Leila Bianchi

Interferon-Gamma Release Assay Improves the Diagnosis of Tuberculosis in Children

Background: Interferon-&ggr; release assays (IGRAs) have been recently developed for the diagnosis of tuberculosis (TB) infection. The aim of the present study was to evaluate the performance of an enzyme-linked immunosorbent assay (ELISA)-based IGRA for detecting TB in children. Methods: A prospective study in 336 children at risk for TB infection was carried out. All children were tested with tuberculin skin test (TST) and a commercial ELISA-based IGRA [QuantiFERON-TB Gold In-Tube (Cellestis)]. Results: TST were positive in 58 of 336 (17.3%) and IGRA in 60 of 336 (17.9%) children. Two (0.6%) IGRA results were indeterminate. The overall agreement between the 2 tests was intermediate (86.2%, κ = 0.533). IGRA was positive in 15 of 16 (93.8%) children with active pulmonary TB. The discordant pattern IGRA−/TST+ was significantly associated with Bacille Calmette-Guérin (BCG) vaccination. Among IGRA+ children (excluding cases of TB disease), TST− were significantly younger than TST+ children. Conclusions: The good agreement between positive IGRA and active TB disease suggests a good sensitivity of IGRA. Discrepancies between IGRA and TST can be a result of higher specificity of IGRA that is not influenced by previous BCG vaccination. IGRA may be more sensitive in children younger than 48 months.

Schistosomiasis Screening of Travelers from Italy with Possible Exposure in Corsica, France

To the Editor: Since 2014, many cases of urogenital schistosomiasis acquired in Corsica, France, have been described (1–4). The infections, which all occurred in persons who had bathed in the Cavu River in 2011 or 2013, represent the first cases of autochthonous Schistosoma haematobium infection acquired in Europe since the last reported case in Portugal in 1965 (5). In June 2014, France established a screening program for persons reporting exposure to the Cavu River during 2011–2013. By March 2015, a national surveillance journal had reported 110 autochthonous urogenital schistosomiasis cases in residents of France (6). We describe the diagnostic work-up for and clinical management of persons from Italy who reported bathing in the Cavu River at least once during 2011–2014. All of the patients had requested screening after learning of the risk for acquiring schistosomiasis after freshwater exposure in Corsica. Exclusion criteria for the study included residence in or travel to a country where schistosomiasis is endemic. At least 3 months after their last exposure to the Cavu River, each participant had a filtered terminal urine sample and a serum sample tested for schistosomiasis. Different commercial tests were used, depending on local availability: 3 different ELISAs and an indirect immunofluorescent antibody test (IIFAT). All serum samples were tested in parallel in a laboratory in Florence, Italy, by using 2 Western blots (WBs): a Schistosoma WB IgG kit containing antigens from adult S. mansoni worms and a second kit containing S. mansoni and S. haematobium antigens from a crude adult extract (LDBio Diagnostics, Lyon, France). Confirmed urogenital schistosomiasis was defined by confirmation of S. haematobium eggs in urine by microscopy, positive WB result, or both. Probable urogenital schistosomiasis was defined by positive serologic test results. Possible urogenital schistosomiasis was defined by signs or symptoms suggestive of schistosomiasis (i.e., urogenital symptoms), eosinophilia (>0.4 × 109 cells/L of blood), or both (7). All participants who met the case definition received 1 oral dose of praziquantel (40 mg/kg). Forty-three persons were consecutively enrolled during January 2014–January 2015; of these, 15 (34%) had confirmed (6 patients), probable (2 patients), or possible (7 patients) urogenital schistosomiasis (Table). Of these 15 patients, 7 (47%) reported repeat visits to Cavu River over a period of at least 2 years. The mean eosinophil count was 295 (range 40–1,540) cells/μL of blood; 6 (40%) patients had eosinophilia. Genitourinary symptoms were reported by 7 (47%) patients, and blood was detected by dipstick in the urine of 1 patient. Schistosoma eggs were not found in any urine samples. Table Demographic, epidemiologic, clinical, and laboratory data for 15 patients with urogenital schistosomiasis acquired after bathing in the Cavu River, Corsica, France* Schistosomiasis screening has been suggested for persons with exposure to the Cavu River (6); however, clinical history and clinical evaluation alone and eosinophilia, have low sensitivity for the diagnosis of urogenital schistosomiasis (7,8). Asymptomatic infection has been reported in 25%–36% of persons with travel-associated schistosomiasis, and eosinophilia was present in 50% of the patients (7,8). In screenings in France, only 27% of schistosomiasis-positive patients reported genitourinary symptoms (6). For the diagnosis of urogenital schistosomiasis, serologic testing is more sensitive than detection of eggs in urine, particularly in mild infections (7–9). Many asymptomatic family members of the index case-patients who acquired infection in Corsica tested positive only by serologic testing (1–4). However, commercial serologic tests for schistosomiasis have low sensitivity (9). Kinkel et al. (9) showed that sensitivity of an IIFAT and 3 ELISAs for S. haematobium ranged from 21.4% to 71.4%. In the Corsica outbreak, serologic testing may be even less sensitive because of the hybrid nature of the schistosoma (S. haematobium/S. bovis) (6). In our study, only 2 patients had positive ELISA results. Combinations of >2 serologic tests can markedly increase testing sensitivity to almost 78.6% (9). Sulahian et al. (10) found that a WB containing S. mansoni antigens had 89.5% sensitivity and 100% specificity for S. mansoni. In our study, no patients with urogenital schistosomiasis tested positive by WB containing S. mansoni antigens, but 6 patients tested positive by WB containing S. haematobium antigens. In mild infections, the absence of schistosoma antibodies cannot exclude a diagnosis of urogenital schistosomiasis (7). Therefore, we provided treatment to patients with possible urogenital schistosomiasis; our decision to treat these patients considered the tolerability of praziquantel and the possible severe genitourinary complications of untreated infections (e.g., bladder carcinoma, infertility). Our findings suggest that a sensitive screening strategy for urogenital schistosomiasis consists of a patient’s travel history (exposure in multiple years), clinical history (any new genitourinary complaints after freshwater exposure), eosinophil count, and serologic testing. Because of the failure of commercial ELISA and IIFAT methods, we emphasize that a WB containing S. haematobium antigen should also be used for screening. Of note, a confirmed urogenital schistosomiasis case acquired after a single exposure in 2014 was never reported (1–4,6). The risk for delayed diagnosis of this insidious, neglected disease, which has recently reappeared in Europe, must be reduced. To accomplish this, information regarding the risk for schistosomiasis after freshwater exposure in Corsica must be disseminated to physicians worldwide.

