Risk Factors Associated with Default from Multi- and Extensively Drug-Resistant Tuberculosis Treatment,Uzbekistan: A Retrospective Cohort Analysis

Background

The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010.

Methods

A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression.

Results

20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6–9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31–0.86), previous default (2.38, 1.09–5.24) and age >45 years (1.77, 1.10–2.87). The default rate was 14% (42/294) for patients enrolled 2003–2006 and 24% (100/416) for 2007–2008 enrolments (p = 0.001).

Conclusions

Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.     

The Rate of Sputum Smear-Positive Tuberculosis after Treatment Default in a High-Burden Setting: A Retrospective Cohort Study

Rationale

High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others.

Objective

To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases.

Methods

Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment.

Results

A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of re-treatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59–8.41) per 100 person-years compared to 2.09 (95% CI: 1.81–2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00–5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11–2.33) was independently associated with smear-positive tuberculosis re-treatment, regardless of treatment outcome.

Conclusions

In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in high-burden settings.     

Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi,Pakistan: A Mixed Methods Study

Purpose

Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.

Methods

In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.

Results

Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default.

Conclusions

In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.     

Prevalence,Risk Factors,and Treatment Outcomes of Isoniazid- and Rifampicin- Mono-Resistant Pulmonary Tuberculosis in Lima,Peru

BackgroundIsoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.MethodsA prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.ResultsOf 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01).ConclusionA high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.     

Alcohol,Hospital Discharge,and Socioeconomic Risk Factors for Default from Multidrug Resistant Tuberculosis Treatment in Rural South Africa: A Retrospective Cohort Study

Background

Default from multidrug-resistant tuberculosis (MDR-TB) treatment remains a major barrier to cure and epidemic control. We sought to identify patient risk factors for default from MDR-TB treatment and high-risk time periods for default in relation to hospitalization and transition to outpatient care.

Methods

We retrospectively analyzed a cohort of 225 patients who initiated MDR-TB treatment between 2007 through 2010 at a rural TB hospital in the Western Cape Province, South Africa.

Results

Fifty percent of patients were cured or completed treatment, 27% defaulted, 14% died, 4% failed treatment, and 5% transferred out. Recent alcohol use was common (63% of patients). In multivariable proportional hazards regression, older age (hazard ratio [HR]= 0.97 [95% confidence interval 0.94-0.99] per year of greater age), formal housing (HR=0.38 [0.19-0.78]), and steady employment (HR=0.41 [0.19-0.90]) were associated with decreased risk of default, while recent alcohol use (HR=2.1 [1.1-4.0]), recent drug use (HR=2.0 [1.0-3.6]), and Coloured (mixed ancestry) ethnicity (HR=2.3 [1.1-5.0]) were associated with increased risk of default (P<0.05). Defaults occurred throughout the first 18 months of the two-year treatment course but were especially frequent among alcohol users after discharge from the initial four-to-five-month in-hospital phase of treatment, with the highest default rates occurring among alcohol users within two months of discharge. Default rates during the first two months after discharge were also elevated for patients who received care from mobile clinics.

Conclusions

Among patients who were not cured or did not complete MDR-TB treatment, the majority defaulted from treatment. Younger, economically-unstable patients and alcohol and drug users were particularly at risk. For alcohol users as well as mobile-clinic patients, the early outpatient treatment phase is a high-risk period for default that could be targeted in efforts to increase treatment completion rates.     

Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study,Peru

Background

Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households'' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs.

Methods and Findings

From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household''s annual income. In poorer households, costs were lower but constituted a higher proportion of the household''s annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1–2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%–28%), similar to that of MDR TB (20% [95% CI = 14%–25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain “dis-saving” variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients.

Conclusions

Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease. Please see later in the article for the Editors'' Summary     

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.     

A Molecular Biologic Study of Enterocytozoon bieneusi in HIV-Infected Patients in Lima, Peru

ABSTRACT. A cross-sectional study was conducted to examine the genotype distribution of Enterocytozoon bieneusi in HIV-infected patients who visited two government hospitals in Lima, Peru from January 2000 through March 2003. Microsporidia were detected by microscopy in 105 (3.9%) of 2,672 patients. A total of 212 stool samples from 89 microsporidia-positive patients were genotyped by sequence analysis of the internal transcribed spacer (ITS) region of the rRNA gene. A 392-bp fragment containing the complete ITS region was amplified and sequenced. Multiple alignments and phylogenetic analysis of these ITS sequences identified 11 distinct genotypes of E. bieneusi (Peru-1 to Peru-11), 6 of which were new genotypes not reported before. The remaining 5 genotypes had nucleotide sequences identical to those previously reported in humans, cats, pigs, and wild mammals. All the 11 E. bieneusi-genotypes identified are genetically related, and members of the group have been previously found in humans, domestic animals, and some wild mammals. Thus, there is a high genetic diversity of E. bieneusi in humans in Peru, and zoonotie transmission is possible if humans are in close contact with infected animals.     

