We report on a 4-month-old infant with delayed HIV-1 diagnosis after maternal antiretroviral therapy with long-acting injectable cabotegravir plus rilpivirine (LA-CAB/RPV) in the third trimester. Prolonged viral suppression in HIV-infected infants exposed to maternal LA-CAB/RPV may necessitate molecular testing beyond three months of age to exclude infection.

Young children who are exposed to people with infectious tuberculosis (TB) have an increased risk of developing TB disease following infection. The risk of infection and disease progression can be minimized by prompt identification of TB-exposed individuals and initiation of prophylactic or preventive treatment. We report on a TB outbreak in a daycare center in Berlin, Germany following a delayed diagnosis of cavitary pulmonary TB in a childhood educator. We describe contact investigation, diagnostic, prophylactic, preventive and therapeutic measures in 62 TB-exposed children (median age 3.9 years), including 30 with prolonged TB exposure. The initial examination took place 5–16 days after the index patient was diagnosed with TB. Ten of the 30 children with intensive contact became infected, six (median age 2.7 years) developed pulmonary TB. Three of these children had a concurrent influenza infection, which may have contributed to disease progression. No child without prolonged exposure to the index patient developed disease. Early diagnosis of TB in adult patients, especially those with persistent cough, is crucial to prevent TB in vulnerable infants. Close collaboration between public health departments and specialized facilities is essential for the effective control of TB outbreaks.

Objectives:Infections with non-tuberculous mycobacteria (NTM) in children usually affect the lymph nodes and surrounding tissue. Although the infection is typically self-limiting, it carries a substantial risk of complications due to persistent inflammation and invasive therapeutic interventions. Yet, the immunopathogenesis of the disease is obscure, as are biomarkers guiding treatment decisions. Methods:In this observational study, we analyzed histological samples collected in the NTMkids study to identify parameters associated with impaired wound healing and complicated disease progression. Samples from 33 patients (median age at first presentation 33 months) were investigated, with two consecutive biopsies in 9 patients. Results:Germinal centers, a scattered distribution of granuloma associated CD4+ T-cells, higher CD8+ T-cell density inside the necrosis and foamy epitheloid cells were associated with a favorable outcome. Tissue damage presenting clinically as liquefaction was associated with an adverse outcome. Conclusions:The identified tissue reaction patterns in NTM infections provide insights into the biology of NTM lymphadenitis in children and may aid in more precise treatment decisions.

OBJECTIVES:Global guidelines increasingly support breastfeeding among women living with HIV (WLWH) under optimized conditions. However, outcome data from high-resource settings remain limited. METHODS:We retrospectively analyzed WLWH who delivered at Charité - Universitätsmedizin Berlin between 2017 and 2023. Eligibility for breastfeeding required VL<50 cop/mL. RESULTS:Of 409 WLWH, 365 (89.2 %) were eligible and 77 (18.8 %) initiated breastfeeding. No case of mother-to-child transmission (MTCT) was observed. Sustained viral suppression and ART adherence were key. Exclusive breastfeeding was associated with longer duration (p=0.001), midwifery care promoted exclusivity (p=0.009), and vaginal delivery was linked to longer duration (p=0.005). CONCLUSIONS:Breastfeeding with VL<50 cop/mL appears safe in high-resource settings. Findings support individualized counseling, close monitoring, and multidisciplinary care. The increasing breastfeeding trend reflects a shift in clinical practice.

BACKGROUND:In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. METHODS:Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020. RESULTS:A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004). CONCLUSIONS:Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

OBJECTIVES:To assess the efficacy and safety of a two-drug regimen (2DR) with dolutegravir (DTG) and lamivudine (3TC) in maintaining viral suppression during pregnancy and breastfeeding, and to evaluate its potential as an alternative to the recommended three-drug regimen (3DR) in preventing mother-to-child transmission (MTCT) of HIV. METHODS:We present a case of a 34-year-old pregnant woman who, after discontinuing 3DR due to side effects and poor adherence, was switched to DTG/3TC at gestational week 23. Maternal viral load (VL) and infant HIV status were monitored throughout pregnancy and a ten-month breastfeeding period. Data on pharmacokinetic changes in pregnancy and the risks associated with 2DR were reviewed. RESULTS:The patient's VL remained suppressed (<20 copies/mL) from gestational week 23 until the end of the breastfeeding period. A healthy HIV-negative baby was born at 39 weeks, and the child remained HIV-negative after ten months of breastfeeding. The 2DR was well-tolerated, improved adherence, and reduced fetal drug exposure. Despite limited experience with 2DR in pregnancy, no viral rebound occurred, and no adverse effects were observed. CONCLUSIONS:Although 3DR remains the preferred therapy during pregnancy and breastfeeding, this case indicates that DTG/3TC may be an effective alternative for patients experiencing intolerance or poor adherence to 3DR. Further studies are needed to explore the impact of pharmacokinetic changes in pregnancy on 2DR efficacy and to confirm its safety and role in preventing MTCT.

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

According to the annual global reports from the Word Health Organization (WHO), children under 15 years of age represent 11% of all cases of tuberculosis (TB) globally. Nearly 50% of these cases are children below 5 years old. This continuing medical education (CME) article provides an overview of the current recommendations and innovations based on the revised WHO guidelines on TB management in children and adolescents published in 2022.

