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.     

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

Background

Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.

Methods

Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.

Results

Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.

Conclusion

In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.     

Evaluation of TNF-α, IL-10 and IL-6 Cytokine Production and Their Correlation with Genotype Variants amongst Tuberculosis Patients and Their Household Contacts

Background

Household contacts of diagnostically established tuberculosis (TB) patients are highly susceptible to disease development. It is surmised that cytokines perhaps play a synergistic and a prognostic role in the activation of the otherwise latent infection in these house hold contacts. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating the immune regulation and the progression of the disease. The cytokines thus released in a paracrine manner in serum may also provide an indirect measure of the cytokine function.

Objective

The present study was aimed to evaluate the levels of TNF-α, IL-10 & IL-6 cytokines and their correlation with genotype variants amongst tuberculosis patients and their household contacts.

Methods

The cytokine levels were estimated in serum by enzyme-linked immunosorbent assay (ELISA) and their polymorphisms were studied by amplification refractory mutation system polymerase chain reaction (ARMs PCR) in active pulmonary tuberculosis patients (APTB = 150), household contacts (HHC = 190), and healthy controls (HC = 150).

Results

The median values of TNF-α cytokine were significantly high among APTB and HHC compared to HCs (P< 0.0001 and 0.0001). IL-6 levels also were elevated among APTB compared to HHC and HC, and a significant difference was observed between APTB and HHC at P<0.0001; APTB & HC at P< 0.04; HHC & HC at P< 0.01. The IL-10 levels were low in APTB compared to HHC and HCs and no significant difference was observed. TNF-α/IL-10 ratio was significant and indicated Th1 predominance in APTB and HHC. IL-6/IL-10 showed pronounced Th1 expression in APTB and Th2 in HHC and HC. The ROC analysis indicated that both IL-10 and IL-6 can be used to decide the risk of exposed individual to a disease. The results of multivariate analysis indicate that IL-10 (-1082) GA genotype was significantly associated with p<0.028 in APTB. No significant association was observed between genotypes, other serum cytokine levels and clinical characteristics between APTB, HHC and HCs.

Conclusion

Large sample size with follow-up at different time points may further illuminate the role of IL-10 and IL-6 cytokines as a prognostic marker in house hold contacts.     

Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics

Rationale

The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10–20% of individuals, but the underlying mechanisms are poorly understood.

Methods

We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.

Measurements and Results

We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02–1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99–1.98, p = 0.06).

Conclusions

We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.     

Imaging Features of Pulmonary CT in Type 2 Diabetic Patients with Multidrug-Resistant Tuberculosis

Background

Until now, radiographic manifestations of multidrug-resistant pulmonary tuberculosis (MDR- TB) in patients with diabetes mellitus (DM) have not been reported. We conducted a study to investigate the imaging features of pulmonary computed tomography (CT) for type 2 diabetic (T2DM) patients with MDR-TB.

Methods

The clinical data and pulmonary CT findings of 39 type 2 diabetic patients with MDR-TB, 46 type 2 diabetic patients with drug-susceptible tuberculosis (DS-TB), and 72 pure drug-susceptible TB cases (without T2DM and MDR) treated at Dalian Tuberculosis Hospital from 2012 to 2015 were collected, and the clinical features and imaging differences of the three groups were compared.

Results

The clinical characteristics of the three groups of patients were not significantly different except with respect to age and previous treatment history. However, on imaging, the patients with MDR-TB showed consolidation in and above the pulmonary segments was significantly more extensive than that seen in the DS-TB group with or without T2DM.

Conclusion

Consolidation in or above multiple pulmonary segments with multiple mouth-eaten cavities and bronchial damage on pulmonary CT images in type 2 diabetic patients with tuberculosis suggests the possibility of multi-drug resistance.     

Impact of Intensive Handwashing Promotion on Secondary Household Influenza-Like Illness in Rural Bangladesh: Findings from a Randomized Controlled Trial

Rationale

There is little evidence for the efficacy of handwashing for prevention of influenza transmission in resource-poor settings. We tested the impact of intensive handwashing promotion on household transmission of influenza-like illness and influenza in rural Bangladesh.

