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Objective: Individuals with Down Syndrome (DS) exhibit a higher susceptibility to infections, suggesting potential immunological alterations within this population. Consequently, this study aims to assess the immune response profile in children with DS to identify potential immune dysfunctions associated with recurrent infections. Methods: The authors conducted a retrospective analysis involving 49 DS patients, examining various epidemiological, clinical, cytogenetic, and laboratory variables. The study's sample comprised patients aged 2-20 years, with a predominance of males. These patients were categorized into two groups based on the presence or absence of recurrent infections, as indicated by the Jeffrey Modell Foundation alert signs. Results: Immunoglobulin (Ig) A, G, and M levels were deemed normal, although individuals with DS experiencing recurrent infections exhibited significantly lower IgA levels. Additionally, CD3, CD4, CD8, and CD19 lymphocyte counts were found to be within normal ranges, with no significant differences between the two groups. While overall data indicated normal seroconversion levels of pneumococcal polysaccharide antibodies, a notable impairment in seroconversion was observed among DS patients with recurrent infections compared to those without such infections. Conclusion: The deficiency of anti-polysaccharide antibodies in individuals with DS may constitute an important immunological comorbidity. Therefore, it warrants further investigation, particularly among individuals with recurrent infections. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time. This evolution may contribute to the decreased frequency and severity of recurrences. To test this notion, we developed a recurrent HSV infection mouse model and evaluated changes in humoral immunity with repeated challenges. Methods: Mice were repeatedly infected intranasally with clinical isolates of HSV-1 or HSV-2 for four months. HSV binding IgG, neutralizing (with or without complement) and ADCC-mediating antibodies were quantified prior to each round of infection. Viral targets were assessed by western blotting. Pooled immune serum (750 μg IgG per mouse) was passively transferred into naïve wild-type or Hvem knockout mice 24 h prior to lethal skin challenge. Results: Repeated exposure to HSV-1 or HSV-2 induced an increase in total HSV-binding IgG but did not boost neutralizing titers. In contrast, ADCC-mediating responses increased significantly from the first to the fourth viral exposure (p < 0.01). The increase was associated with an expanded antigenic repertoire. Passive transfer of fourth round immune serum provided significant protection whereas first round serum failed to protect (p < 0.01). However, protection was lost when serum was transferred into Hvem knockout mice, which are impaired in mediating ADCC killing. Conclusion: This novel model recapitulates clinical responses, highlights the importance of ADCC in protecting against recurrent infection, and provides a strategy for evaluating therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Background. In phthisiology, all recurrent respiratory tract infections are considered risk factors for tuberculosis (TB) in children. A differentiated assessment of the predictive value of recurrent upper and lower respiratory tract infections will improve the effectiveness of selective TB screening.The aim. To carry out a differentiated assessment of the predictive value of recurrent upper and lower respiratory tract infections in children with tuberculosis and HIV coinfection.Materials and methods. We conducted a retrospective study (2010–2020) of the anamnestic prevalence of recurrent respiratory tract infections in 249 children divided into 4 groups: 72 healthy children (HC); TB – 65 children with tuberculosis; TB/HIV – 56 children with HIV-associated TB; HIV – 65 children with HIV infection.Results. Recurrent lower respiratory tract infections were detected in the anamnesis of 15 (23 %) children of the TB group and in 3 (4 %) children of the HC group (p < 0.001; odds ratio (OR) – 8.6). Lower respiratory tract infections were most common during the year preceding TB disease (11 out of 15 cases), within 2 years before the inclusion of children in the study – in 4 out of 15 cases (p = 0.027; OR = 11.0). In the TB/HIV group, the prevalence of lower respiratory tract infections compared to the HIV group was established only during the year preceding TB – 24 out of 33 cases (73 %) versus 10 out of 34 cases (29 %) in the HIV group (χ2 = 10.9; p = 0.001; OR = 6.4). The occurrence of upper respiratory tract infections in pairs of HC group – TB group and HIV group – TB/HIV group had no statistical differences.Conclusion. The predictor of TB in children regardless of their HIV status is the recurrent lower respiratory tract infections, registered during the year preceding the TB disease. The recurrent infections of the upper respiratory tract do not affect the realization of TB in children, regardless of their HIV status.

Toll‐like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well‐studied TLR1–4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C > A, Ser602Ile), TLR2 rs5743708 (2258G > A, Arg753Gln), TLR3 rs3775291 (1234C > T, Leu412Phe) and TLR4 rs4986790 (896A > G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n = 84), severe infections (n = 15) or common variable immunodeficiency (n = 56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45–6.83, p =.004, ap =.016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05–3.12, p =.028, ap =.112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p ≤.0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41–6.47; p =.012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections. [ABSTRACT FROM AUTHOR]

