High Tuberculosis Burden Countries Research Articles

Multi-drug resistant Mycobacterium tuberculosis in Port Harcourt, Nigeria.

BackgroundIn past years, much focus has been on tackling the scourge and spread of tuberculosis worldwide. The recent emergence of multi-drug resistant (MDR) tuberculosis has, however, negatively threatened progress made so far. Nigeria ranks fourth out of the 22 high tuberculosis burden countries in the world and has the highest burden of tuberculosis in Africa. It is therefore necessary to monitor the MDR tuberculosis situation in the country.ObjectivesThis study set out to assess the proportions of MDR tuberculosis in patients attending six directly observed treatment short-course centres in Port Harcourt, Nigeria, from October 2015 to October 2016.MethodsSix hundred and nine participants between the ages of 18 and 75 years were enrolled in this study and comprised suspected and newly diagnosed tuberculosis cases. Sputum samples obtained from the participants were screened for the presence of Mycobacterium tuberculosis using standard culture and phenotypic biochemical techniques, and drug susceptibility testing was carried out using the 1% proportion conventional method.ResultsOf the 609 participants enrolled, 30 (4.9%) were confirmed as M. tuberculosis-positive cases. A high prevalence of drug resistant tuberculosis was noted in this study (14/30, 46.7%), with 26.7% of isolates resistant to streptomycin. MDR tuberculosis, defined as being resistant to isoniazid and rifampicin, was detected in only one case (3.3%).ConclusionThis study reports a low rate of MDR tuberculosis and contributes to the sparse data on drug resistant tuberculosis in Nigeria.

Tuberculosis in Mozambique: Where Do We Stand?

Tuberculosis (TB) is a global health concern, and Mozambique is one of the few high burden tuberculosis countries where the estimated TB incidence has not improved in recent years. The objective of this review is to provide a snapshot of the current situation of the TB epidemic in Mozambique, highlighting the main epidemiological features and particularities of TB care and control in the country. Despite several efforts aimed at improving diagnosis and treatment success, the overall burden of TB, HIV-TB, and multidrug-resistant (MDR)-TB is enormous, with high TB-associated mortality. Improving surveillance is a key step for understanding the TB epidemic in the country, and the first TB prevalence survey is underway. Overall, drug-sensitive and MDR-TB notifications have increased markedly over the last 5 years, likely due in part to a more active case finding approaches, but the diagnosis gap is still substantial. The roll-out of Xpert technology to decentralized settings is improving TB diagnosis in the country, particularly for MDR-TB. Although some progress has been made in TB control in Mozambique, the challenges for TB control and elimination are enormous. More actively finding cases at health facilities and in communities via contact tracing, improving national surveillance/monitoring and evaluation systems, expanding TB molecular diagnosis, implementing shorter MDR-TB treatments, and improving HIV-TB case management (including rigorous TB screening and higher coverage of preventive therapies in people living with HIV) are considered key priorities for the National TB Control Program.

Genetic characterization of Mycobacterium tuberculosis complex isolates circulating in Abuja, Nigeria.

ObjectiveNigeria ranks fourth among the high tuberculosis (TB) burden countries. This study describes the prevalence of drug resistance and the genetic diversity of Mycobacterium tuberculosis in Abuja’s Federal Capital Territory.Materials and methodsTwo hundred and seventy-eight consecutive sputum samples were collected from adults with presumptive TB during 2013–2014. DNA was extracted from Löwenstein–Jensen cultures and analyzed for the identification of nontuberculous mycobacteria species, detection of drug resistance with line probe assays, and high-throughput spacer oligonucleotide typing (spoligotyping) using microbead-based hybridization.ResultsTwo hundred and two cultures were positive for M. tuberculosis complex, 24 negative, 38 contaminated, and 15 positive for nontuberculous mycobacteria. Five (2.5%) M. tuberculosis complex isolates were resistant to rifampicin (RIF) and isoniazid (multidrug resistant), nine (4.5%) to RIF alone, and 15 (7.4%) to isoniazid alone; two RIF-resistant isolates were also resistant to fluoroquinolones and ethambutol, and one multidrug resistant isolate was also resistant to ethambutol. Among the 180 isolates with spoligotyping results, 164 (91.1%) were classified as lineage 4 (Euro-American), 13 (7.2%) as lineage 5 (West African 1), two (1.1%) as lineage 2 (East Asia), and one (0.6%) as lineage 6 (West African 2). One hundred and fifty-six (86.7%) isolates were grouped in 17 clusters (2–108 isolates/cluster), of which 108 (60.0%) were grouped as L4.6.2/Cameroon (spoligotype international type 61).ConclusionThe description of drug resistance prevalence and genetic diversity of M. tuberculosis in this study may be useful for improving TB control in Nigeria.

Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: A trend analysis from 2014 - 2016.

Background: Xpert® MTB/RIF, a rapid tuberculosis (TB) molecular test, was endorsed by the World Health Organization in 2010. Since then, 34.4 million cartridges have been procured under concessional pricing. Although the roll out of this diagnostic is promising, previous studies showed low market penetration. Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the public sector, smear and Xpert MTB/RIF volumes for the year 2016 were evaluated and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied. A structured questionnaire was sent to representatives of 22 HBCs. The questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of modules and days of operation of GeneXpert machines in National TB Programs (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and GeneXpert procurement by other disease control programs were collected. Market penetration was estimated by the ratio of total sputum smear volume for initial diagnosis divided by the number of Xpert MTB/RIF tests procured in the public sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios decreased in 17/21 countries and increased in four countries, since 2014. The median ratio decreased from 32.6 (IQR: 44.6) in 2014 to 6.0 (IQR: 15.4) in 2016. In 2016, the median GeneXpert utilization was 20%, however seven countries (7/19; 37%) were running tests for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV, hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in 2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines were under-utilized for TB, and inadequately exploited as a multi disease technology.

Chronic Respiratory Symptoms and Lung Abnormalities Among People With a History of Tuberculosis in Uganda: A National Survey.

People with pulmonary tuberculosis are at risk of developing chronic respiratory disorders due to residual lung damage. To date, the scope of the problem in high-burden tuberculosis countries is relatively unknown. Chronic respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung abnormalities were compared between adults with and without a history of tuberculosis among the general population of Uganda. Multivariable regression models were used to estimate odds ratios (ORs) with adjustment for age, gender, smoking, education, setting, and region. Random effects models accounted for village clustering effect. Of 45293 invited people from 70 villages, 41154 (90.9%) participated in the survey. A total of 798 had a history of tuberculosis and, among them, 16% had respiratory symptoms and 41% X-ray abnormalities. Adjusted ORs showed strong evidence for individuals with a history of tuberculosis having increased risk of respiratory symptoms (OR, 4.02; 95% confidence interval [CI], 3.25-4.96) and X-ray abnormalities (OR, 17.52; 95% CI, 14.76-20.79), attributing 6% and 24% of the respective population risks. In Uganda, a history of tuberculosis was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating tuberculosis disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.

Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: A trend analysis from 2014 - 2016

Background: Xpert® MTB/RIF, a rapid tuberculosis (TB) molecular test, was endorsed by the World Health Organization in 2010. Since then, 34.4 million cartridges have been procured under concessional pricing. Although the roll out of this diagnostic is promising, previous studies showed low market penetration. Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the public sector, smear and Xpert MTB/RIF volumes for the year 2016 were evaluated and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied. A structured questionnaire was sent to representatives of 22 HBCs. The questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of modules and days of operation of GeneXpert machines in National TB Programs (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and GeneXpert procurement by other disease control programs were collected. Market penetration was estimated by the ratio of total sputum smear volume for initial diagnosis divided by the number of Xpert MTB/RIF tests procured in the public sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios decreased in 17/21 countries and increased in four countries, since 2014. The median ratio decreased from 32.6 (IQR: 44.6) in 2014 to 6.0 (IQR: 15.4) in 2016. In 2016, the median GeneXpert utilization was 20%, however seven countries (7/19; 37%) were running tests for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV, hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in 2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines were under-utilized for TB, and inadequately exploited as a multi disease technology.