Underestimation of Invasive Meningococcal Disease in Italy

Underestimation is attributable to misdiagnosis, especially in fatal cases, and use of insufficiently sensitive laboratory methods.

Severe infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus in infants: report of three cases and review of literature.

We report three cases of severe infections in infants caused by Panton–Valentine leukocidin positive Staphylococcus aureus and evolved with a positive outcome. The literature of Panton–Valentine leukocidin positive Staphylococcus aureus infections in infants is reviewed.

RE:Schistosomiasis screening of travelers to Corsica, France

To the Editor: As members of the French Ministry of Health Working Group on autochthonous urinary schistosomiasis, we read with interest the 2 recently published articles regarding schistosomiasis screening of travelers to Corsica, France (1,2). Surprisingly, the authors of both articles lacked evidence to support the diagnosis of schistosomiasis in most of what they referred to as confirmed cases. The diagnostic standard for confirmation of urinary schistosomiasis is identification of eggs by microscopic examination of urine samples (3–5). If this criterion were applied in both reports, only 1 patient of the 7 allegedly confirmed cases would actually be confirmed. The low sensitivity of microscopy is well known. Therefore, different serologic tests have been developed, including Western blot (WB). In the study based on travelers from Italy (1), the SCHISTO II WB IgG test (LDBIO Diagnostics, Lyon, France) was used. This test, available since 2015, is based on both Schistosoma haematobium and S. mansoni antigens and has not been evaluated by anyone other than the manufacturer. Moreover, the authors did not report any details regarding the molecular weight and number of specific bands observed on the strip. In the study by authors from the GeoSentinel Surveillance Network (2), both cases that could have been infected after 2013, since exposure occurred only in 2014, and 4 cases which reported bathing in rivers in Corsica other than the Cavu River had just 1 weakly positive serologic screening test. Hence, irrespective of the criteria for a confirmed case of schistosomiasis described above, it appears difficult to conclude that confirmation could rely on only 1 positive serologic test, even a WB. Altogether, these 2 studies identified only 1 patient with parasitological evidence of infection that was attributable to the already known 2013 focus in Cavu River. Therefore, these articles do not provide evidence of transmission of schistosomiasis in Corsica after 2013 or outside the Cavu River.

