outcome after 18 months after completion of
Treatment 41 3.3.8.1 Treatment outcomes 18 months after completion ofDOTS
And sex 41 3.3.8.2 Age and treatment outcomes after 18 months after
completion of treatment 42 3.4 Findings of verbal autopsy 42
Discussion-4 4.1 4.2 4.3 4.4 4.5 References
Annexure
Outcomes DOTS factors influencing outcomes Deaths Limitation of the study Conclusion and programme implications
44 48 50 52 52
54
•
AIDS
ATT
DM
DOTS
DTC
GOI
HIV
NACO
NTP
PTB
RNTCP
TB
WHO
MDRTB
SES
LIST OF ABBREVIATIONS
Acquired ImmunoDeficiency Syndrome
Anti Tuberculosis Treatment
Diabetes mellitus
Directly Observed Treatment Short course
District Tuberculosis Center
Government Of India
Human Immunodeficiency Virus
National AIDS control Organization
National Tuberculosis Program
Pulmonary Tuberculosis
Revised National Tuberculosis Control Program
Tuberculosis
World Health Organization
Multi Drug Resistant Tuberculosis
Socio Economic Status
•
Abstract Background: DOTS as a strategy was introduced to the Tuberculosis control programme in the District of Kollam, Kerala in 2000. The impact of the programme on treatment outcomes and the estimation of relapse within the DOTS has not been assessed ever since. The objective of the study is to identify the treatment outcomes of a cohort of new smear positive pulmonary tuberculosis patients registered under RNTCP- DOTS in the first quarter of 2005 after completion of treatment and after 18 months, and to analyze the factors associated with the various treatment outcomes
Methods: Cross sectional study of cohort of new sputum smear positive patient registered under RNTCP-DOTS during the first quarter of 2005 in the district of Kollam. The outcomes were assessed at the end of the DOTS treatment at the end of seven months after start of treatment and the patients interviewed at the end of eighteen months after completion of DOTS. Among 241 patient registered for DOTS, at the end of seven months 20 patients had died and at the time of study, excluding the patients who had died in the interim period and those lost to follow up a total of 193 patients were interviewed of which148 (76.7%) males. Pre tested structured questionnaire was used for data collection. Results: Mean age ofthe cohort was 51.04 (±16.18), males 53.09 (±15.27) and females is 43.58 (±17.35).At the end of seven months 85.9% cure rate death rate was 8.3%. Deaths were more among age group 2: 65, while youngest age group 100% cure. The initial smear status of the cohort was 3+ (57%), 2+ (23%) and 1+ and scanty (20%). Among the sample surveyed, ever smoker male were 124(83.8%) and current smokers 65 (43.9).Alcohol use among males ever used 113 (76.4%), current use 62 (41.9%) and consumption more than twice a week was 32 (21.8%). 180 ( 94.2%) took medicine as supervised or DOTS. The prevalence of diabetics was 30%. In bivariate analysis younger age group, not consuming alcohol more than twice a week was associated with favorable outcome (x2, P <.05). Significant association established with supervised drug intake and type of DOT centre in favorable of door delivery. No associations were found with initial smear status, co morbidities and smoking status with outcome. After 18 months 192 (90.9 %) disease free, 18 (8.5%) dead, and one patient unknown status. One patient relapsed and cured with DOTS retreatment within the period. Relapse rate 1 relapse/334 person years. Death rate is 16.5%.
Conclusion: The main finding of this study was the high cure rate and low relapse and default rates among the cohort of patients who had undergone DOTS. This may be due to the effective program implementation including retrieval of defaulter and timely follow up of those on treatment Use of alcohol was found to be significantly associated with treatment outcomes and there is a need to strengthen the alcohol cessation activities in RNTCP. The negative finding was a death rate of 8.3 percent which is more than double the program indicators which may be due to late arrival of patients for treatment seeking with in the advanced stages of the disease or late detection which requires further exploration. •
1.1 Background
Chapter I Introduction
Out of an estimated 8.8 million new TB cases occurring annually worldwide about 95
percent occur in developing countries, 7.4 million in Asia and sub-Saharan Africa I .A total
of 1.6 million people died of TB, including 195 000 patients infected with HIV2.India
accounts for one fifth of global incidence of TB and tops the list of 22 high TB burden
countries and, affects around 1.8 million Indians newly every year and killing 370,000
annually 3 .In India, more than 40 percent of population is infected with TB bacilli, it . is
estimated. two of every five Indians are infected with the TB bacillus, of them, 1 0 percent
will develop TB disease during their lifetime.3 Every smear-positive person, if left untreated,
has the potential to infect 10-15 persons per year, thereby increasing the pool of infected
persons4 •• Every day, about 5,000 people develop the disease and around 1000 die. Every
year, almost 1.8 million new cases occur in the country, of which almost half are infectious.
Patients with infectious pulmonary TB disease can infect 10-15 persons in a year. 5 Poorly
treated patients can develop drug-resistant and potentially incurable forms of TB. In India,
TB kills more adults in the most productive age group (15-54 years) than any other infectious
disease;
The Revised National Tuberculosis Control Program (RNTCP) has been implemented in the
country for close to a decade now, and more than 6.7 million patients have been put on
Directly Observed Treatment- Short Course (DOTS). It has geographically expanded to
achieve nation-wide coverage in March 2006, while maintaining a success rate higher than
3
the global target of 85 percent, and New Smear Positive case detection rate close to the
global benchmark of 70 percent. Under the TB Control program, priority is given to the
smear positive cases. The spread of HIV during the last two decades and the emergence of
MDR-TB pose additional challenges to effective TB control.
1.2 Literature review
1.2.1. Evolution of Tuberculosis control strategy- Global scenario
Scientific studies carried out on the treatment of TB in India6 had shown the necessity and
feasibility of giving drugs under supervision as also efficacy and safety of domiciliary
treatmene.Directly observed treatment, in which a DOT provider observes and assists as
patients take their medicine, is the most important component ofDOTS8,9' 10' 11 ' 12•
Global efforts to control TB were revamped in 1991, when a World Health Assembly
(WHA) resolution recognized TB as a major global public health problem and "a global
target of cure of 85 percent of sputum-positive patients under treatment and detection of 70
percent of cases by the year 2000"13• These targets were based on epidemiological modeling,
which suggests that achievement of an 85 percent cure rate and 70 percent case detection will
reduce the prevalence of infectious (sputum smear-positive) TB cases, the number of infected
contacts, and the incidence of infectious cases14 In 1994, the internationally recommended
control strategy, later named DOTS, was launched 15• The DOTS framework has
subsequently been expanded, further clarified, and implemented in 182 countries16•
1.2.2. DOTS strategy
Epidemiological evidences suggest that decrease in cases results from an interruption in the
spread of infection because of better rates of completion of treatment and expanded use of
DOTS17. Another positive aspect of DOTS was its cost effectiveness, even though the initial
4
costs are same for the DOTS as well as self administered treatment, but by preventing
failures and drug resistance that cost can be saved. 18 ' 19
Mortality due to TB has been declining and incidence diminishing or stabilizing in all world
regions except sub-Saharan Africa and, to some extent, Eastern Europe. The global treatment
success rate among new smear-positive TB cases had reached 83 percent by 2003 and in
2004 the case detection rate, which has accelerated globally since 2001 was 53 percene0• In
the United States, Baltimore demonstrated a marked reduction in case rates with use of
DOTS despite a higft rate of HIV infection21 • In New York city, by 1991, half of the TB
patients were HIV infected and one in five had multidrug resistant tuberculosis, but DOTS
resulted in a rapid decrease in both tuberculosis and in multidrug resistance22' 20• Experiences
in Malawi, Mozambique and Tanzania, documenting cure rates of 86-90 percent 23.Universal
DOT implementation in Cuba was associated with a substantial decline in tuberculosis24•
Prevalence of smear-positive tuberculosis in Beijing decreased form 127 per 100,000 in 1979
to 16 per 100,000 population in 1990, a decrease of 17 percent annually25• In the South-East
Asia Region, Bangladesh had had excellent success in DOTS implementation, with coverage
of more than two-thirds of the country and cure rates above 80 percent.26
The re emergence of tuberculosis (TB) as a public health problem in industrialized countries
was attributed to the combined effects of the human immunodeficiency virus (HIV) epidemic
and social factors such as rising poverty and homelessness in large cities, increased
demographic pressure, immigration and poorly organized TB control programmes. 27 ' 28 ' 29 ' 30
In short DOTS implementation has helped countries to improve national TB control
programmes (NTPs) and make major progress in TB control.
