INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm(3) or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm(3) , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

BACKGROUND: Measuring clinically relevant opioid-related problems in health care systems is challenging due to the lack of standard definitions and coding practices. Well-defined, opioid-related health problems (ORHPs) would improve prevalence estimates and evaluation of clinical interventions, crisis response, and prevention activities. We sought to estimate prevalence of opioid use disorder (OUD), opioid misuse, and opioid poisoning among inpatients at a large, safety net, health care institution. METHODS: Our study included events documented in the electronic health records (EHRs) among hospitalized patients at Denver Health Medical Center during January 1, 2017 to December 31, 2018. Multiple EHR markers (ie, opioid-related diagnostic codes, clinical assessment, laboratory results, and free-text documentation) were used to develop diagnosis-based and extended definitions for OUD, opioid misuse, and opioid poisoning. We used these definitions to estimate number of hospitalized patients with these conditions. RESULTS: During a 2-year study period, 715 unique patients were identified solely using opioid-related diagnostic codes; OUD codes accounted for the largest proportion (499/715, 69.8%). Extended definitions identified an additional 973 unique patients (~136% increase), which includes 155/973 (15.9%) who were identified by a clinical assessment marker, 1/973 (0.1%) by a laboratory test marker, and 817/973 (84.0%) by a clinical documentation marker. CONCLUSIONS: Solely using diagnostic codes to estimate prevalence of clinically relevant ORHPs missed most patients with ORHPs. More inclusive estimates were generated using additional EHR markers. Improved methods to estimate ORHPs among a health care system's patients would more fully estimate organizational and economic burden to more efficiently allocate resources and ensure capacity to provide clinical services.

BACKGROUND: Mineworkers in Southern Africa have the highest rates of tuberculosis (TB) among working populations in the world (The World Bank, Benefits and costs associated with reducing tuberculosis among Southern Africa's mineworkers, 2014), making mineworkers a key population for TB program efforts. The current evaluation aimed to characterize mineworkers and former (ex-) mineworkers, and assess knowledge, attitudes and practices related to TB and HIV care among mineworkers and healthcare workers (HCWs) in Zambia. METHODS: A mixed-methods evaluation of current and former (ex-) mineworkers and HCWs was conducted in the Copperbelt and North-Western provinces, Zambia. Knowledge, attitudes and practices (KAPs) related to TB care and policies were assessed using a structured survey. Focus Group Discussions (FGDs) were conducted with current and ex-mineworkers to understand perceptions, practices, and barriers related to accessing healthcare for TB. RESULTS: Overall, 2,792 mineworkers and 94 HCWs completed the KAP survey, and 206 (171 current, 71 ex-) mineworkers participated in FGDs. Mineworkers and ex-mineworkers were knowledgeable about TB symptoms (cough; 94%), transmission (81.7%) and treatment (99.2%). Yet, barriers to seeking care were evident with 30% of mineworkers experiencing cough, and 19% reporting 2 or more TB symptoms at the time of the survey. The majority of mineworkers (70.9%) were aware of policies barring persons from working after a diagnosis of TB, and themes from FGDs and HCW comments (n = 32/62; 51.6%) recognized fear of job loss as a critical barrier to providing timely screening and appropriate care for TB among mineworkers. The majority (76.9%) of mineworkers indicated they would not disclose their TB status to their supervisor, but would be willing to share their diagnosis with their spouse (73.8%). CONCLUSION: Fear of job loss, driven by governmental policy and mistrust in mining companies, is a major barrier to healthcare access for TB among mineworkers in Zambia. As a result of these findings, the government policy prohibiting persons from working in the mines following TB disease is being repealed. However, major reforms are urgently needed to mitigate TB among mineworkers, including ensuring the rights of mineworkers and their communities to healthy living and working environments, improved social responsibility of mining companies, and facilitating choice and access to affordable, timely, and high-quality healthcare services.