Introduction: Extraintestinal Escherichia coli infections represent a growing public health threat, However, current studies often overlook important factors such as temporal patterns of infection, phylogenetic and clonal background, or the host gut E. coli population, despite their likely significance. Methods: In this study, we analyzed >7000 clinical E. coli isolates from patients at the Minneapolis Veterans Affairs Health Care System (2012-2019), and concurrent fecal E. coli from uninfected veterans. We assessed phylogenetic group distribution, membership in selected sequence types (STs), and subsets thereof--including the pandemic, resistance-associated ST131-H30R, and ST1193 lineages--and strain type, as defined by pulsed-field gel electrophoresis. We then analyzed these features alongside the temporal patterns of infection in individual hosts. Results: The H30R lineage emerged as the leading lineage, both overall and among fluoroquinolone-resistant isolates, with ST1193 following among fluoroquinolone-resistant isolates. Recurrences were common, occurring in 31% of subjects and 41% of episodes, and often multiple and delayed/prolonged (up to 23 episodes per subject; up to 2655d post-index). Remarkably, these recurrences typically involved the subject's index strain (63% of recurrences), even when affecting extra-urinary sites. ST131, H30R, ST1193, and fluoroquinoloneresistant strains generally caused significantly more recurrences than did other strains, despite similar recurrence intervals. ST131 strain types shifted significantly over the study period. Infection-causing strains were commonly detectable in host feces at times other than during an infection episode; the likelihood of detection varied with surveillance intensity and proximity to the infection. H30R and ST1193 were prominent causes of fecal-clinical clonal overlap. Discussion: These findings provide novel insights into the temporal and clonal characteristics of E. coli infections in veterans and support efforts to develop anti-colonization interventions. [ABSTRACT FROM AUTHOR]

Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network. Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m–21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαβ + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05). In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαβ + CD4-CD8-T-cells, and benefits from treatment with mycophenolate. [ABSTRACT FROM AUTHOR]

Retained needle fragments commonly serve as sources of recurrent infections with a potential to embolize to the heart and lungs and can lead to life-threatening consequences. Here, we report a case of a 46-year-old male with a history of intravenous drug user and chronic forearm wounds, presenting with sepsis. Several retained needles are identified on CT scan, several days postadmission. This case highlights the importance of timely assessment of infectious sources in patients with history of intravenous drug abuse.

Background: ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity (IEIs), specifically categorized as a "disease of immune dysregulation." Cases of this condition, reported by our team and others, are very limited worldwide. As such, our current knowledge of this new disease remains preliminary. This review aims to provide a brief overview of the clinical manifestations, pathogenesis, and treatment strategies for this novel IEI. Data sources: A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency. Our search strategy was "ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor" as of the time of manuscript submission. Results: The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer, abdominal pain, and diarrhea in pediatric males. In some cases, immunodeficiency and autoimmunity can also be prominent. Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene. Western blotting for ELF4 expression of the patient's cells can confirm the pathogenic effect of the variant. To fully confirm the pathogenicity of the variant, further functional test is strongly advised. Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder. Conclusions: Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX. When atypical presentations are prominent, variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function. Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study. [ABSTRACT FROM AUTHOR]

We consider Bayesian nonparametric inference for event time distributions based on current status data. We show that under dependent censoring conventional mixture priors, including the popular Dirichlet process mixture prior, lead to biologically uninterpretable results as they unnaturally skew the probability mass for the event times toward the extremes of the observed data. Simple assumptions on dependent censoring can fix the problem. We then extend the discussion to bivariate current status data with partial ordering of the two outcomes. In addition to dependent censoring, we also exploit some minimal known structure relating the two event times. We design a Markov chain Monte Carlo algorithm for posterior simulation. Applied to a recurrent infection study, the method provides novel insights into how symptoms-related hospital visits are affected by covariates. [ABSTRACT FROM AUTHOR]

The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM_000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects.

IntroductionExtraintestinal Escherichia coli infections represent a growing public health threat, However, current studies often overlook important factors such as temporal patterns of infection, phylogenetic and clonal background, or the host gut E. coli population, despite their likely significance.MethodsIn this study, we analyzed >7000 clinical E. coli isolates from patients at the Minneapolis Veterans Affairs Health Care System (2012–2019), and concurrent fecal E. coli from uninfected veterans. We assessed phylogenetic group distribution, membership in selected sequence types (STs), and subsets thereof—including the pandemic, resistance-associated ST131-H30R, and ST1193 lineages—and strain type, as defined by pulsed-field gel electrophoresis. We then analyzed these features alongside the temporal patterns of infection in individual hosts.ResultsThe H30R lineage emerged as the leading lineage, both overall and among fluoroquinolone-resistant isolates, with ST1193 following among fluoroquinolone-resistant isolates. Recurrences were common, occurring in 31% of subjects and 41% of episodes, and often multiple and delayed/prolonged (up to 23 episodes per subject; up to 2655d post-index). Remarkably, these recurrences typically involved the subject’s index strain (63% of recurrences), even when affecting extra-urinary sites. ST131, H30R, ST1193, and fluoroquinolone-resistant strains generally caused significantly more recurrences than did other strains, despite similar recurrence intervals. ST131 strain types shifted significantly over the study period. Infection-causing strains were commonly detectable in host feces at times other than during an infection episode; the likelihood of detection varied with surveillance intensity and proximity to the infection. H30R and ST1193 were prominent causes of fecal-clinical clonal overlap.DiscussionThese findings provide novel insights into the temporal and clonal characteristics of E. coli infections in veterans and support efforts to develop anti-colonization interventions.