DOTS is a systematic strategy which has five components. These are as follows:
5
• Political and administrative commitment
• Good quality diagnosis, primarily by sputum smear microscopy
• Uninterrupted supply of good qua~ity drugs
• Directly observed treatment (DOT)
• Systematic monitoring and accountability
1.2.3 Evolution of tuberculosis control strategy in India
TB is the number one killer of adults among all infectious diseases, in India 1• 3· The TB
• control strategies started in India, with the establishment of the first open-air sanatorium
during the year 1906 at Tilonia near Ajmer. The Tuberculosis Association of India was
started in February 1939. Bac~llus Calmette Guerin (BCG) vaccination was the only avenue
for protection and prevention of tuberculosis and was introduced in India by 1948.. As a
preventiye measure, it was extensively used in most of the European countries in 1920s. The
National Sample Survey (1955 to 1958) was an eye opener, which revealed that the problem
of TB was uniformly distributed, both in the urban and rural population of the country31 .At
that time, the standard treatment for TB in India, and throughout the world, called for
isolation of TB patients in sanatoria. Thereafter, in 1962 a National TB Control Program was
started under which District TB centers were established. The idea was to set up a clinic
where patients could come and collect their drugs. It failed due to managerial problems and
lack of drug availability.
The burden ofHIV infection in India is estimated to be 5.22 million, which equates to
approximately 0.9 percent of the adult population of the country. Tuberculosis is one of the
earliest opportunistic diseases to develop amongst persons infected with HIV. Based on
6
mathematical modeling, WHO has estimated a prevalence of 5.2 percent of HIV in adult TB
patients in India32•
In 1992, GOI-WHO carried out an in depth review ofTB program in India as a part
of global review and observed glaring deficiencies like, inadequacy in budget allocation,
over-dependence on X-ray, poor treatment compliance, inadequate health infrastructure in
the urban areas and impending threat ofHIV worsening the scenario ofTB.
1.2.4. Revised National Tuberculosis Control Program (RNTCP) •
Based on the review, RNTCP took its roots in India in 1993 with WHO recommended
DOTS, by pilot testing the strategy in a population of about 18 million. From 1998-2001,
the population coverage and expansion was scaled up to cover a population of about 350
million33• Large-scale expansion of DOTS services in India began in 1997. In the past 8
years, RNTCP has been expanding rapidly covering 50 percent of the population in 2002,
and full nation wide coverage was achieved by March.
The goal of RNTCP is to decrease mortality and morbidity due to TB and cut transmission of
infection until TB ceases to be a major public health problem.
The objectives of RNTCP are to achieve and maintain a cure rate of at least 85 percent
among newly detected infectious (new sputum smear positive) cases, and to achieve and
maintain detection of at least 70 percent of such cases in the population.
1.2.5. DOTS regimen
Treatment under direct observation is given thrice weekly. For new smear-positive patients,
intensive phase treatment is given for two months (three months if the sputum smear is
positive at two months) with isoniazid, rifampicin, pyrazinamide and ethambutol. The policy
states that during the intensive phase every dose taken is to be directly observed by a health
7
worker or a community volunteer who is not a family member. In the continuation phase, the
first dose of treatment every week is to be directly observed, with the remaining two follow-
up doses self-administered by the patient30.
Sputum is examined after two and four months of treatment, at the end of treatment, and if
symptoms develop after stopping treatment. The treatment regimens used are those
recommended by the World Health Organization. Patients are considered cured if the results
of two sputum smears for acid-fast bacilli (AFB) are negative, one of which is done at the .. end of treatment. Treatment is considered to have failed if a patient has a positive smear 5
months or more after starting treatment. Relapse is considered to have occurred when a
patient who had previously been cured and was sputum smear-negative has a positive
smear34• A patient, who at any time after registration does not take anti-tuberculosis drugs
consecutively for 2 months or more, is said to have defaulted.
Other than the outcomes of treatment outcomes described two more outcomes are described,
Treatment completed- Sputum smear-positive patient who has completed treatment, with
negative· smears at the end of the . intensive phase but none at the end of treatment and Died-
Patient who died during the course of treatment regardless of cause.
1.2.6. Impact of DOTS strategy in India
The new smear positive (NSP) pulmonary TB case detection rate was 72 percent in 2004, 66
percent in 2005 and 66 percent in 2006, which is close to the global target of 70 percent.
Treatment success rate has been maintained consistently over the 85 percent global target.
Deaths due to TB have been reduced from over 500,000 annually at the beginning of the
program to currently fewer than 370,0002 • The quality of diagnosis was improved, with the
ratio of smear-positive to smear-negative patients being maintained at 1: 1. Treatment success
8
was achieved in 81 percent of new smear-positive patients, 82 pecent of new smear-negative
patients, 89 percent of patients with extra-pulmonary tuberculosis, and 70 percent of re
treatment patients35•
Considering both smear-positive and smear-negative cases in India, DOTS reduces the case
fatality rate by about 80 percene6• Following DOTS implementation, prevalence of culture
positive tuberculosis decreased rapidly following a gradual decline for the previous 30 years
with out DOTS37•
The National case detectio~ rate is 66 percent in 2006 and the cure is 83 percent5• The case
detection in Kerala is 43 percent an<;l cure is 82 percent5·
1.2.7. Factors affecting the treatment outcomes ofTB
Socioeconomic and demographic factors
In the developing countries, the communicable diseases like TB hit the poor much harder
than they hit the rich, though the people of all income ·groups are affected. An episode of
illness may reduce a poor household to penury, especially when they have to sell their
productive assets in order to cover health care expenses and poverty is thrust on to the next
generation38•
Low education level39' 40 ,being poor, overcrowding41 , not having a separate kitchen,38 low
income households, percentage of elderly population in the house hold42 are significant
predictors for tuberculosis disease. Non-working females in urban area, farmers which are
male43 more prone to get disease. A study on adherence from Nepal found that
unemployment, low status occupation, low annual income, and cost of travel to the TB
treatment facility were associated with non adherence oftreatment44•
9
A study from Canada reports an increase of 0.1 ppr (person per room) in a community was
associated with increase in risk of TB cases occurring. This study shows a significant
association between housing density, isolation, income levels, and TB. Overcrowded housing
has the potential to increase exposure of susceptible individuals to infectious TB cases, and
isolation from health services may.increase the likelihoodofTB45 •
Homelessness has been associated with the emergence of MDR-TB. Homeless populations
are less likely to have access to medical care, and the close contact, overcrowding, and lack
of sufficient ventilation that mlfy exist in homeless shelters would foster the spread of
tuberculosis infection and the emergence of drug-resistant strains46•
· A study from India examining the relation between biomass cooking fuels (wood or dung)
and active tuberculosis found persons living in households that primarily use biomass for
cooking fuel have substantially higher prevalence of active tuberculosis than persons living
in households that use cleaner fuels. The analysis also indicates that, among persons age 20
years and over, 51 percent of the prevalence of active tuberculosis is attributable to cooking
smoke47.A study from Chandigarh reports, age, level of education, crowding, type of
housing, water supply and number of consumer articles in the household was found to be
independently and significantly associated with a higher risk of TB48• In short, there is
substantial evidence found that the TB is more among poorer socio-economic class.
Age as a factor in disease and treatment outcome.
Older people that live in nursing homes are at a special high risk for developing pulmonary
TB, as are those on naval vessels, and those in prisons, jails, mental hospitals, chronic disease
hospitals, juvenile detention facilities, and shelters for the homeless49.The reported average
age at death due to TB was 45 years for males and 39 years for females50 - 51 .A meta analytic
10
review, showed that male predominance among TB patients was similar in both younger and
older tuberculous populations. It also revealed a greater evolution time in older patients as
compared to younger patients. The prevalence of concomitant conditions, such as
cardiovascular disorders, COPD, diabetes, gastrectomy history, and malignancies was higher
in older patients to, while alcoholism was more frequently seen in younger patients.
