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Annual Risk of Tuberculous Infection Using Different Methods in Communities with a High Prevalence of TB and HIV in Zambia and South Africa
PLOS ONE
Abstract and Figures
The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated.
Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates.
ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded.
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... Besides identifying those eligible for prophylaxis against TB, accurate determination of latent TB prevalence provides a basis for cross-sectional measures to estimate incidence rate: the annual risk of tuberculosis infection (ARTI) in a population (15,16). ARTI indicates the proportion of a particular population who will become infected in a community within a particular year and is based on Styblo rule that 50 incident cases of tuberculosis /100, 000 ...
... population per year corresponds to 1% ARTI (17,18). Although this rule has been invalidated because it was postulated when there were no functional TB control programs, effective TB treatments, and no HIV epidemic, it nevertheless, provides trend estimates useful in planning TB control activities and measuring the impact of HIV on tuberculosis transmission (16,18). ...
... In a previous study conducted in New York, there was no difference in prevalence when TST cut-off was reduced to ≥5 mm from ≥10 mm as a majority of the participants who had a positive TST had measurements greater than 10 mm (12). In South Africa, prevalence was high at the three cutoff points in a study to determine effect of environmental tobacco smoke exposure on the risk of TB infection amongst children in a high TB endemic locality and also in another study to determine ARTI using different methods in high HIV/TB prevalent communities (16,72). ...
... While repeated testing of uninfected individuals over time is a conventional method for determining incidence of a disease, this methodology is both labour and time intensive, and is further complicated in TB since only indirect measures based on the immune response to infection are available, and these may be affected by the boosting of the immune response, especially with in-vivo tests such as the TST [37,38]. Traditionally, alternative approaches for calculating incidence from cross-sectional data have been used [39]. The annual risk of TB infection (ARTI) is based on a measure of the risk of TB infection averaged over the lifetime of the study participants, and so has traditionally used data from young children [39][40][41]. ...
... Traditionally, alternative approaches for calculating incidence from cross-sectional data have been used [39]. The annual risk of TB infection (ARTI) is based on a measure of the risk of TB infection averaged over the lifetime of the study participants, and so has traditionally used data from young children [39][40][41]. We chose to measure incidence of TB-infection in AYA to identify recent infections and compare the incidence of TB-infection across the arms. ...
... The impact of a combined TB/HIV intervention on the incidence of TB infection proportion of non-infected individuals among AYA [22,39,42]. However, we found a higher prevalence of TB-infection at baseline than had been anticipated, leaving us with a lower proportion of uninfected individuals (2,223 / 4,648, 47.8% across both countries) than assumed in sample size calculations (60%). ...
Background:
HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years.
Methods:
A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up.
Results:
We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063).
Conclusion:
In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the population level dynamics of HIV and TB.
... To investigate how many new TB infection could be covered by contact investigation in the young generation, we calculated annual risk of TB infection in Group B with a simplified method using prevalence (2.08%) and mean age (17 years old) (40). In that way, the number of new TB infection in one-year was ∼119.82 cases per 100,000 population. ...
Background
The Government of South Korea launched a national preemptive latent tuberculosis infection (LTBI) screening program in 2016, including more than 1. 6 million population in congregate settings. The objective of this study was to analyze LTBI prevalence and its risk factors in each setting. Additionally, the proportion of LTBI pool covered by the current national LTBI strategy was investigated.
Methods
Database for results of interferon gamma release assay (IGRA), X-ray, and baseline demographic information was linked with National Health Information Database, national tuberculosis (TB) surveillance database, and national contact investigation database. Participants were categorized into three groups: Group A, workers of postpartum care centers, social welfare facilities and educational institutions; Group B, first year students in high school and out-of-school youths; and Group C, inmates of correctional facilities. Relative risks of LTBI by sex, age, place of living, income level, and comorbidities were calculated.
