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Open Forum Infectious Diseases Oct 2022Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely...
BACKGROUND
Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.
METHODS
We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022. We conducted a systematic literature review via PubMed/Medline and Embase for all English-language publications from 1970 to 10 July 2022, to identify additional cases.
RESULTS
We identified 8 cases of pregnancy-related tuberculous meningitis in Ugandan women living with human immunodeficiency virus (HIV) and 40 additional cases via systematic literature review (none HIV-positive). Of all combined cases, 50% (24/48) were diagnosed postpartum; 50% (24/48) had initial onset during pregnancy, of which 38% (9/24) had worsening of symptoms or disease relapse following pregnancy cessation. Diagnosis was missed or delayed in 33% (16/48) of cases. For those with known outcomes, maternal mortality was 23% (11/48) and fetal/neonatal mortality was 30% (13/44). Of maternal survivors, 30% (11/37) had residual neurologic deficits.
CONCLUSIONS
The true incidence of tuberculous meningitis in pregnancy or the postpartum period is unclear but likely underappreciated. To date, nearly all published cases have occurred in HIV-negative or otherwise immunocompetent women. Given the well-described physiological immunosuppression during pregnancy and subsequent reconstitution postpartum, physicians must be aware of tuberculous meningitis and pregnancy-related immune reconstitution inflammatory syndrome, especially in countries with a high burden of tuberculosis and in women living with HIV.
PubMed: 36267255
DOI: 10.1093/ofid/ofac513 -
AIDS Research and Human Retroviruses Apr 2021The concurrence of infection with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus...
The concurrence of infection with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), presents an intriguing problem with many uncertainties underlying their pathogenesis. Despite over 96.2 million cases of COVID-19 worldwide as of January 22, 2021, reports of patients coinfected with HIV and SARS-CoV-2 are scarce. It remains unknown whether HIV patients are at a greater risk of infection from SARS-CoV-2, despite their immunocompromised status. We present a systematic review of the literature reporting cases of HIV and SARS-CoV-2 coinfection, and examine trends of clinical outcomes among coinfected patients. We systematically compiled 63 reports of HIV-1 and SARS-CoV-2 coinfection, published as of January 22, 2021. These studies were retrieved through targeted search terms applied to PubMed/Medline and manual search. Despite scattered evidence, reports indicate a favorable prognosis for HIV patients with strict adherence to combined antiretroviral therapy (cART). However, the presence of comorbidities was associated with a poorer prognosis in HIV/SARS-CoV-2 patients, despite cART and viral suppression. Studies were limited by geographic coverage, small sample size, lack of patient details, and short follow-up durations. Although some anti-HIV drugs have shown promising activity against SARS-CoV-2, there is no conclusive evidence of the clinical efficacy of any anti-HIV drug in the treatment of COVID-19. Further research is needed to explain the under-representation of severe COVID-19 cases among the HIV patient population and to explore the possible protective mechanisms of cART in this vulnerable population.
Topics: Anti-HIV Agents; COVID-19; HIV Infections; Humans; SARS-CoV-2
PubMed: 33599163
DOI: 10.1089/AID.2020.0284 -
Allergy, Asthma, and Clinical... Aug 2023Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most...
BACKGROUND
Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken.
OBJECTIVES
To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness.
METHODS
For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction.
RESULTS
Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases.
CONCLUSION
Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
PubMed: 37559153
DOI: 10.1186/s13223-023-00831-1 -
The Journal of Allergy and Clinical... Apr 2022Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID)...
BACKGROUND
Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia.
OBJECTIVES
This study sought to determine whether standardized screening terminology could overcome a Babylonian confusion and whether improved case definitions would promote international exchange of knowledge.
METHODS
A systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs.
RESULTS
The study's recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and nonactionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance.
CONCLUSIONS
By bringing together the previously unconnected public health screening community and clinical immunology community, these SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. This study proposes that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide.