Tuberculosis incidence in England hits 30-year low

Tuberculosis incidence in England hits 30-year low

Drug Susceptibility Testing and Mortality in Patients Treated for Tuberculosis in High-Burden Countries

Background: Drug resistance and HIV co-infection are challenges for the global control of tuberculosis. Methods: We collected Mycobacterium tuberculosis isolates from adult patients in Cote d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status. Findings: 634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases, corresponding to a sensitivity of 84.3% and a specificity of 90.8%. In patients with drug-resistant tuberculosis, discordant results were associated with increased mortality (risk ratio 1.81; 95% CI 1.07-3.07). In logistic regression, compared to adequately treated patients with pan-susceptible strains, the adjusted odds ratio for death was 4.23 (95% CI 2.16-8.29) for adequately treated patients with drug-resistant strains and 21.54 (95% CI 3.36-138.1) for inadequately treated patients with drug-resistant strains. HIV status was not associated with mortality. Interpretation: Using a reference laboratory standard, inaccurate DST leading to inappropriate treatment of drug-resistant tuberculosis, but not HIV infection, contributed to mortality. Funding Statement: This research was supported by the Swiss National Science Foundation (grant numbers 153442, 310030_166687 and 174281), the National Institutes of Allergy and Infectious Diseases (NIAID) under award numbers U01 AI096299, U01 AI069919, U01 AI069924, U01 AI069911, U01 AI069907, U01 AI096186, and U01 AI069923, and Swiss National Center for Mycobacteria, University of Zurich, Switzerland. Declaration of Interests: AA has received honoraria fees from Jensen-Cilag, Gilead and Bristol-Myers Squibb. All other authors have no conflicts of interest to declare. Ethics Approval Statement:Local institutional review boards or ethics committees approved the study at all participating sites. Informed consent was obtained where requested per local regulations. The study was also approved by the Cantonal Ethics Committee in Bern, Switzerland.

Prevalence of rifampicin resistant tuberculosis and associated factors among presumptive tuberculosis patients in a secondary referral hospital in Lagos Nigeria.

Nigeria is one of the 30 high burden countries for drug resistant tuberculosis (DR-TB). This study assessed the prevalence and factors associated with rifampicin resistant tuberculosis (RR-TB) in a secondary referral hospital in Lagos State Nigeria. A retrospective review of presumptive TB register of patients screened for Mycobacterium tuberculosis (MTB) and RR-TB using Xpert MTB/RIF assay at Mainland hospital between January 1 2012 and December 31 2016 was conducted. A total of 2497 clients were screened for MTB and RR-TB during the study period. The majority (51.4%) were between 25 - 44 years. Male: Female ratio was 1:0.8. Of the 2497 clients screened, MTB was detected in 942 (37.7%) out of which 220 (23.4%) had RR-TB. Age (AOR 1.8, 95%CI 1.3- 2.6, p = 0.001), symptomatic contact with DR-TB patients (AOR 3.3, 95%CI 2.1-5.1, p <0.001) and type of TB (AOR 2.9, 95% CI 1.7 - 5.0, <0.001) were associated with RR-TB after adjusting for age, gender, HIV status and symptomatic contacts with DR-TB patients. The prevalence of RR-TB in new and previously treated TB patients was high in this study. Urgent steps are needed to avert an impending RR-TB epidemic.

Tuberculosis preventive treatment preferences among care givers of children in Lesotho: a pilot study.

