Expert group recommendation on inhaled mucoactive drugs in pediatric respiratory diseases: an Indian perspective.

Background: Currently, there are no guidelines or consensus statements about the usage of inhaled mucoactive drugs in pediatric respiratory disease conditions from an Indian perspective. Objective: To develop a practical consensus document to help pediatricians in clinical decision-making when choosing an appropriate mucoactive drug for the management of specific respiratory disease conditions. Methods: A committee of nine experts with significant experience in pediatric respiratory disease conditions and a microbiological expert constituted the panel. An electronic search of the PubMed/MEDLINE, Cochrane Library, Scopus, and Embase databases was undertaken to identify relevant articles. Various combinations of keywords such as inhaled, nebulized, mucoactive, mucolytic, mucokinetic, expectorants, mucoregulators, mucociliary clearance, respiratory disorders, pediatric, cystic fibrosis (CF), non-CF bronchiectasis, acute wheezing, asthma, primary ciliary dyskinesia (PCD), critically ill, mechanical ventilation, tracheomalacia, tracheobronchomalacia, esophageal atresia (EA), tracheoesophageal fistula (TEF), acute bronchiolitis, sputum induction, guideline, and management were used. Twelve questions were drafted for discussion. A roundtable meeting of experts was conducted to arrive at a consensus. The level of evidence and class of recommendation were weighed and graded. Conclusions: Inhaled mucoactive drugs (hypertonic saline, dry powder mannitol, and dornase alfa) can enhance mucociliary clearance in children with CF. Experts opined that hypertonic saline could be beneficial in non-CF bronchiectasis, acute bronchiolitis, and PCD. The current state of evidence is inadequate to support the use of inhaled mucoactive drugs in asthma, acute wheezing, tracheomalacia, tracheobronchomalacia, and EA with TEF.

Diagnostic Accuracy of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) in Stool Samples in Pediatric Tuberculosis.

OBJECTIVES: To find out the diagnostic accuracy of stool Cartridge-based nucleic acid amplification test (CBNAAT) as an alternate method as compared to CBNAAT in gastric aspirate (GA) samples in pediatric tuberculosis (TB). METHODS: This cross-sectional study was performed at Department of Pediatrics of a tertiary care hospital. Children aged 0-18 y diagnosed as presumptive tuberculosis were consecutively enrolled. Gastric aspirate and corresponding stool sample was subjected to CBNAAT and its performance was compared in both samples using appropriate statistical tests. RESULTS: Total 100 patients were enrolled in the study. Diagnostic accuracy of CBNAAT was 81% and 80% in gastric aspirate and stool sample respectively. On comparing gastric aspirate with corresponding stool sample there was 97% agreement, with Cohen's kappa value of 0.94. There was a statistically significant association observed between gastric aspirate CBNAAT and stool CBNAAT p <0.001 using chi square test. Sensitivity of gastric aspirate CBNAAT and stool CBNAAT was 75% and 73% respectively and specificity was 100% for both the samples compared against Composite Reference Standard (CRS). CONCLUSIONS: The diagnostic accuracy of stool CBNAAT is comparable to GA CBNAAT in children and can be used as a good alternative to gastric aspirate for diagnosis of pulmonary and disseminated tuberculosis in children.

Multi-response and multi-criteria optimization of acid hydrolyzate detoxification of cocoa pod husks: Effect on the content of phenolic compounds and fermentable sugars.

Dilute acid hydrolysis is the most common and effective method for converting lignocellulosic substrates into fermentable sugars. However, this hydrolysis partially degrades the lignin into phenolic compounds (PC), inhibiting the fermentation medium by retaining it in the hydrolyzate. Response surface methodology is a modeling and optimization technique used to examine the effect of multiple factors on a given response. In this study, shows the removal of PC from cocoa pod husks hydrolyzate, while preserving a considerable level of reducing sugar (RS). An Alkalinization from pH 11 with NaOH, then readjustment of pH to 6 with H2SO4 were first carried out, while eliminating 89.39% of PC and 13.41% of sugars. Then, an optimization of the activated carbon detoxification of the hydrolyzate was carried out by considering the contact time factors (X1), carbon to hydrolyzate ratio (X2) and the agitation speed (X3) in a Box-Behnken plan. The optimal conditions were 60 min of contact, a carbon to hydrolyzate ratio of 1.984% (w/v), and a stirring speed of 180 revolutions per minute (rpm). 0.153 mg/mL of PC and 6.585 mg/mL of RS remained in the hydrolyzate, corresponding to 95.18% of PC and 28.88% of RS lost.

Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L-1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0-24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0-24 and slow acetylators had higher isoniazid AUC0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Comparison of Diagnostic Yield of Tuberculosis Loop-Mediated Isothermal Amplification Assay With Cartridge-Based Nucleic Acid Amplification Test, Acid-Fast Bacilli Microscopy, and Mycobacteria Growth Indicator Tube Culture in Children With Pulmonary Tuberculosis.

BACKGROUND: Cartridge-based nucleic acid amplification test (CB-NAAT) has been recommended for diagnosis of tuberculosis (TB) in children, but its wide use is limited by high cost and the need for well-equipped laboratories. This study was conducted in children with pulmonary TB to compare the diagnostic yield of TB-LAMP (loop-mediated isothermal amplification test) with CB-NAAT and other conventional methods. METHODS: Patients ≤ 14 years of age diagnosed with probable pulmonary TB were included in the study. Induced sputum/gastric aspirate was obtained and subjected to acid-fast bacilli (AFB) microscopy, mycobacteria growth indicator tube (MGIT) culture, CB-NAAT, and TB-LAMP. The TB-LAMP assay was performed using 2 different primers, IS6110 and mpb64, for detection of Mycobacterium tuberculosis (MTB). TB-LAMP assays were compared to other assays using appropriate statistical tests. RESULTS: One hundred fourteen subjects were recruited in the study. AFB microscopy, MGIT culture, CB-NAAT, TB-LAMP IS6110, and TB-LAMP mpb64 showed positivity of 32 (28.1%), 59 (51.7%), 66 (57.9%), 75 (65.8%), and 81 (71%), respectively. TB-LAMP IS6110 showed significantly higher MTB detection in comparison to AFB microscopy and MGIT culture (P = .0001 and P = .03, respectively), and showed no significant difference in MTB detection in comparison with CB-NAAT (P = .219). TB-LAMP mpb64 showed significantly higher MTB detection as compared to AFB microscopy, MGIT culture, and CB-NAAT (P = .0001, P = .003, and P = .037, respectively). TB-LAMP mpb64 and IS6110 showed sensitivity of 94.9% (95% confidence interval [CI], 85.9%-98.9%) and 89.8% (95% CI, 79.7%-96.2%), respectively, in reference to MGIT culture. The degree of agreement between TB-LAMP (mpb64 and IS6110) with CB-NAAT showed κ values of 0.718 and 0.834, respectively. CONCLUSIONS: TB-LAMP assay can be a useful alternative test in diagnosis of pulmonary TB in children.

A Comparative Evaluation of Presepsin with Procalcitonin and CRP in Diagnosing Neonatal Sepsis.

The objectives of this study were to study the clinical and biochemical profile of neonates with sepsis and to evaluate the diagnostic role of presepsin and its comparison with C-reactive protein (CRP) and Procalcitonin (PCT). This study was conducted from March 2015 through October 2016 in Neonatal intensive care unit (NICU) at S N Medical College, Agra. Neonates with ≥1 clinical features of sepsis and/or two risk factors were included. A total of 41 cases and 41 controls were taken. Blood sample was taken for all investigations. ROC curve analysis was performed. Out of 41 cases, 19 were blood culture positive, majority were males (68.3%), low birth weight (LBW: 70.7%) and preterms (53.6%). At chosen cut-off values, sensitivity of CRP, PCT and presepsin was 80.5%, 80.5%, 97.6% and specificity was 97.5%, 80.5%, 95.1% respectively. PCT and CRP were comparable as diagnostic markers of neonatal sepsis. Presepsin, in comparison with CRP and PCT has better sensitivity and negative predictive value (NPV).

Pharmacokinetic study of isoniazid and pyrazinamide in children: impact of age and nutritional status.

