Epidemiology of Tuberculosis in India

TB related goal

Historical milestone

India’s contribution

Natural history of TB

Individual

Community

Situation in India

Some important studies

Factors affecting secular trend in India

Epidemiologic indices

Epidemiologic triad

Prevention & Control

Performances indicator

Introduction

Study of epidemiological situation of tuberculosis has always been a big challenge. The study of epidemiological situation of Tuberculosis is of very importance for formulating the disease control strategies. It also provides an insight into the impact of the control programmes on the disease situation in the country. Tuberculosis has been known to be a major public health problem in India for a long time. However, it was only in 1955-58 that the nationwide study conducted by ICMR during 1955-58 provided for the first time, an insight into the enormity of suffering caused by TB in India. According to Global TB control report-2009, Highest number of TB cases in the world is contributed by India, worlds 1/5th cases are found in India and 2/3rd of south East Asia. It is categories as high burden country along with other high burden countries like china (2nd), Indonesia (3rd), Nigeria (4th), & South Africa (5th).

Tuberculosis related Goals

RNTCP Case detection rate least 70% Cure rate 85%

MDG 6: Combat HIV/AIDS, malaria & other diseases :Have halted by 2015 & begun to reverse the incidence of malaria & other major Diseases

NHP 2002 Reduce mortality by 50% by 2010

NRHM (2005-2012) Tuberculosis DOTS services: maintaining 85% cure rate through entire mission period

11th five year plan Enhancing effort at disease reduction.Reversing trend major ds.

Stop TB Partnership Targets

By 2005:At least 70% people with sputum smear positive TB will be diagnosed &At least 85% cured.By 2015:Global burden of TB (prevalence and death rates) will be reduced by 50% relative to 1990 levels. Reduce prevalence to <150 per lakh population Reduce deaths to <15 per lakh populationNumber of people dying from TB in 2015 should be less than 1 million, including those co-infected with HIVBy 2050:

– Global incidence of TB disease will be less than or equal to 1 case per million population per year

Historical milestone of TB in India

TB is one of the most ancient diseases. It has been referred to in the Vedas and Ayurvedic Samhitas.

• 1906- first open air sanatoriumTiluania (near Ajmer)• 1908-UMTS, Madanapalle(A.P)• 1917 -first TB dispensary was opened in Bombay• 1948-introduction of BCG vaccination • 1939 -TB Association of India (TAI)• recommended the Organized Home Treatment Scheme • 1946 -TB Division, the Directorate General of Health Services (DGHS), established in

New Delhi• 1946-The Bhore Committee, supported organized domiciliary treatment• 1948-BCG work started in India as a pilot project in two centers. BCG Vaccine

Production Center in Guindy, Madras was set up • 1951 - started a mass BCG Campaign. • 1952-53- INH & SM came

• 1956 - Tuberculosis Chemotherapy Center, later TRC• 1955-58 –first study conducted by ICMR • 1959- National Tuberculosis Institute (NTI)• 1962- National Tuberculosis Programme • Seventies availability Rifampicin and Pyrazinamide • 1992- Evaluation of the NTP

1993-RNTCP pilot was began• 1998 -RNTCP scale-up • 2000-2003 First Nationwide Sample survey of ARTI• 2006 March- Entire Country covered under DOTS • 2006- Stop TB strategy adopted.

Natural History of Tuberculosis in IndividualsPhase I—Of Primary Tuberculous InfectionPhase II—Of Primary IllnessPhase IV — Of Localized Extra pulmonary TuberculosisPhase V — Of Satellite or of Adult Type of Disease

Natural History of Tuberculosis in CommunityThe natural history of tuberculosis in community aims at understanding the basic or fundamental laws which govern all the events that take place between tubercle bacilli and the community under natural conditions without active interference in the form of organized control measures. Tuberculosis, once a chief cause of death, has decline in the last two decades to low levels of morbidity and mortality in several countries. So far, it has not been eradicated from any country. Being slow progressing disease, its epidemic nature is not easily discernable. According to Grigg, tuberculosis is a cyclic disease and as such a self limiting phenomenon. The span of epidemic curve of tuberculosis is believed to last centuries and hence called secular curve. To sum up the changes in epidemiological situation with relation to time are classified into three phases: (i) the epidemic phase, (ii) transitional phase, and (iii) endemic phase.

Table 1: Characteristics of secular curve of Tuberculosis Epidemic phase Transitional phase Endemic phase.

Morbidity Very high High but < epidemic phase

Lower & falling

Fatality High High but < epidemic phase

Lower & falling

Age Children, Young adults & Females

Middle age, more in males

Adolescent & elderly men

Residence Urban Mainly urban but starts progressing to rural

Equal in urban & rural

Resistance Poor High Highest

Graph 4. Mean Annual Mortality from all Forms of Tuberculosis in England & Wales in Decennial Periods Among Males & Females, 1851-60

The span of epidemic curve of tuberculosis is believed to last centuries and hence called secular curve. Based on mortality and morbidity notification from various parts of the world at different periods, Grigg was able to project three theoretical epidemiological curves of tuberculosis i.e ofmortality, morbidity and contacts. The mortality curve reaches the peat first. This is an important climax of the phenomenon of tuberculous infection in a virgin soil. He has named it as the “Biological Critical Point”. Persons infected and suffering from disease being plentiful, the curve of morbidity continues to rise and attains the peak much later than that of mortality. Grigg calls it the “Epidemiological Critical Point”. With the march of time, the community and individual immunity is built up, the duration of survival of the sick and the good chronics increases, who in turn increasingly continue to infect their contacts. Therefore, it takes long to attain the “Peak of Contact”. These three peaks occur in succession and not simultaneously. When the community and individual resistance increases further, the progression from infection to disease is checked and this in turn results in reduction in the transmission of infection and transition of epidemic into endemic stage. And, in course of time, the disease may not be considered a major public health problem. But the disease not having reached the zero line,

epidemics of short durations are seen to occur from time to time. They have more or less a semblance of acute epidemics of varying degrees.

Situation in India

The tuberculosis epidemic in India started probably in the mid 19th century, reached its peak some 50 years later, at the beginning of 20th century, and that it has been naturally declining slowly ever since. There is evidence that there was little tuberculosis in most parts of India in the early 19th century. Evidence can be found in the writings of English physicians working in India then. Thus, according to Young in the Transactions of Calcutta (Trans, Bombay Med. Soc. 1838,11,45), tuberculosis was extremely rare in the upper plateau of the Western Ghats, Nilgiri hills and on the northern and southern slopes of the Himalayas. And Chevers, after 36 years of service in India, written his observation in the “Commentary on the Diseases of India (1886)”. We must remember that these authors were quite familiar with tuberculosis as it was a very common disease in Britain at that time. Possibly, the British brought tuberculosis infection to India and it spread in the second half of the 19th century. Towards the end of that century, tuberculosis had become quite common in the Indian population. Tables 2 and 3 show how the disease rose and then started falling in India. The rate gradually fell among the British soldiers while it rose among Indian soldiers serving in the Indian Army. In the 1890s, the line representing incidence among the British soldiers, which was steadily going down, crossed the line representing the incidence of tuberculosis among Indian soldiers in whom the incidence was rising. ( Ind. J. Tub., 1995, 42, 195)

The peak of the epidemic in India occurred probably in the first two decades of this century and since that time, the disease has been gradually declining. Graph 2 shows mortality from tuberculosis in three Indian cities - the peak occurred at the turn of the century. There is some direct evidence of the natural decline of tuberculosis in India available from the four Longitudinal Surveys, i.e. conducted by us in NTI in rural areas of Bangalore District, and from that of Pamra in congested city areas of Delhi & others.

