Building the Case for Localized Approaches to HIV: Structural Conditions and Health System Capacity to Address the HIV/AIDS Epidemic in Six US Cities.

Since the discovery of the secondary preventive benefits of antiretroviral therapy, national and international governing bodies have called for countries to reach 90% diagnosis, ART engagement and viral suppression among people living with HIV/AIDS. The US HIV epidemic is dispersed primarily across large urban centers, each with different underlying epidemiological and structural features. We selected six US cities, including Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle, with the objective of demonstrating the breadth of epidemiological and structural differences affecting the HIV/AIDS response across the US. We synthesized current and publicly-available surveillance, legal statutes, entitlement and discretionary funding, and service location data for each city. The vast differences we observed in each domain reinforce disparities in access to HIV treatment and prevention, and necessitate targeted, localized strategies to optimize the limited resources available for each city's HIV/AIDS response.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

How can mathematical models advance tuberculosis control in high HIV prevalence settings?

Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly.

Community-based multi-disease prevention campaigns for controlling human immunodeficiency virus-associated tuberculosis.

Human immunodeficiency virus (HIV) infection increases the risk of tuberculosis (TB) 21-34 fold, and has fuelled the resurgence of TB in sub-Saharan Africa. The World Health Organization (WHO) recommends the Three I's for HIV/TB (infection control, intensified case finding [ICF] and isoniazid preventive therapy) and earlier initiation of antiretroviral therapy for preventing TB in persons with HIV. Current service delivery frameworks do not identify people early enough to maximally harness the preventive benefits of these interventions. Community-based campaigns were essential components of global efforts to control major public health threats such as polio, measles, guinea worm disease and smallpox. They were also successful in helping to control TB in resource-rich settings. There have been recent community-based efforts to identify persons who have TB and/or HIV. Multi-disease community-based frameworks have been rare. Based on findings from a WHO meta-analysis and a Cochrane review, integrating ICF into the recent multi-disease prevention campaign in Kenya may have had implications in controlling TB. Community-based multi-disease prevention campaigns represent a potentially powerful strategy to deliver prevention interventions, identify people with HIV and/or TB, and link those eligible to care and treatment.

Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings.

The human immunodeficiency virus (HIV) and HIV-associated tuberculosis (TB-HIV) epidemics remain uncontrolled in many resource-limited regions, especially in sub-Saharan Africa. The scale of these epidemics requires the consideration of innovative bold interventions and 'out-of-the-box' thinking. To this end, a symposium entitled 'Controversies in HIV' was held at the 40th Union World Conference on Lung Health in Cancun, Mexico, in December 2009. The first topic debated, entitled 'Annual HIV testing and immediate start of antiretroviral therapy for all HIV-infected persons', received much attention at international conferences and in the literature in 2009. The second topic forms the subject of this article. The rationale for the use of empirical TB treatment is premised on the hypothesis that in settings worst affected by the TB-HIV epidemic, a subset of HIV-infected patients have such a high risk of undiagnosed TB and of associated mortality that their prognosis may be improved by immediate initiation of empirical TB treatment used in conjunction with antiretroviral therapy. In addition to morbidity and mortality reduction, additional benefits may include prevention of nosocomial TB transmission and TB preventive effect. Potential adverse consequences, however, may include failure to consider other non-TB diagnoses, drug co-toxicity, compromised treatment adherence, and logistical and resource challenges. There may also be general reluctance among national TB programmes to endorse such a strategy. Following fruitful debate, the conclusion that this strategy should be carefully evaluated in randomised controlled trials was strongly supported. This paper provides an in-depth consideration of this proposed intervention.

Cross-referral between voluntary HIV counselling and testing centres and TB services, Maharashtra, India, 2003-2004.

SETTING: India has a high tuberculosis (TB) burden, with 1.8 million new cases per year. Although an estimated 2.5 million people are infected with human immunodeficiency virus (HIV), the national HIV prevalence is <1%. India's size and diverse TB-HIV epidemiology pose a major challenge to the implementation of links between TB and HIV/AIDS programme services. METHODS: A pilot cross-referral initiative was instituted between voluntary counselling and testing centres (VCT) and the diagnostic and treatment facilities of the Revised National TB Control Programme (RNTCP) in four districts of Maharashtra, India. OBJECTIVE: To detect TB disease among VCT patients and selectively screen TB patients for referral to VCT services. RESULTS: Between July 2003 and June 2004, 336 (3%) of 9921 VCT patients were identified as TB suspects and 83 (29%) were diagnosed with TB disease. Of the 765 selectively referred TB cases, 181 (24%) were found to be HIV-positive, representing 11% of the newly detected persons living with HIV in the four districts. CONCLUSIONS: The pilot cross-referral initiative yielded significant numbers of active TB cases among VCT patients and HIV-positive persons among TB patients. Collaborative activities between HIV/AIDS and TB programmes need to be rapidly scaled up to other states in India.

