Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis.

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy.  Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients. What is Known: •Data largely derived from adults find that infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. •It is crucial to be aware of the preventive measures that should be implemented to prevent these infections in children, although most guidelines are often extrapolated from adult cases. What is New: •In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could prove useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. •The recommendations focus on tuberculosis, herpes zoster virus, fungal infections, and Pneumocystis jirovecii.

Chorea as the presenting feature of acute rheumatic fever in childhood; case reports from a low-prevalence European setting.

BACKGROUND: Despite a notable decrease in acute rheumatic fever (ARF) incidence in the past few decades, there are still cases in our setting. Sydenham chorea (SC) may be the initial manifestation for this condition in childhood in a significant proportion of children. We report two cases of choreoathetosis in children as the first manifestation of ARF. CASE PRESENTATION: A previously healthy 8-year-old boy presented with right hemichorea with a predominance in the brachial region, orofacial dyskinesias and speech difficulties for the past 2 weeks. The only medical history of interest was a common catarrhal illness 3 weeks before and nonspecific bilateral tenosynovitis in both feet since a year prior. A brain computerized tomography was normal and the echocardiogram showed mild mitral and aortic regurgitation, meeting ARF criteria. He demonstrated clinical improvement with treatment based on prednisone and carbamazepine. The second patient was a 10-year-old girl with choreic movements of the right half of the body and repetitive right eye closure of 1 week duration. She had symptoms of fever and rash the previous week and pharyngitis that resolved without antibiotic 2 months before. Blood tests revealed elevated C reactive protein (12 mg/dl) and erythrocyte sedimentation rate (96 mm/h). Brain magnetic resonance was normal and echocardiogram showed left ventricle dilation and mild mitral regurgitation, leading to the diagnosis of ARF. Due to neurological involvement, she received corticosteroids and intravenous immunoglobulin treatment, with worsening of neurological symptoms that required valproic acid with remission of the hemichorea. In addition skin lessions compatible with erythema marginatum appeared on the upper limbs. CONCLUSIONS: SC should be the main diagnostic consideration in cases of hemichorea with normal neuroimaging in children. The cases reported highlight the need to maintain a high index of suspicion even in settings where incidende of ARF is low and the need to perform cardiological investigations in all patients with suspected SC, due to the possibility of subclinical valve lesions. Good adherence to secondary prophylaxis is crucial to avoid chorea relapses and worsening valve disease.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

"Induced sputum versus gastric lavage for the diagnosis of pulmonary tuberculosis in children".

BACKGROUND: Diagnosis of pulmonary tuberculosis (PTB) is difficult in infants and young children. For microbiological confirmation of PTB children, sequential gastric lavage (GL) is recommended. Induced sputum (IS) may be an alternative or complementary tool, but the information is limited in children in developed countries. The aim of this study is to assess the safety and diagnostic yield from IS combined with GL for PTB diagnosis in non-HIV infected children. METHODS: The study involved 22 children with suspected PTB admitted to the Getafe Hospital from January 2007 to May 2011. IS and GL were performed on three consecutive days, according to a standardized protocol. In all samples, BK staining, culture and PCR were carried out, including Genotype MTBDR plus for resistance to INH-RIF (Isoniazid-Rifampin) since 2008. A preliminary analysis of an ongoing prospective study is presented. RESULTS: Median age was 72 months (range 1 month to 14 years of age). Seven (33%) were ≤ 5 years of age. Seventeen were clinically diagnosed of PTB based on positive PPD and radiological criteria. Microbiological confirmation was achieved in 10 (58.8%) by either GL or IS. M. tuberculosis was identified by GL in 8 children (47.1%) and by IS in 7 (41.2%). One infant (2 IS samples) had transient oxygen desaturation recovered spontaneously. CONCLUSIONS: IS appears to be safe and well tolerated by children for diagnosis of PTB and is more convenient. Increasing the diagnostic yield of PTB in children with PTB may be a complementary technique. Largest studies are necessary to define the role of IS in paediatric PTB.

