Intensive Phase Of Therapy Research Articles

A Review on Pediatric Adverse Effects of First Line Anti-Tubercular Drugs

Tuberculosis is a potentially serious communicable disease caused by mycobacterium tuberculosis. That mainly affects lungs. Tricky mitigation and diagnosis cause the childhood tuberculosis a growing burden for society. Directly Observed Treatment Short course (DOTS) strategy is one of the largest public health programmes found to be beneficial against tuberculosis. Anti-tubercular treatment shows greater level of efficacy high degree of toxicity; however combination treatment, especially during the intensive phase of therapy may produce severe adverse events. First line therapy of Tuberculosis leads to serious adverse effects. Serious adverse effects are less in children receiving drug therapy. Major adverse event associated with anti TB drugs is hepatotoxicity. Keywords: Tuberculosis, DOTS, isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin

TUBERCULOUS ARTHRITIS OF THE ANKLE MIMICKING SYNOVITIS IN CHILD - A CASE REPORT

Background: Extrapulmonary Tuberculosis is approximately 10% of all tuberculosis (TB) cases, and the musculoskeletal system’s involvement was only 2-4. The incidence of ankle TB was found to be less than 2% of all musculoskeletal TB. The rare occurrence, uncommon site, non-specific symptoms, lack of awareness frequently causes diagnosis difficulties.Case Report: A 2,5-year-old child came to the hospital with the main complaints of swelling and pain on the left ankle since one year ago. She was diagnosed with the ankle’s synovitis from the previous hospital and was given analgesics and a warm compress on the left ankle. However, the swelling of her left ankle increased during the last seven months, causing limitation of the left ankle movement, then she was admitted to the hospital for further examination. Radiologic examination revealed peripheral osseous erosions, reduced bone mineral content, and soft tissue swelling. A Mantoux test was positive with 15 mm induration and 25 mm erythema. Anti-tuberculous drugs (ATD) therapy was given with isoniazid 50 mg, rifampicin 75 mg, pyrazinamide 150 mg, and ethambutol 230 mg for two months, as an intensive phase therapy following rifampicin 75 mg and isoniazid 50 mg for ten months.Conclusion: Tuberculous arthritis of the ankle poses a diagnostic-difficulties, it should be considered especially in the endemic area. It is often misdiagnosed with other musculoskeletal conditions, which can delay the initiation of appropriate treatment. TB must be confirmed by histological pathology. A combination of ATD and surgery can lead to clinical improvement.

Pharmacokinetics, SAfety/tolerability, and EFficacy of high-dose RIFampicin in tuberculosis-HIV co-infected patients on efavirenz- or dolutegravir-based antiretroviral therapy: study protocol for an open-label, phase II clinical trial (SAEFRIF)

BackgroundTuberculosis (TB) is a significant public health problem that causes substantial morbidity and mortality. Current first-line anti-TB chemotherapy, although very effective, has limitations including long-treatment duration with a possibility of non-adherence, drug interactions, and toxicities. Dose escalation of rifampicin, an important drug within the regimen, has been proposed as a potential route to higher treatment efficacy with shorter duration and some studies have suggested that dose escalation is safe; however, these have almost entirely been conducted among human immunodeficiency (HIV)-negative TB patients. TB-HIV co-infected patients on antiretroviral therapy (ART) are at increased risk of drug-drug interactions and drug-related toxicities. This study aims to determine the safety of higher doses of rifampicin and its effect on the pharmacokinetics of efavirenz (EFV) and dolutegravir (DTG) in TB-HIV co-infected patients.MethodsThis study is a randomized, open-label, phase IIb clinical trial among TB-HIV infected adult outpatients attending an HIV clinic in Kampala, Uganda. Patients newly diagnosed with TB will be randomized to either standard-dose or high-dose rifampicin (35 mg/kg) alongside standard TB treatment. ART-naïve patients will be randomly assigned to first-line ART regimens (DTG or EFV). Those who are already on ART (DTG or EFV) at enrollment will be continued on the same ART regimen but with dose adjustment of DTG to twice daily dosing. Participants will be followed every 2 weeks with assessment for toxicities at each visit and measurement of drug concentrations at week 6. At the end of intensive-phase therapy (8 weeks), all participants will be initiated on continuation-phase treatment using standard-dose rifampicin and isoniazid.DiscussionThis study should avail us with evidence about the effect of higher doses of rifampicin on the pharmacokinetics of EFV and DTG among TB-HIV co-infected patients. The trial should also help us to understand safety concerns of high-dose rifampicin among this vulnerable cohort.Trial registrationClinicalTrials.gov, ID: NCT03982277. Registered retrospectively on 11 June 2019.