Symptoms also showed variation among older age group52•
A retrospective study in an urban TB clinic in Delhi reports the case fatality rate was
significantly higher in the age gtoup 65 years and above as compared to patients between 50-
65 years . The failure rate was signific~ntly higher in the age group 65 years and above than
among patients in the 50-65 years age-group53 •
Patients in the older age groups had more advanced disease at the time of diagnosis and a
higher proportion had comorbid illnesses. They also had significantly higher mortality
compared with the younger age groups54.0lder people with TB were more likely to be male,
to smok~, to have had TB previously, to have coexisting medical diseases, to be
socioeconomically disadvantaged, and to weigh less than younger people with TB. More
severe form of Tuberculosis' and extensive lung involvement in old age55• Substantial
differences were found between older and younger TB patients and many of these were
associated with unfavorable outcome
Sex differentials in disease patterns and outcomes of treatment
The rate of tuberculosis was consistently higher in men than in women, irrespective of age
group. More women completed treatment, and fewer women missed treatment appointments.
A higher proportion of men had relapse pulmonary disease that was more extensive, a history
11
of previous default from treatment and co morbid illnesses56 ' 57• Male sex is more prone for
default46• One study from Vietnam reports similar prevalence ofTB in men and women58 •
Gender differences in health seeking behavior and utilization of services
Many of these differences by sex have been related to gender. This includes the lesser to
health care seeking and health care qecision making among women and therefore under
reporting to the health system, women having poor access than men to tuberculosis
diagnostic services and to effective treatment59• More specific to care seeking for
tuberculosis, are poor knowled~e of the disease and poor interpretation of its signs and
symptoms by women themselves as well as by health workers, the social stigma associated
with being diagnosed as TB patient affecting women more than men, and financial and time
costs of the prolonged course of tuberculosis treatment55 • Study from Kerala also reports
that women were less likely th~m men to receive DOTS60•
Effect of Smoking and Alcoholism on treatment outcomes
One of the major determinants of population health is its health-related behavior61 .Tobacco
smoking and TB are two of the world's greatest public health problems, although TB is
largely confined to developing countries. There is definitive evidence that it is biologically
plausible that smoking could increase risks for TB infection and TB disease. Suggested
mechanisms include decreased immune response, CD4 lymphopenia, defects in macrophage
immune responses, and mechanical disruption of cilia function in the airways62 • A meta
analysis produced evidence th,.at smoking is a risk factor for TB infection and TB disease or
to be precise results suggest that tobacco smoking interacts with M tuberculosis complex to
the exte.nt of promoting infection and disease63 • Another meta- analytic review found
substantial evidence that tobacco smoking is positively associated with TB, regardless of the
12
specific TB outcomes. Compared with people who do not smoke, smokers have an increased
risk of having a positive tuberculin skin test, of having active TB, and of dying from TB. The
associations of passive smoking and indoor air pollution, increased the risk of TB disease, are
less strongly supported by the available evidence64•
In a cross sectional population survey in Cape Town found association between smoking and
TB infection65• A study from Thiruvallur, Tamilnadu establishes a positive association
between tobacco smoking and pulmonary (bacillary) tuberculosis. The association also
shows a strong dose-response relationship66• Severe form of TB among smokers, both
clinically and radiologically. Mortallity from TB, high levels of default and failures among
smokers established67 ' 41 • A Thomas et al reports, smoking and alcoholism were associated
with a higher likelihood of relapse68 • Biological evidence shows that chronic alcohol
consumption worsens pulmonary infection with M. tuberculosis in a murine model69.Several
studies identified alcoholism as risk factor for default. Low treatment success, high default
rate and non compliance were reported among alcoholics.
Default and treatment outcomes
According to Annik Rouillon former Executive Director of the International Union against
Tuberculosis and Lung Diseases (IUATLD), 'default is the natural reaction of normal,
sensible people, a person who continues to swallow drugs or have injections with complete
regularity in the absence of encourage~ent and help from others is the abnormal one'70.As
one cannot predict which patients are likely to be regular for treatment it becomes mandatory
to give each and every patient, drugs under direct observation. Adherence to treatment in
most diseases requiring long-term treatment is inversely proportional to the length of
13
treatmene1• When a patient with pulmonary TB feels better there is no compelling reason to
continue to take medicines14•
The leading cause of drug resistance was noncompliance or incomplete medical treatment72 •
Factors associated with treatment default and fatality were studied among tuberculosis
patients registered during 1999-2000 in Spain where the default rate was as high as 14
percent and factors like sex, age, homelessness, incarceration, DOT or hospitalization were
not associated with defaule3• A retrospective descriptive study in Nicaragua, from 1988-1996
showed that the default rate decreased from 16 percent in 1988-1991 to 1 0 percent in 1992-
1996 after implementing DO'fS74• Poor knowledge about TB can lead to high chances of
defaule5
A study jn Tamilnadu looking into the risk factors for default in the intensive phase identified
age more than 45, alcoholism, smoking, and those who reported DOTS as being
inconvenient. 84 percent attributed their default to drug related problems, 32 percent to work
related problems and 23 percent each to alcoholism and being symptom free followed by
domestic problems and taking treatment from outside48 •
The national default rate is 8.5 percent ad Kerala is 6.1 percent5•
Co-morbidities affecting Tuberculosis and their treatment outcomes
Chronic disease, mainly diabetes38• 40 history of previous TB, TB exposure (mostly from
family members) associated with relapse.49
Patients with tuberculosis infection are prone to reactivation; one of the conditions that may
predispose to reactivation is diabetes mellitus. The relative risk of developing
bacteriologically confirmed pulmonary tuberculosis is up to five times higher in diabetics76•
14
Significant association of MDR- TB and Diabetes is found also follow up of these patients
with PTB-DM revealed more deaths compared with non diabetic TB 77 •
Previous History of A TT and the duration of treatment also increase the risk of drug
resistance 78 .A study by Costello et al found that 41 percent of 4,017 patients with previous
treatment for TB developed drug-resistant TB, and that the percentage of those excreting
drug-resistant strains increased with increasing duration of the previous treatmene9•
A study from Saudi Arabia reports the mean time taken to achieve sputum AFB smear
conversion was 5.4 weeks in the PTB-DM group compared to 4.6 weeks in the PTB group,
besides diabetes, other factors such as increasing age, multiple cavitary disease, bilateral
disease and numerous AFB on sputum smear examination were significant factors associated
with increased time to sputum conversion80• Study from Congo diabetes appeared to have an
induction and aggravating effect on tuberculosis. Tuberculosis was found to be more frequent
in diabetics, had more pronounced radiological signs, treatment failures and deaths were also
more frequent81 •
The incidence of tuberculosis infection with diabetes in 4,349 diabetics admitted in the
Bombay Hospital was 5.77 percent, the majority of cases were between 40-60 years, males
predominated, and the duration of diabetes in majority were between one year to five years.
