Introduction of the Simple One-Step stool Xpert Ultra method to detect TB in children and adults.

SETTING: In 2020, the National TB Programme (NTP) of Vietnam conducted an implementation pilot of the Simple One-Step (SOS) stool processing method using Xpert® MTB/RIF Ultra (Ultra) among children and people living with HIV (PLHIV) with signs and symptoms of TB.DESIGN and OBJECTIVES: Using data from this pilot and collecting information on healthcare workers´ (HCWs) perceptions, we assessed the feasibility, acceptability and potential impact of routine stool testing for TB.RESULTS: HCWs perceived collection of stools from children as least stressful of all sample types, stool processing as acceptable and the SOS stool method as easy to perform. After a 3-month induction period, the proportion of initial non-determinate Ultra stool tests was less than 5%. Combined Ultra testing of a respiratory sample and stool resulted in an increase in the proportion of bacteriologically confirmed TB among PLHIV and children by respectively 4.1% (95% CI 1.6-6.6) and 3.9% (95% CI 1.6-6.2). Among children, Mycobacterium tuberculosis was more often detected in stool (26.1%) than in respiratory samples (23.4%) (P = 0.06), including one child with rifampicin resistance.CONCLUSION: Stool testing can be feasibly implemented both in adult PLHIV and in children in routine settings, providing a non-invasive alternative sample type for the diagnosis of TB for patients who cannot produce sputum.

Does BCG vaccination protect against infection with M. tuberculosis?

BACKGROUND: Protection against infection by the bacille Calmette-Guérin vaccine against Mycobacterium tuberculosis remains a subject of controversy. We investigated the association between BCG vaccination at birth and infection by M. tuberculosis.MATERIAL and METHODS: This was a secondary analysis of data from tuberculin skin test (TST) surveys in Vietnamese schoolchildren between 1988 and 2001. We investigated whether a BCG scar was associated with a lower prevalence of TST positivity, adjusting for BCG-induced variation by varying cut-off values for a positive TST.RESULTS: We found a positive association between BCG scar and TST positivity. The strength of the association decreased with increasing TST cut-off values; however, it never inverted significantly, irrespective of geographic region and survey year.CONCLUSION: In Vietnam, BCG vaccination was not associated with reduced M. tuberculosis infection prevalence as measured using TST. This in contrary to a similar study conducted in Tanzania. These contradictory findings may be explained by geographical differences and the relatively high prevalence in Vietnam of the M. tuberculosis Beijing genotype, which is reported to be capable of circumventing BCG-induced immunity.

Estimation of subnational tuberculosis burden: generation and application of a new tool in Indonesia.

SETTING: In many high tuberculosis (TB) burden countries, there is substantial geographical heterogeneity in TB burden. In addition, decisions on TB funding and policy are highly decentralised. Subnational estimates of burden, however, are usually unavailable for planning and target setting.OBJECTIVE and DESIGN: We developed a statistical model termed SUBsET to estimate the distribution of the national TB incidence through a weighted score using selected variables, and applied the model to the 514 districts in Indonesia, which have substantial policy and budgetary autonomy in TB. Estimated incidence was compared to reported facility and domicile-based notifications to estimate the case detection rate (CDR). Local stakeholders led model development and dissemination.RESULTS: The final SUBsET model included district population size, level of urbanisation, socio-economic indicators (living floor space and high school completion), human immunodeficiency virus prevalence and air pollution. We estimated district-level TB incidence to be between 201 and 2,485/100 000/year. The facility-based CDR varied between 0 and 190%, with high variation between neighbouring districts, suggesting strong cross-district health utilisation, which was confirmed by domicile-based CDR estimation. SUBsET results informed district-level TB action plans across Indonesia.CONCLUSION: The SUBsET model could be used to estimate the subnational burden in high-burden countries and inform TB policymaking at the relevant decentralised administrative level.

Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.

SETTING: The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests. OBJECTIVE: We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics. DESIGN: Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP. RESULTS: Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found. CONCLUSIONS: Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.

First national tuberculin survey in Viet Nam: characteristics and association with tuberculosis prevalence.