Antituberculosis Drug-induced Hepatotoxicity in Pediatric Tuberculosis

Background : Hepatotoxicity is the most serious side effect caused by using oral antituberculosis (OAT) drugs. This study was performed to determine the characteristics of patients who had antituberculosis drug-induced hepatotoxicity (ADIH) among pediatric inpatient with pulmonary tuberculosis. Methods : This was a cross-sectional study with a total sampling of medical records taken from January–December 2012, including pediatric pulmonary tuberculosis inpatients aged <14 years old at the Department of Child Health of Dr. Hasan Sadikin General Hospital Bandung. The inclusion criteria were children with pulmonary tuberculosis who received OAT drugs. Patients with liver disease were excluded. Data on alanine and aspartate aminotransferase were collected and an increased level of serum aminotransferase was designated as hepatotoxicity. Results : In total, 86 medical records were obtained of whom 24 had ADIH, predominantly occurred in girls (71%), aged 5–9 years old (42%) and in the intensive phase of therapy (58%). Elevated serum alanine aminotransferase (58%), aspartate aminotransferasen (92%), and bilirubin (0.8%) were found. Malnutrition (46%) was common. The difference indeviation of liver function was statistically significant (p<000) between subjects with and without ADIH. Conclusions : Hepatotoxicity is most prominent in patients with malnutrition, girls aged 5–9 years old and in the intensive phase of therapy. Children with malnutrition during antituberculosis therapy are suggested to have a periodic liver function test monitoring to prevent the development of ADIH.

Inequity in catastrophic costs among tuberculosis-affected households in China

BackgroundThere are limited nationally representative studies globally in the post-2015 END tuberculosis (TB) era regarding wealth related inequity in the distribution of catastrophic costs due to TB care. Under the Chinese national tuberculosis programme setting, we aimed to assess extent of equity in distribution of total TB care costs (pre-treatment, treatment and overall) and costs as a proportion of annual household income (AHI), and describe and compare equity in distribution of catastrophic costs (pre-treatment, treatment and overall) across population sub-groups.MethodsAnalytical cross-sectional study using data from national TB patient cost survey carried out in 22 counties from six provinces in China in 2017. Drug-susceptible pulmonary TB registered under programme, who had received at least 2 weeks of intensive phase therapy were included. Equity was depicted using concentration curves and concentration indices were compared using dominance test.ResultsOf 1147 patients, the median cost of pre-treatment, treatment and overall care, were USD 283.5, USD 413.1 and USD 965.5, respectively. Richer quintiles incurred significantly higher pre-treatment and treatment costs compared to poorer quintiles. The distribution of costs as a proportion of AHI and catastrophic costs were significantly pro-poor overall as well as during pre-treatment and treatment phase. All the concentration curves for catastrophic costs (due to pre-treatment, treatment and overall care) stratified by region (east, middle and west), area of residence (urban, rural) and type of insurance (new rural co-operative medical system [NCMS], non-NCMS) also exhibited a pro-poor pattern with statistically significant (P < 0.01) concentration indices. The pro-poor distribution of the catastrophic costs due to TB treatment was significantly more inequitable among rural, compared to urban patients, and NCMS compared to non-NCMS beneficiaries.ConclusionsThere is inequity in the distribution of catastrophic costs due to TB care. Universal health coverage, social protection strategies complemented by quality TB care is vital to reduce inequitable distribution of catastrophic costs due to TB care in China.

