REVIEW OF PULMONARY TUBERCULOSIS PATIENTS WITH POSITIVE CULTURE IN KUALA TERENGGANU, 1998-2001.

Dr Jamalludin Ab Rahman[a]

ABSTRACT

Objective: To review culture-confirmed pulmonary tuberculosis cases in Kuala Terengganu from 1998-2001

Materials and Methods: A retrospective analysis of all the tuberculosis patients registered at the Kuala Terengganu Chest Clinic (KTCC) from 1/1/1998 to 31/12/2001 was done. For the purpose of this analysis certain selection criteria were used: Malaysian citizenship, diagnosis was confirmed by culture, pulmonary tuberculosis with or without extra-pulmonary involvement, and all the treatment done in KTCC.

Results: Only 57 culture-confirmed were included in the review out of 1050 registered patients. Most cases were aged between 45-64 years. The cases were predominantly Malay (94.7%). Thirty nine cases (68.4%) were male, 37 cases (67.3%) were currently married and 37 of them (64.9%) were unemployed (N=55). Fifth teen cases (28.8%) had no formal education at all, 17 cases (32.7%) attained primary education level, 18 cases (34.6%) attained secondary education and only two cases (3.8%) had tertiary education (N=52). Most of the cases were referred from government hospitals or clinics (94.7%). Most of the cases (89.5%) were new tuberculosis cases. A majority of cases (71.9%) had no history of contact with known tuberculosis patients. Seventeen cases (73.9%) had positive Mantoux test (N=23). Sixteen cases (28.1%) were diabetic. Six cases (10.5%) had HIV infection. Only one case (1.8%) was on long term steroid treatment for bronchial asthma. Thirty three cases (57.9%) had at least one positive sputum smear for AFB. Almost 45.6% had advanced chest x-ray findings, 36.8% moderate and 17.5% minimal. Eight cases (14.0%) had extra-pulmonary involvement. The most common anti-tuberculosis treatment regimes started were 2SHRZ/4SHR₂ (70.2%) and 3HRZ/4RH₂ (17.5%). There was no multi-drug resistance case. Thirty one cases (54.4%) had complete treatment, 15 cases (26.3%) died, 10 cases (17.5%) defaulted and one case (1.8%) on treatment.

Discussion and Conclusion: The number of culture-confirmed pulmonary tuberculosis in Kuala Terengganu was very low but had high mortality rate. The explanation requires further study.

Keywords: Pulmonary tuberculosis, culture-positive tuberculosis, Kuala Terengganu.

INTRODUCTION

The magnitude of the tuberculosis problem has increased since 1990, mainly due to spread of human immunodeficiency virus (HIV) and population growth[1]. The World Health Organisation (WHO) estimates that each year there are 8.7 million new cases of tuberculosis with an estimated 1.7 million deaths[2].

Kuala Terengganu is a district in the state of Terengganu, situated on East Coast of Peninsular Malaysia. It spans over an area of 60,528 hectare with a population of 318,040 in 2002. The incidence of tuberculosis in this district was 39 per 100,000 population in the year 2000. All tuberculosis patients in Kuala Terengganu are referred to Kuala Terengganu Chest Clinic (KTCC), which is situated near Kuala Terengganu Hospital[3].

In Malaysia, the mortality rate for tuberculosis patients on treatment increased from 3.3 to 4.4 per 100,000 population between 1995 and 1996 whilst in Terengganu, the rate increased from 5.5 per 100,000 population in 1996 to 7.0 per 100,000 in 2000^3,[4]. A study was done to review the characteristics of pulmonary tuberculosis patients with positive sputum culture treated in KTCC between 1998 and 2001.

METHODOLOGY

A retrospective analysis was done on tuberculosis patients registered in KTCC from 1/1/1998 to 31/12/2001. The cases selected for this analysis were Malaysian patients with culture-confirmed pulmonary tuberculosis and had received complete treatment only from KTCC.

Sputum or other relevant specimens were collected from all patients registered and sent for culture. The culture was done at Kuala Terengganu Hospital's laboratory using the solid Löwenstein-Jensen media.