Background: Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time. This evolution may contribute to the decreased frequency and severity of recurrences. To test this notion, we developed a recurrent HSV infection mouse model and evaluated changes in humoral immunity with repeated challenges. Methods: Mice were repeatedly infected intranasally with clinical isolates of HSV-1 or HSV-2 for four months. HSV binding IgG, neutralizing (with or without complement) and ADCC-mediating antibodies were quantified prior to each round of infection. Viral targets were assessed by western blotting. Pooled immune serum (750 μg IgG per mouse) was passively transferred into naïve wild-type or Hvem knockout mice 24 h prior to lethal skin challenge. Results: Repeated exposure to HSV-1 or HSV-2 induced an increase in total HSV-binding IgG but did not boost neutralizing titers. In contrast, ADCC-mediating responses increased significantly from the first to the fourth viral exposure (p < 0.01). The increase was associated with an expanded antigenic repertoire. Passive transfer of fourth round immune serum provided significant protection whereas first round serum failed to protect (p < 0.01). However, protection was lost when serum was transferred into Hvem knockout mice, which are impaired in mediating ADCC killing. Conclusion: This novel model recapitulates clinical responses, highlights the importance of ADCC in protecting against recurrent infection, and provides a strategy for evaluating therapeutic vaccines.

Objective: To examine the relationship between conferred immunity after standard pneumococcal series and refractory otolaryngologic infections in pediatric patients using post-vaccination antibody titers, and to identify contributory underlying conditions revealed when vaccination/re-vaccination fails to confer protective immunity. Study Design: IRB-reviewed and "exempt" retrospective case series with chart review using the Epic® Electronic Medical Record system from 2013 to 2021. Setting: Dedicated tertiary referral children's hospital. Methods: Pneumococcal antibody titer results were assessed for children ages 0 to 21 years and: (1) at least 1 of 7 otolaryngologic disease diagnoses and (2) having received the 4-dose schedule of pneumococcal conjugate vaccine (PCV 7 or 13). Results: A total of 241 subjects met inclusion criteria with 356 laboratory tests. Recurrent acute otitis media, chronic rhinitis, and chronic otitis media with effusion were the 3 most frequent diagnoses. At presentation, only 27.0% of subjects had titers conferring immunity from their prior vaccinations with PCV. About 85 subjects had been subsequently revaccinated with Pneumococcal Polysaccharide Vaccine (PPSV), and antibody responses conferring immunity reached 91.8%. Seven subjects never developed adequate responses; 5 of these had recurrent acute otitis media as the primary otolaryngologic diagnosis. Secondary "revealed" diagnoses included Juvenile Rheumatoid Arthritis (n = 1), unresolved specific antibody deficiency (n = 2), and Hypogammaglobulinemia (n = 1). Conclusion: In pediatric patients with recurrent infectious otolaryngologic disease refractory to traditional medical and surgical therapy, inadequate responses to pneumococcal vaccination may be revealed. This correlation represents a potential pathway for diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Recurrent urogenital infections such as bacterial vaginosis, vulvovaginal candidiasis, and urinary tract infections have a high prevalence and pronounced psychosocial impact. However, no review has compared the psychosocial impacts across infection types. This narrative review discusses the impact of common recurrent urogenital infections on psychosocial aspects, including quality of life, stress, mental health, sexual health, work productivity, race and ethnicity, and satisfaction of medical care. Validated questionnaires show that women with recurrent vulvovaginal candidiasis and urinary tract infections have decreased scores on all aspects of quality of life. Those with recurrent vulvovaginal candidiasis and urinary tract infections show lower mental health scores compared to the general population, with increased risk of anxiety and depression. Recurrent urogenital infections affect sexual relationships and intimacy, including avoidance due to symptoms or as a method of prevention. Recurrent infections also increase medical cost and negatively affect work productivity, leading to a combined estimated cost of over US$13 billion per year. There are clear effects of racial inequality involving minority populations that affect diagnosis, treatment, prevalence, and reporting of recurrent urogenital infections. Satisfactory medical treatment improves quality of life and mental health in those suffering from these conditions. Research evaluating psychosocial aspects of recurrent urogenital infections is variable and is not comparable across vulvovaginal conditions. Even so, psychosocial factors are important in understanding contribution and consequence of urogenital infections. Education, awareness, normalization, community support, and access to care can help to alleviate the negative implications of recurrent urogenital infections. Plain language summary: A narrative review discussing the psychosocial impact of common recurrent urogenital infections and highlights areas where further research is needed to improve clinical care. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are frequently diagnosed in the Emergency Departments (EDs) in Saudi Arabia. Despite their prevalence, there is a lack of localized data on antibiotic prescribing practices for UTIs in EDs, hampering optimal patient care and antibiotic resistance management. Objective: This study aimed to evaluate the appropriateness of antibiotic prescriptions for UTI patients by examining adherence to treatment guidelines at a tertiary care ED in Saudi Arabia. Methods: A retrospective cohort analysis was performed in UTI patients with ≥18 years of age who were presented to the ED at a tertiary care hospital between January 2022 and January 2023. 179 patients were randomly selected for enrollment, and data related to their demographics, medical history, microbial isolation, administered antibiotics, and incidence of recurrent infections were collected. Results: Ciprofloxacin (38 %), Cefuroxime (26.8 %), and Nitrofurantoin (16.8 %) were the most prescribed antibiotics. The female population accounted for 87.3 % of UTI cases. Notably, 40.7 % lacked microbial growth or data. Inappropriateness was found in 55.3 % of selection, 27.9 % of dosing, and 38.5 % of treatment duration confined to antibiotics in UTI management. Moreover, complicated UTIs rather than duration and indication for antibiotic therapy were independent risk factors for the re-occurrence of UTIs. Conclusions: The study depicted an overall 44.7 % of appropriate antibiotic prescriptions in UTI patients. However, it also highlighted the necessity for tailored interventions and promotional efforts aimed at promoting the rational use of antibiotics in patients, thereby preventing resistance and treatment failure.