out of ~,349 cases of diabetes. It was seen that the incidence of tuberculosis was not related to the
duration of diabetes82.Another study in Mumbai, tuberculosis was found to be the most common
complicating illness (5.9%) in a large cohort of over 8000 patients with diabetes mellitus83•
A study from the Regional Institute of Medical Sciences, Imphal, the prevalence of
pulmonary tuberculosis in diabetics was found to be 27 percent by radiological diagnosis and
6 percent by sputum positivity. A rising prevalence of tuberculosis in diabetes has been seen
15
with age. Mortality rates in these patients are reported to be several times higher than in non-
diabetic . pulmonary tuberculosis patieflts84• Co- morbidities are associated with increased
default rate85•
Provider/ system side factors
DOTS is central to the success of tuberculosis control programmes, it is not easy to
implement. DOTS needs to be given at a location, which is convenient to the patient, and, by
a treatment provider who is accountable to the health system. Several types of providers have
successfully carried out treatment observation in various countries. They include health
workers in China, community volunteers in Africa, religious leaders in Philippines and
members of non-governmental organizations in Bangladesh86' 87' 88' 89' 90•
In Africa, volunteers and community health workers successfully delivered community-based
DOT and were able to maintain higher treatment completion rates than the health worker in a
clinic83.Delay to treatment initiation and diagnosis forced patients to drug shops or
pharmacies and private clinics more commonly than government health units as initial
contacts91 • C Nirupa et al in Tamilnadu reports high treatment success rates can be achieved
by identifying DOT providers, who. are accessible and acceptable to patients and
Governmental DOT providers are skilled in tackling patients' drug related complaints,
whereas Anganwadi workers and .community volunteers have minimal training in health
related issues92• Chandrashekharan et ai reports incoveninece of DOTS as a reason for initial
default41 • A study from Pathanamthitta in Kerala found, although all patients were recorded
as having received DOT, more than a quarter of patients did not actually receive it. The
patients who were not directly observed were much more likely to have treatment failure or
relapse, as compared to those who had received DOr1 .Involvement of non allopathic
16
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I practitioners into RNTCP-DOTS has shown an increase in case detection and improved
patient access without affecting treatment outcomes93• In nine out of 12 Public private mix
(PPM)projects in India showed the treatment outcomes are exceeding the 85percent cure
targets, in which private sector was the DOT provider, 2 projects showed results in par with
the public sector only one project was badly performing, also this PPM increased the case
detection94•
Experience from Kannur, Kerala reveals that there was a substantial increase in case
detection after establishing public-private. partnership, but among those diagnosed in private
sector 11 percent were referred for non DOT treatment in private sector in contrast to 1. 7
percent in Government sector95•
To conclude well- known risk factors for TB infection or disease include overcrowding, poor
nutrition, alcoholism, socioeconomic status, diabetes mellitus, and human immunodeficiency
virus infection96•
1.2.8. Relapse
According to RNTCP Relapse is a ·TB patient who was declared cured or treatment
completed by a physician, but who reports back to the health service and is now found to be
sputum smear-positive. Relapse rate varies from 1.6-19 percent as reported by various
studies, this variation is partly due to the inconsistency of the definition of relapse. Relapse
can be due to re-infection or recurrence. DNA fingerprinting have demonstrated that
exogenous reinfection with M. tuberculosis occurs in immunocompromised persons97• A
study from South Africa refutes longstanding views that exogenous reinfection with M.
tuberculosis is uncommon among immunocompetent persons. In this study, DNA
fingerprinting was performed on isolate pairs for 16 patients with suspected TB relapse.
17
Twelve of the 16 patients had disco~dant fingerprints between the first and second TB
episodes, suggesting exogenous reinfection rather than relapse98 •
A study from Hong Kong reports, history of opiate use, coexisting extrapulmonary
tuberculosis, higher radiographic extent and cavitation on initial chest radiograph, body
weight below 50 kg, thrice-weekly treatment throughout, and persistence of positive culture
after 2 to 3 months of treatment were associated with increased risks ofrelapse99•
Co morbidities, alcoholism, immunosuppression, smoking, poor social conditions which are
the risk factors for TB, it is true for relapse also.
1.3. Rationale for the study
Cure of Tuberculosis is thus a complex construct ofthe patient factors, sociocultural factors
and the provider or health system side factors. DOTS as a strategy envisages to bridge many
of the issues regarding drug availability and supervised administration. A patient who had
DOTS, with a favorable or unfavorable outcome, again remaining exposed to the risk factors
will leave him in the uncertainty of getting the disease again. Studying those who are
currently on DOTS will impose a bias, because they are in an artificial environment created
by the disease status.
RNTCP has been implemented in Kerala since the year 2000. Apart from the routine
program. evaluation, which evaluate within the program conditions, no study has attempted to
look into the various factors affecting treatment outcomes. Moreover the true relapse rate of
DOTS will be obtained by following up a cohort. This study is to explore and describe the
factors associated with the various outcomes of a cohort of patients registered in the Kollam
district during the first quarter of2005.
18
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1.4. Objectives
1. To identify the treatment outcomes of a cohort of smear positive pulmonary tuberculosis
patients registered under RNTCP- DOTS in the first quarter of2005.
2. To analyze the factors associated with the various treatment outcomes.
1.5. Research Questions
1. What are the various treatment outcomes at the end of treatment (7 months) and 18 months
after treatment?
2. What are the individual, community and provider level factors that influence. treatment
outcomes?
3. What is the prevalence of relapse?
4. What are the characteristics of the relapse?
•.
19
2.1. Study type
Chapter 2
Methodology
Cross sectional study of a cohort of new smear positive pulmonary tuberculosis patients
registered under RNTCP- DOTS in the first quarter of2005 in Kollam District, Kerala.
2.2. Study setting
The study was based in Kollam District of Kerala, India. It is bound on the south by
Thiruvaoanthapuram district, on the north by Pathanamthitta and Alappuzha, on the east by
Tamil Nadu and on the west by the Arabian Sea. The total population of the district is 25.84
Lakhs
2.3. Sample size
All newly detected sputum smear positive patients registered under RNTCP -DOTS during
1st January 2005 to 31st March 2005 was included in the study.
2.4. Sample selection procedures
All patients registered under RNTCP -DOTS during 1st January 2005 to 31st March 2005
were included in the study and their characteristics and outcomes assessed at the end of their
DOTS treatment (at the end of seven months) and followed up at the time ofthe study (after
eighteen months after completion of treatment)
2.5 Definition of study variables
a. Patients are considered cured if the results of two sputum smears for acid-fast bacilli
(AFB) are negative, one ofwhich is done at the end of treatment.
b. Treatment is considered to have failed if a patient has a positive smear 5 months or more
after starting treatment.
20
•
c. Definition of relapse: - Any patient from the cohort who turns sputum smear positive at
the period of study and those who are or were on treatment for sputum smear positive
pulmonary tuberculosis after the initial DOTS treatment.
d. Default A patient who at any time after registration does not take anti-tuberculosis drugs
consecutively for 2 months or more, is said to have defaulted.
Other than the outcomes of treatment outcomes described two more outcomes are described,
e. Status unknown- Sputum smear-positive patient who has completed treatment, with
negative smears at the end of the intensive phase but none at the end of treatment ( Defined
as just 'treatment completed' as per RNTCP)
f. Died-Patient who died during the course of treatment regardless of cause.
2.6. Data collection
The name and address of the patients was collected from the TB register from the
corresponding TB units in the district: After obtaining consent of the Medical Officer TB
Control, in charge of the TB unit, addresses ofthe individual patients was collected and with
the help of TB health Visitors, other field staff or DOT provider's patients were traced. TB
register and treatment cards were reviewed for details of the initial sputum smear status
smear conversion and outcome at the end of treatment (7 months).
The interviewer (the researcher himself) collected the data from each respondent after
obtaining the informed consent of each individual respondent After obtaining informed
consent from the patients, those who have cough for more than three weeks at the time of
interview were subjected to sputurri s~ear examination from the nearest microscopic centre.
Verbal autopsy was done in the case of every patient who had died in the interim, by the
researcher himself.
21
2.7. Data collection methods
Secondary data from the TB register and treatment cards and interview using a pre tested
structured questionnaire.
2.8. Data entry and Analysis
Along with data collection, the data was entered in Microsoft Excel spread sheet and
analysed using in SPSS Version 11.5.
2.9. Ethical considerations
The consent was obtained from Medical Officer TB Control and other authorities concerned
for the conduct of the study. A list of patients was prepared and those who were willing to
participate in the survey were contacted by a field worker and appointment was fixed
according to the patient's convenience. The place and time of interview were fixed as per
patient convenience. Informed verbal consent was sought before interview of each
respondent and also for sputum smear examination. Sputum smear examination results were
communicated to the patient tfirough the concerned field worker.
22
Chapter 3
Results
The study cohort consisted of 241 newly detected sputum smear positive patients registered
underRNTCP DOTS in Kollam district, Kerala during 1st January 2005 31st March 2005.
The patient's treatment outcomes at the end of the DOTS treatment (end of seven months)
were assessed from the Tuberculosis Treatment Register and the treatment cards.
At the end of completion of treatment at 7 months after initiation of treatment 20 patients had
died. The study population was thus reduced to 221, and at the time of follow up and
interview of these patients after 18 months from their end of treatment, 18 patients had died,
10 patients were lost to follow up and the number of study subjects interviewed were 193.
All the 1·93 patients participated in the survey resulting in a response rate of 100 percent. Out
of 193, there were 148 males and 45 females.
The results are discussed in two sections; the first section comprises of the outcomes for the
whole cohort and its characteristics which is mainly based on analysis of data from the TB
register and the treatment cards at the TB centre; and the second section regarding the
characteristics of the study subjects interviewed and the treatment outcomes after 18 months
after completion of their treatment.
