Tuberculosis In Young Children Research Articles

Exhaled breath analysis: a promising triage test for tuberculosis in young children

The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86% (CI 62-96%), this resulted in a specificity of 42% (95% CI 30-55%).Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.

Feasibility and utility of a combined nasogastric-tube-and-string-test device for bacteriologic confirmation of pulmonary tuberculosis in young children

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.

Point-of-Care Ultrasound for Tuberculosis in Young Children with Severe Acute Malnutrition.

Point-of-care ultrasound (POCUS) to diagnose tuberculosis (TB) was assessed in 131 children under 5 years old hospitalized with severe acute malnutrition. Of these, 23% had confirmed or unconfirmed TB and 5% were HIV-infected. There were no POCUS findings associated with TB diagnosis. POCUS visualization quality was satisfactory for 65% and examination acceptability was "good" for 52%.

Machine learning to predict bacteriologic confirmation of Mycobacterium tuberculosis in infants and very young children.

Diagnosis of tuberculosis (TB) among young children (<5 years) is challenging due to the paucibacillary nature of clinical disease and clinical similarities to other childhood diseases. We used machine learning to develop accurate prediction models of microbial confirmation with simply defined and easily obtainable clinical, demographic, and radiologic factors. We evaluated eleven supervised machine learning models (using stepwise regression, regularized regression, decision tree, and support vector machine approaches) to predict microbial confirmation in young children (<5 years) using samples from invasive (reference-standard) or noninvasive procedure. Models were trained and tested using data from a large prospective cohort of young children with symptoms suggestive of TB in Kenya. Model performance was evaluated using areas under the receiver operating curve (AUROC) and precision-recall curve (AUPRC), accuracy metrics. (i.e., sensitivity, specificity), F-beta scores, Cohen's Kappa, and Matthew's Correlation Coefficient. Among 262 included children, 29 (11%) were microbially confirmed using any sampling technique. Models were accurate at predicting microbial confirmation in samples obtained from invasive procedures (AUROC range: 0.84-0.90) and from noninvasive procedures (AUROC range: 0.83-0.89). History of household contact with a confirmed case of TB, immunological evidence of TB infection, and a chest x-ray consistent with TB disease were consistently influential across models. Our results suggest machine learning can accurately predict microbial confirmation of M. tuberculosis in young children using simply defined features and increase the bacteriologic yield in diagnostic cohorts. These findings may facilitate clinical decision making and guide clinical research into novel biomarkers of TB disease in young children.

HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study

BackgroundChildren under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya.MethodsThis sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis.ResultsWe enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition (AOR 3.16 [1.14–8.71], p = 0.027). Most TB diagnoses (140/157, 89%) were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity (AOR: 6.10 [1.32–28.17], p = 0.021) was independently associated with a shorter time to TB diagnosis as well as fatigue (AOR: 6.58 [2.28–18.96], p = 0.0005), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58–19.83], p = 0.0075), whereas older age (AOR: 0.35 [0.15–0.85], p = 0.020 for age 2–5 years), night sweats (AOR: 0.24 [0.10–0.60], p = 0.0022) and acute malnutrition (AOR: 0.36 [0.14–0.92], p = 0.034) were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31.ConclusionsThese results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV.Trial registrationNCT03862261, first registration 05/03/2019.

NATCON 2022 Panel discussion: “TB vaccination - Going Forward”

Vaccination is important tuberculosis (TB) preventive strategy that is essential to achieve the goals of the End TB strategy. The BCG vaccination at birth offers protection against TB in young children but not in adolescents and adults. New TB vaccines are the need of the hour. The TB vaccine development pipeline in the past years is encouraging with newer TB vaccines in clinical trials in humans. The focus of the newer TB vaccine is the prevention of infection, disease, and recurrence of TB disease. Therapeutic vaccines focus on better treatment outcomes and prevention of TB recurrence. BCG revaccination is of current interest. Novel, safe, and efficient TB vaccines that prevent TB infection and disease if introduced in 2025 could drastically reduce the rate of TB incidence. However, the development of an effective vaccine for TB is challenging. Engagement of stakeholders, mobilizing funding, and advocacy could accelerate the newer TB vaccine development process.

Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis

BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. National Institutes of Health.

Mother's iliac bone graft for severe collapsed lumbar tuberculosis: A case report

AbstractEarly diagnosis of spinal tuberculosis in young children is difficult due to atypical clinical features. We report a case of lumbar tuberculosis with abscess of the psoas major muscle in a 4‐year‐old child. Spinal reconstruction was challenging due to the involvement of multiple vertebral levels. The child complained of lumbar and back pain. Preoperative magnetic resonance imaging (MRI) revealed bone destruction of the L1–L3 vertebral body and abscess formation of the psoas major muscle. The child underwent excision of the vertebral lesions and a fresh iliac bone graft from his mother through an anterior approach and posterior fixation with T12–L1 and L4–L5 pedicle screws. At the 15‐month follow‐up, the patient had good clinico‐radiologic outcomes with evidence of bony fusion. No functional impairment of lumbar movements was found through physical examination during the follow‐up period. The report highlights the diagnostic dilemma of early childhood spinal tuberculosis due to lesions seen both on radiology and during surgery and discusses challenges in management of the disease and the relevant literature. The mother's iliac bone graft we describe can be a viable option in very young children with severe vertebral bone destruction requiring reconstruction by surgical procedure.

Surgical Treatment for Advanced Thoracic Spinal Tuberculosis in Infants: Case Series and Literature Review.

Spinal tuberculosis (TB), or Pott's disease, is the most common form of osteoarticular TB. Early diagnosis and anti-TB drug therapy are the mainstays of treatment. However, in advanced stages, surgery is essential to correct spinal deformities and avoid neurological damage. Very few cases in young children requiring surgical treatment have been described. We present 2 cases of surgically treated thoracic spinal TB in patients under 2 years of age and review the literature on this entity in young children. Two male toddlers, aged 21 (patient 1) and 23 (patient 2) months, were admitted due to insidious systemic deterioration associated with neck stiffness and nonspecific abdominal pain in patient 1 and limping in patient 2. The findings of laboratory tests were unremarkable despite an increase in acute-phase reactants. After an extensive workup, results of a magnetic resonance imaging were consistent with spinal TB in both patients. Patient 1 underwent costotransversectomy of the left third and fourth ribs, debridement, T3-T4 corpectomy, and T2-T6 posterior fusion, to which an anterior rib autograft was added. Patient 2 had a right-sided thoracotomy performed at the apex in addition to debridement and T8 corpectomy; the resected rib was used as anterior structural autograft. Several samples of purulent, caseous material were sent for study. On follow-up, progression of proximal junctional kyphosis was evidenced in patient 1, requiring revision surgery to restore sagittal alignment; the patient was asymptomatic at 2-year follow-up. Patient 2 evolved satisfactorily without neurological sequelae and was asymptomatic at 4-year follow-up. Spinal TB in young children requires appropriate surgical treatment when presenting at advanced stages or having severe deformity or neurological compromise. Despite the challenges associated with young age and ongoing growth, surgery can be performed safely provided proper surgical expertise. After extensive debridement and decompression, priority should be given to restoring sagittal alignment and balance with stable and durable spinal reconstructions.

Clinical cases of late diagnosis of tuberculosis in young children

Clinical cases of late diagnosis of tuberculosis in young children

Specific Host Signatures for the Detection of Tuberculosis Infection in Children in a Low TB Incidence Country.

