D N Sy

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (30)99.3 Total impact

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    ABSTRACT: Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results.
    PLoS ONE 01/2014; 9(7):e99496. · 3.53 Impact Factor
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    ABSTRACT: Tuberculosis is an infectious disease that continues to cause considerable morbidity and mortality globally. Only 65% of patients worldwide are currently diagnosed. Contact investigation is a strategy that aims to increase case detection and reduce transmission of tuberculosis, yet there is little evidence to show its effectiveness.Methods and design: We will conduct a cluster randomized controlled trial of contact investigation within the national tuberculosis control program of Vietnam. Household contacts of patients with smear-positive pulmonary tuberculosis will be invited to attend district tuberculosis units for symptom screening, examination, and chest radiography on four occasions over a two-year period. The primary endpoint is clinically confirmed tuberculosis among contacts during the 24 months of follow-up, ascertained using capture-recapture analysis. Microbiologically proven tuberculosis and treatment completion rates among contacts diagnosed with tuberculosis will be secondary endpoints. The incremental cost-effectiveness ratio will be estimated. The study will have 80% power to detect a 50% increase in the primary endpoint in the active intervention arm compared with the control arm. The study will include 8,829 contacts in each of the active screening and control groups, within 70 districts in 8 provinces in Vietnam, in both rural and urban settings. The effectiveness of contact investigation as a tool for improved tuberculosis case finding has not been established. This cluster randomized trial will provide valuable operational information for national tuberculosis programs in high-prevalence countries, in order to select the most cost-effective strategies to improve tuberculosis case detection.Trial registration: The ACT2 study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000600044).
    Trials 10/2013; 14(1):342. · 2.21 Impact Factor
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    ABSTRACT: 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. 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. 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). The estimated nationwide ARTI was 1.7%. TST positivity was associated with the presence of a TB case in the household.
    The International Journal of Tuberculosis and Lung Disease 06/2013; 17(6):738-44. · 2.76 Impact Factor
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    ABSTRACT: Background: Drug resistant TB is now one of the main challenges for TB controls worldwide. Understanding of the circulation and emergence of drug resistant TB can help developing effective control strategies. Objectives: To determine the drug resistance levels of different M. tuberculosis lineages in different geographical populations of Vietnam; to determine lineage distribution in drug resistant M. tuberculosis populations isolated in two national hospitals in Vietnam, during 2005-2008. Methods: 300 M. tuberculosis isolates randomly selected from three national hospitals in the three main regions of Vietnam: the North, the Centre and the South; and 400 isolates selected by drug resistance criteria in two national hospitals in the North and the South, were genotyped and analysed by spoligotyping and MIRU-VNTR. Results: M. tuberculosis of all lineages was most resistant to drugs in the South, and most susceptible to drugs in the Centre. Beijing lineage was associated with younger ages and most resistant to drugs, while EAI lineage was associated with older ages and most susceptible. Multidrug resistant (MDR) isolates from the Centre were found only in Beijing lineage (21.4%). The proportion of MDR in Beijing isolates from the Centre was significantly lower than that from the North (34.8%) and the South (36.7%), with p<0.0001. The higher the levels of drug resistance, the higher the proportion of Beijing isolates and the lower the proportion of EAI and EAI4-VNM isolates in the populations. Drug susceptible strains are more genetically diverse compared to drug resistant strains. M. tuberculosis populations evolve increased drug resistance, generating new populations less genetically diverse but more resistant to drugs. Conclusion: Drug resistance levels are different in the different M. tuberculosis lineages and in the different regions of Vietnam. Beijing lineage is invading Vietnam and replacing the EAI lineage, especially the local EAI4-VNM sub-lineage. Beijing lineage is most resistant to drug and will be more and more predominant if the bacillus populations become more and more resistant.to drugs.
    4th Pacific Regional Congress on TB and Lung Diseases, Hanoi; 04/2013
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    Dataset: HoaEID2011
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    ABSTRACT: Tuberculosis (TB) prevalence surveys generally rely on a combination of screening methods to identify suspects eligible for sputum culture. 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. 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. 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. 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.
    The International Journal of Tuberculosis and Lung Disease 04/2012; 16(6):762-7. · 2.76 Impact Factor
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    ABSTRACT: Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered. To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam. Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease. Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17-1451) and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44-131). Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types. Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness.