SARS-CoV-2 Infection in Children and Adolescents Living With HIV in Madrid.

Multicenter study designed to describe epidemiologic and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive cases registered among children and adolescents living with HIV (CALWH). SARS-CoV-2 infection was confirmed in 13.3% of CALWH, with all patients presenting mild symptoms, and the outcome was good in all patients. None of the HIV- and antiretroviral treatment-related variables studied were associated with greater infection risk or could be considered protective.

Prevalence of psychological symptoms and associated risk factors in a Spanish sample of HIV-positive youth compared to uninfected peers.

INTRODUCTION: The aim of the study was twofold: a) to determine the prevalence of symptoms of depression and anxiety and sleep disturbances in young patients with vertically-transmitted HIV infection compared to uninfected peers, and b) to identify sociodemographic, psychosocial and medication-related variables and other clinical risk and protective factors related to psychological symptoms. METHODS: We conducted a cross-sectional study in two groups with independent measures (36 youth with vertically transmitted HIV infection and 39 HIV-negative peers). We used 3 standardised assessment tools and a sociodemographic/psychosocial questionnaire (STAI, BDI, PSQI and adapted sociodemographic test). We performed univariate and multivariable analyses. RESULTS: The univariate analysis did not find significant differences between groups either in psychosocial factors or in the clinical scores. The multivariable analysis found that the presence of psychological symptoms was strongly associated with sociodemographic factors and past events. CONCLUSIONS: Psychosocial factors and the social environment seemed to correlate more strongly to psychological symptoms than HIV status and to explain better the current psychological state of individuals.

Pregnancy Outcomes Among Perinatally HIV-Infected Women in Spain.

BACKGROUND: An increasing number of women living with perinatally acquired HIV are reaching adulthood and becoming pregnant. Achieving viral suppression is challenging in this population frequently exposed to numerous antiretroviral regimens. This study describes the long-term outcomes of pregnant women living with perinatally acquired HIV in Spain. METHODS: Descriptive, retrospective, multicenter study of the women living with perinatally acquired HIV who gave birth between January 2000 and December 2019 in Madrid. Epidemiological, clinical, and HIV-related data were collected from the first delivery to the end of the study period, including antiretroviral therapy, prevention strategies, and outcomes. RESULTS: Sixty-three live births in 33 women were included. The mean number of pregnancies per women was 1.9 (range: 1-6). At first delivery, women's median age was 20 years (interquartile range: 18-23), 11 (33.3%) had been previously diagnosed with AIDS and 6 (18%) with mental health disorders. Forty percent became pregnant unsuppressed, whereas 81% achieved viral suppression at delivery. Treatment interruptions were common after delivery, as were losses to follow-up, with no positive effect of pregnancy on retention to care or the immune virological situation. Five women (15%) experienced a new AIDS event, and there were 2 deaths (6%) during follow-up. There was 1 case of mother-to-child transmission in a nonadherent woman in whom preventive measures could not be implemented. CONCLUSIONS: Pregnancy in this unique population of women living with perinatally acquired HIV poses particular challenges. Specific strategies, including a multidisciplinary approach, are needed to minimize perinatal transmission risks and improve outcomes during the postpartum period.

A Prospective Study of the Serological, Clinical, and Epidemiological Features of a SARS-CoV-2 Positive Pediatric Cohort.