OBJECTIVES: To evaluate pharmacokinetics of first-line antitubercular drugs, isoniazid (INH) and pyrazinamide (PZA), with revised WHO dosages and to assess its adequacy in relation to age and nutritional status. DESIGN: Observational study. SETTING: This study was conducted at Sarojini Naidu Medical College, Agra, and National Institute for Research in Tuberculosis, Chennai. PATIENTS: 40 subjects diagnosed with tuberculosis were registered in the study and started on daily first-line antitubercular regimen based on the revised WHO guidelines. INTERVENTIONS: Blood samples were collected at 0, 2, 4, 6 and 8 hours from these subjects after 15 days of treatment for drug estimations. MAIN OUTCOME MEASURE: The measurement of drug concentrations (maximum peak concentration (Cmax) and area under the time -concentration curve (AUC0-8 hours)) for INH and PZA. Appropriate statistical methods were used to evaluate the impact of age and nutritional status on pharmacokinetic variables. RESULTS: For INH, the difference in drug exposures in children <3 years (Cmax 3.18 µg/mL and AUC0-8 hours15.76 µg/mL hour) and children >3 years (Cmax3.05 µg/mL and AUC0-8 hours 14.37 µg/mL hour) was not significant (P=0.94, P=0.81, respectively). The drug levels in children with low body mass index (BMI) (Cmax3.08 µg/mL; AUC0-8 hours14.81 µg/mL hour) were also comparable with their normal counterparts (Cmax3.09 µg/mL, P=0.99; AUC0-8 hours 14.69 µg/mL hour, P=0.82). PZA drug exposures obtained in children less than 3 years (Cmax29.22 µg/mL, AUC0-8 hours 155.45 µg/mL hour) were significantly lower compared with drug levels in children above 3 years (Cmax 37.12 µg/mL, P=0.03; AUC 202.63 µg/mL hour, P value=0.01). Children with low BMI had significantly lower drug concentrations (Cmax 31.90 µg/mL, AUC0-8 hours167.64 µg/mL hour) when compared with normal counterparts (Cmax 37.60 µg/mL, P=0.02; AUC0-8 hours 208.77 µg/mL hour, P=0.01). CONCLUSIONS: The revised WHO drug dosages were found to be adequate for INH with respect to age and nutritional status, whereas PZA showed significantly lower drug levels in children <3 years and in malnourished children.

Tuberculosis Burden among Household Pediatric Contacts of Adult Tuberculosis Patients.

OBJECTIVES: To find out the prevalence of latent tuberculosis (TB) infection and TB disease among pediatric household contacts of adult drug resistant (MDR) and drug susceptible (DS) TB patients and to identify the risk factors for occurrence of TB infection in the contacts. METHODS: Pediatric household contacts (less than 15 y age) of adult TB patients (both MDR and DS) were included in the study. They were categorized as latent TB infection (LTBI), TB disease and TB exposed based on the results of tuberculin skin testing (TST), clinical examination and chest X-ray. Various factors (age, gender, socioeconomic status, BCG immunization etc.) were evaluated to assess their association with TB transmission. RESULTS: A total of 271 household contacts were included in the study. Prevalence of LTBI was 20.3% (31% in MDR TB group and 14% in DS TB group); difference was significant (p value = 0.0018). TB disease was seen in 3 subjects in DS group while none in MDR group developed TB disease. Lower socioeconomic status was significantly associated with risk of TB infection in MDR group (p value =0.0027). In DS TB group, male gender, BCG non-immunization was significantly associated with risk of developing TB (p value 0.0068 and 0.0167 respectively). CONCLUSIONS: Prevalence of latent TB infection was found to be high in household pediatric contacts especially in contacts of MDR TB patients. Risk factors identified for occurrence of TB included lower socioeconomic status, BCG non-immunization and male gender. The study focuses on the importance of contact screening and the need for its implementation in TB control programs.

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India.

We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 µg/ml versus 7.3 µg/ml; P = 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0-8]) than those above 12 years of age (17.5 µg/ml · h versus 9.4 µg/ml; P = 0.030). Multiple linear regression analysis showed significant influence of gender on Cmax of ETH and age on Cmax and AUC0-8 of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

PCR targeting IS6110 in diagnosing tuberculosis in children in comparison to MGIT culture.