OBJECTIVES: The number of SARS-CoV-2 infections is underestimated in surveillance data. Various approaches to assess the seroprevalence of antibodies to SARS-CoV-2 have different resource requirements and generalizability. We estimated the seroprevalence of antibodies to SARS-CoV-2 in Denver County, Colorado, via a cluster-sampled community survey. METHODS: We estimated the overall seroprevalence of antibodies to SARS-CoV-2 via a community seroprevalence survey in Denver County in July 2020, described patterns associated with seroprevalence, and compared results with cumulative COVID-19 incidence as reported to the health department during the same period. In addition, we compared seroprevalence as assessed with a temporally and geographically concordant convenience sample of residual clinical specimens from a commercial laboratory. RESULTS: Based on 404 specimens collected through the community survey, 8.0% (95% CI, 3.9%-15.7%) of Denver County residents had antibodies to SARS-CoV-2, an infection rate of about 7 times that of the 1.1% cumulative reported COVID-19 incidence during this period. The estimated infection-to-reported case ratio was highest among children (34.7; 95% CI, 11.1-91.2) and males (10.8; 95% CI, 5.7-19.3). Seroprevalence was highest among males of Black race or Hispanic ethnicity and was associated with previous COVID-19-compatible illness, a previous positive SARS-CoV-2 test result, and close contact with someone who had confirmed SARS-CoV-2 infection. Testing of 1598 residual clinical specimens yielded a seroprevalence of 6.8% (95% CI, 5.0%-9.2%); the difference between the 2 estimates was 1.2 percentage points (95% CI, -3.6 to 12.2 percentage points). CONCLUSIONS: Testing residual clinical specimens provided a similar seroprevalence estimate yet yielded limited insight into the local epidemiology of COVID-19 and might be less representative of the source population than a cluster-sampled community survey. Awareness of the limitations of various sampling strategies is necessary when interpreting findings from seroprevalence assessments.

BACKGROUND: The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia. METHODS: In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation. RESULTS: We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training. CONCLUSIONS: TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.

Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population.

BACKGROUND: Timely, precise, and localized surveillance of nonfatal events is needed to improve response and prevention of opioid-related problems in an evolving opioid crisis in the United States. Records of naloxone administration found in prehospital emergency medical services (EMS) data have helped estimate opioid overdose incidence, including nonhospital, field-treated cases. However, as naloxone is often used by EMS personnel in unconsciousness of unknown cause, attributing naloxone administration to opioid misuse and heroin use (OM) may misclassify events. Better methods are needed to identify OM. OBJECTIVE: This study aimed to develop and test a natural language processing method that would improve identification of potential OM from paramedic documentation. METHODS: First, we searched Denver Health paramedic trip reports from August 2017 to April 2018 for keywords naloxone, heroin, and both combined, and we reviewed narratives of identified reports to determine whether they constituted true cases of OM. Then, we used this human classification as reference standard and trained 4 machine learning models (random forest, k-nearest neighbors, support vector machines, and L1-regularized logistic regression). We selected the algorithm that produced the highest area under the receiver operating curve (AUC) for model assessment. Finally, we compared positive predictive value (PPV) of the highest performing machine learning algorithm with PPV of searches of keywords naloxone, heroin, and combination of both in the binary classification of OM in unseen September 2018 data. RESULTS: In total, 54,359 trip reports were filed from August 2017 to April 2018. Approximately 1.09% (594/54,359) indicated naloxone administration. Among trip reports with reviewer agreement regarding OM in the narrative, 57.6% (292/516) were considered to include information revealing OM. Approximately 1.63% (884/54,359) of all trip reports mentioned heroin in the narrative. Among trip reports with reviewer agreement, 95.5% (784/821) were considered to include information revealing OM. Combined results accounted for 2.39% (1298/54,359) of trip reports. Among trip reports with reviewer agreement, 77.79% (907/1166) were considered to include information consistent with OM. The reference standard used to train and test machine learning models included details of 1166 trip reports. L1-regularized logistic regression was the highest performing algorithm (AUC=0.94; 95% CI 0.91-0.97) in identifying OM. Tested on 5983 unseen reports from September 2018, the keyword naloxone inaccurately identified and underestimated probable OM trip report cases (63 cases; PPV=0.68). The keyword heroin yielded more cases with improved performance (129 cases; PPV=0.99). Combined keyword and L1-regularized logistic regression classifier further improved performance (146 cases; PPV=0.99). CONCLUSIONS: A machine learning application enhanced the effectiveness of finding OM among documented paramedic field responses. This approach to refining OM surveillance may lead to improved first-responder and public health responses toward prevention of overdoses and other opioid-related problems in US communities.

