Sheela V. Shenoi

Extensively Drug-Resistant Tuberculosis: A New Face to an Old Pathogen

The presence and consequences of resistance to drugs used for the treatment of tuberculosis have long been neglected. The recent detection and recognition of widespread multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have raised interest and concern among clinicians and public health authorities globally. In this article, we describe the current global status of drug-resistant tuberculosis. We discuss the development of resistance, current management, and strategies for control.

Transmission of Drug-Susceptible and Drug-Resistant Tuberculosis and the Critical Importance of Airborne Infection Control in the Era of HIV Infection and Highly Active Antiretroviral Therapy Rollouts

Comprehensive and successful tuberculosis (TB) care and treatment must incorporate effective airborne infection-control strategies. This is particularly and critically important for health care workers and all persons with or at risk of human immunodeficiency virus (HIV) infection. Past and current outbreaks and epidemics of drug-susceptible, multidrug-resistant, and extensively drug-resistant TB have been fueled by HIV infection, with high rates of morbidity and mortality and linked to the absence or limited application of airborne infection-control strategies in both resource-rich and resource-limited settings. Airborne infection-control strategies are available--grouped into administrative, environmental, and personal protection categories--and have been shown to be associated with decreases in nosocomial transmission of TB; their efficacy has not been fully demonstrated, and their implementation is extremely limited, particularly in resource-limited settings. New research and resources are required to fully realize the potential benefits of infection control in the era of TB and HIV epidemics.

Multidrug-resistant and extensively drug-resistant tuberculosis: consequences for the global HIV community

Purpose of review Physicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within the HIV community in order to guide clinical care, research and resource allocation. Recent findings Extensively drug-resistant TB can no longer be considered as occurring in isolated outbreaks as it has been reported in 45 countries from all regions of the world. HIV has been associated as an independent risk factor for infection with drug-resistant TB. HIV patients appear more likely to suffer from primary, transmitted resistance as opposed to developing acquired resistance during the course of treatment for TB. New rapid diagnostics offer promise of providing clinically useful first-line drug susceptibility information but require validation in HIV patients and smear negative individuals. Demonstration projects of community-based treatment of drug-resistant TB and integration of TB and HIV care provide opportunities to decentralize management of drug-resistant TB. Summary Multidrug-resistant and extensively drug-resistant TB disproportionately affect HIV patients and result in increased morbidity and mortality. In this study, we address these challenging issues and offer some short-term and longer term strategies for their alleviation.

Transmission of Tuberculosis in Resource-Limited Settings

Unrecognized transmission is a major contributor to ongoing TB epidemics in high-burden, resource-constrained settings. Limitations in diagnosis, treatment, and infection control in health-care and community settings allow for continued transmission of drug-sensitive and drug-resistant TB, particularly in regions of high HIV prevalence. Health-care facilities are common sites of TB transmission. Improved implementation of infection control practices appropriate for the local setting and in combination, has been associated with reduced transmission. Community settings account for the majority of TB transmission and deserve increased focus. Strengthening and intensifying existing high-yield strategies, including household contact tracing, can reduce onward TB transmission. Recent studies documenting high transmission risk community sites and strategies for community-based intensive case finding hold promise for feasible, effective transmission reduction. Infection control in community settings has been neglected and requires urgent attention. Developing and implementing improved strategies for decreasing transmission to children, within prisons and of drug-resistant TB are needed.

Natural ventilation reduces high TB transmission risk in traditional homes in rural KwaZulu-Natal, South Africa

BackgroundTransmission of drug susceptible and drug resistant TB occurs in health care facilities, and community and households settings, particularly in highly prevalent TB and HIV areas. There is a paucity of data regarding factors that may affect TB transmission risk in household settings. We evaluated air exchange and the impact of natural ventilation on estimated TB transmission risk in traditional Zulu homes in rural South Africa.MethodsWe utilized a carbon dioxide decay technique to measure ventilation in air changes per hour (ACH). We evaluated predominant home types to determine factors affecting ACH and used the Wells-Riley equation to estimate TB transmission risk.ResultsTwo hundred eighteen ventilation measurements were taken in 24 traditional homes. All had low ventilation at baseline when windows were closed (mean ACH = 3, SD = 3.0), with estimated TB transmission risk of 55.4% over a ten hour period of exposure to an infectious TB patient. There was significant improvement with opening windows and door, reaching a mean ACH of 20 (SD = 13.1, p < 0.0001) resulting in significant decrease in estimated TB transmission risk to 9.6% (p < 0.0001). Multivariate analysis identified factors predicting ACH, including ventilation conditions (windows/doors open) and window to volume ratio. Expanding ventilation increased the odds of achieving ≥12 ACH by 60-fold.ConclusionsThere is high estimated risk of TB transmission in traditional homes of infectious TB patients in rural South Africa. Improving natural ventilation may decrease household TB transmission risk and, combined with other strategies, may enhance TB control efforts.