Background: SARS-CoV-2 was a global pandemic. Children develop a mild disease and may have a different rate of seroconversion compared to adults. The objective was to determine the number of seronegative patients in a pediatric cohort. We also reviewed the clinical−epidemiological features associated with seroconversion. Methods: A multicenter prospective observational study during September−November 2020, of COVID-19, confirmed by reverse transcription-polymerase chain reaction. Data were obtained 4−8 weeks after diagnosis. Blood samples were collected to investigate the humoral response, using three different serological methods. Results: A total of 111 patients were included (98 symptomatic), 8 were admitted to hospital, none required an Intensive Care Unit visit. Median age: 88 months (IQR: 24−149). Median time between diagnosis and serological test: 37 days (IQR: 34−44). A total of 19 patients were non-seroconverters when using three serological techniques (17.1%; 95% CI: 10.6−25.4); most were aged 2−10 years (35%, p < 0.05). Univariate analysis yielded a lower rate of seroconversion when COVID-19 confirmation was not present amongst household contacts (51.7%; p < 0.05). Conclusions: There was a high proportion of non-seroconverters. This is more commonly encountered in childhood than in adults. Most seronegative patients were in the group aged 2−10 years, and when COVID-19 was not documented in household contacts. Most developed a mild disease. Frequently, children were not the index case within the family.

Longitudinal survey of humoral and cellular response to SARS-CoV-2 infection in children.

BACKGROUND: Data regarding humoral and cellular response against SARS-CoV-2 in children are scarce. We analysed seroconversion rate, decrease of anti-RBD IgG antibodies over time and T-cell response in paediatric patients who suffered COVID-19. METHODS: Longitudinal study of paediatric patients COVID-19 diagnosed by positive molecular assay in nasopharyngeal swabs. Blood samples were drawn 1-2 months and 6-7 months after acute infection. Anti-RBD IgG were determined using the Alinity® SARS-CoV-2 IgG II Quant assay (Abbott). Cellular immune response was analysed by T-SPOT® SARS-CoV-2 assay kit (Oxford Immunotec Ltd.). RESULTS: 27/39 (69,2%) patients seroconverted. Despite a significant decrease in antibody levels over time (p < 0,01), no children seroreverted between first and second visits. Only 6/16 (37,2%) children under 6 years-old were seropositive compared to 21/23 (91,3%) over 6 years-old (p < 0,01). Highest antibody levels were found in seropositive younger children (p = 0,036). Thirteen (33,3%) children showed T-cell response. Among participants showing humoral response, no cellular response was detected in 14 (51,9%). CONCLUSIONS: Anti-RBD IgG antibodies persistence at 6-7-months after SARS-CoV-2 infection was observed. A different IgG response was found depending on age. As measured by T-SPOT, most patients did not display cellular response 6-7 months after infection.

Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.

Background: Children with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients. Methods: A prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model. Results: A total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5-11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1-1.5) in JIA and 1.12 (95%CI 0.9-1.3) in non-JIA participants (p = 0.19). Age <4 years increased the infection rate by 2.5 times (2.72 vs. 1.12, p < 0.001) in both groups. The most frequent infection sites were upper respiratory (62.6% vs. 74.5%) and gastrointestinal (18.8% vs. 11.4%). There were no differences in severe infections (2.5% vs. 2%, p = 0.65) between the groups. In children with JIA, younger age and higher disease activity (JADAS71) were associated with a higher infection rate. Conclusion: We found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.

Clinical and Epidemiologic Characteristics of a Cohort of HIV-Infected Mother-Infant Pairs During 21 Years.

BACKGROUND: HIV infection continues to be a worldwide public health problem. After the introduction of effective preventive measures, perinatal transmission dramatically decreased. Our aim was to assess the sociodemographic changes in pregnant women living with HIV infection and trends in perinatal transmission rates over time. SETTING: The Madrid cohort of HIV-infected mother-infant pairs is a multicenter, prospective, observational, and cohort study that collects information on HIV-infected pregnant women and their children. METHODS: Information on clinical-epidemiological characteristics of HIV-infected pregnant women until delivery and their children from 9 public hospitals was included. Data were collected from a standardized questionnaire from medical records. The results were classified in 3 periods: period 1 (P1) 2000-2006, period 2 (P2) 2007-2013, and period 3 (P3) 2014-2020. RESULTS: A total of 1521 women living with HIV and 1548 newborns were included. In P1, most mothers (75.8%) were Spanish, whereas in P2 and P3 there was a predominance of foreign origin [62.8% and 70.5% respectively ( P < 0.01)]. The percentage of women with antiretroviral treatment before pregnancy increased significantly in P3 ( P < 0.01). The proportion of Caesarean sections decreased over time ( P < 0.01): 66.2% (n = 472) in P1, 54.9% (n = 245) in P2, and 46.7% (n = 141) in P3. The percentage of preterm and low birth weight newborns showed a statistically significant decrease. Even though there were no statistically significant differences ( P = 0.154), a decrease in cases of perinatal infection was observed (1.6% in P1, 1.3% in P2 and 0.3% in P3). CONCLUSIONS: The epidemiologic characteristics of pregnant women with HIV infection have changed over time in our setting, with an increase of non-Caucasian, heterosexual, and perinatally infected mothers. Although there are still perinatal infections, especially in vulnerable populations such as immigrant women, transmission rate has markedly decreased in recent years and is still of major concern. Prevention measures should be reinforced in the most socially disadvantaged groups.