Table 2. Admission Rates Among Prisoners Table 3. Admission Rates in Army in India for Tuberculosis Jails, Bombay Presidency for TB of lungs(per 1000) in Lungs (Per 1000) Year Year 1891

Rate

1893 0.8 1895 7.8 1897 7.1 1899 5.9 1901 5.6 1903 6.3 1905 5.0 1907 5.8 1909 3.7 1911 3.7

Graph 6 shows incidence of tuberculosis in the longitudinal study conducted by the NTI, Bangalore and Graph 7 of that in Chingleput study area. This graph shows clearly that this pattern of decline is seen in both these areas but decline is more in females.

Year Indian Troops

European Troops

1891 1.7 3.2 1893 1.6 3.0 1895 2.3 4.8 1897 2.6 4.2 1899 3.3 3.1 1901 4.2 3.4 1903 5.9 3.4 1905 3.1 2.1 1907 2.5 1.6 1909 2.3 1.1 1911 2.1 0.0

Now India is experiencing decline endemic phase. The rate of this natural decline can be accelerated by good treatment programmes in which the speed of decline accelerated from 2.3 per cent natural

decline.

Findings from Longitudinal studiesTuberculosis in the Bangalore rural area (1962-1985) : It was follow up study for 12 yrs. It is apt to describe the same as natural trend up to the first 5 yr. Thereafter an element of NTP intervention was introduced in the area after the 4th survey (5 th yr). (i) No change in Prevalence and incidence rates of C+ cases and X + cases in the period of 12 yr (1961-68 to 1977-78), (Fig.2). Without active intervention, a third of the existing pool of bacillary cases in a year would get eliminated through death and natural cure. But during the interval, the same proportion gets added to it. The ratio of incidence: prevalence in India was remained 1:3 (ii) mean age of cases was higher at later surveys, up to 12 yr period studied. (iii) ARI had declined from 1.1 to 0.65 per cent in 23 yr (1962-1985) at rate of 2.35 per year. (iv) Incidence of smear-positive cases declined 65 to 23 per 100,000 in the same period.

The natural dynamics were compared with likely disease situations, under various programme effectivity modes, hypothesised for the purpose and fed into the model. The above model showed that even in 50 yr, tuberculosis case rates would come down only minimally. Very large population sizes would be required to be surveyed repeatedly to appreciate a change, if any.

Tuberculosis in rural Tamil Nadu (1968-1984) : This study carried out in a rural population of Chingleput in Tamil Nadu by TRC, Chennai (1968-1984, and in a subset of population, again in 1991-1992 and 1994-1996), ARI had remained unchanged for the entire period. It was between 1.8 and 1.9 per cent in the earlier period (1969-84) and 2.9-3.2 per cent (1991-92, 1994-96)

Prevalence of cases: (i) The study has shown no change in C+ case prevalence during the period 1968-75 (Fig.5).

However, as the resurveys were extended further up to 1984-86, a decline of 2.3 per cent per year was recorded for the later period (overall being 1.4% per annum). Such a decline was not seen in Bangalore rural area (surveyed for first 12 yr). (ii) There was a declining trend in C+ cases in all ages, especially in 10-14 yr. This was in line with the age wise trend seen in the 12 yr follow up in the Bangalore rural area. (iii) There was no change in S+ case prevalence, for all ages. but, statically significant decrease among 10-14 yr old children was visible iv) There was a strong evidence of decline in both C+ as well as S+ case prevalence in females: 3.8 and 2.8 per cent annually. C+ cases had shown decline at a later period of the follow up in males, (i.e., between 1975-1978 to 1979-1981), without any significant change in the trend of S+ cases. (v) Because of the above gender related difference, the male : female ratio in C+ case prevalence had increased from 3.5 in 1968-70 to 5.2 in 1984-86 survey (average 4.7). The average for S+ cases for the entire period stood at 1.7 only.

Incidence of cases: (i) There was a steady decline in the incidence of C+ cases (at 4.3% per annum) from 352 /100,000 between the first two surveys (1968, 1971) to 189 between the last two (1981, 1984). The decline was seen in both sexes and in all age groups. (ii) There was only a tendency for decline in incidence of S+ cases. (iii) Ratio of prevalence and incidence of S+ cases remained 3.6, at the surveys, probably indicating that new S+ patients would probably continue as S+ cases after occurrence, cumulating themselves for 3.6 yr in the community, to constitute prevalence. Findings are more or less similar for both rural Bangalore and urban Delhi (between 3.33 and 3.7).X+ cases: There was significant and substantial decline in X+ case prevalence rate from 1289 / 100,000 to 827/100,000 between 1968 and 1986 (average decline 3.2% per year). The pattern was not gender specific.Comments on findings: (i) It was revealing to observe that incidence of S+ cases, arising at a later survey,from the radiographic class of tuberculous shadows on X ray in an earlier survey, was coming down significantly, with time for the area. This was likely to be due to the treatment programme in place for the area, as pursued under NTP, no doubt accentuated due to the presence and interaction with the research field staff of TRC, Chennai. They could act either by motivating patients and probably ensuring drug supply at treatment centres also. Being the long term study area for the TRC evidently had influenced intervention situations and brought long term benefit to the area. (ii) The decline in C+ cases, not initially seen, could also be evidenced on a longer term follow up, as different from the NTI rural area. There was substantial reduction in C+ case prevalence in later surveys (1991/1996 surveys). Whether it had anything to do with reduction of incidence from X + case class, is a point to consider. (iii) A hypothesis could be considered that when the ARI and S+ case prevalence (and incidence) are relatively high in an area, as it appears to be so in Tamil Nadu rural area, active and intense interventions

for a long enough and sustained span of time, are necessary to record change in them. The situation in the subset, for example, in Chingleput area, could record a change in C+ / S+ case situation, only in later surveys. In the subset studied longer (1991, 1994) a significant decline (2.7% per year) had occurred in the prevalence of S+ cases (398 to 262 per 100,000) (Fig.5). However, for reducing breakdown from among the X+ cases into C+ cases, on the other hand, a relatively low key treatment, as followed in the programme, could suffice to achieve the objective early enough. (iv) It is of consequence to programme managers while estimating the S+ case load from ARI data, to observe that the rate of incidence of S+ for 1 per cent of ARI had decreased from 74 to 42 per 100,000 in about 7.5 yr of observation (a decreased by over 40%). The decline in the relationship between S+ incidence and ARI with time, in the Indian context, is reported earlier from the Bangalore rural areas, under long term repeat surveys 42 . (v) The findings of the Chingleput area appear to be in line with the overall projections of change made in the 50 yr construct of epidemiological situation with a 2.3 per cent reduction annually, in response to a relatively low key programme dispensation43. (vi) One of the most significant findings from this study concerned the incidence of C+ and S+ cases, from out of the persons sputum negative but identified as having radiographic abnormality at an earlier survey. There was no decline in incidence from those with a normal X-ray or in those with non tuberculosis X-ray abnormality at an earlier survey. However, in those with a TB abnormality initially, the incidence of C+ cases had declined substantially (4.7% annually). It is also true for S+ cases. Of the total C+ S+ cases, arising in 1971-73, about a third had originated from those with an X-ray abnormality interpreted as tuberculosis. This proportion declined consistently from year to year and was only 8 per cent at the 1984-86 survey (Fig.6). It could be interpreted that the treatment given to the specific epidemiological class of X-ray shadows consistent with tuberculosis disease (X+ cases), had caused a substantially reduced incidence of S+ / C+ cases from this class. The selective decline in incidence by radiological classes moreover indicates a good standard of interpretation and classification of various radiographic abnormalities throughout the survey period. An alternative hypothesis of likely socio-economic change in the area reducing breakdown, may not be tenable, as the same was not reflected in ARI and incidence of S+ cases. The socioeconomic improvement, if responsible, could have caused reduction in incidence in all radiographic classes, not confined to X+ cases alone. It is generally recognised that for appreciation of change with time, culture-positive case prevalence rate of tuberculosis is not the appropriate index to rely on. In the Styblo study24, the C+ prevalence rate had been observed to register a high only during the survey years. However, it was also a crucial observation in the above study that the S+ cases, detected in a survey, and not confirmed on culture, were mostly found not to be the real cases. It thus stands to reason that in considering trend in the Chingleput studies, S+ cases are considered as cases, only when they are C+. The same was the case in NTI longitudinal surveys also. Thus prevalence of smear-positivity in a survey, unless supported by culture, is not considered representative. At the same time, prevalence of real smear-positive cases, in situations where there is considerable pooling of untreated or inadequately treated cases, is the index which is influenced in an effective control programme. For example, in a situation like as it is in India, where prevalence is about thrice the annual incidence, an effective control programme could possibly work by reducing the smear-positive case prevalence. It is in this context that the reduction in C+ prevalence cases over time, even earlier to that in S+ incidence cases, needs to be understood. It appears to be due to reduced breakdown, and the consequent incidence, specifically from among the X+ cases, through their treatment (a sort of secondary chemoprophylaxis). It appears possible that transmission in the present time did not come down sufficiently largely to be reflected in ARI. It needs to be kept in mind that the treatment of S+ cases was not energetic enough under the routine NTP treatment regimens, as pursued in the study areas. Even though it had salutory effect with regard to the breakdown from X+ class, in the manner of secondary chemoprophylaxis it could not reduce S+ case incidence/prevalence as a whole, and consequently the ARI for the area. Trend in an urban area: Findings from a study carried out in the New Delhi TB Centre area (NDTBC) are unique in the sense that it gives the only trend for an urban area in the country. The study was conducted for a sufficiently long span of 30 yr, following up the same community seven times after the first survey. The diagnosis in the survey was based only on culture and X-ray result. All the X+ and C+ cases were

