European shortage of purified protein derivative and its impact on tuberculosis screening practices.

SETTING: In June 2014, we became aware that shortages of purified protein derivative (PPD), the test substance used for the tuberculin skin test (TST), had occurred in several European health care institutions providing care for children with tuberculosis (TB). OBJECTIVE: To establish the extent of the shortage, a survey was performed. DESIGN: Survey conducted over a 1-month period (June-July 2014) among members of the Paediatric Tuberculosis Network European Trials Group (ptbnet). RESULTS: Thirty-five physicians from 23 European countries contributed data. The most commonly used PPD product was RT23 (Statens Serum Institut; n = 22, 63%). Twenty-one (60%) participants reported that their institution was experiencing a PPD shortage. The majority (n = 17, 81%) of those reporting a shortage were using RT23. Thirteen (37%) participants reported changes in screening practices resulting from the shortage, including sourcing PPD from alternative manufacturers, restricting remaining supplies to patients at greatest risk or replacing TST by an interferon-gamma release assay. CONCLUSIONS: The data show that a PPD shortage occurred in 2014, affecting multiple European countries. The shortage resulted in changes in TB screening capabilities and practices, potentially compromising both patient care as well as public health efforts. Appropriate actions to prevent future PPD shortages should be explored urgently by public health agencies and key stakeholders.

X-linked agammaglobulinemia in community-acquired pneumonia cases revealed by immunoglobulin level screening at hospital admission.

In children with primary immunodeficiencies, the onset of symptoms precedes the diagnosis and the initiation of appropriate treatment by months or years. This delay in diagnosis is due to the fact that while these disorders are rare, some of the infections seen in immunodeficient patients are common. Defective antibody production represents the largest group among these disorders, with otitis, sinusitis and pneumonia as the most frequent initial manifestation. We performed a prospective study of humoral immunity in children hospitalized due to community-acquired pneumonia in tertiary care hospital. Out of 254 patients (131 boys, 123 girls, median age 4.5 years) recruited over 3 years, we found 2 boys (age 11 and 21 months) lacking serum immunoglobulins and circulating B cells. Subsequent genetic analysis confirmed diagnosis of X-linked agammaglobulinemia. Despite their immunodeficiency, the pneumonia was uncomplicated in both patients and did not call for immunological evaluation. However, the immunoglobulin screening at admission allowed for an early diagnosis of the immunodeficiency and timely initiation of immunoglobulin substitution, the key prerequisite for a favorable course of the disease.Simple and inexpensive immuno-globulin measurement during the manage-ment of hospitalized children with community-acquired pneumonia may help in early identification of patients with compromised humoral immunity and prevent serious complications.

Perinatal cytomegalovirus hepatitis: to treat or not to treat with ganciclovir.

OBJECTIVE: The use on ganciclovir for perinatal cytomegalovirus (CMV) infection is controversial. We aim to evaluate the use of ganciclovir treatment for neonatal CMV hepatitis. METHODS: We present five infants with perinatally-acquired CMV hepatitis as a single organ manifestation of CMV infection. The three more severely affected children, i.e. those with cholestasis and elevation of serum hepatic enzymes to more than twice the normal values, were treated for 15 days with intravenous ganciclovir. RESULTS: The three treated infants improved clinically and CMV DNA in the blood disappeared during treatment. After cessation of ganciclovir treatment all of the patients had a relapse of the infection. The two untreated patients recovered completely. CONCLUSION: The long-term outcome of infants with CMV hepatitis is unpredictable. Some patients have persistent liver injury despite ganciclovir therapy. Ganciclovir therapy did not prevent chronic liver disease in any of the patients in our study. Owing to the possible serious side-effects the cost-benefit of ganciclovir treatment should be carefully evaluated.

The early postnatal development of salivary antibody and immunoglobulin response in children orally colonized with a nonpathogenic, probiotic strain of E. coli.

The development of levels of secretory immunoglobulins (SIgs) in newborns' saliva was examined under physiological conditions and after artificial colonization with nonpathogenic, probiotic bacterial strain E. coli O83. Higher levels of secretory immunoglobulin M (SIgM) and secretory immunoglobulin A (SIgA) were detected in the saliva of breast-fed children when compared with those of bottle-fed infants. SIgM was found earlier than SIgA, the levels of both SIgM and SIgA decreased after weaning. Breastfeeding actively stimulates local immunity on mucosal membranes of newborn infants. Early mucosal colonization with nonpathogenic E. coli bacteria stimulates the mucosal immune system to produce specific antibodies as well as nonspecific secretory immunoglobulins.

Mucosal immunity--basic principles, ontogeny, cystic fibrosis and mucosal vaccination.

The mucosal immune system is an integral part of the whole-body immune system, however its regulation, maturation and function are to a great degree independent. Mucosal lymphoid tissue is the largest immune organ of the body, that stands in the first line of defence against foreign invaders. The goal of the immune system is immunity, however immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, because the organism must tolerate thousands of ingested and inhaled harmless food and bacterial antigens. The phenomenon of oral tolerance is the unique feature of the mucosal immune system. If abrogated, severe autoimmune diseases like Crohn's disease, ulcerative colitis or coeliac sprue can develop. The quality of mucosal immune responses during newborn and infant age strongly influences the immune reactivity later in life. The most important factors influencing the development of mucosal immune reactivity are the feeding practices and microbial colonization. Manipulation of the mucosal immune system offers interesting possibilities to prevent infection as well as autoimmune diseases directly in the affected tissue, without participation of the whole-body immune system. In this review we present the most recent basic information about the mechanisms of mucosal immunity, ontogeny of mucosal immunity, mucosal tolerance and immunisation and the role of mucosal immunity in an inherited disease in which the main battlefield is the lung mucosa-cystic fibrosis.