BACKGROUND: Diagnosis of tuberculosis (TB) in children is difficult in children especially in extrapulmonary tuberculosis (EPTB). This study was conducted to evaluate the use of polymerase chain reaction (PCR) targeting IS6110 in the diagnosis of TB in children with pulmonary TB and EPTB and also to compare its performance with MGIT 960 culture and conventional microscopy. METHODS: A total of 142 cases (50 pulmonary, 92 extrapulmonary) of suspected TB patients <15 years of age were included in the study. The clinical specimens obtained from these cases were subjected to Ziehl-Neelsen staining (ZN), MGIT 960 TB culture and PCR targeting insertion sequence IS6110. Sensitivity and specificity of PCR were calculated in pulmonary and extrapulmonary specimens. The results were compared to MGIT culture. RESULTS: PCR targeting IS6110 sequence had sensitivity of 69.01% in various clinical specimens which was significantly more than MGIT culture showing a sensitivity of 47.41% (p<0.05). Sensitivity of PCR IS6110 in extrapulmonary specimens was 65.21% which was lower than sensitivity in pulmonary specimens (76%) but was not statistically significant (p>0.05). CONCLUSIONS: Diagnostic efficacy of PCR IS6110 in pulmonary and extrapulmonary TB cases was similar. PCR using IS6110 primer had significantly better efficiency than MGIT culture in diagnosing TB in children.

GeneXpert for Diagnosis of Tubercular Meningitis.

Diagnosis of tubercular meningitis (TBM) is difficult in children. The GeneXpert MTB/RIF assay has been recommended by WHO in 2013 to be used in children and in extra pulmonary clinical specimens. The present study was designed to assess the diagnostic utility of GeneXpert in detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF) in TBM cases and to compare the results with liquid culture BACTEC 460. Thirty four subjects <15 y were diagnosed as TBM based on clinical, CSF and imaging details. Sensitivity of GeneXpert in CSF was 38.24 % as compared to Bactec culture which was only 14.71 % (p 0.0279). To conclude, GeneXpert MTB/RIF test is able to rapidly confirm diagnosis of TBM with higher sensitivity as compared to conventional methods and liquid culture.

Fever in Children and Fever of Unknown Origin.

Fever is the most common symptom in children and can be classified as fever with or without focus. Fever without focus can be less than 7 d and is subclassified as fever without localizing signs and fever of unknown origin (FUO). FUO is defined as a temperature greater than 38.3 °C, for more than 3 wk or failure to reach a diagnosis after 1 wk of inpatient investigations. The most common causes of FUO in children are infections, connective tissue disorders and neoplasms. Infectious diseases most commonly implicated in children with FUO are salmonellosis, tuberculosis, malaria and rickettsial diseases. Juvenile rheumatic arthritis is the connective tissue disease frequently associated with FUO. Malignancy is the third largest group responsible for FUO in children. Diagnostic approach of FUO includes detailed history and examination supported with investigations. Age, history of contact, exposure to wild animals and medications should be noted. Examination should include, apart from general appearance, presence of sweating, rashes, tonsillitis, sinusitis and lymph node enlargement. Other signs such as abdominal tenderness and hepatosplenomegly should be looked for. The muscles and bones should be carefully examined for connective tissue disorders. Complete blood count, blood smear examination and level of acute phase reactants should be part of initial investigations. Radiological imaging is useful aid in diagnosing FUO. Trials of antimicrobial agents should not be given as they can obscure the diagnosis of the disease in FUO.

Real time PCR in childhood tuberculosis: a valuable diagnostic tool.

The present study was conducted to detect and quantitate Mycobacterium tuberculosis from various body fluid specimens of cases of tuberculosis by real time PCR technique and compare results with conventional PCR technique and culture. One hundred fifteen children (<18 y) with tuberculosis (diagnosed as per IAP guidelines) and 32 disease matched controls from the Department of Pediatrics, S.N. Medical College, Agra, were included in the study. Different body fluids (CSF, gastric aspirate, pleural fluid, ascitic fluid and lymph node aspirate) were subjected to culture, conventional PCR targeting insertion sequence 1S6110 and Real time PCR targeting 16srRNA of Mycobacterium tuberculosis. Real time PCR showed significantly better results than culture in all body fluids (p < 0.05). It was superior to conventional PCR in CSF (p < 0.05) but showed comparable results in gastric aspirate, pleural fluid, ascitic fluid and lymph node aspirate (p > 0.05). Hence, real time PCR is a promising diagnostic tool for childhood tuberculosis, particularly tubercular meningitis.