23
I Transition of cohort over time. I Study Group 241
6 to 7 months of DOTS treatment
+ + + + ~ ~·
Cured Status Died Default Failure Transferred 207 unknown-1 20 7 5 out -1
.
18 months after completi >n. of treatment
Cohort size 221
Died Lost follow-up 18 (not traced)-1 0
Sample interviewed 193
l One patient relapsed l and cured Disease Status free unknown 192 1
24
3.1. Characteristics of the cohort
3.1.1. Age and Sex wise distribution of the cohort
The total size of the cohort was 241, out of which 78.4 percent were males and 21.6 percent
were females.
Table 3:1. Age and Sex distribution of the cohort. Age group Male#(%) Female#(%) Total#(%)
The mean age of the population was 51.04 (±16.18) minimum being 19 and maximum 86.
The mean age of males was 53.09 (±15.27)minimum being 22 and maximum 86 while the
mean age of females is 43.58 (±17.35) and ranging from 19 to 76.
Females accounted for 73.3 percent in the age group 15-24 females and the maximum
proportion of patients belongea to the older age group of 65 tears and above.
3.1.2. Initial Smear--status .
The initfal smear status among 57 percent of the patients were 3+, 23 percent belonged to the
category of 2+ while 20 percent of the cohort were either in the 1 + and scanty category.
Fifty seven percent of the males and 60 percent of the females belonged to the 3+ category
25
3.1.3. Outcome at the end of DOTS treatment (at the end of7 months)
The definitions used for the treatment outcomes classification were adopted from RNTCP.
Patients who had completed the course of treatment but their sputum results at the end of
treatment was not done is classified as just 'treatment completed' in RNTCP. In the study
this group was redefined as status unknown.
At the end of the DOTS treatment (seven months after initiation of treatment) out of the 241
patients 207 patients were cured, one patient was classified as status unknown, seven had
defaulted, five had treatment failure, one transferred out of district· and 20 died during the
treatment period.
Table 3.2. Treatment outcome of the DOTS cohort at the end of 7 months. Outcomes Male(#-%) Female(#-%) Total(#-%)
Cured 159 (84.1) 48(92.3) 207(85.9)
Status Unknown 1 (.~) 0 1 (.4)
Died 18 (9.5) 2 (3.8) 20 (8.3)
Failure 4 (2.1) 1(1.9) 5 (2.1)
Defaulted 7 (3.7) 0 7(2.9)
Transferred out 0 1 (1.9) 1 (.4)
Total 189 (100) 52 (100) 241(100)
In the sample the cure rate was 85.9 percent, with 84.1 percent among males and 92.3 percent
among females. Death rate was 8.3 percent with more deaths among males; 18 out of the 20
who died were males. Cure rates among males were also low in comparison to females. It
was also interesting to note that there were no defaulters among females The cure rate was
26
almost 100 percent among the younger age groups, while deaths were maximum among the
age group 65 and above. (Table 3.3)
Table 3.3. Treatment outcome of the DOTS cohort at the end of 7 months by age Age Cured Treatment Died Failure Default Transferred Total group completed out
15-24 15 (100) 0 0 0 0 0
25-34 27 (90) 0 2 (6.7) 0 1 (3.3) 0
35-44 32 (91.4) 0 0 0 2 (5.7) 1{2.9)
45-54 42(84) 0 3 (6) 2 (4) 3 (6) 0
55-64 48 (88.9) 1 (1.9) 3 (5.6) 2 (3.7) 0 0
65&> 43 (75.4) 0 12 (21.1) 1 (1.8) I (1.8) 0
Total 207 20 5 7 1
3.2. Survey findings (Among the cohort, eighteen months after completion of
treatment)
3.2.1 Characteristics of the sample
15
30
35
50
54
57
241
Total patients remaining of the initial cohort was 221, out of which 18 had died in the period
between the completion of treatment and the time of interview. among the surviving 203
patients and excluding the ten patients who were lost to follow up, the number of patients
available for interview was 193.The total sample population surveyed was thus 193 of which
148 (76.7 percent) were males and 45 (22.3 percent) were females.
27
3.2.2. Educational status
Table 3. 4. Educational status of the sample population Education level Male#(%) Female#(%) Total#(%)
No education 7 (70) 3 (30) 10 (5.2)
Lower primary 44 (91.7) 4 (8.3) 48 (24.9)
Upper primary 48 (82.8) 10 (17.2) 58 (30)
Secondary 31(62) 19 (38) 50 (25.9)
Degree and above 18 (66.7) 9 (33.3) 27 ( 14)
Total 148 (76.7) 45 (23.3) 193 (100)
3.2.3. Employment status
Of the sample surveyed 149 (77.2 percent) were currently employed. 77 percent of the
maless and 77.8 percent (35) ofthe females were currently employed.
Majority of the males were manual .labourers followed by agriculture and small scale
business. Majority of the females were homemakers
3.2.4. Marital Status
Twenty four patients in the sample (12.4 percent) were never married 159 (82.4 percent) of
the study population were currently married and 10 (5.2 percent) were either widow/
widower. Males constituted 40 percent of the widowers males and females 60 percent.
3.2.5. House hold characteristics
Mean number of members i"n the house hold is 4.64 (± 1.3) ranging from zero to 10.
Regarding the type of family, nuclear family accounts for 58.5 percent followed by
38.3perc·erit. joint family.
Ninety seven percent of the subjects were staying with the family, only three percent
responded as staying alone or away from the family. Seventy eight percent of the subjects
28
were res~ding in their own house. Mean number of rooms in the house hold was 2.8 (± 1.16).
Mean number of persons per room is 1.9 (± 0.79). Ninety seven percent of the houses had a
separate room for cooking and the 36 percent of the houses were using exclusively biomass
(fire wood) as fuel for cooking, 31 percent using mixed fuels which include biomass also,
rest using other type of fuels. Use of biomass fuels is an indicator of indoor air pollution.
3.2.6. Type of the house
Forty four percent of the houses were semipucca followed by 32.6percent pucca and 23.3
percent Kuccha houses. .
3.2.7. Place of residence
Eighty one percent of the study population were resided in the rural area where as 19 percent
in the urban area.
3.2.8. Socioeconomic status (SES)
SES was assessed subjectively by the researcher and accordingly, 59.6 percent (115) of the
patients were in the low SES category and 30.1 percent (58) in the middle SES. Only 10.4
percent of the study population belonged to the high SES category.
3.2.9. Smoking status
Table 3 .5. Prevalence of smoking among the study population Smoking status · #( %)
Ever smoker 124 (83.8)
Current smoker 65 (43.9)
No females in the study population reported either ever or current tobacco smoking. Mean
duration of smoking was 17.9 years (± 17 .3) years ranging from 1- 60 years.
29
Table 3.6. Change in smoking after diagnosis of TB Smoking decreased following TB diagnosis 63 (42.6%)
Quit smoking following TB diagnosis 37(25%)
Sixty three (97 percent) of current smokers responded that they reduced smoking after being
diagnosed ofTB. Out of ever smokers 30 percent (37) quit smoking following diagnosis of
TB. Current smoker is those had experienced tobacco smoke in the last 30 days.
3.2.10. Smokeless tobacco use
Smokeless tobacco use among the study sample was eight percent (15) ever used and seven
percent were (13) current users .Out of current users 53.3 percent (8) had reduced use
following TB. Out of the 15 ever users 13.3 percent (2) quit following TB disease. While one
patient use snuff the rest of the smokeless tobacco users were chewers.
Among males ever use of smokeless tobacco was reported by seven percent (1 0) and current
use by 5.4 percent (8).0ut of current users 50 percent (4) decreased use following TB
diagnosis and 20 percent (2) of ever users quit smokeless tobacco following TB disease.
Though smoking (ever and current use) was nil among the females, smokeless tobacco use
was reported by 11.1 percent ( 5) of females. The prevalence of current use of smokeless
tobacco among women was 11.1 percent (5). Eighty percent (4) of them reported decrease in
use following TB while none of the .women had quit use after being diagnosed with TB
30
3.2.11. Alcohol use
Table 3.7 Prevalence of alcohol use among the study population Alcohol Use # ( %)
Ever user
Current user
Use more than 2 times/week
114(59.1)
63 (32.6)
32 (16.6)
Sixteen percent of subjects used alcohol while they were taking DOTS, but only two percent
missed anti TBdrugs due to alcohol use. Only one female responded as ever and current user
of alcohol, but she never took it more than twice a week. Current use was defined as
consumption of alcohol with in the last 30 days.