efficiently treated through the survey period (90% cure rate achieved during 1995-96). The findings and comments on the trend are summarised as follows: (i) About a tenth (8%) of the bacillary cases had continued as such for about a decade (i.e., between the last two follow up 1982 to 1991). This was despite a good service programme in the area. Of the C+ cases 30 per cent were dead in the period. The proportions remaining as C+ or as X+ cases during the above period were significantly lower than observed between earlier two periods of follow up. (ii) The standardised prevalence rate of C+ cases had not changed over the period, being around 4.0per thousand (i.e., for 95% confidence level: 2.54-4.84). However, as in Bangalore and Chingleput study areas, there was a higher C+ prevalence at survey VIII among population 55+ yr age group, compared to earlier surveys. The peak of C+ cases at survey VIII in females, had shifted to around 45-54yr from around 25-34 yr, as seen between survey I through VI. However, a proportional concentration in the number of cases in higher ages with time, as seen in Bangalore rural area14, did not occur in the New Delhi area. This was interpreted to be due to a significantly reducing population size in the area, in the age group of 45+, compared to that in survey I, 30 yr back. Influx of wage earners in younger group and exodus of those in higher age (possibly considered to be without ostensible economic worth) from out of city area, was the essential demographic feature in the New Delhi city area45. This was not observed to be so in the rural areas of Bangalore, possibly causing the difference in the nature of epidemiological pooling of cases by age with time, between the areas. (iii) There was considerable decline in prevalence of X + cases at later compared to the earlier surveys (Survey I: 13.2, Survey VII, VIII: 6.5 and 5.4 per 1000). (iv) The X+ cases of earlier surveys had the highest rate of breakdown into C+ cases subsequently, this being the highest risk group. The reduction in rate of incidence from among X+ cases with time, as observed in Chingleput study was not observed in New Delhi. (v) Data on sputum smear positive (S+) cases as well as on infection rates (ARI) were not studied in these surveys.

Trend in a tribal area: Car Nicobar is an island in the Bay of Bengal, with a total population of 15,575 residing in 15 villages. An intensified tuberculosis control project was launched there by the Island Administration in 198646,47. All S + as well as C+ prevalence cases were detected on house-to-house survey and treated adequately. Children aged 5+ yr were given chemoprophylaxis for six months after tuberculin testing and those 0-4 yr given BCG vaccination. Infection prevalence was 10 per cent among the 0-14 yr old (Table XIII). The prevalence rate of S+ cases was 4.1 per 1000 and X + case, 7.9per 1000. At the end of a nine month short course chemotherapy 94 per cent of S+ cases were sputum negative. At a resurvey after a 16 month period, no fresh infected children were detected by the differences of reactions method17,47. Number of new S+ cases arising in the area in the period of 16 months was only a third of the previous prevalence (i.e., in conformity with NTI surveys38). The intensive programme was then discontinued at a time when there was no observed cumulative prevalence and no fresh infection taking place in 16 months. At this point, the NTP was implemented, leaving the routine district tuberculosis programe (DTP) to operate in the area. The survey in the area has been repeated in 2001-2002. It appears from treatment records, available with the local health authorities that over the years, the programme was not maintained in the island. Investigation and follow up of cases diagnosed from per cent of the S+ cases on register completing treatment, their sputum results unavailable. Incomplete treatment, if taking place in these cases year-to-year, could have prevented death, not ensuring sputum negativity though (Annual case fatality 3.7% among the cases on record since 1988, as against the likely rate of over 20 per cent among the cases in an area without an organized programme38, the latter taken to represent the natural dynamics of tuberculosis). In all likelihood this cumulation of cases over the years had returned the tribal community, back to where their epidemiological trend originally was, infact much worse than it was, before 1986. The force of infection of the relatively fresh cases all diagnosed afresh after 1986, must have caused an escalation of ARI as well, the incidence cases being more prone to cause higher transmission of infection in the community. Similar trend reversal from a tribal community in Greenland48 has been observed. Obviously, programmes need to be continued with an accepted level of efficiency for a long enough time. Lack of advocacy and priority could be important causes of attenuation of epidemiological

trend in a community. Trends of reduction in a community, achieved through care and effort as in Car Nicobar, could be rudely halted or reversed through lack of prioritisation at a later stage. This could be seen even in the most developed countries, as in Japan. year-to-year since 1988 in the area, showed only 66

So the learning from Car Nicobar study is that to control TB, interventions has to be sustained for long periodEpidemiological indices & Trends in India

In most of the western European countries and others in the industrially advanced world, the data on disease and death are obtained mainly from national statistical reports, provided by the Ministry of Health and National TB Organization. No such data are available for vast population groups in India. Tuberculosis is not considered to be a notifiable disease in India and hence routine health data have not served as the source of information for estimating the disease state in the community. Periodic community surveys, sporadic and in different areas, dependent solely on investigator’s convenience, are therefore relied upon, and extrapolated to observe and assess the tuberculosis disease situation in India

1) Death Occurrence of death is the first of the indices to decline in the secular curve of a tuberculosis epidemic, followed by morbidity and infection in that order ; subsequently however, it is not much informative to trace the course of the epidemic and to classify countries on the basis of their progress in the epidemiological situation. As an immediate and the most visible effect of anti-tuberculosis intervention, the prevention of death appears without doubt, to be an attractive index to the programme planners. For example, tuberculosis death toll in several European metropolitan areas was nearly 1 per cent annually at the height of the epidemic. It had reduced during the centuries long epidemic process, to be 1 to 2 per 1,00,000 population by the end of 1980s, a 500-1000 fold reduction. Though death has ceased to be a significant epidemiological information for the most advanced countries, it could still possibly be a measure of the extent of the most visible success of at least the antituberculosis programme delivery and its management, in the developing countries. For example, it is reported that nearly 70 per cent of possible deaths between 1991-2000 in Peru11, and nearly 46 per cent in China between 1991-1997, were treated among smear-positive cases of tuberculosis, through a more efficient process of programme delivery. In India death measured as (i) Mortality(ii) Case fatality rate

Mortality

It is death that attributable to tuberculosis among total population in the community. TB mortality in the country has reduced from over 400/100,000 population in 1955-58 to 28/100,000 population in 2006 (WHO Global TB control Report 2009). The target for mortality was 21/100,000 population per year.