PFAPA syndrome in siblings. Is there a genetic background?

UNLABELLED: "PFAPA syndrome" is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom corticosteroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever. CONCLUSION: PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic background has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.

[Why might micafungin be the drug of choice in pediatric patients?]. / ¿Por qué micafungina puede ser de elección en el paciente pediátrico?

Micafungin is an echinocandin approved by the European Medicines Evaluation Agency for the treatment of invasive candidiasis in children, including premature infants born before 29 weeks of pregnancy, and as prophylaxis in children undergoing hematopoietic stem-cell transplantation or patients at risk of prolonged neutropenia. This drug has good activity in several Candida spp., including those resistant to fluconazole. Although micafungin is active against Aspergillus spp., it has been used mainly in combination therapy for invasive aspergillosis. There is ample information on the use of micafungin in children, including neonates, and this drug is the only echinocandin approved for use in infants aged less than 3 months. The efficacy, pharmacokinetics and safety of micafungin have been evaluated in phase II and III clinical trials in children, in which its efficacy and safety were demonstrated in comparison with liposomal amphotericin B and fluconazole. The pharmacokinetic profile of micafungin in children allows once daily intravenous administration, with greater clearance than in adults, and consequently pediatric doses are relatively higher. The most appropriate dose in children weighing less than 40 kg is 2 mg/kg/day in the treatment of invasive candidiasis and 1 mg/kg/day as prophylaxis in children undergoing hematopoietic stem-cell transplantation. Doses in neonates should be higher. In premature infants, the most appropriate doses to achieve levels in the brain parenchyma are 7 mg/kg/day and 10 mg/kg/day in those weighing more and less than 1,000 g, respectively. Micafungin has few drug-drug interactions and an acceptable safety profile. Withdrawal of this drug due to adverse effects is rare, although transaminase monitoring is recommended during treatment, as well as evaluation of the risk-benefit balance in patients with liver disease or concomitant administration of hepatotoxic drugs.

Disseminated Tuberculosis Complicated With Pneumatoceles in 2 Infants.

Pneumatoceles are rare complications of pulmonary tuberculosis in children. We present 2 cases in infants of disseminated tuberculosis complicated by pneumatoceles with different evolution. This complication should be considered if worsening of respiratory symptoms occurs after initiating anti-tuberculous treatment. Treatment of pneumatoceles is usually conservative and surgical treatment should be used in patients with giant cysts which cause respiratory distress.

Safety and Experience With Combined Antiretroviral Prophylaxis in Newborn at High-risk of Perinatal HIV Infection, in a Cohort of Mother Living With HIV-infant Pairs.

