Primary MDR Research Articles

DISTRIBUTION AND MORTALITY PATTERNS IN PATIENTS CO-INFECTED WITH HIV AND TB IN KARELIA

The time course and distribution patterns of combined HIV/TB infection in the Republic of Karelia over the last eight years were studied. Additionally, 127 case histories of HIV/TB patients related to the period from 2001 to 2015 were examined. It is found that the high prevalence of multiple drug resistance of M. tuberculosis (primary MDR prevalence is 46,5%) is associated with delayed diagnoses of combined HIV/TB infection (stage 4-5 HIV in 70% of cases). This factor in combination with the significant input of HIV/TB patients from the Federal Penitentiary System promotes the rapid spread of HIV/TB infection over the whole territory of the Republic. These features make it expedient to develop dedicated programs aimed at close monitoring of risk groups and at the social support for homeless people and for convicts set free after imprisoning. With account of the high rate of other concomitant infections, the atypical clinical and roentgenologic manifestations of TB upon immunosuppression, and the high rate of MDR, speeding up of TB diagnosis requires the use of molecular diagnostic tools, such as Gene-X-Pert, when TB is suspected in HIV patients.

DRUG RESISTANCE PATTERN AMONG AFB SMEAR POSI-TIVE RETREATMENT COMPLETED CASES

Abstract Background: Worldwide, multidrug resistance (MDR TB) is a serious issue. It has increased over the last decade. Re-treatment completed sputum smear posi-tive cases have much higher incidence of MDR-TB as compared to primary MDR - TB. Objective: To estimate the incidence of drug resis-tance pattern among AFB smear positive re-treatment completed cases. Study Design: Evidence based prospective study. Study Setting: Institute of Chest Medicine, Mayo Khalid M. Ch. 1 Associate Professor, Department of Chest Medicine KEMU / Mayo Hospital, Lahore Hassan S. 2 Registrar, Department of Chest Medicine Mayo Hospital, Lahore Saeed M.S. 3 Chairman, Department of Chest Medicine KEMU / Mayo Hospital, Lahore Younus M. 4 Senior Registrar, Dept of Chest Medicine Mayo Hospital, Lahore Iqbal R. 5 Senior Research Officer Pakistan Medical Research Council Hospital Lahore, Tertiary care hospital affiliated with King Edward Medical University, Lahore, Pakistan. Methodology: A total 50 (Male 22, Female 28) pul-monary TB patients who had completed Re- treatment regimen in the past and are still sputum smear positive for acid fast Bacilli were included in the study. Three consecutive sputum specimens were collected at Aga Khan University collection center at Lahore. The spe-cimen were sent to Agha Khan University Lab Karachi for AFB smear, culture and drug sensitivity both for essential and reserve drugs. Reports for AFB smear were received within a week, while culture and drug sensitivity reports after 6 weeks. Reports data was analyzed for essential and reserve anti tuberculous drug sensitivity for mycobacterium tuberculosis. Results: Data Analysis revealed MDR TB in 31(62%) patients which include 11 males and 23 females. Indi-vidual drug resistance to essential drugs was INH - 62%, Rifampicin - 68%, Ethambutol - 24%, PZA - 25% and Streptomycin - 21%. Poly drug resistance was determined in 38% cases. Individual drug resis-tance to reserve drugs - kanamycin, Amikacin, ofloxa-cin, Ethionamide and PAS was 4%, 4%, 36%, 10% and 2% respectively. Conclusion: There is a very high proportion of MDR TB in sputum smear AFB positive retreatment cases. Suggestion: Comprehensive measures including DO-TS PLUS are needed to control MDR TB in Pakistan. Key words: MDR TB, XDR TB, Re-treatment regi-men, Essential drugs, Reserve drugs, AFB - acid fast bacilli.

Molecular and Genetic Research in Tuberculosis Clinical Practice and Epidemiology.

