Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Should we consider a 'fourth 90' for tuberculosis?

The international community has committed to end the tuberculosis (TB) epidemic by 2030. To facilitate the meeting of the global incidence and mortality indicators set by the World Health Organization's End TB Strategy, the Stop TB Partnership launched the three 90-(90)-90 diagnostic and treatment targets in 2014. In this paper, we argue that a 'fourth 90'-Ensuring that 90% of all people successfully completing treatment for TB can have a good health-related quality of life'-should be considered. Many individuals who successfully complete anti-TB treatment are burdened with lifelong comorbidities-human immunodeficiency virus (HIV) and diabetes mellitus, obstructive and restrictive lung disease, involving lung destruction, cavitation, fibrosis and bronchiectasis, that either pre-existed or developed as a result of TB (e.g., chronic pulmonary aspergillosis), permanent disabilities such as hearing loss resulting from second-line anti-TB drugs, and mental health disorders. These need to be identified during TB treatment and appropriate care and support provided after anti-TB treatment is successfully completed. A 'fourth 90' has also been proposed for the UNAIDS 90-90-90 targets similar in scope to what is being suggested here for TB. Adoption by both HIV and TB control programmes would highlight the current focus on integrated person- and family-centred services.

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care.

The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a 'syndemic' due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the 'MPOWER' package recommended by the World Health Organization's Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking.

Health solutions for the poor.

The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organisation involved in the fight against tuberculosis. In 2008, the Institute of The Union was challenged to think boldly about the future and to develop a diverse work portfolio covering a wide spectrum of lung health and other disease-related problems. The vision adopted by The Union at that time was 'Health solutions for the poor'. More recently, there has been lengthy debate about the need for the Union to concentrate just on its core mandate of tuberculosis and lung health and for the Union's vision to reflect this narrower spectrum of activity as 'Lung health solutions for the poor'. In this viewpoint article we outline our reasons for believing that this narrower vision is incompatible with The Union's mission statement, and we argue that making such a change would be a mistake.

L'Union Internationale contre la Tuberculose et les Maladies respiratoires (L'Union) est la plus ancienne organisation non-gouvernementale impliquée dans la lutte contre la tuberculose. En 2008, l'Institut de L'Union a été confronté au défi de son avenir et à la nécessité d'élaborer un domaine de travail plus large en matière de santé des poumons et d'autres problèmes liés aux maladies. La vision adoptée par L'Union à ce moment était « Solutions de santé pour les pauvres ¼. Plus récemment a eu lieu un débat prolongé sur la nécessité pour L'Union de se concentrer seulement sur son mandat principal, c'est-à-dire la tuberculose et les maladies respiratoires, et pour sa vision, de refléter ce spectre d'activité plus étroit « Solutions de santé respiratoire pour les pauvres ¼. Dans cet article nous soulignons nos raisons de penser que ce spectre plus étroit est incompatible avec l'énoncé de mission de L'Union et nous défendons notre point de vue, c'est-à-dire que ce changement serait une erreur.

La Unión Internacional contra la Tuberculosis y las Enfermedades Respiratorias (La Unión) representa la organización no gubernamental internacional más antigua que participa en la lucha contra la tuberculosis. En el 2008, se retó al Instituto de La Unión a practicar una reflexión audaz sobre el futuro y a elaborar un plan de trabajo diverso que cubriese un amplio espectro de la salud respiratoria y otros problemas relacionados con las enfermedades. En ese momento, La Unión adoptó el concepto 'Soluciones de salud para los pobres'. Más recientemente, ha tenido lugar un extenso debate sobre la necesidad de que La Unión se concentre en su mandato primordial alrededor de la tuberculosis y las enfermedades respiratorias y adopte el concepto 'Soluciones de salud respiratoria para los pobres', que corresponde a un espectro más estrecho de sus actividades. En el presente artículo de opinión se ponen de relieve las razones que fundamentan la convicción de que esta perspectiva restringida es incompatible con la declaración de mi sión de La Unión y se argumenta que esta modificación sería un error.

Integrating HIV testing and care into tuberculosis services in Benin: programmatic aspects.

SETTING: Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin. RESULTS: The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities. CONCLUSION: The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Results of rapid and successful integration of HIV diagnosis and care into tuberculosis services in Benin.