Topics: Child; Data Collection; Humans; Infant; Infant, Newborn; Lymphopenia; Neonatal Screening; Severe Combined Immunodeficiency
PubMed: 34537207
DOI: 10.1016/j.jaci.2021.08.026 -
Clinical and Experimental Medicine Jun 2024To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted... (Meta-Analysis)
Meta-Analysis Review
To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted following PRISMA criteria. Searching Pubmed and Web of Science databases, the following keywords were used in the search: ("Next-generation sequencing") OR "whole exome sequencing" OR "whole genome sequencing") AND ("primary immunodeficiency disease" OR "PIDs"). We used STARD items to assess the risk of bias in the included studies. The meta-analysis included 29 studies with 5847 patients, revealing a pooled positive detection rate of 42% (95% CI 0.29-0.54, P < 0.001) for NGS in suspected PID cases. Subgroup analyses based on family history demonstrated a higher detection rate of 58% (95% CI 0.43-0.71) in patients with a family history compared to 33% (95% CI 0.21-0.46) in those without (P < 0.001). Stratification by disease types showed varied detection rates, with Severe Combined Immunodeficiency leading at 58% (P < 0.001). Among 253 PID-related genes, RAG1, ATM, BTK, and others constituted major contributors, with 34 genes not included in the 2022 IUIS gene list. The application of NGS in suspected PID patients can provide significant diagnostic results, especially in patients with a family history. Meanwhile, NGS performs excellently in accurately diagnosing disease types, and early identification of disease types can benefit patients in treatment.
Topics: Humans; High-Throughput Nucleotide Sequencing; Primary Immunodeficiency Diseases
PubMed: 38890201
DOI: 10.1007/s10238-024-01392-2 -
Frontiers in Immunology 2020Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare combined immunodeficiency (CID) caused by recessive homozygous/compound heterozygous...
Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare combined immunodeficiency (CID) caused by recessive homozygous/compound heterozygous loss-of-function mutations in the gene. Patients with ZAP-70 deficiency present with a variety of clinical manifestations, particularly recurrent respiratory infections and cutaneous involvements. Therefore, a systematic review of ZAP-70 deficiency is helpful to achieve a comprehensive view of this disease. We searched PubMed, Web of Science, and Scopus databases for all reported ZAP-70 deficient patients and screened against the described eligibility criteria. A total of 49 ZAP-70 deficient patients were identified from 33 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. ZAP-70 deficient patients have been reported in the literature with a broad spectrum of clinical manifestations including recurrent respiratory infections (81.8%), cutaneous involvement (57.9%), lymphoproliferation (32.4%), autoimmunity (19.4%), enteropathy (18.4%), and increased risk of malignancies (8.1%). The predominant immunologic phenotype was low CD8+ T cell counts (97.9%). Immunologic profiling showed defective antibody production (57%) and decreased lymphocyte responses to mitogenic stimuli such as phytohemagglutinin (PHA) (95%). Mutations of the gene were located throughout the gene, and there was no mutational hotspot. However, most of the mutations were located in the kinase domain. Hematopoietic stem cell transplantation (HSCT) was applied as the major curative treatment in 25 (51%) of the patients, 18 patients survived transplantation, while two patients died and three required a second transplant in order to achieve full remission. Newborns with consanguineous parents, positive family history of CID, and low CD8+ T cell counts should be considered for ZAP-70 deficiency screening, since early diagnosis and treatment with HSCT can lead to a more favorable outcome. Based on the current evidence, there is no genotype-phenotype correlation in ZAP-70 deficient patients.
Topics: Autoimmunity; CD8-Positive T-Lymphocytes; Delayed Diagnosis; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Loss of Function Mutation; Lymphopenia; Male; Phenotype; Severe Combined Immunodeficiency; Treatment Outcome; ZAP-70 Protein-Tyrosine Kinase
PubMed: 32431715
DOI: 10.3389/fimmu.2020.00831 -
Journal of Translational Autoimmunity Jun 2024Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS...
Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.
PubMed: 38188041
DOI: 10.1016/j.jtauto.2023.100230