Optimizing the efficiency of tuberculosis active case-finding in health facilities and communities.

SETTING: Efficient tuberculosis (TB) active case-finding strategies are important in settings with high TB burdens and limited resources, such as those in western Kenya.OBJECTIVE: To guide efforts to optimize screening efficiency, we identified the predictors of TB among people screened in health facilities and communities.DESIGN: During February 2015-June 2016, adults aged ≥15 years reporting any TB symptom were identified in health facilities and community mobile screening units, and evaluated for TB. We assessed the predictors of TB using a modified Poisson regression with generalized estimating equations to account for clustering according to screening site.RESULTS: TB was diagnosed in 484 (20.3%) of 2394 symptomatic adults in health facilities and 39 (3.4%) of 1424 in communities. In health facilities, >10% of symptomatic adults in all demographic groups had TB, and no predictors were associated with a ≥2-fold increased risk. In communities, the independent predictors of TB were male sex (adjusted prevalence ratio [aPR] = 4.26, 95%CI 2.43-7.45), HIV infection (aPR 2.37, 95%CI 1.18-4.77), and household TB contact in the last 2 years (aPR 2.84, 95%CI 1.62-4.96).CONCLUSION: Our findings support the notion of general TB screening in health facilities and evaluation of the adult household contacts of TB patients.

Lessons learned from community-based tuberculosis case-finding in western Kenya.

SETTING: Although Kenya has a high burden of tuberculosis (TB), only 46% of cases were diagnosed in 2016. OBJECTIVE: To identify strategies for increasing attendance at community-based mobile screening units. DESIGN: We analysed operational data from a cluster-randomised trial, which included community-based mobile screening implemented during February 2015-April 2016. Community health volunteers (CHVs) recruited individuals with symptoms from the community, who were offered testing for human immunodeficiency virus (HIV) and sputum collection for Xpert® MTB/RIF testing. We compared attendance across different mobile unit sites using Wilcoxon rank-sum test. RESULTS: A total of 1424 adults with symptoms were screened at 25 mobile unit sites. The median total attendance among sites was 54 (range 6-134, interquartile range [IQR] 24-84). The median yields of TB diagnoses and new HIV diagnoses were respectively 2.4% (range 0.0-16.7, IQR 0.0-5.3) and 2.5% (range 0.0-33.3, IQR 1.2-4.2). Attendance at urban sites was variable; attendance at rural sites where CHVs were paid a daily minimum wage was significantly higher than at rural sites where CHVs were paid a nominal monthly stipend (P < 0.001). CONCLUSION: Mobile units were most effective and efficient when implemented as a single event with community health workers who are paid a daily wage.

Detection of Apparent Cell-free M. tuberculosis DNA from Plasma.

New diagnostics are needed to improve clinicians' ability to detect tuberculosis (TB) disease in key populations such as children and persons living with HIV and to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma is a diagnostic target in new obstetric and oncologic applications, but its utility for diagnosing TB is not known. Here we show that Mycobacterium tuberculosis complex DNA can be detected in plasma of persons with sputum smear-positive TB, even in the absence of mycobacteremia. Among 40 participants with bacteriologically-confirmed smear-positive TB disease who had plasma tested by quantitative PCR (qPCR), 18/40 (45%) had a positive result on at least one triplicate reaction. Our results suggest that plasma DNA may be a useful target for improving clinicians' ability to diagnose TB. We anticipate these findings to be the starting point for optimized methods of TB ccfDNA testing and sequence-based diagnostic applications such as molecular detection of drug resistance.

Assessing the effect of decentralisation of laboratory diagnosis for drug-resistant tuberculosis in Kenya.