OBJECTIVES: To estimate the prevalence of infection with Mycobacterium tuberculosis and the annual risk of tuberculous infection (ARTI) and to compare this with the prevalence of tuberculosis (TB) over study clusters and households. METHODS: A nationwide, stratified cluster sample survey was carried out in 2006-2007 in Viet Nam to assess the prevalence of infection with M. tuberculosis. A representative sample of children aged 6-14 years underwent a tuberculin skin test (TST) using the Mantoux method. RESULTS: Of 23,160 children registered, 21,487 (92.8%) were tested and read and available for analysis. Using a cut-off point of 10 mm, the estimated prevalence of TST positivity was 16.7%, and the ARTI was 1.7% (95%CI 1.5-1.8). Higher infection rates were found in urban than in rural and remote areas, and infection rates increased with age. There was significant association between the prevalence of TB disease and infection at the cluster level (regression coefficient 0.54, 95%CI 0.06-1.01, P = 0.027, correlation coefficient R(2) 0.120). Children with a (recent) case of TB in the household were 1.6 times more likely to be TST-positive than children in households with no recent cases (P < 0.05). CONCLUSION: The estimated nationwide ARTI was 1.7%. TST positivity was associated with the presence of a TB case in the household.

Yield of interview screening and chest X-ray abnormalities in a tuberculosis prevalence survey.

BACKGROUND: Tuberculosis (TB) prevalence surveys generally rely on a combination of screening methods to identify suspects eligible for sputum culture. OBJECTIVE: To assess the yield of screening methods applied in a recent prevalence survey in Viet Nam and estimate the proportion of TB cases missed due to incomplete participation. METHODS: TB suspects were identified based on self-reported TB history or productive cough by interview and chest X-ray (CXR). We calculated the case yield of these two screening methods by dividing the number of cases detected per method by the total number of cases detected. As not all participants underwent the full screening procedure, we recalculated the maximum yield of the screening methods using multiple imputation methods. RESULTS: The yield from screening by interview and CXR were respectively 38% and 91%. Adjusting for missing data by multiple imputation, we estimated that we missed 9.9% (95%CI 6.8-14.2) of expected TB cases. CONCLUSION: In prevalence surveys, screening by pre-structured interview is insufficient, and should be supplemented with CXR to achieve sufficient identification of TB cases. The effect of incomplete participation in the full screening procedure may be substantial and should be adjusted for in the analysis.

Health-seeking behaviour among adults with prolonged cough in Vietnam.

OBJECTIVE: To assess health-seeking behaviour among adults with prolonged cough in a population-based, nationally representative sample in Vietnam. METHODS: Cross-sectional survey conducted from September 2006 to July 2007. All inhabitants aged ≥15 years were invited for screening for cough, history of tuberculosis (TB) treatment and chest X-ray (CXR) examination. TB suspects, defined as any survey participant with CXR abnormalities consistent with TB, or productive cough for more than 2 weeks or TB treatment either currently or in the preceding 2 years submitted sputum specimens for smear examination and culture and provided information on health-seeking behaviour in an in-depth interview. RESULTS: Of 94 179 persons participating in the survey, 4.6% had prolonged productive cough. Forty-four percentage of those had sought health care and reported pharmacies (35%), commune health posts (29%), public hospitals (24%) and private physicians (10%) as first point of contact. Only 7% had undergone sputum smear examination. Of TB suspects with prolonged productive cough, 2.9% were diagnosed with TB; 10.2% of these reported smear and 21.9% reported X-ray examination when visiting a health care facility. The average patient delay was 4.1 weeks (95% CI: 3.9-4.4) among cough suspects and 4.0 weeks (95% CI: 3.1-4.9) among TB cases. CONCLUSIONS: In this Vietnamese survey, nearly half of persons with cough for more than 2 weeks had visited a health care provider. The commonest first health facility contacted was the pharmacy. Sputum smears were rarely examined, except in the provincial TB hospital. Our findings highlight the need to improve diagnostic practices by retraining health staff on the performance of sputum examination for TB suspects.

Household expenditure and tuberculosis prevalence in VietNam: prediction by a set of household indicators.

OBJECTIVE: To study the association between TB and household expenditure in a nationwide TB prevalence survey in Viet Nam using nine household characteristics. METHOD: To assess the prevalence of TB in Viet Nam, a nationwide stratified cluster sample survey was conducted from 2006 to 2007. Nine household characteristics used in the second Viet Nam Living Standards Survey (VLSS) were scored per household. In the VLSS dataset, we regressed these nine characteristics against household expenditure per capita, and used the coefficients to predict household expenditure level (in quintiles) in our survey and assess its relation with TB prevalence. RESULTS: The prevalence of bacteriologically confirmed TB was 307 per 100,000 population in persons aged ≥ 15 years (95%CI 249-366). After adjustment for confounders, prevalence was found to be associated with household expenditure level: the rate was 2.5 times higher for those in the lowest household expenditure quintile (95%CI 1.6-3.9) than those in the highest quintile. CONCLUSION: With a set of nine household characteristics, we were able to predict household expenditure level fairly accurately. There was a significant association between TB prevalence rates and estimated household expenditure level, showing that TB is related to poverty in Viet Nam.

