Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study

Background

The rising prevalence of diabetes mellitus (DM) worldwide, especially in developing countries, and the persistence of tuberculosis (TB) as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil.

Methods

We performed a retrospective analysis of a TB patient cohort (treatment naïve) of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT) initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups.

Results

DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups.

Conclusions

These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB reference centers in endemic areas.     

Glycemic Control and the Risk of Tuberculosis: A Cohort Study

BackgroundDiabetes is a well-known risk factor for tuberculosis (TB) and is increasingly prevalent in low- and middle-income countries, where the burden of TB is high. Glycemic control has the potential to modify the risk of TB. However, there are few studies on the association between glycemic control and TB risk, and the results are inconsistent.ConclusionsGood glycemic control could potentially modify the risk of TB among diabetic patients and may contribute to the control of TB in settings where diabetes and TB are prevalent.     

Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan

Background

Proportional mortality ratio data indicate that healthcare workers (HCWs) have an elevated tuberculosis (TB) mortality. Whether this is caused by an increased TB incidence, a worse TB treatment outcome, or a combination of effects, remains unclear. To elucidate the hazard components of occupational TB, we assessed TB incidence and TB treatment outcome among HCWs in Taiwan.

Methods

We compared the incidence of active TB among HCWs at a major medical center in Taiwan with that of Taiwan general population in 2004–2012. We also compared the TB treatment outcome of HCWs with that of age/sex-matched non-HCW patients treated at the same hospital, as well as that of nationally registered TB patients.

Results

The standardized TB incidence ratio of the HCWs was 1.9 (95% confidence interval [CI]: 1.2–2.9), compared with the general population. HCWs with pulmonary TB (n = 30) were less likely to have underlying diseases, delay in diagnosis, delay in treatment, or side effects of treatment, compared with age/sex-matched non-HCW TB patients (n = 120) (all Ps<0.05). The TB treatment outcome of HCWs was significantly better than that of non-HCW patients (TB-related mortality: 0.0% vs. 5.8%, P = 0.008, Mantel-Haenszel test). The standardized TB-related mortality rate was 1.08% [95% CI: 0.96% - 1.20%] for all of the nationally registered TB patients in Taiwan.

Conclusions

HCWs are at increased risk of active TB, compared with general population. To mitigate this occupational hazard, more efforts need to be directed towards the prevention of nosocomial TB transmission. Healthy worker effect, more rapid diagnosis, and less delay in treatment contribute to a lower TB-related mortality in HCWs.     

Plasma Metabolomics in Human Pulmonary Tuberculosis Disease: A Pilot Study

We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution.     

Extrapulmonary Tuberculosis: Mycobacterium tuberculosis Strains and Host Risk Factors in a Large Urban Setting in Brazil

Background

Factors related to the development of extrapulmonary forms of tuberculosis (EPTB) are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB) strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil.

Methods and Findings

We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB) cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB) and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each. By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%) fell into patterns with no family assignment; 297 (48%) isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23-54.18) were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB.

Conclusions

These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics.     

Adherence to Tuberculosis Treatment among Migrant Pulmonary Tuberculosis Patients in Shandong,China: A Quantitative Survey Study

Adherence to TB treatment is the most important requirement for efficient TB control. Migrant TB patients’ “migratory” nature affects the adherence negatively, which presents an important barrier for National TB Control Program in China. Therefore, TB control among migrants is of high importance.The aim of this study is to describe adherence to TB treatment among migrant TB patients and to identify factors associated with adherence. A total of 12 counties/districts of Shandong Province, China were selected as study sites. 314 confirmed smear positive TB patients were enrolled between August 2^nd 2008 and October 17^th 2008, 16% of whom were non-adherent to TB therapy. Risk factors for non-adherence were: the divorced or bereft of spouse, patients not receiving TB-related health education before chemotherapy, weak incentives for treatment adherence, and self supervision on treatment. Based on the risk factors identified, measures are recommended such as implementing health education for all migrant patients before chemotherapy and encouraging primary care workers to supervise patients.     

Impact of Replacing Smear Microscopy with Xpert MTB/RIF for Diagnosing Tuberculosis in Brazil: A Stepped-Wedge Cluster-Randomized Trial

BackgroundAbundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints).ConclusionsReplacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01363765","term_id":"NCT01363765"}}NCT01363765Please see later in the article for the Editors'' Summary     

Cumulative Effect in Information Diffusion: Empirical Study on a Microblogging Network

Cumulative effect in social contagion underlies many studies on the spread of innovation, behavior, and influence. However, few large-scale empirical studies are conducted to validate the existence of cumulative effect in information diffusion on social networks. In this paper, using the population-scale dataset from the largest Chinese microblogging website, we conduct a comprehensive study on the cumulative effect in information diffusion. We base our study on the diffusion network of message, where nodes are the involved users and links characterize forwarding relationship among them. We find that multiple exposures to the same message indeed increase the possibility of forwarding it. However, additional exposures cannot further improve the chance of forwarding when the number of exposures crosses its peak at two. This finding questions the cumulative effect hypothesis in information diffusion. Furthermore, to clarify the forwarding preference among users, we investigate both structural motif in the diffusion network and temporal pattern in information diffusion process. Findings provide some insights for understanding the variation of message popularity and explain the characteristics of diffusion network.     

