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.     

Total Delay in Treatment among Smear Positive Pulmonary Tuberculosis Patients in Five Primary Health Centers,Southern Ethiopia: A Cross Sectional Study

Introduction

The global burden of Tuberculosis (TB) remains enormous. Delay in TB diagnosis may lead to a higher infectious pool in the community and a more advanced disease state at presentation increasing the risk of mortality. This study is conducted to determine the total delay before treatment among smear positive Pulmonary Tuberculosis (PTB) patients.

Methods

A health institution based cross sectional study was conducted in five primary health centers in southern Ethiopia from June to December 2012. A total of 328 smear positive PTB patients were enrolled in the study. A structured and pre-tested questionnaire was used. Median patient, diagnostic, and treatment delays were calculated to determine the total delay. Multiple logistic regression analysis was used to identify factors associated with total delay.

Results

The median patient, diagnostic, treatment and total delays measured in days were 30 (IQR 20.2, 60), 7 (IQR: 3, 14), 3 (IQR: 1, 4) and 45 (IQR: 34.5, 69.5) days respectively. Patients for whom treatment was not initiated within 45 days of onset of symptom(s) (total delay) constituted 49% of the study participants (59.5% among males and 39.2% among females; P<0.001). Total delay was found to be associated with: being female [AOR  = 0.34, 95% CI: 0.18–0.62], having attended tertiary level education [AOR  = 0.11, 95% CI: 0.02–0.55], perceived severity of stigma during the current TB disease course [AOR = 2. 18, 95% CI: 1.07, 4.42] and living in houses with higher family size [AOR = 0.26, 95% CI: 0.11, 0.61].

Conclusion

Total delay in treatment of TB is still high in the study area. Patient''s sex, perceived stigma, educational status and family size are significantly contributing for total delay. Therefore, a concerted effort should be taken in order to improve health seeking behavior of the community on TB and to reduce delays from seeking care after experiencing TB symptoms.     

Factors Associated with Problem Drinking among Women Employed in Food and Recreational Facilities in Northern Tanzania

Background

There is growing evidence that alcohol consumption is associated with increased risk of HIV infection. To determine factors associated with problem drinking, we analyzed data collected in two prospective cohorts of at-risk female food and recreational facility workers in northern Tanzania.

Methods

We enrolled HIV seronegative women aged 18–44 years and employed in the towns of Geita, Kahama, Moshi, and Shinyanga. At enrolment, women were interviewed to obtain information about alcohol use, using CAGE and AUDIT screening scales, and risk factors for HIV infection. Blood and genital samples were collected for detection of HIV and sexually transmitted infections (STIs). We characterized alcohol use, concordance, and agreement of the scales, and examined the associations between characteristics of participants and problem drinking as defined by both scales using logistic regression. Lastly, we assessed problem drinking as a risk factor for recent sexual behavior and prevalent STIs.

Results

Among enrollees, 68% women reported ever drinking alcohol; of these 76% reported drinking alcohol in the past 12 months. The prevalence of problem drinking was 20% using CAGE and 13% using AUDIT. Overall concordance between the scales was 75.0% with a Kappa statistic of 0.58. After adjusting for age, independent factors associated with problem drinking, on both scales, were marital status, occupation, facility type, increasing number of lifetime sexual partners, and transactional sex in the past 12 months. In addition, women who were problem drinkers on either scale were more likely to report having ≥1 sexual partner (CAGE: aOR = 1.56, 95% confidence interval, CI: 1.10–2.23; AUDIT: aOR = 2.00, 95% CI: 1.34–3.00) and transactional sex (CAGE: aOR = 1.79, 95% CI: 1.26–2.56; AUDIT: aOR = 1.51, 95% CI: 1.04–2.18), in the past 3 months.

Conclusion

These findings suggest that interventions to reduce problem drinking in this population may reduce high-risk sexual behaviors and contribute in lowering the risk of HIV infection.     

Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

Background

In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.

Methods and Findings

A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%).