SETTING: Sixteen South African correctional facilities.OBJECTIVE: To determine the prevalence of and risk factors for tuberculosis (TB) in South African correctional facilities using data collected during a TB screening program in South African correctional facilities in 2015.DESIGN: Inmates in 16 South African correctional facilities were screened for TB from January to December 2015. Inmates reporting >/=1 TB symptom or having an abnormal computer-assisted digital chest X-ray (CXR) provided sputum. Abnormal CXRs were interpreted by a radiologist. Sputum was tested for Mycobacterium tuberculosis using Xpert((R)) MTB/RIF. Data from 16 South African correctional facilities were used in regression analysis, and prevalence estimates calculated for 12 South African correctional facilities with >30% screening coverage.RESULTS: In 12 South African correctional facilities included in the prevalence estimates, 837 inmates had TB disease (2653/100 000) as indicated by current TB treatment or screening-identified TB by radiologist or Xpert. Previous TB was associated with increased odds of screening-identified TB in HIV-positive inmates (OR 4.3, 95%CI 2.5-7.3). For HIV-negative inmates, previous TB (adjusted OR [aOR] 4.9, 95%CI 1.7-14.1) and self-reported symptoms vs. none (1 symptom, aOR 8.8, 95%CI 1.2-67.7; >2 symptoms, aOR 21.7, 95%CI 3.0-158.8) were independently associated with increased odds of screening-identified TB.CONCLUSIONS: Routine TB screening, including CXR, is needed in South African correctional facilities to identify and refer inmates with active TB.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

BACKGROUND: Adherence to tuberculosis (TB) treatment and antiretroviral therapy (ART) reduces morbidity and mortality among persons co-infected with TB/HIV. We measured adherence and determined factors associated with non-adherence to concurrent TB treatment and ART among co-infected persons in two provinces in South Africa. METHODS: A convenience sample of 35 clinics providing integrated TB/HIV care was included due to financial and logistic considerations. Retrospective chart reviews were conducted among persons who received concurrent TB treatment and ART and who had a TB treatment outcome recorded during 1 January 2008-31 December 2010. Adherence to concurrent TB and HIV treatment was defined as: (1) taking ≥80% of TB prescribed doses by directly observed therapy (DOT) as noted in the patient card; and (2) taking >90% ART doses as documented in the ART medical record during the concurrent treatment period (period of time when the patient was prescribed both TB treatment and ART). Risk ratios (RRs) and 95% confidence intervals (CIs) were used to identify factors associated with non-adherence. RESULTS: Of the 1,252 persons receiving concurrent treatment, 138 (11.0%) were not adherent. Non-adherent persons were more likely to have extrapulmonary TB (RR: 1.71, 95% CI: 1.12 to 2.60) and had not disclosed their HIV status (RR: 1.96, 95% CI: 1.96 to 3.76). CONCLUSIONS: The majority of persons with TB/HIV were adherent to concurrent treatment. Close monitoring and support of persons with extrapulmonary TB and for persons who have not disclosed their HIV status may further improve adherence to concurrent TB and antiretroviral treatment.

INTRODUCTION: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. METHODS: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. RESULTS: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. DISCUSSION: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. CONCLUSION: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

BACKGROUND: The importance of using surveillance data to monitor and evaluate programme activities has been emphasised in international policies for tuberculosis (TB) control. OBJECTIVES: A survey was conducted to assess the use of TB surveillance data to monitor and guide TB programme activities in South Africa (SA). METHODS: As part of an evaluation of the SA national TB surveillance system, semi-structured interviews were conducted among TB staff at health facilities and offices in three provinces. At each site, all persons involved with TB care, management and surveillance were invited to participate. RESULTS: At least one person (range 1 - 4) was interviewed at 47/54 health facilities (87.0%), 11/13 subdistrict and district TB offices (84.6%), 2/3 provincial TB offices (66.7%), and at the national level (1/1, 100.0%). Of 119 TB staff, 64.7% recognised the purpose of TB surveillance as guiding programme planning, implementation and evaluation. However, only 16.0% reported using data to measure disease burden, 8.4% to monitor trends, and 9.2% to inform resource allocation. The majority reported using TB management tools provided by the national programme, but 44.5% also described using additional tools. Personnel mentioned the need for dedicated surveillance staff, training on recording and reporting, improved computer access, and methods to apply information from surveillance data to the programme. CONCLUSIONS: The majority of TB staff understood the purpose of surveillance but did not routinely use data to guide programme planning, implementation and evaluation. Training and supporting TB staff to utilise surveillance data will help improve the TB surveillance system.

