Long-Term Outcomes of Allergic Bronchopulmonary Aspergillosis and Aspergillus Colonization in Children and Adolescents with Cystic Fibrosis.

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8-17 years in 2009-2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term.

A multinational report on SARS-COV-2 infection outcomes in people with CF and Aspergillus infection or ABPA.

BACKGROUND: Aspergillus infection is known to be associated with worse respiratory outcomes in people with CF (pwCF) and is a well-recognised complication of severe SARS-CoV-2 infection. The aim of this observational cross-sectional study was to examine the association of pre-existing Aspergillus infection and/or allergic bronchopulmonary aspergillosis (ABPA) in pwCF and severity of COVID-19. METHODS: Data on SARS-CoV-2 infections in pwCF from January 2020 to June 2021 were collected by the European Cystic Fibrosis Society Patient Registry. The primary outcome was COVID-19 severity measured by hospitalisation comparing those with Aspergillus infection and/or ABPA in the 12 months preceding COVID-19and those without. RESULTS: In total, 1095 pwCF were diagnosed with SARS-CoV-2 and information on pre-existing Aspergillus/ABPA status was available from 807. PwCF and SARS-CoV-2 in the Aspergillus/ABPA group (n = 153), in comparison to the non-Aspergillus/ABPA group (n = 654), were more likely to be hospitalised (adjusted OR 1.79 (1.19 to 2.85); p = 0.005) and their disease course was more likely to be complicated by sepsis (adjusted OR 7.78 (1.78 to 49.43); p = 0.008). The association with hospital admission was no longer significant after excluding patients with ABPA. Secondary analysis comparing pwCF who received antifungal treatment (n = 18), versus those who did not (n = 474) during COVID-19, showed a higher rate of hospitalisation (p < 0.001); intensive care unit admission (p < 0.001), and requirement for invasive ventilation (p < 0.001) in the antifungal treated group. CONCLUSION: We show that pre-existing Aspergillus/ABPAis associated with increased rates of hospitalisation and sepsis during COVID-19 in pwCF.

The prevention, diagnosis and management of central venous line infections in children.

With advancing paediatric healthcare, the use of central venous lines has become a fundamental part of management of neonates and children. Uses include haemodynamic monitoring and the delivery of lifesaving treatments such as intravenous fluids, blood products, antibiotics, chemotherapy, haemodialysis and total parenteral nutrition (TPN). Despite preventative measures, central venous catheter-related infections are common, with rates of 0.5-2.8/1000 catheter days in children and 0.6-2.5/1000 catheter days in neonates. Central line infections in children are associated with increased mortality, increased length of hospital and intensive care unit stay, treatment interruptions, and increased complications. Prevention is paramount, using a variety of measures including tunnelling of long-term devices, chlorhexidine antisepsis, maximum sterile barriers, aseptic non-touch technique, minimal line accessing, and evidence-based care bundles. Diagnosis of central line infections in children is challenging. Available samples are often limited to a single central line blood culture, as clinicians are reluctant to perform painful venepuncture on children with a central, pain-free, access device. With the advancing evidence basis for antibiotic lock therapy for treatment, paediatricians are pushing the boundaries of line retention if safe to do so, due to among other reasons, often limited venous access sites. This review evaluates the available paediatric studies on management of central venous line infections and refers to consensus guidelines such as those of the Infectious Diseases Society of America (IDSA).

Steady-state nevirapine, lamivudine and stavudine levels in Malawian HIV-infected children on antiretroviral therapy using split Triomune 30 tablets.