Zusammenfassung Im Dezember 2022 hat die Weltgesundheitsorganisation (WHO) die Empfehlungen für die Behandlung der medikamentenresistenten Tuberkulose (TB) aktualisiert. Die Bewertung dieser Empfehlungen und der neuen Studiendaten macht auch für den deutschsprachigen Raum eine Aktualisierung der Leitlinienempfehlungen zur Therapie der mindestens Rifampicin-resistenten Tuberkulose notwendig, welche die entsprechenden Kapitel ersetzt. Auch für Deutschland, Österreich und die Schweiz wird nun eine verkürzte, mindestens 6-monatige MDR-TB-Therapie unter Einsatz der festgelegten und nicht veränderbaren Medikamentenkombination Bedaquilin, Pretomanid, Linezolid und Moxifloxacin (BPaLM) empfohlen, wenn alle hierfür notwendigen Voraussetzungen erfüllt sind. Diese Empfehlung gilt für TB-Fälle mit nachgewiesener Rifampicin-Resistenz einschließlich der Rifampicin-Monoresistenz. Zur Behandlung der präextensiven (prä-XDR) TB wird weiterhin in erster Linie eine individualisierte, an die Resistenzdaten angepasste Therapie über 18 Monate empfohlen. Die nicht veränderbare Medikamentenkombination Bedaquilin, Pretomanid und Linezolid (BPaL) kann bei prä-XDR alternativ angewendet werden, wenn alle Voraussetzungen dafür erfüllt sind. Die notwendigen Voraussetzungen für den Einsatz von BPaLM und BPaL werden in diesem Amendment zur S2k-Leitlinie „Tuberkulose im Erwachsenenalter“ begründet dargestellt.

Weltweit stellen nach Schätzungen der Weltgesundheitsorganisation (WHO) Kinder und Jugendliche unter 15 Jahren etwa 11

Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients.

Objectives The aim of this study was to investigate the rate of Mother-to-child-transmission (MTCT) in women living with HIV (WLWH) in a tertiary care institution. Furthermore, we aimed to assess prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection.” Methods In this single-center study, retrospective data related to pregnancy and childbirth were collected from 420 WLWH. All data were evaluated descriptively. Results From January 2014 to December 2020, a total number of 420 pregnant WLWH delivered 428 newborns. 415 (98.8%) were receiving antiretroviral therapy (ART) and 88.8% had a viral load of < 50 cop/ml prior delivery. 46 (11%) of the newborns were born prematurely. Low birth weight < 2500 g occurred in 38 (9.1%) of the children. 219 (52.1%) caesarean sections (CS) were performed. The most frequent indication for an elective CS was a previous CS (70.2%). 8 severe malformations were detected using first and second trimester ultrasound. In one child, MTCT was detected postpartum, resulting in an HIV transmission rate of 0.2% in the presented cohort. Conclusions The low rate of vertical HIV-transmission in our cohort of 0.2% is the result of interdisciplinary prenatal care and high experience of healthcare providers in treatment of WLWH. Despite high ART coverage and adherence, good maternal immune system and very low vertical HIV transmission rate, maternal HIV infection remains a challenge in obstetric care. First and second ultrasound screening should be a part of prenatal care for HIV-infected women and should also be offered to HIV-negative women. A reduction of the rate of unnecessary elective caesarean deliveries in WLWH is necessary to reduce complications in subsequent pregnancies.

Hintergrund Mit einer Inzidenz von 0,5-1% stellt die intrauterine CMV Infektion weltweit die häufigste konnatale Infektion dar. Unter den bei Geburt zu 90% asymptomatischen Kindern entwickeln ca. 14% innerhalb der ersten zwei Lebensjahre eine sensorineurale Innenohrschwerhörigkeit [1]. Die Wirksamkeit von Valganciclovir bei symptomatischen Neugeborenen ist inzwischen gut belegt. Jedoch fehlen Daten zur Effektivität der virustatischen Therapie bei initial asymptomatischer CMV-Infektion [2]. Die konnatale CMV-Infektion ist mit 10-20% die häufigste nicht genetische bedingte Ursache für eine Hörstörung im Kindesalter [3] und wird bei late-onset Verläufen häufig nicht im Neugeborenenhörscreening erfasst.

ZUSAMMENFASSUNGAufgrund des erhöhten Risikos einer Tuberkulose beim Einsatz von Tumor-Nekrose-Faktor (TNF)-α-Inhibitoren in der Therapie der juvenilen idiopathischen Arthritis und anderer chronisch-entzündlicher Erkrankungen soll bei allen Kindern und Jugendlichen vor Beginn einer Therapie mit TNF-α-Inhibitoren eine Tuberkulose ausgeschlossen werden und ein Screening auf das Vorliegen einer latenten tuberkulösen Infektion erfolgen. Das Screening beinhaltet eine sorgfältige Anamnese, die Durchführung eines Interferon-Gamma-Release-Assays und/oder Tuberkulin-Hauttests sowie eine Röntgen-Thorax-Aufnahme bei einem positiven Testresultat und/oder klinischem Hinweis auf eine Tuberkulose. Eine präventive Therapie der latenten tuberkulösen Infektion soll mit Isoniazid und Rifampicin über 3 Monate oder alternativ mit Isoniazid für 9 Monate durchgeführt werden.

Es handelt sich um eine 14 Jahre alte Patientin, die vor 10 Jahren mit ihrer Familie aus Syrien geflohen ist und sich seit 6 Jahren in Deutschland aufhält. Die Unterbringung erfolgte in verschiedenen Flüchtlingsunterkünften. Bei der Erstuntersuchung war kein Tuberkulose-Screening bei dem Mädchen erfolgt. Seit zwei Wochen sei es zu nicht produktivem Husten, linksseitigen Thoraxschmerzen, Abgeschlagenheit und seit einer Woche zu leichtem Fieber gekommen. Ein Gewichtsverlust sei nicht aufgetreten. Die Vorstellung in unserer Klinik erfolgte bei ausbleibender Besserung unter ambulanter Amoxicillin-Therapie. Die Familien- und Eigenanamnese war unauffällig, aus der Umgebungsanamnese ergab sich kein Hinweis auf eine Tuberkulose (TB).