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru

Background

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.

Methodology and Results

A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.

Conclusions

Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.     

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

Background

For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen.

Methods and Findings

We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005–2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16–23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients’ baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph.In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09–1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65–2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48–1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18–1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09–1.76, per drug when three effective drugs present in regimen).The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.

Conclusions

MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.     

Factors Associated with Patient and Provider Delays for Tuberculosis Diagnosis and Treatment in Asia: A Systematic Review and Meta-Analysis

Background

Delays in tuberculosis (TB) diagnosis and treatment is a major barrier to effective management of the disease. Determining the factors associated with patient and provider delay of TB diagnosis and treatment in Asia may contribute to TB prevention and control.

Methods

We searched the PubMed, EMBASE and Web of Science for studies that assessed factors associated with delays in care-seeking, diagnosis, or at the beginning of treatment, which were published from January 1992 to September 2014. Two reviewers independently identified studies that were related to our meta-analysis and extracted data from each study. Independent variables were categorized in separate tables for patient and provider delays.

Results

Among 45 eligible studies, 40 studies assessed patient delay whereas 30 assessed provider delay. Cross-sectional surveys were used in all but two articles, which included 17 countries and regions. Socio-demographic characteristics, TB-related symptoms and medical examination, and conditions of seeking medical care in TB patients were frequently reported. Male patients and long travel time/distance to the first healthcare provider led to both shorter patient delays [odds ratio (OR) (95% confidence intervals, CI) = 0.85 (0.78, 0.92); 1.39 (1.08, 1.78)] and shorter provider delays [OR (95%CI) = 0.96 (0.93, 1.00); 1.68 (1.12, 2.51)]. Unemployment, low income, hemoptysis, and positive sputum smears were consistently associated with patient delay [ORs (95%CI) = 1.18 (1.07, 1.30), 1.23 (1.02, 1.49), 0.64 (0.40, 1.00), 1.77 (1.07, 2.94), respectively]. Additionally, consultation at a public hospital was associated with provider delay [OR (95%CI) = 0.43 (0.20, 0.91)].

Conclusions

We propose that the major opportunities to reduce delays involve enabling socio-demographic factors and medical conditions. Male, unemployed, rural residence, low income, hemoptysis, positive sputum smear, and long travel time/distance significantly correlated with patient delay. Male, long travel time/distance and consultation at a public hospital were related to provider delay.     

The Patient-Provider Relationship Is Associated with Hepatitis C Treatment Eligibility: A Prospective Mixed-Methods Cohort Study

Hepatitis C virus (HCV) treatment has the potential to cure the leading cause of cirrhosis and hepatocellular carcinoma. However, only those deemed eligible for treatment have the possibility of this cure. Therefore, understanding the determinants of HCV treatment eligibility is critical. Given that effective communication with and trust in healthcare providers significantly influences treatment eligibility decisions in other diseases, we aimed to understand patient-provider interactions in the HCV treatment eligibility process. This prospective cohort study was conducted in the VA Pittsburgh Healthcare System. Patients were recruited after referral for gastroenterology consultation for HCV treatment with interferon and ribavirin. Consented patients completed semi-structured interviews and validated measures of depression, substance and alcohol use, and HCV knowledge. Two coders analyzed the semi-structured interviews. Factors associated with patient eligibility for interferon-based therapy were assessed using multivariate logistic regression. Of 339 subjects included in this analysis, only 56 (16.5%) were deemed eligible for HCV therapy by gastroenterology (GI) providers. In the multivariate logistic regression, patients who were older (OR = 0.96, 95%CI = 0.92–0.99, p = .049), reported concerns about the GI provider (OR = 0.40, 95%CI = 0.10–0.87, p = 0.02) and had depression symptoms (OR = 0.32, 95%CI = 0.17–0.63, p = 0.001) were less likely to be eligible. Patients described barriers that included feeling stigmatized and poor provider interpersonal or communication skills. In conclusion, we found that patients’ perceptions of the relationship with their GI providers were associated with treatment eligibility. Establishing trust and effective communication channels between patients and providers may lower barriers to potential HCV cure.     

Contact Investigation in Households of Patients with Tuberculosis in Hanoi,Vietnam: A Prospective Cohort Study

Setting

Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered.