Background: Recurrent urinary tract infections (rUTIs) are common after renal transplantation (RTx), and the impact on graft and patient survival remains controversial. Objective: In this study, we investigate the incidence and risk factors for rUTIs in a cohort of RTx recipients and evaluate the effect on graft and patient survival. Design, setting, and participants: A retrospective cohort of adult patients who underwent RTx at Rigshospitalet, Denmark, between 2014 and 2021 was evaluated in this study. Outcome measurements and statistical analysis: Risk factors for rUTIs were explored with a multivariable cause-specific Cox proportional hazard analysis. The Kaplan-Meier estimate was used to assess overall survival. Results and limitations: A total of 571 RTx recipients were included. The median age was 52 yr (interquartile range: 42–62 yr). Of the cases, 62% were deceased donor RTx. A total of 103 recipients experienced rUTIs. We found increasing age (hazard ratio [HR]: 1.02 per year increase, 95% confidence interval [95% CI]: 1.00–1.04, p = 0.02), female gender (HR: 2.1, 95% CI: 1.4–3.3, p

Background: A few studies assessed the clinical and immunological features of selective IgM deficiency (SIgMD), especially in the pediatric age. We aimed to characterize the clinical and immunological phenotypes of a cohort of pediatric patients with SIgMD according to the different diagnostic criteria available. Methods: In this multicenter study, we evaluated pediatric SIgMD patients diagnosed at the Pediatric Clinic in Pavia, Italy, or through the Italian Primary Immunodeficiency NETwork (IPINET) and monitored changes in their diagnosis over a time frame that ranges from several months to several years. Results: Forty‐eight patients with SIgMD were included (mean serum IgM: 33 mg/dL). The most common clinical manifestations were recurrent infections (67%) and allergies (48%). Subgroup analysis according to SIgMD definition criteria of the European Society for Immunodeficiencies (ESID) showed no significant difference in clinical manifestations, also considering the group with additional immunological abnormalities. Sixteen patients had long‐term follow‐up, during which 87% preserved their SIgMD diagnosis, while two patients showed a reduction in IgA in addition to low IgM. Conclusions: Our data suggest that the identification of a reduction in serum IgM in children should lead to a complete immunological work‐up to obtain a comprehensive clinical and immunological characterization of the patient. The follow‐up of these patients is fundamental to define the disease evolution and appropriate management. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya. Methods Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections. Results The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample. Conclusions The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.

MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder resulting from the duplication of the methyl-CpG-binding protein 2 (MECP2) gene. The clinical features of MDS include severe intellectual disability, global developmental delay, seizures, recurrent respiratory infections, and gastrointestinal problems. The aim of this qualitative study was to explore how the parents of children with MDS manage their child's seizures, recurrent respiratory infections, and gastrointestinal symptoms, and the impact on them as parents. The data were coded into three categories: (1) complex care needs in the home, (2) highly skilled caregivers, and (3) impact on caregivers and families. Complex 24 h care was required and parents developed complex skillsets to ensure that this was delivered well to their child. The provision of extensive complex medical care in the home had an impact on parent mental and physical health, family dynamics, and finances. This study captures the management of high-burden comorbidities in MDS at home. Investigations into how best to support caregiver wellbeing to reduce their stresses, whilst maintaining optimal child health and wellbeing, are needed. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya. Methods: Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections. Results: The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample. Conclusions: The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission. [ABSTRACT FROM AUTHOR]

Introduction: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). Objective: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. Methods: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). Results: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018–2021 period. Approximately half of the patients had no infections during 2018–2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. Conclusions: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients. [ABSTRACT FROM AUTHOR]

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A 3-month-old female was referred to our facility for evaluation of recurrent severe infections. Her medical history was rich with frequent hospital admissions for intravenous antibiotic courses, blood transfusions on two separate occasions, and a recent growth of Pseudomonas aeruginosa on bronchoalveolar lavage culture. During inpatient stay, culture-sensitive antibiotics, broad-spectrum antifungals, and blood products were administered. Her blood, urine, and spinal fluid cultures, as well as serum/respiratory viral screening panels, yielded nil. In view of persistent high-grade fever, raised inflammatory markers, and recurrent infections, whole-exome sequencing was performed with the suspicion of an underlying immunodeficiency syndrome and/or primary hemophagocytic lymphohistiocytosis (HLH). A homozygous pathogenic variant c.229C>T(p.R77X) in the NCF-2 (neutrophil cytosolic factor 2) gene was detected, with no concurrent primary HLH mutations. Thus, a diagnosis of chronic granulomatous disease with secondary HLH was confirmed. Aggressive continuation of antimicrobial therapy soon led to defervescence, recession of inflammatory markers, and improvement in general wellbeing. Notably, the institution of definitive HLH treatment protocol was not required as the triggering element was targeted. The patient was then repatriated on prophylactic antibiotics with strong recommendation for bone marrow transplantation.

