Incomplete sputum smear microscopy monitoring among smear-positive tuberculosis patients in Uganda.

SETTING: All 11 tuberculosis (TB) diagnostic and treatment units in Kyankwanzi and Kiboga Districts in Uganda. OBJECTIVES: To determine the frequency of, factors associated with and barriers related to incomplete anti-tuberculosis treatment sputum monitoring. DESIGN: Data were abstracted from anti-tuberculosis treatment and laboratory registers of sputum smear-positive patients who started treatment between January 2009 and December 2011 in the study districts. Patients missing documentation for any smear results at 2 or 3, 5, and 6 or 8 months were classified as having incomplete monitoring. Health providers and patients were interviewed about barriers to sputum monitoring. RESULTS: Overall, 272 (55%) of 492 patients had incomplete monitoring: 16% (78/492) at 2 or 3 months, 39% (181/465) at 5 months and 28% (119/428) at 6 or 8 months of treatment. More sputum results were recorded in laboratory than in TB treatment registers. Incomplete monitoring was significantly associated with being male, living in Kyankwanzi District and not receiving directly observed treatment. Patients' inability to produce sputum, long laboratory waiting times, and insufficient patient and provider education were primary reasons for incomplete monitoring. CONCLUSION: Over half of patients missed at least one smear result during treatment, which has implications for treatment monitoring and treatment outcomes in Uganda.

Under-reporting of sputum smear-positive tuberculosis cases in Kenya.

BACKGROUND: Although an estimated three million tuberculosis (TB) cases worldwide are missed by national TB programs annually, the level of under-reporting of diagnosed cases in high TB burden settings is largely unknown. OBJECTIVE: To quantify and describe under-reporting of sputum smear-positive TB cases in Kenya. DESIGN: A national-level retrospective TB inventory study was conducted. All sputum smear-positive TB cases diagnosed by public or private laboratories during 1 April-30 June 2013 were extracted from laboratory registers in 73 randomly sampled subcounties and matched to TB cases in the national TB surveillance system (TIBU). Bivariate and multivariate analyses were conducted. RESULTS: In the subcounties sampled, 715 of 3409 smear-positive TB cases in laboratory registers were not found in TIBU. The estimated level of under-reporting of smear-positive TB cases in Kenya was 20.7% (95%CI 18.4-23.0). Under-reporting was greatest in subcounties with a high TB burden. Unreported cases were more likely to be patients aged ⩾55 years, have scanty smear results, and be diagnosed at large facilities, private facilities, and facilities in high TB burden regions. CONCLUSION: In Kenya, one fifth of smear-positive TB cases diagnosed during the study period went unreported, suggesting that the true TB burden is higher than reported. TB surveillance in Kenya should be strengthened to ensure all diagnosed TB cases are reported.

Burden of tuberculosis in indigenous peoples globally: a systematic review.

BACKGROUND: The burden of tuberculosis (TB) in the estimated 370 million indigenous peoples worldwide is unknown. OBJECTIVE: To conduct a literature review to summarize the TB burden in indigenous peoples, identify gaps in current knowledge, and provide the foundation for a research agenda prioritizing indigenous health within TB control. METHODS: A systematic literature review identified articles published between January 1990 and November 2011 quantifying TB disease burden in indigenous populations worldwide. RESULTS: Among the 91 articles from 19 countries included in the review, only 56 were from outside Australia, Canada, New Zealand and the United States. The majority of the studies showed higher TB rates among indigenous groups than non-indigenous groups. Studies from the Amazon generally reported the highest TB prevalence and incidence, but select populations from South-East Asia and Africa were found to have similarly high rates of TB. In North America, the Inuit had the highest reported TB incidence (156/100000), whereas the Metis of Canada and American Indians/Alaska Natives experienced rates of <10/100000. New Zealand's Maori and Pacific Islanders had higher TB incidence rates than Australian Aborigines, but all were at greater risk of developing TB than non-indigenous groups. CONCLUSION: Where data exist, indigenous peoples were generally found to have higher rates of TB disease than non-indigenous peoples; however, this burden varied greatly. The paucity of published information on TB burden among indigenous peoples highlights the need to implement and improve TB surveillance to better measure and understand global disparities in TB rates.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Lessons learned during tuberculosis screening in public medical clinics in Francistown, Botswana.