BACKGROUND: Perinatal transmission of HIV has dramatically decreased in high-income countries in the last few years with current rates below 1%, but it still occurs in high-risk situations, mainly pregnant women with late diagnosis of infection, poor antiretroviral adherence and a high viral load (VL). In these high-risk situations, many providers recommend combined neonatal prophylaxis (CNP). Our aim was to evaluate the safety and toxicity of CNP in infants deemed at high-risk of HIV infection among mother-infant pairs in the Madrid Cohort. MATERIALS AND METHODS: Prospective, multicenter, observational cohort study between years 2000 and 2019. The subgroup of newborns on CNP and their mothers were retrospectively selected (cohort A) and compared with those who received monotherapy with zidovudine (cohort B). Infants with monotherapy were classified according to treatment regimes in long (6 weeks) and short (4 weeks) course. RESULTS: We identified 227 newborns (33.3% preterm and 7 sets of twins) with CNP. A maternal diagnosis of HIV-1 infection was established during the current pregnancy in 72 cases (36.4%) and intrapartum or postpartum in 31 cases (15.7%). Most infants received triple combination antiretroviral therapy (65.6%; n = 149). The perinatal transmission rate in cohort A was 3.5% (95% confidence interval: 1.13%-5.92%). Infants from cohort A developed anemia (26.1% vs. 19.4%, P = 0.14) and neutropenia more frequently at 50-120 days (21.4% vs. 10.9%, P < 0.01), without significant differences in grade 3 and 4 anemia or neutropenia between the two cohorts. There were no differences in increased alanine aminotransferase. Neutropenia was more common in the long zidovudine regimes. CONCLUSIONS: Our findings provide further evidence of the safety of CNP in infants with high-risk of HIV-1 perinatal transmission.

[Prevalence of psychological symptoms and associated risk factors in a Spanish sample of HIV-positive youth compared to uninfected peers]. / Prevalencia y factores de riesgo de síntomas psicológicos en una muestra española de jóvenes con VIH en comparación con pares no infectados.

INTRODUCTION: The aim of the study was twofold: (i)to determine the prevalence of symptoms of depression and anxiety and sleep disturbances in young patients with vertically-transmitted HIV infection compared to uninfected peers, and (ii)to identify sociodemographic, psychosocial and medication-related variables and other clinical risk and protective factors related to psychological symptoms. METHODS: We conducted a cross-sectional study in two groups with independent measures (36 youth with vertically transmitted HIV infection and 39 HIV-negative peers). We used three standardised assessment tools and a sociodemographic/psychosocial questionnaire (STAI, BDI, PSQI and adapted sociodemographic test). We performed univariate and multivariable analyses. RESULTS: The univariate analysis did not find significant differences between groups either in psychosocial factors or in the clinical scores. The multivariable analysis found that the presence of psychological symptoms was strongly associated with sociodemographic factors and past events. CONCLUSIONS: Psychosocial factors and the social environment seemed to correlate more strongly to psychological symptoms than HIV status and to explain better the current psychological state of individuals.

Neurocognitive and quality of life study in perinatally HIV-infected young people and their peers. NeuroCoRISpeS study.

BACKGROUND: Assessing the role of HIV and non-HIV related factors is essential for a better understanding of the neurocognitive outcomes in perinatally HIV-infected (PHIV+) young people. The aim of our study was to assess cognition and quality of life (QoL) of a PHIV+ cohort of young people and to compare it with a control group. METHODS: Thirty PHIV+ and 30 HIV(-) healthy young adults matched by age, sex and socioeconomic status completed a protocol that included neurocognitive tests, a psychosocial semi-structured interview and a QoL questionnaire (PedsQL). Neurocognitive domain-specific and domain-general (NPZ-5) Z-scores were calculated. CDC AIDS-defining category C or not C (PHIV+/C, PHIV+/noC) was considered to evaluate differences within the PHIV+ group. Univariate and multivariate analysis were performed. RESULTS: Sixty patients were included; 67% were female; median age (IQR) 19 years (18-21). Regarding PHIV+ young people, 27% showed CDC C category (none encephalopathy), 93% were on ART and 77% had undetectable viral load. No differences regarding occupation were found, although the HIV(-) group repeated less grades (p=0.028) and had a higher education level (p=0.021). No differences were found between PHIV+/noC and HIV(-) participants. However, the PHIV+/C group showed poorer performance than PHIV+/noC (NPZ-5, p=0.037) and HIV(-) subjects (crystallised intelligence, p=0.025; intelligence quotient, p=0.016). Higher nadir CD4+ T-cell count was related to better Z-score in memory (p=0.007) and NPZ-5 (p=0.025). Earlier and longer exposure to ART resulted in better performance in memory (p=0.004) and executive functions (p=0.015), respectively. CONCLUSIONS: No significant differences were found in the neurocognitive profile nor QoL between PHIV+/noC and HIV(-) adolescents; however, PHIV+/C participants obtained lower scores. The use of longer and earlier ART seems to have a beneficial effect.