Infectious diseases prevalence, vaccination coverage, and diagnostic challenges in a population of internationally adopted children referred to a Tertiary Care Childrenʼs Hospital from 2009 to 2015

Abstract Infectious diseases are common in internationally adopted children (IAC). With the objective to evaluate infectious diseases prevalence in a large cohort of IAC and to explore possible risk factors for tuberculosis (TB) and parasitic infections, clinical and laboratory data at first screening visit of all IAC (<18 years) consecutively referred to our Center in 2009 to 2015 were collected and analyzed. In total, 1612 children (median age: 5.40 years; interquartile range: 3.00–7.90) were enrolled, 123/1612 (7.60%) having medical conditions included in the special needs definition. The most frequent cutaneous infections were Molluscum contagiosum (42/1612; 2.60%) and Tinea capitis (37/1612; 2.30%). Viral hepatitis prevalence was <1% (hepatitis B virus [HBV]: 13 children, 0.80%; hepatitis C virus: 1 child, 0.10%; hepatitis A virus: 6 children, 0.40%). A parasitic infection was diagnosed in 372/1612 (23.10%) children. No risk factors for parasitosis were evidenced. Active TB was diagnosed in 4/1355 (0.3%) children, latent TB in 222/1355 (16.40%). Only 3.7% (51/1355) children had concordant positive tuberculin skin test (TST) and QuantiFERON-TB-Gold In-Tube (QFT-G-IT) results. Risk factors for TST+/QFT-G-IT− results were previous Bacille de Calmette-Guérin vaccination (adjusted odds ratio [aOR]: 2.18; 96% confidence interval [CI]: 1.26–3.79; P = 0.006), and age ≥5 years (aOR: 1.49; 95% CI: 1.06–2.11; P = 0.02). The proportion of children with nonprotective titers for vaccine-preventable diseases (VPD) ranged from 15.70% (208/1323) for tetanus to 35.10% (469/1337) for HBV. Infectious diseases were commonly observed in our cohort. The high rate of discordant TST/QFT-G results brings up questions regarding the optimal management of these children, and suggests that, at least in children older than 5 years, only QFT-G-IT results may be reliable. The low proportion of children protected for VPD, confirms importance of a timely screening.

The Risk of Mycobacterium tuberculosis Transmission from Pediatric Index Cases to School Pupils.

This study is the largest report on Mycobacterium tuberculosis transmission rate (TR) from children with pulmonary tuberculosis to school pupils. Higher TR (around 21.6%) was observed in contacts of smear-positive children. TR from pediatric smear-negative index cases was around 0. If our data are confirmed, school contacts of a smear-negative index case could be screened only by clinical evaluation and tuberculin skin test, avoiding the routine use of chest radiographs in children less than 5 years of age as well.

Latent tuberculosis in childhood: tolerability of two different therapeutic approaches

ABSTRACT Background: Isoniazid monotherapy for six or nine months and the combination of isoniazid and rifampicin for three or four months are the most used regimens for treating latent tuberculosis. The main aim of this retrospective study is to evaluate the safety of latent tuberculosis treatment by analysing side effects in both regimens. Research design and methods: Children with latent tuberculosis and treated with isoniazid or isoniazid and rifampicin were included. Periodic evaluations with clinical assessment and blood exams were carried out to detect any adverse reaction, including elevated serum transaminases. Results: 441 children were included, 14.5% treated with isoniazid and 85.5% with isoniazid and rifampicin. Five patients under combined treatment developed hepatotoxicity within the first month. None of the patients under isoniazid monotherapy presented hepatotoxicity. A slight increase of transaminases level was found in both groups (18.7% in isoniazid and 10.3% in isoniazid/rifampicin groups, respectively) without causing discontinuation of treatment, with values normalization at the subsequent checks. Conclusions: Both regimens resulted safe. Hepatotoxicity occurred rarely and within the first month. For this reason, it may be appropriate to perform liver function tests after about one month from the beginning of therapy to avoid diagnostic delays.

Newborn screening for PIDs using both TREC and KREC identifies late occurrence of B cells

Tuscany is the first region in Italy to have implemented a neonatal screening for congenital immunodeficiencies using both tandem mass spectrometry for early and late-onset adenosine deaminase and purine-nucleoside phosphorylase deficiency (1) and multiplex Real-Time PCR for TREC and KREC quantification on Dried Blood Spots (DBS) (2). The screening program with TREC and KREC started on December 2013 and, basing on the last data update of March 2017, it has screened a total of 18981 newborns in these first 3 years. We have had no cases of low or diminished TRECs but 5 cases of low/absent KRECs. This article is protected by copyright. All rights reserved.