Humoral immune responses to Pneumocystis jirovecii antigens in HIV-infected and uninfected young children with pneumocystis pneumonia

BACKGROUND: Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. METHODS: Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. RESULTS: 149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. CONCLUSIONS: Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP

Sero-Epidemiology of Pneumocystis Infection among Infants, Children, and Adults in Chile

Previous serologic surveys show >80% of infants in Chile have anti-Pneumocystis antibodies by 2 years of age, but the seroepidemiology of Pneumocystis infection beyond infancy is unknown. We describe the sero-epidemiology in infants, children, and adults at different locations in Chile. Serum samples were prospectively obtained from 681 healthy adults (age ≥ 17 years) and 690 non-immunocompromised infants/children attending eight blood banks or outpatient clinics (2 in Santiago) in Chile. ELISA was used to measure serum IgM and IgG antibodies to Pneumocystis jirovecii major surface antigen (Msg) constructs MsgA and MsgC1. Serologic responses to Pneumocystis Msg showed a high frequency of reactivity, inferring infection. Among infants/children increasing age and the proportion with detectable IgM responses to MsgA, and IgG responses to MsgA, and MsgC1 were positively associated. Among adults there was almost universal seropositivity to one or more Pneumocystis Msg constructs. In infants and children rates of detectable IgM responses to MsgC1 and MsgA were greater than IgG responses. In Santiago, rates of seropositivity among infants/children were greater in clinics located in a more socio-economically deprived part of the city. In Chile, a serological response to Pneumocystis Msg constructs was common across ages regardless of geographical location and climatic conditions. Observed higher rates of IgM responses than IgG responses is consistent with concept of recent/ongoing exposure to Pneumocystis in children and adults. Higher rates of seropositivity in infants/children residing in more densely populated areas of Santiago infers crowding poses an increased risk of transmission

Antibody Response to Pneumocystis jirovecii: Antibody Response to Pneumocystis jirovecii Major Surface Glycoprotein

We conducted a prospective pilot study of the serologic responses to overlapping recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other causes. Similar baseline geometric mean antibody levels to the fragments measured by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii patients rose to a peak level 3–4 weeks (p<0.001) after recovery from pneumocystosis; baseline CD4+ count >50 cells/μL and first episode of pneumocystosis were the principal host factors associated with this rise (both p<0.001). Thus, MsgC shows promise as a serologic reagent and should be tested further in clinical and epidemiologic studies

Serum Antibody Levels to the Pneumocystis jirovecii Major Surface Glycoprotein in the Diagnosis of P. jirovecii Pneumonia in HIV+ Patients

infection has never been developed. major surface glycoprotein recombinant fragment C1 (MsgC1) in 110 HIV+ patients with active PcP (cases) and 63 HIV+ patients with pneumonia due to other causes (controls) by an enzyme-linked immunosorbent assay (ELISA). The cases had significantly higher IgG and IgM antibody levels to MsgC1 than the controls at hospital admission (week 0) and intervals up to at least 1 month thereafter. The sensitivity, specificity and positive predictive value (PPV) of IgG antibody levels increased from 57.2%, 61.7% and 71.5% at week 0 to 63.4%, 100%, and 100%, respectively, at weeks 3–4. The sensitivity, specificity and PPV of IgM antibody levels rose from 59.7%, 61.3%, and 79.3% at week 0 to 74.6%, 73.7%, and 89.8%, respectively, at weeks 3–4. Multivariate analysis revealed that a diagnosis of PcP was the only independent predictor of high IgG and IgM antibody levels to MsgC1. A high LDH level, a nonspecific marker of lung damage, was an independent predictor of low IgG antibody levels to MsgC1.The results suggest that the ELISA shows promise as an aid to the diagnosis of PCP in situations where diagnostic procedures cannot be performed. Further studies in other patient populations are needed to better define the usefulness of this serologic test

Healthcare Worker Occupation and Immune Response to Pneumocystis jirovecii

Humans may be a reservoir for this pathogen and transmit it from person to person

Enzyme-Linked Immunosorbent Assay and Serologic Responses to Pneumocystis jiroveci

Seroepidemiologic studies of Pneumocystis pneumonia (PCP) in humans have been limited by inadequate reagents. We have developed an enzyme-linked immunosorbent assay (ELISA) using three overlapping recombinant fragments of the human Pneumocystis major surface glycoprotein (MsgA, MsgB, and MsgC) for analysis of antibody responses in HIV-positive patients and healthy blood donors. HIV-positive patients had significantly higher antibody levels to all Msg fragments. Furthermore, HIV-positive patients who experienced a previous episode of PCP (PCP-positive) had higher level of antibodies to MsgC than patients who never had PCP. A significant association was found between ELISA antibody level and reactivity by Western blot in HIV-positive patients, especially those who were PCP-positive. Thus, this ELISA will be useful in studying serum antibody responses to Pneumocystis in different human populations

A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome

<p>Abstract</p> <p>Background</p> <p>Individuals who carry deleterious BRCA mutations face significantly elevated risks of breast, ovarian, and other cancers. These individuals are also responsible for informing relatives of their increased risk for carrying the family BRCA mutation. Few interventions have been developed to facilitate this family communication process.</p> <p>Methods</p> <p>We developed the Sharing Risk Information Tool (ShaRIT), a personalized educational intervention, to support BRCA carriers as they discuss BRCA positive results and their implications with relatives. We conducted a pilot study of 19 BRCA carriers identified through the University of California San Francisco Cancer Risk Program. Our study had two aims: 1) to assess the feasibility and acceptability of ShaRIT, and 2) describe characteristics associated with increased family communication and BRCA testing. Participants in our study were divided into two groups: those who had not received ShaRIT as part of their genetic counseling protocol (control group, n = 10) and those who received ShaRIT (n = 9).</p> <p>Results</p> <p>All 9 women who received ShaRIT reported that it was a useful resource. Characteristics associated with increased sharing and testing included: female gender, degree of relationship, and frequency of communication. Increased pedigree knowledge showed a trend toward higher rates of sharing.</p> <p>Conclusions</p> <p>Both participants and genetic counselors considered ShaRIT a well-received, comprehensive tool for disseminating individual risk information and clinical care guidelines to Hereditary Breast and Ovarian Cancer Syndrome families. Because of this, ShaRIT has been incorporated as standard of care at our institution. In the future we hope to evaluate the effects of ShaRIT on family communication and family testing in larger populations of BRCA positive families.</p