Results
A total of 444,394 participants in Group A, 272,224 participants in Group B, and 11,511 participants in Group C who participated in the national LTBI screening program between 2017 and 2018 were included, with LTBI prevalence of 20.7, 2.0, and 33.2%, respectively. Age was the single most important risk factor in Group A and Group C. Low-income level was another risk factor commonly identified in all groups. Among participants with positive IGRA results, 2.7, 4.4, and 3.3% in Groups A, B and C, respectively, had past TB exposure history since 2013. Current LTBI guideline targeting high or moderate TB risk disease covered 6.5, 0.6, and 1.1% of participants with positive IGRA results in Groups A, B and C, respectively.
Conclusion
Only a small proportion of participants with positive IGRA results could be covered by the current LTBI strategy. Expansion of LTBI strategy by identifying further high-TB risk group in the general population is required.
... This is worryingly high. To put these figures into context, standard methods estimate an annual risk of infection in the general population of 0.5-2% [39] in high-burden countries, with a slightly higher force of infection reported in community surveys in the Western Cape [40][41][42]. Whilst standard methods may underestimate the extent of community transmission [39], the risk to health workers is clearly much higher. Our calculations are consistent with empirical estimates of the force of infection among South African health workers, which suggest 29% are infected with Mtb per year [7]. ...
Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis . Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk. We measured ventilation in clinic spaces using a tracer-gas release method. In spaces where this was not possible, we estimated ventilation using data on indoor and outdoor carbon dioxide levels. Ventilation was measured i) under usual conditions and ii) with all windows and doors fully open. Under various assumptions about infectiousness and duration of exposure, measured absolute ventilation rates were related to risk of Mycobacterium tuberculosis transmission using the Wells-Riley Equation. In 2019, we obtained ventilation measurements in 33 clinical spaces in 10 clinics: 13 consultation rooms, 16 waiting areas and 4 other clinical spaces. Under usual conditions, the absolute ventilation rate was much higher in waiting rooms (median 1769 m ³ /hr, range 338–4815 m ³ /hr) than in consultation rooms (median 197 m ³ /hr, range 0–1451 m ³ /hr). When compared with usual conditions, fully opening existing doors and windows resulted in a median two-fold increase in ventilation. Using standard assumptions about infectiousness, we estimated that a health worker would have a 24.8% annual risk of becoming infected with Mycobacterium tuberculosis , and that a patient would have an 0.1% risk of becoming infected per visit. Opening existing doors and windows and rearranging patient pathways to preferentially use better ventilated clinic spaces result in important reductions in Mycobacterium tuberculosis transmission risk. However, unless combined with other tuberculosis infection prevention and control interventions, these changes are insufficient to reduce risk to health workers, and other highly exposed individuals, to acceptable levels.
... 5,6 The disease burden in prevalent South African communities is sustained by high rates of community transmission. 7,8 The majority of South Africa's TB disease has resulted from recent infections. 9,10 The South African National Strategic plan for Human Immunodeficiency Virus (HIV), TB, and Sexually Transmitted Infections prioritizes "breaking the cycle of transmission" and accelerating prevention to reduce new TB infections. ...
Objective
Novel approaches are needed to understand and disrupt Mycobacterium tuberculosis transmission. In this proof-of-concept study, we investigated the use of environmental air samplings to detect and quantify M. tuberculosis in different clinic settings in a high-burden area.
Design
Cross-sectional, environmental sampling.
Setting
Primary-care clinic.
Methods
A portable, high-flow dry filter unit (DFU) was used to draw air through polyester felt filters for 2 hours. Samples were collected in the waiting area and TB room of a primary care clinic. Controls included sterile filters placed directly into collection tubes at the DFU sampling site, and filter samplings performed outdoors. DNA was extracted from the filters, and droplet digital polymerase chain reaction (ddPCR) was used to quantify M. tuberculosis DNA copies. Carbon dioxide (CO 2 ) data loggers captured CO 2 concentrations in the sampled areas.