Gastrointestinal (GI) manifestations are the second most common complications of primary immune deficiencies (PIDs) after pulmonary disease, affecting up to one-half of children with PIDs. Non-infectious GI manifestations such as allergic, autoimmune, and inflammatory disorders can be the predominant manifestations of PIDs. We present a series of five children who presented predominantly with these GI manifestations of PID, not attributable to infections. Very early age of onset (infancy), parental consanguinity, and failure to respond to hypoallergenic formula led to strong suspicion for underlying PIDs. Next-generation sequencing led to the underlying genetic diagnosis. Early diagnosis and hematopoietic stem cell transplantation could be life-saving in these children. [ABSTRACT FROM AUTHOR]

Fawzia Hassan Abo Ali,1 Nehal Elfawy Mahmoud,1 Amr Yakout Mohamed El-Sayed,1 Mariam Fathy Abdelmaksoud,2 Alaa K Shata,3 Shaimaa Hani Fouad1 1Department of Internal Medicine/Allergy and Clinical Immunology, Ain-Shams University, Cairo, Egypt; 2Department of Clinical Pathology, Ain-Shams University, Cairo, Egypt; 3Department of Pulmonology, Ain Shams University, Cairo, EgyptCorrespondence: Shaimaa Hani FouadDepartment of Internal Medicine/ Allergy and Clinical Immunology, Ain Shams University, Abbasia, Cairo, 11566, EgyptTel/Fax +202 24346888; Tel +2 01116110004Email shaimaahani@med.asu.edu.egBackground: Selective immunoglobulin A (IgA) deficiency is characterized by a high incidence of both recurrent infections and atopic diseases. Asthma is one of the most common lung diseases affecting around 300 million people worldwide and is associated with risk of serious pneumococcal disease and microbial infections. Multiple studies have attributed this to impaired innate and adaptive immunity in asthmatics. An additional probable hypothesis is the existence of an underlying primary immunodeficiency (PID), such as selective IgA deficiency (sIgAD).Aim: To assess the prevalence of selective IgA deficiency and its correlation to recurrent infections in asthmatic patients.Methods: A case–control study was conducted on 80 subjects who were divided into 3 groups: 20 Asthmatic patients with recurrent chest infections (Group A), 20 asthmatic patients without recurrent chest infections (Group B) and 40 healthy controls (Group C).Results: On comparing the 3 studied groups, there was a statistically significant difference between the three groups (p = ˂0.001) concerning serum IgA. The mean serum IgA was statistically significantly lower in Group A&B than in Group C. Furthermore, it was significantly lower in Group A than in Group B and C (p1,2 < 0.002 and < 0.001&ast;, respectively). The percentage of selective IgA deficiency or partial IgA deficiency in asthmatic patients was 56% (26 patients). Group A showed a statistically significant higher percentage of selective/partial IgA deficiency.Keywords: sIgA, sIgE, sIgM, sIgG, asthma, recurrent infections, immune deficiency

C3 is a crucial protein of the complement system. Congenital C3 deficiency is extremely rare and manifests through recurrent, severe infections and should always be considered as a differential diagnosis of recurrent pyogenic infections. We report a case of a patient with a novel C3 gene mutation, responsible for complete C3 deficiency with impaired complement system activation and recurrent infections.

MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder resulting from the duplication of the methyl-CpG-binding protein 2 (MECP2) gene. The clinical features of MDS include severe intellectual disability, global developmental delay, seizures, recurrent respiratory infections, and gastrointestinal problems. The aim of this qualitative study was to explore how the parents of children with MDS manage their child’s seizures, recurrent respiratory infections, and gastrointestinal symptoms, and the impact on them as parents. The data were coded into three categories: (1) complex care needs in the home, (2) highly skilled caregivers, and (3) impact on caregivers and families. Complex 24 h care was required and parents developed complex skillsets to ensure that this was delivered well to their child. The provision of extensive complex medical care in the home had an impact on parent mental and physical health, family dynamics, and finances. This study captures the management of high-burden comorbidities in MDS at home. Investigations into how best to support caregiver wellbeing to reduce their stresses, whilst maintaining optimal child health and wellbeing, are needed.