Case fatality

It is death among the known cases of tuberculosis. Data from specific surveys, however, suggest that case fatality rates prior to RNTCP were generally greater than 25%. In the RNTCP era, case fatality has remained below 5% for new cases registered for treatment under the Programme. Deaths due to TB exceed the combined deaths from all other communicable diseases and account for 26% of all avoidable adult deaths.

2) Prevalence of disease

It refers to persons diseased at a point of time in the given community. Prevalence & incidence of disease is considered in term of sputum positivity, Culture positivity & x-ray positivity. It is second indice to fall after fall of morbidity. In 1955-58 that the nationwide study conducted first time by ICMR, provided an insight into the enormity of suffering caused by TB in India. The survey findings revealed the prevalence of sputum positive PTB to be about 400 per 100,000 population. The prevalence was found to be similar in rural and urban areas. Considering the country's population, there were an estimated 1.5 million infectious cases at that time spreading infection in the community. In fact, before the abovementioned survey, TB was generally believed to be an urban disease.

Year No. of death / 100000 population/year

1955-58 4001972 1001990 422002 372003 332006 282015 target 21

Year No. of Bacteriological cases/ 100000 population/year

1955-581990 5682006 2992009 2832015 target 293

3) Incidence of disease It refers to occurrence of disease between two points of time in the community among those not initially affected. Prevalence and incidence of disease are considered in terms of culture with or without smear positivity (C+), smear positive cases (S+) or, X- ray positive culture/smear negative cases (X+). According to WHO Global TB Report, 2009, the incidence of new SS+ cases – 75 cases/100000 population & all forms TB 168 case/100000 population per year

4) Prevalence and incidence of infection –Persons in the community infected with tubercle bacilli at a point of time is prevalence of infection; persons infected between two points of time among those not infected or, BCG vaccinated initially is incidence of infection.

Earlier prevalence studies have been conducted in limited geographical areas. The methodology also varied in terms of the age group studied, the screening and diagnostic methods as well as defining TB cases. The disease prevalence studies require significant resources and the sample sizes required are often large. Such studies are also time consuming and are therefore difficult to conduct. For the same reasons, the studies of disease incidence are even more difficult because of the need to subject the same study population to repeated surveys at periodic intervals. Therefore, very few incidence studies have been conducted in the country. The routine surveillance data compiled from case finding reports obtained from health facilities under TB control programmes also do not reflect on the epidemiological situation of tuberculosis.

Therefore other epidemiological parameter that is widely used to assess the TB situation in the community is the Annual Risk of Tuberculosis Infection (ARTI). The ARTI indicates the probability of an uninfected person getting infected or re-infected with tubercle bacilli during the course of one year. It reflects the overall impact of various factors influencing the transmission of the tubercle bacilli like the load of infectious cases in the community and the efficiency of public health measures to control tuberculosis. The studies to estimate the ARTI are relatively inexpensive and require simpler technology. The ARTI is the first epidemiological parameter to be affected following a change in the situation of tuberculosis in the community. However, most of the studies on the estimation of ARTI were localized to pockets in the southern parts of the country in the vicinity of the two pillars of strength on TB research - NTI and TRC.

Prevalence of infection in the Indian context cannot be estimated accurately in those aged 14 yr or more. Failure to demarcate the infected from the non infected due to high prevalence of intermediate reactors in India in older ages, does not allow prevalence of infection among the unvaccinated subjects, to be a sensitive indicator. In fact incidence of infection as studied in younger age groups is the appropriate index to measure the tuberculosis situation in a community. However, estimating incidence would call for repeat testing of the same children. To avoid repeat tuberculin testing of the same children, a mathematical estimation is carried out, using the figures on the prevalence of infection in younger children (0-14 yr) to obtain the incidence of infection. The latter is termed the annual risk of infection (ARI). The estimated ARI is actually observed to be the same as the incidence of infection, when worked out by repeat testing of the same population under Indian conditions It is understood that ARI is studied among the unvaccinated subjects only. However, in situations where mass BCG vaccination at birth or soon after is the national policy, it is not a convenient to use these children as study subject, as most of them will already be vaccinated. The alternative could be to study the incidence of infection in the vaccinated, for identifying the newly infected subjects by the differences of reactions method. Chadha et al18 have shown the infection estimates in the vaccinated and unvaccinated as not materially

different(Similar study was done in Deptt of Micribilogy, MGIMS,2003). The same does not stand corroborated from some Indian experiences (Regional Medical Research Centre, Port Blair, 2002, personal communication). It should be noted that for developing the information base on infection both for prevalence and incidence, periodic community surveys have necessarily to be carried out as these serve as the only data source.

ARTI Survey (2000-2003)

The study was conducted among children 1 to 9 years of age. 26 District from 4 zones was selected. The sample size for each zone was estimated considering the expected prevalence of tuberculosis infection as 8% and to obtain the estimates within 10% of the true value at 5% level of significance. A design effect of 2.33 based on previous tuberculin surveys was applied for the estimation of the sample size. The estimated sample size was distributed into rural and urban strata in proportion to the rural-urban population in the zone. A two-stage sampling procedure was adopted for selection of clusters within the stratum. At the first stage, a sample of six districts was selected by systematic sampling, in each of the north, south and west zones. Within a stratum, the assignment of number of clusters to districts was done in proportion to the respective district population. In east zone, the sample size was distributed into eight similarly selected districts in order to have larger representation from northeastern states.

The fieldwork in north, west and east zones was conducted by NTI and that in south zone by TRC. The necessary local support was provided by the district health authorities. The NDTC

assisted in the supervision of fieldwork in three districts of north zone and MGIMS in three districts of west zone.

The zonal estimates were pooled to estimate the national level ARTI, which worked out to 1.5%. i.e. 75 new smear positive pulmonary TB cases are expected per 100,000 populations annually. Nearly 40% of the Indian population was infected with the TB bacillus.

The study provided useful information on the prevailing epidemiological situation of TB in the four zones of India. The results indicate a high rate of transmission of infection due to high load of infectious cases in the community. The high ARTI rates imply that the incidence of disease shall continue to be high in the coming years and therefore TB control measures need to be intensified on a prolonged basis.

Prevalence of suspect

This is based on x-ray examination of chest. Drawback is as it is not diagnostic of TB, therefore bacteriological confirmation is needed. Not much epidemiological significance.

Urban & Rural

As per 2000-03 ARTI survey, the estimates were carried out as above, by pooling the zonal level estimates that were obtained by cut-off point method (Method I) as well as by mirror-image technique (Method II). The resultant national estimates are as under: National sample survey 2000-2003

Factors influencing the epidemics phase in secular trendDeterminants like urbanisation, crowding, economic situation, inter-current diseases, epidemics, standards of living, sanitation, environmental conditions, nutrition, tuberculinisation of the community and effective steps in treatment and prevention. The common belief, that tuberculosis is a disease of urban population rather than that of rural communities, is not tenable for all phases of epidemic. The increase in urbanisation speeds up the epidemic. But as the tuberculosis wave advances the infection and disease spread to the rural areas. Larger number of people all over urban and rural areas is soon exposed to infection. The increase in degree of urbanisation and industrialisation speeds up the epidemic with transient hump followed by faster drop due to premature death of susceptibles. Simliar1y, the temporary increase, in mortality and morbidity, is encountered under conditions of stress, like war, famine etc. and is believed to be due to weakening of host resistance. These factors transiently influence the natural course of the disease giving rise to minor fluctuations as small epidemics which soon level off. The relative influence of these factors, the manner and extent of their contribution to development, maintenance and decline of the disease among population groups is a subject matterct of debate and inquiry.Influence of ATT on epidemic phase of secular trendThe phenomenon of decline as seen in developed countries had started much before the use of segregation, collapse therapy, surgery or BCG Vaccination. The discovery of antituberculosis drugs lead to the belief that The slogan of the American National Tuberculosis Association in 1930s was “No Tuberculosis by 1960”. This dream, despite all the resources at their command could not be realised even by 1976. Even if all the sputum positive patients are found at a moment’s notice, followed by effective isolation and treatment, the occurrence of new cases, from the large reservoir of infected population or with inactive disease, cannot cease. However, the decline of tuberculosis, which has been taking place even prior to any organized attempt to fight the disease, can be accelerated by anti-tuberculosis measures. The anti-tuberculosis drugs, in particular, have not only changed the outlook for individual tuberculosis patients but by reducing the period of their infectivity and relapse rates, these along with socio-economic betterment have speeded up the decline of tuberculosis — as seen in Japan and among Eskimos of Canada. The important aspect of anti-TB Another facet of this situation lies in the fact that in many places half or more than half of the smear positive cases of TB are accounted for by those who have been treated unsuccessfully. They are either chronics or relapses. In the prevalence survey in China, more than half of the smear positive cases gave history of previous treatment.