Data was obtained from patients' clinical records (TBC22), patients' treatment records (TBC61-revised 4/93) and the chest clinic registration book (TBC101). Factors studied were socio-demographic characteristics (age, gender, ethnicity, education level, marital status and occupation), place of residence (mukim), history of factors that might impair immunity (history of intravenous drug use (IVDU), diabetes mellitus and long term steroid), type of treatment received, their clinical manifestations (severity of chest x-ray findings and sputum smear for acid-fast bacilli-AFB) and treatment outcome.

Diabetics were defined as cases who were known to have diabetes mellitus and on regular treatment, or cases who were newly diagnosed with diabetes mellitus. Severity of chest x-ray was divided into four categories; no lesion identified, minimal, moderate and advanced[5]. Multi-drug resistance was defined as the presence of drug resistance at least to Isoniazid and Rifampicin[6]. Treatment outcome was defined as cured or completed treatment, died, treatment failure and defaulted treatment[7]. Transferred out patients were not included in this study.

Data was analysed using SPSS (SPSS Inc, Chicago, Illinois, USA). Chi-squared was used to test the difference between categorical factors studied and One-way ANOVA was used for the continuous variables. Appropriate non-parametric tests were used when applicable.

RESULTS

There were only 57 cases selected for the analysis from a total of 1050 patients registered. The small number of subjects resulted from the strict selection criteria. The cases' age was normally distributed between 19 to 91 years with the mean age of 50.9 ± 15.6 years. Most cases were aged between 45-64 years. The cases were predominantly Malay (94.7%). Thirty nine cases (68.4%) were male, 37 cases (67.3%) were currently married and 37 of them (64.9%) were unemployed (N=55). Fifth teen cases (28.8%) had no formal education at all, 17 cases (32.7%) attained primary education level, 18 cases (34.6%) attained secondary education and only two cases (3.8%) had tertiary education (N=52). Most of the cases were referred from government hospitals or clinics (94.7%) (Table 1).

As expected, most cases came from Kuala Terengganu District with three mukims had more than 10% cases. They were Bukit Besar (17.9%), Manir (15.4%) and Chabang Tiga (10.3%). Cases were also came from the surrounding districts, which were Marang (21.1%), Setiu (7.0%), Kuala Berang (1.8%) and Besut (1.8%) (Table 2).

As depicted in Table 3, most of the cases (89.5%) were new tuberculosis cases. Majority of them (71.9%) had no history of contact with known tuberculosis patients. Seventeen cases (73.9%) had positive Mantoux test (N=23). Sixteen cases (28.1%) were diabetic. Six cases (10.5%) had HIV infection with history of IVDU. Only one case (1.8%) was on long term steroid treatment for bronchial asthma. There were no cases with other co-existing pathology.

Thirty three cases (57.9%) had at least one positive sputum smear for AFB. All cases had at least minimal degree of chest x-ray finding. Almost 45.6% had advanced chest x-ray findings, 36.8% moderate and 17.5% minimal. Eight cases (14.0%) had extra-pulmonary involvement and the commonest site was cervical lymph nodes (37.5%). Other sites extra pulmonary manifestation included military tuberculosis (12.5%) and pleura (25.0%).

Only HIV status differed significantly among cases with and without extra-pulmonary involvement. Fifty percent of the cases with extra-pulmonary involvement were HIV positive as compared to only 4% among those without extra-pulmonary involvement (p=0.002). All other factors were not significantly associated with extra-pulmonary involvement.

The most common anti-tuberculosis treatment regimes started were 2SHRZ/4SHR₂ (70.2%) and 3HRZ/4RH₂ (17.5%). There was no multi-drug resistance case. Thirty one cases (54.4%) had complete treatment, 15 cases (26.3%) died, 10 cases (17.5%) defaulted and one case (1.8%) on treatment.

The mortality rate was 26.3%. The mortality was not significantly associated to any factor.