Conclusions

For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors'' Summary     

Enhancing TB Case Detection: Experience in Offering Upfront Xpert MTB/RIF Testing to Pediatric Presumptive TB and DR TB Cases for Early Rapid Diagnosis of Drug Sensitive and Drug Resistant TB

Background

Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.

Methods

The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.

Results

4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8–13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5–11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2–5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1–99.9), with no statistically significant variation with respect to past history of treatment.

Conclusion

Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.     

Opportunities for Tuberculosis Diagnosis and Prevention among Persons Living with HIV: A Cross-Sectional Study of Policies and Practices at Four Large Ryan White Program-Funded HIV Clinics

Objective

We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics.

Methods

We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008–2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices.

Results

Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008–2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101–165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6–9.5), and employment (aOR = 1.9, 95% CI = 1.0–3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4–3.3), non-black race (aOR = 1.7, 95% CI = 1.3–2.5), and unemployment (aOR = 1.5, 95% CI = 1.1–2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention.

Conclusions

Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention.     

Active Case Finding of Tuberculosis (TB) in an Emergency Room in a Region with High Prevalence of TB in Brazil

Setting

Public hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection.

Objective

To determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis.

Methods

Cross sectional study. All patients ≥18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture.

Results

Among 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92–0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06–0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45–32.93; p<0.0001).

Conclusions

This study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting.     

Vitamin D Status among Pulmonary TB Patients and Non-TB Controls: A Cross-Sectional Study from Mwanza,Tanzania

Background

Little is known about vitamin D status in low-income populations burdened with infectious diseases. Hence, there is a need for data on correlates of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections.

Objective

To assess the role of pulmonary TB (PTB) and HIV as correlates of S-25(OH)D.

Design

Age-sex-matched cross-sectional study among PTB patients and non-TB controls.

Methods

PTB patients were categorized as sputum negative (PTB−) and positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex-matched neighbours to PTB+ patients. Height, weight, arm circumference and triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP) and α₁-acid glycoprotein (S-AGP) were determined. Linear regression analysis with controls and PTB patients combined was used to identify correlates of S-25(OH)D.

Results

S-25(OH)D data were available on 97.8% (1570) of 1605 participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S-AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2) nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9) nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95% CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not with infections or S-AGP in the model.

Conclusion

While S-25(OH)D may decline transiently during a mild acute phase response, it may increase if the acute phase response leads to loss of fat. The validity of S-25(OH)D as a marker of vitamin D status may be affected by infections.     

Low Birth Weight,Small for Gestational Age and Preterm Births before and after the Economic Collapse in Iceland: A Population Based Cohort Study

Objective

Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes.

Study design

The study population constituted all Icelandic women giving birth to live-born singletons from January 1^st 2006 to December 31^st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD''s) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6^th 2008.

Results

Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse.

Conclusion

The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation.     

Men Who Have Sex with Men (MSM) and Factors Associated with Not Using a Condom at Last Sexual Intercourse with a Man and with a Woman in Senegal

Background

Men who have sex with other men (MSM) are a vulnerable population in Africa that has been insufficiently explored. Given the high rate of bisexuality among MSM (73% in the past year), it is important to understand their risk-taking behaviors regarding both men and women.

Methodology/Principal Findings

A socio-behavioral survey was carried out in 2007 among 501 MSM recruited using the snowball sampling method. We explore in this article why a condom was not used during last sexual intercourse with a man and with a woman, taking into account the respondent''s characteristics, type of relationship and the context of the sexual act. In the survey, 489 men reported that they had had sexual intercourse at least once with another man during the previous year, and 358 with a man and with a woman. The main risk factors for not using a condom at last sexual intercourse with another man were having sex in a public place (aOR = 6.26 [95%CI: 2.71–14.46]), non-participation in an MSM prevention program (aOR = 3.47 [95%CI: 2.12–5.69]), a 19 years old or younger partner (aOR = 2.6 [95%CI: 1.23–4.53]), being 24 years or younger (aOR = 2.07 [95%CI: 1.20–3.58]) or being 35 years or over (aOR = 3.08 [95%CI:1.11–8.53]) and being unemployed (aOR = 0.36 [95%CI: 0.10–1.25]). The last sexual intercourse with the respondent''s wife was hardly ever protected (2%). With women, the other factors were a 15 years or younger partner (aOR = 6.45 [95%CI: 2.56–16.28]), being educated (primary: aOR = 0.45 [95%CI: 0.21–0.95], secondary or higher: aOR = 0.26 [95%CI: 0.11–0.62]), being a student (aOR = 2.20 [95%CI: 1.07–4.54]) or unemployed (aOR = 3.72 [95%CI: 1.31–10.61]) and having participated in a MSM prevention program (aOR = 0.57 [95%CI: 0.34–0.93]).