SETTING: Drug susceptibility testing (DST) is recommended in Kenya to identify multidrug-resistant tuberculosis (MDR-TB) in persons registered for tuberculosis (TB) retreatment. DST is performed at a central laboratory with a two-step growth-based process and a regional laboratory with a simultaneous molecular- and growth-based process. OBJECTIVE: To compare proportions of retreatment cases who underwent DST and turnaround times for hospitals referring to the central vs. regional laboratory. DESIGN: Cases were persons registered for TB retreatment from 1 January 2012 to 31 December 2013. Records of 11 hospitals and 7 hospitals referring patients to the regional and central laboratories, respectively, were reviewed. RESULTS: Respectively 238/432 (55%) and 88/355 (25%) cases from hospitals referring to the regional and central laboratories underwent DST. The mean time from case registration to receipt of DST results and initiation of MDR-TB treatment was quicker in hospitals referring to the regional laboratory. The time required for the transportation of specimens, specimen testing and receipt of DST results at hospitals was shorter for the regional laboratory (P < 0.05). CONCLUSION: Testing was faster and more complete at hospitals referring to the regional laboratory. A comprehensive review of MDR-TB detection in Kenya is required to increase the proportion of cases receiving DST.

The disconnect between a national tuberculosis drug resistance survey and treatment outcomes: a lost opportunity.

We linked results from the Fourth Botswana National Drug Resistance Survey (DRS), 2007-2008, to patient records from the national Electronic Tuberculosis Registry to determine treatment outcomes. Of 915 new patients, 651 (71%) had treatment data available. Completion or cure was achieved for 10/15 (67%, 95%CI 42-85) with isoniazid monoresistance, (6/16, 38%, 95%CI 18-61) with multidrug resistance, while 73% (391/537, 95%CI 69-76) were susceptible to first-line drugs. The analysis was limited because of unavailable treatment records and undocumented outcomes. Prospective analyses following DRSs should be considered to ensure adequate outcome data.

Increase in anti-tuberculosis drug resistance in Botswana: results from the fourth National Drug Resistance Survey.

SETTING: Although approximately 0.5 million cases of multidrug-resistant tuberculosis (MDR-TB) occur globally each year, surveillance data are limited. Botswana is one of the few high TB burden countries to have carried out multiple anti-tuberculosis drug resistance surveys (in 1995-1996, 1999 and 2002). OBJECTIVE: In 2007-2008, we conducted the fourth national survey of anti-tuberculosis drug resistance in Botswana to assess anti-tuberculosis drug resistance, including trends over time. In the previous survey, 0.8% (95%CI 0.4-1.5) of new patients and 10.4% (95%CI 5.6-17.3) of previously treated patients had MDR-TB. DESIGN: During the survey period, eligible specimens from all new sputum-smear positive TB patients and from all TB patients with history of previous anti-tuberculosis treatment underwent mycobacterial culture and anti-tuberculosis drug susceptibility testing (DST). RESULTS: Of 924 new TB patients and 137 with previous anti-tuberculosis treatment with DST results, respectively 23 (2.5%, 95%CI 1.6-3.7) and 9 (6.6%, 95%CI 3.3-11.7) had MDR-TB. The proportion of new TB patients with MDR-TB has tripled in Botswana since the previous survey. CONCLUSION: Combatting drug-resistant TB will require the scale-up of MDR-TB diagnosis and treatment to prevent the transmission of MDR-TB and strengthening of general TB control to prevent the emergence of resistance.

