RISK OF PULMONARY TUBERCULOSIS ASSOCIATED WITH EXOGENOUS REINFECTION AND ENDOGENOUS REACTIVATION IN A SOUTH INDIAN RURAL POPULATION-A MATHEMATICAL ESTIMATE* doc

Among the new cases diagnosed, 28% would have progressive primary disease, 41% cases arise due to exogenous reinfection and 31% due to endogenous reactivation.. It is also reported th

Ind J Tub., 1990, 37, 63

RISK OF PULMONARY TUBERCULOSIS ASSOCIATED WITH EXOGENOUS REINFECTION AND ENDOGENOUS REACTIVATION IN A SOUTH INDIAN

RURAL POPULATION-A MATHEMATICAL ESTIMATE*

V.V Krishnamurthy 1 and K Chaudhuri 2

Summary : It has been reported that a substantial

proportion of the new cases arise from the previously

infected population Hence, it appears that exogenous

reinfection and/or endogenous reactivation play a major

role in the development of post-primary disease Though

the risk of disease due to recent infection is known, the risk

of disease associated with exogenous reinfection and

endogenous reactivation has not been computed in Indian

conditions The data collected during a longitudinal study

by NTI, Bangalore was analysed to estimate the above

mentioned risk rates The risk of disease associated with

exogenous reinfection was 6.55% per year compared with

0.21% yearly due to endogenous reactivation To test the

validity of the computed risk rates these were applied to

the interval between the 3rd and 4th surveys It was then

estimated that 64 new cases should have been diagnosed in

that survey interval as against 57 cases actually diagnosed

It was also estimated that 1.9% of the total

population would be having recent infection, 1.3%

would be previously infected with recent infection

and 32.7% with previous infection but no recent

infection leaving 64.1% who are not infected at all

(uninfected) Among the new cases diagnosed, 28%

would have progressive primary disease, 41% cases

arise due to exogenous reinfection and 31% due to

endogenous reactivation In other words, the 1.9%

population with recent infection contributes 28% of

the total new cases, the 1.3% reinfected population

contributes 41% and the 32.7% infected population

without further reinfection contributes the

remaining 31% of the total new cases

Introduction

It is estimated that about one third of the Indian

population are infected with M.tuberculosis (National

Tuberculosis Institute, 1974) It is also reported that

about 75% of the total new pulmonary tuberculosis cases

are diagnosed from the previously infected and 25% from the uninfected persons (Krishnamurthy et al., 1976) The new cases arising from the previously infected population may have developed the disease either due to exogenous superinfection/reinfection (EXRI) or endogenous reactivation (ENRA) On the other hand, new cases from the uninfected population arise following a comparatively recent primary infection

As a substantial proportion of the new cases are diagnosed from the previously infected persons, EXRI and/or ENRA should be playing a major role in the development of post-primary disease Though the risk of disease among the previously infected persons is five times that among the uninfected, the risk of disease associated with EXRI and ENRA is not known in Indian conditions In this analysis, an attempt has been made to mathematically estimate the above mentioned risk rates for the Indian population aged five years and above

Materials and Methods

The data collected from four epidemiological surveys during a longitudinal study of tuberculosis in a rural population of South India is analysed (National Tuberculosis Institute, 1974) As the interval between the I-II and II-III surveys was identical (1½ years), the data collected during the first three surveys are analysed For the details of the survey procedures, the above cited study may be referred Persons having normal chest x-ray or those with abnormal chest x-ray in the preceding survey(s) but bacteriologically negative who became culture positive with persisting X-ray abnormality in the subsequent survey were termed new cases Infection occurring within 1½ years is considered

as new infection or reinfection, as the case may be New cases arise from three different groups of population viz.,

64 V.V KRISHNAMURTHY AND K CHAUDHURI

1 Previously uninfected population with recent

infection or the newly infected (NI)

-progressive primary tuberculosis,

2 previously infected population with added recent

infection (RI)

-exogenous tuberculosis (from superinfection or

reinfection, "reinfection" hereafter) and

3 Previously infected population with no recent

reinfection (NRI)

-endogenous tuberculosis (as a result of

reacti-vation)

The formulation of the three groups at the II survey

is shown in the accompanying diagram

The development of new pulmonary tuberculosis

from the above cited three groups could be

mathematically written as:

NI × A + RI × B + NRI × C = Total new cases

where A, B and C are the risks of disease associated

with new infection, reinfection and endogenous

reactivation respectively and the abbreviations NI, RI

and NRI are as explained above The first term in the above equation viz., NI x A is equivalent to the total new cases arising from the group of persons with recent infection If cases diagnosed from the newly infected population could be identified and removed, then the above equation reduces itself to :

RI × B + NRI × C = New cases arising from the previously infected population

When the size of RI and NRI groups becomes known,

there will be two unknowns i.e B and C in the

equation By formulating two equations, the values of

B and C could be worked out

Findings

Size of the population with "recent reinfection (RI) " and "no recent reinfection (NRI) "

To estimate the size of RI and NRI, it is assumed that the risk of infection is uniform for the population

as a whole, comprising both infected and uninfected persons Similar assumption has been made by other workers also (Sutherland, 1973) The incidence