Objective

To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam.

Methods

Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease.

Results

Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17–1451) and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44–131). Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types.

Conclusion

Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness.     

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.     

Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide,Population-Based Cohort Study

Background

The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.

Methods and Findings

This study identified 3 mutually exclusive cohorts using the 1999–2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999–2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999–2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56–2.29 and 1.09–1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57–2.30 and 1.09–1.67, respectively).

Conclusion

PD was associated with an increased risk of RA development.     

The High Cost of Free Tuberculosis Services: Patient and Household Costs Associated with Tuberculosis Care in Ebonyi State,Nigeria

Objective

Poverty is both a cause and consequence of tuberculosis. The objective of this study is to quantify patient/household costs for an episode of tuberculosis (TB), its relationships with household impoverishment, and the strategies used to cope with the costs by TB patients in a resource-limited high TB/HIV setting.

Methods

A cross-sectional study was conducted in three rural hospitals in southeast Nigeria. Consecutive adults with newly diagnosed pulmonary TB were interviewed to determine the costs each incurred in their care-seeking pathway using a standardised questionnaire. We defined direct costs as out-of-pocket payments, and indirect costs as lost income.

Results

Of 452 patients enrolled, majority were male 55% (249), and rural residents 79% (356), with a mean age of 34 (±11.6) years. Median direct pre-diagnosis/diagnosis cost was $49 per patient. Median direct treatment cost was $36 per patient. Indirect pre-diagnostic and treatment costs were $416, or 79% of total patient costs, $528. The median total cost of TB care per household was $592; corresponding to 37% of median annual household income pre-TB. Most patients reported having to borrow money 212(47%), sell assets 42(9%), or both 144(32%) to cope with the cost of care. Following an episode of TB, household income reduced increasing the proportion of households classified as poor from 54% to 79%. Before TB illness, independent predictors of household poverty were; rural residence (adjusted odds ratio [aOR] 2.8), HIV-positive status (aOR 4.8), and care-seeking at a private facility (aOR 5.1). After TB care, independent determinants of household poverty were; younger age (≤35 years; aOR 2.4), male gender (aOR 2.1), and HIV-positive status (aOR 2.5).

Conclusion

Patient and household costs for TB care are potentially catastrophic even where services are provided free-of-charge. There is an urgent need to implement strategies for TB care that are affordable for the poor.     

Patient Characteristics Associated with Measurement of Routine Diabetes Care: An Observational Study

Background

Non-modifiable patient characteristics, including age, gender, ethnicity as well as the occurrence of multi-morbidities, are associated with processes and outcomes of diabetes care. Information on these factors can be used in case mix adjustment of performance measures. However, the practical relevance of such adjustment is not clear. The aim of this study was to assess the strength of associations between patient factors and diabetes care processes and outcomes.

Methods

We performed an observational study based on routinely collected data of 12,498 diabetes patients in 59 Dutch primary care practices. Data were collected on patient age, gender, whether the patient lived in a deprived area, body mass index and the co-occurrence of cardiovascular disease, chronic obstructive pulmonary disease, depression or anxiety. Outcomes included 6 dichotomous measures (3 process and 3 outcome related) regarding glycosylated hemoglobin, systolic blood pressure and low density lipoprotein-cholesterol. We performed separate hierarchical logistic mixed model regression models for each of the outcome measures.

Results

Each of the process measure models showed moderate effect sizes, with pooled areas under the curve that varied between 0.66 and 0.76. The frequency of diabetes related consultations as a measure of patient compliance to treatment showed the strongest association with all process measures (odds ratios between 5.6 and 14.5). The effect sizes of the outcome measure models were considerably smaller than the process measure models, with pooled areas under the curve varying from 0.57 to 0.61.

Conclusions

Several non-modifiable patient factors could be associated with processes and outcomes of diabetes care. However, associations were small. These results suggest that case-mix correction or stratification in assessing diabetes care has limited practical relevance.     

Reappearance of Aedes aegypti (Diptera: Culicidae) in Lima, Peru

We report here the reappearance of Aedes aegypti in the Rimac district, and summarize the history of this mosquito species in Peru since its first detection in 1852. On March 17 2000 were found Ae. aegypti and Culex quinquefasciatus in Mariscal Castilla town, Flor de Amancaes, San Juan de Amancaes, El Altillo and Santa Rosa in the Rimac district, Lima Province.     

Poor Survival in Rheumatoid Arthritis Associated with Bronchiectasis: A Family-Based Cohort Study

Background

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.

Methods

We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.

Results

During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5–48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1–81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1–113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4–37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10⁻⁵).

Conclusion

DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.