The serologic screening for celiac disease in the general population (blood donors) and in some high-risk groups of adults (patients with autoimmune diseases, osteoporosis and infertility) in the Czech republic.

The prevalence of celiac disease (CD) was determined in healthy blood donors and in high-risk groups of adults (a total of 1835 adults--randomly selected 1312 healthy blood donors, 102 patients with primary osteoporosis, 58 patients with autoimmune diseases and 365 infertile women). It was calculated on the basis of a two-step serologic screening method--in the first step IgA and IgG antigliadin antibodies (AGA) and IgA anti-gamma-glutamyltransferase ('transglutaminase') antibodies (ATG) were estimated, in the second step sera positive for IgA AGA and/or IgA ATG were examined for antiendomysial IgA (AEA) antibodies. Immunoenzymic assay (ELISA) was used for determining of AGA and ATG antibodies; immunofluorescence method, performed on human umbilical cord tissue, was used for assaying of AEA antibodies. Total serum IgA level in only IgG AGA positive subjects was measured by routine turbidimetric method. 0.45% of healthy blood donors, 0.98% of osteoporotic patients, 2.7% of patients suffering from autoimmune disease and 1.13% of women with infertility considered as immunologically mediated were found to be positive in both steps of serologic screening (AGA and/or ATG and antiendomysium positive). The presumed high prevalence of seropositivity for CD in apparently healthy Czech adult population was confirmed. In the high-risk groups, the prevalence of seropositivity for CD was approximately 2-4 times higher than in healthy blood donors. The real prevalence of CD in the tested groups, however, can be estimated after performing small intestinal biopsy in the seropositive patients.

Cytomegalovirus infection in immunocompetent and immunocompromised individuals--a review.

This review summarizes the state-of-the-art knowledge on diagnosis, pathogenesis, immune response to, clinical picture, treatment and prevention of cytomegalovirus (CMV) infection in humans. CMVs are ubiquitous betaherpesviruses that infect animals as well as humans. Primary infection with human cytomegalovirus (HCMV) is followed by persistence of the virus in a latent form. During life, the virus can reactivate, resulting in renewed shedding of the virus or development of disease. Redundant molecular mechanisms have been identified by which CMVs interfere with the host immune control, but finally, the infection is held in check by the host's immune response. As a consequence, CMV disease is restricted to the immunocompromised or immunologically immature host. HCMV is the leading cause of congenital infections, with an incidence of 1-2.4% of live births, with possible severe classic "cytomegalovirus inclusion disease" in 10% of them. Congenital CMV infection is the leading infectious cause of brain damage and hearing loss in children and also a relevant health issue to transplant recipients and human immunodeficiency virus (HIV)-infected patients. Significant progress has been made in the last few years in detecting CMV, but in the immunocompromised patients, establishing the diagnosis of CMV infection can still be problematic. The most sensitive molecular amplification methods such as polymerase chain reaction (PCR) should be used. The decision how to treat the infection depends mainly on the immune status of the host. In immunocompetent patients only symptomatic treatment is recommended, while in immunocompromised patients antiviral therapy and immunotherapy should be used. The most commonly used antivirotics are: ganciclovir, foscarnet, cidofovir, valganciclovir, valaciclovir.

Principles of the photodynamic therapy and its impact on the immune system.

Photodynamic therapy (PDT) is an encouraging procedure for treatment and diagnosis of a wide variety of malignant processes. There are three main mechanisms by which tumors are destroyed during PDT: direct cell destruction, damage to the vascular stroma and immune elimination. PDT of high intensity, targeted to a large number of cells results in immunosuppression. Low dose/energy or localized PDT stimulates the immune response against the tumor. The review reports recently performed animal experimental studies as well as the first human clinical studies.

Characterization of human, mouse and rabbit anti-gliadin antibodies by ELISA and western blotting.

Monoclonal, hyperimmune rabbit and human serum anti-gliadin antibodies were analyzed by ELISA and immunoblotting techniques. In Western blotting the difference in reactivity between monoclonal and human antibodies was quantitative rather than qualitative. Rabbit antisera differed in reactivity according to the protein used for immunization. The rabbits immunized by the peptic-tryptic pancreatic digest of gliadin reacted similarly to the patients. In ELISA, significantly higher reactivity with crude, A-, glyc-gli, alpha-, beta- and omega-gliadins was found in the patients' sera than in controls.

Class IgG, IgM and IgA antibodies against Staphylococcus aureus antigens in human serum and saliva.

Using the ELISA method antibodies against the sonicate, teichoic acid (TA) and exoproducts of Staphylococcus aureus were determined in sera and saliva of healthy individuals. Main serum antibodies against all the antigens used were shown to be class IgG antibodies. However, antigens of the sonicate stimulated significantly even the systemic IgA response. In the saliva class IgA antibodies predominated, but IgG antibody levels against TA and exoproducts approached the level of IgA antibodies. Levels of IgM antibodies against all antigens tested were low in both the serum and saliva which corresponds with the anamnestic type of response. On the basis of these results one may assume that not only IgG, but also IgA antibodies are important in the systemic immunity against staphylococcal infection and in the immunity of mucous membranes; besides IgA, even class IgG antibodies play an important role.