High rate of hypothyroidism among patients treated for multidrug-resistant tuberculosis in Lesotho.

BACKGROUND: Hypothyroidism is a known side effect of treatment for multidrug-resistant tuberculosis (MDR-TB), but it is considered to be rare. Hypothyroidism has vague and non-specific symptoms, and can be easily missed by clinicians. OBJECTIVE: To report the high rate of hypothyroidism in a cohort of MDR-TB patients in Lesotho and to describe our approach to diagnosis and management. DESIGN: A retrospective study of 212 patients who initiated treatment for MDR-TB in Lesotho between 27 July 2007 and 24 March 2009 was performed. RESULTS: Among 186 patients screened, 129 (69%) had hypothyroidism, defined as at least one documented thyroid-stimulating hormone (TSH) result > 10.0 mIU/l; 100 (54%) patients had a maximum TSH > 20.0 mIU/l. At 93 days after starting MDR-TB treatment, half of the patients had developed hypothyroidism. CONCLUSION: Hypothyroidism may be more common during MDR-TB treatment than previously recognized. Screening all patients, even those without symptoms, for hypothyroidism within 2-3 months of starting MDR-TB treatment should be considered until prospective studies can inform screening guidelines.

Economic risk factors for HIV infection among women in rural Haiti: implications for HIV prevention policies and programs in resource-poor settings.

AIMS: The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population. METHODS: Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%. RESULTS: In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection. CONCLUSIONS: Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.

Expanding global HIV treatment: case studies from the field.

In the last 25 years, human immunodeficiency virus (HIV) has become the leading infectious killer of adults globally, with an estimated 44 million people infected with the virus worldwide. Most of these individuals live in poor regions of the world, particularly sub-Saharan Africa. Although a great deal of work has been done in identifying and treating individuals with the disease, there has been little action to date to address the complex socioeconomic factors that lie at the heart of this global pandemic. Understanding and responding to such factors is of paramount importance if HIV infection is to be managed in a meaningful way. This article explores the social context of people living with HIV in three different geographic and epidemiologic settings and highlights the social factors that shape and define an individual's risk of acquiring HIV. It also discusses unique programs aimed at addressing the complex realities of the world in which HIV thrives. These programs can act as models of HIV prevention and treatment.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.

Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.

BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the toxicity of second-line medications. Little is known about whether adverse events impact treatment outcome. METHODS: We conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk between 10 September 2000 and 10 September 2002. Adverse reactions were determined by laboratory data and/or clinical criteria. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome. RESULTS: In this cohort, 76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were observed in 73.3% of patients, occurring in 74.8% of patients who were adherent (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals (P = 0.11). The impact of adverse events on outcome was modified by non-adherence; among adherent patients, the occurrence of any adverse reaction was associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval 1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence of adverse reactions among adherent patients was associated with treatment cure.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB.

BACKGROUND: There is no gold standard on how national tuberculosis programs should design retreatment regimens. Often drug susceptibility testing (DST) is not available for all patients, and representative DST patterns in patient populations are used to guide therapy. OBJECTIVES: To examine DST patterns in different patient populations based on previous treatment and to estimate the number of effective anti-tuberculosis agents in several retreatment regimens. METHODS: We reviewed DST results from patients treated with individualized regimens in Peru between January 1998 and July 2004. We stratified patients into four groups based on previous treatment exposure from Group 1 who had failed only one regimen to Group 4 who had failed three regimens. We compared resistance frequencies across the four groups. In Groups 1 and 3, the number of likely effective agents under six possible retreatment regimen scenarios was estimated. RESULTS: Resistance to second-line drugs was significantly higher in groups with more previous courses of treatment. A few retreatment regimens could be identified that would allow at least 80% of patients to receive at least four likely effective drugs. CONCLUSION: Because it is associated with resistance frequencies, previous treatment exposure can serve to guide the design of non-individualized MDR-TB regimens.

rpoB gene mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis in northern Lima, Peru.

In many developing countries and outside hospital settings, the characteristics of endemic Mycobacterium tuberculosis strains resistant to multiple drugs remain unknown. In a community-based referral and therapy program in northern Lima, Peru, beginning in 1996, patients found to be failures on standard regimens were referred for drug-susceptibility testing of their isolates, and those found to be infected with M. tuberculosis isolates resistant to at least rifampin were treated with individualized regimens based on their infecting strains. Isolates from 42 of these patients were subjected to DNA sequencing of the rpoB gene region responsible for rifampin resistance. We determined the frequency of types of mutations in the rpoB gene among these Peruvian isolates.

Factors associated with forced sex among women accessing health services in rural Haiti: implications for the prevention of HIV infection and other sexually transmitted diseases.

The goals of the current study were to: (1) estimate the prevalence of forced sex among women accessing services at a women's health clinic in rural Haiti; and (2) examine factors associated with forced sex in this population. Based on data from a case-control study of risk factors for sexually transmitted diseases (STDs), a cross-sectional analysis to examine factors associated with forced sex was performed. A number of factors related to gender inequality/socioeconomic vulnerability placed women in rural Haiti at higher risk of forced sex. The strongest factors associated with forced sex in multivariate analyses were: age, length of time in a relationship, occupation of the woman's partner, STD-related symptoms, and factors demonstrating economic vulnerability. The findings suggest that prevention efforts must go beyond provision of information and education to the pursuit of broader initiatives at both local and national levels. At the community level, policy-makers should consider advancing economic opportunities for women who are vulnerable to forced sex. Improving access to community-based income-generating activities may begin to address this problem. However, the viability of these local projects depends largely upon Haiti's 'macro-economic' situation. In order to ensure the success of local initiatives, external humanitarian and development assistance to Haiti should be supported. By broadening the definition of "prevention" interventions, we may begin to address the systemic problems that contribute to the occurrence of forced sex and the increasing incidence of HIV infection throughout the world, such as gender inequality and economic vulnerability. Taking into account factors influencing risk at the local level as well as the macro-level will potentially improve our capacity to reduce the risk of forced sex and the spread of STDs, including HIV infection, for millions of women living in poverty worldwide.