Pharmacokinetics of first-line antituberculosis drugs in HIV-infected children with tuberculosis treated with intermittent regimens in India.

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0-8]) of INH (Cmax, 2.5 versus 5.1 µg/ml, respectively [P=0.016]; AUC0-8, 11.1 versus 22.0 µg/ml·h, respectively [P=0.047[) and PZA (Cmax, 34.1 versus 42.3 µg/ml, respectively [P=0.055]; AUC0-8, 177.9 versus 221.7 µg/ml·h, respectively [P=0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 µg/ml, respectively; P=0.002) and PZA (31.9 versus 44.4 µg/ml, respectively; P=0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P=0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.

A toolbox for tuberculosis (TB) diagnosis: an Indian multi-centric study (2006-2008); evaluation of serological assays based on PGL-Tb1 and ESAT-6/CFP10 antigens for TB diagnosis.

BACKGROUND: The aim of this multi-centric prospective study in India was to assess the accuracy of a serological test as an additional tool for diagnosing active tuberculosis (ATB). In particular, an assay based on ELISA using a phenolic glycolipid (PGL-Tb1) or a fusion protein (ESAT-6/CFP10) was compared to the tuberculin skin test (TST) and the microbiological results according to HIV status. METHODS: Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data. RESULTS: Among the 778 ATB patients, 102 were HIV-infected, 316 HIV-uninfected and 360 had an HIV-unknown status. Of the 945 non-ATB subjects, 559 were at low risk (community adults) and 386 at high risk of M. tuberculosis exposure. Among those with ATB, the sensitivity of ELISA-PGL-Tb1 for ATB was higher than that of ELISA-ESAT-6/CFP10, both in HIV-infected (72.3% versus 63.7%, p = 0.29) and HIV-uninfected/HIV-unknown groups (40.5% versus 28.6%; p<0.0001), whereas the specificity was around 91% for both tests. Sensitivity for ATB increased when the results of the two ELISA were combined, reaching 75.5% in the HIV-infected and 50.9% in the group of HIV-uninfected/HIV-unknown ATB, with a significant decrease of the global specificity (83.9%). Analyzing the ELISA results with the microbiological results, we observed that the sensitivity of both serology tests was independent of the ATB patients' smear microscopy (SM) status and grade. Combining the results of SM with both ELISA, the detection of ATB patients significantly increased (p<0.0001), particularly in those with extrapulmonary TB (up to 45.1%) or HIV infection (up to 83.3%). No significant association was observed between TST and serology results. CONCLUSIONS: In this prospective multi-centric study, the combination of two rapid tests, such as SM and serology, might be useful in detecting ATB, especially in HIV-infected patients.

Role of multivitamins, micronutrients and probiotics supplementation in management of HIV infected children.

OBJECTIVES: To assess the immuno-clinical response of micronutrients supplementation in human immunodeficiency virus (HIV) infected children (both on and without antiretroviral therapy) and to assess the role of probiotics in improvement of CD4 counts in HIV infected children not on antiretroviral therapy. METHODS: This was an open labeled randomized control study, conducted in Department of Pediatrics and Antiretrovial Therapy (ART) Center, S.N. Medical College, Agra. One hundred and twenty seven HIV infected children aged ≤ 15 y were included in the study. Enrolled children were randomized to receive micronutrients for 6 mo or probiotics for 3 mo. Children who did not receive supplements served as control. Change in WHO clinical stage, immunological stage, CD4 counts and body mass index (BMI) status were taken at the end of 6 mo. In probiotic group, mean CD4 count were taken as outcome measure. A detailed history, examination and WHO clinical staging were recorded for all the patients. RESULTS: In micronutrient supplemented group (not on ART), significant improvement was seen in WHO clinical staging (p = 0.049) when compared to controls after 6 mo. Probiotic supplemented group showed significant increase in CD4 counts compared to control group (p = 0.0022) in children >5 y. Control group showed significant decline in CD4 count in children ≤5 y (-65.3 cells/mm(3), p=0.005) and in children >5 y (-87.9 cells/mm(3), p=0.05) after 12 wk of supplementation. CONCLUSIONS: Probiotics supplementation has shown significant improvement in CD4 counts. Micronutrients supplementation has shown significant delay in the progression towards advance stage of disease.