Conclusion

Having participated in a prevention program specifically targeting MSM constitutes a major prevention factor. However, these programs targeting MSM must address their heterosexual practices and the specific risks involved.     

Evaluation of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults

Background

In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB) in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays.

Methods and Findings

Cohort study of TB suspects in four tuberculosis (TB) clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9%) of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0%) agreed to be tested, 79 (7.0%) were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3%) with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB), 28.6% smear-positive PTB, 15.2% EPTB). The median time to TB treatment initiation was 5 days (IQR: 2–13 days), ranging from 2 days (IQR: 1–11.5 days) for EPTB, over 2.5 days (IQR: 1–4 days) for smear-positive PTB to 9 days (IQR: 3–17 days) for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%–73.6%) and 79.4% (95%CI: 74.8%–82.4%) respectively.

Conclusions

Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment initiation.     

In a Safety Net Population HPV4 Vaccine Adherence Worsens as BMI Increases

Objectives

Obesity adversely inhibits antibody response to vaccination. Three doses of HPV4 may or may not provide adequate long term protection against HPV 16/18 in obese females. The aim of this study was to determine whether adherence to HPV4 vaccination in a safety net population was reduced with increasing body mass index (BMI).

Methods

We designed a historical prospective study evaluating the number and dates of HPV4 dosing that occurred from July 1, 2006 through October 1, 2009 by the demographic characteristics of the 10–26 year old recipient females. The defined dosing intervals were adapted from the literature and obesity categories were defined by the WHO.

Results

1240 females with BMI measurements received at least one dose of HPV4; 38% were obese (class I, II and III) and 25% were overweight. Females with normal BMI received on-time triplet dosing significantly more often than did the obese class II and III females (30% vs. 18%, p<0.001). Obese class II/III females have a significant 45% less chance of completing the on-time triplet HPV4 series than normal women (OR = 0.55, 95% CI: 0.37, 0.83). Pregnancy history has a significant influence on BMI and HPV4 dosing compliance in this safety net population where 71% had been gravid. Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR = 0.39, 95% CI: 0.16, 0.95).

Conclusions

Obesity, as well as gravidity and Hispanic race, are risk factors for lack of HPV4 vaccine adherence among young females in a safety net population.     

Alcohol Consumption and Breast Cancer Risk among Women in Three Sub-Saharan African Countries

Background

Alcohol drinking is linked to the development of breast cancer. However, there is little knowledge about the impact of alcohol consumption on breast cancer risk among African women.

Methods

We conducted a case-control study among 2,138 women with invasive breast cancer and 2,589 controls in Nigeria, Cameroon, and Uganda from 1998 to 2013. A structured questionnaire was used to collect information on alcohol consumption, defined as consuming alcoholic beverages at least once a week for six months or more. Logistic regression was used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI).

Results

Among healthy controls, the overall alcohol consumption prevalence was 10.4%, and the prevalence in Nigeria, Cameroon, and Uganda were 5.0%, 34.6%, and 50.0%, respectively. Cases were more likely to have consumed alcohol (aOR = 1.62, 95% CI: 1.33–1.97). Both past (aOR = 1.54; 95% CI: 1.19–2.00) and current drinking (aOR = 1.71; 95% CI: 1.30–2.23) were associated with breast cancer risk. A dose-response relationship was observed for duration of alcohol drinking (P-trend <0.001), with 10-year increase of drinking associated with a 54% increased risk (95% CI: 1.29–1.84).

