Prevalence of Granulomas in Patients With Primary Immunodeficiency Disorders, United States: Data From National Health Care Claims and the US Immunodeficiency Network Registry.

PURPOSE: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). We assessed the prevalence of granulomas in patients with PIDD. METHODS: We used the Truven Health MarketScan® 2005-2015 Commercial Claims and Encounters and 2006-2015 Medicaid databases and the US Immunodeficiency Network (USIDNET) PIDD registry (a program of the Immune Deficiency Foundation). Our study population consisted of persons age < 65 years with PIDD, defined as persons with ≥ 2 claims with a diagnostic code for PIDD in MarketScan databases, or patients enrolled in USIDNET. Granulomas were identified using diagnostic codes in MarketScan or provider report in USIDNET. We calculated annual prevalence of PIDD and of granulomas among PIDD patients. RESULTS: We identified 247,474 and 40,395 persons with PIDD among commercially and Medicaid-insured persons, respectively. PIDD prevalence was 6.0/10,000 in 2005 and 11.7/10,000 in 2015 among commercially insured persons and 5.5/10,000 in 2006 and 9.6/10,000 in 2015 among Medicaid-insured persons. The prevalence of granulomas among PIDD patients was 1.2 and 1.5% among commercially and Medicaid-insured persons, respectively. In USIDNET, prevalence of granulomas was 4.4% (177/4021). The proportion with granulomas was similar across age groups in MarketScan, but varied from 2 to 9% in USIDNET. The reported prevalence of granulomas differed depending on PIDD condition: 1-2% in the MarketScan data and 0-13% in USIDNET. CONCLUSION: Granuloma prevalence in PIDD patients was 1-4%. Our study provides an estimate of the proportion of PIDD patients and suggests that granulomas are an uncommon occurrence among patients with PIDD.

Burden of Poor Health Conditions and Quality of Life in 656 Children with Primary Immunodeficiency.

OBJECTIVE: To gain insight into how primary immunodeficiencies (PIDs) affect children's health status and quality of life. STUDY DESIGN: The French Reference Center for PIDs conducted a prospective multicenter cohort that enrolled participants who met all criteria: patients included in the French Reference Center for PIDs registry, children younger than18 years, and living in France. Participants were asked to complete both a health questionnaire and a health-related quality of life (HR-QoL) questionnaire. A severity score was assigned to each health condition: grade 1 (mild) to grade 4 (life-threatening). HR-QoL in children was compared with age- and sex-matched French norms. RESULTS: Among 1047 eligible children, 656 were included in the study, and 117 had undergone hematopoietic stem cell transplantation; 40% experienced at least one grade 4 condition, and 83% experienced at least one grade 3 or 4 condition. Compared with the French norms, children with PID scored significantly lower for most HR-QoL domains. Low HR-QoL scores were associated strongly with burden of poor conditions. CONCLUSIONS: Our results quantify the magnitude of conditions in children with PID and demonstrate that the deleterious health effects borne by patients already are evident in childhood. These results emphasize the need to closely monitor this vulnerable population and establish multidisciplinary healthcare teams from childhood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02868333 and EudraCT 2012-A0033-35.

Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs.

BACKGROUND: A small number of individuals with B-cell-related primary immunodeficiency diseases (PIDs) may exhibit long-term (prolonged or chronic) excretion of immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) following infection with oral poliovirus vaccine (OPV). These individuals pose a risk of live poliovirus reintroduction into the population after global wild poliovirus eradication and subsequent OPV cessation. Treatment with polio antiviral drugs may potentially stop excretion in some of these individuals and thus may reduce the future population risk. METHODS: We developed a discrete event simulation model to characterize the global prevalence of long-term iVDPV excretors based on the best available evidence. We explored the impact of different assumptions about the effectiveness of polio antiviral drugs and the fraction of long-term excretors identified and treated. RESULTS: Due to the rarity of long-term iVDPV excretion and limited data on the survival of PID patients in developing countries, uncertainty remains about the current and future prevalence of long-term iVDPV excretors. While the model suggests only approximately 30 current excretors globally and a rapid decrease after OPV cessation, most of these excrete asymptomatically and remain undetected. The possibility that one or more PID patients may continue to excrete iVDPVs for several years after OPV cessation represents a risk for reintroduction of live polioviruses after OPV cessation, particularly for middle-income countries. With the effectiveness of a single polio antiviral drug possibly as low as 40% and no system in place to identify and treat asymptomatic excretors, the impact of passive use of a single polio antiviral drug to treat identified excretors appears limited. Higher drug effectiveness and active efforts to identify long-term excretors will dramatically increase the benefits of polio antiviral drugs. CONCLUSIONS: Efforts to develop a second polio antiviral compound to increase polio antiviral effectiveness and/or to maximize the identification and treatment of affected individuals represent important risk management opportunities for the polio endgame. Better data on the survival of PID patients in developing countries and more longitudinal data on their exposure to and recovery from OPV infections would improve our understanding of the risks associated with iVDPV excretors and the benefits of further investments in polio antiviral drugs.