Shorter-duration regimens for preventing drug-susceptible tuberculosis (TB) have been shown to be safe and efficacious in children, and may improve acceptability, adherence, and treatment completion. While these regimens have been used in children in low TB burden countries, they are not yet widely used in high TB burden countries. Five health facilities in one district in Lesotho, a high TB burden country. Assess the preventive treatment preferences of care givers of child TB contacts. Qualitative data were collected using in-depth interviews with 12 care givers whose children completed preventive treatment, and analyzed using grounded theory. Care givers were interested in being involved in the children's treatment decisions. Pill burden, treatment duration and related frequency of dosing were identified as important factors that influenced preventive treatment preferences among care givers. Understanding care giver preferences and involving them in treatment decisions may facilitate efforts to implement successful preventive treatment for TB among children in high TB burden countries.

Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: A trend analysis from 2014 - 2016.

Background: Xpert® MTB/RIF, a rapid tuberculosis (TB) molecular test, was endorsed by the World Health Organization in 2010. Since then, 34.4 million cartridges have been procured under concessional pricing. Although the roll out of this diagnostic is promising, previous studies showed low market penetration. Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the public sector, smear and Xpert MTB/RIF volumes for the year 2016 were assessed and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied. A structured questionnaire was sent to representatives of 22 HBCs. The questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of modules and days of operation of GeneXpert machines in National TB Programs (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and GeneXpert procurement by other disease control programs were collected. Market penetration was estimated by the ratio of total sputum smear volume for initial diagnosis divided by the number of Xpert MTB/RIF tests procured in the public sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios decreased in 17/21 countries and increased in four countries, since 2014. The median ratio decreased from 32.6 (Q1:14.3, Q3: 58.9) in 2014 to 6.0 (Q1: 1.6, Q3: 17.0) in 2016. Nineteen countries (19/19; 100%) were not using GeneXpert machines to their full capacity, however seven countries (7/19; 37%) were running tests for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV, hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in 2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines were under-utilized for TB, and inadequately exploited as a multi disease technology.

Effects of preventive therapy for latent tuberculosis infection and factors associated with treatment abandonment: a cross-sectional study.

Routine data on the use of preventive therapy (PT) for latent tuberculosis infection (LTBI) in students are scarce in high tuberculosis (TB) burden countries. This study aimed to investigate the effects of PT and identify factors related to PT abandonment during the school TB epidemic in Guangzhou, southern China. Purified protein derivative (PPD) skin testing was performed on all staff and students in a vocational school in Guangzhou, southern China during December 2014. Subjects (n=362) with a reactive PPD induration ≥15 mm, or with papules, blisters, and a normal chest X-ray image were recommended for PT. The subjects were assigned to a PT group (n=156) and control group (n=206), respectively, on a voluntary basis. Subjects in the PT group received isoniazid (INH) combined with rifampicin (RFP) for 3 consecutive months; after which, the incidence of TB and protective rate of PT for reducing TB were observed during a 2-year follow up period. An improved questionnaire was used to identify factors that influenced treatment abandonment. All data were subjected to univariate and multivariate logistic regression analyses. Two cases in the PT group and 20 cases in the control group developed TB. The protective rate of PT for reducing TB was 86.8%. In the PT group, 69 cases finished PT, with a completion rate of 44.2%, and the incidence rates of adverse events and hepatotoxicity were 12.2% and 1.9%, respectively. Among 362 LTBI cases, a total of 293 cases abandoned PT. Discrimination (OR =7.173, 95% CI, 3.361-15.307), worry about adverse drug reactions (OR =2.752, 95% CI, 1.459-5.192), a low parental education level (OR =2.605, 95% CI, 1.420-4.777), and accepting the opinion of a non-TB specialist (OR =6.017, 95% CI, 3.077-11.765) were identified as high-risk factors for abandoning PT. A PT regimen consisting of INH combined with RFP for 3 consecutive months is reasonable for use in schools. Discrimination, worry about adverse drug reactions, a low parental education level, and accepting the opinion of a non-TB specialist are all factors that may increase the risk for treatment abandonment among LTBI cases. To overcome psychological obstacles is critical for improving treatment adherence.