BACKGROUND: Children remain under-represented in national antiretroviral treatment (ART) programmes in settings with limited resources and high HIV prevalence. In Malawi, an increasing number of HIV-infected children have been started on ART with split tablets of an adult fixed-dose combination drug in the past few years. In 2006, the national paediatric ART regime was changed from Triomune 40 (T40) to Triomune 30 (T30). METHODS: This was a cross-sectional study conducted at the paediatric ART clinic in Blantyre (Malawi) from September 2006 to July 2007. Children taking T30 for > 6 weeks from each dosing weight band (<5, 5-<8, 8-<12, 12-<14, 14-<19, 19-<26, 26-<30 and > or = 30 kg) were recruited. Plasma drug concentration, CD4+ T-cell count and HIV viral load were measured. RESULTS: A total of 74 children were analysed. The median nevirapine (NVP) concentration was 7.35 mg/l. A therapeutic NVP plasma level > 3 mg/l was found in 62 (87.8%) children. A subtherapeutic NVP level (< 3 mg/l) occurred significantly more often in children treated with T30 doses between one-quarter tablet once daily and one-half tablet twice daily (P=0.035). Median prescribed NVP dose was 342 mg/m(2)/day, but 13 (17.6%) children received a dose below the recommended dose of 300 mg/m(2)/day. Compared with a historical control, the median prescribed NVP dose was increased (from 243 to 342 mg/m(2)/day). CONCLUSIONS: Our findings indicate that with the Malawian T30-based ART regime, the majority (87.8%) of children in the study group achieved a therapeutic NVP level. However, treatment remains suboptimal especially for young children receiving T30 dosages less than or equal to one-half tablets twice daily and child appropriate formulations are warranted.

Presentation of child sexual abuse cases to Queen Elizabeth Central Hospital following the establishment of an HIV post-exposure prophylaxis programme.

AIM: To review the presentation and management of child sexual abuse cases presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, since the introduction of an HIV postexposure prophylaxis programme. METHODS: Demographic and medical data was collected from all children presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi between January 2005 and February 2007 with alleged child sexual abuse (CSA). RESULTS: Between January 2005 and February 2007, 217 children presented with alleged CSA. This an average of 3 more per month since the previous year, a 57 percent increase. Physical examination showed signs of trauma 60% (130/217) of cases. 63% (137/217) of the cases presented within 72 hours of defilement. Overall in 42% (92/217) of children a one month course of HIV PEP was indicated and given. In 58% (125/217) HIV PEP was not indicated in view of normal examination, presentation too late (>72 hrs after abuse), multiple abuse episodes in the last 6 months, HIV test positive or HIV test refused. In 66% (144/217) of assessed children antibiotic treatment was given for the prevention and/ or treatment of sexually transmitted infections (STIs). CONCLUSIONS: The introduction of an HIV PEP programme for victims of CSA has lead to increased numbers presenting and being treated. In conclusion it is likely that a significant number of children have been prevented from acquiring HIV and other STIs following CSA. The key area where our service needs to be improved is in establishing documented follow up of all cases to monitor medication compliance, side effects and rates of HIV seroconversion following CSA.

Comparison of previous and present World Health Organization clinical staging criteria in HIV-infected Malawian children.

In many settings, HIV infected children are looked after with limited access to CD4 cell count or viral load. The decision to initiate antiretroviral therapy (ART) is made clinically, based on the WHO paediatric staging criteria, which were revised in 2006. Results of using new and old criteria were compared. Of 694 children, 626 (90.2%) fulfilled criteria to start ART when applying the new WHO staging guidelines, whereas 330 (47.6%) children were eligible for ART when using the old WHO criteria. This signifies a marked rise in the number of paediatric patients qualifying for ART on clinical grounds.

Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen, the major constituent of lung basement membrane. We studied the effects of chorioamnionitis and antenatal corticosteroids on bronchoalveolar lavage (BAL) fluid levels of MMP-9, and its inhibitor, TIMP-1 in preterm infants. STUDY DESIGN: A prospective study was performed on serial BAL samples from 79 ventilated preterm infants at less than 33 weeks' gestation, 18 of whom were from pregnancies complicated by chorioamnionitis. MMP-9 levels were measured by gelatin zymography and TIMP-1 by enzyme-linked immunosorbent assay, and the median value for each infant was calculated. The presence and severity of chorioamnionitis were defined histologically. RESULTS: BAL fluid MMP-9 levels were higher in preterm infants in the chorioamnionitis group (86 [29-518] vs 13 [3-43] ng/mL, P =.001), and levels increased stepwise with the increasing severity of chorioamnionitis. Antenatal corticosteroids had no effect on median MMP-9 levels. Infants in the chorioamnionitis group were more likely to have chronic lung disease (CLD) develop (55% vs 28%, P <.05). TIMP-1 levels were no different between groups. CONCLUSION: Chorioamnionitis is associated with increased lung type IV collagenase levels in the ventilated preterm infant. Antenatal lung inflammation with up-regulation of MMP-9 may be important in the pathogenesis of CLD.