Sputum Smear-positive Pulmonary Tuberculosis Patients Research Articles

PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial

IntroductionTuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for...

Prevalence of Rifampicin resistance tuberculosis among presumptive tuberculosis patients in Egypt-2021: a national health facility-based survey

BackgroundThe magnitude of MDR-TB cases was noticeable in Egypt. However, the last national survey was 11-years ago. The current survey was conducted to determine the prevalence of rifampicin resistance among sputum smear-positive pulmonary tuberculosis patients in Egypt.MethodsA national health facility-based cross-sectional study was conducted in 14 randomly selected governorates in Egypt between August 2020 and September 2021. All presumptive TB cases, either new or previously treated according to WHO definitions, with no gender, age, or nationality limitations, and provided informed consent were included in the study. Each patient completed a case report form (CRF). The CRF included socio-demographic and clinical data. Sputum samples were collected according to standard techniques and cultured on Lowenstein-Jensen (L-J) medium. Gene X-pert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. The prevalence of RR was calculated using crude, cluster, and weighted methods. Factors associated with RR were analyzed by bivariate and multivariate techniques.ResultsAmong the total 849 presumptive TB patients enrolled in the study, 710 (83.6%) patients were subjected to Gene X-pert testing (MTB/RIF). The crude prevalence of RR was 3.32% (95% CI: 1.89–4.76%) among the new cases and 9.46% (95% CI: 2.63–16.29%) among the retreated cases with an overall estimate of 3.99%; (95% CI: 2.51–5.47%). By cluster analysis the overall prevalence of RR was 5.01% (95% CI: 2.90–7.13). Factors associated with the prevalence of RR were co-morbidity with bronchial asthma, drug abuse and history of contact with a family member with TB.ConclusionThe prevalence of RR among either new or retreated cases TB patients was lower than the previous Egyptian rates in 2010–2012. The strongest predictor associated with RR was comorbidity with bronchial asthma.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

BackgroundRecent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.MethodsFour SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.ResultsWe found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.ConclusionNEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

English

BACKGROUND Sputum smear conversion is the negative conversion of the sputum smear at the end of the second month of treatment regimen under the National Tuberculosis Elimination Program (NTEP). When the acid-fast bacillus (AFB) smear comes negative at the end of an intensive phase, the treatment regimen can shift to the continuation phase that indicates bacillary load is a minimum. Although some authors consider the conversion of cultures when the AFB smear is negative, two potent drugs in the continuation phase are sufficient to kill the remaining bacilli. The drug that can kill bacteria in the first 2 days of treatment is called early bactericidal activity (EBA). This can be assessed by the percentage of negative conversion of cultures at the end of the intensive phase of the treatment regimen. EBA is very essential because it reduces the transmission in the community and chances of patient death. When the purpose is to kill as many bacilli as possible in the first few days and weeks of treatment, it is very important to include bactericidal drugs in the treatment regimen so that it reduces the chances of patient death and infectiousness and the negative conversion of the cultures after 2-month treatment regimen is an indication of the bactericidal capacity of the drug. The purpose of this study was to compare sputum smear conversion in daily versus intermittent treatment regimens in diagnosed cases of new sputum smear-positive pulmonary tuberculosis patients. METHODS This retrospective observational study was carried out in the Department of Respiratory medicine and nodal drug resistance tuberculosis centre (DR-TB) at the Government medical college and hospital, Akola. In this study, a total of 120 new patients were taken. 60 patients were given daily and intermittent regimens respectively under NTEP. RESULTS Out of 120 patients, 56 (93.33 %) patients in intermittent and 53 (88.33 %) patients in daily regimen were sputum smear-negative at the end of 2nd month (intensive phase) and at the end of 6th month (continuation phase). 1 patient (1.6 %) remained sputum smear-positive after the intensive phase. That patient was given 1 month of extension of anti-tuberculosis treatment (AKT) in the intensive phase and the patient became sputum negative after 1 month of extension. CONCLUSIONS It was concluded in this study, daily regimens and intermittent regimens were equally effective in negative conversion of the sputum smear at the end of the intensive phase and the end of the continuation phase. Negative conversion of the sputum smear is quite important because the bacillary load will be so low at the end of 2nd month that reduces the chances of patient death and transmission in the community. KEY WORDS Pulmonary Tuberculosis (PTB), Drug-Resistant TB (DR-TB), National Tuberculosis Programme (NTP), Revised National TB Control Program (RNTCP), Intensive Phase (IP), continuation Phase (CP), National Tuberculosis Elimination Program (NTEP).