A toolbox for tuberculosis (TB) diagnosis: an Indian multicentric study (2006-2008). Evaluation of QuantiFERON-TB gold in tube for TB diagnosis.

BACKGROUND: The aim of this multicentric prospective study in India was to assess the performance of the QuantiFERON TB-Gold in tube (QFT-GIT), Tuberculin Skin Test (TST) and microbiological results as additional tools for diagnosing active tuberculosis (TB) and latent infection (LTBI) according to Human Immunodeficiency Virus (HIV) status. METHODS: Individuals with and without active TB and HIV infection were enrolled between 2006-2008. QFT-GIT and TST results were analyzed per se and in combination with microbiological data. RESULTS: Among the 276 individuals (96 active pulmonary TB and 180 no active TB) tested by QFT-GIT, 18 indeterminate results (6.5%) were found, more significantly numerous in the HIV-infected (15/92; 16.3%) than the HIV-uninfected (3/184; 1.6%)(p<0.0001). QFT-GIT sensitivity for active TB was 82.3% and 92.9% respectively after including or excluding indeterminate results. Clinical sensitivity was significantly lower in the HIV-infected (68.4%) than the HIV-uninfected (91.4%) patients (p = 0.0059). LTBI was detected in 49.3% of subjects without active TB but varied according to TB exposure. When the TST and QFT-GIT were concomitantly performed, the respective sensitivity for active TB diagnosis was 95.0% and 85.0% in the HIV-uninfected (p = 0.60), and 66.7% and 51.5% in the HIV-infected patients (p = 0.32). QFT-GIT and TST respective specificity for active TB in the HIV-uninfected was 25.0% and 57.1% (p = 0.028), and 64.8% and 83.3% in the HIV-infected (p = 0.047). In those with active TB, QFT-GIT results were not associated with microbiological parameters (smear grade, liquid culture status, time-to-positivity of culture) or clinical suspicion of active TB score (provided by the clinicians at enrollment). Combining microbiological tests with both immunological tests significantly increased sensitivity for active TB diagnosis (p = 0.0002), especially in the HIV-infected individuals (p = 0.0016). CONCLUSION: QFT-GIT and TST have similar diagnostic value for active TB diagnosis. In HIV-infected patients, combining microbiological tests with both immunological tests significantly increases the sensitivity for active TB diagnosis.

A toolbox for tuberculosis diagnosis: an Indian multicentric study (2006-2008): microbiological results.

BACKGROUND: The aim of this multicentric prospective study in India was to assess the value of several microbiological tools that contribute to the diagnosis of tuberculosis (TB) according to HIV status. METHODS: Standard microbiological tools on individual specimens were analyzed. RESULTS: Among the 807 patients with active TB, 131 were HIV-infected, 316 HIV-uninfected and 360 had HIV-unknown status. Among the 980 non-active TB subjects, 559 were at low risk and 421 were at high risk of M. tuberculosis (Mtb) exposure. Sensitivity of smear microscopy (SM) was significantly lower in HIV-infected (42.2%) than HIV-uninfected (75.9%) (p = 0.0001) and HIV-unknown pulmonary TB patients (61.4%) (p = 0.004). Specificity was 94.5% in non-TB patients and 100% in health care workers (HCW) and healthy family contacts. Automated liquid culture has significantly higher diagnostic performances than solid culture, measured by sensitivity (74.7% vs. 55.9%) (p = 0.0001) and shorter median time to detection (TTD) (12.0 vs. 34.0 days) (p = 0.0001). Specificity was 100% in HCW and cured-TB patients, but was lower in non-TB patients (89%) due to isolation of Mycobacteria other than tuberculosis (MOTT). TTD by both methods was related to AFB score. Contamination rate was low (1.4%). AccuProbe hybridization technique detected Mtb in almost all culture-positive specimens, but MOTT were found in 4.7% with a significantly higher frequency in HIV-infected (15%) than HIV-uninfected TB patients (0.5%) (p = 0.0007). Pre-test classification significantly increased the diagnostic value of all microbiological tests in pulmonary TB patients (p<0.0001) but to a lesser degree in extrapulmonary TB patients. CONCLUSIONS: Conventional microbiological tools led to results similar to those already described in India special features for HIV-infected TB patients included lower detection by SM and culture. New microbiological assays, such as the automated liquid culture system, showed increased accuracy and speed of detection.