Factors affecting sputum smear conversion time in newly diagnosed pulmonary tuberculosis patients

Background: Patients having tuberculosis are registered in the TB DOTS program for their treatment. During the treatment sputum samples are sent periodically to the laboratory to check treatment efficacy. Usually after two months of treatment sputum smear becomes negative but presence of multiple cavities in the lung, bacillary load, diabetes mellitus and tobacco smoking, slows the sputum smear conversion time

Objectives: To determine the factors affecting sputum smear conversion time in newly diagnosed pulmonary tuberculosis patients

Study design, settings and duration: This cross sectional, analytical study was done by Pakistan Medical Research Council, TB Research Centre in collaboration with Institute of TB and Chest Medicine King Edward Medical University/Mayo Hospital, Lahore from April 2013 to March, 2014

Patients and Methods: All newly diagnosed pulmonary tuberculosis patients who were registered and given treatment by the DOTS program were included in the study. All patients underwent sputum smear microscopy along with Complete Blood Count and ESR at the time of enrollment. The patients were followed for next 6 months while on treatment. Sputum samples were tested at 2[nd] and 6[th] month to check the sputum conversion rate and indirectly to see the efficacy/compliance to treatment

Results: A total of 400 patients were enrolled with slightly more males [52%] as compared to females [48%]. Smear became negative within two months of starting treatment in 85.7% patients while in 14.2% it remained positive at 2[nd] and 6[th] months of therapy. There were more females [10.7%] whose sputum smear did not became negative as compared to males [3.5%]. Predominant factors affecting sputum smear conversion were low resistance, raised initial bacillary load, decreased hemoglobin level, and long duration of symptoms at the time of diagnosis

Conclusion: Factors like low resistance, high initial bacillary load and decreased hemoglobin levels affect the sputum smear conversion and should be addressed while assessing efficacy of anti-tuberculosis treatment

Active case detection among household contacts of multi drug resistant tuberculosis patients in a tertiary care setting

Close contacts of multi drug resistant tuberculosis patients are expected to be at increased risk of developing the disease and therefore need screening on priority basis to have an effective TB control program. Active household contact screening is an effective and cheaper way to detect and treat MDR-TB at its early stages. To determine active TB cases among household contacts of MDR-TB patients in a tertiary care setting. Descriptive study, conducted at PMRC TB Research Centre in collaboration with Institute of Chest Medicine, King Edward Medical University/Mayo Hospital, Lahore from November 2012 to December 2013. Patients suffering from MDR-TB and seeking treatment from Institute of Chest Medicine were selected as index patients. Their contacts [spouses, children, parents, siblings and other relatives] underwent sputum smear microscopy. Those found positive for AFB were subjected for MTB RIF assay by GeneXpert to determine rifampicin resistance. Data was analysed using IBM Statistics SPSS version 20.0. A total of 692 contacts of 112 MDR-TB patients were studied. Among them, 374[54%] were males and 318[46%] female. Seventeen contacts were found smear positive and of these 15[88%] were also confirmed as MTB by GeneXpert. Four [23%] contacts were rifampicin resistant. Of the affected contacts, majority were sisters [23.5%]. Active TB was detected in contacts of patients having MDR-TB with few also showing rifampicin resistance. TB screening should be done in all contacts of TB patients, especially those having drug resistance