3.2.12. History of exposure to Tuberculosis
Twelve percent of the subjects give history of contact with Tuberculosis patients in the house
hold, neighborhood or work place. Most of the contacts were family members within the
same house hold only.
3.2.13. Knowledge and perception about Tuberculosis disease and its treatment
This was assessed by a questionnaire (Hoa et al) comprising of 12 questions and accordingly
scored. .With respect to the scores obtained the responses were categorized as good,
satisfactory and bad. Fifteen patients did not respond to these questions
Table 3.8.Knowledge and perceptions about TB disease and treatment Knowledge level Male#(%) Female#(%) Total#(%)
Bad Satisfactory Good Total
26 (19.3) 35(25.9) 74(54.8) 135 (100)
* Fifteen patients not responded to these questions.
10 (23.3) 5 (11.6) 28 (65.1) 43 (100)
36 (20.2) 40 (22.5) 102 (57.3) 178* (100)
31
3.2.14. History of previous anti tuberculosis drugs
Eight pe~cent (16) of the study subjects.gave history of previous anti tuberculosis treatment.
3.2.15. Facility first sought by the patient for diagnosis
Eighty one percent sought a government facility first for diagnosis where as 19 percent
sought private facilities. Eighty percent of males sought government services as first facility
for diagnosis of TB while in females it was eighty four percent. Twenty percent and 16
percent in males and females respectively sought the private sector facilities first for .
diagnosis ofTB.
3.2.16. DOTS and its compmients
All patients were put under category -1 (thrice weekly Directly Observed intermittent
Antituberculous Treatment {ATT). Not a single patient was on non DOTS or daily ATT.
Ninety percent of patients reported that they had a detailed briefing. about the treatment
before starting the treatment, three percent said that they were not briefed, and four percent
could not recollect any such details.
The components of the counseling were treatment duration, drug dosing, drug side effects,
need for regular drug intake, follow up for smear examination. Twelve percent of the subjects
were not able to recollect the .components of the counseling. Fifty two percent reported that
they were told about all the components and the rest gave mixed responses.
Regarding specifics during counseling like smoking cessation, al~ohol cessation and
nutritional advices, 65 percent responded that they were told about tobacco cessation, alcohol
cessation and were given nutritional advice, 10 percent had problems with recall and the rest
gave mixed responses.
32
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I The persons involved in counseling were government doctors and health workers as reported
by 42 percent, followed by health worker alone by 33 percent. Thus in almost 75 percent
counseling efforts the health worker is involved and 10.4 percent patients were not able to
recollect the event. .
With respect to the behaviour of the DOTS provider, ninety nine percent of the patients were
satisfied with the behavior of the DOT provider; none responded any conflict with the DOT
provider.
3.2.17. Profile of the DOT centre
Table 3.9. Type of DOT centre DOT centre Male Female Total#(%)
Here also the same picture prevails as in the outcome after treatment at the end of 7 months,
with the younger age group maintaining maximum of disease free status compared to others.
Further analysis was not possible because the data exits only for those who were alive at the
time of interview, in that case we cannot compare any risk factor with outcome, only possible
analysis was with age and sex.
3.4. Findings of verbal autopsy
Verbal autopsy of38 patients died was performed and coded
Table 3.22 Findings of verbal autopsy. Cause of death # (%) High certaintyofTB 15 ( 39.4) Medium certainty ofTB 5 (13.2) Other causes 18 (47.4) Total ·38 (100)
At the e~d of seven months, among the 20 patients who died, the cause of death could be
coded as may be due to TB high certainty 50 percent (10) of patients and in 20 percent (4))
it was with medium certainty, other causes account for 30 percent. Twelwe deaths occurred
in the intensive phase (within the first 2 months)and rest in the continuation phase of
treatment.
42
Eighteen months after the treatment completion, among the 18 who died, the cause of death
with high certainty for TB was 27.8 percent (5) and medium certainty for TB was 5.5 percent
(1), rest may be death due to other causes 66.8 percent (12).
43
Chapter 4
Discussion
The main objectives ofthe study were to assess the treatment outcomes of DOTS and to fmd
the factors associated with it in a district in Kerala. The outcomes were assessed at the end of
the course of treatment at 7 months and 18 months after the completion of treatment. The
discussion on the treatment outcomes, the factors that might have contributed to the
outcome'S including the DOTS factors and how it compares with the available studies and
reports and the programme implications are presented in this chapter.
4.1. Outcomes
Cure rate:
While exploring the outcomes of DOTS, the most important finding of this study was the
maintenance of high cure rate and low relapse rate among the patients registered for
treatment. According to the study findings the cure rate at the end of treatment was 85.9
percent. This figure is the RNTCP ·target which is 85 percent and also in tune with the cure
rates reported by various studies from across the country ranging from 74 to 98
percentJoo,JoJ,J02,J03 .
Default rate:
The observed default rate in the present study was 2.9 percent and the failure rate was 2.1
percent. Both these figures fall well with in the accepted program upper limits of 5 percent
and 4 percent respectively. However the default rate of 2.9 percent as observed in this study
is very low compared to the national and Kerala averages, also seems low compared. with
44
other studies Indian and international which range from 4 to 25 percene5•101•103•104•105• Failure
rates also are low with compm:ed to the reports and studies which range from 1 to 4101•103•105•
Relapse rate:
The relapse rate among the cohort at the end of treatment was 0.4 percent. The relapse rate
otherwise reported range from zero percent to 3.8 percent 60•100•104•105•
Death rate:
A significant finding in the study cohort was that the death rate of the study cohort after the
DOTS treatment (after 7 months) was 8.3 percent which is more than twice the program
expectation of four percent. Many follow up cohort studies report eight percent to 35
percent55•106•107•108• The variations in the figures also depend on the duration of follow up. The
death rate at the end of 18 months was 16.5 percent which is higher in comparison to the
figures reported by other studies.
Factors affecting treatment outcomes
One of the factors affecting the treatment outcome was age with more favorable outcome in
younger age groups. Other evidence also suggests that older age group is prone for
tuberculosis and unfavorable treatment outcomes. The reasons for this according to studies
available suggest that it could be due to the waning immunity and presence of co
morbidities50••
Significant association was found between the supervised intake of drpgs and type of DOT
centre in favor of door delivery and Anganwadi. Similar fmding exist in a study done in
Delhi reports success rates among patients treated by different DOT providers as Anganwadi
workers (80%), governmental outreach workers (81 %), community volunteers (76%) and
PHI staff(76%)109•
45
Regarding the sex differentials, global experience indicates that rate of tuberculosis was
consistently higher in men than in women, irrespective of age group. This held true even in
the present study with majority of the cohort being male. However in the current study in the
age group 15-24, females accounted for 73.3 percent of cases. The finding is similar to
another Indian study which also found that in younger age groups females· constituted 61.3
percent and males 38.7 perceht respectively104• It needs to be further explored wh~ther the
detection of women in the higher age groups are lower due to the stigma associated with TB,
marital status and other social factors preventing their access to health care seeking and
treatment.
Cure rates. among males are low compared to females and there were no defaulters among
females. Low default may be a proxy indicator of treatment adherence that will account for
the higher cure rates in the females.
The default rate and bad treatment outcomes was higher among alcohol users and smokers62•
In our study even though the. default rates were not high, default occurred in males only.
Studies have indicated that male sex itself is more prone for default42•
Sixteen {8.3 percent) of patients gave a history of ATT prior to taking DOTS. This indicates
that these patients were misclassified as new smear positive cases. The reason for the
misclassification cited by the RNTCP staff was the lack of proper awareness about the
definition of the previous treatment.
Alcohol intake more than twice a week was found to be significantly associated with the
unfavorable treatment outcomes, even though the number of patients having unfavorable
outcome is less. The only limitation is that the alcohol use patterns of patients who died in .
the interim or those who were lost to follow up are not known.
46
The high prevalence {30 percent of diabetics is emphasizing the need for, early detection and
treatment of diabetics and need for proper screening of all diabetic chest symptomatic.