IntroductionTuberculosis (TB) remains a global public health problem. In order for multi-drug resistant tuberculosis (MDR-TB) to be more effectively managed, there is a need for better tools for diagnosis, treatment, and prevention. The decline of TB incidence and mortality in Kazakhstan during last decade was accompanied with consistent growth of MDR-TB. This study aimed to investigate genotype characteristics of Mycobacterium tuberculosis (MT) isolated from TB patients from different regions of the country and its clinical and epidemiological significance.MethodsOver 500 clinical MT isolates from pulmonary TB patients between 2003–2008 were genotyped using spoligotyping, MIRU-VNTR, IS6110 RFLP, and hybridization on an oligonucleotide biochip “TB–biochip.”ResultsOut of 250 isolates with interpretable results, 31 different spoligopatterns were detected. The Beijing genotype was the most predominant lineage detected (71.6%), characterized by heterogenicity on ETR A, B, C, D, and E markers, and 56.6% of them had an allelic profile 42435. The Beijing genotype and dominating variant strains have a high transmission rate, a high rate of primary MDR (associated with infiltrating lung TB and complications), and a high level resistance to rifampicin and izoniazid due to mutation of rpoB531TTG and katG315ACC. MIRU-VNTR–typing by 15 loci of 33 isolates from 13 family TB foci revealed that strains from supposed sources and contact persons completely coincide in only 5 foci in the genomic structure.ConclusionThere is a heterogeneous pool of genotypes that circulate in Kazakhstan, with the Beijing lineage being the most predominant. It appears that at the present stage of circulation, MT Beijing genotype has an endemic character. However, clonal spreading of epidemiologically and clinically significant MDR strains of this genotype is also a serious threat to the population. To increase TB control efficiency and prevent further transmission, it is necessary to compile a modern countrywide system of microbiological monitoring for the agent by use of a computer bank of spoligotyping and MIRU-VNTR-typing profiles of circulating strains.

Are Primary MDR and XDR Tuberculosis a New Version of Tuberculosis in Romania?

Are Primary MDR and XDR Tuberculosis a New Version of Tuberculosis in Romania?

Radiological Findings of Primary Multidrug-resistant Pulmonary Tuberculosis in HIV-seronegative Patients

Objective: To compare the computed tomography findings of patients with primary multidrug-resistant tuberculosis (MDR TB) and those with drug-sensitive tuberculosis (DS TB) who were human immunodeficiency virus (HIV) seronegative. Methods: The computed tomography findings of 40 patients with MDR TB and 40 with DS TB were retrospectively reviewed. The presence of centrilobular nodules, consolidation, cavity, bronchiectasis, calcification, pleural effusion, lymphadenopathy, laterality and number of involved lobes were looked for. Statistical comparison entailed the use of Student’s T test, the Chi-square test, and the Mann-Whitney U test. Results: Cavities were more frequently observed in patients with primary MDR TB than those with DS TB (p = 0.007), and when present, these were more numerous in the former patients than in the latter (p = 0.001). There was no statistically significant difference between primary MDR TB and DS TB in terms of centrilobular nodules, consolidation, bronchiectasis, calcification, pleural effusions, lymphadenopathy, laterality, and number of involved lobes. Conclusions: In HIV-seronegative patients, the presence of multiple cavities was a significantly more common computed tomography finding in the MDR TB patients than in the DS TB patients. This computed tomography finding may enable early detection and appropriate therapy for such infected patients, as it can be obtained rapidly.

Primary MDR Tuberculosis in an Apparently Low Risk Infant

SESSION TYPE: Infectious Disease Cases III

Social aspects multi-drug resistant tuberculosis

The comparative analysis of features of clinical symptoms, spectrum and the importance of burdening medico-social factors of a tuberculosis of lungs with primary MDR М . tuberculosis in comparison with a drug sensitive variant of disease is carried out. Presence of associations between burdening factors of disease and MDR М . tuberculosis is proved. We defined degree of risk of detection MBT with MDR at new cases tuberculosis of lungs with narcotism, a tobacco smoking, a syndrome of alcoholic abuse, stay in imprisonment places, a diabetes of 2nd type, hepatitises B, C, В + С.