Viable Mycobacterium tuberculosis in sputum after pulmonary tuberculosis cure

BackgroundPulmonary tuberculosis (TB) with detectable Mycobacterium tuberculosis in the sputum is a major source of transmission. In resource limited TB endemic settings, cure is declared through sputum smear examination for acid fast bacilli without performing culture. This may lead to erroneous treatment outcomes as viable bacteria may be missed due to the low sensitivity of direct smear method. The aim of this study was to investigate if sterilizing cure is achieved among the new pulmonary TB cases declared cured by sputum smear conversion and to evaluate the impact of addition of ethambutol in the continuation phase in achieving it.MethodsNew sputum smear-positive pulmonary TB patients registered at a tertiary care hospital in Pakistan from November 2013 to March 2014 were followed under standard Directly Observed Treatment Short Course strategy for 6 months. Half of these patients received ethambutol in addition to isoniazid and rifampicin in the continuation phase. Sputum specimens were examined on microscopy at 2 months and at the end of treatment. Sputa of patients with negative direct smear examination at the end of treatment were cultured.ResultsAmong 5746 TB suspects, 1595 were new sputum smear positive pulmonary TB cases, and 533 were registered at our hospital. Among these, 504 converted sputum negative at 2 months and 348 converted at the end of 6 months of treatment and were declared cured. Sputa of 204/348 patients were cultured, and 12/204 (6%) were culture-positive. Culture positivity at 6 months was not associated with bacterial load, smoking, diabetes, presence of cavities, history of contact with TB patients, age, sex, socioeconomic status, or addition of ethambutol in the continuation phase.ConclusionViable cultivable bacilli were detected in 6% of cured patients, which would have significant impact on the control of TB. This highlights the need for an inexpensive and accurate surrogate marker for culture as it is not feasible to perform culture in routine for monitoring treatment response in the low-resource settings. The treatment outcome did not improve by addition of ethambutol emphasizing the need to find the optimal duration of treatment for individual or carefully selected groups of patients.

Microorganisms isolated at admission and treatment outcome in sputum smear-positive pulmonary tuberculosis.

Cured or completed cases in newly diagnosed sputum smear-positive pulmonary tuberculosis (TB) is 47.7% in Japan in 2016. Aging of TB patients and their underlying conditions could affect treatment outcome. Weanalyzed the association between the isolation of microorganisms from sputum at admission and the 180-day mortality rate of the sputum smear-positive pulmonary TB patients in Chiba-East Hospital in Japan. Total subjects were 761 (median age: 63 years). Sputum test for microorganisms was conducted in 708 patients. Microorganisms other than the normal oral flora were isolated in 128 cases (18.1%). Details of the isolated microorganisms were as follows: methicillin-resistant Staphylococcus aureus 23 cases, Klebsiella pneumoniae 17 cases, Pseudomonas aeruginosa 16 cases. Mortality was significantly elevated in the patients with those microorganisms than the others (39.8% vs. 10.2%) (P<0.01). Fifty-one of 128 patients with those microorganisms died, and 10 of them died of infectious disease, which is the most frequent cause of deaths. The factors associated with the isolation of those microorganisms were as follows: respiratory failure (adjusted odds ratio (aOR):2.5 [95% confidence interval (CI) 1.3-4.7]), performance status 3 or 4 (aOR:2.9 [95% CI 1.6-5.4]), serum albumin <3.0mg/dL (aOR:2.1 [95% CI 1.3-3.6], age of 65 years or older (aOR:2.0 [95% CI 1.2-3.4]). Those strains were isolated from one of sixth patients. Patients with those microorganisms did not always develop infectious diseases; however, treatment outcomes were poor, with higher mortality. The isolations of microorganisms were associated with various underlying conditions, leading to death. Thus, attention should be paid to TB patients with the above factors.

Sex and age differences in Mycobacterium tuberculosis infection in Brazil.

Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30-87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1-2.2; P = 0.02) and between ages 0-4 and 15-39 years among male contacts (OR 2.7, 95% CI 0.83-8.9 and 1.1, 95% CI 0.99-1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.