Insight into multidrug-resistant Beijing genotype Mycobacterium tuberculosis isolates in Myanmar

ObjectivesMyanmar is a World Health Organization high tuberculosis (TB) burden country with a high multidrug-resistant (MDR)-TB burden. Of significance, a high prevalence of the Beijing genotype of Mycobacterium tuberculosis (MTB) among MDR-MTB has been reported previously. A detailed genetic characterization of TB clinical isolates was performed in order to explore whether there is an association between the prevalence of the Beijing MTB genotype and MDR-TB in Myanmar. MethodsA total of 265 MDR-MTB clinical isolates collected in 2010 and 2012 were subjected to spoligotyping, mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) analysis, single nucleotide polymorphism (SNP) typing, and drug resistance-associated gene sequencing, including rpoC to detect potential compensatory evolution. ResultsOf the total MDR-MTB isolates, 79.2% (210/265) were of the Beijing genotype, the majority of which were the ‘modern’ subtype. Beijing genotype isolates were differentiated by 15-locus MIRU-VNTR and a high clustering rate (53.0%) was observed in the modern subtype. These MIRU-VNTR patterns were similar to Beijing genotype clones spreading across Russia and Central Asia. A high prevalence of katG Ser315Thr, and genetic evidence of extensive drug resistance (XDR) and pre-XDR and compensatory mutations in rpoC were observed among clustered isolates. ConclusionsMDR-MTB strains of the Beijing genotype might be spreading in Myanmar and present a major challenge to TB control in this country.

Implementation of an active, clinic-based child tuberculosis contact management strategy in western Kenya.

Tuberculosis (TB) is a leading cause of childhood mortality. Isoniazid preventive therapy significantly reduces progression to TB disease. The World Health Organization recommends that high TB burden countries conduct child contact management (CCM) to identify exposed child contacts aged <5 years for screening and appropriate treatment. An active, clinic-based CCM strategy incorporating transport/screening reimbursement, monitoring and evaluation tools, and health care worker education was implemented in western Kenya. Among 169 identified child contacts aged <5 years, 146 (86%) underwent successful screening, of whom 43 (29%) were diagnosed with active TB. We describe our CCM strategy and its potential for enhancing screening and treatment efforts.

Same-day Smear Method Compared with Conventional Sputum Method for Diagnosing Pulmonary Tuberculosis.

BackgroundPatient compliance with the two-day Revised National Tuberculosis Control Programme’s (RNTCP) diagnostic process for pulmonary tuberculosis (TB) is poor in high case load settings, with a high dropout rate observed on the second day. Hence, the World Health Organization (WHO) has recommended the same-day (spot-spot) sputum test for high-burden TB countries to help reduce diagnostic dropouts. This study addresses the paucity of comparative data on the accuracy and agreement of the two methods, while the WHO recommendations are yet to be implemented by the RNTCP. The objective of this study was to assess and compare the smear positivity rates of the same-day and conventional sputum examination methods for the diagnosis of sputum smear-positive pulmonary TB.MethodologyWe conducted a cross-sectional, analytical, nonrandomized comparative study on presumptive TB patients attending a designated microscopy center in a tertiary care hospital. Three sputum samples were collected: a first spot, a second spot (one hour after the first spot), and an early morning sample taken on the following day. The first and the second spot samples taken one hour apart were included for microscopic analysis. The conventional (i.e., two-day sputum) method used the first spot and the early morning sputum sample taken on the following day. A positive result from any one of the three sputum samples was recorded as a proven TB case. We then compared the results of the smear microscopy obtained by the two methods.ResultsThe same-day sputum microscopic method diagnosed 181 out of a total 189 TB cases. The conventional method diagnosed 188 cases. Thus, same-day sputum microscopy missed eight cases, whereas the conventional method missed only one case. The sputum positivity rate was 18.8% in the same-day sputum microscopy samples and 19.5% in the conventional method samples. The incremental yield of the second sputum sample in the same-day (second spot) sample was five cases (2.7%). In the conventional method (early morning sample), the yield was 12 cases (6.3%). The sensitivity of the same-day microscopy and conventional methods were 95.76% and 99.5%, respectively.ConclusionThe conventional method of diagnosing sputum-positive pulmonary TB had more sensitivity compared to the same-day sputum microscopy approach.