In India, data are available from the Chingleput BCG trial area. 71% of the total bacteriologically proven cases were old cases. Treatment, however, was the same as given in the National Tuberculosis Programme. This situation in which half or more than half of smear positive cases in the country are treatment failures, chronics or relapses gives us an opportunity to design a really effective programme. This was causing, poor chemotherapy prevents deaths but often keeps large numbers of chronic excreter alive. And the epidemiological situation depends mainly on the number of sources of infectious cases. So, a poorly operating treatment programme may result in slowing down of the natural rate of decline, Graph 9 shows that even a very poor treatment programme, such as, mono-therapy, or poorly taken treatment which is so common in many third world countries, reduces very substantially the number of deaths from tuberculosis. It also leads to cure of many patients who would otherwise succumb to this disease. Many tuberculosis treatment programmes, however, do not contribute to the reduction of tuberculosis problem. This is simply due to the fact that these programmes frequently produce chronic cases of tuberculosis, the chronic bacillary excretors. Therefore, the actual number of sources of infection

in the community becomes even greater, than would have been if no treatment was given & causing worsening of epidemiological situation

Factors that affecting epidemic curve in IndiaThese are

1. Socio-economic status 2. Poor treatment3. HIV/AIDS4. Drug resistance

Socio-economic statusThis is evident that from developed countries where disease was well controlled before introduction of ATT due high living standard & acquired resistance. India also had acquired resistance but probably on account of the poor socio-economic status of the general masses the decline is not apparent. HIV-AIDS - TB-interface: epidemiological situation

Tuberculosis is the only AIDS-related opportunistic infection which is public health problem. It is the most powerful risk factor for the progression of TB infection to TB disease, of those infected with TB bacilli. People infected with tubercle bacilli and HIV are 30 times more likely to develop active tuberculosis in a given year, than those infected with tuberculosis alone. An HIV positive person also infected with TB bacilli has 50-60% life time risk of developing TB disease, as compared to an HIV negative person who has a 10% life-time risk of developing TB disease. Studies in India show that the proportion of HIV seropositivity in tuberculosis patients in hospitals in Chennai and in Mumbai has risen from 2.6 per cent in 1988-89 to 15.28 per cent in 1999. On the other hand, it has risen in Pune from initial level of between 3.25 and 3.6 per cent in 1991 to about 20.1 per cent in 1996. A study from Tanjavur (Tamil Nadu) rural areas reports a rise in HIV seropositivity among tuberculosis patients from 0.59 per cent in 1996 to 8.89 per cent in 1999. It is estimated that nearly 5% of the TB patients are HIV infected. The periodic HIV survey in TB patients, which was carried out in 4 districts in 2005-06, was scaled up to 15 districts in 2006-07. The 2007 survey represents the most detailed evaluation to date of HIV epidemiology among TB patients in India. The survey demonstrated that the prevalence of HIV among TB patients varied substantially across the geographic regions between 1% and 13.8% across the 15 surveyed districts. According to the 4 th qrt 2008 RNTCP status report from 9 states 34% among TB cases were tested for HIV & 14 % were found to be HIV positive.

From the global model on spread of HIV-AIDS and how it could be affecting tuberculosis epidemic in India, it is derived by Williams that under the hypothetically simulated scenario of even the best possible

expansion rate and the most effective implementation of RNTCP in India, together with the best possible situation of a low HIV-spread, there could still be a rising number of tuberculosis cases in the country The number of tuberculosis cases could still be higher by 59 per cent by 2020 (cumulative no. of incidence 21 million). The above situation could be seen as better than an alternative worst possible case scenario with a likely rise in tuberculosis incidence by 82 per cent during the period, under a favorable HIV situation but without an RNTCP, with the requisite expansion and adequate efficiency. However, with the worst case scenario of high rise of HIV and slow expansion of RNTCP, the cumulative number of cases could be 46 million by 2020, i.e., more than double, with the spectre of a 20 per cent rise in the incidence of fresh cases of tuberculosis.

The collaborative activities which were being undertaken in 14 states earlier have been scaled up to involve all the states in 2008. NACP & RNTCP have developed “National framework of joint TB/HIV Collaborative activities” in 2007, and then revised in Feb 2008, which redefines the scopes of TB/HIV collaborative activities being implemented in the country in Fiscal 2008. Year 2008 saw continued increase in the quantum of referrals between the programme. In the year 2008 more than 0.16 million ICTC clients were referred to RNTCP for TB diagnostic evaluation. 0.13 million TB patients were tested for HIV and more than 20,000 patients were detected to also be HIV-infected.

Prevalence of MDR TBThe next indice that can affect the epidemic curves decline is the prevalence of MDR TB cases. & has become an obstacle for effective TB control. Several small surveys conducted across the country have shown the prevalence rates of MDR-TB in the country at around 3% among new cases, and 12% among retreatment cases. A large scale population based survey in the states of Gujarat and Maharashtra has also shown similar resistance levels (new-3% and retreatment- 12-17%). Available information suggests that the proportion of MDR-TB is relatively low in India. However, this translates into a large absolute number of cases, with an estimated annual incidence of 110,000 cases of MDR-TB. At DOTS plus site GMC, Nagpur 90 cases were suspected of MDR tested, out of them 32 were diagnosed as MDR & 16 were registered under category(4th Qrtr 2008).

In a recent review of the Indian situation, eminent workers from the TRC, Chennai, have concluded that the magnitude of the drug resistance problem is principally due to acquired resistance (i.e among previously treated cases). In Gujarat, the patients with treatment failure or relapses, had shown an increased Rifampicin resistance from 2.8 per cent (1980) to 37.3 per cent in 1986, and Isoniazid (INH) resistance from 34.5 to 55.8 per cent. MDR TB was of the order of 30 per cent. In New Delhi, a similar extent of acquired drug resistance was reported. Institute of Thoracic medicine in Chennai had shown acquired resistance of about 63 per cent among patients from District Tuberculosis Centres of Tamil Nadu. Resistance to INH and Rifampicin (MDR TB) was of the order of 20.3 per cent. It was considered that initial drug resistance in India (freshly defined as, drug resistance among new cases) could be at a lower order than similarly placed countries globally, as distinct from the acquired drug resistance situation given above. There could be 5-10 per cent resistance to INH, 2-11.45 for streptomycin and nil for Rifampicin in Indian children. This could be reflecting the primary drug resistance problem in the Indian context, and there could be no immediate cause for alarm on this score. The situation thus could be interpreted that (i)there is inadequate and inappropriate treatment, both in private and public, including the NTP; (ii) the situation has caused high levels of widespread drug resistance in previously treated patients.

Prevalence of XMDR

XDR-TB has been reported in India by isolated studies with non-representative and highly selected clinical samples. The magnitude of the problem remains to be determined due to the absence of laboratories capable of conducting quality assured second line Drug Susceptibility Testing (DST). However, what is frightening is the potential threat of XDR-TB in India, with unregulated availability and injudicious use of the second line drugs along with non-existence of systems to ensure standardized regimens and treatment adherence for MDR-TB outside the national programme. The problem of MDR and XDR-TB in India and across the world raises the possibility that the current TB epidemic of mostly drug susceptible TB will be replaced with a form of TB with severely restricted treatment options. If this happens it would jeopardize the progress made in recent years to control TB globally as well as in India and would also put at risk the plans to progress towards a world where TB ceases to be a public health problem.