BACKGROUND: KwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses. METHODS: Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers. RESULTS: We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border. CONCLUSION: Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

Many hospital inpatients in South Africa have undiagnosed active and drug-resistant tuberculosis (TB). Early detection of TB is essential to inform immediate infection control actions to minimize transmission risk. We assessed the utility of Xpert((R)) MTB/RIF (GeneXpert) as a screening tool for medical admissions at a large public hospital in South Africa. Consecutive adult patients admitted to medical wards between March-June 2013 were enrolled; sputum specimens were collected and tested by GeneXpert, smear microscopy, and culture. Chest X-rays (CXRs) were conducted as standard care for all patients admitted. We evaluated the proportion of patients identified with TB disease through each diagnostic method. Among enrolled patients whose medical charts were available for review post-discharge, 61 (27%) were diagnosed with TB; 34 (56% of diagnosed TB cases) were GeneXpert positive. When patients in whom TB was identified by other means were excluded, GeneXpert yielded only four additional TB cases. However, GeneXpert identified rifampicin-resistant TB in one patient, who was initially diagnosed based on CXR. The utility of GeneXpert for TB screening was limited in an institution where CXR is conducted routinely and which serves a population in which TB and TB/HIV co-infection are highly prevalent, but it allowed for rapid detection of rifampicin resistance.

BACKGROUND: Accurate surveillance data are paramount to effective TB control. The Republic of South Africa's National TB Control Program (NTP) has conducted TB surveillance since 1995 and adopted the Electronic TB Register (ETR) in 2005. This evaluation aimed to determine the completeness and reliability of data in the Republic of South Africa's TB Surveillance System. METHODS: Three of nine provinces, three subdistricts per province, and 54 health facilities were selected by stratified random sampling. At each facility, 30 (or all if <30) patients diagnosed in Quarter 1 2009 were randomly selected for review. Patient information was evaluated across two paper and four electronic sources. Completeness of program indicators between paper and electronic sources was compared with chi-square tests. The kappa statistic was used to evaluate agreement of values. RESULTS: Over one-third (33.7 %) of all persons with presumptive TB recorded as smear positive in the TB Suspect Register did not have any records documenting notification, treatment, or management for TB disease. Of 1339 persons with a record as a TB patient at the facility, 1077 (80 %) were recorded in all data sources. Over 98 % of records contained complete age and sex data. Completeness varied for HIV status (53-86 %; p < 0.001) and DOT during the intensive phase of treatment (17-54 %; p < 0.001). Agreement for sex was excellent across sources (kappa 0.94); moderate for patient type (0.78), treatment regimen (0.79), treatment outcome (0.71); and poor for HIV status (0.33). CONCLUSIONS: The current evaluation revealed that one-third of persons diagnosed with TB disease may not have been notified of their disease or initiated on treatment ('initial defaulters'). The ETR is not capturing all TB patients. Further, among patients with a TB record, completeness and reliability of information in the TB Surveillance System is inconsistent across data sources. Actions are urgently needed to ensure that all diagnosed patients are treated and managed and improve the integrity of surveillance information.