Screening for tuberculosis among household contacts of index patients

Household contacts of sputum positive pulmonary TB cases are at a high risk of getting infected with tuberculosis therefore symptomatic or vulnerable individuals should be screened and treated early. To determine the prevalence of pulmonary tuberculosis in the households contacts of index patients having pulmonary tuberculosis infection using standard diagnostic tests and refer the positive cases to DOTS program for treatment. This national descriptive study was conducted in seven Centers of PMRC throughout Pakistan form November 2010 to March 2012. A total of 580 index adult patients suffering from pulmonary tuberculosis, being treated at DOTs Centers of major tertiary care hospitals of Karachi, Lahore, Multan, Peshawar and Quetta living within 5-8 kilometers of the hospital, who consented to participate in the study were selected from the DOTs centres. Generally one but occasionally two close contacts of these index patients [spouses, parents or siblings] were called to the hospital for screening of TB using chest Xray, smear microscopy and tuberculin skin test. Out of 800 contacts screened, 125 [15.6%] were positive on sputum smear examination while 113 had infiltration on X-rays along with positive tuberculin skin test [Indurations of >10 mm] making a definitive diagnosis of TB. Calcified lesions were seen on X-rays in another 91 cases giving evidence of past infection, however 26 of these were AFB positive indicating either the relapse of disease or active lesion. Low grade fever and weight loss were the most significant findings in contacts that were positive on sputum smear and radiology. Almost 15.6% household contacts of pulmonary tuberculosis patients have pulmonary tuberculosis. Health care providers in general and DOTs staff in particular should be trained to inform all index cases that their close contacts especially those suffering from weight loss and fever should be screened for tuberculosis and treated if required

Incremental yield of submitting three sputum specimens for the diagnosis of pulmonary tuberculosis

To assess the efficacy and diagnostic yield of third sputum smear among pulmonary TB patients. This retrospective data analysis was done at PMRC TB Research Centre in collaboration with Institute of Chest Medicine, King Edward Medical University/Mayo Hospital Lahore, from January 2010 to December 2011. Patients presenting with respiratory symptoms, having abnormal chest X-rays and having a clinical suspicion of tuberculosis were asked to submit three sputum samples on two consecutive days [1[st]spot, 2[nd]early morning, 3[rd]spot] for acid-fast bacilli smear microscopy. Smears were prepared and stained by Ziehl-Neelsen method. A total of 7785 TB suspects submitted three sputum samples making a total of 23,355 slides for checking acid-fast bacilli using smear microcopy examinations. The smear positivity rate was 11.8%. About 12% suspects fulfilled the case definition of having one positive smear confirmed by a second smear, while, only 2.5% suspects fulfilled the case definition based on third smear in combination with first or second. A total 1164[15%] suspects had at least one positive smear; of these 896[77%] were positive in first smear, 190[16%] were negative in first smear but positive in second and 78[6.7%] were positive in third smear after two negative smears. Recently changed WHO criteria for examination of two sputum smears is based on evidences collected from the globe however, for Pakistan the value of third smear which picked almost 7% cases is quite significant and should still be practiced. Checking AFB using 3 sputum smears should still be practiced in Pakistan especially, for those who are initially negative on 2 smears

Factors responsible for failure to initiate tuberculosis treatment among smear positive tuberculosis patients

Tuberculosis is a major health problem in many parts of the world. Delay in initiation of the treatment may result in prolonged infectious state, drug resistance, relapse and death. To determine the factors responsible for not starting tuberculosis treatment among smear positive tuberculosis patients. Study type, settings and duration: This cross sectional study was done at Pakistan Medical Research Council TB Research Center, King Edward Medical University, Lahore, from 5th March 2010 to 5th December 2010. Patients and Methods: Fifty sputum smear positive patients of tuberculosis who did not register themselves in treatment register and presumably did not initiate anti tuberculosis treatment were contacted using telephone or traced by their home addresses. Once contact was established, they were inquired about the reasons for not starting tuberculosis treatment. Of 50 patients 38[76%] belonged to the lower socio economic class and 12[24%] to the lower middle class. Fourteen patients [28%] were illiterate and 23[46%] had only 8 years of education. Of the 50 cases 41[82%] were taking treatment from traditional healers and 4% did not go back to the DOTS program. Physical condition of the patient, social, domestic and religious issues also played some role in default. Lack of health education and poverty were the main factors responsible for non compliance from treatment. Policy message: Sputum testing sites should have a paramedic who should educate the patients about the benefits of treatment and the dangers of default or partial treatment