Centre-based Evaluation of Some Biochemical Effects of the Initial Phase of Anti-tuberculosis Therapy in Bayelsa State

Aim of the Study: This study aimed at evaluating the adverse drug effects on some biochemical parameters of anti-tuberculosis drugs among patients with primary tuberculosis infection.&#x0D; Study Design: Non-probability (purposive) sampling technique was employed in this study. &#x0D; Place and Duration of Study: This study was carried out at the Chest Clinic unit of the Tuberculosis and Leprosy referral Hospital, Yenagoa, Bayelsa State, Nigeria. This study was conducted from July, 2017 to April, 2018.&#x0D; Methodology: Tuberculosis patients were selected using standard methods for clinical diagnosis and confirmed by laboratory analysis for Mycobacterium tuberculosis using acid fast bacilli as preliminary and Gene-Xpert® as confirmatory test. A total of 44 tuberculosis patients met the study inclusion and exclusion criteria and completed the study at the Tuberculosis and Leprosy Referral Hospital Yenegoa, Bayelsa State. Eligible patients were administered with appropriate daily dose of (rifampicin-150 mg, isoniazid-75 mg, pyrazinamide-400mg and ethambutol-275 mg) single drug combination for two months based on bodyweight. Blood was collected and evaluated for liver enzymes, Alkaline phosphatase (ALP), Alanine transaminase (ALT), Aspartate aminotransferase (AST); Total proteins, Bilirubin and Cholesterol at baseline, week 4 and week 8. Data were descriptively analyzed using statistical package for social sciences (SPSS 21).&#x0D; Results: Treatment in the intensive therapy phase resulted in significant increase of alanine aminotransferase and alkaline phosphatase levels (P=0.5). There was also significant decrease in total cholesterol and albumin (P=0.5). There were no significant changes in aspartate aminotransferase, total protein and total bilirubin.&#x0D; Conclusion: The study results showed changes in some biochemical parameters but were not severe enough to warrant discontinuation of therapy.

Nutritional status of pulmonary tuberculosis patients: A hospital-based cross-sectional study

Introduction: Undernutrition among tuberculosis (TB) patients is associated with adverse treatment outcomes and increases risk of mortality. The nutritional status of pulmonary TB patients attending Outpatient Department of Combined Hospital, Thakurganj, Lucknow, Uttar Pradesh, India. Material and Methods: Two hundred recently diagnosed patients and those who were on intensive phase therapy were selected prospectively. A structured questionnaire was used to collect sociodemographic, lifestyle, health, and dietary information of the selected TB patients. Clinical information was collected from medical records. Nutritional status was measured as body mass index (BMI) (weight and height) using standard techniques. Results: Nutritional status measured as BMI was categorized as underweight ( 18.5) was the primary outcome of the study. Ninety-eight (49%) TB patients were very severely undernourished (BMI Conclusion: This study has demonstrated high proportion of severe undernutrition among pulmonary TB patients. There is an urgent need for the provision of proper nutrition management and counseling of TB hospitals at the hospitals as per the national nutrition guidelines for TB patients.

Antituberculosis Drug-induced Liver Injury in Children: Incidence and Risk Factors During the Two-month Intensive Phase of Therapy.

As one of the most frequent and serious adverse reactions during tuberculosis (TB) treatment, antituberculosis drug-induced liver injury (ATLI) in children has been studied insufficiently compared with adults. We aimed to determine the incidence and risk factors of ATLI in children during the first 2 months of TB therapy. A total of 41 children with TB and treated with first-line anti-TB drugs were prospectively followed-up for the development of ATLI. Liver function tests were performed at baseline and after 2 weeks of therapy. Subsequent tests were conducted at 4, 6 and 8 weeks if the initial 2-week measurement was abnormal or if symptoms of hepatotoxicity were reported. ATLI was detected in 11 (27%) patients within 14 to 42 days from the start of therapy, with most of them (54%) occurred after 2 weeks. TB treatment was stopped immediately in 6 of 11 patients who developed ATLI, and no recurrent hepatotoxicity after drug reintroductions in these patients. Univariate analysis showed that ATLI was significantly associated with TB meningitis (P < 0.01), hypoalbuminemia (P < 0.05) and hepatotoxic comedications (P < 0.01). Age, sex, nutritional status, HIV status and baseline liver function abnormalities were not associated with ATLI. Multivariate analysis identified hypoalbuminemia and hepatotoxic comedications (both P < 0.1) tend to be independently associated with ATLI. Children with hypoalbuminemia and use of hepatotoxic comedications are suggested to be monitored closely for the development of ATLI.