Anti-tuberculosis drug resistance in Japan and in the world

In 1994, the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD) launched a global project on anti-tuberculosis drug resistance surveillance. The results from the first 4 years (1994-1997) and the second 4 years (1996-1999) of the projects were reported in 1998 and 2000, respectively. These surveillance results showed that resistance to anti-tuberculosis drugs is a global problem. The reports also showed that there were several hot spots around the world where prevalence of multidrug resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampin) was particularly high and could possibly threaten control programs. The Tuberculosis Research Committee of Japan (Ryoken) has conducted nationwide surveys for drug resistant tuberculosis at 2- or 5-yearly intervals since 1957. The 1997 survey showed that among patients with no prior treatment, resistance to any of the four drugs was found in 10.3%, and the prevalence of primary MDR was 0.8%. The prevalence of drug resistance in the previously treated cases was 42.4% for any of the four drugs and 19.7% for MDR, indicating a high prevalence rate compared with those reported in the global project. Compared with the previous survey in 1992, the current survey shows increased prevalence of drug resistance in both new and re-treatment cases. No significant differences in resistance rates by sex, age group, nationality, district, and/or accompanying diseases were observed in any of the new or re-treatment cases. Other factors associated with the high prevalence in re-treatment cases remain to be determined. A total of 78 hospitals in various districts of Japan participated the cooperative study. Each collaborating laboratory sent all the isolated mycobacterial cultures to the Research Institute of Tuberculosis (RIT). In the local laboratories, the absolute concentration method using 1% Ogawa egg slant, its modified methods using a 48-well plate and a 16-well plate, combination of above 2 or 3 methods, and other method were used for drugsusceptibility testing, and the proportion method using 1% Ogawa egg slant was used in the RIT. The results in the local laboratories were compared with those in the RIT. There was no significant difference in the concordance rates according to the test drugs among methods for drug susceptibility testing used in the local laboratories. Relatively lower concordance rates were seen in the laboratories using the Microtiter method related to high overestimation rates, compared with those in the laboratories using the standard method and Well-pack method. However, relatively lower concordance rates (less than 90%) were seen in the laboratories using any of the three methods, indicating that there are variations among facilities.

Tuberculosis en la población indígena del Perú 2008

Objective. To identify the indigenous inhabitants affected by tuberculosis (TB) in Peru during the year 2008. Material and methods. Descriptive observational study, performed from August to December 2009, including all indigenous patients affected by tuberculosis that were including in the Control Program during the year 2008 in the 25 regions of Peru. Results. We identified 702 indigenous patients with tuberculosis. The ethnical groups that have most patients were the Quechua group (417/702; 59.4%) and the Amazonic indigenous (201/702, 28.6%). Out of the Amazonic, more than 60% belonged to the Ashaninka (Campas), Shipibo and Matsiguenga groups. In third place, we found the Aymara natives, who had 84/702 (11.97%) of cases of tuberculosis. It is important to mention that the distribution of the cases of multidrugresistant tuberculosis (MDR TB) involves five departments (nine cases of MDR TB), being the greater number of cases of MDR TB in patients previously treated (6/9), and only 3 cases were primary MDR TB, belonging to the quechua group. Conclusions. High incidence rates of tuberculosis in indigenous population have been found, which raises the need of further research in order to guarantee the correct gathering of information in ethnic groups in order to have more and better evidence about the situation of tuberculosis in the indigenous population of Peru.

Tuberculosis en la población indígena del Perú 2008

To identify the indigenous inhabitants affected by tuberculosis (TB) in Peru during the year 2008. Descriptive observational study, performed from August to December 2009, including all indigenous patients affected by tuberculosis that were including in the Control Program during the year 2008 in the 25 regions of Peru. We identified 702 indigenous patients with tuberculosis. The ethnical groups that have most patients were the Quechua group (417/702; 59.4%) and the Amazonic indigenous (201/702, 28.6%). Out of the Amazonic, more than 60% belonged to the Ashaninka (Campas), Shipibo and Matsiguenga groups. In third place, we found the Aymara natives, who had 84/702 (11.97%) of cases of tuberculosis. It is important to mention that the distribution of the cases of multidrugresistant tuberculosis (MDR TB) involves five departments (nine cases of MDR TB), being the greater number of cases of MDR TB in patients previously treated (6/9), and only 3 cases were primary MDR TB, belonging to the quechua group. High incidence rates of tuberculosis in indigenous population have been found, which raises the need of further research in order to guarantee the correct gathering of information in ethnic groups in order to have more and better evidence about the situation of tuberculosis in the indigenous population of Peru.