Nutritional status in sputum positive and sputum negative cases of pulmonary tuberculosis

Background: In a developing country like India, tuberculosis (TB) and malnutrition, both the problems are of prime concern. There is an increase in the occurrence of sputum negative TB in regions having high human immunodeficiency virus prevalence. Furthermore, it seems that nutritional status may predict clinical outcome in TB. Aims and Objectives: To determine nutritional status in sputum smear positive and sputum smear-negative cases of pulmonary TB (PTB). Methods and Materials: A total of 54 male patients, diagnosed with PTB by an expert physician, based on sputum smear microscopy and radiography were recruited for study. They were divided into sputum smear-positive pulmonary tuberculosis (SPPT) and sputum smear-negative pulmonary tuberculosis (SNPT) group. Age, medical history (cough, fever, anorexia, weight loss, and hemoptysis), weight, height, body mass index, hemoglobin, and serum protein were recorded and compared in both groups. Results: About 62.96% of patients were smear positive and 37.03% were smear negative. Cough, fever, anorexia, and weight loss were more common in SPPT patients than in SNPT group, but it was not statistically significant except cough (P < 0.05). Nearly, 38% of SPPT patients were severely underweight and almost 30% of SNPT were severely underweight. Conclusions: It appears that undernutrition among SPPT and SNPT patients of PTB is a result of preexisting chronic undernutrition as well as concurrent active infection, which increases the severity of weight loss. As a result, nutritional support is of prime importance for the patient and must be given during treatment phase.

Treatment adherence among sputum smear-positive pulmonary tuberculosis patients in Xinjiang, China: a prospective study.

Background: Despite great effort to control tuberculosis (TB), low treatment adherence threatens the success of drug therapy, increases the risk of TB transmission, and leads to the development of drug resistance. The present study assessed anti-TB treatment adherence in sputum smear-positive TB patients and examined the risk factors for poor patient adherence to identify targets for intervention. Methods: We monitored and followed up TB patients who were diagnosed between July 2014 and June 2015 in Xinjiang, China. A total of 8289 sputum smear-positive TB patients were included in this study. All patients registered their information during the first hospital visit or with the Centers for Disease Control, had regular follow-up visits, and accepted the anti-TB treatment. Insufficient re-examination adherence was defined as undergoing fewer than the recommended three sputum smear examinations during the treatment course. Results: Among 8289 patients, 3827 men (84.4% of male patients) and 3220 women (85.7% of female patients) had good adherence during treatment follow-up. 1242 patients (15.0%) did not complete regular follow-up. 332 (4.0%) patients lost contact. An adjusted logistic regression model showed that ethnicity, household address, treatment classification, patient source, and the actual management were significantly associated with non-adherence. Conclusion: The Xinjiang TB epidemic situation remains grim. Smear-positive patients had a higher proportion of non-adherence, which increased treatment difficulties and the risk of death from TB. Relevant medical departments should strengthen their supervision and interventions during the TB treatment process to improve patient adherence to anti-TB treatment.

Novel mutations in the exon 5, intron 2 and 3′ UTR regions of IL-12B gene were observed in clinically proven tuberculosis patients of south India

Interleukin-12 (IL-12) is formed by the interaction of IL-12p35 and IL-12p40 expressed independently from IL-12A and IL-12B genes. This interleukin plays prominent role in the T-helper type-1 (Th1) response against intracellular pathogens. Variations in IL-12B gene causes disruption of various activities one of them is suppression of Th1 response and is one of the characteristic features observed in patients with active tuberculosis. Hence, in the present study IL-12B gene status was evaluated in 50 new sputum smear-positive pulmonary tuberculosis patients (NSP-PTB) as identified by Ziehl-Nielsen (ZN) staining and 50 apparently healthy control subjects (HCS) who were sputum smear-negative. The sequence analysis showed novel missense mutations p.Ser205Ile, p.Leu206Glu, p.Pro207Ser, p.Glu209Lys, p.Val210Ser, p.(Ser205_Cys327delinsIleGlu) and p.(Lys217_Leu218delinsIle) were found in exon 5 of the IL-12B gene in nine patients resulting formation of inactive IL-12 and three patients showed novel frame shift mutations p.(Asn222Leufs∗23) in exon 5 of causing the formation of truncated protein. Several mutations were noted in intron 2 of the IL-12B gene in 5 patients and in 13 patients mutations were observed in 3′ UTR region. All together 30/50 patients (60%) showed mutations in IL-12B gene. Decreased levels of interferon-gamma (IFN-γ) and IL-12 as determined by ELISA and flow cytometry were observed in the peripheral blood mononuclear cell culture supernatants in TB patients having mutations compared with control subjects. Further, in silico analysis revealed due to frame shift mutations in exon 5 at Asn222 resulted in deletion of functional fibronectin type-III (FN3) domain which leads to formation of inactive IL-12 in these patients.

