•TB recurrence has a multifactorial etiology.•Factors related to quality of initial treatment, including adherence and adverse side effects, contribute significantly to recurrence in ...Vietnam.•Multidrug resistant TB in the primary case is a highly significant independent risk factor, potentially due to under-detection in Vietnam.•Measures to detect severe disease early on and increase adherence could have a significant impact on rates of TB recurrence.
Patients completing treatment for tuberculosis (TB) in high-prevalence settings face a risk of developing recurrent disease. This has important consequences for public health, given its association with drug resistance and a poor prognosis. Previous research has implicated individual factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug resistant disease as risk factors for recurrence. However, little is known about how these factors co-act to produce recurrent disease. Furthermore, perhaps factors related to the index disease means higher burden/low resource settings may be more prone to recurrent disease that could be preventable.
We conducted a case-control study nested within a cohort of consecutively enrolled adults who were being treated for smear positive pulmonary TB in 70 randomly selected district clinics in Vietnam. Cases were patients with recurrent TB, identified by follow-up from the parent cohort study. Controls were selected from the cohort by random sampling. Information on demographic, clinical and disease-related characteristics was obtained by interview. Treatment information was extracted from clinic registries. Logistic regression, with stepwise selection, was used to develop a fully adjusted model for the odds of recurrence of TB.
We recruited 10,964 patients between October 2010 and July 2013. Median follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with recurrence were identified as cases and 630 other patients were randomly selected as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB (adjusted odds ratio 79.6; 95% CI: 25.1-252.0), self-reported prior TB therapy (aOR=2.5; 95% CI: 1.7-3.5), and incomplete adherence (aOR=1.9; 95% CI 1.1-3.1).
Index disease treatment history is a leading determinant of relapse among patients with TB in Vietnam. Further research is required to identify interventions that will reduce the risk of recurrent disease and enhance its early detection within high-risk populations.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed ...the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data.
We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence.
Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 1.91-37.42), renal dysfunction (HR = 8.46 1.91-37.42), alcoholism (HR = 13.28 5.04-34.99), and a higher average daily dose of injectable drugs (HR = 1.28 1.14-1.43).
While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives Vietnam is a high-prevalence country for tuberculosis (TB). Xpert MTB/RIF is a novel PCR-based diagnostic test that is substantially more sensitive for detecting M. tuberculosis than ...traditional smear-based techniques. However, locally-derived evidence of Xpert MTB/RIF in HIV-infected people is limited. This study evaluates the performance of the Xpert MTB/RIF in HIV-infected patients with smear-negative pulmonary TB (SNTB). Methods This was a cross-sectional study in 3 hospitals. The performance of Xpert MTB/RIF was compared with the reference standard of liquid culture and phenotypic drug-susceptibility testing for rifampicin (RIF) resistance. Results Out of 123 patients, the median age was 37.0 (IQR: 32.0-41.0) and 81.3% were male. The area under the receiver operating characteristic curve, sensitivity (Se) and specificity (Sp) of Xpert MTB/RIF for pulmonary TB diagnosis were 0.72 (95% confidence interval CI: 0.63-0.81), 66.7% (95%CI: 54.8-77.1) and 77.1% (95%CI: 62.7-88.0), respectively, while Se and Sp of Xpert MTB/RIF in detecting RIF resistance were 50.0 (11.8-88.2) and 86.4% (95%CI: 72.7-94.8). Conclusion The performance of Xpert MTB/RIF in HIV-infected patients with SNTB for the diagnosis of TB and RIF-resistance was low. Further studies are required to evaluate the results of Xpert MTB/RIF assay in HIV-infected patients with SNTB and the role of Xpert repetition on the same specimens.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second ...national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country.
Eighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree.
Of 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB.
With highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess sex disparities in tuberculosis in Vietnam, we conducted a nested, case-control study based on a 2017 tuberculosis prevalence survey. We defined the case group as all survey participants ...with laboratory-confirmed tuberculosis and the control group as a randomly selected group of participants with no tuberculosis. We used structural equation modeling to describe pathways from sex to tuberculosis according to an a priori conceptual framework. Our analysis included 1,319 participants, of whom 250 were case-patients. We found that sex was directly associated with tuberculosis prevalence (adjusted odds ratio for men compared with women 3.0 95% CI 1.7-5.0) and indirectly associated through other domains. The strong sex difference in tuberculosis prevalence is explained by a complex interplay of factors relating to behavioral and environmental risks, access to healthcare, and clinical manifestations. However, after controlling for all those factors, a direct sex effect remains that might be caused by biological factors.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
About the Authors: Grania Brigden * E-mail: grania.brigden@theunion.org Affiliation: Department of Tuberculosis, The International Union Against TB and Lung Disease, Geneva, Switzerland ORCID logo ...http://orcid.org/0000-0001-5184-4121 Nguyen Viet Nhung Affiliation: National Lung Hospital, Vietnam NTP, Vietnam Alena Skrahina Affiliation: Republican Scientific and Practical Centre for Pulmonology and TB, Minsk, Belarus Norbert Ndjeka Affiliation: Drug-Resistant TB, TB and HIV directorate, National Department of Health, Pretoria, South Africa Dennis Falzon Affiliation: Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland ORCID logo http://orcid.org/0000-0001-8798-7909 Matteo Zignol Affiliation: Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland Introduction One of the key missions of national tuberculosis (TB) programmes (NTPs) is to issue policy and technical guidance for clinicians and healthcare workers involved in TB care at the country level. Translating research findings into policies may be a challenging task, given that the design of clinical studies may not always address the main public health priority directly, and recommended interventions require substantial adaptation to the particular programme conditions and settings 4. A recent review 17 of national policies in 29 countries highlighted national policy gaps when compared to WHO policies. ...in the case of WHO’s recommended 9–12-month-shorter MDR-TB regimen, 45% of the countries had developed policies, but only 69% of those countries had implemented them. Since late 2018, the NTP introduced under operational research conditions a shorter regimen of 9 months consisting of all group A and B medicines recommended in MDR-TB regimens.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundOf the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular ...problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.MethodsA cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs’ referral.ResultsIn total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan.ConclusionsFew SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.
Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; ...sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention ...and control interventions. We aimed to identify risk factors associated with developing TB among HHCs.
Methods
We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs.
Results
We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio aOR, 1.4; 95% confidence interval CI, 1.03–2.0), residing in an urban setting (aOR, 1.8; 1.3–2.5), prior TB (aOR, 4.6; 2.5–8.7), history of diabetes (aOR, 3.1; 1.7–5.8), current smoking (aOR, 3.1; 2.2–4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1–2.3).
Conclusions
Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.
Among household contacts of source cases in a high-tuberculosisburden setting, risk factors for tuberculosis development related to the household contact (male gender, urban setting, smoking, diabetes, and prior tuberculosis) and their source case (prior tuberculosis and prolonged cough).
To estimate the prevalence of tuberculosis in Viet Nam with data from a population-based survey, compare it with the prevalence estimated by the World Health Organization, and identify major ...demographic determinants of tuberculosis prevalence.
A cross-sectional survey with multistage cluster sampling, stratified by urban, rural and remote areas, was done in 2006-2007 in 70 communes. All inhabitants aged > or = 15 years were invited for cough and chest X-ray examination. Participants with findings suggestive of tuberculosis provided sputum specimens for smear examination and culture. Point prevalence estimates, 95% confidence intervals and design effects were calculated. Confidence intervals and P-values were adjusted for the cluster design.
Of 114,389 adult inhabitants, 94 179 (82.3%) were screened. Of 87,314 (92.7%) screened by both questionnaire and chest X-ray, 3522 (4.0%) had productive cough, 518 (0.6%) had a recent history of tuberculosis and 2972 (3.4%) had chest X-ray abnormalities suggestive of tuberculosis. Sputum tests were done for 7648 participants. Sputum test, bacterial culture or both confirmed 269 tuberculosis cases, 174 of which were smear-positive. The prevalence rate of smear-positive tuberculosis was 145 per 100,000 (95% confidence interval: 110-180) assuming no tuberculosis in persons aged < 15 years. Prevalence was 5.1 times as high in men as in women, increased with age, was higher in rural than in urban or remote areas and showed a north-to-south gradient.
In Viet Nam, the tuberculosis prevalence rate based on positive sputum smear tests was 1.6 times as high as previously estimated. Age and sex patterns were consistent with notification data. Tuberculosis control should remain a high priority in Viet Nam.
Full text
Available for:
CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
PDF