SETTING: Benin, where 20 of 54 tuberculosis (TB) clinics caring for 80% of all TB patients began providing integrated human immunodeficiency virus (HIV) care in 2005. OBJECTIVE: To describe the characteristics and TB treatment outcomes of the first cohorts of TB-HIV patients, and to assess programmatic outcomes. METHODS: Retrospective cohort study using data from the TB register and the register of co-infected patients. RESULTS: During the study period, 8368 TB patients were registered, 7787 (93%) were tested for HIV and 1255 (16%) were HIV-positive, including 385 (32%) who already knew their positive status. Most patients (88%) were tested within 15 days of TB diagnosis. Female and young patients were overrepresented among the co-infected. Cotrimoxazole preventive therapy was administered to 1152 patients (95%) during anti-tuberculosis treatment, and antiretroviral treatment (ART) to 469 (42%). The likelihood of receiving ART increased as initial CD4 lymphocyte counts decreased. Fifteen per cent of TB-HIV patients died during anti-tuberculosis treatment. Patients already on ART prior to anti-tuberculosis treatment experienced the worst outcomes. Patients who initiated ART early during anti-tuberculosis treatment or in the timeframe recommended by the guidelines fared the best. CONCLUSION: HIV care has been successfully and sustainably integrated into TB services in Benin. However, ensuring the access of co-infected patients to more favourable treatment outcomes still represents significant challenges.

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda.

SETTING: Three regional referral hospitals in Uganda with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) cases. OBJECTIVE: To determine the treatment outcomes of TB retreatment cases and factors influencing these outcomes. DESIGN: A retrospective cohort study of routinely collected National Tuberculosis Programme data between 1 January 2009 and 31 December 2010. RESULTS: The study included 331 retreatment patients (68% males), with a median age of 36 years, 93 (28%) of whom were relapse smear-positive, 21 (6%) treatment after failure, 159 (48%) return after loss to follow-up, 26 (8%) relapse smear-negative and 32 (10%) relapse cases with no smear performed. Treatment success rates for all categories of retreatment cases ranged between 28% and 54%. Relapse smear-positive (P = 0.002) and treatment after failure (P = 0.038) cases were less likely to have a successful treatment outcome. Only 32% of the retreatment cases received a Category II treatment regimen; there was no difference in treatment success among patients who received Category II or Category I treatment regimens (P = 0.73). CONCLUSION: Management of TB retreatment cases and treatment success for all categories in three referral hospitals in Uganda was poor. Relapse smear-positive or treatment after failure cases were less likely to have a successful treatment outcome.

Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

The Union and Médecins Sans Frontières approach to operational research.

Operational research (OR) has become a hot topic at national meetings, international conferences and donor fora. The International Union Against Tuberculosis and Lung Disease (The Union) and Médecins Sans Frontières (MSF) Operational Centre Brussels strongly promote and implement OR with colleagues in low- and middle-income countries. Here we describe how the two organisations define OR, and explain the guiding principles and methodology that underpin the strategy for developing and expanding OR in those countries. We articulate The Union's and MSF's approach to supporting OR, highlighting the main synergies and differences. Then, using the Malawi National Tuberculosis Control Programme as an example, we show how OR can be embedded within tuberculosis control activities, leading to changes in policy and practice at the national level. We discuss the difficult, yet vitally important, issue of capacity building, and share our vision of a new paradigm of product-related training and performance-based OR fellowships as two ways of developing the necessary skills at country level to ensure research is actually performed. Finally, we highlight the need to consider and incorporate into practice the ethical components of OR. This is a key moment to be involved in OR. We are confident that in partnership with interested stakeholders, including the World Health Organization, we can stimulate the implementation of quality, relevant OR as an integral part of health service delivery that in turn will lead to better health for people, particularly for those living in the poorer parts of the world.

Factors associated with human immunodeficiency virus testing among tuberculosis patients receiving treatment at health facilities in Uganda.