Effects of Probiotics and Vitamin B Supplementation on IFN-γ and IL-12 Levels During Intensive Phase Treatment of Tuberculosis

Tuberculosis is an acute infectious disease that primarily affects the lungs. Probiotics supplementation can increase the number and activity of NK cell in peripheral blood by modulation of IL-12, thus increasing IFN-γ production by Th1 response. Vitamin B 1 acts on macrophages and affects neutrophil motility. Vitamin B 6 is associated with the release of cytokines and the responsiveness of NK cells, while vitamin B 12 affects to lymphocytes, Tcell proliferation, CD4 + ratios, and NK cell activity. To analyze the effects of probiotics and vitamin B 1 , B 6 , B 12 supplementation on IFN-γ and IL-12 levels during intensive phase of antituberculosis treatment. The study was pre-post test randomised control by time series. The control group was TB patients with standard therapy of antituberculosis and vitamin B6, while the intervention group was TB patients receiving therapy plus once daily probiotics and vitamin B 1 , B 6 , B 12 supplementation during the intensive phase. Blood samples were withdrawn at baseline, one month, and two months after therapy to measure plasma IFN-γ and IL-12 levels using the ELISA method. Twenty two patients were divided equally into two groups. There was a tendency to greater increase of IFN-γ in the first month of the intervention group, followed by a significant decline after two-month therapy ( p 0.05). However, the percentage was higher in the supplementation group. Adding probiotics and vitamins B 1 , B 6 , B 12 could improve immune response through IL-12 and IFN-γ modulation during intensive phase therapy.

In-Vitro Activity of Doxycycline and β-Lactam Combinations Against Different Strains of Burkholderia pseudomallei.

Although doxycycline is active against Burkholderia pseudomallei and has been used in the eradication stage of melioidosis therapy, it is not regularly used during the initial intensive phase. In order to assess its potential use in intensive phase therapy, we investigated in vitro pharmacodynamic activity of doxycycline and β-lactams alone and in combination against four Malaysian strains of B. pseudomallei. Using a checkerboard assay, the combinations of doxycycline and imipenem, doxycycline and ceftazidime, and doxycycline and amoxicillin-clavulanate tested against four strains showed indifferent effects with summation fractional inhibitory concentration values ranging from 0.62 to 2.12. Time-kill experiments also indicated that the combinations of doxycycline/β-lactam antibiotics against four tested strains did not fulfil synergy criteria, in which all combinations showed indifferent effects with -1.36 to 1.26-log CFU/mL compared to the most active monotherapy regimen in each combination. No re-growth of bacteria was detected after the early killing in doxycycline/β-lactam combination regimens compared to β-lactam monotherapy regimens, in which 9 out of 10 were associated with re-growth of bacteria. As no synergistic activity was observed, this in vitro study showed that doxycycline offers no additional benefit to be used in combination with β-lactams in the intensive phase of therapy.

The influence of acetylation status of tuberculosis patients on the isoniazid serum concentrations and sputum conversion after intensive phase therapy

Isoniazid (INH), one of the major antituberculosis drugs, is metabolized by acetylation. Previously study proved the significant differences of serum INH concentration between subject with fast and slow acetylation status. However, the correlation of acetylation status with treatment outcome after fixed-dose combination antituberculosis therapy (FDC-ATT) was not explained. The aim of this study was to evaluate the influence of acetylation status on the treatment outcome and the serum INH concentrations in the adult tuberculosis patients underwent FDC-ATT. A cross sectional study was carried out on 31 tuberculosis patients. Acetylation status was measured by spectrophotometer and serum INH concentration was measured by high performance liquid chromatography (HPLC). Sputum conversion assay was conducted by Ziehl Nelsen method. t-Test, chi square, Mann-Whitney, and Fisherman were used to analyze the data. The proportion of the fast acetylator was 61.3%, whereas the slow acetylator was 38.7%. The proportion of success and failure sputum conversion were 83.9% and 16.1%, respectively. The mean serum INH concentration in the fast acetylator groups (1.52 ± 0.15 μg/mL) was significantly lower than that in the slow acetylator groups (3.84 ± 0.35 μg/mL). The failure conversion risk of the fast acetylator group was about two folds higher than the slow acetylator group, although it was not significantly different (RR=2.53; 95% CI=0.32-20.00; p>0.05). Moreover, the mean serum INH concentration in success (2.46 ± 0.31 μg/mL) and failure (1.89 ± 0.20 μg/mL) sputum conversion was not significantly different (p>0.05). In conclusion, the acetylation status does not influence the sputum conversion in adult tuberculosis patients after FDC-ATT although the serum INH concentration on slow acetylation status is higher than that fast acetylation status.