Pulmonary Tuberculosis Incidence and Risk Factors in Rural Areas of China: A Cohort Study

The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies.     

Caesarean Delivery and Postpartum Maternal Mortality: A Population-Based Case Control Study in Brazil

BackgroundCesarean delivery rates continue to increase worldwide and reached 57% in Brazil in 2014. Although the safety of this surgery has improved in the last decades, this trend is a concern because it carries potential risks to women’s health and may be a modifiable risk factor of maternal mortality. This paper aims to investigate the risk of postpartum maternal death directly associated with cesarean delivery in comparison to vaginal delivery in Brazil.MethodsThis was a population-based case—control study performed in eight Brazilian states. To control for indication bias, deaths due to antenatal morbidity were excluded. We included 73 cases of postpartum maternal deaths from 2009–2012. Controls were selected from the Birth in Brazil Study, a 2011 nationwide survey including 9,221 postpartum women. We examined the association of cesarean section and postpartum maternal death by multivariate logistic regression, adjusting for confounders.ResultsAfter controlling for indication bias and confounders, the risk of postpartum maternal death was almost three-fold higher with cesarean than vaginal delivery (OR 2.87, 95% CI 1.63–5.06), mainly due to deaths from postpartum hemorrhage and complications of anesthesia.ConclusionCesarean delivery is an independent risk factor of postpartum maternal death. Clinicians and patients should consider this fact in balancing the benefits and risks of the procedure.     

Outcomes and Treatment of Lumbosacral Spinal Tuberculosis: A Retrospective Study of 53 Patients

Study Strategy

A retrospective clinic study.

Purpose

To evaluate the efficacy of conservative and surgical treatment for lumbosacral tuberculosis.

Methods

This study retrospectively reviewed 53 patients with lumbosacral tuberculosis who were treated in our institution between January 2005 and January 2011. There were 29 males and 24 females with average ages of 37.53 ± 17.28 years (range 6–72 years). 11 patients were given only anti-TB drugs; the remainder underwent anterior debridement, interbody fusion with and without instrumentation, or one-stage anterior debridement combined with posterior instrumentation. Outcome data for these patients included neurologic status, lumbosacral angle, erythrocyte sedimentation rate value(ESR) and C-reactive protein value(CRP) were assessed before and after treatment.

Results

The mean lumbosacral angles were 23.00°± 2.90°in the conservatively treated patients and 22.36°± 3.92o in the surgically treated patients. At the final follow-up, this had improved to 24.10o ± 2.96°in the conservatively treated patients and 28.13° ± 1.93°in the surgically treated patients (all P < 0.05). There were statistically significant differences before and after treatment in terms of ESR and CRP (all P < 0.05). All patients achieved bone fusion. The mean follow-up period was 32.34 ± 8.13 months (range 18 to 55 months). The neurological deficit did not worsen in any of the patients.

Conclusions

It has been proven that conservative and surgical treatments are safe and effective and produce good clinical outcomes for patients with lumbosacral tuberculosis. The advantages of operation include thoroughness of debridement, decompression of the spinal cord, and adequate spinal stabilization.     

Association of Maternal and Child Nutritional Status in Brazil: A Population Based Cross-Sectional Study

Background

Although child undernutrition and stunting has been decreasing worldwide while obesity rates increase, these extreme conditions might coexist in families from low- and middle-income countries. We examined the association between maternal and child anthropometric indicators using a population representative sample.

Methods

4,258 non-pregnant women and their children <60 months who participated in the 2006 Brazilian Demographic Health Survey. We compared the distributions of two nutritional indexes of children, height-for-age (HAZ) and body mass index-for age (BAZ) z-scores, by categories of maternal height, body mass index (BMI), and waist circumference (WC). Adjusted mean differences and 95% confidence intervals (95% CI) were estimated from linear regression, taking into account the complex survey design. We also examined the associations of maternal anthropometry with the prevalence of child stunting (HAZ<−2) and overweight/obesity (BAZ>2).