Risk factors associated with multidrug-resistant tuberculosis (MDR-TB) in a tertiary armed force referral and teaching hospital, Ethiopia

BackgroundEthiopia is one of the world health organization defined higher tuberculosis (TB) burden countries where the disease remains a massive public health threat. This study aimed to identify the prevalence and associated factors of multidrug-resistant tuberculosis (MDR-TB) using all armed force and civilian TB attendants in a tertiary level armed force hospital, where data for MDR-TB are previously unpublished.MethodsCross-sectional study was conducted from September 2014 to August 2015 in a tertiary level Armed Force Referral and Teaching Hospital (AFRTH), Ethiopia. Armed force members (n = 251) and civilians (n = 130) which has been undergone TB diagnosis at AFRTH were included. All the specimens collected were subjected to microscopic smear observation, culture growth and drug susceptibility testing. Data were analyzed using statistical package for social sciences following binary logistic regression and Chi-square. P-values < 0.05 were considered statistically significant.ResultsAmong 381 TB patients, 355 (93.2%) new and 26 (6.8%) retreatment cases were identified. Culture and smear positive TB cases were identified in 297 (77.9%) and 252 (66.1%) patients, respectively. The overall prevalence of MDR-TB in AFRTH was found 1.8% (1.3% for armed force members and 0.5% for civilian patients) all of which were previously TB treated cases. The entire treatment success rates were 92.6% achieved highest in the armed force (active and pension) than the civilian patients. The failure and dead cases were also found 2.5 and 4.6%, respectively. Using bivariate analysis, category of attendants and TB contact history were strong predictors of MDR-TB in armed force and civilian patients. Moreover, human immunodeficiency virus (HIV) infection also identified a significant (OR = 14.6; 95% CI = 2.3–92.1; p = 0.004) predicting factor for MDR-TB in armed force members. However, sex, age and body mass index were not associated factor for MDR-TB.ConclusionsIn AFRTH, lower prevalence of MDR-TB was identified in armed force and civilian patients that were significantly associated with category of attendants, HIV infection and TB contact history. Considering armed force society as one segment of population significantly helps to plan a better MDR-TB control management, especially for countries classified as TB high burden country.

Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review.

Efavirenz (EFV) and rifampicin-isoniazid (RH) are cornerstone drugs in human immunodeficiency virus (HIV)-tuberculosis (TB) coinfection treatment but with complex drug interactions, efficacy and safety challenges. We reviewed recent data on EFV and RH interaction in TB/HIV high-burden countries. We conducted a systematic review of studies conducted in the high TB/HIV-burden countries between 1990 and 2016 on EFV pharmacokinetics during RH coadministration in coinfected patients. Two reviewers conducted article screening and data collection. Of 119 records retrieved, 22 were included (two conducted in children), reporting either EFV mid-dose or pre-dose concentrations. In 19 studies, median or mean concentrations of RH range between 1000 and 4000ngml-1 , the so-called therapeutic range. The proportion of patients with subtherapeutic concentration of RH ranged between 3.1 and 72.2%, in 12 studies including one conducted in children. The proportion of patients with supratherapeutic concentration ranged from 19.6 to 48.0% in six adult studies and one child study. Five of eight studies reported virological suppression >80%. The association between any grade hepatic and central nervous system adverse effects with EFV/RH interaction was demonstrated in two and three studies, respectively. The frequency of the CYP2B6 516G>T polymorphism ranged from 10 to 28% and was associated with higher plasma EFV concentrations, irrespective of ethnicity. Anti-TB drug coadministration minimally affect the EFV exposure, efficacy and safety among TB-HIV coinfected African and Asian patients. This supports the current 600mg EFV dosing when coadministered with anti-TB drugs.