Conclusion

We found a positive relationship between alcohol consumption and breast cancer risk, suggesting that this modifiable risk factor should be addressed in breast cancer prevention programs in Africa.     

Seasonal Variations in Notification of Active Tuberculosis Cases in China, 2005–2012

Background

Although seasonal variation in tuberculosis (TB) incidence has been described in many countries, it remains unknown in China.

Methods

A time series decomposition analysis (X-12-ARIMA) was performed to examine the seasonal variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal amplitude was calculated for the evaluation of TB seasonal variation.

Results

A total of 7.78 million active TB cases were reported over a period of 8 years. A spring peak (April) was observed with seasonal amplitude of 46.3%, compared with the winter trough (February). Most cases in provinces with subtropical and tropical monsoon climate showed lower amplitudes than those in temperate continental, plateau and mountain climate regions. The magnitude of seasonality varied inversely with annual average temperature, r (95% CI) = -0.71 (-0.79, -0.61). The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients aged ≤14, 15–24, 25–44, 45–64, and ≥65 years, respectively. Students demonstrated greater seasonal amplitude than peasants, migrant workers and workers (115.3% vs. 43.5, 41.6 and 48.1%). Patients with pulmonary TB had lower amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB) (45.9% vs. 52.0 and 56.3%). Relapse cases with sputum smear positive TB (SS+ TB) had significantly higher seasonal amplitude compared to new cases with sputum smear positive TB (52.2% vs. 41.6%).

Conclusions

TB is a seasonal disease in China. The peak and trough of TB transmission actually are in winter and in autumn respectively after factors of delay are removed. Higher amplitudes of TB seasonality are more likely to happen in temperate continental, plateau and mountain climate regions and regions with lower annual average temperature, and young person, students, patients with EPTB and relapse cases with SS+ TB are more likely to be affected by TB seasonality.     

Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda

Rationale

The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.

Objective

To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.

Methods

We prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.

Results

477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).

Conclusions

Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.     

Tuberculosis Treatment Managed by Providers outside the Public Health Department: Lessons for the Affordable Care Act

Introduction

Tuberculosis (TB) requires at least six months of multidrug treatment and necessitates monitoring for response to treatment. Historically, public health departments (HDs) have cared for most TB patients in the United States. The Affordable Care Act (ACA) provides coverage for uninsured persons and may increase the proportion of TB patients cared for by private medical providers and other providers outside HDs (PMPs). We sought to determine whether there were differences in care provided by HDs and PMPs to inform public health planning under the ACA.

Methods

We conducted a retrospective, cross-sectional analysis of California TB registry data. We included adult TB patients with culture-positive, pulmonary TB reported in California during 2007–2011. We examined trends, described case characteristics, and created multivariate models measuring two standards of TB care in PMP- and HD-managed patients: documented culture conversion within 60 days, and use of directly observed therapy (DOT).

Results

The proportion of PMP-managed TB patients increased during 2007–2011 (p = 0.002). On univariable analysis (N = 4,606), older age, white, black or Asian/Pacific Islander race, and birth in the United States were significantly associated with PMP care (p<0.05). Younger age, Hispanic ethnicity, homelessness, drug or alcohol use, and cavitary and/or smear-positive TB disease, were associated with HD care. Multivariable analysis showed PMP care was associated with lack of documented culture conversion (adjusted relative risk [aRR] = 1.37, confidence interval [CI] 1.25–1.51) and lack of DOT (aRR = 8.56, CI 6.59–11.1).

Conclusion

While HDs cared for TB cases with more social and clinical complexities, patients under PMP care were less likely to receive DOT and have documented culture conversion. This indicates a need for close collaboration between PMPs and HDs to ensure that optimal care is provided to all TB patients and TB transmission is halted. Strategies to enhance collaboration between HDs and PMPs should be included in ACA implementation.     

Which Urban Migrants Default from Tuberculosis Treatment in Shanghai,China?