Measurement of exhaled nitric oxide as a potential screening tool for pulmonary tuberculosis.

BACKGROUND: There is a need for low-technology, inexpensive screening tools for active tuberculosis (TB) case finding. OBJECTIVE: to assess the potential usefulness of measuring exhaled nitric oxide (eNO). DESIGN: Cross-sectional comparison in Hanoi, Viet Nam, comparing 90 consecutive smear-positive, culture-confirmed TB patients presenting at a referral hospital with office workers (no X-ray confirming TB) at this hospital (n = 52) and at a construction firm (n = 84). eNO levels were analysed using a validated handheld analyser. RESULTS: eNO levels among TB patients (median 15 parts per billion [ppb], interquartile range [IQR] 10-20) were equal to those among construction firm workers (15 ppb, IQR 12-19, P = 0.517) but higher than those among hospital workers (8.5 ppb, IQR 5-12.5, P < 0.001). Taking the hospital workers as the comparison group, best performance as a diagnostic tool was at a cut-off of 10 ppb, with sensitivity 78% (95%CI 68-86) and specificity 62% (95%CI 47-75). Test characteristics could be optimised to 84% vs. 67% by excluding individuals who had recently smoked or consumed alcohol. CONCLUSION: While eNO measurement has limited value in the direct diagnosis of pulmonary TB, it may be worth developing and evaluating as a cost-effective replacement of chest X-ray in screening algorithms of pulmonary TB where X-ray is not available.

Methicillin-resistant Staphylococcus aureus in people living and working in pig farms.

We compared the prevalence of human and animal methicillin-resistant Staphylococcus aureus (MRSA) at pig farms in The Netherlands, and related this to individual and farm-level characteristics. More than half of the farms investigated (28/50) had MRSA in pigs or stable dust and about one third (15/50) of person(s) were identified as MRSA carriers. Human carriage was found only on farms with MRSA-positive pigs or dust. MRSA strains in human samples were the same spa-type as found in pigs and all were not typable by pulsed-field gel electrophoresis (NT-MRSA). Multivariate analyses showed that risk factors for human MRSA carriage were: working in pig stables (OR 40, 95% CI 8-209) and the presence of sows and finishing pigs (OR 9, 95% CI 3-30). Veterinary sample collectors sampling the pigs showed transient MRSA carriage only during the day of the farm visit. Working in pig stables with MRSA-positive pigs poses a high risk for acquiring MRSA, increasingly so when contact with live pigs is more intensive or long lasting.

Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma.

Exposure to aflatoxins is a risk factor for hepatocellular carcinoma (HCC). Aflatoxins occur in peanut butter and are metabolized by genetically polymorphic enzymes such as glutathione-S-transferases encoded by glutathione-S-transferase mu 1 gene (GSTM1) and glutathione-S-transferase theta 1 gene (GSTT1) and microsomal epoxide hydrolase encoded by epoxide hydrolase gene (EPHX). The rate at which aflatoxins become activated or detoxified may depend on polymorphisms in the encoding genes. GSTM1 homozygous deletion was indeed found to modify the association between peanut butter consumption and HCC. In this study, we investigate possible roles of GSTT1 and EPHX polymorphisms in this relationship. From a Sudanese case-control study on HCC, we analyzed data of 112 incident cases and 194 controls. All participants were interviewed using a standardized questionnaire inquiring about social and demographic factors, peanut butter consumption, and other known HCC risk factors. Univariate analysis showed that GSTT1 polymorphism was not associated with HCC, whereas EPHX 113HH and 139HH genotypes increased the risk of HCC (Odds ratio, 3.10; 95% Confidence interval, 1.18-8.12). Adjustment for age and region of origin slightly attenuated this association (Odds ratio, 2.56; 95% Confidence interval, 0.83-7.95). Interestingly, unlike GSTM1, both GSTT1 and EPHX polymorphism did not modify the association between peanut butter consumption and HCC. In conclusion, these epidemiological findings do not suggest significant roles of GSTT1 and EPHX in aflatoxin metabolism, although EPHX polymorphism is possibly related to the increased risk of HCC. Further studies are needed to investigate mechanisms by which the EPHX polymorphism potentially modifies cancer risk.