Diagnosis of tuberculosis (TB) in children remains challenging due to unspecific clinical presentation and low bacillary load. In low TB incidence countries, most cases are diagnosed by a contact screening strategy after exposure to an index TB case. Due to the severity of TB in young children, the priority is to determine whether a child is infected or not, whereas differential diagnosis between active TB (aTB) and latent TB constitutes a second step. In Belgium, a low TB incidence country, we prospectively included 47 children with a defined M. tuberculosis infection status (12 children with aTB, 18 with latent TB, and 17 uninfected) (exploratory cohort), and determined the optimal combinations of cytokines secreted by their peripheral blood mononuclear cells in response to a 5-days in vitro stimulation with four different mycobacterial antigens, in an attempt to classify the children according to their infectious status. Correct identification of all infected children was obtained by several combinations of two purified protein derivative (PPD)-induced cytokines (IFN-γ and either GM-CSF, MIP-1α, sCD40L or TNF-α), or by combining PPD-induced IFN-γ with culture-filtrate protein-10 (CFP-10)-induced TNF-α. Alternatively, combining CFP-10-induced TNF-α and IP-10 with heparin-binding haemagglutinin (HBHA)-induced-IFN-γ was more effective in testing recently BCG-vaccinated children or those suspected to be infected with non-tuberculous mycobacteria, providing a correct classification of 97% of the M. tuberculosis-infected children. This combination also correctly classified 98% of the children from a validation cohort comprising 40 M. tuberculosis infected children and 20 non-infected children. Further differentiation between aTB and children with latent TB was more difficult. Combining ESAT-6-induced MIP1-α and IP-10, CFP-10-induced MIG, and HBHA-induced MIG provided a correct classification of 77% of the children from the exploratory cohort but only of 57.5% of those from the validation cohort. We conclude that combining the measurement of 2–4 cytokines induced by three different mycobacterial antigens allows an excellent identification of M. tuberculosis-infected children, whereas differentiating children with aTB from those with latent TB remains far from perfect.

Sensitive and Feasible Specimen Collection and Testing Strategies for Diagnosing Tuberculosis in Young Children

Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.

Туберкулез ЛОР-органов у детей раннего возраста

The identification of millions of newly infected with tuberculosis while maintaining a sufficiently high mortality rate, despite the existing treatment protocols, confirms the urgency of the problem of diagnosing this disease and dictates the need for an interdisciplinary approach to this problem. In the overwhelming majority of cases, tuberculosis is associated with lung damage, but its “extrapulmonary” manifestations are also possible, in particular with localization in the head and neck region (about 10%), including in the ENT organs. According to the literature, the incidence of tuberculous lesions is maximum for the larynx (from 14,5 to 15–37%), minimum for ear diseases (from 0,04–0.09% to 2,4–4,18%). To focus the attention of otorhinolaryngologists on the problem of “extrapulmonary tuberculosis” of ENT localization in pediatric practice, this study analyzes the case histories of 496 patients of tuberculous pulmonary pediatric department No. 1 of the Moscow Research and Clinical Center for Tuberculosis Control. Tuberculous lesion of ENT localization against the background of a generalized process was found in 7 patients (1.4%) aged from 2,5 months to 1 year 9 months. Tuberculous otitis media was most often detected (4 patients (0.6%)), in single cases – tuberculosis of the larynx, tuberculosis of the pharynx, tuberculosis of the salivary gland, including in combination with other organic ENT pathology (for example, papillomatosis and tuberculosis of the larynx). Thus, the lesion of the head and neck (including the ENT organs) is one of the “underestimated” extrapulmonary localizations of tuberculosis, and the diagnosis and verification are delayed. Among the “extrapulmonary” ENT manifestations of tuberculosis in young children, according to our data, otitis media prevails. To verify the diagnosis of “Tuberculosis” of any localization, it is necessary to inoculate Mycobacterium tuberculosis and be sure to consult the material obtained with histologists. Doctors of various specialties should not forget about the possibility of setting Mantoux tests with 2 tuberculin units (TU) and adenosine triphosphate (ATP) test for diagnostic purposes, despite the absence of a routine immunological examination in the national immunization schedule for children of the first year of life. Tuberculosis is curable, the main thing is to remember the need for early and timely diagnosis and adequate long-term treatment.

Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB.

The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4+ T cell responses, thought to be important for protection against TB disease, but not known to be sufficient or critical for protection. Advances in knowledge of host responses to TB afford opportunities for developing TB vaccines that target immune components not conventionally considered. Here, we describe the potential of targeting NK cells, innate immune training, B cells and antibodies, and Th17 cells in novel TB vaccine development. We also discuss attempts to target vaccine immunity specifically to the lung, the primary disease site in humans.

The role of social factors in the development of chronic primary tuberculosis in early childhood

The objective of the article: to demonstrate the peculiarities of tuberculosis in young children and the high probability of the transition of primary tuberculosis in a child from a sociopathic family to a chronic process due to the absence of medical supervision after chemotherapy. The article describes a clinical case demonstrating the influence of dysfunctional social risk factors on the development of chronic primary tuberculosis in a child. The authors provide a detailed information of medical care to the child, including surgery.

Curcumin Nanoparticles Enhance Mycobacterium bovis BCG Vaccine Efficacy by Modulating Host Immune Responses.

Tuberculosis (TB) is one of the deadliest diseases, causing ∼2 million deaths annually worldwide. Mycobacterium bovis bacillus Calmette-Guérin (BCG), the only TB vaccine in common use, is effective against disseminated and meningeal TB in young children but is not effective against adult pulmonary TB. T helper 1 (Th1) cells producing interferon gamma (IFN-γ) and Th17 cells producing interleukin-17 (IL-17) play key roles in host protection against TB, whereas Th2 cells producing IL-4 and regulatory T cells (Tregs) facilitate TB disease progression by inhibiting protective Th1 and Th17 responses. Furthermore, the longevity of vaccine efficacy critically depends on the magnitude of long-lasting central memory T (TCM) cell responses. Hence, immunomodulators that promote TCM responses of the Th1 and Th17 cell lineages may improve BCG vaccine efficacy. Here, we show that curcumin nanoparticles enhance various antigen-presenting cell (APC) functions, including autophagy, costimulatory activity, and the production of inflammatory cytokines and other mediators. We further show that curcumin nanoparticles enhance the capacity of BCG to induce TCM cells of the Th1 and Th17 lineages, which augments host protection against TB infection. Thus, curcumin nanoparticles hold promise for enhancing the efficacy of TB vaccines.

INDUCED SPUTUM VERSUS GASTRIC ASPIRATE FOR MICROBIOLOGICAL CONFIRMATION OF PULMONARY TUBERCULOSIS IN INFANTS AND YOUNG CHILDREN: A PROSPECTIVE COHORT STUDY

Introduction: The diagnosis of tuberculosis (TB) is challenging in children due to the paucibacillary nature of disease and difficulty in sample collection. Gastric lavage (GL) is recommended in children because children tend to swallow sputum and do not expectorate; however, it is invasive, stressful and requires admission. Objective: The objective of this study was to compare the yield of GL samples with that of induced sputum, which is a non-invasive method and can be done on an outpatient basis. Methods: A prospective cohort study was done on 55 children, who were <6 years of age, admitted for suspected pulmonary TB (PTB) in Medical College, Aligarh, from December 2011 to December 2013. Sputum induction and GL were done on 3 consecutive days according to the standard procedure. All samples were stained for acid-fast bacilli and each sample was cultured for Mycobacterium tuberculosis. Results: The median age of the children in the study group was 28 months. A positive smear and culture were positive for M. tuberculosis in 7.2% and 20% of children, respectively. There was no significant difference in smear positivity from induced sputum samples compared to gastric aspirate samples. However, the culture positivity for M. tuberculosis was better with induced sputum than gastric aspirate and the difference was statistically significant (p<0.05). Sputum induction procedures were well tolerated; minor side effects were vomiting, mild epistaxis, coughing, or transient wheezing. Conclusion: Sputum induction is safe and useful for microbiological confirmation of TB in young children. This technique is preferable to GL for diagnosis of PTB.