Children with frequent infections: a proposal for a stepwise assessment and investigation of the immune system.

Although many children develop frequent infections, only a few have an underlying immune disorder. Children with dysfunction of the immune system develop frequent infections and/or recurrent, persistent, severe, and rare infections. The aim of this review is to provide to the clinician a valuable tool for recognizing any 'discords' of the 'immune-system symphonic orchestra'. By following a reverse route, it will be possible to brighten up the dark and winding road of immunodeficiencies and identify the exact point of immune dysfunction. This is fundamental and crucial to perceive etiologic management and subsequently achieve the best for these young patients and their families.

Health care-associated pneumonia and community-acquired pneumonia: a single-center experience.

Pneumonia occurring outside of the hospital setting has traditionally been categorized as community-acquired pneumonia (CAP). However, when pneumonia is associated with health care risk factors (prior hospitalization, dialysis, residing in a nursing home, immunocompromised state), it is now more appropriately classified as a health care-associated pneumonia (HCAP). The relative incidences of CAP and HCAP among patients requiring hospital admission is not well described. The objective of this retrospective cohort study, involving 639 patients with culture-positive CAP and HCAP admitted between 1 January 2003 and 31 December 2005, was to characterize the incidences, microbiology, and treatment patterns for CAP and HCAP among patients requiring hospital admission. HCAP was more common than CAP (67.4% versus 32.6%). The most common pathogens identified overall included methicillin-resistant Staphylococcus aureus (24.6%), Streptococcus pneumoniae (20.3%), Pseudomonas aeruginosa (18.8%), methicillin-sensitive Staphylococcus aureus (13.8%), and Haemophilus influenzae (8.5%). The hospital mortality rate was statistically greater among patients with HCAP than among those with CAP (24.6% versus 9.1%; P < 0.001). Administration of inappropriate initial antimicrobial treatment was statistically more common among HCAP patients (28.3% versus 13.0%; P < 0.001) and was identified as an independent risk factor for hospital mortality. Our study found that the incidence of HCAP was greater than that of CAP among patients with culture-positive pneumonia requiring hospitalization at Barnes-Jewish Hospital. Patients with HCAP were more likely to initially receive inappropriate antimicrobial treatment and had a greater risk of hospital mortality. Health care providers should differentiate patients with HCAP from those with CAP in order to provide more appropriate initial antimicrobial therapy.

Epidemiological assessment of mucocutaneous infections in patients with recurrent infection syndrome.

BACKGROUND: Recurrent infection syndrome (RIS) results from repeated interactions between hosts and environmental infectious agents and is considered normal (NRIS) because of its benign evolution and positive effects in the development of normal immune responses. Abnormal RIS (ARIS) is characterized by the unusually high frequency of severe infections, either as a result of anatomical or functional abnormalities or due to primary or secondary immunodeficiencies (PIDs and SIDs, respectively). Recurrent mucocutaneous infections (MCIs) can be manifestations of RIS or ARIS and could be more frequent in primary immunodeficiencies. Similarly, etiologic agents might vary from what is observed in the general population. METHODS: We carried out a descriptive study to determine the prevalence of aerobic bacterial and fungal mucocutaneous infections in 452 patients with recurrent infections, using clinical records to establish immunological status associated with the presence and characteristics of the infections. Microbiological analyses from mucocutaneous lesions were used to confirm the etiology. RESULTS: We found mucocutaneous infections in 50 patients for a total of 62 episodes (bacterial or fungal infections in 38 vs. 12 patients, respectively). Mucocutaneous infections were more frequent (21.8% vs. 9.1%; OR = 2.8) and recurrent (8.7% vs. 0.2%; P = 0.000) in primary immunodeficient patients. Furthermore, those with defects in phagocytic cells presented more mucocutaneous infections (56.2%) than patients with other primary immunodeficiencies (11.3%; OR = 10.1). CONCLUSIONS: Bacterial and fungal mucocutaneous infections are more frequent and severe in primary immunodeficient patients, particularly those with defective phagocytosis. Early and adequate assessment of the nature of mucocutaneous infections in ARIS should impact the ability of physicians to treat promptly, avoid complications and reduce the costs of medical assistance.