Methods

In 2009–10, we identified index case-patients with influenza-like illness (fever with cough or sore throat) who were the only symptomatic person in their household. Household compounds of index case-patients were randomized to control or intervention (soap and daily handwashing promotion). We conducted daily surveillance and collected oropharyngeal specimens. Secondary attack ratios (SAR) were calculated for influenza and ILI in each arm. Among controls, we investigated individual risk factors for ILI among household contacts of index case-patients.

Results

Among 377 index case-patients, the mean number of days between fever onset and study enrollment was 2.1 (SD 1.7) among the 184 controls and 2.6 (SD 2.9) among 193 intervention case-patients. Influenza infection was confirmed in 20% of controls and 12% of intervention index case-patients. The SAR for influenza-like illness among household contacts was 9.5% among intervention (158/1661) and 7.7% among control households (115/1498) (SAR ratio 1.24, 95% CI 0.92–1.65). The SAR ratio for influenza was 2.40 (95% CI 0.68–8.47). In the control arm, susceptible contacts <2 years old (RR_adj 5.51, 95% CI 3.43–8.85), those living with an index case-patient enrolled ≤24 hours after symptom onset (RR_adj 1.91, 95% CI 1.18–3.10), and those who reported multiple daily interactions with the index case-patient (RR_adj 1.94, 95% CI 1.71–3.26) were at increased risk of influenza-like illness.

Discussion

Handwashing promotion initiated after illness onset in a household member did not protect against influenza-like illness or influenza. Behavior may not have changed rapidly enough to curb transmission between household members. A reactive approach to reduce household influenza transmission through handwashing promotion may be ineffective in the context of rural Bangladesh.

Trial Registration

ClinicalTrials.gov NCT00880659     

High Utility of Contact Investigation for Latent and Active Tuberculosis Case Detection among the Contacts: A Retrospective Cohort Study in Tbilisi,Georgia, 2010–2011

Setting

The study was conducted at the National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Georgia.

Objective

To assess the utility of contact investigation for tuberculosis (TB) case detection. We also assessed the prevalence and risk factors for active TB disease and latent TB infection (LTBI) among contacts of active pulmonary TB cases.

Design

A retrospective cohort study was conducted among the contacts of active pulmonary TB cases registered in 2010–2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were investigated according to an “invitation model”: they were referred to the NCTBLD by the index case; were queried about clinical symptoms suggestive of active TB disease; tuberculin skin testing and chest radiographs were performed. Demographic, laboratory, and clinical data of TB patients and their contacts were abstracted from existing records up to February 2013.

Results

869 contacts of 396 index cases were enrolled in the study; a median of 2 contacts were referred per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow-up period (mean follow up of 21 months) (incident TB cases). The incidence rate of active TB disease among contacts was 1126.0 per 100 000 person years (95% CI 655.7–1802.0 per 100,000 person-years). Among the 402 contacts who had a tuberculin skin test (TST) performed, 52.7% (95% CI 47.7–57.7%) had LTBI.

Conclusions

A high prevalence of LTBI and active TB disease was found among the contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an “invitation” model of contact investigation was an effective method of case detection. Therefore, contact investigation should be scaled up in Georgia.     

Patient and Provider Reported Reasons for Lost to Follow Up in MDRTB Treatment: A Qualitative Study from a Drug Resistant TB Centre in India

Introduction

Multidrug-resistant Tuberculosis (MDR TB) is emerging public health concern globally. Lost to follow-up (LTFU) is one of the key challenge in MDRTB treatment. In 2013, 18% of MDR TB patients were reported LTFU in India. A qualitative study was conducted to obtain better understanding of both patient and provider related factors for LTFU among MDR TB treatment.

Methods

Qualitative semi-structured personal interviews were conducted with 20 MDRTB patients reported as LTFU and 10 treatment providers in seven districts linked to Nagpur Drug resistant TB Centre (DRTBC) during August 2012–February 2013. Interviews were transcribed and inductive content analysis was performed to derive emergent themes.

