Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America.

Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.

Advancing the management of primary immunodeficiency diseases in Latin America: Latin American Society for Immunodeficiencies (LASID) Initiatives.

Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy.

Primary immunodeficiency diseases in Latin America: proceedings of the Second Latin American Society for Immunodeficiencies (LASID) Advisory Board.

Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an ongoing effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities throughout Latin America. These programmes are: an educational outreach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes.

Bacteriophages induced from lysogenic root canal isolates of Enterococcus faecalis.

INTRODUCTION: Bacterial viruses play crucial roles in the pathogenesis of many systemic diseases. They are known to inhabit the oral cavity, both as free virions and as prophages in lysogenic bacterial strains; however, there has been no report of bacteriophages in endodontic infections. In this study, we sought to detect, isolate, and describe temperate bacteriophages harbored by Enterococcus faecalis strains isolated from endodontic infections. METHODS: Ten E. faecalis strains were isolated from root canals of teeth undergoing retreatment following unsuccessful endodontic therapy. Mitomycin C was used to induce any prophages present in the bacterial isolates. The induced phages were purified and examined using electron microscopy. The DNA extracted from one of the phage isolates was subjected to restriction endonuclease digestion and agarose electrophoresis analysis. RESULTS: Lysogeny was demonstrated in 4 of the 10 E. faecalis strains. Three of the lysogenic strains yielded phages exhibiting a Siphoviridae morphology, with long, non-contractile tails 130 nm in length, and spherical/icosahedral heads 41 nm in diameter. The virus induced from the fourth lysogenic E. faecalis strain had a contractile tail characteristic of Myoviridae. Restriction endonuclease analysis of NsiI and NdeI DNA fragments from one of the Siphoviridae phage isolates (phage phiEf11) indicated a genome size of approximately 41 kbp. CONCLUSION: This is the first report of lysogenic bacteria and their inducible viruses in infected root canals.

ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload.

We set out to identify molecular mechanisms underlying the onset of necrotic Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca(2+) chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca(2+) was reduced by 60%, thus discarding a role for Ca(2+) channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca(2+) ATPase (PMCA). Remarkably, inhibition of the Na(+)/K(+) ATPase rescued the PMCA and reverted the Ca(2+) rise. Thermodynamic considerations suggest that the Ca(2+) overload develops when the Na(+)/K(+) ATPase, by virtue of the Na(+) overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca(2+) overload, the crosstalk between cation pumps offers a novel explanation for the role of Na(+) in cell death.

Cytosolic [Ca(2+)] modulates basal GLUT1 activity and plays a permissive role in its activation by metabolic stress and insulin in rat epithelial cells.

The aim of this work was to investigate the role of cytosolic free calcium ([Ca(2+)]c) in the stimulation of GLUT1 by metabolic stress and insulin. Chelation of [Ca(2+)]c with bapta, introduced in rat liver epithelial Clone 9 cells in the acetoxymethyl (AM) form, decreased their basal rate of 2-deoxyglucose uptake in a dose-dependent fashion. Maximal inhibition at 75 microM bapta was by 38 +/- 8% (n = 8). The effect was partially reversed by ionomycin. Basal sugar uptake was also decreased by lowering extracellular [Ca(2+)] in ionomycin-permeabilized cells. Increasing [Ca(2+)]c over its resting level of 168 +/- 32 (n = 27) had no affect on sugar uptake. Chelation of [Ca(2+)]c did not change the abundance of surface GLUT1 and had no significant effect on the affinity of GLUT1 for sugars. In addition, calcium chelation abolished the activation of GLUT1 by azide, arsenate, 2,4-dinitrophenol and insulin. However, [Ca(2+)]c did not increase in the presence of azide. We conclude that [Ca(2+)]c, near or below its resting level, modulates GLUT1 activity over a considerable range and plays a permissive role in the activation of the carrier by metabolic stress and insulin.

Protective factors in milk and the development of the immune system.

The neonate is immature in certain immunologic functions. The slow development of secretory immunoglobin A (IgA) seems to be compensated by selective transfer of secretory IgM into exocrine secretions on mucous membranes during the first few months of life. Secretory IgA and secretory IgM antibodies against Escherichia coli and poliovirus are already found in the neonate, possibly in response to the maternal anti-idiotypic IgG antibodies transplacentally exposing the fetus. Via such a mechanism, food antibodies could occur before direct food exposure in the infant. Human milk provides large amounts of antibodies (as a crude comparison, about 50 times the amount of antibodies given to a patient with hypogammaglobulinemia). The milk antibodies, dominated by secretory IgA, protect especially against intestinal infections. The milk also contains oligosaccharide analogues to epithelial receptors for bacteria. They, as well as a number of milk components such as lactoferrin and lysozyme, may contribute to host defense. The food antibodies in human milk may influence the infant's immune response to foreign food proteins introduced during weaning.