The utility of stool cultures for diagnosing tuberculosis in people living with the human immunodeficiency virus.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) increases mortality. OBJECTIVE: To evaluate whether stool culture improves the diagnosis of TB in people living with the human immunodeficiency virus (PLHIV). DESIGN: We analysed cross-sectional data of TB diagnosis in PLHIV in Cambodia, Thailand and Viet Nam. Logistic regression was used to assess the association between positive stool culture and TB, and to calculate the incremental yield of stool culture. RESULTS: A total of 1693 PLHIV were enrolled with a stool culture result. Of 228 PLHIV with culture-confirmed TB from any site, 101 (44%) had a positive stool culture; of these, 91 (90%) had pulmonary TB (PTB). After adjusting for confounding factors, a positive stool culture was associated with smear-negative (odds ratio [OR] 26, 95% confidence interval [CI] 12-58), moderately smear-positive (OR 60, 95%CI 23-159) and highly smear-positive (OR 179, 95%CI 59-546) PTB compared with no PTB. No statistically significant association existed with extra-pulmonary TB compared with no extra-pulmonary TB (OR 2, 95%CI 1-5). The incremental yield of one stool culture above two sputum cultures (5%, 95%CI 3-8) was comparable to an additional sputum culture (7%, 95%CI 4-11). CONCLUSION: Nearly half of the PLHIV with TB had a positive stool culture that was strongly associated with PTB. Stool cultures may be used to diagnose TB in PLHIV.

Screening for pulmonary tuberculosis in HIV-infected individuals: AIDS Clinical Trials Group Protocol A5253.

BACKGROUND: Improved tuberculosis (TB) screening is urgently needed for human immunodeficiency virus (HIV) infected patients. METHODS: An observational, multi-country, cross-sectional study of HIV-infected patients to compare a standardized diagnostic evaluation (SDE) for TB with standard of care (SOC). SOC evaluations included TB symptom review (current cough, fever, night sweats and/or weight loss), sputum Ziehl-Neelsen staining and chest radiography. SDE screening added extended clinical signs and symptoms and fluorescent microscopy (FM). All participants underwent all evaluations. Mycobacterium tuberculosis on sputum culture was the primary outcome. RESULTS: A total of 801 participants were enrolled from Botswana, Malawi, South Africa, Zimbabwe, India, Peru and Brazil. The median age was 33 years; 37% were male, and median CD4 count was 275 cells/mm(3). Thirty-one participants (4%) had a positive culture on Löwenstein-Jensen media and 54 (8%) on MGIT. All but one positive culture came from sub-Saharan Africa, where the prevalence of TB was 54/445 (12%). SOC screening had 54% sensitivity (95%CI 40-67) and 76% specificity (95%CI 72-80). Positive and negative predictive values were respectively 24% and 92%. No elements of the SDE improved the predictive values of SOC. CONCLUSIONS: Symptom-based screening with smear microscopy was insufficiently sensitive. More sensitive diagnostic testing is required for HIV-infected patients.

Alcohol use, drunkenness and tobacco smoking in rural western Kenya.

OBJECTIVES: To describe the prevalence of smoking and alcohol use and abuse in an impoverished rural region of western Kenya. METHODS: Picked from a population-based longitudinal database of demographic and health census data, 72 292 adults (≥18 years) were asked to self-report their recent (within the past 30 days) and lifetime use of tobacco and alcohol and frequency of recent 'drunkenness'. RESULTS: Overall prevalence of ever smoking was 11.2% (11.0-11.5) and of ever drinking, 20.7% (20.4-21.0). The prevalence of current smoking was 6.3% (6.1-6.5); 5.7% (5.5-5.9) smoked daily. 7.3% (7.1-7.5) reported drinking alcohol within the past 30 days. Of these, 60.3% (58.9-61.6) reported being drunk on half or more of all drinking occasions. The percentage of current smokers rose with the number of drinking days in a month (P < 0.0001). Tobacco and alcohol use increased with decreasing socio-economic status and amongst women in the oldest age group (P < 0.0001). CONCLUSIONS: Tobacco and alcohol use are prevalent in this rural region of Kenya. Abuse of alcohol is common and likely influenced by the availability of cheap, home-manufactured alcohol. Appropriate evidence-based policies to reduce alcohol and tobacco use should be widely implemented and complemented by public health efforts to increase awareness of their harmful effects.

Epidemiology of smear-negative pulmonary tuberculosis in the United States, 1993-2008.