Trends in Treatment Success Rate and Associated Factors among Tuberculosis Patients in Ethiopia: A Retrospective Cohort Study

Background: Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis. TB remains a major global health problem and cause of illness in millions of people each year. This study aimed to reveal trends in treatment success and independent predictors of TB in public health facilities in Sodo Town, Ethiopia. Methods: This was a facility-based retrospective study at public health facilities in Sodo Town, Ethiopia. 725 patients over a three-year period were analyzed by logistic regression. Data were entered in to Epi Info v3.5.4, thoroughly cleaned and analyzed in SPSS v20. Results: Of 725 TB patients, 591 (81.5%) were successfully treated, 41 (5.7%) died, 43 (5.9%) defaulted, 6 (0.8%) failed treatment, and 44 (6.1%) were transferred out. The odds of treatment success was 4.43-times greater for patients treated in 2012 compared to those treated in 2015 (aOR 4.43, 95% CI 1.11-16.33), while patients treated in 2014 had a 4.11-times greater probability of succeeding treatment than those treated in 2015 (aOR 4.11, 95% CI 1.20-14.12). Pulmonary-negative TB patients had a 4.72-times greater odds of succeeding treatment than extra-pulmonary TB patients (aOR 4.72, 95% CI 1.03-21.67). Likewise, HIV-positive TB patients who started co-trimoxazole preventive therapy (CPT) were 4.8- times more likely to succeed treatment than their untreated counterparts (aOR 4.80, 95% CI 1.01-22.78). Pulmonary-positive TB patients at directly-observed treatment, short-course (DOTS) initiation with negative sputum smear results at the end of the 2nd month had 31.73-times greater chance of succeeding treatment than those who were smear positive after two months of intensive-phase therapy (aOR 31.73, 95% CI 5.9-58.63). Conclusion: The overall treatment success rate was low.

Immunodeficiency and Intermittent Dosing Promote Acquired Rifamycin Monoresistance in Murine Tuberculosis.

More-permissive preclinical models may be useful in evaluating antituberculosis regimens for their propensity to select drug-resistant mutants. To evaluate whether acquired rifamycin monoresistance could be recapitulated in mice and, if so, to evaluate the effects of immunodeficiency, intermittent dosing, and drug exposures, athymic nude and BALB/c mice were infected. Controls received daily rifapentine alone or 2 months of rifampin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampin/isoniazid, either daily or twice weekly with one of two isoniazid doses. Test groups received the same intensive regimen followed by once-weekly rifapentine or isoniazid/rifapentine with rifapentine doses of 10, 15, or 20 mg/kg of body weight plus one of two isoniazid doses. All combination regimens rendered BALB/c mouse cultures negative but selected mutants resistant to isoniazid (8.5%, 12/140) or rifampin (3.5%, 5/140) in nude mice (P < 0.001). Intermittently dosed intensive-phase therapy selected isoniazid and rifampin resistance in 10% (8/80, P < 0.001) and 20% (16/80, P = 0.009) of nude mice, respectively, compared to 0% treated with a daily regimen. Once-weekly rifapentine-containing continuation-phase regimens selected rifampin-resistant mutants at a rate of 18.0% (18/100, P = 0.035 compared to rifampin/isoniazid regimens). Higher isoniazid doses in the intermittent-treatment control regimen and higher rifapentine doses in once-weekly regimens were associated with less selection of isoniazid resistance. Acquired resistance, including rifamycin monoresistance, was more likely to occur in nude mice despite administration of combination therapy. These results recapitulate clinical outcomes and indicate that nude mice may be useful for evaluating the ability of novel regimens to prevent the selection of resistance.