In the present article we report the case of a patient at high risk of infection wearing a subcutaneous ICD (S‐ICD) due to previous system extractions, hospitalized for symptomatic BBR VT and underwent radiofrequency catheter (RF) ablation. Afterwards, to prevent the possible progression of the infra‐His conduction disease to a complete block, it was decided to implant a pacemaker system. Since the high infectious risk, and the patient's firm refusal to implant another transvenous system given the previous extractions he underwent in the past, it was decided to implant a leadless pacemaker with atrioventricular synchrony. [ABSTRACT FROM AUTHOR]

Introduction: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). Objective: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. Methods: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). Results: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018–2021 period. Approximately half of the patients had no infections during 2018–2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. Conclusions: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others. This study is the largest to date, featuring 134 males and 20 females, ascertained from the international MECP2 Duplication Database (MDBase). We report a higher frequency of pneumonia, bronchitis, bronchiolitis, gastroesophageal reflux and slow gut motility in males compared to females. We further examine the prevalence of other medical comorbidities such as epilepsy, gastrointestinal problems, feeding difficulties, scoliosis, bone fractures, sleep apnoea, autonomic disturbance and decreased pain sensitivity. A novel feature of urinary retention is reported and requires further investigation. Further research is required to understand the developmental trajectory of this disorder and to examine the context of these medical comorbidities in a quality of life framework. [ABSTRACT FROM AUTHOR]

Purpose: MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods: The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. Results: The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). Conclusion: This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life. [ABSTRACT FROM AUTHOR]

Severe congenital neutropenia (SCN) is a primary immune deficiency disease characterized by a rare deficiency of mature neutrophils. Clinical features include recurrent and life-threatening infections and a reduced absolute neutrophil count from birth. There is also an increased risk of myelodysplastic syndrome and acute myeloblastic leukemia. A four-year-old girl has recurrent oral aft, tonsillopharyngitis, soft tissue, and lung infections. Due to the complaints of the patient, she was hospitalized several times, once in intensive care. She needed intravenous or oral antibiotics about 15 times a year due to recurrent infections. The patient applied to our clinic with fever, fatigue, swelling, and redness in the frontal region. In her history has the patient was administered drainage and antibiotic therapy one year ago due to an abscess in the frontal region. There was a kinship between the parents. There were no individuals with similar complaints in the family. In our patient's genetic analysis, there was a homozygous mutation in the HAX1 (HCLS1-associated protein X-1) gene, and SCN type 3 was diagnosed. The heterozygous same mutation was present in the mother and father. We reported this case to emphasize that Kostmann Syndrome as a rare disease in children with recurrent infections and neutropenia. [ABSTRACT FROM AUTHOR]

Primary Immunodeficiency Disorders (PID) are inherent defects of the immune system that may present in infants and children. The main presentations include increased susceptibility to infections (a narrow or broad spectrum of pathogens), autoimmunity, autoinflammation, allergy and/or malignancy. PIDs are increasingly diagnosed and may present with different phenotypes that range from subtle to severe ones. They are classified into ten major categories according to the International Union of Immunological Societies (IUIS). Autosomal recessive disorders are noticeably more common because of the high consanguinity rates in the society. The spectrum of PID is highlighted with a brief walk through the challenges of establishing a PID service in a resource limited setting like catching up with the rapidly changing field, provision of state of the art diagnostic services and actual provision of medical care to PID patients. Several opportunities for growth of the field and overcoming obstacles are discussed.

The genus Helicobacter is classified into two main groups according to its habitat: gastric and enterohepatic. Patients with X-linked agammaglobulinemia (XLA) appear to be associated with invasive infection with enterohepatic non-Helicobacter pylori species (NHPH), mainly H. cinaedi and H. bilis. Such infections are difficult to control and have a high potential for recurrence. The spectrum of illnesses caused by these species includes recurrent fever, bacteremia, arthritis, osteomyelitis, cellulitis, abdominal abscesses, and pyoderma gangrenosum-like ulcer. The presence of these Helicobacters is particularly difficult to diagnose and eradicate, as they are very fastidious bacteria and present resistance to several types of antibiotics. We report two clinical cases of XLA patients infected with H. bilis. These infections were chronic in these patients and could not be eradicated in one of them. We also review the cases of enterohepatic non- Helicobacter pylori species (NHPH) in patients with this inborn error of immunity. [ABSTRACT FROM AUTHOR]

Introduction. Recurrent respiratory infections in the pediatric population are among the most frequent reasons for requesting medical care. The physician must have a clear judgment to establish the diagnosis, as the causes are very heterogeneous. A thorough evaluation of the family history, environmental exposures and allergies are the key elements in the diagnostic process. A rare cause of recurrent respiratory tract infections is the vascular ring, resulting in the compression of the trachea and/or the esophagus, causing respiratory and/or digestive symptoms. It is often misdiagnosed due to its rarity, and the proper treatment is delayed. Case report. We present the case of a 7-month-old infant who was transferred to our gastroenterology department to treat an invasive Campylobacter jejuni infection, which rapidly evolved well. However, during her hospital stay, we learned that our patient had a significant history of recurrent respiratory infections of medium severity, leading us to investigate further a possible immunodeficiency, either primary or secondary. The clinical exam showed no relevant anomalies, but laboratory studies revealed a deficit in immunoglobulins A and M and a low CD4/CD8 T-cell ratio. Initially, the case was interpreted as a primary humoral immunodeficiency; however, the immunoglobulin levels later normalized. Chest X-ray showed an extrinsic compression of the trachea and the absence of the aortic knob. Bronchoscopy confirmed the narrowing of the tracheal lumen and thoracic CT angiogram revealed the presence of an aortic arch anomaly, namely a right aortic arch with an aberrant left carotid artery. Therefore, the diagnosis of vascular ring was established. Conclusions. Recurrent respiratory infections in children can be a diagnostic challenge. Anamnesis, clinical exam, laboratory and imaging data must be logically structured to have a clear insight into the case. Otherwise, crucial details can be omitted, and the correct diagnosis cannot be established. Although vascular rings are rare, they should not be overseen when the more common causes of frequent respiratory infections have been excluded. [ABSTRACT FROM AUTHOR]