Lack of correlation of in vitro adherence of Haemophilus influenzae to epithelial cells with frequent occurrence of otitis media.

The adherence to human epithelial cells, biotype and capsular type of 175 Haemophilus influenzae cultured from the upper respiratory tract were studied in a prospective study of children with recurrent otitis media. Forty-three children who had greater than 2 episodes of acute otitis media (AOM) during the first year of life were followed for at least 1 year. Cultures of the oropharynx were done periodically, and the middle ear fluid (MEF) was cultured at the time of AOM. H. influenzae was recovered from MEF in 44% of the 136 AOM episodes recorded. Thirty-one children had at least one episode of AOM caused by H. influenzae; the remaining 12 children, designated as "controls," had no otitis or had AOM caused by other organisms. The possible differences between carriage and infection strains were evaluated by comparison of MEF and oropharyngeal isolates, by pairwise comparison of MEF and oropharyngeal isolates and by pairwise comparison of multiple isolates from each host recovered at the time of AOM and during infection-free intervals. No significant differences in patterns of adherence, capsular type or biotype were found. The lack of correlation between these characteristics and infection suggests either that H. influenzae organisms have determinants of virulence yet to be defined or that variations in host susceptibility permit infection by the strain colonizing the upper respiratory tract. Adherence per se may be less important in the development of infection than in establishing and maintaining colonization within the host.

Juvenile chronic arthritis in Costa Rica. A pilot referral study.

In order to adequately care for patients with chronic disorders and to properly allocate resources, the epidemiology of the underlying disease must be know. Proper population based studies involve substantial planning and educational programs, however. To prepare for such a study of pediatric rheumatic disorders, we performed a referral-based pilot study. During an eleven-month period pediatricians all over Costa Rica were asked to refer to us all new cases of possible rheumatic disorders among children less than 16 years of age, using the EULAR criteria for juvenile chronic arthritis. The children were evaluated at the National Children's Hospital. An annual incidence of 5.9 cases of all types of pediatric rheumatic diseases per 100,000 was found. Incidences of 5.4 per 100,000 children below 16 years of age and 6.1 for children below 12 years of age were observed for juvenile chronic arthritis (JCA). 77% of the JCA cases were of pauciarticular onset, and 23% were of polyarticular onset. No cases of systemic JCA were diagnosed. The female to male ratio was 3:2. Antinuclear antibodies were positive in 13% of the JCA cases, and IgM rheumatoid factor was found in 15% of the children. Chronic iritis was noted in only 2 cases; both were girls and both were ANA positive. The incidence found was low compared to population-based studies, but in the same range as hospital-based investigations.

Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to an approximately 850 kb region on chromosome 11q23.1.

The genotyping data given localize the major A-T gene to an approximately 850 kb region. They also localize the group A A-T gene (ATA) to a region that contains the approximately 850 kb region. They are compatible with linking A-TFresno to 11q22-23. NBS-V2 does not link to this region. Four non-linking families contain only single affecteds, suggesting that these may be spontaneous mutations rather than evidence for an A-T gene outside the 11q22-23 region. Finally, two other non-linking families contain recombinant haplotypes that are compatible with a second A-T gene at 11q22-23, slightly distal to the approximately 850 kb region. However, convincing evidence for a second gene is still lacking.

[Tuberculosis associated with HIV infection]. / Tuberculosis asociada a infección por el virus VIH.

Tuberculosis and human immunodeficiency virus (HIV) infection are two important linked public health problems in the world of today. Tuberculosis in HIV infected patients is frequently atypical in its clinical and radiological findings and commonly has an extrapulmonary dissemination. Atypical mycobacteriosis have also been reported in patients with HIV infection. We review here all the patients admitted from 1986 to 1991 with definitive diagnosis of tuberculosis and HIV infection at the National Institute of Respiratory Diseases in Mexico City. Out of 220 patients with HIV infection and pulmonary complications, 19 had proven tuberculosis. Their mean age was 34 +/- 8 years and seven were homosexual males. In 16 patients (84%), respiratory symptoms (cough with sputum) and fever were the first manifestations of the HIV infection. Only two patients had the typical cavitary lesions but also coexisting with miliary tuberculosis. The rest had several types of non cavitated pulmonary opacities or other thoracic or pleural alterations. Eleven patients (58%) had, in addition, extrapulmonary tuberculosis. Mycobacterium tuberculosis was cultured in 11 of 12 patients but no atypical mycobacteria were isolated. Only seven of the 19 patients completed at least six months of treatment and two of them relapsed. Three patients died in their first admission; the rest were lost in the follow up. Our results show that the clinical features of tuberculosis associated to HIV infection are similar to those described in other countries.