Pharmacovigilance of first line anti-tubercular therapy in category I patients of pulmonary tuberculosis

Background: Study was done to determine incidence of ADR’s in sputum positive, pulmonary TB patients, on DOTS category I and to determine the effect of ADR’s on sputum conversion.Methods: Open, prospective, observational, non-comparative study conducted in the Department of Pharmacology in collaboration with Department of Tuberculosis and Chest Diseases, Government Medical College, Amritsar for the duration of 18 months (March 2015 to September 2016). One hundred sputum positive patients of pulmonary tuberculosis on DOTS category I, of either sex, in age group of 14 years to 65 years, were recruited and followed up during intensive phase of therapy at end of 1st and 2nd month. Causality and Severity assessment were done by using WHO-UMC causality scale and Hartwig’s severity scale respectively.Results: Out of 100 patients 84 (84%) developed one or more ADR’s and a total of 118 ADR’s occurred in our study. The most common ADR was GI upset 45(38.13%), followed by hepatitis 42 (35.59%), rash 12 (10.16%), CNS 8 (6.77%), arthritic symptoms 5 (4.23%), visual disturbance 2 (1.69%), bleeding problems 2 (1.69%), hyperuricemia 1 (0.84%) and peripheral neuropathy 1 (0.84%). Causality assessment revealed that most of ADR’s(60) were in probable category and severity assessment revealed that most of ADR’s(55) belonged to level 4 (Moderate severity). Most of the ADR’s occurred within 30 days of the start of treatment (84.74%).Conclusions: With such a high incidence of ADR’s there is a need of incorporating pharmacovigilance programme into this vital health programme for more comprehensive monitoring of tuberculosis patients on DOTS for timely prevention, detection, and management of ADR’s. This will decrease non-adherence and dropouts, and thus result in better treatment outcomes.

Clinical predictors of aminoglycoside-induced ototoxicity in drug-resistant Tuberculosis patients on intensive therapy

ObjectiveThe study objectives were to determine the incidence of aminoglycoside-induced ototoxicity in institutionalized patients on intensive phase of therapy for drug-resistant Tuberculosis (DR Tb) and also to assess clinical factors which could predict the ototoxicity. MethodsThe study was a prospective analytical study among consecutive DR Tb patients who were admitted for intensive phase of therapy (of 4 months) at the DR-Tb center over a 12-month period. Patients were diagnosed as DR Tb using the Gene Xpert machine to confirm Rifampicin resistance. All eligible 70 out of 87 consenting patients were consecutively recruited into the study. Patients had baseline (admission) and serial pure tone audiometries (PTAs) performed at 4 weekly intervals until discharge after 4 months of admission. Audiometric confirmation of aminoglycoside-induced ototoxicity was done by comparing serial with baseline PTA. ResultsAmong the 70 patients the male:female ratio was 1.7:1. Nine patients (12.9%) were retroviral-positive, and 16 patients (22.9%) were confirmed to have ototoxicity by audiometric criteria. The duration of treatment when ototoxicity was detected in the patients ranged 4–17 (Mean±SD; 9.4±3.4) weeks. Ototoxicity was detected in the audiometric low frequency ranges in 7 (43.8%) and at the high frequencies in 4 (25.0%) of the patients. Univariate analyses of clinical parameters found that age, underlying diabetes mellitus, deranged baseline PTAv >25dB HL, BMI on admission and retroviral status were significantly associated, while sex and previous drug regimen failure were not associated with ototoxicity. Multivariate adjusted logistic regression analyses, controlling for sex, revealed age (OR=1.068, p=0.018), BMI on admission (OR=0.673, p=0.012) and retroviral positivity (OR=8.822, p=0.014) of patients could significantly predict aminoglycoside-induced ototoxicity. ConclusionIncidence of aminoglycoside-induced ototoxicity in DR Tb patients was 22.9%. The clinical predictors for ototoxicity were age, BMI on admission, and co-existing retroviral infection in the patients. Clinicians should consider these factors in making choices of aminoglycosides to be used during intensive phase of treatment with second line anti-Tuberculous therapy.