Patients with diabetes mellitus are also at a higher risk of tuberculosis. This has been
highlighted by several retro.spective and prospective studies. In a study in Mumbai,
tuberculosis was found to be the most common complicating illness (5.9 percent) in a large
cohort o.f over 8000 patients with diabetes mellitus. In a recent study from the Regional
Institute of Medical Sciences, Imp hal, the prevalence of pulmonary tuberculosis in diabetics
was found to be 27 percent by radiological diagnosis and 6 percent by sputum positivity. A
rising prevalence of tuberculosis in diabetes has been seen with age. Mortality rates in these
patients are reported to be several times higher than in non-diabetic pulmonary tuberculosis
patients. The limitation of the current study is the prevalence of Diabetes Mellitus among
patients who had died is not known. The TB registers do not mention the co morbidities and
their control though it is a proven fact that many of them affect treatment outcomes ofTB.
Studies conducted after the introduction of the glucose tolerance test in 1950s, have shown
high prevalence of impaired glucose tolerance test in patients with tuberculosis with rates
ranging from 2 to 41 percent. The use of different criteria for diagnosis of diabetes mellitus
makes comparisons between the results of the studies almost impossible.
Regarding stigma towards TB patients, it was not an issue for treatment in the present study.
only one patient had reported stigma from others due to the lack of awareness regarding TB.
However the fact that many of them did not disclose their disease status either to family or
friends reflect the nature of stigma that is still associated with the disease.
There was no association between pretreatment smear status and cure, which implies what
ever be the smear grading the DOTS regime could cure it. This finding is extremely valid in
47
the face of apprehension among at least some physicians who argue against DOTS as a
strategy.
4.2. DOTS factors influencing outcomes
The reason for the good outcomes as reflected by the study findings may be many.
The. good cure rates would not have been possible without many of the programme factors
working well. A cure rate of 85 percent would happen when the programme factors work
hand in hand with the treatment and patient factors These factors start with timely diagnosis,
identification of an appropriate DOT provider that is acceptable to the patient and
accountable to the health system, effectiveness of monitoring, spotting of default and relapse
and retrieval of them back to DOTS. The study findings may be indicative of a good
programme in the District which is reflected by the high supervised intake of medicine and
the favorable outcomes.
The finding that the only patient who had relapse was traced and cured by retreatment
through DOTS and cured indicates the good follow up and also faith of patient in the health
system. Even though RNTCP is a horizontal program, the vertical components that it has
like staff with exclusive responsibility of tuberculosis control including senior treatment
supervisors, middle level supervisory staff like Medical officer TB control and a District
level District TB Officer might be a crucial factor. Meticulous managem~nt, data
management including data consolidati9n, analysis and timely feedback of the WHO medical
consultants also may be factors facilitating the monitoring and midcourse corrections within
programme implementation.
These vertical components of the program also ensures, patients house visit and intermittent
monitoring and motivation for timely follow up of the patients by the RNTCP staff. The
48
relation the staff maintains with the patients is commendable, as they are identified as "TB
sirs" or "Sense of family between staff, patients". Broadly what we discussed above can be
referred as good program conditions. These good conditions which is ensuring the contact
with the patient, and allows good follow up makes the DOTS meaningful rather than a
supervised swallowing of drug. More over Kerala the prevalence of HIV is low, which in a
big way skew the outcomes towards unfavorable. So it needs to emphasize all these
achievements are in a HIV low setting.
Moving to the some subtle factors of DOTS, the pretreatment counseling of the patient is a
key component to ensure that the patient should understand the need for taking drugs and
also refrain from the bad behavior. This is not a one time process, and will happen at
different levels also, starting ·from the Doctor who prescribes the treatment to the DOTS
provider. This effect seems to be reflected in the reduction in the number of smokers in the
cohort. The effective counseling reduced smoking among TB patients as evidenced by almost
30% patients quit smoking following the TB. Smoking identified as a risk factor for
relapse68. However the aim of the programme should be on reinforcement of tobacco
cessation messages throughout the course of treatment and afterwards. Capacity building of
staff including medical officers regarding the need and the techniques of tobacco cessation
may be an additional area of emphasis that the programme needs to take
Kerala tops the country in terms of per capita consumption of alcohol. In this context
it is interesting to note that alcohol intake for more than two times a week was significantly
associatttd with unfavourable treatment outcomes. In addition to tobacco cessation, stress
needs to be made on alcohol cessation among patients on DOTS and this may require
additional capacity building of the programme implementers.
49
4.3. Deaths
This high death rate of 8.3 percent in the study population in contrast to the RNTCP
programme limit of 4 percent may . be due to the fact that patients present themselves for
treatment in already advanced stages of the disease emphasizing the need to consider ways
and means to encourage early treatment seeking. more prompt referral and diagnosis so that
patients .can be treated earlier in the course of their TB illness. Since it may also be due to
late treatment seeking. urgent steps needs to be taken to further widely disseminate the
information regarding TB and its symptoms and the effective treatment options among all
sections of the public.
Most of the deaths in the seven months after start of DOTS seems to have happened within
two months of initiation of treatment (intensive phase). It needs to be further explored
whether the death rates are similarly high among other cohorts and whether it has any
relation to the bacterial load. immune status. symptom profile. presence of co morbidities.
compliance. adherence or other related factors. It is not possible to completely rule out the
chance that the patients who had died might have defaulted treatment and were not
supervised effectively.
Other possibility is the high prevalence of HIV infection among TB patients. that was not
possible in 2005 since the HIV TB programme coordination was not existent at that period in
the study area. The age groups in which deaths have occurred in this,study is slightly higher
than that one would expect with HN.
The possibility of late detection still remains high since detection rates of the study district
are far behind (around 40 in the 1st· quarter 2005) the program target of 70 percent. All other
50
-------------··--·------··--~---- ·-----
parameters, like default rate, failure rate, treatment completed rates are well within the
program targets.
This picture illustrates that once the patient is diagnosed, the good program conditions ensure
excellent follow up of the patients, leading to favorable treatment outcome. This might also
meant that though the programme is succeeding in provision of effective treatment it may not
be detecting and reaching out to many cases in the community. The objective of case
detection is to detect at least. 70 percent of the estimated load and the case detection rate
should increase over a period of time. It is anticipated that with the spread of the concept of
eff~ctiveness of RNTCP in the community, more individuals would seek treatment. It is
estimated that there would be 7 5 new smear positive patients per lakh population per year
(estimated ARI: 1.5%) in India
The low detection may be due to change in prevalence of the TB disease. The average age at
contracting illness also has showed an upward trend indicating the epidemiological impact.
This is evident in the change in the mean age of New Smear Positive TB cases in Kerala
from 46 to 48 ( male -48 - 50 and females 38 - 40), which is the same for the study district
also.
Even though the study district has a go.od public private mix in RNTCP it is not reflected in
the total case detection which is falling over the years. The increasing case detection form the
private sector and the decreasing trend in detection in the public sector may be due to the
successful linkage of the programme with the private sector. There has been a steady increase
in the number of TB cases enrolled for DOTS from the private private sector indirectly
indicating the success of the PPM (private public mix) component of the RNTCP. The
51
private sector was earlier co~pletely treating their patients with non DOTS or daily drugs
regimen.
The pa~em of death in the cohort is also interesting. Out of the 20 deaths that occurred
within the treatment period 12 (60 percent) deaths occurred in the intensive phase of the
treatment, which indicates patient might have been in advanced stage of disease. So it
emphasizes the need for institutional or specialized monitoring by a physician for those who
are in advanced disease condition and those in the older age groups. In case of elderly
whether we need to review the diagnostic criteria, like reducing the duration of chest
symptoms to cough more than 2 weeks rather than 3 weeks for sputum examination, presence
of co morbidities and their control and an assessment of their general condition may be
necessary to avoid progression of disease and prevention of deaths.
4.4. Limitation of the study
The study being done in the patients those who are registered under RNTCP, so the findings
will not reflect the true relapse rates of TB. The morbidity data collected was all self reported
by the patient, problems of recall were there. The program setting is different in different
districts of the state, so the findings may be difficult to project to the entire Kerala.