Human malignant osteopetrosis: pathophysiology, management and the role of bone marrow transplantation.

Osteopetrosis is a heterogeneous group of diseases characterized by lack of osteoclast function. Osteopetrosis is found spontaneously in most mammalian species and many transgenic animals have been created, but so far no animal model has been found that genetically corresponds to human malignant autosomal recessive osteopetrosis. The only curative treatment for malignant osteopetrosis is bone marrow transplantation. A review of the literature and preliminary data from IBMTR shows that infants transplanted with marrow from an HLA-identical sibling or unrelated volunteer donor have an actuarian five-year survival with a functioning graft of 50-70%, while those transplanted with a T-cell-depleted mismatched marrow have a very poor survival of only about 10%.

Development of a Costa Rican version of the Childhood Health Assessment Questionnaire.

OBJECTIVE: To validate a Spanish language version of the Childhood Health Assessment Questionnaire (CHAQ) for use in Costa Rica and to evaluate the feasibility, reliability, and cross cultural equivalency of this version. METHODS: The original questionnaire, translated without modification into Spanish, was administered to 12 children, all above 10 years of age, with the diagnosis of juvenile chronic arthritis (JCA) and to their parents. There were several problems in comprehension, and self-administration with this version was not possible. For this reason a teacher and a psychologist were consulted to create a modified Costa Rican version. We administered this 2nd version to 46 children with JCA and 62 of their parents. RESULTS: The modified Costa Rican HAQ (CR-CHAQ) was self-administered by 93.5% of the patients and 84% of the parents. The median time to complete the questionnaire was 12 min for the children, 10 min for the parents. The main difficulty in comprehension was the pain score for both groups. Test-retest (Spearman R = 0.73) and interobserver (Spearman R = 0.70) reliability were good. Validity of the instrument was confirmed by the high correlation between the disability and discomfort scores and conventional clinical variables. There was satisfactory correlation between the disability score and conventional clinical variables. Discriminant validity was confirmed by the capacity of the CR-CHAQ to evaluate patients as being in different categories of disease activity. CONCLUSION: After modifications, the CR-CHAQ achieved cross cultural equivalency.

Juvenile chronic arthritis in urban San José, Costa Rica: a 2 year prospective study.

OBJECTIVE: To find the incidence and prevalence of juvenile chronic arthritis (JCA) in the urban area of San José, Costa Rica. METHODS: During the year preceding our 2 year prospective, population based study, we conducted an educational program on JCA. The physicians caring for children < 16 years of age from all centers in the study area followed the program. They were asked to refer all cases of possible JCA according to EULAR criteria. The children were all evaluated at the National Children's Hospital. RESULTS: Of 189 children referred, 48 fulfilled EULAR criteria for JCA. The 2 year incidence rate for JCA was 13.7 per 100,000 children < 16 years old. This corresponds to an annual incidence per 100,000 children of 6.8 (95% CI 4.1-9.6). The incidence rate for pauciarticular onset JCA was 3.9 per 100,000. At the prevalence date, 122 cases of JCA were recorded, corresponding to a prevalence of 34.9 per 100,000 children < 16 years. When patients in remission were excluded, the prevalence was 31.4 per 100,000 (95% CI 25.5-37.2). The pauciarticular onset form was the most common, 71% of all prevalence cases. The highest incidence and prevalence were noted for pauciarticular girls with late onset JCA. No incidence peak was found in preschool age. The girl-to-boy ratio was 1.5/1. Antinuclear antibodies (ANA) were positive in only 7 cases (6.3%). IgM rheumatoid factor was found in 13 children (10.6%). Chronic iritis was observed in 4 cases, all of them ANA negative and older than 7 years of age at onset of arthritis. CONCLUSION: The incidence and prevalence observed were lower than those reported in other population based studies, but within the confidence intervals of their data. The incidence rate for pauciarticular JCA was significantly lower than that reported in other comparable studies. ANA positive pauciarticular preschool girls and associated uveitis were rarely encountered.

Serum antibody response to polysaccharides in children with recurrent respiratory tract infections.