    PLoS ONE 01/2012; 7(11):e49880. · 3.53 Impact Factor
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    ABSTRACT: Two general hospitals in Viet Nam. To assess the risk of tuberculosis (TB) infection associated with hospital employment. During October-December 2009, we performed a cross-sectional study of hospital personnel and, for community comparison groups, staff from nearby schools. We tested for TB infection using the tuberculin skin test; an induration ≥ 10 mm indicated TB infection. Of 956 hospital personnel, 380 (40%) had TB infection compared to 40 (26%) of 155 school personnel. Hospital personnel had twice the odds of TB infection compared with school personnel (OR 2.0, 95%CI 1.3-3.0) after adjustment for age and sex. Compared to hospital administrative staff, the odds of TB infection were similar among clinical staff (OR 1.0, 95%CI 0.6- 1.3), clinical support staff (OR 0.9, 95%CI 0.5-1.6) and auxiliary staff (OR 1.1, 95%CI 0.6-2.0) at the hospitals. No additional infection risk was detected in high-risk departments (OR 1.1, 95%CI 0.6-2.0). Hospital personnel are at increased risk of TB infection. Among hospital personnel, risk was independent of job or department, suggesting that personnel are commonly at risk and that improvements in infection control are needed throughout hospitals.
    The International Journal of Tuberculosis and Lung Disease 12/2011; 15(12):1643-9. · 2.76 Impact Factor
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    ABSTRACT: 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.
    Tropical Medicine & International Health 06/2011; 16(10):1260-7. · 2.94 Impact Factor
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    ABSTRACT: To the Editor: In many countries, the private sector (practitioners not employed by government and nongovernment institutions, e.g., hospitals, pharmacies) is a major source of care, even for poor persons, and the area where services for the public are widely available (1,2). However, little information is available from high-incidence countries about the role of the private sector in tuberculosis (TB) detection and treatment (3). In Vietnam, ≤40% of all TB cases in Ho Chi Minh City (the largest city in Vietnam and with the highest rate of economic growth in the country) were estimated to be treated in the private sector (4), and half of all patients with a diagnosis of TB in the public sector (National Tuberculosis Program [NTP]) in Ho Chi Minh City initially sought help in the private sector (5). However, this estimate does not reflect private care in the entire country.
    Emerging Infectious Diseases 03/2011; 17(3):562-4. · 6.79 Impact Factor
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    ABSTRACT: There is a need for low-technology, inexpensive screening tools for active tuberculosis (TB) case finding. to assess the potential usefulness of measuring exhaled nitric oxide (eNO). 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. 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. 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.
    The International Journal of Tuberculosis and Lung Disease 02/2011; 15(2):185-92. · 2.76 Impact Factor
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    ABSTRACT: To study the association between TB and household expenditure in a nationwide TB prevalence survey in Viet Nam using nine household characteristics. 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. 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. 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.
    The International Journal of Tuberculosis and Lung Disease 01/2011; 15(1):32-7. · 2.76 Impact Factor
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    ABSTRACT: 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.
    The International Journal of Tuberculosis and Lung Disease 12/2010; 15(1):32-37. · 2.76 Impact Factor
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    ABSTRACT: Vietnam has an emerging human immunodeficiency virus (HIV) epidemic (estimated population prevalence 0.5%), but valid data on HIV prevalence among tuberculosis (TB) patients are limited. Recent increases in TB notification rates among young adults may be related to HIV. To assess the prevalence of HIV infection among smear-positive TB patients in six provinces with relatively high HIV population prevalence in Vietnam. All patients who registered for treatment of smear-positive TB during the fourth quarter of 2005 were offered HIV testing. Of the 1217 TB patients included in the study, 100 (8.2%) tested HIV-positive. HIV prevalence varied between 2% and 17% in the provinces, and was strongly associated with age < 35 years, injecting drug use, commercial sex work and a history of sexually transmitted disease. Among men aged 15-34 years, the rate of notification of new smear-positive TB that was attributable to HIV infection varied from 3-4 per 100,000 population in mainly rural provinces to 20-42/100,000 in provinces with rapid industrial and commercial development. Among TB patients in Vietnam, HIV infection is concentrated in drug users, as well as in specific geographic areas where it has considerable impact on TB notification rates among men aged 15-34 years.
    The International Journal of Tuberculosis and Lung Disease 08/2010; 14(8):986-93. · 2.76 Impact Factor
