The Reciprocal Interplay between Infections and Inherited Metabolic Disorders.

Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). The basic molecular mechanisms behind the role of infections in these conditions have not been completely clarified. This review points out the different mechanisms behind the relationship between IMDs and infections, providing an overview of this still-under-investigated area. Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. In addition, a dietary regimen with a reduced intake of both micro- and macronutrients can potentially compromise the ability of the immune system to deal with an infection. There is recent pre-clinical evidence showing that during infections there may be a disruption of substrates of various metabolic pathways, leading to further cellular metabolic alteration. Therefore, infective agents may affect cellular metabolic pathways, by mediation or not of an altered immune system. The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.

COVID-19 Vaccine in Inherited Metabolic Disorders Patients: A Cross-Sectional Study on Rate of Acceptance, Safety Profile and Effect on Disease.

BACKGROUND: Vaccines for COVID-19 have had a significant impact on the spread of COVID-19 infection, reducing the incidence and mortality of the infection in several countries. However, hesitancy toward this vaccine is a global health issue for the general population The Vaccine acceptance rate among patients affected with inherited metabolic disorders (IMD), as well as safety profile, has not been described. METHODS: We conducted a cross-sectional study, based on a telephone survey, investigating the COVID-19 vaccination rate, the incidence and type of adverse effects (AEs), the reasons for vaccine refusal and the effects on the underlying disease in a cohort of IMD patients followed at a single center and invited directly to vaccination by specialistic team. RESULTS: Seventy-four patients were included in the study, the median age was 23.4 years (min 12.1-max 61.7), 47% (n = 85) were females and 61% (107) were affected from impaired metabolism of phenylalanine. By October 2021, 94% (n = 163) of them had received at least one dose of the vaccine, which was, in 98% of cases, mRNA-based vaccine, given at the referral hospital in 65% of cases. Overall, 72% of patients with IMD reported AE to the vaccine: 60% after the first dose, 81% after the second. The highest rate of adverse events at the first dose was reported in patients with amino acids related disorders other than impaired phenylalanine metabolism (PKU/HPA) (88%). For the second dose, the PKU/HPA group reported the highest rate of AEs (89% of cases). There was no effect on the underlying disease or acute decompensation after the vaccine. Eleven patients (6%) were not vaccinated because they considered it dangerous. CONCLUSION: Among individuals with IMD, the vaccination rate was high, the incidence and severity of AEs were comparable to those in the general population with no effects on the disease. Direct contact with the specialist medical team, has proven to reassure patients and effectively contrast hesitancy.

Two years of on-site influenza vaccination strategy in an Italian university hospital: main results and lessons learned.

Although the vaccination of healthcare workers (HCWs) is considered essential for preventing influenza circulation in the hospital setting, vaccination coverage (VC) in this group remains low. Among the reasons cited by HCWs is a lack of time to attend the vaccination clinic. For the 2018/2019 influenza season, active (on-site) influenza vaccination was offered directly in 44 operative units (OUs) of the Bari Policlinico hospital (50 OUs, 3,397 HCWs). At the same time, the hospital granted the HCW access to the vaccination clinic during October and December 2018. VC achieved among HCWs of Bari Policlinico during the 2018/2019 influenza season was then analyzed, and the results compared with those of the 2017/18 season. During the 2018/19 season, VC was 20.4% (n = 798) and thus higher than the 14.2% of the 2017/18 season (+6.2%). The highest VC was among physicians (33.4%), followed by other HCWs (23.8%), auxiliary staff (8.6%), and nurses (7.2%). Overall, 284 (36.5%) HCWs were vaccinated at on-site sessions. Multivariate analysis showed that vaccination uptake was associated with male gender and with work in OU where vaccination was actively offered. On the other hand, being a nurse or auxiliary staff member and working in the surgical area were deterrents. Although VC remained unsatisfactory, active on-site vaccination proved to be an important strategy to improve vaccination compliance, increasing 44% compared to the previous season. Nonetheless, mandatory vaccination directed by public health institutions may be the only way to reach a minimum level of coverage.

COVID-19 and Inherited Metabolic Disorders: One-Year Experience of a Referral Center.

Understanding the potential risks of patients with inherited metabolic disorder (IMD) exposed to the COVID-19 pandemic is an unmet need for those involved in their management. Here, we report on the incidence of COVID-19 in a cohort of patients with IMD treated at a children's hospital and compare them with a matched control group. Among the total number of 272 patients actively followed at a referral center, 19 (7%) tested positive for SARS-CoV-2 between March 2020 and March 2021. Their median age was 16.2 years (range 1.4-32.8 years). In two-thirds of the cases, the source of infection was a family member; 12/19 patients (63%) were asymptomatic, only one required hospitalization, and none of them died. In our single-center experience, COVID-19 had a moderate impact on a relatively large cohort of patients with IMD, including children and young adults. The clinical course was very mild in all but one case. The proportion of symptomatic cases and the clinical course were comparable in patients with IMD and in a group of matched, non-IMD COVID-19 controls from the general population.