Imaging Findings of Primary Multidrug-Resistant Tuberculosis

This study was designed to identify and describe thin-section computed tomographic (CT) findings of primary multidrug-resistant tuberculosis (MDR TB) as compared with the findings for drug-sensitive TB. Between October 2002 and December 2007, thin-section chest CT findings of 39 patients with primary MDR TB and 39 patients with drug-sensitive TB were retrospectively reviewed. The frequency and patterns of lung lesions (including centrilobular nodules, large nodules, consolidation, cavity, fibrotic bands, bronchiectasis, calcification, pleural effusion, lymphadenopathy, number of lobes affected by parenchymal lesions, and laterality) were compared. Statistical comparisons were performed with the use of the chi2 and the Mann-Whitney U tests for univariate analysis, and a stepwise logistic regression method was used for multivariate analysis. Based on univariate analysis, bilateral involvement (P < 0.001), segmental or lobar consolidation (P < 0.001), and cavities (P < 0.001) were more frequently seen in primary MDR TB patients. A stepwise logistic regression analysis demonstrated that bilateral involvement of parenchymal lesions (odds ratio, 4.7; 95% confidence interval, 1.4-15.6; P = 0.012) and multiple cavities (odds ratio, 1.7; 95% confidence interval, 1.2-2.5; P = 0.004) were significant CT findings associated with primary MDR TB. The presence of primary MDR TB as detected on a CT scan may help the use of appropriate therapy for infected patients before obtaining a definite diagnosis based on bacteriology.

Vigilancia nacional de la resistencia a medicamentos antituberculosos, Perú 2005-2006

Objective. To determine the anti-tuberculosis drug resistance prevalence in Peru. Material and methods. We performed a conglomerated sampling in 33 health regions from Peru. We used a Canneti proportions method in solid medium L-J for testing Mycobacterium tuberculosis susceptibility with isoniazid (INH) rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). Strains with TB MDR was evaluated to second line drug susceptibility by proportion methods in 7H10 agar in plates. Results. We analyzed 1809 cultures from new patients and 360 pre treated. 51.6 coming from Lima and 59.3% were males. The national prevalence of primary resistance was 23.2% (CI95%: 21.3 - 25.1) and acquired resistance was 41.7% (95% CI: 36.5 - 46.8). We detected 180 TB MDR cases, the prevalence of primary TB MDR was 5.3% (95%CI: 4.2 - 6.3) and acquired was 23.6% (95%CI: 19.2 - 28.0). 20% of never treated patients isolated were resistant to INH or RIf. Global resistance and primary TB MDR were more prevalent in Lima than rest of the country. TB XDR was present in 5.9% of patients with TB MDR and 36% of TB MDR strains were resistant at least one secondline drug. Conclusions. Compared with previous studies, primary and acquired anti-tuberculosis drug resistant have significantly increased in the last 10 years in Peru.

TB Control and Access to Second-Line Drugs: Better Model Needed. (Round Table Discussion)