Epidemiological triad

Agent factors: M. tuberculosis is facultative intracellular parasite i.e. is it readily ingested by phagocyte & is resistant to intracellular killing. There are two strains human & bovine. Bovine affects cattle & other animals. Regarding virulence Indian tubercular bacillus is said to be less virulent than the European bacillus.

Human tuberculosis is of mixed type of infection i.e. Slow multiplier & rapid multiplier. Slow multiplier is seeds for relapse cases in community, they can remain dormant can turn in to disease till favorable conditions arrived.

Atypical mycobacterium

Photochromogen (e.g. M. kansasii) Scotochromogen ( M. Scrofulaceaum), Non-photochromogen (e.g M. intercullulare) & rapid grower ( m.fortuitum). these are saprophytic. They have got importance due to HIV/AIDS.

Host factors:

Age: Tuberculosis affects all ages. In developing countries shows sharp rise of in infection rates from infancy to adolescence. It badly affects reproductive population.

Age (yrs) 1968-70 1973-75 1979-81 1984-86 2000 2005<14 35(0.88) 14(0.30) 8(0.20) 3(0.07) 3,838(2.02) (1.85)15-24 108(2.73) 111(2.40) 105(2.61) 62(1.54) 35,458(18.65) (21.18)25-34 425(10.74) 461(9.96) 404(10.06) 292(7.25) 45377(23.86) (23.65)35-44 729(18.42) 691(14.93) 570(14.19) 693(17.20) 42597(22.40) (20.75)45-54 899(22.71) 1127(24.36) 1050(26.14) 921(22.86) 31746(16.69) (16.09)55-64 994(25.11) 1218(26.32) 966(24.05) 1144(28.40) 11902(10.470 (10.53)64+ 768(19.40) 1,005(21.72) 914(22.75) 913(22.67) 11231(5.91) (5.91)Ref. 2, Ref.11, RNTCP status report 2006

Sex: more prevalent in male as compare to female

Nutrition: Malnutrition is widely believed to predispose to tuberculosis. but the available evidence is the indirect. & also it won’t affect the recovery of patient in the context of potent chemotherapy drug.

Immunity : no inherited immunity against tuberculosis. It is acquired by natural infection or BCG vaccination. Past infection with atypical mycobacterium also credited some immunity. Immunity is of two type i.e delayed hypersensitivity & cell mediated response. In most of cases cellular immunity proves adequate to limit further multiplication & spread of bacilli. Pre-chemotherapy era, the t/t of TB was mainly strengthening of immune system of of host(rest,

fresh air, nutrition) but after advent of chemotherapy host factor are considered to be less relavent in the epidemiology of TB.

Environmental factor:

Poor housing (ill ventilated), overcrowding,

Air circulation and ventilation

Volume of air into which the bacilli are expelled determines the probability that a susceptible individual becomes infected

Ventilation dilutes the concentration of infectious droplets nuclei

Social factors:

Tuberculosis is social disease with medical aspect. It has been considered as barometer of social welfare. Poor quality of life, population explosion, lack of education, lack of awareness of causes of illness is the predisposing factors. In fact TB has decline in western world wel before the advent of chemotherapy just because of improvement in quality of life.

Besides the disease burden, TB also causes an enormous socioeconomic burden to India. TB primarily affects people in their most productive years with important socio-economic consequences for the household when an individual falls sick with TB. The disease is even more common among the poorest and marginalized sections of the community. Almost 70% of TB patients are aged between the ages of 15 and 54 years. While two thirds of the cases are male, TB takes a disproportionately larger toll among young females, with more than 50% of female cases occurring before 34 years of age. In addition there is a devastating social cost – more than 300,000 children are forced to leave school because their parents have TB, and more than 100,000 women with TB are rejected by their families. The direct and indirect cost of TB to India for morbidity alone amounts to an estimated $3 billion annually (in 2000). Studies suggest that on an average, 3 to 4 months of work time is lost as a result of TB, resulting in an average potential loss of 20-30% of the annual household income. This leads to increased debt burden, particularly for the poor and marginalized sections of the population.

The survey carried out in Wardha District (Maharashtra) is the only source of survey data (unpublished) linking tuberculosis in the community to socio-economic criteria

Source of infection

Two important sources 1. Human source & 2. Bovine source

Most common source of infection is the human case whose sputum is positive or who are not received treatment or treated incompletely. An estimated annual average of 10-20 persons contract the infection from one case of infectious pulmonary tuberculosis. When infectious people cough, sneeze, talk or spit, they propel TB germs, known as bacilli, into the air. A person needs only to inhale a small number of these to be infected.

Bovin source is usually infected milk. There no definite evidence that this strin is problem in India because of practice of boiling millk before drinking.

Mode of transmission: by the droplet infections & droplet nuclei generated by sputum positive patient with pulmonary tuberculosis. Tuberculosis is not transmitted by fomites, such as dishes & other articles used by patients.

Incubation period: the time from infection to the development of positive tuberculine test ranges from 3-6wks & thereafter the development of disease depends upon the closeness of contact, extent of disease & sputum positivity of source case(dose of infection), host-parasite relationship. Thus it range from in days,months or years.

Communicability: patient are infective as long as they remained untreated. A single patient can infect 10 or more people in a year.

Probability of infection depends on:

Number of droplets nuclei in air Duration of exposure of a susceptible individual to that droplet

Airborne transmission

To be transmissible through air, agent must remain buoyant in the air. Velocity of a droplet falling to the ground depends on: surface and diameter. For example: in moisture-saturated air droplets would fall to the ground from a height of 2 mts. in

less than 10 sec. Liquid droplets tend to evaporate, diminishing their size. The duration of time droplets remain in unsaturated air is proportional to its size.

• Very small droplets evaporate immediately• Large drops settle rapidly and reach ground without evaporation.

Droplets with a size less than 0.1 mm. are more likely to reach alveoli and then produce infection. Droplets higher than 5 mm will not produce infection.

Control & preventionTuberculosis control means reduction in the prevalence &n incidence of disease in the community. Control of TB: define as prevalence of natural infection in the the age group of 0-14years is of order of 1percent. This is about 40% in India.Elimination of TB: <1 case /1 million populations.Control measures consist of curative component –namely cases finding & treatment & preventive component – namely BCG vaccination.

BCG vaccination Early diagnosis & treatment – Case finding & treatment Preventive therapy of household members

BCG Vaccination

The BCG vaccine was first used to immunize humans in 1921.

Composition

It is a live freeze-dried vaccine derived from attenuated strain of mycobacterium bovis. (Bacillus Calmette Gueri) used for the prevention of tuberculosis. The current vaccine strains are all descendants of the original M. bovis isolate that Calmette and Guérin passaged through numerous cycles (230 subcultures)during the 13-year period 1909–1921. Subsequent passages under different laboratory conditions resulted in a variety of new BCG strains showing phenotypic as well as genotypic differences. A number of BCG vaccine strains are available, although the French Pasteur strain 1173 P2, the Danish strain 1331, the Glaxo strain 1077 and the Tokyo strain 172 account for about 90% of BCG vaccinations worldwide. In terms of efficacy, no BCG strain is demonstrably better than another, and there is no global consensus as to which strain of BCG is optimal for general use. It is freeze-dried, Live, attenuated BCG Vaccine(Bacillus Calmette Gueristrain)Each 0.1 ml contains between: 1x105 and 33x105 C.F.U. Reconstitute with Sodium Chloride Injection

ReconsttutionBCG Vaccine vial of 10 doses (0.05 ml) for infants under one year old, to be reconstituted with 0.5 ml of sodium chloride injection. BCG Vaccine vial of 20 doses (0.05 ml) for infants under one year old, to be reconstituted with 1 ml of sodium chloride injection.

