Tuberculous dactylitis—an easily missed diagnosis

The prevalence of tuberculosis (TB) continues to rise worldwide. Current migration patterns and increased travel to high-prevalence TB countries will result in more frequent presentations of less common forms of TB. Tuberculous dactylitis, a form of tuberculous osteomyelitis, is well recognised in countries with a high prevalence of TB. We provide a systematic review of all published cases of tuberculous dactylitis in children and adolescents and describe a case to illustrate the typical features of the disease. Our review revealed 37 cases of tuberculous dactylitis in children and adolescents, all reported in the last 17years. Children less than 10 years of age are most frequently affected and the hand is the most commonly affected site. Concurrent pulmonary TB is present in a fifth of cases and systemic symptoms are usually absent. Positive TST and IGRA support the presumptive diagnosis, but cannot be used as rule-out tests. The definitive diagnosis relies on the detection M. tuberculosis by PCR or culture. Treatment should comprise of a standard three to four drug anti-tuberculous regimen. The optimal treatment duration remains unknown. Surgery has a limited role in the treatment in general but may play a supportive role, and curettage of the cavity has been recommended for avascular lesion

Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis

Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance.The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients. Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study.Meta-regression was used to further explore the influence of study level variables on heterogeneity. Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02-0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04-0.06) showed similar proportions of indeterminate results; pooled risk difference was – 0.01 (95% CI 0.03-0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients (p < 0.001). Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results

Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance. The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients.Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study. Meta-regression was used to further explore the influence of study level variables on heterogeneity.Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02–0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04–0.06) showed similar proportions of indeterminate results; pooled risk difference was−0.01 (95% CI −0.03 to 0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients (p &lt; 0.001).Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results

Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

OBJECTIVE Racecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea, without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on Racecadotril for the treatment of acute diarrhoea in children. DESIGN A Cochrane format systematic review of Randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool. PATIENTS Children with acute diarrhoea, as defined by the primary studies. INTERVENTIONS RCTs comparing racecadotril to placebo or other interventions. MAIN OUTCOME MEASURS Duration of illness, stool output/volume and adverse events. RESULTS Seven RCTs were included. Five comparing racecadotril with placebo or no intervention, one with pectin / caolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril to loperamide. Meta-analysis of 3 studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared to placebo (Mean Difference (MD) -53.48 hours, 95% CI -65.64 to -41.33,). Meta-analysis of 5 studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (Risk Ratio (RR) 0.99, 95% CI 0.73 to 1.34). CONCLUSIONS There is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears safe and well tolerate

Nontuberculous mycobacterial disease in children :epidemiology, diagnosis and management at a tertiary center

Background There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children. Methods Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia. Results A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6–1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23). Conclusions There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials

The Age-Related Risk of Co-Existing Meningitis in Children with Urinary Tract Infection

Objective: The primary aim of this study was to determine age-stratified rates of co-existing bacterial meningitis in children with urinary tract infection (UTI). The secondary aims of this study were to determine the causative pathogens of UTI, and the clinical features and outcome of children with co-existing meningitis.Methods: Analysis of data collected over a nine-year period at a tertiary pediatric hospital in Australia. Study population: children below 16 years of age with culture-confirmed UTI and a paired CSF sample.Results: A total of 748 episodes in 735 cases were included in the final analysis. The commonest pathogens causing UTI were Escherichia coli (67.4%), Enterococcus faecalis (8.4%), Klebsiella oxytoca (3.5%) and Klebsiella pneumoniae (3.5%). Only two (1.2%; 95% CI: 0.15–4.36%) of 163 neonates (between 0 and 28 days of age) with UTI had co-existing meningitis. Both presented with pyrexia, irritability and lethargy, and recovered uneventfully with antibiotic treatment. There were no cases of co-existing meningitis among 499 infants (between 29 days and 12 months of age) with UTI (95% CI: 0.00–0.74%), or any of the 86 children aged 12 months or over (95% CI: 0.00–4.20%).Conclusions: These findings indicate that clinicians should have a low threshold to perform a lumbar puncture in neonates with UTI, as the risk of co-existing meningitis is not insignificant in this age group. In contrast, beyond the neonatal period, the risk is small and a more selective approach is warranted

Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK:a cost-effectiveness analysis

OBJECTIVES: To assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to high-risk women. DESIGN: A decision tree model was developed to assess the incremental costs and health benefits of the two screening strategies. The base case analysis considered short-term costs during the pregnancy and the initial weeks after delivery. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted to assess the robustness of the results. SETTING: UK antenatal screening programme. POPULATION: Hypothetical cohort of pregnant women who access antenatal care and receive a syphilis screen in 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the cost to avoid one case of congenital syphilis (CS). Secondary outcomes were the cost to avoid one case of intrauterine fetal demise (IUFD) or neonatal death and the number of women needing to be screened/treated to avoid one case of CS, IUFD or neonatal death. The cost per quality-adjusted life year gained was assessed in scenario analyses. RESULTS: Base case results indicated that for pregnant women in the UK (n=725 891), the repeat screening strategy would result in 5.5 fewer cases of CS (from 8.8 to 3.3), 0.1 fewer cases of neonatal death and 0.3 fewer cases of IUFD annually compared with the single screening strategy. This equates to an additional £1.8 million per case of CS prevented. When lifetime horizon was considered, the incremental cost-effectiveness ratio for the repeat screening strategy was £120 494. CONCLUSIONS: Universal repeat screening for syphilis in pregnancy is unlikely to be cost-effective in the current UK setting where syphilis prevalence is low. Repeat screening may be cost-effective in countries with a higher syphilis incidence in pregnancy, particularly if the cost per screen is low