Relationship between Nutritional Support and Tuberculosis Treatment Outcomes in West Bengal, India.

IntroductionPoverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome.MethodsThis was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death).ResultsOf 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86).ConclusionUnder programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.

IPT uptake among child contacts of TB patients: Experience from the Indus Hospital TB program, Karachi, Pakistan

BackgroundInfants and young children are particularly susceptible to developing tuberculosis (TB) following exposure and infection, and isoniazid preventive therapy can substantially reduce this risk. This evidence-base provides the rationale for the policy and guidelines to screen and manage children that are household contacts of TB cases, prioritizing those with sputum smear-positive TB. The guidelines have been in place for decades, but are rarely implemented. IPT programs in high-TB burden countries are rare and fraught with low uptake and low rates of therapy completion. MethodsThis study describes the demographics and outcomes of contact management and the IPT program for <5years old at the Indus Hospital in Karachi, Pakistan from 2011 to 2014. Children <5years old in contact with newly diagnosed sputum smear-positive pulmonary TB patients were referred by the counselor for contact evaluation. All children underwent a history, physical, CXR and TST. All contacts were started on IPT based on WHO recommendations after confirming that they had no TB disease. Outcomes were defined as children who were enrolled, started on IPT but never returned for follow-up (primary default), children who had one or more follow-up visits but did not complete treatment (default) and children who completed IPT (treatment completed). ResultsA total of 240 children were enrolled in the Indus IPT program from 2011 to 2014. Of these, data from 184 contacts was analyzed in detail as the remainder were still on IPT. All children enrolled were less than 5years of age (mean age 3years) and 96 (52%) were males. Of all the enrolled children, 76/240 (31.6%) were <5% weight for their age (underweight), of these 52% were female children. A symptom of either cough or fever was reported by 29/184 (15.7%) children; however, all responded to routine antibiotics and did not have CXR findings suggestive of TB disease. Of the enrolled who had a TST done, 12/209 (5.8%) had a positive result. Analysis of outcomes revealed that only 60/184 (32.6%) completed 6months of IPT (with no gender predisposition). Among those who completed therapy, none developed TB disease during follow-up. Outcome trends revealed an increase in completion rate (40% in 2013 compared with 26% in 2012), which may reflect improvement in counseling services in 2013. Children who had an initial symptom or were underweight at the start of IPT were more likely to complete treatment (p<0.01). ConclusionDespite a large cohort of TB patients in the Indus TB program-5487 SS+ patients registered during the study period – this IPT program enrollment has been low. A high rate of patient default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness enhancing efforts by community field teams will help improve outcomes. It is vital that the National TB Program strengthens and expands contact management with a community-based approach and incentives.

Utility of B-cell epitopes based peptides of RD1 and RD2 antigens for immunodiagnosis of pulmonary tuberculosis

Tuberculosis (TB) continues to be a major health problem due to lack of accurate, rapid, and cost-effective diagnostic tests. Serodiagnostic tests incorporating highly specific region of difference (RD) antigens (early secretory antigenic target 6 [ESAT-6], culture filtrate protein 10 [CFP-10], culture filtrate protein 21 [CFP-21], and mycobacterial protein from species tuberculosis 64 [MPT-64]) have recently been shown to be promising for specific diagnosis of TB in our lab. However, only few studies have reported the use of synthetic peptides of RD antigens, and none has used them to differentiate TB from sarcoidosis, a close mimic of smear-negative pulmonary TB (PTB) with entirely different management. The present study was conducted with an aim to study the utility of B-cell epitopes based peptides of RD1 (ESAT-6, CFP-10) and RD2 (CFP-21, MPT-64) antigens for immunodiagnosis of PTB for which sputum smear-positive PTB patients, sputum smear-negative PTB patients, sarcoidosis patients, and healthy controls (n = 24/group) were recruited. Bioinformatic software Bcepred was used to predict linear B-cell epitopes, using physico-chemical properties on a non-redundant dataset. Seven peptides as representative B-cell epitopes of ESAT-6, CFP-10, CFP-21, and MPT-64 were evaluated as targets of the antibody responses in TB patients and controls by enzyme-linked immunosorbent assay (ELISA). The current study showed sensitivity with individual peptides ranging from 37.5% to 83.3% for smear positive, 25% to 58.3% for smear negative as compared to 4.16% to 20.8% for sarcoidosis. Four out of 7 peptides that showed higher reactivity with TB patients and better discrimination from sarcoidosis patients representing ESAT-6, CFP-10, CFP-21, and MPT-64 were selected for multiepitope ELISA. The combination of peptides yielded 83.3% sensitivity for smear positive, 62.5% for smear negative, and only 4.16% for sarcoidosis. The specificity, however, for all the peptides/combination was 100%. Combination of peptides has proven to be better than individual peptides as per the latest criteria of the World Health Organization according to which a test that can replace smear microscopy with sensitivity of >90% for smear-positive patients and >65% for smear-negative TB patients with a specificity >95%, and thus, the present study suggests that a test based on combination of peptides selected from mycobacterial RD1 and RD2 antigens could be important for promoting an early diagnosis and management of otherwise difficult to diagnose smear-negative PTB patients. Moreover, it can also be used to discriminate sarcoidosis from PTB, thus preventing the misdiagnosis and mismanagement.