Results
The median sampling time was 123 minutes (interquartile range [IQR], 121–126). A median of 121 (IQR, 35–243) M. tuberculosis DNA copies were obtained from 74 clinic samplings, compared to a median of 3 (IQR, 1–33; P < .001) obtained from 47 controls. At a threshold of 320 DNA copies, specificity was 100%, and 18% of clinic samples would be classified as positive.
Conclusions
This proof-of-concept study suggests that the potential for airborne M. tuberculosis detection based on M. tuberculosis DNA copy yield to enable the identification of high-risk transmission locations. Further optimization of the M. tuberculosis extraction technique and ddPCR data analysis would improve detection and enable robust interpretation of these data.
... The ARTI outcome is calculated from estimated TB infection prevalence using the formula ARTI=1 -(1 -TB infection prevalence) 1/a , where a=mean age, estimated as 1.8%/year in primary school-aged children (mean age 9 years, TB infection prevalence 15%). 47 The ability to detect a 50% reduction in ARTI with a power of 0.8 (alpha of 0.05), comparing two samples of children at baseline and after the intervention, requires a sample size of 2580 children at each measurement (G*Power V.3.1). 48 Primary school children will be representatively sampled from the same age categories and schools at both measurements. ...
Introduction
Population-wide interventions offer a pathway to tuberculosis (TB) and leprosy elimination, but ‘real-world’ implementation in a high-burden setting using a combined approach has not been demonstrated. This implementation study aims to demonstrate the feasibility and evaluate the effect of population-wide screening, treatment and prevention on TB and leprosy incidence rates, as well as TB transmission.
Methods and analysis
A non-randomised ‘screen-and-treat’ intervention conducted in the Pacific atoll of South Tarawa, Kiribati. Households are enumerated and all residents ≥3 years, as well as children <3 years with recent household exposure to TB or leprosy, invited for screening. Participants are screened using tuberculin skin testing, signs and symptoms of TB or leprosy, digital chest X-ray with computer-aided detection and sputum testing (Xpert MTB/RIF Ultra). Those diagnosed with disease are referred to the National TB and Leprosy Programme for management. Participants with TB infection are offered TB preventive treatment and those without TB disease or infection, or leprosy, are offered leprosy prophylaxis. The primary study outcome is the difference in the annual TB case notification rate before and after the intervention; a similar outcome is included for leprosy. The effect on TB transmission will be measured by comparing the estimated annual risk of TB infection in primary school children before and after the intervention, as a co-primary outcome used for power calculations. Comparison of TB and leprosy case notification rates in South Tarawa (the intervention group) and the rest of Kiribati (the control group) before, during and after the intervention is a secondary outcome.
Ethics and dissemination
Approval was obtained from the University of Sydney Human Research Ethics Committee (project no. 2021/127) and the Kiribati Ministry of Health and Medical Services (MHMS). Findings will be shared with the MHMS and local communities, published in peer-reviewed journals and presented at international conferences.
Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of a clinically manifested active tuberculosis (TB) disease. One third of the world’s population is affected by M. tuberculosis, among which a majority of them may not have active TB disease; around 5 to 10% of them can develop active TB disease after 5 years of initial infection. The risk factor for progression to active TB disease depends on the immunological status of an individual. Testing for LTBI can be done by tuberculin skin test (TST) and interferon-gamma release assays (IGRAs); however, these tests can neither differentiate LTBI from active TB nor predict if an individual with LTBI can progress to active TB. The treatment options include 3 months of weekly regimen of isoniazid plus rifapentine (3HP) or 3 months of daily regimen of isoniazid plus rifampicin (3HR) or 6/9 months of daily isoniazid (6H/9H). Short-course regimens 3HP and 4R are effective and safe and have higher completion rates over long 6H/9H regimens. The treatment of LTBI, therefore, by preventing active TB disease and developing newer diagnostic tests better than the current ones is crucial to achieving the World Health Organization’s (WHO’s) End TB target and reducing global TB incidence to 80% by 2030.
