Immunological features in pediatric patients with recurrent and severe infection: Identification of Primary Immunodeficiency Diseases in Merida, Venezuela.

INTRODUCTION AND OBJECTIVES: Primary immunodeficiency diseases (PIDs) are disorders associated mainly with recurrent and severe infection and an increase in susceptibility to autoimmune conditions and cancer. In Venezuela, PIDs are underdiagnosed and there is usually a delay in their diagnosis. Hence there are no data concerning the frequency and type of PIDs that occur. The aim of this study was to identify and quantify the types of PIDs that occur in Merida, a population within Venezuela. PATIENTS OR MATERIALS AND METHODS: Following an informative program designed to alert local health professionals to the warning signs for PIDs, patients with a history of recurrent infections were referred to the Instituto de Inmunologia Clinica, Universidad de Los Andes. RESULTS AND CONCLUSIONS: During the three-year period January 2014 to January 2017, thirty-two cases of PIDs were identified in pediatric patients, and 17 different types of PIDs, were identified. Predominantly antibody deficiencies were most frequent (40.6%), followed by immunodeficiencies affecting cellular and humoral immunity (21.8%), congenital defects of phagocyte (18.7%), CID with associated or syndromic features (9.3%), defects in intrinsic and innate immunity (6.4%) and diseases of immune dysregulation (3.2%). These results have important implications not only to the future approach for management of patients in our regions, but add important knowledge concerning PIDs in Latin America and worldwide.

T-cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that can infect almost all warm-blooded species and induce a chronic infection in human hosts. The aim of this work was to investigate Th1, Th2, Th17 and Treg polarization, induced by four important T. gondii antigens (SAG1, ROP1, GRA8 and MAG1) in acutely and chronically infected patients. For this purpose, SAG1, ROP1, GRA8 and MAG1 were expressed as recombinant proteins, purified, and used to evaluate the proinflammatory and regulatory immune response profiles in seropositive and seronegative individuals. Our results show that SAG1 and ROP1 elicited a proinflammatory profile (INF-γ, IL-12 and IL-17) in individuals in the acute phase, whereas MAG1 and GRA8 induced a regulatory pattern (Treg and TGF-ß) in chronically infected patients. These results reveal fundamental differences in T-cell polarization induced by T. gondii antigens, which could have important implications in the immunopathogenesis of the disease and in future proposals of therapeutic strategies.

Major salivary gland damage in allogeneic hematopoietic progenitor cell transplantation assessed by scintigraphic methods.

Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.

Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon.

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.

Infant mortality among subsequent siblings of infants who died of sudden infant death syndrome.

A specially designed method for measuring infant mortality among families with subsequent siblings of sudden infant death syndrome (SIDS) victims in the state of Washington, 1969 to 1984, yielded results similar to those from an earlier study in Norway. In both studies the SIDS rates among siblings were substantially lower than prior estimates. The rate of SIDS in siblings of infants who died of SIDS did not differ significantly from the SIDS rate among control infants matched for maternal age and birth order. Total infant mortality rates in the two groups were virtually identical. From the data at hand, it appears that earlier estimates of the risk of SIDS in siblings were inflated and that parents of SIDS victims can be counseled accordingly.

Prospective assessment of recurrence risk in sudden infant death syndrome siblings.

Knowledge of the likelihood of a repetition of sudden infant death syndrome within a sibship, particularly in the next sibling, is important to parents. Methodologic considerations with respect to the studies of recurrence risk already published indicate that the rates reported are overestimates. This suspicion is confirmed by our study based on 826,162 infants surviving the first week of life on file in the Medical Birth Registry of Norway. A total of 1062 (1.3 per 1,000) infants died of SIDS; five deaths occurred as the second case in a family. The recurrence risk for the nextborn sibling was 5.6 per 1000, and for all subsequent siblings 4.8 per 1000, which would seem encouragingly low from a counseling point of view.

Sudden infant death syndrome and hypertriiodothyroninemia: comparison of neonatal and postmortem measurements.

Serum triiodothyronine concentrations in victims of sudden infant death syndrome, when compared with those of both living and dead controls, were found to be elevated to a degree comparable to those found in a previous study. Thyroxine, thyroid-stimulating hormone, and thyroglobulin values were not elevated. Neonatal triiodothyronine and thyroxine values, determined on specimens collected within a few days of birth for most of the sudden infant death syndrome victims, did not differ significantly from those of comparable peers in their birth cohort. These results indicate that hypertriiodothyroninemia may serve as a useful postmortem diagnostic marker for the syndrome but not as a premortem predictor. Parenthetically, thyroid hormones appear to remain stable in either a frozen or dried state for up to two years.