Pablos-Mendez et al. rightly point out that multidrug-resistant tuberculosis (MDR-TB) is hot a major pandemic (see pp. 489-494). However, as drug-susceptible TB is a worldwide problem, the first priority for national TB programmes should be the implementation or expansion of the DOTS strategy. MDR-TB is in most cases a sign of poor programme performance, although there may be highly virulent strains spreading rapidly. A weak national programme can do more harm than good if its main focus is the widespread introduction of second-line drugs to manage this problem. To tackle MDR-TB Pablos-Mendez et al. propose a matrix based on two variables: treatment success for new TB cases, and prevalence of primary MDR-TB. They propose that the use of second-line drugs should be limited to countries which belong in specified quadrants according to these two variables. We find it questionable that the management of a MDR-TB, or any other disease, should be based on only two variables. We lire in a world in which the control of illness calls for modern multidisciplinary approaches (1). We will come back to this point. The proposal of Pablos-Mendez et al. is difficult to accept for at least two reasons. Firstly, more than two variables axe needed to decide if a country should treat MDR-TB. For instance, a country may score well on treatment success, have a low number of primary MDR-TB cases but still have a high number of treatment failure cases (a variable hot taken into account in the proposed model), which axe likely to have MDR (2). Such a country may need to implement management of MDR-TB as well as DOTS, regardless of its level of primary MDR and treatment success, Furthermore, treatment success could be a very misleading variable since it is the result of cure plus treatment completion. There axe some examples of poor national TB programmes having high rates of success upon completion of treatment but low cure rates. Secondly, do we really need cut-off points to manage a disease? On what basis can we choose 5% and not, say 3% for MDR prevalence, or 70% and not, say, 60% for treatment success? No biological, statistical or epidemiological reason is given for choosing such cut-off points. A straightforward indication of the point at which to start management of MDR-TB could be helpful, but the issue is hot that simple, and other matters need to be carefully looked at when taking such a decision. The assertion that DOTS can reduce MDR-TB has not been fully proved, although it is clear that short-course chemotherapy can prevent MDR-TB. Countries that have reduced MDR-TB have also used second-line drugs and it is not clear to what extent the use of both first-line and second-line drugs have contributed to reducing MDR-TB. …

Trends in multidrug-resistant Mycobacterium tuberculosis in relation to sputum smear positivity in Hong Kong, 1989-1999.

We studied retrospectively the territory-wide occurrence and trends of multidrug-resistant tuberculosis (MDR-TB) in Hong Kong over an 11-year period during which a short-course directly observed therapy ("DOTS-Plus") strategy has been in operation. The overall MDR rate was 2.1% (primary, 1.4% and acquired, 9.5%) and declined at 0.08% per year: smear-positive primary MDR cases declined at yearly rate of -0.065% (R2=.23), and smear-negative primary MDR cases increased at 0.035% yearly. With declining rates of smear positivity, sputum culture has become the mainstay of detection of MDR-TB. Although the overall notification rates showed the elderly (age >65 years) age group to be most affected, the occurrence of MDR-TB has been consistently highest in the 35-65 year age group (60.4% of MDR caseload). We demonstrated declining rates of sputum smear positivity of MDR-TB in a DOTS-plus environment and that a centralized laboratory database is essential in gathering epidemiological information for identifying particular risk groups and monitoring trends of MDR-TB in a community.

Tuberculosis and drug resistance among patients seen at an AIDS reference center in São Paulo, Brazil

Objectives: To assess the frequency of resistance of Mycobacterium tuberculosis to antituberculosis drugs and the factors associated with it among patients with tuberculosis (TB) and acquired immunodeficiency syndrome (AIDS). Materials and Methods: The medical records of TB and AIDS cases diagnosed from 1992 to 1997 in a public service for AIDS care were reviewed. Results: Resistance was diagnosed in 82 (19%) of 431 cases. The mean and median values between the diagnosis of AIDS and the diagnosis of TB were 214.8 days and 70.5 days, respectively. Multidrug-resistant TB (MDR TB) occurred in 11.3% of cases. Of the 186 patients with no previous treatment, 13 (6.9%) presented primary MDR TB. Of the 90 cases with previous treatment, six (6.7%) presented monoresistance to rifampin and 27 (30%) presented MDR TB. The distribution of cases with sensitive and resistant M. tuberculosis strains was homogeneous in terms of the following variables: gender, age, category of exposure to human immunodeficiency virus (HIV), alcoholism, and homelessness. Multivariate analysis showed an association between resistance and the two following variables: previous treatment and duration of AIDS prior to TB exceeding 71 days. The rates of primary multiresistance and of monoresistance to rifampin were higher than those detected in HIV-negative patients in Brazil. Conclusions: In this patient series, M. tuberculosis resistance was predominantly of the acquired type, and resistance was independently associated with previous treatment for TB and with duration of AIDS prior to TB exceeding 71 days.