Background:
Nigeria is one of the thirty high burden countries with significant contribution to the global childhood tuberculosis epidemic. Tuberculosis annual risk for children could be as high as 4% particularly in high tuberculosis (TB) prevalent communities. Isoniazid (INH) Preventive Therapy has been shown to prevent TB incidence but data on its implementation among children are scarce.
Aim:
To determine the completion of INH among under six children that were exposed to adults with smear positive pulmonary TB in Lagos, Nigeria.
Methods:
This was a hospital-based retrospective cross-sectional review of 265 medical records of eligible children < 6 years old enrolled for INH across 32 private hospitals in Lagos, Nigeria. The study took place between July and September 2020. Data was collected on independent variables (age, gender, type of facility, TB screening, dose and weight) and outcome variables (INH outcome and proportion lost to follow up across months 1-6 of INH treatment).
Results:
About 53.8% of the participants were female, 95.4% were screened for TB and none was diagnosed of having TB. The participants' age ranged from 1 to 72 mo with a mean of 36.01 ± 19.67 mo, and 40.2% were between the ages of 1-24 mo. Only 155 (59.2%) of the 262 participants initiated on INH completed the six-month treatment. Cumulatively, 107 (41.0%) children were lost to follow-up at the end of the sixth month. Of the cumulative 107 loss to follow-up while on INH, largest drop-offs were reported at the end of month 2, 52 (49%) followed by 20 (19%), 17 (16%), 11 (10.2%) and 7 (6.5%) at months 3, 4, 5 and 6 respectively. The analysis showed that there was no significant association between age, gender, type of facility and completion of INH treatment (P > 0.005).
Conclusion:
This study demonstrated suboptimal INH completion rate among children with only 6 out of 10 children initiated on INH who completed a 6-mo treatment in Lagos, Nigeria. The huge drop-offs in the first 2 mo of INH calls for innovative strategies such as the use of 60-d INH calendar that would facilitate reminder and early engagement of children on INH and their caregivers in care and across the entire period of treatment.
Objectives
: To track the prevalence trend of latent tuberculosis infection (LTBI) at the global, regional, and country levels.
Methods
: Data on the prevalence of LTBI were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was estimated by Joinpoint Regression and was used to evaluate the epidemic of the disease.
Results
: Globally, the prevalence rate of LTBI decreased from 30.66% in 1990 to 23.67% in 2019 with an AAPC of -0.9%. The prevalence rate of LTBI varied from 5.02% (Jordan) to 48.35% (Uganda) in 1990 and from 2.51% (Jordan) to 43.75% (Viet Nam) in 2019 at the country level. The prevalence decreased in all the six WHO regions and in the vast majority of countries, with the AAPC ranging from -0.5% in the Western Pacific Region to -2.1% in the European Region, and from -4.3% (Bhutan) to -0.1% (Malaysia, Myanmar, South Africa, Tokelau, and Viet Nam), respectively. Disparities were also observed among different sex and age groups.
Conclusions
: The prevalence of LTBI decreased slightly globally in the last three decades, but the decrease is slow and not sufficient to meet the targets of WHO TB elimination. Much more effort and progress should be made in order to reduce the prevalence of LTBI.
The prevalence of tuberculous infection was estimated among 12,032 persons with a Bacillus Calmette-Guerin (BCG) vaccination scar and 7,788 persons without such a scar who participated in a nationwide tuberculin skin test survey conducted in the Republic of Korea in 1975. The analysis was built upon mixture models that captured the heterogeneity of indurations arising from tuberculous infection, cross-reactions due to infection with environmental mycobacteria, and BCG vaccination. The three distributions were allowed to vary by age, sex, and BCG vaccination status in the Bayesian manner, according to the prior opinion of the authors. Estimated prevalences of tuberculous infection were similar among persons with a BCG scar and persons without one: 7.5% (95% credibility interval (Cl): 3.1, 12.5) and 5.2% (95% CI: 4.2, 6.3), respectively, at age 0-4 years and 87.3% (95% CI: 84.0, 90.2) and 84.0% (95% Cl: 81.9, 85.8), respectively, at age 25-29 years. From this analysis it can be concluded that mixture models allow investigators, for the first time, to estimate the prevalence of tuberculous infection not only in unvaccinated persons but also in the BCG-vaccinated population. Mixture models are a versatile tool for analyzing diagnostic test data and more general classification problems of considerable complexity.