Results

We found multiple factors influencing MDR TB treatment adherence. Barriers to treatment adherence included drug side effects, a perceived lack of provider support, patient financial constraints, conflicts with the timing of treatment services, alcoholism and social stigma.

Conclusions

Patient adherence to treatment is multi-factorial and involves individual patient factors, provider factors, and community factors. Addressing issue of LTFU during MDRTB treatment requires enhanced efforts towards resolving medical problems like adverse drug effects, developing short duration treatment regimens, reducing pill burden, motivational counselling, flexible timings for DOT services, social, family support for patients & improving awareness about disease.     

Comparative Meta-Analysis of Tuberculosis Contact Investigation Interventions in Eleven High Burden Countries

Background

Screening of household contacts of tuberculosis (TB) patients is a recommended strategy to improve early case detection. While it has been widely implemented in low prevalence countries, the most optimal protocols for contact investigation in high prevalence, low resource settings is yet to be determined. This study evaluated contact investigation interventions in eleven lower and middle income countries and reviewed the association between context or program-related factors and the yield of cases among contacts.

Methods

We reviewed data from nineteen first wave TB REACH funded projects piloting innovations to improve case detection. These nineteen had fulfilled the eligibility criteria: contact investigation implementation and complete data reporting. We performed a cross-sectional analysis of the percentage yield and case notifications for each project. Implementation strategies were delineated and the association between independent variables and yield was analyzed by fitting a random effects logistic regression.

Findings

Overall, the nineteen interventions screened 139,052 household contacts, showing great heterogeneity in the percentage yield of microscopy confirmed cases (SS+), ranging from 0.1% to 6.2%). Compared to the most restrictive testing criteria (at least two weeks of cough) the aOR’s for lesser (any TB related symptom) and least (all contacts) restrictive testing criteria were 1.71 (95%CI 0.94−3.13) and 6.90 (95% CI 3.42−13.93) respectively. The aOR for inclusion of SS- and extra-pulmonary TB was 0.31 (95% CI 0.15−0.62) compared to restricting index cases to SS+ TB. Contact investigation contributed between <1% and 14% to all SS+ cases diagnosed in the intervention areas.

Conclusions

This study confirms that high numbers of active TB cases can be identified through contact investigation in a variety of contexts. However, design and program implementation factors appear to influence the yield of contact investigation and its concomitant contribution to TB case detection.     

A Comparison of Accelerometer Cut-Points among Individuals with Coronary Artery Disease

Background

Accurate assessment of physical activity among coronary artery disease patients is important for assessing adherence to interventions. The study compared moderate-to-vigorous physical intensity activity and relationships with cardiometabolic health/fitness indicators using accelerometer cut-points developed for coronary artery disease patients versus those developed in younger and middle-aged adults.

Methods

A total of 231 adults with coronary artery disease wore an Actigraph GT3X accelerometer for ≥4 days (≥10 hours/day). Moderate-to-vigorous intensity physical activity between cut-points was compared using Bland-Altman analyses. Partial spearman correlations assessed relationships between moderate-to-vigorous intensity physical activity from each cut-point with markers of cardiometabolic health and fitness while controlling for age and sex.

Results

Average time spent in bouts of moderate-to-vigorous intensity physical activity using coronary artery disease cut-points was significantly higher than the young (mean difference: 13.0±12.8 minutes/day) or middle-aged (17.0±15.2 minutes/day) cut-points. Young and middle-aged cut-points were more strongly correlated with body mass index, waist circumference and systolic blood pressure, while coronary artery disease cut-points had stronger relationships with triglycerides, high-density and low-density lipoproteins. All were similarly correlated with measures of fitness.

Conclusion

Researchers need to exert caution when deciding on which cut-points to apply to their population. Further work is needed to validate which cut-points provide a true reflection of moderate-to-vigorous intensity physical activity and to examine relationships among patients with varying fitness.     