first and second line anti TB drug resistance pattern in Lahore

For the control of tuberculosis at national level, DOTS strategy [Directly observed therapy short course] is being implemented by National TB Control Program in collaboration with WHO. This programme if managed properly can cure nearly all-new TB patients. To determine the in vitro susceptibility pattern of second line drugs in multi drug resistant tuberculosis and inform tuberculosis control authorities and clinicians for appropriate management. A total of 1180 Mycobacterium tuberculosis positive patients receiving anti tuberculosis drugs and suspected of having drug resistance were referred to this Center for drug susceptibility testing. Sputa of all these patients were subjected to culture against first line of anti TB drugs. Those resistant to both INH and RIF were subjected to 2nd line of drug susceptibility testing. Out of 1180 suspected MDR-TB cases, 201[17%] showed resistance against both INH and RIF thus, confirming MDR-TB. Using the definition of extreme drug resistant TB [XDR-TB] i.e. MDR TB plus resistance to any one of floroquinolone and one of three injectables i.e. amikicin, kanynamicin and capreomycin, 4[2%] cases were XDR-TB. The frequency of XDR-TB was 2%. For MDR TB cases second line of anti tuberculosis drugs are still very effective

Multi drug resistance tuberculosis: pattern seen in last 13 years

Drug resistance in tuberculosis is a serious problem throughout the world especially, after the emergence of multi drug resistant TB strains. To estimate drug resistance in TB patients and compare it with previous studies to see the changing trends. The PMRC Research Centre receives sputum samples from all the leading hospitals of Lahore. This retrospective analysis was done from 1996 to 2008 on the multi drug resistant TB strains that were seen during these years. Five first lines tuberculosis drugs were tested on Lowenstein Jensen medium using standard proportion method. A total of 2661 confirmed isolates of Mycobacterium tuberculosis were seen over the past 13 years. Of the total, 2182 were pulmonary and 479 were extra pulmonary specimens. The patients comprised of those with and without history of previous treatment. These specimens were subjected to drug susceptibility testing. Almost half of the patient had some resistance; multiple drug resistance were seen in 12.3% and 23.0% cases without and with history of previous treatment respectively. overall resistance to rifampicin was 26.4%, isoniazid 24.1% streptomycin 21.6% ethambutol 13.4% and pyrazinamide 28.4% respectively. Statistically significant difference was seen between primary and acquired resistance. When compared with the reports from previous studies from the same area, there was a trend a gradual increase of drug resistance. Resistance to anti tuberculosis drugs in high. TB Control Program should start "DOTS Plus" schemes for which drug susceptibility testing facilities should be available for correctly managing the patients

Diagnosis of tuberculosis: molecular versus conventional method

Tuberculosis is as old as mankind. One third of the world's population carries the bacillus. Tuberculosis remains the single greatest contributor to the world's morbidity and mortality. Zheil Neelsen stained smears for acid-fast bacilli and culture on Lowenstein Jensen media are the methods being used for the diagnosis of Mycobacterium tuberculosis in most developing countries. Zheil Neelsen smear is rapid but less sensitive and culture is more sensitive and specific but results in delay in definitive diagnosis. Polymerase chain reaction test for the diagnosis of tuberculosis is not well evaluated in developing countries. To compare the ability of polymerase chain reaction to diagnose Mycobacterium tuberculosis rapidly in pulmonary and extra-pulmonary clinical specimens, and compare it with the yield of smear positivity and culture. This was a comparative study which was carried out at PMRC TB Research Center, King Edward Medical University, Mayo Hospital Lahore in collaboration with Shaukat Khanum Memorial Cancer Hospital from November 2008 to October 2009. Clinically suspected cases of pulmonary and extra-pulmonary patients with symptoms of fever, fatigue, anorexia and weight loss were asked to submit their sputum or respective samples for the diagnosis of tuberculosis. Direct and concentrated smears were prepared and stained by Zheil Neelsen method and were subjected to culture on Lowenstein Jensen media. Decontaminated specimens were checked for mycobacteria using polymerase chain reaction where amplicons were used for detection to membrane bound probes on the strips. A total of 98 specimens were processed for acid-fast bacilli smear, culture and polymerase chain reaction. These included 67 specimens from cases having strong clinical suspicion of tuberculosis while, 31 sputum specimens from non-tuberculosis subjects served as negative controls. Over all polymerase chain reaction positivity was 62.2%, culture positivity was 52% and smear positivity was 35.7%. Polymerase chain reaction testing was the most specific, rapid and sensitive method for the diagnosis of tuberculosis while culture is specific but it takes 4 to 6 weeks to provide results and smear testing is the cheapest but least sensitive test. Early diagnosis of TB is cornerstone for proper treatment and control of this deadly disease. PCR testing is specific, rapid and sensitive method for diagnosis of TB especially in complicated cases