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    ABSTRACT: BACKGROUND: Vietnam has an emerging human immunodeficiency virus (HIV) epidemic (estimated population prevalence 0.5%), but valid data on HIV prevalence among tuberculosis (TB) patients are limited. Recent increases in TB notification rates among young adults may be related to HIV.OBJECTIVES: To assess the prevalence of HIV infection among smear-positive TB patients in six provinces with relatively high HIV population prevalence in Vietnam.METHODS: All patients who registered for treatment of smear-positive TB during the fourth quarter of 2005 were offered HIV testing.RESULTS: Of the 1217 TB patients included in the study, 100 (8.2%) tested HIV-positive. HIV prevalence varied between 2% and 17% in the provinces, and was strongly associated with age < 35 years, injecting drug use, commercial sex work and a history of sexually transmitted disease. Among men aged 15-34 years, the rate of notification of new smear-positive TB that was attributable to HIV infection varied from 3-4 per 100 000 population in mainly rural provinces to 20-42/100 000 in provinces with rapid industrial and commercial development.CONCLUSION: Among TB patients in Vietnam, HIV infection is concentrated in drug users, as well as in specific geographic areas where it has considerable impact on TB notification rates among men aged 15-34 years.
    The International Journal of Tuberculosis and Lung Disease 07/2010; 14(8):986-993. · 2.76 Impact Factor
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    ABSTRACT: 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.
    Bulletin of the World Health Organisation 04/2010; 88(4):273-80. · 5.25 Impact Factor
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    ABSTRACT: To assess whether the increase in tuberculosis (TB) notification rates among young adults in Vietnam reflects increased transmission in the population at large. Trends of case notification rates of new smear-positive TB were calculated from routinely reported data of district TB units over the period 1996-2005. Results from repeated tuberculin surveys among children aged 6-9 years were obtained to calculate the trend in annual risk of TB infection (ARTI). From 1996 to 2006, notification rates in the age group 15-24 years increased by 4.3% per year, and more so in highly urbanised (6.7%) than in rural districts (1.7%). The ARTI in urban districts declined from 2.4% in 1992 to 1.2% in 1998 and 0.9% in 2005. In rural districts, the ARTI increased from 0.7% in 1991 to 1.2% in 1997, and then declined to 0.9% in 2006. The increase in TB notification rates among young adults in Ho Chi Minh Province is accompanied by a decrease in ARTI in children. This suggests that the trend in TB notification among young adults reflects increased rates of progression from infection to disease and/or increased transmission within this age group, rather than increased transmission in the population at large.
    The International Journal of Tuberculosis and Lung Disease 03/2010; 14(3):289-95. · 2.76 Impact Factor
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    ABSTRACT: Abstract Background To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType<sup>® </sup>MTBDR plus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance. We assessed sensitivity and specificity of the assay by using a geographically representative set of MTB isolates from the South of Vietnam. Methods We re-cultured 111 MTB isolates that were MDR, rifampin-resistant or pan-susceptible according to conventional DST and tested these with the GenoType<sup>® </sup>MTBDR plus test. Results By conventional DST, 55 strains were classified as MDR-TB, four strains were rifampicin mono-resistant and 52 strains were susceptible to all first-line drugs. The sensitivity of the GenoType<sup>® </sup>MTBDR plus was 93.1% for rifampicin, 92.6% for isoniazid and 88.9% for the combination of both; its specificity was 100%. The positive predictive value of the GenoType<sup>® </sup>MTBDR plus test for MDR-TB was 100% and the negative predictive value 90.3%. Conclusions We found a high specificity and positive predictive value of the GenoType<sup>® </sup>MTBDR plus test for MDR-TB which merits its use in the MDR-TB treatment program in Vietnam.
    BMC Infectious Diseases. 01/2010;
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    ABSTRACT: To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType MTBDRplus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance.We assessed sensitivity and specificity of the assay by using a geographically representative set of MTB isolates from the South of Vietnam. We re-cultured 111 MTB isolates that were MDR, rifampin-resistant or pan-susceptible according to conventional DST and tested these with the GenoType MTBDRplus test. By conventional DST, 55 strains were classified as MDR-TB, four strains were rifampicin mono-resistant and 52 strains were susceptible to all first-line drugs. The sensitivity of the GenoType MTBDRplus was 93.1% for rifampicin, 92.6% for isoniazid and 88.9% for the combination of both; its specificity was 100%. The positive predictive value of the GenoType MTBDRplus test for MDR-TB was 100% and the negative predictive value 90.3%. We found a high specificity and positive predictive value of the GenoType MTBDRplus test for MDR-TB which merits its use in the MDR-TB treatment program in Vietnam.
    BMC Infectious Diseases 01/2010; 10:149. · 3.03 Impact Factor
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    ABSTRACT: Little is known about tuberculosis (TB) prevalence in psychiatric hospitals in Vietnam, but prevalence may be higher than in the general population. We assessed the TB prevalence among in-patients of a psychiatric hospital in 2005 in Danang City, Vietnam. Of 300 in-patients, 70 had an abnormal X-ray or prolonged cough, and underwent sputum smear examinations. The prevalence of smear-positive TB was 0.33% (1/300, 95%CI 0.008-1.9). Twenty-three (7.7%) patients had X-ray lesions suggesting active TB and 22 (7.3%) had a history of TB treatment. TB prevalence was high in this psychiatric hospital, and TB infection control needs strengthening.
    The International Journal of Tuberculosis and Lung Disease 07/2008; 12(6):686-8. · 2.76 Impact Factor

Publication Stats

185 Citations
99.30 Total Impact Points

Institutions

  • 2011
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2007–2011
    • Vietnam National University, Hanoi
      Hà Nội, Ha Nội, Vietnam
    • Ministry of Health, Vietnam
      Hà Nội, Ha Nội, Vietnam
  • 2010
    • Pham Ngoc Thach University of Medicine
      Hao Binh, Hòa Bình, Vietnam