OBJECTIVE: We validated cases of active tuberculosis (TB) recorded in the Indian Health Service (IHS) National Patient Information Reporting System (NPIRS) and evaluated the completeness of TB case reporting from IHS facilities to state health departments. METHODS: We reviewed the medical records of American Indian/Alaska Native (AI/AN) patients at IHS health facilities who were classified as having active TB using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes from 2006 to 2009 for clinical and laboratory evidence of TB disease. Individuals were reclassified as having active TB disease; recent latent TB infection (LTBI); past positive tuberculin skin test (TST) only; or as having no evidence of TB, LTBI, or a past positive TST. We compared validated active TB cases with corresponding state records to determine if they were reported. RESULTS: The study included 596 patients with active TB as per ICD-9-CM codes. Based on chart review, 111 (18.6%) had active TB; 156 (26.2%) had LTBI; 104 (17.4%) had a past positive TST; and 221 (37.1%) had no evidence of TB disease, LTBI, or a past positive TST. Of the 111 confirmed cases of active TB, 89 (80.2%) resided in participating states; 81 of 89 (91.2%) were verified as reported TB cases. CONCLUSIONS: ICD-9-CM codes for active TB disease in the IHS NPIRS do not accurately reflect the burden of TB among AI/ANs. Most confirmed active TB cases in the IHS health system were reported to the state; the national TB surveillance system may accurately represent the burden of TB in the AI/AN population.

Rapid influenza diagnostic tests (RIDTs) had low test sensitivity for detecting 2009 pandemic influenza A (H1N1pdm09) infection, causing public health authorities to recommend that treatment decisions be based primarily upon risk for influenza complications. We used multivariate Poisson regression analysis to estimate the contribution of RIDT results and risk for H1N1pdm09 complications to receipt of early antiviral (AV) treatment among 290 people with influenza-like illness (ILI) who received an RIDT ≤48 hours after symptom onset from May to December 2009 at four southwestern U.S. facilities. RIDT results had a stronger association with receipt of early AVs (rate ratio [RR] = 3.3, 95% confidence interval [CI] 2.4, 4.6) than did the presence of risk factors for H1N1pdm09 complications (age <5 years or high-risk medical conditions) (RR=1.9, 95% CI 1.3, 2.7). Few at-risk people (28/126, 22%) who had a negative RIDT received early AVs, suggesting the need for sustained efforts by public health to influence clinician practices.

BACKGROUND: Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. OBJECTIVES: To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. METHODS: We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. RESULTS: Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). CONCLUSION: Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes.

In 2004, routine use of culture and drug-susceptibility testing (DST) was implemented for persons in 5 Thailand provinces with a diagnosis of tuberculosis (TB). To determine if DST results were being used to guide treatment, we conducted a retrospective chart review for patients with rifampin-resistant or multidrug-resistant (MDR) TB during 2004-2008. A total of 208 patients were identified. Median time from clinical sample collection to physician review of DST results was 114 days. Only 5.8% of patients with MDR TB were empirically prescribed an appropriate regimen; an additional 31.3% received an appropriate regimen after DST results were reviewed. Most patients with rifampin -resistant or MDR TB had successful treatment outcomes. Patients with HIV co-infection and patients who were unmarried or had received category II treatment before DST results were reviewed had less successful outcomes. Overall, review of available DST results was delayed, and results were rarely used to improve treatment.

BACKGROUND: The accuracy of tuberculosis (TB) surveillance systems is paramount in TB control. In South Africa, information from the laboratory is not directly linked to the Electronic TB Register (ETR). OBJECTIVE: To validate smear results recorded in the ETR with those recorded in the laboratory. METHODS: A retrospective evaluation was conducted among all sputum smear-positive TB patients recorded in the ETR during the fourth quarter of 2009 in KwaZulu-Natal Province. RESULTS: Of 1036 smear-positive patients recorded in the ETR, 683 (65.9%) had positive results recorded in the laboratory register. Only 364 (53.2%) had their smear results recorded in the ETR at the end of the intensive phase of treatment; of 326 (89.6%) recorded as converted to smear-negative, 224 (61.5%) were confirmed as smear-negative in the laboratory. Of 331 patients with end-of-treatment results in the ETR, 302 (91.2%) were recorded as cured, but only 105 (34.8%) were confirmed in the laboratory. CONCLUSIONS: Over a third of TB patients registered as smear-positive in the ETR could not be confirmed based on laboratory results. Many patients did not have a laboratory record, lending to uncertainty as to the validity of the smear results and treatment outcomes recorded in the ETR.