4.5. Conclusion and programme implications
The RNTCP programme and·the DOTS strategy seems to have favorable outcomes for the
patients post treatment (after 7 months) and long term (18 months after completion of
treatment) .The cure rates were high and relapse rates low irrespective of the initial smear
status or bacterial load. The nature of the DOTS provider or other factors like trained staff
accountability and follow up may be the reasons contributing to this.
52
Low detection rate however is a concern emphasizing the need for training of the doctors and
other staff so as to ensure prompt referral of the chest symptomatics .Further explorations
also may be necessary to identify whether the falling detection rates are due to the impact of
the programme itself, the epidemiological transition or some programmatic failures that may
be prevailing.
The programme even now seems to give little importance to co morbidities like Diabetes
Mellitus and coexisting risk behaviours like smoking and alcohol consumption. RNTCP
might achieve higher cure rates and lower relapse, failure and deaths if these are taken into
consideration and controlled. The effect of co morbidities with treatment outcomes of DOTS
also requires more research and attention. Tobacco and Alcohol cessation measures should
work hand in hand with RNTCP. The RNTCP having good follow up and contact with the
patients, give opportunity non pharmacological tobacco cessation measures. To reach this
goal the RNTCP field staffs could be trained in this direction.
The high prevalence of mortaiity in the higher age group also needs to be compared with the
age specific death rates of the district. The death rates among TB patients undergoing DOTS
may have to be monitored and compared with the age standardized mortality. Whether it is
due to late detection or due to other factors needs to be studied.
53
References:
l.Report on the Tuberculosis Epidemic. WHO/TB/97.224. World Health Organization,
Geneva, 1997
2.WHO REPORT 2007,Global Tuberculosis Control WHO 2007.
3. Chadha VK: Global Trends ofTB- An epidemiological review; NTI Bulletin, 1997,33,1
1-18.
4. Sepkowitz, Kent A. "How Contagious is Tuberculosis?" Clinical Infectious Diseases, pp
954 -62, 1996
5. TB INDIA 2007 RNTCP status repott 2007.
6.Fox, W. The problem of self administration of drugs with particular reference to pulmonary
tuberculosis. J Br Tuberc Assoc 39: 269, 1958.
7.Tuberculosis Chemotherapy Centre. A concurrent comparison of home and sanatorium
treatment of pulmonary tuberculosis in south India. Bull World Health Organ, 21: 51, 1959.
8. Uplekar M, Walley J, Newell J. Directly observed treatment of tuberculosis. Lancet 1999;
353: 145.
9. Lienhardt C, Rowley J, Manneh K. Directly observed treatment of tuberculosis. Lancet
1999; 353: 145.
10. Frieden T R. Directly observed treatment of tuberculosis. Lancet 1999; 353: 145.
11. Harries A D, Salaniponi F M, K wanjana J H. Directly observed treatment of tuberculosis.
37 What was the type of I-DOTS treatment received? 2-continious treatment
3-Intermittent 38 Do you had a detailed 1. Yes
briefing before starting the 2. No treatment?
39a If yes, what all things were 1. Treatment duration discussed? 2. Drug dosing
3. Drug side effects 4. need for regular drug intake
D
5. Follow up for smear examination.
39b If yes, who did it? 1. Government doctor 2.Health worker 3. DOT Provider 4.Private doctor 5. Others (specify 1. Yes 2. No
39c Did they advice you Stop smoking 1. Yes 2. anything listed? No
Stop alcohol 1. Yes 2. No Nutritional advice 1. Yes 2. No No advice was given 1. Yes 2. No
40 If he/she used DOTS l.Good treatment, how was the behavior of the DOTS 2.Bad provider?
41. Did you have any conflict 1. Yes 2. No with the DOTS provider?
42 If yes explain? 43 From where did you l.Anganwadi
collect the drugs? 2. Home delivery 3 .PHC/sub center 4 .Govt Hospital 5.Pvt Hospital 6. Others
44 How many times a week 1 Thrice a week were you going to collect 2 Once a week the drugs? 3 Once in 4 weeks
4 Others (specify)
Intensive Period:
Continuation Period: 45 Was there any 1. Yes 2. No
improvement in your health condition after starting treatment?
46 What was the duration of the treatment?
47 Did you complete the 1. Yes 2. No treatment?
48 If no, why didn't you l.Lack of motivation
E
l i ~·
complete treatment? 2 .Lack of awareness 3 .Distance from the provider
I l
4 .Lack of drug availability 5.Lack of money to purchase drugs 6.Side effects from the drugs ?.Timings were not convenient 8. I hate long duration treatment 9. DOT provider's attitude was hostile.
49 Did you get any visit or 1. Yes 2. No any type of alert message from the health workers/health services when you missed the drugs?
50 Were you offered any 1. Yes 2. No incentive for completing treatment?
51 Did you have any side 1. Yes 2. No effects while on treatment?
52 What were the side 1- Drowsiness; effects? 2- Red/orange
urine/tears; 3- Gastrointestinal
upset; 4- vomiting 5- Burning in
hands and feet; 6- Joint pains; 7- Impaired vision; 8- Ringing in the
ears; 9- Dizziness; 10- Loss of hearing; 11- Loss ofbalance; 12- Jaundice;
53 Did you know that there 1. Yes 2. No would be side effects of treatment?
54 Did all your family 1. Yes 2. No members know that you had Tuberculosis?
55 Did you inform your 1. Yes 2. No If no 58
F
family members that you had TB at that time?
56 If yes, how did the family react to you?
57 Were there any changes in 1. Yes 2. No the family's attitude to you?
58 If you did not inform you family, why didn't you inform?
59 Did your neighbours know 2. Yes 2. No ____. that you had TB at that If no time? 60
60 Why didn't you tell? 61 Have you experienced any 1. Yes 2. No
discrimination from anybody being a TB patient?
62 If Yes, explain 63 COMORBIDITIES AND TREATMENT If no
64 Do you have Yes/No Ifyes, time How long
any of the since diagnosis have you
following in been taking ____.
disease/ years/months. treatment for
diseases the condition
Diabetes
HighBP
Heart disease
Lung disease
Others
RE-TREATMENT HISTORY 64 When was the treatment
begun? 65 What were the symptoms 1. Chronic cough
that prompted you to seek 2. Fever treatment? 3. Weakness
4. Weight loss 5. Blood in sputum
G
-------··------·-··~---~---
l 1 I
66 When did the symptoms started?( days , weeks, or months after the initial DOTS)
67 Who referred you for l.Private doctor treatment? 2.Government doctor
3 .Health worker 4.Family member 5.Friend 6.0thers (specify)
68 Where did you undergone 3. Government facility treatment? 4. Private facility
5. Others. 69 What was the type of l.Thrice weekly regime with
treatment? injections 2. Thrice weekly regime without injections 3. Daily drugs. 4. Others if specify.
70 Are you suffering from l.Yes cough more than 3 weeks? 2.No
Information from the treatment card/TB registers
Name: Age: TBNo.
Address:
Treatment Category:
TB Unit: Initial Sputum Status: Date of Starting the Treatment: Sputum conversion status:
1. At the end of 2 months. 2. At the end of 3 months 3. At the end of 4 months 4. At the end of 5months 5. At the end of treatment
Treatment Unit:
Current Phase of treatment:
H
INFORMED CONSENT
I am Dr Shibu Vijayan , a post graduate student in Public Health studying in Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, Kerala. Thank you for permitting me to contact you. I would like to ask you some information about yourself, your previous Tuberculosis treatment, and your current health status as a part of my study. This interview might take a maximum of forty five minutes. If you are currently suffering from cough more than three weeks, your sputum will be examined. I am collecting information from around two hundred and fifty persons like you. You have freedom to take the decision whether or not to continue with the interview at any point oftime. Your identity and the information given by you will be analysed by myself alone for research purposes only. If you do not want to answer any question or series of questions, you can refuse to say at any point in time. If you have any queries or doubt please feel free to clarify those. I will try my level best to answer to any of your queries right now or in future as well. My contact number is 9446261303 .If you want to know any further information regarding this study you can contact Head of tb.e Department, Achutha Menon Centre for Health Science Studies (AMCHSS), SCTIMST, Trivandrum at phone number0471-2443152. After getting the oral agreement from the participant the signature of a witness will be taken.
Place Signature of the witness
Date -------
Signature of the researcher Signature ,ofthe patient