Results

HAZ was positively associated with maternal height and WC in a linear fashion. After adjustment, for sociodemographic characteristics, children whose mothers'' height was<145 cm had 1.2 lower HAZ than children whose mothers were ≥160 cm tall (p-trend<0.0001). After further adjustment for maternal height and maternal BMI, children of mothers with a waist circumference ≥88 cm had 0.3 higher HAZ than those of mothers with WC<80 cm (p-trend<0.01). Adjusted prevalence ratios and 95% CI for stunting by the categories of maternal height (<145, 145–149, 150–154, 155–159 and ≥160 cm) were, respectively, 2.95 (1.51;5.77), 2.29 (1.33;3.93), 1.09 (0.63;1.87), and 0.89 (0.45;1.77), (p-trend = 0.001). BAZ was positively associated with maternal BMI and WC.

Conclusion

We observed a strong, positive association of maternal and child nutritional status. Mothers of low stature had children with lower stature, mothers with central obesity had taller children, and mothers with overall or abdominal obesity had children with higher BAZ.     

Epidemiology,Diagnosis and Management of Extra-Pulmonary Tuberculosis in a Low-Prevalence Country: A Four Year Retrospective Study in an Australian Tertiary Infectious Diseases Unit

Objectives

Extra-pulmonary tuberculosis (EPTB) is relatively neglected and increasing in incidence, in comparison to pulmonary tuberculosis (PTB) in low-burden settings. It poses particular diagnostic and management challenges. We aimed to determine the characteristics of EPTB in Western Sydney, Australia, and to conduct a quality assurance investigation of adherence to guidelines among Infectious Diseases (ID) practitioners managing EPTB cases.

Methods

All adult EPTB cases managed by a large ID service during 01/01/2008–31/12/2011 were eligible for inclusion in the retrospective review. Data were extracted from patient medical records on demographic, diagnostic, clinical and management details, and on clinician adherence to local and international TB guidelines.

Results

129 cases managed by the ID service were identified, with files available for 117. 98 cases were managed by the Respiratory service and were excluded. 98.2%(112/114) had been born in a country other than Australia. HIV status was tested or previously known in 97 people, and positive in 4 (4%). Microbiological confirmation was obtained in 68/117 (58.1%), an additional 24 had histopathological findings considered confirmatory (92/117, 78.6%), with the remainder diagnosed on clinical and/or radiological grounds. Median time to diagnosis post-migration from a high TB-burden country was 5 years (range 0–41). 95 cases were successfully treated, 11 cases defaulted, refused therapy or transferred, 2 cases relapsed and outcomes unknown or pending in 9 cases. No deaths occurred in the sample analysed. Clinician adherence to guidelines was high, but with scope for improvement in offering testing for co-infections, performing eye checks, monitoring blood glucose in patients receiving adjunctive corticosteroids, and considering drug interactions.

Conclusions

Despite excellent TB outcomes in this setting, the low proportion of cases with susceptibility data is worrying in this era of increasing drug resistance, and illustrates the diagnostic difficulties faced even in a well-resourced setting. Vigilance for EPTB needs to remain high in those moving from high prevalence countries to Australia, even decades after immigration.     

Development of Multidrug Resistant Tuberculosis in Bangladesh: A Case-Control Study on Risk Factors

Objective

To determine the risk factors for developing multidrug resistant tuberculosis in Bangladesh.

Methods

This case-control study was set in central, district and sub-district level hospitals of rural and urban Bangladesh. Included were 250 multidrug resistant tuberculosis (MDR-TB) patients as cases and 750 drug susceptible tuberculosis patients as controls. We recruited cases from all three government hospitals treating MDR-TB in Bangladesh during the study period. Controls were selected randomly from those local treatment units that had referred the cases. Information was collected through face-to-face interviews and record reviews. Unadjusted and multivariable logistic regression were used to analyse the data.

Results

Previous treatment history was shown to be the major contributing factor to MDR-TB in univariate analysis. After adjusting for other factors in multivariable analysis, age group “18–25” (OR 1.77, CI 1.07–2.93) and “26–45” (OR 1.72, CI 1.12–2.66), some level of education (OR 1.94, CI 1.32–2.85), service and business as occupation (OR 2.88, CI 1.29–6.44; OR 3.71, CI 1.59–8.66, respectively), smoking history (OR 1.58, CI 0.99–2.5), and type 2 diabetes (OR 2.56 CI 1.51–4.34) were associated with MDR-TB. Previous treatment was not included in the multivariable analysis as it was correlated with multiple predictors.

Conclusion

Previous tuberculosis treatment was found to be the major risk factor for MDR-TB. This study also identified age 18 to 45 years, some education up to secondary level, service and business as occupation, past smoking status, and type 2 diabetes as comorbid illness as risk factors. National Tuberculosis programme should address these risk factors in MDR-TB control strategy. The integration of MDR-TB control activities with diabetes and tobacco control programmes is needed in Bangladesh.