Use immediately after reconstitution. If the vaccine is not used immediately then it should be stored in the dark at 2° to 8° C for no longer 6 hours (1 immunisation session). Any opened vial remaining at the end of a vaccination session (within six hours of reconstitution) must be discarded

Dosage and administrationIt is given intradermal route, avoiding the subcutaneous route just above the insertion of deltoid muscle. Dose is 0.05 ml for children under one year of age including the new born, of the reconstituted vaccine. The skin should not be cleaned with antiseptic. The vaccine should be preferably given with a tuberculin syringe or 25G/26G sterile needle and syringe. A satisfactory injection should produce a wheal of 5mm in diameter.

Indications and immunization schedule

BCG Vaccine should be given routinely to all infants at risk of early exposure to tuberculosis. This vaccine should be given soon after the child is born. BCG administered early in life provides high level of protection particularly against sever forms of childhood tuberculosis and tubercular meningitis. In countries with low prevalence of tuberculosis, BCG vaccination should be restricted to high-risk groups such as hospital personnel and tuberculin negative contacts of known cases of tuberculosis. long-term follow-up of BCG-vaccinated infants of known HIV-positive mothers is desirable for early treatment, shoulddisseminated BCG disease occur in children with rapid development of immunodeficiency. In cases where infants have been exposed to smear-positive pulmonary TB shortly after birth, BCG vaccination should be delayed until completion of 6 months of prophylactic isoniazid treatment. The vaccine can be given simultaneously with DTP, DT, TT, Measles, Polio and Hepatitis B vaccines, but at a separate site.Adverse eventsAdverse events occur in 1-10% of individuals who receive BCG and vary depending upon dosage, method of administration and age of vaccinee. Lymphadenitis can also occur. Lymphangitis can occur if the vaccine is administered too close to the shoulder and is characterized by streaking from site of injection towards the regional lymph nodes. Lymphadenopathy of regional lymph nodes, which resolves spontaneously, occurs occasionally in young children. Osteomyelitis has been reported to occur rarely (one case per million vacinees) and most frequently in neonates. Disseminated BCG infection, which can be fatal, occurs rarely in 1-10 cases per 10 million vaccinees and is more common in immunodeficient children. Correct intradermal BCG vaccination almost invariably results in minor local reactions (erythema, induration, tenderness) often followed by a small ulceration at the site of the injection. The age and immune status of the vaccinee, the skills of the vaccinator, as well as the strain and dose of the BCG vaccine, may influence the extent of these responses. Within a few months, the local reaction is followed by a small scar. Presence of a typical scar is used as a marker of previous BCG vaccination but is not a marker of protectionagainst TB. In the absence of a scar in children in high-burden countries, BCG vaccination is indicated.

Contraindications and precautions

BCG vaccine is contraindicated in hypogamma- globulinemia, congenital immunodeficiency, sarcoidosis, leukaemia, generalized malignancy, Symptomatic HIV infections or any other disorder in which natural immune response is altered, as also those on immunosuppressive therapy, corticosteroids, radiotheraphy. In chronic eczema or other dermatological disease, the vaccine can be given in a healthy area of skin. Keloid and lupoid reactions may also occur at the site of injection and such children should not be revaccinated.

Children born to hiv seropositive mothers

The obligatory passage of maternal antibodies of the lgG type through the placenta makes it impossible to interpret the serology of the child until the age of about 9-10 months (persistence of the maternal antibodies has been detected up to 14 months). It is therefore necessary to wait until the child has been found to be seronegative, as determined by immuno-transfer (Western Blot) with the support, if necessary, of techniques for detecting the viral genome, before confirming that the child is not infected. If the child is not infected BCG vaccine is contraindicated irrespective of the child’s condition, given the potential risk of development of ’’BCG-itis’’ in the vaccinated child. The advice of a specialized medical team is required. Neither absence of BCG scar formation nor negative PPD reaction is indicative pf poor BCG uptake. There is no need to repeat BCG inoculation in babies who do not develop BCG scar as advocated in the guidelines of IAP1996.Side effects

Complications following BCG vaccination are rare: the incidence of fatal dissemination of BCG is estimated to be 0.19–1.56 per million vaccinees and has almost exclusively occurred in inadvertently immunized persons with severely compromised cellular immunity. Significant local reactions, such as extensive local ulceration and regional lymphadenitis occur in <1:1000 and in most cases (>99%) in immunodeficient persons. Since neonates have a higher risk of vaccine-induced suppurative lymphadenitis than older children, infants aged <30 days should receive a reduced dose of the vaccine. Osteitis has been reported in connection with certain vaccine batches but now occurs very rarely.

A local reaction is normal. Following BCG vaccination, 2 to 3 weeks later a papule develops at the site of vaccination and increases slowly in size of a diameter of 4-8 mm in 5 weeks. It then subsides or breaks into a shallow ulcer covered with a crust. Healing occurs spontaneously in 6-12 weeks leaving a permanent, tiny round scar 2-10 mm in diameter. In rare cases an abscess may appear at the point of injection, or satellite adenitis, leading in exceptional cases to suppuration. Exceptional cases of lupus vulgaris at the point of injection have been reported. Inadvertent subcutaneous injection produces abscess formation and may lead to ugly scars. A risk generalized reaction to BCG exists in immunodepressed individuals vaccinated with BCG or living in contact with a vaccinated individual.

BCG vaccination is indicated

– for all infants living in areas where TB is highly endemic (concerning HIV, see below);– for infants and children at particular risk of TB exposure in otherwise low-endemic areas;– for persons exposed to multidrug-resistant Mtb (impact not established.)

BCG vaccination is contraindicated

– for persons with impaired immunity (symptomatic HIV infection, known or suspected congenital immunodeficiency, leukaemia, lymphoma or generalized malignant disease);– for patients under immunosupressive treatment (corticosteroids, alkylating agents, antimetabolites, radiation);– in pregnancy.

Efficacy

BCG vaccine has a documented protective effect against meningitis and disseminated TB in children.It does not prevent primary infection, pulmonary TB and, more importantly, does not prevent reactivation of latent pulmonary infection, the principal source of bacillary spread in the community. The impact of BCG vaccination on transmission of Mtb is therefore limited. During the period 1935–1975, extensive trials to assess the protective efficacy of BCG against pulmonary TB provided conflicting results.

Generally, the highest rates of protection (60–80%) were achieved in north America and northern Europe, whereas in tropical regions trials usually showed low or no protection. For example, the Tice BCG strain that was formerly widely used in the United States induced protection among vaccinees ranging from 0–75%. Likewise, the Copenhagen vaccine strain showed 77% protection following vaccination of schoolchildren in England and 0% protection when used in the general population of southern India.

Duration of protection

The duration of protection after neonatal BCG vaccination is not well known but commonly believed to decline gradually to non-significant levels after 10–20 years. BCG vaccination does not prevent reactivation of latent TB, the main source of bacillary dissemination in the community. Hence, BCG vaccination has essentially no impact on TB transmission. Mantoux-positive after a period of 8 weeks has elapsed, but sometimes about 14 weeks are needed.

StorageBCG Vaccine (Freeze-dried) should be stored in dark between 2°C and 8°C. It is even more stable if stored in temperatures as low as -20°C. Protect from light. The diluent should not be frozen, but should be kept cool.

Shelf life24 months from the date of last satisfactory potency test if stored in a dark place at recommended temperature.

Presentation10 dose vial plus diluent(0.5 ml)2 0 dose vial plus diluent (1 ml)

New vaccines against TB

Better understanding of the immunological deficits of BCG and impressive progress in knowledge of Mycobacterial genomics have paved the way for promising new products. The main vaccine targets are prevention of infection in naïve individuals, prevention of reactivation of latent infection and therapeutic vaccines to prevent relapses in TB patients. Currently, the most favoured research strategies include recombinant modified BCG vaccines, attenuated strains of Mtb, subunit vaccines and DNA vaccines.