A Household-Based Study of Contact Networks Relevant for the Spread of Infectious Diseases in the Highlands of Peru

Background

Few studies have quantified social mixing in remote rural areas of developing countries, where the burden of infectious diseases is usually the highest. Understanding social mixing patterns in those settings is crucial to inform the implementation of strategies for disease prevention and control. We characterized contact and social mixing patterns in rural communities of the Peruvian highlands.

Methods and Findings

This cross-sectional study was nested in a large prospective household-based study of respiratory infections conducted in the province of San Marcos, Cajamarca-Peru. Members of study households were interviewed using a structured questionnaire of social contacts (conversation or physical interaction) experienced during the last 24 hours. We identified 9015 reported contacts from 588 study household members. The median age of respondents was 17 years (interquartile range [IQR] 4–34 years). The median number of reported contacts was 12 (IQR 8–20) whereas the median number of physical (i.e. skin-to-skin) contacts was 8.5 (IQR 5–14). Study participants had contacts mostly with people of similar age, and with their offspring or parents. The number of reported contacts was mainly determined by the participants’ age, household size and occupation. School-aged children had more contacts than other age groups. Within-household reciprocity of contacts reporting declined with household size (range 70%-100%). Ninety percent of household contact networks were complete, and furthermore, household members'' contacts with non-household members showed significant overlap (range 33%-86%), indicating a high degree of contact clustering. A two-level mixing epidemic model was simulated to compare within-household mixing based on observed contact networks and within-household random mixing. No differences in the size or duration of the simulated epidemics were revealed.

Conclusion

This study of rural low-density communities in the highlands of Peru suggests contact patterns are highly assortative. Study findings support the use of within-household homogenous mixing assumptions for epidemic modeling in this setting.     

A Bundle of Services Increased Ascertainment of Tuberculosis among HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa

Objectives

To report on trends of tuberculosis ascertainment among HIV patients in a rural HIV cohort in Tanzania, and assessing the impact of a bundle of services implemented in December 2012, consisting of three components:(i)integration of HIV and tuberculosis services; (ii)GeneXpert for tuberculosis diagnosis; and (iii)electronic data collection.

Design

Retrospective cohort study of patients enrolled in the Kilombero Ulanga Antiretroviral Cohort (KIULARCO), Tanzania.)

Methods

HIV patients without prior history of tuberculosis enrolled in the KIULARCO cohort between 2005 and 2013 were included.Cox proportional hazard models were used to estimate rates and predictors of tuberculosis ascertainment

Results

Of 7114 HIV positive patients enrolled, 5123(72%) had no history of tuberculosis. Of these, 66% were female, median age was 38 years, median baseline CD4+ cell count was 243 cells/µl, and 43% had WHO clinical stage 3 or 4. During follow-up, 421 incident tuberculosis cases were notified with an estimated incidence of 3.6 per 100 person-years(p-y)[95% confidence interval(CI)3.26-3.97]. The incidence rate varied over time and increased significantly from 2.96 to 43.98 cases per 100 p-y after the introduction of the bundle of services in December 2012. Four independent predictors of tuberculosis ascertainment were identified:poor clinical condition at baseline (Hazard Ratio (HR) 3.89, 95% CI 2.87-5.28), WHO clinical stage 3 or 4 (HR 2.48, 95% CI 1.88-3.26), being antiretroviralnaïve (HR 2.97, 95% CI 2.25-3.94), and registration in 2013(HR 6.07, 95% CI 4.39-8.38).

Conclusion

The integration of tuberculosis and HIV services together with comprehensive electronic data collection and use of GeneXpert increased dramatically the ascertainment of tuberculosis in this rural African HIV cohort.     

Increase in the Number of Tuberculosis Cases Treated following Tuberculin Skin Testing in First-Year Schoolchildren in Madagascar

Background

Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts.

Methods

All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (≤5 mm, [5–15)mm, ≥15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories.

Results

We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category ≤5 mm, 3 in TST category [5–15) mm and 8 in TST category ≥15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST ≥5 mm group.