Lower back pain caused by tophaceous gout of the spine

A 75-year-old man with a history of gout presented with 5 days of fever and diffuse lower back pain. His temperature was 101.5 °F, and he had tenderness over both thoracic and lumbar vertebrae. His neurologic examination was largely normal. Erythrocyte sedimentation rate was 100 mm/h, and serum uric acid 18.6 …

Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among hospitalised patients with tuberculosis in rural Kwazulu-Natal.

BACKGROUND There is little information regarding the presence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA), an important nosocomial pathogen, in rural African hospitals. OBJECTIVES To determine the prevalence of MRSA colonisation in patients admitted to a rural hospital with tuberculosis (TB) in an endemic HIV area and to describe transmission dynamics and resistance patterns among MRSA isolates. METHODS A prospective prevalence survey in the adult TB wards of the Church of Scotland Hospital, a provincial government district hospital in Tugela Ferry, KwaZulu-Natal. Patients were eligible if over the age of 15 and admitted to the TB wards between 15 November and 15 December 2008. Nasal swabs were cultured within 24 hours of admission and repeated at hospital-day 14 or upon discharge. Susceptibility testing was performed with standard disk diffusion. Demographic and clinical information was extracted from medical charts. RESULTS Of 52 patients with an admission nasal swab, 11 (21%) were positive for MRSA. An additional 4 (10%) of patients with negative admission swabs were positive for MRSA on repeat testing. MRSA carriage on admission was more common among patients with previous hospitalisation, and among HIV-infected patients was significantly associated with lower CD4 counts (p = 0.03). All MRSA isolates were resistant to cotrimoxazole, and 74% were resistant to > 5 dclasses of antibiotics; all retained susceptibility to vancomycin. CONCLUSIONS A high prevalence of multidrug-resistant MRSA nasal carriage was found. Studies are needed to validate nosocomial acquisition and to evaluate the impact of MRSA on morbidity and mortality among TB patients in similar settings.

Survival from XDR-TB Is Associated with Modifiable Clinical Characteristics in Rural South Africa

Background Drug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drug-resistant TB (XDR-TB), particularly those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected. Methodology/Principal Findings A retrospective case control study was conducted of XDR-TB patients diagnosed from 2005–2008. Survivors, those alive at 180 days from diagnostic sputum collection date, were compared with controls who died within 180 days. Clinical, laboratory and microbiological correlates of survival were assessed in 69 survivors (median survival 565 days [IQR 384–774] and 73 non-survivors (median survival 34 days [IQR 18–90]). Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative AFB smear (AOR 8.4, CI 1.84–38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22–1.02), CD4>200 cells/mm3 (AOR 11.53, 1.1–119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16–376.83) were independently associated with survival from XDR-TB. Conclusions/Significance Survival from XDR-TB with HIV-coinfection is associated with less advanced stages of both diseases at time of diagnosis, absence of laboratory markers indicative of multiorgan dysfunction, and provision of antiretroviral therapy. Survival can be increased by addressing these modifiable risk factors through policy changes and improved clinical management. Health planners and clinicians should develop programmes focusing on earlier case finding and integration of HIV and drug-resistant TB diagnostic, therapeutic, and preventive activities.

Trends in hospital deaths among human immunodeficiency virus–infected patients during the antiretroviral therapy era, 1995 to 2011

OBJECTIVE Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality. METHODS We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths. RESULTS In-hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of ≤400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively. CONCLUSIONS Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients.

Active case finding for tuberculosis among people who inject drugs on methadone treatment in Dar es Salaam, Tanzania

SETTING Active case finding is a World Health Organization (WHO) endorsed strategy for improving tuberculosis (TB) case detection. Despite WHO recommendations for active case finding among people who inject drugs (PWID), few studies have been published. The historical focus of case finding has been in populations that are human immunodeficiency virus-positive, incarcerated or at higher occupational risk. OBJECTIVE We sought to examine the yield of active case finding among PWID newly started on methadone in Tanzania. DESIGN Of 222 methadone clients, 156 (70%) met with study administrators; 150 consented to participate, 139 (93%) of whom were male. The median age was 34 years. A symptom-based questionnaire was developed by the investigators and administered to every consenting patient by a native Swahili speaker. RESULTS Of the 150 patients surveyed, 16 (11%) had one or more TB symptoms and were referred for laboratory testing. Six new TB cases were identified in this active case finding program, with a prevalence of 4%. CONCLUSION This study presents the first data on TB prevalence in a population of PWID in Tanzania. This prevalence is 23 times that of the general Tanzanian TB prevalence of 0.2%. These results have significant implications for TB control.