Hyperimmunoglobulinemia E or hyper-IgE syndrome (HIES) is a complex primary immunodeficiency disorder characterized by recurrent skin and pulmonary infections, eczema, eosinophilia, and high serum levels of IgE. The exact prevalence of HIES remains unknown, although this condition is considered to affect less than 1 per million people worldwide. We present a case-report of a 9 year-old girl, symptomatic since early infancy, with distinctive facial features (broad nasal bridge, antimongoloid palpebral fissures), eczema, persistence of primary teeth and recurrent bacterial infections (skin and pulmonary abscesses) due to Staphyloccocus aureus. The diagnosis of HIES was established according to National Institutes of Health scoring system based on both clinical and laboratory findings. Despite antibacterial prophylaxis with trimethoprim-sulfamethoxazole, the patient developed a staphylococcal abscess of right temporal region one year after the last admission in the hospital.

Abstract Background Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor. It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients. Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity. Methods Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively. All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants. PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups. Results 197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1–3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2–3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7–19.3] (p = 0.006)). Conclusion We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients’ quality of life.

Immunoglobulin M (IgM) is the first antibody to be produced during an immune response, and most of the primary humoral immune response is mediated by IgM. Selective IgM deficiency (sIgMD) is a rare immune disorder that has been reported in the association with serious infections. Patients with sIgMD may be asymptomatic; however, approximately 80% of patients present with infections with bacteria, viruses, or protozoa or with an associated allergic, malignant, or autoimmune condition. sIgMD is usually identified when evaluating a patient for recurrent or serious infections. Attempts should be made to document the infection, as well as the responsible organism, whenever possible. It is a diagnosis of exclusion, and formal diagnostic criteria have not been established. We report three adult cases that were diagnosed to have sIgMD during the evaluation for serious polymicrobial infections with bacteria, fungi, mycobacterium, and viruses. One of them was diagnosed to have associated lymphocytic leukemia. All were successfully managed with intravenous Immunoglobulin (Ig), antibiotics, antiviral, supportive treatment, and discharged. We conclude that patients presenting with polymicrobial infections with encapsulated bacteria, fungi, mycobacterium, and viruses should be evaluated for specific antibody deficiency responses, and they appear to improve clinically on Ig therapy. It appears that the disorder is underdiagnosed.

Cystic fibrosis (CF) is a genetic disorder that affects various bodily organs, predominantly the pulmonary and gastrointestinal systems. Identifying CF at an early stage can pose a significant challenge, especially when symptoms manifest unusually. The following case study depicts an exceptional and atypical instance of CF in a neonate. A male infant aged 4 months exhibited symptoms such as failure to thrive (FTT), inadequate weight gain, feeding difficulties, slight developmental delay (presence of head lag), and sporadic irritability. The patient experienced an uncomplicated prenatal and postnatal period. Subsequently, the patient suffered from recurring infections and a notable inability to gain weight. Initial tests, encompassing assessments of liver functionality and metabolic processes, yielded inconclusive results. A genetic assessment pinpointed a detrimental cystic fibrosis transmembrane conductance regulator ( CFTR ) gene mutation on Exon 8, thereby confirming the presence of CF. This analysis underscores the importance of considering CF even in the absence of typical indications. Timely and precise identification through genetic analysis is imperative for effective treatment and enhanced prognoses among individuals with CF., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Malwade et al.)

Introduction: Prolidase deficiency is a rare multisystemic disease associated with collagen metabolism. Clinical manifestations and age of onset are highly variable. Prolidase deficiency is caused by homozygous variants in the PEPD gene. In this report, three siblings with c.1103T>G (L368R) variant in the PEPD gene are presented. They had features not described in the literature and marked intrafamilial clinical heterogeneity. This is the first family of Syrian ancestral origin with prolidase deficiency., Case Presentation: We performed whole-exome sequencing for the index case, and detected a homozygous c.1103T>G variant, in the PEPD gene. All family members were then screened for the same variant by Sanger sequencing analysis. Two siblings were found to be homozygous, and one of them had not yet developed clinical symptoms., Conclusion: Our data expand the clinical spectrum of prolidase deficiency. It also improves our knowledge of phenotype and genotype relationships of prolidase deficiency patients., Competing Interests: The authors have no conflict of interest to declare., (© 2024 S. Karger AG, Basel.)