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report.

BACKGROUND: Propionic acidemia is a rare autosomal recessive inherited metabolic disorder that can inhibit the synthesis of N-acetylglutamate, the obligatory activator in urea synthesis, leading to hyperammonemia. N-carbamylglutamate ameliorates hyperammonemia in decompensated propionic acidemia. The effects of long-term continuous N-acetylglutamate administration in such patients are unknown. We report our clinical experience with continuous administration of N-acetylglutamate for 6 years in a patient with propionic acidemia frequently presenting with hyperammonemia. CASE PRESENTATION: A male Caucasian patient with frequently decompensated propionic acidemia and hyperammonemia was admitted 78 times for acute attacks during the first 9 years of his life. Continuous daily treatment with oral N-carbamylglutamate 100 mg/kg (50 mg/kg after 6 months) was initiated. During 6 years of treatment, he had a significant decrease in his mean plasma ammonia levels (75.7 µmol/L vs. 140.3 µmol/L before N-carbamylglutamate therapy, p < 0.005 [normal range 50-80 µmol/L]) and fewer acute episodes (two in 6 years). CONCLUSION: Our results suggest a benefit of N-acetylglutamate administration outside the emergency setting. If this observation is confirmed, future studies should aim to optimize the dosage and explore effects of the dosage requirements on other drugs and on protein tolerance.

Tuberculosis screening in migrant reception centers: results of a 2009 Italian survey.

BACKGROUND: Tuberculosis (TB) is a social disease that is common in immigrants who are forced to live in difficult circumstances. In Italy, the guidelines for preventing TB include X-ray screening and application of the Mantoux test for migrants from high-TB-endemic countries as soon as possible after admission to Italy. This article describes a field survey conducted in the reception center for asylum seekers in Bari Palese in southern Italy following the death of a center resident from pulmonary TB. METHODS: A Mantoux screening test, followed by chest X-ray, was carried out in March 2009 on 982 immigrants, representing 97.5% of the residents of the center. RESULTS: A positive Mantoux test result was seen in 60.7% of the residents screened. The chest X-rays were performed on 92.9% of cuti-positive patients and on cuti-negative patients who were recent contacts of the deceased TB case and/or with symptoms suspicious for TB. Eight residents were diagnosed with active TB (0.8% of residents), and 117 residents (11.9%) had TB sequelae. In our survey, the Mantoux test demonstrated 88% sensitivity, 17% specificity, and a positive predictive value of 1% for active TB. CONCLUSION: The survey results suggest that residents in asylum centers are a special type of immigrant. Specific risk factors, such as overcrowding, may expose these residents to a greater risk for infectious diseases.

Prevalence of Hepatitis B, C, HIV and syphilis markers among refugees in Bari, Italy.

BACKGROUND: The aim of this study was to assess the prevalence of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) serological markers and the prevalence of VDRL positive subjects in a population of refugees of various nationalities, living in the Asylum Seeker Centre in Bari Palese, Southern Italy. METHODS: The study was carried out in the period May-July 2008 and recruited only voluntarily enrolled healthy refugees. HBsAg, anti-HBc, anti-HCV and anti-HIV virus antibodies were detected. VDRL syphilis screening was also carried out on the serum samples. RESULTS: A total of 529 refugees, 442 males and 87 females, aged between 7 and 52 years, were studied. Of these, 510 were from Africa and 19 from Asia.Forty-four individuals (8.3%) were HBsAg positive and 241 (45.6%) were anti-HBc positive. A total of 24 (4.5%) individuals were anti-HCV positive. Eight asylum seekers (1.5%) were HIV positive. VDRL tests were performed on 269 subjects and 4 (1.5%) were positive. 12.3% of the study population had serological markers of chronic and transmissible infections with potential blood-borne or sexual transmission. CONCLUSIONS: In Italy, a suitable protocol is necessary for the early diagnosis of infectious diseases on entering Asylum Centres, so allowing the adoption of prevention measures to safeguard the health of the individuals, the residents and workers in the Centres and the general population.

High level immunity against poliomyelitis in African and Asian refugees in southern Italy.

The aim of this study was to evaluate the level of poliomyelitis immunization in refugees residing in the Asylum Seeker Center in Bari. The study was carried out during 2008 and involved 573 refugees. An antibody titer >or=1:8 was found in 99.6% for poliovirus 1, in 99.8% for poliovirus 2, and in 99.5% for poliovirus 3.