Occupational transmission of Mycobacterium tuberculosis to health care workers in a university hospital in Lima, Peru.

From November 1996 through March 1997, presumptive active pulmonary tuberculosis (TB) was detected in 44 health care workers (HCWs) at a university hospital in Lima, Peru. To further assess the magnitude of the outbreak and determine risk factors for occupational Mycobacterium tuberculosis transmission, we identified HCWs in whom active pulmonary TB was diagnosed from January 1994 through January 1998, calculated rates by year and hospital work area, and conducted a tuberculin skin test (TST) survey. Thirty-six HCWs had confirmed active pulmonary TB. The rate of TB was significantly higher among the 171 HCWs employed in the laboratory than among HCWs employed in all other areas. In multivariate analysis, the only independent risk factor for HCW M. tuberculosis infection in HWCs employed in the laboratory was the use of common staff areas. Very high rates of active pulmonary TB were detected among HCWs at this hospital, and occupational acquisition in the laboratory was associated with HCW-to-HCW transmission.

Drug-resistant tuberculosis in foreign-born persons from Mexico, the Philippines, and Vietnam-United States, 1993-1997.

SETTING: Foreign-born persons in the United States represent a growing proportion of the nation's tuberculosis (TB) cases. OBJECTIVE: To characterize drug resistance patterns in foreign-born TB patients from the three most common birth countries. DESIGN: A descriptive analysis of national TB surveillance data for 1993-1997. TB case reports for foreign-born persons who were at least 15 years old and born either in Mexico (6221), the Philippines (3624), or Vietnam (3351) were included. RESULTS: Among those with no prior history of TB, the proportions with isoniazid-resistant TB and MDR-TB (resistance to at least isoniazid and rifampin) were 9.2% and 1.6% for persons from Mexico, 13.7% and 1.4% for those from the Philippines, and 17.8% and 1.4% for those from Vietnam. Levels of isoniazid resistance and MDR-TB did not change during the 5-year study period. Levels of isoniazid resistance decreased with older age for persons with no prior TB from all three countries; however, rates of MDR-TB did not vary with age. Persons with <1 year of residence in the US were more likely to have MDR-TB; however, duration of residence in the US was not associated with isoniazid resistance. CONCLUSION: Increased drug resistance in younger and more recent arrivals suggests that vigorous efforts to prevent further development of MDR-TB in the three countries are essential.

Survey of drug resistance of Mycobacterium tuberculosis in 3 Mexican states, 1997.

BACKGROUND: Drug resistance threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Mexico. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Mexico. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in the states of Baja California, Sinaloa, and Oaxaca, Mexico. We performed cultures and drug susceptibility testing on M tuberculosis isolates from patients with newly diagnosed, smear-positive TB from April 1 to October 31, 1997. RESULTS: Mycobacterium tuberculosis was isolated from 460 (75%) of the 614 patients. Levels of resistance in new and retreatment TB cases to 1 or more of the 3 current first-line drugs used in Mexico (isoniazid, rifampin, and pyrazinamide) were 12.9% and 50.5%, respectively; the corresponding levels of multi-drug-resistant TB were 2.4% and 22.4%. Retreatment cases were significantly more likely than new cases to have isolates resistant to 1 or more of the 3 first-line drugs (relative risk [RR], 3.9; 95% confidence interval [CI], 2.8-5.5), to have isoniazid resistance (RR, 3.6; 95% CI, 2.5-5.2), and to have multi-drug-resistant TB (RR, 9.4; 95% CI, 4.3-20.2). CONCLUSIONS: This population-based study of M tuberculosis demonstrates moderately high levels of drug resistance. Important issues to consider in the national strategy to prevent M tuberculosis resistance in Mexico include consideration of the most appropriate initial therapy in patients with TB, the treatment of patients with multiple drug resistance, and surveillance or periodic surveys of resistance among new TB patients to monitor drug resistance trends.

Tuberculosis among foreign-born residents of southern Florida, 1995.

OBJECTIVE: To examine the characteristics of foreign-born people with tuberculosis (TB) in Southern Florida, their contribution to the total number of TB cases, and available data on their HIV status as well as to determine the number of cases detected by the overseas medical screening of immigrants and refugees. METHODS: The authors reviewed TB cases reported by Broward, Dade, and Palm Beach counties in 1995. Case records were matched against the CDC Division of Quarantine database of immigrants and refugees suspected to have TB at the time of visa application overseas. RESULTS: Nearly half (49%) of TB cases in the three counties were among people born outside the United States--34% in Broward County, 58% in Dade County, and 40% in Palm Beach County. A high percentage (26%) were co-infected with HIV. Of those with known date of arrival, 68% had been in the United States for five or more years. Only three cases had been identified by overseas immigrant screening. CONCLUSIONS: A low percentage of TB cases in foreign-born people were identified through the overseas screening system. Controlling TB in South Florida will require efforts targeted toward high risk populations, including people with HIV infection.