Introduction and Importance: Hyper-IgE syndrome (HIES), also known as Job syndrome, is a rare immunodeficiency disorder characterized by elevated immunoglobulin E levels and recurrent infections. Diagnosing and managing HIES in resource-limited settings is challenging due to the lack of advanced diagnostic tools. This report highlights the necessity of clinical evaluation and basic laboratory investigations for diagnosing HIES., Case Presentation: A 3-year-old male presented with fever, cough, and widespread pustular lesions. He had a history of recurrent respiratory infections and otitis media. Physical examination revealed characteristic facial features, skin findings, and laboratory investigations showed elevated immunoglobulin E levels (>3000 IU/ml) and leukocytosis. A clinical diagnosis of HIES was made, and the patient responded well to antibiotics, antihistamines, and topical steroids., Clinical Discussion: HIES is caused by genetic mutations affecting immune function, primarily involving STAT3 and DOCK8 genes. Diagnosis in resource-limited settings relies on clinical features and basic investigations. Challenges include the unavailability of genetic testing. Management includes antibiotics and symptomatic relief adapted to available resources., Conclusion: Diagnosing and managing HIES in resource-limited settings requires adaptation of clinical approaches to available resources. This case underscores the importance of clinical vigilance and basic diagnostic tools in diagnosing rare immunodeficiencies., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The complement system, a vital component of innate immunity, consists of various proteins and pathways crucial for the recognition and elimination of pathogens. In addition, it plays a major role in the initiation of adaptive response through the opsonization of antigens, contributing to B-cell activation and memory maintenance. Deficiencies in complement proteins, particularly C3, can lead to severe and recurrent infections as well as immune complex disorders. Here, we present a case report of two siblings with total C3 deficiency resulting from compound heterozygous mutations in C3 (NM&#95;000064.4): c.305dup; [p.Asn103GlnfsTer66] and c.1269 + 5G>T, previously unreported in C3-related diseases. Both, the index case and her sister, presented a history of recurrent infections since early childhood and one of them developed hemolytic uremic syndrome (HUS). Immunological evaluation revealed absent plasma C3 levels, decreased memory B cells, hypogammaglobulinemia, and impaired response to polysaccharide antigens. The siblings showed partial responses to antimicrobial prophylaxis and vaccination, requiring intravenous immunoglobulin replacement therapy, resulting in clinical improvement. Genetic analysis identified additional risk polymorphisms associated with atypical HUS. This case highlights the importance of comprehensive genetic and immunological evaluations in complement deficiencies, along with the potential role of immunoglobulin replacement therapy in managing associated antibody defects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bernacchia, Ginaca, Rotondo, Tejada and Di Giovanni.)

The relationship between warts and hyper-immunoglobulin E (IgE) syndrome lies in the fact that patients with this syndrome may have recurrent or persistent skin warts because of their immune dysfunction. Therefore, it is important to consider this possibility when evaluating a patient with skin warts, especially if they are associated with other symptoms such as recurrent infections or pulmonary issues. Warts can thus be an important clinical sign indicating the presence of this syndrome. We report the case of a young girl presenting with numerous warts accompanied by pulmonary involvement and weight delay, in whom the diagnosis of hyper IgE syndrome was established., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tkak et al.)

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patients developed agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise., (Sociedad Argentina de Pediatría.)

aimaa Hani Fouad11Department of Internal Medicine/Allergy and Clinical Immunology, Ain-Shams University, Cairo, Egypt; 2Department of Clinical Pathology, Ain-Shams University, Cairo, Egypt; 3Department of Pulmonology, Ain Shams University, Cairo, EgyptCorrespondence: Shaimaa Hani FouadDepartment of Internal Medicine/ Allergy and Clinical Immunology, Ain Shams University, Abbasia, Cairo, 11566, EgyptTel/Fax +202 24346888; Tel +2 01116110004Email [email protected] Background: Selective immunoglobulin A (IgA) deficiency is characterized by a high incidence of both recurrent infections and atopic diseases. Asthma is one of the most common lung diseases affecting around 300 million people worldwide and is associated with risk of serious pneumococcal disease and microbial infections. Multiple studies have attributed this to impaired innate and adaptive immunity in asthmatics. An additional probable hypothesis is the existence of an underlying primary immunodeficiency (PID), such as selective IgA deficiency (sIgAD). Aim: To assess the prevalence of selective IgA deficiency and its correlation to recurrent infections in asthmatic patients. Methods: A case–control study was conducted on 80 subjects who were divided into 3 groups: 20 Asthmatic patients with recurrent chest infections (Group A), 20 asthmatic patients without recurrent chest infections (Group B) and 40 healthy controls (Group C). Results: On comparing the 3 studied groups, there was a statistically significant difference between the three groups (p = ˂0.001) concerning serum IgA. The mean serum IgA was statistically significantly lower in Group A&B than in Group C. Furthermore, it was significantly lower in Group A than in Group B and C (p1,2 < 0.002 and < 0.001*, respectively). The percentage of selective IgA deficiency or partial IgA deficiency in asthmatic patients was 56% (26 patients). Group A showed a statistically significant higher percentage of selective/partial IgA deficiency. [ABSTRACT FROM AUTHOR]

Abstract Asthma and anaphylaxis are two atypical presentations of hyper‐IgE syndrome (HIES). Early diagnosis and management of HIES can improve quality of life of patients through minimizing orthodontic problems and other complications related to this disorder.

IntroductionConventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use.ObjectiveTo evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs.MethodsAn observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year.ResultsForty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p