SETTING: One peri-urban and four rural districts in Uganda. OBJECTIVES: To determine the level of and factors associated with human immunodeficiency virus (HIV) testing among tuberculosis (TB) patients. DESIGN: A cross-sectional study was conducted in five selected districts from August to November 2007. Patients aged > or = 18 years returning for TB treatment refills at facilities offering TB and HIV services were included. Patients were excluded if they were very sick or unable to speak English or any of the local study languages. The outcome was self-reported HIV testing after TB diagnosis, validated using clinic registers. RESULTS: Of 261 patients analysed, 169 (65%) had been tested for HIV following TB diagnosis. In a multivariate analysis, age >45 years (OR 0.27, 95%CI 0.08-0.87), not receiving information about the TB-HIV association (OR 0.35, 95%CI 0.15-0.77), not being offered HIV testing by health provider (OR 0.02, 95%CI 0.006-0.042), dissatisfaction with privacy (OR 2.49, 95%CI 1.11-5.55) and spending 30-60 min at the clinic (OR 4.48, 95%CI 1.66-12.10) significantly influenced level of HIV testing. CONCLUSION: The level of HIV testing among TB patients was suboptimal, as per policy all patients should be tested. The Uganda Ministry of Health should continue to scale-up HIV testing and other collaborative TB-HIV services at health facilities.

Isoniazid preventive therapy for people living with HIV: public health challenges and implementation issues.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

Ensuring accountability: the contribution of the cohort review method to tuberculosis control in New York City.

SETTING: In 1993, the New York City (NYC) Bureau of Tuberculosis Control developed the cohort review process as a quality assurance method to track and improve patient outcomes. METHODS: The Bureau Director reviews every tuberculosis (TB) case quarterly in a multi-disciplinary staff meeting. In 2004 we also began collecting details on issues identified at cohort review to quantify how this process directly impacts TB control efforts. RESULTS: From 1992 to 2004, NYC TB cases decreased by 72.7% and treatment success rates significantly increased by 26.7%. Implementing the cohort review was key to improving case management, thus leading to these results. For the 1039 patients in 2004, 596 issues were identified among 424 patients; 55.0% were incorrect, unclear or unknown patient information, 13.8% were treatment issues, 12.4% were case management issues and 10.6% were incomplete contact investigations. Most (76.5%) issues were addressed within 30 days of the cohort reviews. CONCLUSION: A systematic review of every TB case improves the quality of patient information, enhances patient treatment and ensures accountability at all levels of the TB control program.

Management of adults living with HIV/AIDS in low-income, high-burden settings, with special reference to persons with tuberculosis.

Because of the increasing availability of antiretroviral (ARV) agents for HIV in low-income countries, many clinicians now need training on their use. This is especially true for clinicians caring for individuals with tuberculosis (TB), given its close relationship with HIV/AIDS. This article summarizes the key decisions facing clinicians who manage HIV-infected persons, with particular reference to issues regarding those dually infected with TB. Health care provider-initiated diagnostic testing using rapid HIV tests should be offered to all individuals with symptoms and signs suggesting HIV infection, including all persons with TB. Issues to be included in pre- and post-test counseling sessions are discussed. HIV-infected patients should be evaluated to determine clinical staging of HIV; certain laboratory examinations should ideally be performed to assess the degree of immunosuppression and to aid decisions about when best to start ARV therapy and preventive therapies. The recommended ARV regimens and guidance on proposed patient follow-up are presented. Good adherence to ARVs is required and factors that induce and reinforce compliance are suggested. The treatment of TB is a high priority, and follows the same principles whether the patient is HIV-infected or not. Suggestions are made about ARV use in patients with TB. A standardized and complementary information system should be developed to monitor management of HIV-TB patients and performance of joint TB and HIV care efforts. By diagnosing and managing additional HIV cases detected through the portal of the TB control programme, clinicians will contribute to diminishing the burden of HIV, and thus, TB.

Should tuberculosis treatment and control be addressed differently in HIV-infected and -uninfected individuals?

Infection with HIV drives the tuberculosis epidemic, especially in sub-Saharan Africa, where up to 75% of individuals with tuberculosis are co-infected with HIV. This article reviews the epidemiological link between the conditions, how tuberculosis diagnosis and treatment differ between HIV-infected versus -uninfected individuals and the span of additional measures required to prevent and control HIV-related tuberculosis. Tuberculosis chemotherapy using standard short-course regimens is highly effective in both groups, and treatment follows the same principles. It differs in certain aspects, such as when antiretroviral treatment should be started in HIV-infected individuals with tuberculosis and consideration of drug-drug interactions between the rifamycins and certain antiretroviral drugs. Control of HIV-related tuberculosis requires, fundamentally, control of HIV transmission. Meanwhile, it is necessary to make concentrated efforts to intensify high-quality tuberculosis services employing the directly observed treatment, short-course (DOTS) strategy, carry out extensive research towards an evidence-based model for the expanded scope of collaborative tuberculosis and HIV/AIDS interventions, and ensure efficient implementation of the findings and recommended policies. The challenge is gigantic, and both robust within-country and international leadership and competent management capabilities will be required, in addition to substantial human and financial resources.