BACKGROUND: Smear-negative tuberculosis (TB) is difficult to diagnose and has been associated with poor treatment outcomes and excessive mortality, particularly in high human immunodeficiency virus (HIV) prevalent settings. However, few studies have used mycobacterial culture to rigorously confirm all smear-negative TB cases in a population-based cohort. DESIGN: We included all culture-confirmed, pulmonary TB cases reported to the US National TB Surveillance System from 1993 to 2008. We analyzed smear-negative TB risk factors and survival, as compared to smear-positive TB. We calculated prevalence ratios (PRs) and adjusted for confounders (aPR). RESULTS: From 1993 to 2008, 159,121 cases of culture-confirmed pulmonary TB were reported in the United States, of which 58,786 (37%) were sputum smear-negative. Smear-negative TB cases were more likely to be foreign-born (aPR 1.10, 95%CI 1.08-1.12), incarcerated (aPR 1.52, 95%CI 1.48-1.56) or HIV-infected (aPR 1.27, 95%CI 1.24-1.30). Hispanics and non-Hispanic Blacks were less likely to have smear-negative TB (respectively aPR 0.87, 95%CI 0.85-0.89 and aPR 0.90, 95%CI 0.89-0.92). Smear-negative TB cases had lower mortality (aRR 0.78, 95%CI 0.74-0.81), independent of HIV status. CONCLUSION: Smear-negative TB represents a large proportion of TB cases in the United States, and occurs more often among persons in groups more likely to undergo TB screening. The lower mortality may indicate earlier TB detection, and underscores the need for continued vigilance in screening of high-risk persons.

Global policies and practices for managing persons exposed to multidrug-resistant tuberculosis.

SETTING: In the 1960s, treatment for latent tuberculosis infection (LTBI) with isoniazid proved to be so effective, safe, and inexpensive that research into alternative treatments virtually ceased. Now that multidrug-resistant tuberculosis (MDR-TB) is widespread, no data are available to guide the management of persons exposed to MDR-TB (contacts). METHODS: We surveyed National TB Program directors and MDR-TB program managers about current practices for managing MDR-TB contacts in countries with an MDR-TB prevalence of >2% in new patients and those with programs for managing MDR-TB. RESULTS: Of 35 countries that met the survey criteria, 25 (71%) responded; 24 of these (96%) have a guideline for managing TB contacts. Of these, 19 (76%) usually or always evaluated contacts and treated LTBI. In contrast, 10 (40%) countries reported having a guideline for managing MDR-TB contacts, 11 (44%) usually or always evaluated MDR-TB contacts, and 9 (36%) treated LTBI. Only two (8%) used a regimen that has activity against MDR-TB. Lack of evidence or guidelines was the main reason for not treating MDR-TB contacts. CONCLUSIONS: Management of MDR-TB contacts is inconsistent and ineffective due to lack of evidence-based guidelines. There is an urgent need to generate evidence to guide policy.

Adjunctive resectional lung surgery for extensively drug-resistant tuberculosis.

Extensively drug-resistant (XDR) tuberculosis (TB) poses significant management challenges as there are limited pharmacological treatment options for cure. Adjunctive resectional lung surgery decreases case-fatality rates for some patients with multidrug-resistant tuberculosis (MDR-TB), but its use has not been well documented for patients with XDR-TB. We describe 17 XDR-TB patients treated with surgery as part of their case management in Latvia during 1999-2005. One patient had no previous TB treatment history, 10 were previously treated for drug-susceptible TB and six were previously treated for MDR-TB. Mycobacterium tuberculosis isolates from the 17 patients were resistant to a mean of 9.2 drugs. Due to failure of pharmacological therapy, one due to a large cavity and one due to pulmonary haemorrhage, 15 patients were treated with surgery. Despite failure of pharmacological treatment in 15 out of 17 patients, eight (47%) were cured with adjunctive surgical treatment. Surgery should be explored as a possible treatment option for patients with XDR-TB.

