Tuberculosis (TB) is a major global health burden, with an estimated quarter of the world's population being infected. The World Health Organization (WHO) launched the "End TB Strategy" in 2014 ...emphasising knowing the epidemic. WHO ranks Vietnam 12th in the world of high burden countries. TB spatial and temporal patterns have been observed globally with evidence of Vitamin D playing a role in seasonality. We explored the presence of temporal and spatial clustering of TB in Vietnam and their determinants to aid public health measures.
Data were collected by the National TB program of Vietnam from 2010 to 2015 and linked to the following datasets: socio-demographic characteristics; climatic variables; influenza-like-illness (ILI) incidence; geospatial data. The TB dataset was aggregated by province and quarter. Descriptive time series analyses using LOESS regression were completed per province to determine seasonality and trend. Harmonic regression was used to determine the amplitude of seasonality by province. A mixed-effect linear model was used with province and year as random effects and all other variables as fixed effects.
There were 610,676 cases of TB notified between 2010 and 2015 in Vietnam. Heat maps of TB incidence per quarter per province showed substantial temporal and geospatial variation. Time series analysis demonstrated seasonality throughout the country, with peaks in spring/summer and troughs in autumn/winter. Incidence was consistently higher in the south, the three provinces with the highest incidence per 100,000 population were Tay Ninh, An Giang and Ho Chi Minh City. However, relative seasonal amplitude was more pronounced in the north. Mixed-effect linear model confirmed that TB incidence was associated with time and latitude. Of the demographic, socio-economic and health related variables, population density, percentage of those under 15 years of age, and HIV infection prevalence per province were associated with TB incidence. Of the climate variables, absolute humidity, average temperature and sunlight were associated with TB incidence.
Preventative public health measures should be focused in the south of Viet Nam where incidence is highest. Vitamin D is unlikely to be a strong driver of seasonality but supplementation may play a role in a package of interventions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute encephalitis syndrome (AES) differs in its spatio-temporal distribution in Vietnam with the highest incidence seen during the summer months in the northern provinces. AES has multiple ...aetiologies, and the cause remains unknown in many cases. While vector-borne disease such as Japanese encephalitis and dengue virus and non-vector-borne diseases such as influenza and enterovirus show evidence of seasonality, associations with climate variables and the spatio-temporal distribution in Vietnam differs between these. The aim of this study was therefore to understand the spatio-temporal distribution of, and risk factors for AES in Vietnam to help hypothesise the aetiology.
The number of monthly cases per province for AES, meningitis and diseases including dengue fever; influenza-like-illness (ILI); hand, foot, and mouth disease (HFMD); and Streptococcus suis were obtained from the General Department for Preventive Medicine (GDPM) from 1998-2016. Covariates including climate, normalized difference vegetation index (NDVI), elevation, the number of pigs, socio-demographics, JEV vaccination coverage and the number of hospitals were also collected. Spatio-temporal multivariable mixed-effects negative binomial Bayesian models with an outcome of the number of cases of AES, a combination of the covariates and harmonic terms to determine the magnitude of seasonality were developed.
The national monthly incidence of AES declined by 63.3% over the study period. However, incidence increased in some provinces, particularly in the Northwest region. In northern Vietnam, the incidence peaked in the summer months in contrast to the southern provinces where incidence remained relatively constant throughout the year. The incidence of meningitis, ILI and S. suis infection; temperature, relative humidity with no lag, NDVI at a lag of one month, and the number of pigs per 100,000 population were positively associated with the number of cases of AES in all models in which these covariates were included.
The positive correlation of AES with temperature and humidity suggest that a number of cases may be due to vector-borne diseases, suggesting a need to focus on vaccination campaigns. However, further surveillance and research are recommended to investigate other possible aetiologies such as S. suis or Orientia tsutsugamushi.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pyrazinamide (PZA) is a key antibiotic in current anti-tuberculosis regimens. Although the WHO has stressed the urgent need to obtain data on PZA resistance, in high tuberculosis burden countries, ...little is known about the level of PZA resistance, the genetic basis of such resistance or its link with Mycobacterium tuberculosis families. In this context, this study assessed PZA resistance through the molecular analysis of 260 Vietnamese M. tuberculosis isolates. First-line drug susceptibility testing, pncA gene sequencing, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing were performed. Overall, the pncA mutation frequency was 38.1% (99 out of 260 isolates) but was higher than 72% (89 out of 123 isolates) in multidrug and quadruple-drug resistant isolates. Many different pncA mutations (71 types) were detected, of which 55 have been previously described and 50 were linked to PZA resistance. Among the 16 novel mutations, 14 are likely to be linked to PZA resistance because of their mutation types or codon positions. Genotype analysis revealed that PZA resistance can emerge in any M. tuberculosis cluster or family, although the mutation frequency was the highest in Beijing family isolates (47.7%, 62 out of 130 isolates). These data highlight the high rate of PZA resistance-associated mutations in M. tuberculosis clinical isolates in Vietnam and bring into question the use of PZA for current and future treatment regimens of multidrug-resistant tuberculosis without PZA resistance testing.
Between December 2020 and April 2023, the COVID-19 Scenario Modeling Hub (SMH) generated operational multi-month projections of COVID-19 burden in the US to guide pandemic planning and ...decision-making in the context of high uncertainty. This effort was born out of an attempt to coordinate, synthesize and effectively use the unprecedented amount of predictive modeling that emerged throughout the COVID-19 pandemic. Here we describe the history of this massive collective research effort, the process of convening and maintaining an open modeling hub active over multiple years, and attempt to provide a blueprint for future efforts. We detail the process of generating 17 rounds of scenarios and projections at different stages of the COVID-19 pandemic, and disseminating results to the public health community and lay public. We also highlight how SMH was expanded to generate influenza projections during the 2022–23 season. We identify key impacts of SMH results on public health and draw lessons to improve future collaborative modeling efforts, research on scenario projections, and the interface between models and policy.