Tuberculosis in the paediatric population of Madrid in the last 26 years. / Enfermedad tuberculosa en población pediátrica en Madrid en los últimos 26 años.

INTRODUCTION: Tuberculosis (TB) continues to be a serious public health problem and establishing a definitive diagnosis among children is extremely challenging. Pulmonary tuberculosis is the most prevalent form, with children under the age of 2 years being at greatest risk of severe and disseminated forms. The aim of this study was to describe TB among children in Spain in recent years. PATIENTS AND METHODS: A retrospective study of paediatric patients diagnosed with TB in two hospitals of the Community of Madrid over a 26-year period (1991-2017). Epidemiological and clinical variables, additional tests and treatments received were analysed. RESULTS: 170 children were included. The two most-affected age groups were infancy and adolescence. 42.9% of patients were immigrant children (South-America or Morocco). The main reasons for consultation were TB contact (20.6%) and fever (15.3%). At diagnosis, 61.8% of cases referred an epidemic environment, and 30.6% were asymptomatic. The Mantoux tuberculin skin test was positive in 92.2% of patients and IGRA was positive in 70.6%. Pulmonary TB was identified in 91.8% of children vs. 8.2% with extrapulmonary forms. Gastric juice culture was positive in 36.9% of cases and three strains resistant to isoniazid were isolated. All patients were cured without complications except one who died. CONCLUSIONS: Pulmonary TB continues to be the most prevalent form among children and presumptive diagnosis (symptoms consistent with positive Mantoux test or suggestive X-ray) is the most common form of diagnosis. It is important to conduct a contact investigation in order to control the spread of TB.

[Evaluation of an Xpert EV (Cepheid®) molecular diagnostic technique for enteroviral meningitis]. / Evaluación de una técnica de diagnóstico molecular Xpert EV (Cepheid®) en la meningitis por enterovirus.

INTRODUCTION: Polymerase chain reaction (PCR) assays have shown to be useful and quick for the diagnosis of enterovirus in aseptic meningitis. The aim of our study was to analyse the changes in clinical practice after the introduction of a real-time polymerase chain reaction (RT-PCR) technique using the Xpert EV (Cepheid®) assay for the qualitative detection of enterovirus RNA in cerebrospinal fluid specimens from children with suspected viral meningitis. METHODS: A retrospective study was performed in children older than 1year, diagnosed with enterovirus meningitis in a third level hospital from November 2006 to February 2013. The first period, before the availability of Xpert EV (Cepheid®) (Group1, November 2006-August 2010) was compared with the later period (Group2, September 2010-February 2013). Clinical characteristics, the mean length of stay, and the cost per inpatient cases, were compared between the 2periods. RESULTS: Forty-one patients (60.9% male) were included, with a median age of 64 months (interquartile range 28-96). Twenty-six patients (63.4%) were included in Group2. There were non-statistically significant differences in the epidemiological, disease severity, and laboratory characteristics between both periods of study. A significant difference was observed in the mean length of stay, with it being shorter in Group2 (48hours vs 40.5hours, P=.039), and a significant lower inpatient cost per case (€779.77 vs €656.05, P<.05). CONCLUSION: Xpert EV (Cepheid®) assay was useful for decreasing the length of hospital stay and the costs associated with hospitalisation in children with enterovirus meningitis.