[Nosocomial infections in pediatrics. Problems and perspectives]. / Infections nosocomiales en pédiatrie--problèmes et perspectives.

High incidence of nosocomial infections in children is largely explained by immunodeficiency, particularly in newborns. Central venous catheter is the main risk factor and coagulase negative staphylococcus the main pathogen in cause. Large variations of nosocomial infection incidences are observed by Nososcomial Infection Surveillance Networks and depend on the pediatric speciality. The highest rate is observed in neonatal intensive care, where incidence density of catheter-related sepsis varies from four to 23 infections for 1000 catheter-days. Local surveillance in each ward, risk factors and knowledge of bacterial epidemiology allow the development of rational preventive and therapeutic protocols. However, prophylactic use of vancomycin is dangerous and immunoglobulins are inefficient.

Computed tomography scan assessment of lung disease in primary immunodeficiencies.

UNLABELLED: A wide spectrum of lung disease can complicate primary immunodeficiencies and early recognition influences management and prognosis. Computed tomography (CT) especially high resolution computed tomography (HRCT) has been shown to detect lung disease in adult immunodeficient patients often when the chest radiograph (CXR) is normal, but this has not been studied in children. Twenty-five CT scans [10 HRCT] and CXRs were reviewed in 23 children [14 male, 9 female] with primary immunodeficiency. Eighteen [72%] of the CT scans were abnormal, bronchiectasis being the commonest finding present in eight CT scans in patients with antibody deficiency. In eight cases CT scan revealed changes not seen on CXR (bronchiectasis; interstitial changes; small parenchymal nodules; air trapping;and a small upper lobe cyst) which influenced treatment in six cases. CONCLUSION: CT scans have a valuable role in assessing lung disease in children with primary immunodeficiencies and will detect important changes not visible on CXR.

Home treatment of antibody-deficiency syndromes with intravenous immune globulin.

Immune globulin replacement is a safe and effective therapy for patients with antibody-deficiency syndromes. The need for frequent hospital visits for treatment and high cost remain significant problems. To surmount these problems, we developed a program of patient/family-performed home administration of intravenous immune globulin. Fourteen patients were selected with predetermined eligibility criteria. Nine patients chose to enter the study. Patients and/or relatives were taught the technique of intravenous administration. A signed agreement to perform the infusion under physician instructions was required. All patients successfully performed home treatment, with an average of 19 infusions completed per patient (range 10 to 24). Home treatment decreased absence from work and school. Another benefit noted was a better self-image for patients who require life-long therapy. Regular follow-up visits with the physician are important for adequate care of patients. We conclude that home self-administration of intravenous immune globulin is feasible, safe, and effective in selected patients.

Environmental control in management of immunodeficient patients: experience with "David".

Environmental control in managing patients with immunodeficiency ranges from the exceedingly complex to the relatively simple. At one end of the spectrum is the total isolation technology applied to David, the "Bubble Boy" who lived his entire life behind sterile plastic barriers. At the other end of the spectrum is the simpler technology applied to patients receiving bone marrow transplants who are maintained in ordinary private hospital rooms and attended by personnel who merely observe handwashing precautions. Most properly performed and controlled studies of the use of special isolation procedures to reduce infections derive from patients receiving bone marrow transplants for conditions of aplastic anemia and leukemia or patients receiving chemotherapy for malignancy. The design of isolation procedures for immunodeficient patients borrows from these studies because of the relatively small number of immunodeficient patients. These studies have shown that laminar airflow rooms produce a significantly lower incidence of infections but may not change the mortality of all patients. Also, protective isolation has clearly reduced the incidence and severity of graft-versus-host disease in transplanted patients with aplastic anemia. Recently there has been a trend away from strict isolation procedures because careful studies have indicated that host rather than acquired pathogens are responsible for at least 85% of infections in these special patients. Also, the human stress of prolonged isolation is becoming increasingly recognized. The complex and expensive isolation techniques that were used in David's case are no longer being utilized in immunodeficient subjects, partly because new transplantation technology has made it possible to cross histocompatibility barriers, obviating the need for permanent isolation.

Viral hepatitis vaccines.

Purified from the plasma of hepatitis B carriers, hepatitis B surface antigen particles have been used in a vaccine to prevent hepatitis B. This plasma-derived vaccine is immunogenic, protective, and has an excellent safety record. Indications and strategies for preexposure and postexposure prophylaxis are reviewed. In addition, novel approaches to hepatitis B vaccine development are being pursued and will provide the basis for the next generation of vaccines. Early progress has also been made toward a hepatitis A vaccine, but clinical availability is not imminent.