Prevalence and Diagnosis of Latent Tuberculosis Infection Among Pediatric Household Contacts of Iranian Tuberculosis Cases

Abstract Background: Although the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran.Methods: We conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active disease through evaluation of symptoms and if active disease was suspected were investigated by chest radiograph and bacilli detection in sputum or nasogastric lavage. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10 (IP-10) concentrations were measured in QFT-Plus supernatants for all participants. Results: A total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study.Conclusion: This study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

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Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- γ release assay and IFN-γ-induced protein-10

BMC Pediatrics ◽

10.1186/s12887-021-02524-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Roxana Mansour Ghanaie ◽

Abdollah Karimi ◽

Leila Azimi ◽

Seddon James ◽

Mahshid Nasehi ◽

...

Keyword(s):

Tuberculin Skin Test ◽

Skin Test ◽

Close Contact ◽

Latent Tuberculosis ◽

High Risk Group ◽

World Health ◽

Tuberculous Infection ◽

High Burden ◽

Household Contacts ◽

Ifn Γ

Abstract Background Although the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran. Methods We conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active TB disease. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10(IP-10) concentrations were measured for all participants. Results A total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study. Significantly increased IP-10 levels were found in LTBI patients compared to healthy contacts. Accordingly, more than 50% of LTBI contacts and about 10% of healthy contacts were considered as IP-10-positive. Conclusion This study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

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Tuberculosis infection screening in children with close contact: a hospital-based study

BMC Infectious Diseases ◽

10.1186/s12879-021-06480-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lin Sun ◽

Xue Qi ◽

Yajie Guo ◽

Hui Qi ◽

Jieqiong Li ◽

...

Keyword(s):

Close Contact ◽

Latent Tuberculosis ◽

Clinical Importance ◽

Interferon Γ ◽

Screening Strategy ◽

Household Contact ◽

Tuberculosis Infection ◽

Household Contacts ◽

Ltbi Screening ◽

Positive Results

Abstract Background Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance. Methods During 2013–2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk. Results A total 6202 children (median age: 4.76 years; interquartile range: 1.0–8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA− /TST+ results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result. Conclusions Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.

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Lurking in the Dark: Latent Tuberculosis Infection

International Journal of Medical and Dental Sciences ◽

10.19056/ijmdsjssmes/2014/v3i1/80731 ◽

2014 ◽

Vol 3 (1) ◽

pp. 369

Author(s):

Kavita Krishna ◽

Sachin Adukia ◽

Ayantika Dhara

Keyword(s):

Early Diagnosis ◽

Latent Tuberculosis Infection ◽

Close Contact ◽

Latent Tuberculosis ◽

Tuberculin Test ◽

Tuberculosis Infection ◽

World Health ◽

Interferon Gamma Release Assay ◽

Tuberculous Infection ◽

Diagnostic Modality

A subset of the tuberculous population has latent tuberculosis infection (LTBI). It is a condition wherein the affected individual is infected with Mycobacterium tuberculosis, but does not have any signs or symptoms of tuberculosis nor is he infectious to others. Risk of progression to active tuberculous infection is influenced by co-morbidities like HIV, diabetes, malignancy requiring chemotherapy, infants and children in close contact with susceptible individuals, and healthcare workers. Early diagnosis of LTBI is paramount. In addition to tuberculin test, Interferon gamma release assay (IGRA) is the new diagnostic modality that can be used for this purpose. Quantiferon-TB Gold In-Tube (QFT-GIT) and T-SPOT TB are the two currently available IGRAs, of which the latter is slightly more preferred. More recently, TB PCR (Polymerase Chain Reaction) has aided accurate and early diagnosis of all forms of TB. While treating LTBI, it is observed that Isoniazid (INH) has stood the test of time and still prevails as the treatment of choice for active infection and for LTBI. Of course, adverse effects of INH and need for regular laboratory monitoring persist. Recently, moxifloxacin has been used as a substitute for INH. Newer drugs like rifapentine, nitromidazopyran, metronidazole and nitrofurans have all been tried with variable success and several clinical limitations, depending on comorbid conditions. India’s burden of extensive prevalence of TB is compounded by paucity of data on the same. The World Health Organization has estimated a mortality of 36 million by 2020 due to TB. This projection should encourage aggressive research into this entity.

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The global prevalence of latent tuberculosis: a systematic review and meta-analysis

European Respiratory Journal ◽

10.1183/13993003.00655-2019 ◽

2019 ◽

Vol 54 (3) ◽

pp. 1900655 ◽

Cited By ~ 38

Author(s):

Adam Cohen ◽

Victor Dahl Mathiasen ◽

Thomas Schön ◽

Christian Wejse

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Latent Tuberculosis ◽

Interferon Γ ◽

Preventive Therapy ◽

Incidence Rates ◽

World Health ◽

Global Prevalence ◽

Ltbi Prevalence ◽

Health Organization

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model.Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7–30.0%) and 21.2% (95% CI 17.9–24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

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Negative latent tuberculosis at time of incarceration: identifying a very high-risk group for infection

Epidemiology and Infection ◽

10.1017/s0950268817001558 ◽

2017 ◽

Vol 145 (12) ◽

pp. 2491-2499 ◽

Cited By ~ 8

Author(s):