BACKGROUND: The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence. OBJECTIVE: To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes. METHODS: Retrospective analysis of MDR TB patients. A treatment interruption was defined as any time that a patient missed a prescribed dose of treatment for at least 1 day but for a period of less than 2 consecutive months. Patients were characterized by the number, length and variability of interruptions, variability of time between interruptions, and percent of missed doses. Final treatment outcome was dichotomized as a successful (cured or completed) or poor outcome (defaulted, failed, or died). Risk ratios were calculated to determine the association between characteristics of treatment interruption and treatment outcomes. All analyses were conducted in 6 month treatment intervals. RESULTS: Only 7.0% of 583 patients completed treatment without interruption. Of the remaining 542 patients, the median time to the first interruption was 2 (1/2) months (70 days). In multivariate analysis, patients who had longer interruptions with sporadic variability during the 6-12 month or the 12-18 month treatment period had a significantly increased risk for poor outcomes compared to patients who had short, regular interruptions (RRadj 4.37, 95% CI 1.2-15.8; = 0.03 and RRadj 3.38, 95% CI 1.6-7.1; p = 0.001, respectively). In addition, missing 10% or more of the prescribed doses during any 6 month period in the initial 18 months of therapy significantly increased the risk for poor outcomes (RRadj range 1.55-2.35; p-value range 0.01-0.005). CONCLUSION: Patients that miss more consecutive days of treatment with sporadic interruption patterns or a greater proportion of treatment are at an increased risk for poor treatment outcomes.

Analysis of diagnostic smear positive records from the laboratory from KwaZulu-Natal in South Africa shows that not all patients are counted in surveillance efforts. However, review of paper-based patient records suggests the majority of identified TB patients are being treated. Directly linking laboratory and clinical records would enhance surveillance information.

SETTING: South Africa currently maintains separate surveillance systems for tuberculosis (TB) and human immunodeficiency virus (HIV). There are future plans for integration of these systems; however, the consistency of information across the existing systems has not previously been assessed. OBJECTIVE: To determine the completeness and concordance of data in the TB and HIV surveillance systems for TB-HIV co-infected patients. DESIGN: In a retrospective cohort evaluation of the records of TB-HIV co-infected patients in the Eden District of the Western Cape, data were abstracted from paper-based and electronic TB and HIV surveillance sources. Concordance was measured using Fleiss' kappa coefficient. RESULTS: Demographic variables had high completeness and concordance across the TB and HIV systems. Completeness and concordance for clinical variables was somewhat lower, particularly for TB variables in the HIV systems and HIV variables in the TB systems. CONCLUSION: Varying levels of completeness and concordance of surveillance data for TB-HIV co-infected patients highlight challenges in the current TB and HIV surveillance systems. Future integration of TB and HIV programs in this region will need to support more accurate data collection at all levels.

SETTING: In the Philippines, programmatic treatment of drug-resistant tuberculosis (TB) was initiated by the Tropical Disease Foundation in 1999 and transitioned to the National TB Program in 2006. OBJECTIVE: To determine patient and socio-demographic characteristics associated with default, and the impact of patient support measures on default. DESIGN: Retrospective cohort analysis of 583 MDR-TB patients treated from 1999 to 2006. RESULTS: A total of 88 (15%) patients defaulted from treatment. The median follow-up time for patients who defaulted was 289 days (range 1-846). In multivariate analysis adjusted for age, sex and previous TB treatment, receiving a greater number of treatment drugs (≥5 vs. 2-3 drugs, HR 7.2, 95%CI 3.3-16.0, P < 0.001) was significantly associated with an increased risk of default, while decentralization reduced the risk of default (HR 0.3, 95%CI 0.2-0.7, P < 0.001). CONCLUSION: Improving access to treatment for MDR-TB through decentralization of care to centers near the patient's residence reduced the risk of default. Further research is needed to evaluate the feasibility, impact and cost-effectiveness of decentralized care models for MDR-TB treatment.