Which attributes within target product profiles for tuberculosis diagnostics are the most important to focus on?

New diagnostic tools for tuberculosis (TB) are urgently needed. To guide investment decisions, sufficient information regarding which test attributes are the most important for users and decision makers interested in introducing TB diagnostics should be made available. To rank test attributes in a target product profile (TPP) in order of importance for a sputum smear replacement test for TB. An online survey was administered among 33 participants representing 14 of the 22 TB high-burden countries. Respondents included laboratory personnel, national TB program managers, donors, technical experts, patients and researchers. Participants were asked to rank 21 TPP test attributes in order of importance using a maximum-differential method that required ranking of relative trade-offs. Sensitivity was ranked as the most important test attribute, followed by maintenance/calibration, reagent kit storage/stability, sample preparation steps and time to results. Consulting widely regarding which TPP attributes are valued most by users and decision-makers involved in introducing TB diagnostics can assist TB test developers to prioritize their investments, and guide decision making if trade-offs are necessary.

Unsuccessful Xpert® MTB/RIF results: the Nigerian experience.

Setting: Nigeria, a high tuberculosis (TB) burden country. Objective: To study the rate, distribution and causes of unsuccessful Xpert® MTB/RIF test outcomes, with the aim of identifying key areas that need to be strengthened for optimal performance of the assay. Design: This was a retrospective analysis of data uploaded between January and December 2015 from Xpert facilities to the central server using GXAlert. Result: Of 52 219 test results uploaded from 176 Xpert machines, 22.5% were positive for Mycobacterium tuberculosis, 10.8% of which were rifampicin-resistant; 4.7% of the total number of results were invalid, 4.2% had error results and 2.1% no result outcomes. Technical errors were most frequent (69%); these were non-seasonal and occurred in all geopolitical regions and at all health facility levels. Temperature-related errors were more prevalent in the North-West Region, with peaks in April to June. Peak periods for temperature and machine malfunction errors coincided with the periods of low utilisation of the assay. Conclusion: The key challenge affecting performance was poor adherence to standard operating procedures. Periodic refresher training courses, regular supervision, preventive maintenance of Xpert machines and proper storage of cartridges are strategies that could improve Xpert performance.

Evaluating a framework for tuberculosis screening among healthcare workers in clinical settings, Inner Mongolia, China

BackgroundHealth care workers are at high risk for tuberculosis (TB). China, a high burden TB country, has no policy on medical surveillance for TB among healthcare workers. In this paper, we evaluate whether China’s national TB diagnostic guidelines could be used as a framework to screen healthcare workers for pulmonary TB disease in a clinical setting in China.MethodsBetween April–August 2010, healthcare workers from 28 facilities in Inner Mongolia Autonomous Region, China were eligible for TB screening, comprised of symptom check, chest X-ray and tuberculin skin testing. Healthcare workers were categorized as having presumptive, confirmed, or clinically-diagnosed pulmonary TB, using Chinese national guidelines.ResultsAll healthcare workers (N=4347) were eligible for TB screening, of which 4285 (99%) participated in at least one TB screening test. Of the healthcare workers screened, 2% had cough for ≥ 14 days, 3% had a chest X-ray consistent with TB, and 10% had a tuberculin skin test induration ≥ 20 mm. Of these, 124 healthcare workers were identified with presumptive TB (i.e., cough for ≥ 14 days in the past 4 weeks or x-ray consistent with TB). Twelve healthcare workers met the case definition for clinically-diagnosed pulmonary TB, but none were diagnosed with TB during the study period.ConclusionA substantial proportion of healthcare workers in Inner Mongolia had signs, symptoms, or test results suggestive of TB disease that could have been identified using national TB diagnostic guidelines as a screening framework. However, achieving medical surveillance in China will require a framework that increases the ease, accuracy, and acceptance of TB screening in the medical community. Routine screening with improved diagnostics should be considered to detect tuberculosis disease among healthcare workers and reduce transmission in health care settings in China.