DISCUSSION

This was a simple analysis of the data obtained from KTCC in 1998 through 2001 to describe all culture-confirmed tuberculosis cases. The analysis showed that the proportion of definite tuberculosis cases in Kuala Terengganu was 5.4%. This small number of cultured-confirmed cases was due to the strict selection criteria that included only Malaysian, pulmonary tuberculosis (with or without extra-pulmonary involvement) and treated completely in KTCC only (no transferred-in or transferred-out cases selected). According to the report produced by KTCC for 2001, the number of sputum's specimen sent for culture was 398 (out of 407 pulmonary tuberculosis case) and 64 cases (16.1%) were positive for Mycobacterium tuberculosis[8]. The figure was still very low especially when compared to 69% in United States of America (USA) in 2002[9]. The reason for the very low positive result was not known. Further research has to be done to find the explanation.

In term of age distribution, the cultured-confirmed tuberculosis cases selected for this analysis were older as compared to the all-type tuberculosis cases in Kuala Terengganu, Kuala Lumpur or even USA^{8, 9, [10]}. In Malaysia, since 1991, tuberculosis cases were more commonly seen in people aged 16-45 years as compared to those at 46-60 years in the years before[11]. In Western Pacific region, about 69% of new smear-positive cases were aged between 15 and 54 with the highest concentration (20%) in the group aged 25-34 year old⁷. In other words, younger population is now more at risk to get tuberculosis. However in country like Canada and Germany, tuberculosis is considered as the disease of the elderly[12]^{, [13]}.

It is generally known that a lot of people, or in some endemic countries, almost all, will be infected with Mycobacterium tuberculosis at some time of their life but only a few will develop to disease, that is, tuberculosis[14]. Known factor that contribute to this disease is reduced or impaired immunity. Braun et al. in 1993 observed a new age peak spanning the ages 20 to 49 years accompanying the preexisting peak in the elderly in USA. These people were also had AIDS listed on their death certificates[15].

In this analysis HIC co-infection cases was 10.5%. It was higher if compared to the rate of HIV co-infection in the region. WHO of Western Pacific region received notification of HIV co-infection ranging from 0.3% to 8.4%⁷.

Almost 60% of the culture-positive cases were also positive for AFB. The figure was similar with the proportion of smear positive tuberculosis among the culture-confirmed cases elsewhere[16].

As regards to chest x-ray findings, culture-confirmed tuberculosis patients had at least minimal radiological changes and most of them had advanced changes. Pablos-Mendez et al. however did not find any relationship between lung cavitation and mortality of tuberculosis patients[17].

Only 14% of the culture-confirmed cases had extra-pulmonary involvement. This figure consistent with other studies¹⁶.

The most striking finding was the mortality rate. More than 26% of the cases died during the study period. This rate was very high when compared to national mortality rate for all-type tuberculosis of 4.4 per 100,000 population or 0.004% in Malaysia ^{NOTEREF _Ref58145592 \h  \* MERGEFORMAT 11}. In Western Pacific region, Singapore had reported the highest number of death among smear-positive tuberculosis of 19% in year 2000⁷.

Culture is a method of diagnosing tuberculosis. It indicates definite tuberculosis cases. As mentioned earlier, up to 70% of tuberculosis cases in USA were confirmed with culture. The only disadvantage of culture is the long time it takes to grow the organism. It will take up to 6 weeks or even longer to culture Mycobacterium tuberculosis but growth generally occurs within 7-21 days with liquid culture media¹⁶. Factors that contribute to the growth of organism include the way it is collected, stored and transported. The length of time for the organism to grow is dependent on the number of organisms in the specimen. Is the ability to be cultured indicates severity of tuberculosis? The answer is yes; because the inoculum had to contain at least 1000 bacteria¹³. So if the concentration of the bacteria is high, the higher the probability of the specimen to be successfully cultured. Unfortunately this study cannot prove such statement because no comparison was made between culture-positive and culture-negative cases. 

CONCLUSION

The number of culture-confirmed tuberculosis cases in Kuala Terengganu was low in relation to the total cases of tuberculosis registered. Further study is needed to explain more about the characteristics of culture-confirmed tuberculosis.

Table  SEQ Table \* ARABIC 1 Sociodemographic Data

Table  SEQ Table \* ARABIC 2 Distribution of Cases By Mukim

                                                                                                 * District

Table  SEQ Table \* ARABIC 3 Characteristics of Culture-confirmed Tuberculosis