•The Scenario Modeling Hub generated scenario projections throughout the COVID-19 pandemic.•Multi-model efforts are important for understanding interventions and mitigation strategies.•The Hub has had tangible impacts operating at the interface between models and policy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug ...resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (<69%). The mutation patterns revealed 23.1% of pre-XDR and 7.7% of XDR isolates, mostly belonging to Beijing family. The genotypic diversity and the variety of mutations reflect the existence of various evolutionary paths leading to FLD and SLD resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored.
•Pre-XDR and XDR isolates were detected in quadruple-drug resistant isolates collected between 2005–2009 in Vietnam.•The sequence analysis of 9 genes and promoter revealed high diversity of drug resistance-associated mutation patterns.•However, high frequency of preeminent mutations linked to high level of resistance and low fitness costs were detected.•The data suggest a cumulative effect of mutations and a role of epistasis in the evolution of multiple-drug resistance.•The spread of highly drug resistant Beijing isolates with successful genotypes makes TB situation more worrying.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
At present, the successful transmission of drug‐resistant Mycobacterium tuberculosis, including multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains, in human populations, threatens ...tuberculosis control worldwide. Differently from many other bacteria, M. tuberculosis drug resistance is acquired mainly through mutations in specific drug resistance‐associated genes. The panel of mutations is highly diverse, but depends on the affected gene and M. tuberculosis genetic background. The variety of genetic profiles observed in drug‐resistant clinical isolates underlines different evolutionary trajectories towards multiple drug resistance, although some mutation patterns are prominent. This review discusses the intrinsic processes that may influence drug resistance evolution in M. tuberculosis, such as mutation rate, drug resistance‐associated mutations, fitness cost, compensatory mutations and epistasis. This knowledge should help to better predict the risk of emergence of highly resistant M. tuberculosis strains and to develop new tools and strategies to limit the development and spread of MDR and XDR strains.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5–11 years on COVID-19 burden and resilience against variant ...strains.
Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5–11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses.
Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5–11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio IR 0.928, 95% confidence interval CI 0.880–0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834–0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797–1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed.
Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5–11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.
Various (see acknowledgments).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pyrazinamide (PZA) is a key antibiotic in current anti-tuberculosis regimens. Although the WHO has stressed the urgent need to obtain data on PZA resistance, in high tuberculosis burden countries, ...little is known about the level of PZA resistance, the genetic basis of such resistance or its link with Mycobacterium tuberculosis families. In this context, this study assessed PZA resistance through the molecular analysis of 260 Vietnamese M. tuberculosis isolates. First-line drug susceptibility testing, pncA gene sequencing, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing were performed. Overall, the pncA mutation frequency was 38.1% (99 out of 260 isolates) but was higher than 72% (89 out of 123 isolates) in multidrug and quadruple-drug resistant isolates. Many different pncA mutations (71 types) were detected, of which 55 have been previously described and 50 were linked to PZA resistance. Among the 16 novel mutations, 14 are likely to be linked to PZA resistance because of their mutation types or codon positions. Genotype analysis revealed that PZA resistance can emerge in any M. tuberculosis cluster or family, although the mutation frequency was the highest in Beijing family isolates (47.7%, 62 out of 130 isolates). These data highlight the high rate of PZA resistance-associated mutations in M. tuberculosis clinical isolates in Vietnam and bring into question the use of PZA for current and future treatment regimens of multidrug-resistant tuberculosis without PZA resistance testing.
Emerging Microbes & Infections (2017) 6, e86; doi:
10.1038/emi.2017.73
; published online 11 October 2017
Background: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5–11 years on COVID-19 burden and resilience ...against variant strains. Methods: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5–11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. Findings: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5–11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio IR 0.928, 95% confidence interval CI 0.880–0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834–0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797–1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. Interpretation: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5–11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Funding: Various (see acknowledgments).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pyrazinamide (PZA) is a key antibiotic in current anti-tuberculosis regimens. Although the WHO has stressed the urgent need to obtain data on PZA resistance, in high tuberculosis burden countries, ...little is known about the level of PZA resistance, the genetic basis of such resistance or its link with Mycobacterium tuberculosis families. In this context, this study assessed PZA resistance through the molecular analysis of 260 Vietnamese M. tuberculosis isolates. First-line drug susceptibility testing, pncA gene sequencing, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing were performed. Overall, the pncA mutation frequency was 38.1% (99 out of 260 isolates) but was higher than 72% (89 out of 123 isolates) in multidrug and quadruple-drug resistant isolates. Many different pncA mutations (71 types) were detected, of which 55 have been previously described and 50 were linked to PZA resistance. Among the 16 novel mutations, 14 are likely to be linked to PZA resistance because of their mutation types or codon positions. Genotype analysis revealed that PZA resistance can emerge in any M. tuberculosis cluster or family, although the mutation frequency was the highest in Beijing family isolates (47.7%, 62 out of 130 isolates). These data highlight the high rate of PZA resistance-associated mutations in M. tuberculosis clinical isolates in Vietnam and bring into question the use of PZA for current and future treatment regimens of multidrug-resistant tuberculosis without PZA resistance testing.Emerging Microbes & Infections (2017) 6, e86; doi:10.1038/emi.2017.73; published online 11 October 2017
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