Clinico-pathological profile and treatment outcome in smear negative pulmonary tuberculosis patients at a teaching hospital

Tuberculosis remains the single highest contributor to the world's morbidity and mortality. Early diagnosis and prompt treatment is essential to prevent its transmission. To see the treatment response of anti tuberculosis drugs in smear negative patients and study the predictors of culture positive among smear negative tuberculosis patients. This descriptive study was carried out at Chest Clinic, Sir Ganga Ram hospital in collaboration with PMRC TB Research Centre Mayo hospital, Lahore. Ninety four sputum smear negative patients clinically and radiologically suggestive of tuberculosis were selected. These patients were put on anti tuberculosis drugs without waiting for their culture results. They were then followed for 8 months to see their treatment outcome. A total of 94 smear negative patients were selected and given anti tuberculosis treatment. Of these 37 [39%] were culture positive and 57 [61%] were culture negative. Of the 37 culture positive patients 36 [97%] showed clinical or radiological improvement as compared to 46 [81%] out of 57 in culture negative cases. Symptoms of cough with sputum production was significantly associated with culture positivity. On x-ray chest moderate lesion with diffuse infiltration was more common finding in 64% while extensive and cavitatory lesion was seen in 24% of all cases. Association of extensive and cavitatory lesion were seen in culture positive group. Response to anti tuberculosis drugs in sputum smear negative tubercolosis suspects was found to be effective in majority of the patients. Cough, sputum and extensive cavitatory lung lesion were the predictors of culture positive cases. There is need to train physicians on the use of anti tuberculosis therapy in smear negative suspected pulmonary tuberculosis cases, especially if they have productive cough and cavitatory lung lesions

Multidrug resistance tuberculosis in Lahore

To estimate drug resistance in TB patients and compare it with the previous studies to see if there is a changing trend. PMRC TB research centre Mayo hospital Lahore which is a specialized centre on research and diagnosis of tuberculosis. The centre receives sputum samples from all the leading hospitals of Lahore. This work was done from 2004 to 2006 where five first lines anti tuberculosis drugs were tested on LJ.medium using standard proportion method. A total of 582 confirmed isolates of Mycobacterium tuberculosis were seen. Of the total 454 were pulmonary and 128 extra pulmonary specimens from 582 patients. These patients comprised of those with and without history of previous treatment. These sputa were subjected to drug susceptibility testing. Almost half of the patients had some resistance; multiple drug resistance [MDR] was seen in 12.8% and 27.0% cases without and with history of previous treatment respectively. Overall resistance to rifampicin was 26.6%, to isoniazid 23.5%, streptomycin 19.5%, ethambutol 11.8%, and to pyrazinamide 29.7%. Statistically significant difference was seen between primary and acquired resistances. When compared with the reports from previous studies from the same area, there was a trend of gradual increase of drug resistance in this area. Resistance to anti tuberculosis drugs is high in Lahore. The current approach may not be adequate and innovative approaches such as DOTS-Plus may have to be employed to effectively control MDR TB