WHO position on BCG vaccination

Despite the shortcomings of this vaccine, WHO continues to recommend that a single dose of BCG be given to neonates or as soon as possible after birth in countries with a high prevalence of TB. The rationale for this is he significant protection achieved against life-threatening TB in young children, the often early exposure to Mtb and the short incubation period for TB meningitis and military disease.

2. Case finding & treatment- NTP, RNTCP & Stop TB strategy

National Tuberculosis Program was started in 1962. Later on revised in 1992 Now it is revised national tuberculosis control program. This programme has two important components, good quality diagnosis and treatment.

Objectives:

To detect at least 70% of the estimated incidence of smear positive pulmonary tuberculosis patients by quality microscopy.

Achievement of at least 85% cure rate of infectious cases through DOTS. Involvement of NGOs, information, Education & communication &

improved operational research.

Case finding

It is passive case finding. The New guidelines for diagnosis is effective from 1st April 2009

Identification of TB suspectsA pulmonary TB suspect is any person with cough for 2 weeks, or more.

Collection of sputum

A good sputum specimen consists of recently discharged material from the bronchial tree, with minimum amounts of oral or nasopharyngeal material. Satisfactory quality implies the presence of mucoid or mucopurulent material. Ideally, a sputum specimen should have a volume of 3-5ml.Specimens should be transported to the laboratory as soon as possible after collection. If delay is unavoidable, the specimens should be refrigerated to inhibit the growth of unwanted micro-organisms. If refrigeration is not possible and a delay of more than 3 days is anticipated, a suitable preservative viz., an equal volume of a mixture of 1% CPC and 2 % sodium chloride (NaCl) solution is recommended to be used.

Diagnosis of smear positive TB amongst TB suspects

Diagnosis is done by Ziehl-Neelsen staining.It requires some 5,000 bacilli in 1 ml. of sputum to yield positive a smear, and 10,000 to identify a smear as positive with a 95% probability.

The number of specimen required for diagnosis of smear positive pulmonary TB is two, with one of them being a morning sputum specimen.

One specimen positive out of the two is enough to declare a patient as smear positive TB.Treatment with DOTSEffective treatment with anti-microbial treatment reduces infectivity by 90% within 48hrs.

Category

Characteristic of a TB case Treatment regimen

Intensive phase Continuation phase

Category I New sputum smear-positive Seriously ill, sputum smear-negativeSeriously ill, extra-pulmonary

2 ( HRZE )3 4 ( HR )3

Category Relapse, Failure, Treatment after 2 5 ( HRE )3

II default, Others ( SHRZE )3 followed by 1 ( HRZE )3

Category III

Sputum smear-negative Not seriously ill, extra-pulmonary

2 ( HRZ )3 4 ( HR ) 3

Category IV RNTCP will be using a Standardised Treatment Regimen ( Cat IV) for the treatment of MDR-TB cases under the programme. Cat IV regimen comprises of 6 drugs (kanamycin, ofloxacin, ethionamide, pyrazinamide, ethambutol and cycloserine) during 6-9 months of the Intensive Phase and 4 drugs (ofloxacin, ethionamide, ethambutol and cycloserine) during the 18 months of the Continuation Phase. p-aminosalicylic acid (PAS) is included in the regimen as a substitute drug if any bactericidal drug (K, Ofl, Z and Eto) or 2 bacteriostatic (E and Cs) drugs are not tolerated.Dosages for Adult Isoniazid – 600mgRifampacine-450mg /For pts weighing >60 additional 150mgPyrazinamide-1500mgStreptomycine-750mg/pt >50yrs 500mgEthambutol-1200mg

TB In Children

TB in children is due to failure to control tb in adults. Pulmonary TB is primarily an adult disease and it has been estimated that the 0-19 year old population contains only 7% of the total prevalent cases. In 2002, of the 2,45,051 new smear positive PTB cases initiated on treatment under RNTCP, 4,159 (1.7%) were aged 0-14 years. From a survey of RNTCP implementing districts, Paediatric cases were seen to make up 3% of the total load of new cases registered under RNTCP. Lymph node (LN) TB cases predominated (>75%) amongst the paediatric EPTB cases registered under RNTCP. Many EPTB cases (>40% of LN cases) were diagnosed on clinical grounds with no confirmatory examinations performed. An almost equivalent number of Pediatric TB cases were being diagnosed in the same health facilities, but were not being registered under RNTCP. Of those Pediatric cases treated under RNTCP, cure and completion rates were both above 90%. Comparative figures for those cases not treated under RNTCP were 80% and 70%, with default rates between 27-33%. (Central TB Division). DiagnosisSuspect cases of PTB will include children presenting with: fever and / or cough for more than 3 weeks, with or without weight loss or no weight gain; and history of contact with a suspected or diagnosed case of active TB disease within the last 2 years. * Diagnosis to be based on a combination of clinical presentation, sputum examination wherever possible, Chest X ray (PA view), Mantoux test (1 TU PPD RT23 with Tween 80, positive if induration >10mm after 48-72 hours) and history of contact. Diagnosis of TB in children should be made by a Medical Officer. Where diagnostic difficulties are faced, referral of the child should be made to a Pediatrician for further management. The existing RNTCP case definitions will be used for all cases diagnosed. The use of currently available scoring systems is not recommended for diagnosis of pediatric TB patients.

For the purpose of treatment, the pediatric population is divided into four weight bands:• 6 – 10 kgs -product code no.13• 11 – 17 kgs- product code no.14

• 18 – 25 kgs- product code no.15• 26 – 30 kgs- product code no.16Dosages for childredIsoniazid – 10-15mg/kgRifampacine-10mg/kgPyrazinamide-35mg/kgStreptomycine-15mg/kgEthambutol-30mg/kg(should not be given<6month)Chemoprophylaxis for ChildrenHousehold contacts of smear-positive TB cases, especially those below 6 years of age, must be screened for symptoms of tuberculosis. In case of symptoms being present, the diagnostic algorithm for pediatric TB should be followed and the child should be given a full course of anti TB treatment if s/he is diagnosed as a TB case. For asymptomatic children and those who are not found to be suffering from TB, chemoprophylaxis with Isoniazid (5 mg per kg body wt) should be administered daily for a period of six months. This is regardless of the BCG vaccination status.

Performance indicators

Annualized Case Detection Rate for New Smear Positive CasesIs the number of new smear-positive tuberculosis cases registered for treatment per 100,000 population. In India, the estimated incidence of cases is 75 New smear-positive cases per 100,000 population per year. The global and the national target is to detect at least 70% of the total estimated cases - i.e. 53 cases per 100,000 per year. 

Proportion of New Sputum positive out of Total New Pulmonary CasesIn a well performing area, 50% of all new pulmonary cases would be sputum smear-positive (infectious, confirmed in the laboratory) case, i.e. there will be no more than approximately one smear-negative case for every smear-positive case. This proportion however should not be less than 45%. 

Smear Conversion RatePercentage of new smear positive (infectious) patients who are documented to have become non-infectious (smear-negative) within 3 months of starting treatment. In a well performing area, a conversion rate of at least 85-90% will be achieved. This indicator is reported one quarter (4-6 months) after patients are registered for treatment, and applies to every patient started on treatment, without exceptions. 

Treatment Success RatePercentage of new smear positive patients who are documented to be cured, or to be successfully completed treatment. In a well performing area, 80-85% of patients will be successfully treated. The global and national target is to achieve and maintain 85% treatment success. This indicator is reported 13-15 months after patient are registered for treatment, and applies to every patient started on treatment, without exceptions.

Maharashtra

Wardha

Case detection rate 52%, Cure rate- 63%, Treatment outcome(1st qtr2008), Cured- 62.6%, Completed – 20.7%, Died- 3.9

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