High Sensitivity C-Reactive Protein (hsCRP) as a Biomarker of Treatment Response After the Intensive Phase Among Pediatric Patients With TB

SESSION TITLE: Pediatrics SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Childhood tuberculosis has an increasing incidence worldwide. Its occurrence represents an important event indicating a recent transmission usually from an infectious adult. The identification of a surrogate biomarker for treatment response and risk for poor outcome in tuberculosis will be a beneficial tool in the patient’s management. Thus, a biomarker like high sensitivity C-reactive protein (hsCRP) was proposed to be a prognostic marker in this study. METHODS: Children diagnosed with tuberculosis based on the Philippine Pediatric Society and National Tuberculosis Program guidelines were included in the study. Clinical data were reviewed and recorded, and blood samples were collected for serum hsCRP determination at 2 point of time (before treatment, and after the intensive phase). Data analysis was done using Stata SE version 12. Mean, standard deviation, frequency, percent distribution, paired T test and scatter plot were used. The level of significance is set at 0.05. RESULTS: There were 40 subjects diagnosed with pulmonary tuberculosis who participated the study. Twenty-three were male (57.5%) and 17 were female (42.5%). The age ranges from 1 to 18 years with a mean age of 8.6 + 5.5. Out of the 40 participants, 32 had completed the study. In this study, the analysis of data showed that the level of serum hsCRP after the intensive phase of treatment is significantly lower compared to the level before treatment (p value of 0.0002). On the other hand, body mass index (BMI), which is being used as one of the objective parameters of treatment response in children, demonstrated a statistically significant difference before and after the intensive phase at a p value of 0.0007. High sensitivity C-reactive protein and BMI were indirectly correlated, however, it was statistically insignificant before and after 2 months of treatment at p value of 0.26 and 0.35, respectively. CONCLUSIONS: This study has shown that there is a statistically significant lower serum hsCRP level and statistically significant improvement in BMI after the intensive phase of treatment among pediatric patients with tuberculosis, however, there is a weak indirect correlation between the 2 parameters. It is the therefore concluded that hsCRP can only be an additional tool to evaluate treatment response after the intensive phase of therapy. CLINICAL IMPLICATIONS: It is important for the clinicians to have good monitoring parameters on treatment efficacy in patients with tuberculosis. The inability to do so will contribute to the poor outcome and continued disease transmission. DISCLOSURE: The following authors have nothing to disclose: Annalee de Leon-Manalo, Ma. Dulce Requiron-Sy, Maria Encarnita Limpin No Product/Research Disclosure Information

Genotype-independent association between profound vitamin D deficiency and delayed sputum smear conversion in pulmonary tuberculosis.

BackgroundBoth vitamin D deficiency and genetic variants in the vitamin D receptor (VDR) have been reported to associate with delayed response to intensive-phase therapy for pulmonary tuberculosis. Studies investigating the influence of genetic variants in vitamin D binding protein (DBP) and vitamin D 25-hydroxylase (CYP2R1) on vitamin D status and response to antituberculous therapy are lacking.MethodsWe conducted a longitudinal study in 260 patients initiating treatment for smear-positive pulmonary tuberculosis in Lahore, Pakistan. Vitamin D status and genotypes for polymorphisms in VDR (rs2228570, rs731236, rs1544410), DBP (rs7041, rs4588) and CYP2R1 (rs2060793, rs10500804, rs10766197) were determined at baseline. Sputum smear microscopy was performed at 2, 4, 6 and 8 weeks, and time to sputum smear conversion was estimated for each participant. Analyses were conducted to determine demographic, clinical and genetic determinants of baseline vitamin D status and time to sputum smear conversion.ResultsProfound vitamin D deficiency (serum 25[OH]D < 25 nmol/L) was highly prevalent at TB diagnosis (present in 54 % of patients), and was independently associated with female vs. male sex (adjusted OR 2.60, 95 % CI 1.50 to 4.52, P = 0.001), recruitment in October to March inclusive (adjusted OR 1.75, 95 % CI 1.00 to 3.04, P = 0.047) and bilateral vs. unilateral disease (adjusted OR 1.89, 95 % CI 1.49 to 4.52 P = 0.025). Profound vitamin D deficiency was also independently associated with impaired response to antituberculous therapy (median time to sputum smear conversion 22.5 vs. 7.5 days for patients with serum 25[OH]D <25 nmol/L vs. ≥ 25 nmol/L, respectively; aHR 4.36, 95 % CI 3.25 to 6.65, P < 0.001). No polymorphisms in VDR, CYP2R1 and DBP studied associated with either baseline vitamin D status or time to sputum smear conversion.ConclusionsProfound vitamin D deficiency is very common among TB patients in Lahore, Pakistan, and is independently associated with significantly delayed sputum smear conversion. Polymorphisms in VDR, CYP2R1 and DBP did not associate with baseline vitamin D status or response to intensive-phase treatment in this patient group.

Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis

Biomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda. We consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age. All but one analyte decreased from baseline to week 8 (all p<0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer-Lemeshow P>0.2). Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.

Growth in Children Treated for Acute Lymphoblastic Leukemia: Single Institution Report from North India.

Survivors of childhood leukemia are at risk of impaired growth and short stature as adults due to intensive combination chemotherapy and radiation injury. This study was undertaken to evaluate anthropometry in children treated for acute lymphoblastic leukemia (ALL). Children treated for ALL and off treatment for a minimum period of 2years were evaluated for height, weight and BMI. Z scores were calculated for height, weight and BMI: at induction, 6months after starting treatment, at end of treatment and at 2years after completion of therapy. Change in z scores were calculated and compared with CDC criteria and Agarwal standards for Indian children. Fifty two boys and 21 girls were analyzed. Height and weight z scores were seen to show a steep decrease during the initial intensive phase of therapy. The gain in height and weight continued to be slow during therapy and catch up occurred after cessation of therapy. On completion of therapy, patients were shorter, but not significantly so. Girls <9years were significantly shorter. Weight remained on the lower side of normal. Change of z scores was statistically significant for weight at end of treatment (p=0.032) and 2years after completion of treatment (p=0.00). BMI z score increased throughout the study period. Peak growth velocities were also late in the study subjects Anthropometric variables of height, weight and BMI are affected by ALL during therapy. Growth deceleration is maximum during the intensive phase of therapy. Catch up growth occurs but children remain smaller than their peers.

Intensive Phase of Therapy of Tuberculosis and HIV Co-infection: CD4, CD8, and Certain Hematological Finding Amongst Patients in Yaounde Cameroon

Tuberculosis (TB) is an infectious disease which could cause depressive phenomena like those observed in Human Immunodeficiency Virus (HIV). Our study aimed at evaluating the changes of T-cells and certain blood parameters during intensive phase of TB treatment. In this prospective cohort, 140 consenting tuberculosis patients were enrolled. 5ml of blood was collected at baseline (M0), after one month (M1) and after two months (M2). Enumeration of CD4 cells, CD8 cells, and hematological parameters were done following standard protocols.The 118 participants comprised 63 (53.4%) TB/HIV negative patients (group 1) and 55 (46.6%) TB/HIV positive patients (group 2). At M0, blood levels of CD4, hemoglobin, total lymphocytes and platelets in group 2 were significantly lower than those of group 1 with p values of 0.001, 0.002, 0.018 and 0.032 respectively. CD8 level was significantly low in group 1 as compared to group 2 (p value: 0.38). Monocytes were low in both groups with no significant difference (p value: 0.097). At M2, there was a significant increase in the levels of CD4, CD8, monocytes, and hemoglobin as compared to M0. There was no significant change on level of total lymphocytes and platelets. In group 2: At M2, there was a significant increase in the levels of CD4, monocytes, hemoglobin, and platelets, and no statistically significant change on levels of CD8 cells and total lymphocytes. TB infection may result in lymphopenia, monopenia, and anemia, while co-infection with HIV may add thrombopenia to the mentioned disorders.