Diagram showing groups of Population by status of tuberculous infection

Population at

I Survey

Not infected

At II Survey

Infected

At II Survey

Not

infected

Recently infected NI

Reinfected

RI

No Reinfection NRI

New cases Primary Tuberculosis

New cases due to endogenous reactivation

New cases due

to exogenous reinfection

RISK OF PULMONARY TUBERCULOSIS 65

rate of infection (column 4) between I and II and II and

III surveys is available from the already reported five

year study, (National Tuberculosis Institute, 1974) By

applying these incidence rates to the infected

population, the respective sizes of RI and NRI can be

estimated

It was estimated that among 10,565 persons (aged

5 years and above) infected at the I survey and

examined at the II survey, 415 persons had become

reinfected between I-II surveys and I0,150 had no

reinfection (Table 1) The corresponding figures for

II-III surveys were 229 and 9,165 persons respectively

(Table not presented)

Among the 70 new cases diagnosed at the II

survey, 48 cases were diagnosed from the group of

infected persons at I survey, 19 cases from the

uninfected (the tuberculin sensitivity status at I survey

was not available for three cases) The corresponding

figures for the new cases diagnosed at the III survey

were 34, 5 and 1 respectively

Two equations are:

Between surveys I-II : 415 x B + 10150 C = 48

Between surveys II-III : 229 x B + 9165 C = 34

Solving the two equation :

The value of B = 0.0655 or 6.55%

The value of C = 0.002108 or 0.21%

To test the validity of the risk rates computed

above (6.55% and 0.21%), these rates were applied to

the interval between III and IV surveys It was found that 64 new cases could have been diagnosed as against

57 actually diagnosed

The risk of disease associated with the cited different types of tuberculosis infection is given in Table 2

The risk of disease associated with reinfection is

31 times that for endogenous reactivation and twice that for recent infection

Table 2 Risk of disease associated with different

types of infection

Type of infection

Risk of disease (%) (Annual)

Exogenous reinfection

* Krishnamurthy et al

With the information on the size of previously infected population, with or without recent reinfection,

it is possible to construct the profile of the population

in respect of tuberculous infection (Table 3) The table

is self explanatory

Among the infected persons (11, 161), 5% were initially uninfected but got recently infected between surveys I and II (596), 4% were reinfected (415) and 91% (10,150) had no reinfection

Table 1 Size of the population with or without recent reinfection between I and II surveys (estimated)

Among I survey

Incidence rate of infection (%) between*

Age at I survey Uninfected Infected I and II surveys

Plus recent reinfection (RI)**

No recent reinfection (NRI)**

66 V.V KRISHNAMURTHY AND K CHAUDHURI

Table 3 Population aged 5 years and above (examined at I and II surveys) at II survey by infection status

Previously infected with no recent reinfection 10150 32.7

* Total uninfected = 20492; ** National Tuberculosis Institute, 1974

Among the 67 new cases diagnosed at the II

survey, for whom tuberculin sensitivity was known at I

survey, 28% had progressive primary tuberculosis,

41% had disease due to exogenous reinfection and the

remaining 31% due to endogenous reactivation (Table

4)

Contribution by different groups of population to the

total new cases at the II survey

Population with recent infection constituting

1.9% of the total population have contributed 28%

of the total new cases (progressive primary disease); infected population with reinfection constituting 1.3% of the population have contributed 41% of the new cases (disease due to exogenous reinfection), and tie remaining 31% of the total new cases (disease due to endoge nous reactivation) have come from the population previously infected with no reinfection constituting 32.7% of the total population (Fig 1) It could be seen that the infected population with reinfection are not only at the highest risk of developing fresh pulmonary tuberculosis (6.55%) but they make the

RISK OF PULMONARY TUBERCULOSIS 67

Table 4 Composition of new cases diagnosed at II survey

Type of infection No of persons Risk of disease (%) New cases new cases % to total

* Krishnamurthy et al

highest proportional contribution to the total new

cases arising in the community More over, the

newly infected persons together with the group of

population previously infected and recently

reinfected together contribute 69% on the total new

cases arising in the community Only 31% of the

new cases arise from the previously infected persons

with no recent reinfection, presumably due to

endogenous reactivation

Acknowledgement

The authors are grateful to Dr A.K Chakraborty,

Deputy Director, CGHS, Bangalore for his comments

and suggestions at the draft stage of the paper,

Mrs.Anuradha for statistical assistance, Miss T.J

Alamelu for secretarial help and Mr B.R Narayana Prasad graphics

References

Krishnamurthy, VV, Nair, SS, Gothi, GD, a Chakraborty, AK Incidence of Tuberculosis among newly infected population and in relation to the duration of infected status; Indian Journal of Tuberculosis 1976, Vol 33/1, 3

National Tuberculosis Institute, Bangalore Tuberculosis in a rural population of South India :

a five year epidemiological study, Bull World Health Orgn, 1974, 51, 473

Sutherland, I Endogenous reactivation and exogenous reinfection, IUAT 1972,47,123