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Bacterial infections in a pediatric cohort of primary and acquired complement deficiencies.

ABSTRACT: BACKGROUND:Acquired complement deficiency can occur in the setting of autoimmune syndromes, such as systemic lupus erythematosus (SLE), with very low or, occasionally, undetectable C3 levels. Based on inherited complement defects, patients with transiently low complement may be at similar risk for serious bacterial infection, but the degree of risk related to C3 level and temporal association is unknown. METHODS:We performed a retrospective study including pediatric patients with undetectable total complement activity or absent individual complement components measured at our institution from 2002 to 2018. We assessed annual rate of serious bacterial infection (SBI) defined as requiring hospitalization and/or parenteral antibiotics by manual chart review. Among included SLE patients, we assessed the 30-day probability of SBI for given C3 measurements using a logistic regression model to determine risk. Primary complement deficiency was analyzed for SBI rate as comparison. Covariates included age, level of immune suppression and history of lupus nephritis. RESULTS:Acquired complement deficiency secondary to SLE-related disease [n =?44] was the most common underlying diagnosis associated with depressed complement levels and were compared to a cohort of primary complement deficient patients [n =?18]. SBI per 100 person-years and cohort demographics were described in parallel. Our logistic regression analysis of pediatric patients with SLE showed low C3 level was temporally associated with having an SBI event. Given equivalent immunosuppression, patients with an SBI had lower C3 levels at the beginning of the observation period relative to patients without SBI. CONCLUSION:Pediatric patients with the diagnosis of SLE can develop very low C3 levels that associate with risk of serious bacterial infection comparable to that of patients with primary complement deficiency. Patients prone to severe complement consumption may particularly be at risk.

SUBMITTER: Al-Shaikhly T

PROVIDER: S-EPMC7513499 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Bacterial infections in a pediatric cohort of primary and acquired complement deficiencies.

Al-Shaikhly Taha T Hayward Kristen K Basiaga Matthew L ML Allenspach Eric J EJ

Pediatric rheumatology online journal 20200924 1

<h4>Background</h4>Acquired complement deficiency can occur in the setting of autoimmune syndromes, such as systemic lupus erythematosus (SLE), with very low or, occasionally, undetectable C3 levels. Based on inherited complement defects, patients with transiently low complement may be at similar risk for serious bacterial infection, but the degree of risk related to C3 level and temporal association is unknown.<h4>Methods</h4>We performed a retrospective study including pediatric patients with ...[more]

PMID: 32972440

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Project description:The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as "nonself" in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes "tagged" with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

Project description:BackgroundIn the absence of ultrasound, symphysis-fundal height (SFH) can assess maternal-fetal well-being as it is associated with gestational age, fetal weight, and amniotic fluid volume. However, other modifiers of SFH, including maternal infections, nutrient deficiencies, and inflammation (MINDI), have not been widely explored.ObjectivesOur objectives were 2-fold: 1) to assess prevalence of low SFH in indigenous Panamanian women using both Pan-American Health Organization (PAHO) and INTERGROWTH-21 standards and 2) to explore associations of SFH with maternal health indicators: infections (oral, skin, urogenital, nematode infections), nutrient deficiencies [protein and iron indicators (ferritin, serum iron, serum transferrin receptor, hepcidin), folate, and vitamins A, D, and B-12], and inflammation [leukocytes, C-reactive protein (CRP), cytokines].MethodsFor this cross-sectional study, low-SFH-for-gestational-age was assessed using PAHO and INTERGROWTH <10th centile in 174 women at ≥16 weeks of gestation. Bootstrapping selected MINDI variables for inclusion in multivariable fractional polynomial (MFP) logistic regressions for low SFH. Associations of MINDI variables with hepcidin were also investigated.ResultsPrevalence of low SFH was 8% using PAHO, but using INTERGROWTH, 50.6% had SFH <10th centile, including 37.9% <3rd centile. Both PAHO-SFH <10th centile and INTERGROWTH-SFH <3rd centile were associated with higher hepcidin (OR = 1.12, P = 0.008, and OR = 3.04, P = 0.001, respectively) and with lower TNF-α (OR = 0.73, P = 0.012, and OR = 0.93, P = 0.015, respectively). Wood-smoke exposure increased the odds of PAHO-SFH <10th centile (OR = 1.19, P = 0.009), whereas higher BMI decreased the odds of INTERGROWTH-SFH <3rd centile (OR = 0.87, P = 0.012). Lower pulse pressure (OR = 0.90, P = 0.009) and lower inflammatory responses [lower lymphocytes (OR = 0.21, P = 0.026), IL-17 (OR = 0.89, P = 0.011)] distinguished SFH <3rd centile from SFH ≥3rd to <10th centiles using INTERGROWTH-21 standards. The MFP regression for hepcidin controlling for SFH (adjusted R 2 = 0.40, P = 0.001) revealed associations with indicators of inflammation (CRP, P < 0.0001; IL-17, P = 0.012), acidic urinary pH (P = 0.008), and higher intake of supplements (P = 0.035).ConclusionsAssociations of low SFH with MINDI variables, including hepcidin, highlight its potential for early detection of multicausal in utero growth faltering.

Project description:ObjectiveThis study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates.DesignCohort study.Setting706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017.Participants10.1 million registered patients with 69.3 million patient-years' follow-up.ExposuresAll antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications.Main outcome measuresFirst episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates.ResultsThe age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430-1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074).ConclusionsWe did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.

Dataset Information

Bacterial infections in a pediatric cohort of primary and acquired complement deficiencies.

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Bacterial infections in a pediatric cohort of primary and acquired complement deficiencies.

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