BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm). METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies. RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country. CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
The risk of acquiring additional drug resistance in strains of multidrug-resistant tuberculosis (MDR-TB) during failure of empiric standardized retreatment regimens is poorly defined. We sought to estimate this risk by comparing drug susceptibility profiles and RFLP patterns of paired MDR-TB isolates collected from 27 patients before and after retreatment failure. Among 23 patients with paired isolates with concordant RFLP patterns, 19 (83%) had become resistant to at least one additional drug after failed retreatment. In this limited group of MDR-TB patients, acquisition of resistance was common during failure of empiric drug regimens. Further study is needed to confirm these findings.
Background Although it is now widely recognized that reductions in maternal mortality and improvements in women's health cannot be achieved through simple, vertical strategies, few programs have provided successful models for how to integrate services into a comprehensive program for maternal health. We report our experience in rural Lesotho, where Partners In Health (PIH) in partnership with the Ministry of Health and Social Welfare implemented a program that provides comprehensive care of pregnant women from the community to the clinic level. Methods Between May and July 2009, PIH trained 100 women, many of whom were former traditional birth attendants, to serve as clinic-affiliated maternal health workers. They received performance-based incentives for accompanying pregnant women during antenatal care (ANC) visits and facility-based delivery. A nurse-midwife provided ANC and delivery care and supervised the maternal health workers. To overcome geographic barriers to delivering at the clinic, women who lived far from the clinic stayed at a maternal lying-in house prior to their expected delivery dates. We analyzed data routinely collected from delivery and ANC registers to compare service utilization before and after implementation of the program. Results After the establishment of the program, the average number first ANC visits increased from 20 to 31 per month. The clinic recorded 178 deliveries in the first year of the program and 216 in the second year, compared to 46 in the year preceding the program. During the first two years of the program, 49 women with complications were successfully transported to the district hospital, and no maternal deaths occurred among the women served by the program. Conclusions Our results demonstrate that it is possible to achieve dramatic improvements in the utilization of maternal health services and facility-based delivery by strengthening human resource capacity, implementing active follow-up in the community, and de-incentivizing home births.
Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB.To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs.Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy.Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.
This article presents a unique approach to HIV/AIDS training in resource-poor settings that incorporates the use of standardized patients (SPs). Integrated Management of Adolescent and Adult Illness (IMAI) is a World Health Organization health systems strengthening initiative with a strong emphasis on training health workers in the management of common diseases and conditions. In IMAI, SPs are called Expert Patient-Trainers (EPTs) to emphasize their role in the training of health workers. EPTs were first used in IMAI training in Uganda in 2004. Since then, the method has been adopted by a number of other countries in Africa, Latin America, and Asia. EPTs are usually recruited from groups of people living with HIV/AIDS. In the classroom, EPTs discuss living with HIV and help participants understand HIV as it affects patients. Course participants spend approximately two hours per day in "skill stations," multiple-station assessments consisting of one-on-one encounters with EPTs. In each encounter, the health worker interacts with an EPT portraying a standardized case. Instructions on how to portray each case provide only broad outlines of the major clinical and counseling points; the EPT is expected to use his or her own life experiences to fill in emotional details. Course facilitators noted that health workers were often initially skeptical about EPTs, but this generally turned to enthusiasm after participating in the skill stations. EPTs benefited from the sense of being part of the training team, the satisfaction of improving the skills of health workers, and learning more about their illness.
Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.
Treating drug-resistant tuberculosis (DR-TB) is particularly challenging in high human immunodeficiency virus (HIV) prevalence settings. Neither antiretroviral resistance testing nor viral load monitoring is widely available in sub-Saharan Africa, and antiretroviral resistance can complicate the clinical management for DR-TB/HIV coinfected patients. We describe six cases of antiretroviral resistance in DR-TB patients with HIV coinfection in Lesotho. Two patients died before or immediately after antiretroviral resistance was detected by genotyping; the remaining four patients were switched to effective antiretroviral therapy (ART) regimens. Favorable DR-TB treatment outcomes in coinfected patients require successful management of their HIV infection, including treatment with an effective ART regimen. Coinfected patients undergoing DR-TB treatment may require closer monitoring of their response to ART, including routine viral load testing, to ensure that they receive an effective ART regimen concurrent with DR-TB treatment.
Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa.We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/microl (range 5-824 cells/microl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12-451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12-374 days).In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings.
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