We evaluated children (15-months old and older) with recurrent upper respiratory tract infections and normal levels of immunoglobulins in serum for specific polysaccharide immunodeficiency using an enzyme-linked immunosorbent assay method. Results showed that of 12 patients vaccinated with Act-HIB vaccine, one did not develop specific antibodies to Haemophilus influenzae type b, demonstrating that such immunodeficiency is present in Costa Rican children.

Inhibition of attachment of Streptococcus pneumoniae and Haemophilus influenzae by human milk and receptor oligosaccharides.

Human milk inhibited the attachment of Streptococcus pneumoniae and Haemophilus influenzae to human pharyngeal or buccal epithelial cells. Infant formulas and cow and buffalo milk showed a lower inhibitory activity against pneumococci and enhanced the adhesion of H. influenzae. The antiadhesive effect against S. pneumoniae was found in both the high- and the low-molecular-weight fractions of milk. The inhibitory activity in the high-molecular-weight fraction was independent of specific antibody content; it was present after immunoadsorption and in the milk from IgA-deficient women. The inhibitory activity in the low-molecular-weight fraction was in part explained by the content of oligosaccharides corresponding to the carbohydrate moieties of the neolactoseries of glycolipids, which have previously been shown to act as receptors for attaching pneumococci. The antiadhesive activity against H. influenzae was restricted to the high-molecular-weight fraction of the milk and was unaffected by immunoadsorption. Milk may protect against otitis by reducing colonization.

Application of multilocus enzyme gel electrophoresis to Haemophilus influenzae.

Multilocus enzyme electrophoresis was adapted to the study of Haemophilus influenzae. Protein extracts from sonicated whole bacteria were subjected to starch gel electrophoresis. After staining with substrates, the position of each isoenzyme (electromorph) was registered. Each isolate was assigned an electrophoretic type (ET) by the combination of electromorphs for the enzymes stained. Twenty-seven enzymes were tested; 12 were expressed in H. influenzae. Six enzymes were selected for subsequent study: malate dehydrogenase (MDH), phenylalanylleucine peptidase (PE2), 6-phosphogluconate dehydrogenase (6PG), adenylate kinase (AK), glucose 6-phosphate dehydrogenase (G6P), and phosphoglucose isomerase (PGI). They were polymorphic and occurred in all isolates. Six electromorphs were found for PE2, G6P, and PGI, five for MDH, four for 6PG, and three for AK. PE2, G6P, and PGI contributed most of the ET resolution (48 of 49 ETs). Multilocus enzyme electrophoresis showed several advantages over previous typing techniques. An ET could be assigned to both typable and nontypable (NT) isolates. The technique was powerful in resolving differences among isolates. The 94 isolates comprised 49 ETs, five biotypes, and six capsular types and NT isolates. Strains known to be related expressed the same ET, e.g., RAB b+ and b-, ET12; Ma a+ and a-, ET1. ET variability among type b isolates was low; 26 of 28 clinical isolates expressed ET14; 2 of 28 expressed ET13 and ET15, differing from ET14 by one electromorph each. In contrast, the 47 NT isolates comprised 38 different ETs. No ETs were shared between non-type b capsulated strains and type b or NT strains. Interestingly, five NT isolates expressed the same ET as type b strains. (iv) Strains of the same capsular type but different biotypes expressed different ETs. ET determinations will thus be useful in studying the epidemiology and evolution of H. influenzae.

Food and immunological development.

The infant's host defence is deficient in IgA for mucosal protection and also in IgG2 for protection against encapsulated bacteria. The baby is provided with about one gram a day of milk secretory IgA antibodies against most intestinal microorganisms and also food proteins. These milk antibodies together with a number of other defence factors in the milk protect the baby against gastrointestinal and respiratory infections. Maternal undernutrition does not necessarily diminish the milk IgA concentration or 24 hour output. The infant seems to be low in secretory IgA antibodies for several months as studied in saliva. It is of great importance to protect mucosal membranes especially the intestinal mucosa, so that its nutrient uptake is not disturbed. Infections in infancy especially in the gastrointestinal tract is an important cause of undernutrition. The human milk antibodies against cow's milk and soy protein may decrease the exposure to these food proteins during weaning and possibly decrease the risk of developing allergy. Soy oil can contain soy protein, which may explain some food intolerance reactions.

Visceral leishmaniasis in Costa Rica: first case report.

We describe a 15-month-old eutrophic immunocompetent male who presented with fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Leishmania amastigotes were identified in spleen and bone marrow specimens. In addition, tissue culture, animal inoculation, and isoenzyme analysis identified the parasite as Leishmania donovani infantum or Leishmania donovani chagasi. The infant was successfully treated with an antimonial drug. These findings represent the first case of visceral leishmaniasis reported in Costa Rica.