Factors Influencing Sputum Conversion among Smear-Positive Pulmonary Tuberculosis Patients in Morocco

Background. Sputum smear-positive pulmonary tuberculosis patients expel infectious viable bacilli for a period following the commencement of treatment. Objective. To determine the time to sputum smear conversion and study the factors influencing it. Design. A prospective study was undertaken at our hospital in Rabat over a six-month period on a cohort of 119 sputum smear positive patients. Patients were followed up fortnightly. At each followup, specimens were collected and processed for microscopy using standard protocol. Results. 96.6% of our patients completed the study (4 deaths). Sputum conversion rate was 42% after two weeks, 73% after one month, and 95% after two months. Univariate and stepwise regression analysis showed that patients who had high smear grading, miliary, and bilateral radiologic lesions were more likely to undergo delayed sputum conversion (P&lt;0.05). Other factors were thought to influence sputum conversion but were not statistically proven in our study. Conclusion. Since viable bacilli continue to be expelled for up to two months, infection control measures should be maintained for such a time. Patients with high smear grading, miliary, and bilateral radiologic lesions need to be monitored more closely.

Randomized Dose-Ranging Study of the 14-Day Early Bactericidal Activity of Bedaquiline (TMC207) in Patients with Sputum Microscopy Smear-Positive Pulmonary Tuberculosis

Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.

Treatment adherence among sputum smear-positive pulmonary tuberculosis patients in mountainous areas in China

BackgroundWe carried out an investigation in five provinces in China to assess treatment adherence and identify factors associated with insufficient treatment adherence in tuberculosis (TB) patients in mountainous, rural areas of China.MethodsIn each of the five provinces, all counties with > 80% mountainous area were stratified into three groups according to their gross domestic product. In each stratum, one county was randomly sampled. Study subjects were sampled from all smear positive TB cases registered in 2007 in the target counties. TB patients, village doctors, county doctors and directors of the TB prevention and control institutes were interviewed. Insufficient medication adherence was defined as taking less than 90% of anti-TB drug doses prescribed. Insufficient re-examination adherence was defined as having less than the recommended three sputum smear examinations during the treatment course.ResultsA minority of patients took drugs under direct observation: on average 29% during the intensive phase of treatment. In total, 524 TB patients were included, of whom 49 (9.4%) took less than 90% of all doses prescribed and 92 (17.6%) did not have all sputum smear examinations, with substantial variations between the provinces. In multivariable analysis, no direct observation of treatment during the intensive phase and the presence of adverse events were associated both with insufficient medication adherence and insufficient re-examination adherence. Overall, 79% of patients were adherent both to treatment and re-examinations.ConclusionsIn these remote and poor areas of China, the TB control program is not fully functioning according to the guidelines. The majority of patients are not treated under direct observation, while direct observation by health care staff was associated with better adherence, both to drug therapy and re-examinations. Insufficient adherence increases the risk of unsuccessful treatment outcomes and development of drug resistance. Measures should be taken urgently in these areas to strengthen implementation of the international Stop TB strategy.

Mycobacterium tuberculosisGenotype and Case Notification Rates, Rural Vietnam, 2003–2006

Tuberculosis case notification rates (CNRs) for young adults in Vietnam are increasing. To determine whether this finding could reflect emergence of Mycobacterium tuberculosis Beijing genotype, we studied all new sputum smear-positive pulmonary tuberculosis patients registered for treatment in 3 rural districts in Vietnam during 2003-2006. Beijing strain infections were more frequent in younger patients (15-24 years of age, 53%) than in older patients (31%; p<0.001). The increase in CNRs for youngest patients was larger for disease caused by the Beijing genotype than by other genotypes, but the difference was not significant. For patients 15-24 years of age, 85% of fluctuations in CNRs between years was caused by fluctuations in Beijing genotype infections compared with 53% and 23% in the groups 25-64 and >or=65 years of age, respectively (p<0.001). These findings suggest that young adults may be responsible for introducing Beijing strains into rural Vietnam.