Association between distance to HIV testing site and uptake of HIV testing for tuberculosis patients in Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: Cambodia has the highest incidence of tuberculosis (TB) in Asia. Not all TB patients are tested for human immunodeficiency virus (HIV). We assessed the association between distance to HIV testing facility and HIV testing rates. METHODS: We analyzed data on TB patients from 11 clinics to determine the proportion tested for HIV infection. We categorized each TB clinic as having a voluntary confidential counseling and testing (VCCT) center onsite, or being at <15 min, 15-30 min or >30 min driving distance to the nearest VCCT. RESULTS: Of 1017 TB patients not previously tested for HIV, 708 (70%) were tested. Of 481 TB patients without onsite VCCT, 297 (62%) were tested, compared to 410 (77%) of 535 TB patients with onsite VCCT (RR 0.6, 95%CI 0.5-0.7). When the VCCT site was >15 min from the TB clinic, HIV testing occurred only half as frequently as when onsite VCCT was available. CONCLUSION: TB patients treated at clinics without onsite or nearby HIV testing are less commonly tested for HIV infection. Making HIV testing available to TB patients without the necessity of traveling to a distant HIV testing site is likely to increase HIV testing rates.

Tuberculosis risk among staff of a large public hospital in Kenya.

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.

Using program evaluation to improve the performance of a TB-HIV project in Banteay Meanchey, Cambodia.

SETTING: Cambodia has the highest human immunodeficiency virus (HIV) prevalence (1.9%) and tuberculosis (TB) incidence (508/100000) in Asia. Banteay Meanchey, a province with high HIV prevalence of 1.9%, established a pilot project in 2003 to enhance TB-HIV activities. We evaluated this project to improve performance. METHODS: In March 2005, we analyzed 17 months of data on all persons diagnosed with HIV or TB at 11 participating clinics. We determined barriers to HIV testing and TB screening, modified the program to reduce these barriers and assessed whether our interventions improved testing and screening rates. RESULTS: Among 952 patients newly diagnosed with TB disease, 138 (14%) had known HIV infection at the time of TB diagnosis. Of the 814 TB patients with unknown HIV status, 432 (53%) were HIV tested. Of 1228 persons newly diagnosed with HIV infection, 450 (37%) were screened for TB disease. We found and addressed barriers to HIV testing and TB screening. In the 9 months after the interventions, 240/322 (71%) TB patients were HIV tested, an increase of 34% (P < 0.01); 426/751 (57%) HIV-infected patients were screened for TB, an increase of 54% (P < 0.01). CONCLUSION: Evaluations of TB-HIV collaborative activities can lead to increased TB screening and HIV testing rates.

The epidemiology of HIV-associated tuberculosis in rural Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: The World Health Organization recommends human immunodeficiency virus (HIV) testing for all tuberculosis (TB) patients and TB screening for all HIV-infected persons in countries with a TB-HIV syndemic. We sought to determine whether evidence supports implementing these recommendations in South-East Asia. DESIGN: We conducted a cross-sectional survey and retrospective cohort study of patients newly diagnosed with HIV or TB from October 2003 to February 2005 to identify risk factors for HIV infection and TB, and for death during TB treatment. RESULTS: HIV infection was diagnosed in 216/574 (38%) TB patients. TB disease was found in 124/450 (24%) HIV-infected persons. No sub-groups of patients had a low risk of HIV infection or TB. Of 180 TB patients with HIV infection and a recorded treatment outcome, 49 (27%) died compared to 17/357 (5%) without HIV infection (relative risk [RR] 5.2, 95% confidence interval [CI] 3.1-8.7). HIV-infected TB patients with smear-negative pulmonary disease died less frequently than those with smear-positive pulmonary disease (RR 0.39, 95%CI 0.16-0.93). CONCLUSIONS: No sub-groups of patients had low risk for HIV infection or TB, and mortality among HIV-infected TB patients was high. These data justify using the WHO global TB-HIV recommendations in South-East Asia. Urgent interventions are needed to reduce the high mortality rate in HIV-infected TB patients.