Radiological aspects in computed tomography as determinants in the diagnosis of pulmonary tuberculosis in immunocompetent infants.

ObjectiveTo describe the chest computed tomography (CT) findings in immunocompetent children under 36 months of age with pulmonary tuberculosis.Materials and MethodsThis was a descriptive case series conducted in the city of Rio de Janeiro, Brazil, between January 2004 and July 2013, involving 20 young children who underwent CT after undergoing chest X-rays that did not provide a definitive diagnosis.ResultsAll of the participants had lymph node enlargement and consolidations. In 15 cases (75%), the consolidations were accompanied by atelectasis. Pulmonary cavitation was seen in 10 cases (50%), and cavitation within consolidations was seen in 7 (35%). The areas of cavitation and parenchymal destruction were not seen on conventional chest X-rays.ConclusionThe radiological presentation of pulmonary tuberculosis in young children differs from that described in older children and adults. CT is an effective method for the early diagnosis of pulmonary tuberculosis in immunocompetent infants, allowing the rapid institution of specific treatment, which is crucial for halting disease progression, as well as for preventing local and systemic complications.

A comparative study of Mantoux test and BCG test in diagnosis of childhood tuberculosis

Background: India has one of the highest tuberculosis (TB) burdens globally. However, few studies have focused on TB in young children, a vulnerable population, where lack of early diagnosis results in poor outcomes.Methods: The present study was undertaken to assess the sensitivity and specificity of tuberculin test (Mantoux) and BCG test in diagnosis of childhood tuberculosis and to compare above tests as a diagnostic tool and to assess the impact of factors affecting the test. Mantoux test was done with 1 TU contained in 0.1 ml of PPD R23 with tween 80 solution. BCG test was done using a heat stable freeze-dried vaccine, after fresh reconstitution and injected intradermally in left deltoid region with a tuberculin syringe and 27 G hypodermic needle.Results: Tuberculous cases were more common in malnourished subjects more so with severe malnutrition. While maximum positivity 89% was obtained with BCG test, it was only 63% with Mantoux test, done with 5TU of PPD-RT-23. BCG was always positive whenever PPD was positive in any group of children. Sensitivity of Mantoux test was around 63% whereas that of BCG test was 89%. BCG test was more significantly associated with disease than tuberculin test (p &lt;0.001).Conclusions: BCG test is a very sensitive and specific test for diagnosis of childhood tuberculosis. Mantoux test is affected by malnutrition and severity of disease whereas BCG test is affected only minimally. BCG test is more sensitive than Mantoux test (with 5TU PPD RT 23 Tween 80). A BCG induration of ≥10 mm or Mantoux induration ≥15 mm or an accelerated BCG test is indicative of active disease, irrespective of vaccination status of the patient.

Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis

The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential for disseminated TB in young children its disease protection rates in adults is highly variable while it confers little protection against latent TB. With these limitations a new vaccine is desperately needed. We investigated the efficacy of three members of the mycobacterial membrane protein Large (MmpL) family as potential subunit vaccines for TB. MmpLs are large, multifunctional integral membrane proteins, and as such are recalcitrant to purification. Here, we describe a strategy of producing synthetic antigens comprised of the soluble, extracellular regions of MmpL (SERoM)-1, MmpL8 and MmpL10 (SERoM-8 and 10 respectively) as potential vaccine candidates. SERoM-1 and SERoM-8 were determined to be highly immunogenic by IFN-γ ELISpot assays, with 0.1% of all splenocytes from SERoM-1 vaccinated mice producing IFN-γ when re-stimulated with MmpL1. A combined SERoM-1, −8 and −10 vaccine demonstrated significant protection against M. tuberculosis challenge in a murine model of TB, resulting in approximately 10-fold reduction in bacterial numbers following challenge in both the lungs and spleens compared to adjuvant only vaccinated mice. These protective effects were comparable to that achieved with BCG.