BACKGROUND: Confirmation of cure for multidrugresistant tuberculosis (MDR-TB) patients requires laboratory tests for Mycobacterium tuberculosis growth on culture media. Outcome decisions dictate patient management, and inaccuracies place patients at an increased risk of morbidity and mortality, and may contribute to continued transmission of MDR-TB. OBJECTIVE: To examine concordance between programmatic and laboratory-based MDR-TB treatment outcomes. METHODS: The study population included 1658 MDRTB patients in Peru treated between 1996 and 2002 with both program and laboratory-based outcomes. Laboratory-based outcomes were assigned according to international standards requiring at least five consecutive negative cultures in the last 12 months of treatment to confirm cure. RESULTS: Compared to the global culture-defined standard classification, only 1.1% of treatment successes, but 54.3% of failures, were misclassified programmatically. Overall, 10.4% of patients identified by a clinician as having a successful treatment outcome still had cultures positive for MDR-TB. CONCLUSION: Most patients with successful treatment outcomes by strict culture definitions were also classified by clinicians as having successful outcomes. However, many culture-confirmed failures were missed. In light of delays and incomplete access to culture in MDR-TB programs, efforts should be made to improve the accuracy of programmatically determined treatment outcomes. (2012 The Union.)

OBJECTIVES: We examined trends and epidemiology of tuberculosis (TB) across racial/ethnic groups to better understand TB disparities in the United States, with particular focus on American Indians/Alaska Natives (AI/ANs) and Native Hawaiians/other Pacific Islanders (NH/PIs). METHODS: We analyzed cases in the U.S. National Tuberculosis Surveillance System and calculated TB case rates among all racial/ethnic groups from 2003 to 2008. Socioeconomic and health indicators for counties in which TB cases were reported came from the Health Resources and Services Administration Area Resource File. RESULTS: Among the 82,836 TB cases, 914 (1.1%) were in AI/ANs and 362 (0.4%) were in NH/PIs. In 2008, TB case rates for AI/ANs and NH/PIs were 5.9 and 14.7 per 100,000 population, respectively, rates that were more than five and 13 times greater than for non-Hispanic white people (1.1 per 100,000 population). From 2003 to 2008, AI/ANs had the largest percentage decline in TB case rates (-27.4%) for any racial/ethnic group, but NH/PIs had the smallest percentage decline (-3.5%). AI/ANs were more likely than other racial/ethnic groups to be homeless, excessively use alcohol, receive totally directly observed therapy, and come from counties with a greater proportion of people living in poverty and without health insurance. A greater proportion of NH/PIs had extrapulmonary disease and came from counties with a higher proportion of people with a high school diploma. CONCLUSIONS: There is a need to develop flexible TB-control strategies that address the social determinants of health and that are tailored to the specific needs of AI/ANs and NH/PIs in the U.S.

OBJECTIVES: Deaths due to diarrhea among US children declined substantially from the 1960s through the 1980s, but have not been recently assessed. We examined diarrhea-associated mortality among young US children from 1992 to 2006 to establish baseline estimates through which the effect of rotavirus vaccines, introduced in 2006, can be assessed. METHODS: National Center for Health Statistics multiple cause-of-death mortality data were used to examine diarrhea-associated deaths and death rates among US children 1 to 59 months of age during 1992-2006. The winter residual method was used to indirectly estimate the annual number of diarrhea-associated deaths attributable to rotavirus. RESULTS: An average of 369 diarrhea-associated deaths/year (3320 total deaths) occurred among US children 1 to 59 months of age during 1992-1998 and 2005-2006. The diarrhea-associated death rate increased 40% between the first 3 and last 2 years of the study period, from an average of 1.6 deaths per 100,000 to 2.3 deaths per 100,000. Black children died at almost 4 times the rate of white children. Diarrhea-associated deaths showed a winter seasonal pattern similar to that of rotavirus, particularly among children 4 to 23 months of age. Using indirect methods, we estimated 25 yearly rotavirus-associated deaths during the study period. Rotavirus vaccination could potentially prevent 21 of these deaths annually. CONCLUSIONS: Diarrhea-associated mortality among US children stabilized but appears to be increasing in recent years. Rotavirus was associated with a small but significant number of preventable deaths. The national multiple cause-of-death data should prove useful for assessing mortality impact of rotavirus vaccination in the United States.