Treatment outcomes among pulmonary tuberculosis patients at treatment centers in Ibadan, Nigeria

To assess treatment outcomes and determinants of outcome among tuberculosis patients. A longitudinal study design involving a cohort of sputum smear-positive pulmonary tuberculosis patients at initiation of therapy, who were followed up to the end of treatment at eighth month. Tuberculosis treatment centers in Ibadan, Nigeria. A total of 1,254 patients were followed up with a mean age of 35.0+/-3.3 years. The percentages of patients with treatment outcomes assessed in the study were as follows: cure (76.6%), failure (8.1%), default (6.6%), transferred out (4.8%), and death (1.9%). The cure rate varied significantly between treatment centers from 40 to 94.4% (P<0.05). The treatment centers located within the specialist health centers at Jericho and the University College Hospital had 50 and 75% cure rates, respectively.The mean age of cured patients was 31.2+/3.1 years which was significantly lower than the mean age of those with poor treatment outcomes (36.7+/3.5 years; P<0.05). Males had a higher risk of a poor treatment outcome (RR=1.8; 95% CI: 1.02-1.94) than females. Also, patients with a poor knowledge of tuberculosis had a higher risk of having a poor treatment outcome (RR=1.35; 95% CI: 1.25-1.62) compared to those with knowledge. Variations in health center treatment outcomes and poor knowledge of tuberculosis among patients suggest that poor program implementation quality may be a major modifiable determinant of treatment outcomes in our environment.

Prevalence of Resistance to Antituberculosis Drugs in Riyadh and A Review of Previous Reports

Resistance to antituberculosis drugs is an important cause of treatment failure. We evaluated the prevalence and pattern of antituberculosis drug resistance in the central region of Saudi Arabia, and reviewed previous reports from Saudi Arabia. We retrospectively examined the records of sputum smear and culture-positive pulmonary tuberculosis patients admitted consecutively from 1998 through 1999 in a main referral hospital in Riyadh, and analyzed drug sensitivity reports. We also reviewed previous reports on antituberculosis drug resistance in Saudi Arabia. Of 515 patients with pulmonary tuberculosis, 80 (15.5%) had resistance to at least one antituberculosis drug. Resistance to streptomycin was most frequent (9.7% ), followed by rifampicin (9.5%), isoniazid (4.3%), and ethambutol (0.2%). Resistance to one antituberculosis drug was found in 8.9%, resistance to two drugs in 5.2%, resistance to three drugs in 1.2%, and resistance to four drugs in 0.2%. Multidrug resistance (defined as resistance to at least isoniazid and rifampicin) was found in 1.9% of patients. A literature review including 6114 patients in Saudi Arabia showed that resistance against streptomycin was most common (8.8%), followed by rifampicin (8%), and isoniazid (7.2%). Of the 6114 patients, 6.8% patients were resistant to only one drug, 3.6% were resistant to two drugs, and 3.7% to three drugs. The high prevalence of rifampicin resistance and resistance to multiple drugs in the Riyadh region and in other parts of Saudi Arabia is a major challenge to the control of tuberculosis in this country. Efforts should be made to prevent the emergence of further antituberculosis drug resistance.

Sensitivity to anti-tuberculosis drugs in HIV-positive and -negative patients in Addis Ababa.

A cross-sectional survey was conducted between 1 August and 31 December, 1998 in Addis Ababa, Ethiopia to determine the rate of primary drug resistance to anti-tuberculosis drugs and to investigate its possible association with HIV infection. Sputum culture, sensitivity to first-line anti-tuberculosis drugs and HIV testing were done for 236 sputum smear-positive pulmonary tuberculosis patients. Primary drug resistance level (single or multidrug resistance) had not changed significantly since 1994. Primary resistance occurred more often among HIV-positive than among HIV-negative patients. The association between drug resistance and HIV will have a serious impact in the control of tuberculosis because in recent years the prevalence of HIV has increased dramatically in Ethiopia. Therefore, further studies on drug resistance and HIV infection and the establishment of drug resistance surveillance are recommended.