In Botswana, where one quarter of the adult population is infected with the human immunodeficiency virus and the annual tuberculosis (TB) incidence is among the highest globally, intensified TB case finding is needed in health care facilities to detect and treat TB cases early and prevent transmission. During August-December 2009, TB screening was implemented among adults at patient intake in five clinics in Francistown. Among 11 779 TB screenings at intake, 926 were positive. Nineteen patients were diagnosed with TB. Routine TB screening at intake was operationally feasible, but had low yield. Innovative case-finding strategies are needed in Botswana.

Increasing directly observed therapy related to improved tuberculosis treatment outcomes in Taiwan.

SETTING: Directly observed therapy (DOT) is a core element of tuberculosis (TB) care and control efforts. In Taiwan, DOT was implemented in 2006, when the Stop TB Strategy was adopted as a national policy. OBJECTIVE: To quantify DOT among patients on anti-tuberculosis treatment and measure the association between proportion of DOT and TB treatment outcomes at a national level in Taiwan. DESIGN: We analyzed data prospectively collected on all new pulmonary TB cases reported to the national web-based registry between 1 January 2007 and 30 June 2008. We compared treatment outcomes and proportion of DOT in multivariable analyses. RESULTS: Among 11,528 patients initiating anti-tuberculosis treatment, the proportion of days during which an official DOT observer witnessed treatment was >60% for 5150 (45%) patients and ≤60% for 4601 (40%) patients, whereas for 1777 (15%) patients no days of DOT were recorded. Being older, male, having positive bacteriology results and a non-World Health Organization recommended treatment regimen at baseline were independently related to unsuccessful treatment outcomes and mortality. A dose-response effect was found between proportion of DOT and these outcomes. CONCLUSION: These findings highlight the importance of ensuring universal DOT in improving treatment outcomes among new pulmonary TB patients.

Adverse events related to multidrug-resistant tuberculosis treatment, Latvia, 2000-2004.

SETTING: Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) globally. Clinical management of MDR-TB requires lengthy multidrug regimens that often cause adverse events. DESIGN: We retrospectively reviewed records of patients who began MDR-TB treatment between 2000 and 2004. Treatment-related adverse events and factors associated with experiencing adverse events were evaluated. We also examined the frequency of and reasons for changing drug regimens. RESULTS: Among 1027 cases, 807 (79%) experienced at least one adverse event, with a median of three events per case. The most commonly reported events were nausea (58%), vomiting (39%) and abdominal pain (24%). More serious events, such as psychiatric episodes (13%), hepatitis (9%) and renal failure (4%), were relatively frequent. A change in drug dose due to an adverse event occurred in 201 (20%) cases, while 661 (64%) had at least one drug discontinued temporarily or permanently. Being older, female, having bilateral lung cavities and a greater number of TB symptoms at baseline were associated with an increased number of events. CONCLUSION: Adverse events were prevalent among MDR-TB cases treated in Latvia, with over two thirds requiring discontinuation of at least one drug. MDR-TB patients who are female, older or have severe TB disease should be closely monitored for treatment-related adverse events.

Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery.

Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of IL layer V pyramidal neurons from male Sprague-Dawley rats subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over extension of proximal dendritic arbors and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry reestablishment may underlie elements of recovery. Accordingly, we believe that pharmacological treatments targeted at preventing dendritic retraction and spine loss or encouraging circuitry re-establishment and stabilization may be advantageous in the prevention and treatment of mood and anxiety disorders.