Conclusion

TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts.     

Secondary attack rate of tuberculosis in urban households in Kampala, Uganda

Background

Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case.

Methods

In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection. The ratio of these rates is the likelihood of progressive primary disease after recent household infection.

Results

The secondary attack rate for tuberculosis disease was 3.0% (95% confidence interval: 2.2, 3.8). The overall secondary attack rate for tuberculosis infection was 47.4 (95% confidence interval: 44.3, 50.6) and did not vary widely with age, HIV status or BCG vaccination. The risk for progressive primary disease was highest among the young or HIV infected and was reduced by BCG vaccination.

Conclusions

Early case detection and treatment may limit household transmission of M. tuberculosis. Household members at high risk for disease should be protected through vaccination or treatment of latent tuberculosis infection.     

Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa

Objective

To report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB.

Design

A prospective cohort study in the Matlosana sub-district of North West Province, South Africa.

Methods

Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined.

Results

For 2,377 household contacts, the overall observed TB incidence rate was 1.3 per 100 person years (95% CI 0.9–1.9/100py) and TB incidence for individuals who were HIV-infected and HIV seronegative at baseline was 5.4/100py (95% CI 2.9–9.0/100py) and 0.7/100py (95% CI 0.3–1.4/100py), respectively. The overall HIV incidence rate was 2.2/100py (95% CI 1.3–8.4/100py).

Conclusions

In the year following a household case finding visit when household contacts were tested for TB and HIV, the incidence rate of both active TB and HIV infection was found to be extremely high. Clearly, implementing proven strategies to prevent HIV acquisition and preventing TB transmission and progression to disease remains a priority in settings such as South Africa.     

Pertussis Post-Exposure Prophylaxis among Household Contacts: A Cost-Utility Analysis

Background

Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective.

Methods

A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts (“infant”, “child”, and “adult”). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results.

Findings

Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and $2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976, $132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.

Interpretation

Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups.     

Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Background

Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.

Methods

Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.

Results

From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies.

Conclusions

Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.     

Household Transmission of Rotavirus in a Community with Rotavirus Vaccination in Quininde,Ecuador

Background

We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era.

Methods

Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (household-contact characteristics).

Results

Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was <18 months and had vomiting, with household contact <10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission.

Conclusion

Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees.     

Incidence and Prevalence of Tuberculosis among Household Contacts of Pulmonary Tuberculosis Patients in a Peri-Urban Population of South Delhi,India

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of mortality and morbidity across all age groups throughout the world, especially in developing countries.

Methodology/Principal Findings

In this study, we have included 432 open index cases with their 1608 household contacts in a prospective cohort study conducted from May 2007 to March 2009. The follow-up period was 2 years. All Index cases were diagnosed on the basis of suggestive signs and symptoms and sputum being AFB positive. Among the 432 index patients, 250 (57.9%) were males and 182 (42.1%) females; with mean age of 34±14.4 yr and 26±11.1 yr, respectively. Out of 1608 household contacts, 866 (53.9%) were males and 742 (46.1%) females; with mean age of 26.5±15.8 and 26.5±16.0 yr, respectively. Of the total 432 households, 304 (70.4%) had ≤4 members and 128 (29.6%) had ≥5 members. The median size of the family was four. Of the 1608 contacts, 1206 were able to provide sputum samples, of whom 83 (6.9%) were found MTB culture positive. Household contacts belonging to adult age group were predominantly (74, 89.2%) infected as compared to the children (9, 10.8%). On screening the contact relationship status with index patients, 52 (62.7%) were first-degree relatives, 18 (34.6%) second-degree relatives and 12 (14.5%) spouses who got infected from their respective index patients. Co-prevalent and incident tuberculosis was found in 52 (4.3%) and 31 (2.6%) contacts, respectively. In incident cases, the diagnosis could be made between 4 to 24 months of follow-up, after their baseline evaluation.

Conclusion

Active household contact investigation is a powerful tool to detect and treat tuberculosis at early stages and the only method to control TB in high-TB-burden countries.     

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.