Finding contacts of homeless tuberculosis patients in New York City.

OBJECTIVE: To determine factors associated with no contacts identified for homeless patients in New York City. DESIGN: Culture-confirmed pulmonary tuberculosis cases in persons >18 years old diagnosed in 1997-1999 were included. Demographic and clinical characteristics of tuberculosis patients associated with the number of contacts identified according to homeless status were analyzed using unconditional logistic regression. RESULTS: Homeless patients (n = 152) had a significantly lower median number of contacts than non-homeless patients (n = 2836) (1 vs. 4, P < 0.001). Among homeless patients, having AFB smear-positive sputum with cavitary lesions reduced the likelihood of having no contacts identified. Homeless patients who lived on the street at the time of diagnosis were more likely to have no contacts identified compared to those with contacts identified (61.4% vs. 56.1%); however, the difference was not statistically significant (P = 0.506). Unlike non-homeless patients, being hospitalized at the time of tuberculosis diagnosis was not associated with having contacts identified in homeless patients. CONCLUSIONS: Homelessness independently predicted the likelihood of having no contacts identified. Strategies such as interviews that focus on location rather than persons may be more effective for identifying contacts. Furthermore, being homeless at the time of diagnosis should be used as an indicator for prioritizing prompt contact evaluation.

Differential decline in tuberculosis incidence among US- and non-US-born persons in New York City.

SETTING: A large urban tuberculosis control program. OBJECTIVES: To examine changes in tuberculosis incidence and characteristics of cases in New York City (NYC), and assess the epidemiology of tuberculosis among non-US-born persons. DESIGN: Tuberculosis surveillance data (1995-1999) for NYC were analyzed. RESULTS: Tuberculosis incidence decreased by 56.6% in US-born and 19.6% in non-US-born persons (age-adjusted) over the study period. The decline in tuberculosis incidence among US-born persons was more substantial in the first half of the study period (23-24%) than in the second half (13-15%). The greatest decline in incidence was among US-born Hispanic or Black males aged 25-64. However, although there was an overall decline in incidence among non-US-born persons, there was no significant change in any sex or racial/ethnic subgroup. The percent of multidrug-resistant (MDR) cases among non-US-born patients remained stable, but recent arrivals accounted for 79% of non-US-born MDR-TB patients in 1999, a significant increase from 16% in 1997. CONCLUSIONS: Continuing current tuberculosis control efforts and treatment of immigrants with latent tuberculosis infection are of highest priority for reducing incident cases in NYC. Global collaboration towards earlier detection and treatment of active tuberculosis cases in high incidence countries is also essential.

Yield of continued monthly sputum evaluation among tuberculosis patients after culture conversion.

SETTING: New York City. OBJECTIVE: To evaluate the yield of continued monthly sputum monitoring after culture conversion. DESIGN: A retrospective review of tuberculosis patients verified between 1 January 1995 and 31 December 1996 who had: 1) pulmonary tuberculosis with organisms susceptible to isoniazid and rifampin; 2) culture conversion; and 3) completed therapy. We assessed time to smear and culture conversion and number of persons who developed a positive culture after culture conversion (culture reversion). RESULTS: Of 1440 patients, 379 were cared for by tuberculosis control program providers and 1061 were cared for by other providers; 813 (56%) were initially smear-positive. After the fifth month, 44 (5.3%) were smear-positive; four of these were culture-positive. Eighteen (1.3%) had culture reversions; eight were smear-positive. Excluding one specimen per patient collected at treatment completion, 7967 sputum samples were collected after culture conversion. The minimum estimated cost per culture reversion detected was $26,557. CONCLUSION: Continued monthly monitoring of sputum after culture conversion identified a very small number of patients who had culture reversion. However, patients who cannot tolerate or adhere to a standard regimen may need continued monitoring to assess response to treatment. For all patients a specimen should be collected at the end of treatment to document cure.