BACKGROUND: Over the past several years, new diagnostic techniques have been developed to allow for the rapid detection of multidrug resistant tuberculosis. The GenoType MTBDRplus test is a deoxyribonucleic acid (DNA) strip assay which uses polymerase chain reaction (PCR) and hybridization to detect genetic mutations in the genes that confer isoniazid (INH) and rifampn (RIF) resistance. This assay has demonstrated good performance and a rapid time to results, making this a promising tool to accelerate MDR-TB diagnosis and improve MDR-TB control. Validation of rapid tests for MDR-TB detection in different settings is needed to ensure acceptable performance, particularly in Asia, which has the largest number of MDR-TB cases in the world but only one previous report, in Vietnam, about the performance of the GenoType MDRplus assay. Thailand is ranked 18th of 22 "high-burden" TB countries in the world, and there is evidence to suggest that rates of MDR-TB are increasing in Thailand. We compared the performance of the GenoType MTBDRplus assay to Mycobacterial Growth Indicator Tube for Antimycobacterial Susceptibility Testing (MGIT AST) for detection INH resistance, RIF resistance, and MDR-TB in stored acid-fast bacilli (AFB)-positive sputum specimens and isolates at a Public TB laboratory in Bangkok, Thailand. METHODS: 50 stored isolates and 164 stored AFB-positive sputum specimens were tested using both the MGIT AST and the GenoType MTBDRplus assay. RESULTS: The GenoType MTBDRplus assay had a sensitivity of 95.3%, 100%, and 94.4% for INH resistance, RIF resistance, and MDR-TB, respectively. The difference in sensitivity between sputum specimens (93%) and isolates (100%) for INH resistance was not statistically significant (p = 0.08). Specificity was 100% for all resistance patterns and for both specimens and isolates. The laboratory processing time was a median of 25 days for MGIT AST and 5 days for the GenoType MTBDRplus (p < 0.01). CONCLUSION: The GenoType MTBDRplus assay has been validated as a rapid and reliable first-line diagnostic test on AFB-positive sputum or MTB isolates for INH resistance, RIF resistance, and MDR-TB in Bangkok, Thailand. Further studies are needed to evaluate its impact on treatment outcome and the feasibility and cost associated with widespread implementation.

Despite the adoption of strategies to prevent and treat multidrug-resistant tuberculosis (MDR-TB) over the past decade, Latvia continues to have one of the highest rates of MDR-TB in the world. It is important to identify modifiable factors that may impact on MDR-TB patient outcomes. A study was conducted to elucidate the association between nutritional status and clinical presentation, clinical course, and mortality in 995 adult patients treated for MDR-TB from 2000 to 2004. Twenty percent of patients were underweight, defined as a body mass index <18.5, at the time of diagnosis. These patients were significantly more likely to have clinical evidence of advanced disease, and had a greater risk of experiencing 3 side-effects [adjusted odds ratio 1.5, 95% confidence interval (CI) 1.1-2.1] and death (adjusted hazard ratio 1.9, 95% CI 1.1-3.5) compared to patients who were normal or overweight. Interventions aimed at these high-risk patients, including nutritional supplementation as an adjunct to anti-TB therapy, should be considered and evaluated by TB programmes.

BACKGROUND: Rotavirus is the leading cause of severe gastroenteritis in children worldwide. We evaluated the economic burden of rotavirus and the cost-effectiveness of vaccination from the health care perspective. METHODS: Estimates were based on existing epidemiological data, cost estimates, vaccine coverage, and efficacy data, as well as hypothetical vaccine prices. Outcome measures included health care and societal costs of rotavirus and benefits and incremental cost-effectiveness ratio of vaccination. Sensitivity analyses evaluated the impact of estimate uncertainty. RESULTS: Treatment costs increased with income level, and health burden decreased; however, burden varied across regions. On the basis of current vaccination coverage and timing, rotavirus vaccination would annually prevent 228,000 deaths, 13.7 million hospital visits, and 8.7 million disability-adjusted life-years, saving $188 million in treatment costs and $243 million in societal costs. At $5 per dose, the incremental cost-effectiveness ratio in low-, lower-middle-, and upper-middle-income countries was $88, $291, and $329 per disability-adjusted life-year averted, respectively, and $3,015, $9,951 and $11,296 per life saved, respectively. Vaccination would prevent approximately 45% of deaths and approximately 58% of associated medical visits and costs. CONCLUSIONS: Vaccination is a cost-effective strategy to reduce the health and economic burden of rotavirus. The cost-effectiveness of vaccination depends mostly on vaccine price and reaching children at highest risk of mortality.