Background

Migration is a major challenge to tuberculosis (TB) control worldwide. TB treatment requires multiple drugs for at least six months. Some TB patients default before completing their treatment regimen, which can lead to ongoing infectiousness and drug resistance.

Methods

We conducted a retrospective analysis of 29,943 active TB cases among urban migrants that were reported between 2000 to 2008 in Shanghai, China. We used logistic regression models to identify factors independently associated with treatment defaults in TB patients among urban migrants during 2005-2008.

Results

Fifty-two percent of the total TB patients reported in Shanghai during the study period were among urban migrants. Three factors increased the odds of a treatment default: case management using self-administered therapy (OR, 5.84, 95% CI, 3.14-10.86, p<0.0005), being a retreatment case (OR, 1.47, 95% CI, 1.25-1.71, p<0.0005), and age >60 years old (OR, 1.33, 95% CI, 1.05-1.67, p=0.017). The presence of a cavity in the initial chest radiograph decreased the odds for a treatment default (OR, 0.87, 95% CI, 0.77-0.97, p=0.015), as did migration from central China (OR, 0.85, 95% CI, 0.73-0.99, p=0.042), case management by family members (OR, 0.73, 95% CI 0.66-0.81, p<0.0005), and the combination of case detection by a required physical exam and case management by health care staff (OR, 0.64, 95% CI, 0.45-0.93, p=0.019).

Conclusion

Among TB patients who were urban migrants in Shanghai, case management using self-administered therapy was the strongest modifiable risk factor that was independently associated with treatment defaults. Interventions that target retreated TB cases could also reduce treatment defaults among urban migrants. Health departments should develop effective measures to prevent treatment defaults among urban migrants, to ensure completion of therapy among urban migrants who move between cities and provinces, and to improve reporting of treatment outcomes.     

Socio-Demographic and Clinical Differences in Subjects with Tuberculosis with and without Diabetes Mellitus in Brazil – A Multivariate Analysis

Background

Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM.

Methods

Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients.

Results

Subjects with TB – DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26–1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03–2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60–0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51–0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51–0.86).

Conclusions

Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.     

Ethnic Variations in Severe Maternal Morbidity in the UK– A Case Control Study

Background

Previous studies showed a higher risk of maternal morbidity amongst black and other minority ethnic (BME) groups, but were unable to investigate whether this excess risk was concentrated within specific BME groups in the UK. Our aim was to analyse the specific risks and to investigate reasons for any disparity.

Methods

Unmatched case-control analysis using data from the United Kingdom Obstetric Surveillance System (UKOSS), February 2005-January 2013. Cases were 1,753 women who experienced severe morbidity during the peripartum period. Controls were 3,310 women who delivered immediately before the cases in the same hospital. Multivariable logistic regression modelling was used to adjust for known confounders and to understand their effects.

Results

Compared with white European women, the odds of severe maternal morbidity were 83% higher among black African women (adjusted odds ratio (aOR) = 1.83; 95% Confidence Interval (CI) = 1.39–2.40), 80% higher among black Caribbean (aOR = 1.80; 95% CI = 1.14–2.82), 74% higher in Bangladeshi (aOR = 1.74; 95% CI = 1.05–2.88), 56% higher in other non-whites (non-Asian) (aOR = 1.56; 95% CI = 1.05–2.33) and 43% higher among Pakistani women (aOR = 1.43; 95% CI = 1.07–1.92). There was no evidence of substantial confounding. Anaemia in current pregnancy, previous pregnancy problems, inadequate utilisation of antenatal care, pre-existing medical conditions, parity>3, and being younger and older were independent risk factors but, the odds of severe maternal morbidity did not differ by socioeconomic status, between smokers and non-smokers or by BMI.

Discussion

This national study demonstrates an increased risk of severe maternal morbidity among women of ethnic minority backgrounds which could not be explained by known risk factors for severe maternal morbidity.     

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Background

The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection.

Methods

CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance.

Results

Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35–0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99–1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4).

Conclusions

The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.