SETTING: In Tanzania, a national tuberculosis programme (NTP) was established in 1979 based on the principles currently known as the World Health Organization DOTS strategy. From the period 1983-1987 to 1994-1998, notification rates of smear-positive tuberculosis increased from 32 to 69 per 100 000 population, mainly due to the human immunodeficiency virus (HIV) epidemic. OBJECTIVES: To estimate the trend in the annual risk of tuberculosis infection and to establish to what extent the opposing forces of improved tuberculosis control and HIV have had an impact on tuberculosis transmission. METHODS: Three national surveys were conducted in Tanzania among primary school children at 5-year intervals. The annual risk of tuberculosis infection and its trend were determined by tuberculin skin testing. RESULTS: The annual risk of infection in children with- out BCG scar using the criterion '17 mm + 2 × 18 mm' or more was estimated at 1.1% in 1983-1987, 1.0 in 1988-1992, and 0.9% in 1993-1998. There appears to have been little change in the annual risk of infection over the study period, either when using other criteria to define infection or in children with a BCG scar. The estimated number of infections per notified case decreased over time from 36 to 19. CONCLUSIONS: Despite strongly increased tuberculosis notification rates in adults, associated with the HIV epidemic, the risk of tuberculosis infection in children appears to have been stable over the past 15 years in Tanzania. This remarkable achievement is probably due to the impact of the NTP on tuberculosis transmission.
Comprehensive new guidelines for screening, targeted testing, and treating latent tuberculosis infection (LTBI) in children and adolescents are presented. The recent epidemiology of TB and data on risk factors for LTBI are reviewed. The evidence-based recommendations provided emphasize the paradigm that children and adolescents should be screened for risk factors by using a risk-factor questionnaire for TB and LTBI and tested with the tuberculin skin test only if ≥1 risk factor is present. The use of administrative or mandated tuberculin skin tests for entry to day care, school, or summer camp is strongly discouraged. Treatment regimens, suggestions to improve adherence, and methods to monitor toxicities are summarized. Children and adolescents with LTBI represent the future reservoir for cases of TB. Thus, detecting and treating LTBI in children and adolescents will contribute to the elimination of TB in the United States.
The prevalence and incidence rates of tuberculous infection were calculated from 170 000 Mantoux test results gathered by the Tuberculosis Research Institute between 1974 and 1980 and also from tuberculin survey results from other sources covering the periods 1944-45 and 1953-54. Prevalence rates in 10-year-olds were generally low in the Asian and White groups, less than 5 % at present, and fairly high in the Coloured and Black groups, whose rates ranged from 10 % to 20 %. Very little difference was found between the prevalence rates of the urban and rural populations in any of the age groups surveyed, but as a rule higher rates were found in lowland (mostly coastal) than in highland regions. An overall annual decrease over the past 25-30 years of 5 % in the infection rates of Blacks and Coloureds was estimated, and of 7 % and 8 % in Asians and Whites. However, it is suggested that these downward trends have increased progressively in all ethnic groups in South Africa in recentyears, but that annually they do not exceed 13%. Annual rates of infection in 7-year-olds were expected to reach 1-2 per 1000 Blacks by 1982. One tuberculous infection annually per 1000 population may be considered sufficiently low for the disease to be regarded as of minimal importance. In South African Whites this level has already been reached and it is expected to be in Asians within the next 5-10 years. In Coloureds and Blacks another 20 to 30 years will have to pass before this level is reached.