L. ARROYAVE ◽

Y. KEYNAN ◽

L. LÓPEZ ◽

D. MARIN ◽

M. P. ARBELÁEZ ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Latent Tuberculosis ◽

Risk Groups ◽

High Risk Group ◽

World Health ◽

Formerly Incarcerated ◽

Adjusted Risk ◽

Number Needed To Screen ◽

Health Organization

SUMMARYThe main aim was to measure the incidence of latent tuberculosis infection (LTBI) and identify risk factors associated with infection. In addition, we determined the number needed to screen (NNS) to identify LTBI and active tuberculosis. We followed 129 prisoners for 2 years following a negative two-step tuberculin skin test (TST). The cumulative incidence of TST conversion over 2 years was 29·5% (38/129), among the new TST converters, nine developed active TB. Among persons with no evidence of LTBI, the NNS to identify a LTBI case was 3·4 and an active TB case was 14·3. The adjusted risk factors for LTBI conversion were incarceration in prison number 1, being formerly incarcerated, and overweight. In conclusion, prisoners have higher risk of LTBI acquisition compared with high-risk groups, such as HIV-infected individuals and children for whom LTBI testing should be performed according to World Health Organization guidance. The high conversion rate is associated with high incidence of active TB disease, and therefore we recommend mandatory LTBI screening at the time of prison entry. Individuals with a negative TST at the time of entry to prison are at high risk of acquiring infection, and should therefore be followed in order to detect convertors and offer LTBI treatment. This approach has a very low NNS for each identified case, and it can be utilized to decrease development of active TB disease and transmission.

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Short-course regimens of rifapentine plus isoniazid to treat latent tuberculosis infection in older Chinese patients: a randomised controlled study

European Respiratory Journal ◽

10.1183/13993003.01470-2018 ◽

2018 ◽

Vol 52 (6) ◽

pp. 1801470 ◽

Cited By ~ 12

Author(s):

Lei Gao ◽

Haoran Zhang ◽

Henan Xin ◽

Jianmin Liu ◽

Shouguo Pan ◽

...

Keyword(s):

Adverse Effects ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

World Health ◽

Controlled Study ◽

Short Course ◽

Significant Difference ◽

Randomised Controlled ◽

Active Disease

Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organization's End TB Strategy.In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50–69 years with LTBI in China.Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). In the modified intention-to-treat analysis on the completed doses, the cumulative rate of active disease during 2 years of follow-up was 1.21% (14 out of 1155) in the untreated controls, 0.78% (10 out of 1284) in the group that received the 8-week once-weekly regimen and 0.46% (six out of 1299) in the group that received the 6-week twice-weekly regimen. The risk of active disease was decreased, with an adjusted hazard ratio of 0.63 (95% CI 0.27–1.43) and 0.41 (95% CI 0.15–1.09) for the treatments, respectively. No significant difference was found in the occurrence of hepatotoxicity (1.02% (13 out of 1279) versus 1.17% (15 out of 1279); p=0.704).The short regimens tested must be used with caution among the elderly because of the high rates of adverse effects. Further work is necessary to test the ultrashort regimens in younger people with LTBI.

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The impact of isoniazid preventive therapy on tuberculosis among household contacts of isoniazid-resistant patients

10.1101/479865 ◽

2018 ◽

Author(s):

Chuan-Chin Huang ◽

Mercedes C. Becerra ◽

Roger Calderon ◽

Carmen Contreras ◽

Jerome Galea ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Latent Tuberculosis ◽

Preventive Therapy ◽

Independent Study ◽

World Health ◽

Household Contacts ◽

Mdr Tb ◽

Health Organization ◽

The Impact

ABSTRACTBackgroundThe World Health Organization recommends the use of isoniazid (INH) alone or combination INH and rifapentine therapy to treat latent tuberculosis infection (LTBI) in groups at high risk of tuberculosis (TB) progression. The recent rise of INH– and multi–drug resistant (MDR) TB has complicated the choice of LTBI treatment regimen. We examine the risk of TB disease among household contacts (HHCs) who received INH after being exposed to patients with drug–sensitive, INH–resistant, or MDR tuberculosis.MethodsIn this prospective cohort study conducted Between September 2009 and August 2012 in Lima, Peru, we identified 4,500 index TB patients and measured incident TB disease in their 14,044 HHCs over a one–year follow–up period. HHCs under 19 years of age were offered INH preventive therapy (IPT). We used a Cox frailty proportional hazards model to evaluate whether the effect of IPT on incident TB disease varied by the resistance profile of the index case. We repeated the analyses in a second independent dataset.FindingsAmong 4,216 HHCs under 19 years of age, 2,106 (50%) initiated IPT at enrolment. The protective effect of INH was more extreme in HHCs exposed to drug–sensitive (Hazard Ratio [95% confidence interval]=0·2[0·20–0·50]) and to MDR–TB (0·26[0·08–0·77]) compared to those exposed to mono–INH–resistant (0·80[0·23 to 2·79]). Among those who received at least three months of INH, effectiveness increased across all three groups (INH–sensitive:0·20 [0·10 to 040]; MDR:0·16 [0 02–127]; mono–INH–resistant:0·72 [0·16–3·16]). In the second independent study, TB occurred in none of the 76 HHCs who received IPT compared to 3% (8/273) of those who did not.InterpretationWe found that IPT use is associated with reduced incidence of TB disease among contacts of MDR–TB patients. This finding suggests that INH may have role in the management of MDR–LTBI.FundingNational Institutes of Health and the National Institute of Allergy and Infectious Diseases CETR (U19AI109755) and TBRU (U19AI111224)

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