From directly observed therapy to accompagnateurs: enhancing AIDS treatment outcomes in Haiti and in Boston.

Like tuberculosis, human immunodeficiency virus (HIV) disease is associated with poverty and social inequalities, conditions that hamper the delivery of care. Like tuberculosis, treatment of HIV infection requires multidrug regimens, and the causative agent acquires drug resistance, which can be transmitted to others. A pilot project in rural Haiti introduced DOT-HAART (directly observed therapy with highly active antiretroviral therapy) for the care of patients with advanced acquired immune deficiency syndrome. A similar DOT-HAART effort was launched in Boston for patients with drug-resistant HIV disease who had experienced failure of unsupervised therapy. In both settings, community health promoters or accompagnateurs provide more than DOT: they offer psychosocial support and link patients to clinical staff and available resources. DOT-HAART in these 2 settings presents both challenges and opportunities. These models of care can be applied to other poverty-stricken populations in resource-poor settings.

Prevalence and risk factors of STDs in rural Haiti: implications for policy and programming in resource-poor settings.

The goals of the current study are to: (1) estimate the prevalence of sexually transmitted diseases (STDs) among women accessing services at a women's health clinic in rural Haiti; and (2) identify risk factors for STDs in this setting. The design is a case control study, comparing risk factors for women who demonstrated positive laboratory results for chlamydia and/or gonorrhoea to women who tested negative for both of these pathogens. The strongest risk factors for chlamydia and/or gonorrhoea were largely economic variables, with work as a domestic servant increasing the risk by four-fold. Working as a market vendor reduced a woman's risk of having an STD by approximately 45%. Given that economic factors are strongly associated with STD risk in this context, one potential mechanism for reducing the risk of STDs, including HIV, would involve increasing economic opportunities for women in rural Haiti.

Peripheral neuropathy associated with treatment for multidrug-resistant tuberculosis.

OBJECTIVE: To review the incidence and management of peripheral neuropathy in patients receiving therapy for MDR-TB. METHODS: A case series with retrospective chart review of 75 patients who initiated individualized therapy for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru, between 1 August 1996 and 31 January 1999. RESULTS: All patients had confirmed MDR-TB and were receiving individualized therapy, comprised of an average of six drugs. Ten (13%) of these patients presented with symptoms of peripheral neuropathy, confirmed by electromyography. All symptoms were reported in the lower extremities, and all were sensory in nature. Median time to presentation from initiation of MDR-TB therapy was 9.1 months. No significant risk factors associated with development of peripheral neuropathy were identified. Management strategies depended on the severity of symptoms and included the treatment of contributing co-morbidities, medications for neuropathic pain, and adjustment of doses of possible offending agents. All patients responded to management; three patients were left with mild residual symptoms. Patients whose neuropathy resolved had symptoms for a median of 7 months. CONCLUSIONS: Peripheral neuropathy was encountered in 13% of our cohort of MDR-TB patients. The diagnosis of peripheral neuropathy can be based on clinical presentation alone, and effective management of this side-effect is possible without sacrificing MDR-TB treatment efficacy.

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Redefining MDR-TB transmission 'hot spots'.

Halting further spread of multidrug-resistant tuberculosis (MDR-TB) requires both new resources and a renewed discussion of priority setting informed by estimates of the existing burden of this disease. The 1997 report of the first phase of the global survey by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) uses the indicator of the proportion of TB cases that are MDR-TB to identify MDR-TB 'hot spots'. We sought to refine the definition of MDR-TB transmission 'hot spots'. For this purpose, we obtained estimates of two additional indicators for regions where data are available: MDR-TB incidence per 100,000 population per year, and expected numbers of new patients with MDR-TB per year. There is generally much agreement in the three indicators considered, and some differences also appear. We conclude that it is useful, when defining indicators of MDR-TB transmission 'hot spots', to include estimates of underlying TB incidence rates and of absolute numbers of MDR-TB cases. Estimating the force of morbidity of MDR-TB in a population is important for comparing this burden across settings with very different underlying TB incidence rates; estimating the absolute number of MDR-TB patients will be critical for planning the delivery of directly observed MDR-TB therapy and the rational procurement of second-line drugs. Through this exercise, we aim to initiate discussion about improved methods of quantifying and comparing current MDR-TB transmission 'hot spots' that require intervention.

Effect of administering short-course, standardized regimens in individuals infected with drug-resistant Mycobacterium tuberculosis strains.

Presented here are the cases of three siblings with multidrug-resistant tuberculosis who demonstrated increased antituberculous-drug resistance during the periods in which they received standard regimens of directly observed, short-course chemotherapy that were administered before the susceptibility patterns of their Mycobacterium tuberculosis isolates had been checked. More specifically, they acquired resistance to drugs they received as part of ineffective standard treatment and retreatment regimens. Development of antituberculous-drug resistance through inadvertent, inadequate therapy appears to be the most likely explanation for the increased resistance seen in these three patients.

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.