Gastric perforation due to mucormycosis after heart-lung and heart transplantation.

BACKGROUND: Gastrointestinal complications are a well-documented source of morbidity and mortality after heart and lung transplantation. METHODS: We report on two patients who presented with gastric perforation caused by mucormycosis during the first 2 months after heart-lung and heart transplantation. RESULTS: In the first patient, the clinical presentation was insidious and the diagnosis was made at an advanced stage of the disease. Despite surgery and aggressive antifungal treatment, the patient died. In the second patient, the diagnosis was made promptly, but despite antifungal treatment, he presented with gastric perforation within a week. CONCLUSIONS: These cases illustrate that fungal invasive disease may be a cause of early gastrointestinal perforation after solid organ transplantation.

A fatal case of Mycoplasma hominis meningoencephalitis in a full-term newborn.

We report the case of a 20-day-old full-term baby, born to a mother who had had an uncomplicated pregnancy and delivery, who died 13 days after the onset of meningitis. Mycoplasma hominis was the sole agent repeatedly recovered from cerebrospinal fluid and from postmortem brain tissue.

Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate cells To produce pro- and anti-inflammatory cytokines.

The possibility of maternal in utero modulation of the innate and/or adaptive immune responses of uninfected newborns from Trypanosoma cruzi-infected mothers was investigated by studying the capacity of their whole blood cells to produce cytokines in response to T. cruzi lysate or lipopolysaccharide-plus-phytohemagglutinin (LPS-PHA) stimulation. Cells of such newborns occasionally released gamma interferon (IFN-gamma) and no interleukin-2 (IL-2) and IL-4 upon specific stimulation, while their mothers responded by the production of IFN-gamma, IL-2, and IL-4. Infection in mothers was also associated with a hyperactivation of maternal cells and also, strikingly, of cells of their uninfected neonates, since their release of proinflammatory (IL-1beta, IL-6, and tumor necrosis factor alpha [TNF-alpha]) as well as of anti-inflammatory (IL-10 and soluble TNF receptor) cytokines or factors was upregulated in the presence of LPS-PHA and/or parasite lysate. These results show that T. cruzi infection in mothers induces profound perturbations in the cytokine response of their uninfected neonates. Such maternal influence on neonatal innate immunity might contribute to limit the occurrence and severity of congenital infection.

Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria.

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.

B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10.

We analyzed the effects of rIL-10 on IL-5 production by human resting T cells isolated from peripheral blood. Resting T cells of healthy individuals required activation for 48 h with either anti-CD3 mAb cross-linked on B7/CD32-transfected mouse fibroblasts or PMA in conjunction with anti-CD28 mAb for optimal IL-5 secretion. In each condition, IL-5 secretion measured by ELISA was inhibited in a dose-dependent manner by rIL-10, whereas IFN-gamma production was not suppressed. The inhibitory effect of rIL-10 on IL-5 synthesis induced by PMA and anti-CD28 mAb was also observed at the mRNA level. In contrast with its action on T cells costimulated by B7/CD28 signaling, rIL-10 did not block IL-5 secretion in response to PMA and A23187 calcium ionophore. The inhibition of IL-5 production by rIL-10 was not due to IL-2 deprivation because it was not modified by the addition of exogenous rIL-2. Moreover, cyclosporin A, which inhibited IL-2 more efficiently than rIL-10 in response to anti-CD3 mAb and B7/CD32 transfected fibroblasts, did not reduce and even enhanced IL-5 production. Finally, we analyzed the influence of endogenously produced IL-10 on IL-5 secretion by T cells stimulated by PMA and anti-CD28 mAb. Addition of a neutralizing anti-IL-10 mAb increased IL-5 release in this system, indicating that endogenous IL-10 controls IL-5 production. We conclude that both rIL-10 and endogenous IL-10 inhibit IL-5 production by T cells costimulated by B7/CD28 signaling.

Tratamiento integral de la enfermedad de Chagas congenita: la experiencia boliviana / Integral treatment of congenital Chagas disease: the Bolivian experience

We have analyzed the response to the treatment with benznidazol in newborns and nurslings in the Hospital Materno Infantil Germán Urquidi of Cochabamba, Bolivia, between 1999 and 2002. It is important an integral treatment of the nursling with a subsequent information directed to the family. The response was close to 100% when the treatment was correctly administrated. They were not adverse effects and the detected biochemical alterations did not present clinical significance.

Estatus inmunológico de las madres infectadas por T. cruzi / Immunological status of mothers infected with Trypanosoma cruzi

The mechanisms of congenital transmission of Chagas disease remain largely unknown. To better understand the role of maternal immunology during pregnancy in congenital Chagas transmission, we studied the cytokine production and the parasitic load in three groups of mothers: infected mothers who transmitted the disease to their babies (M+B+-), infected mothers who did not transmit the disease to their babies (M+B-) and not infected mothers as a control group (M-B-). M+B+ mothers produced less IFNgamma and more IL-10 than the M+B- mothers, and they are not able to produce IL-2. M+B+ mothers showed a higher parasitic load. These results, indicated that the congenital Chagas transmission is associated with an immunological imbalance and a high parasitic load in the M+B+ mothers.

Respuesta inmune en neonatos no infectados nacidos de madres infectadas por Trypanosoma cruzi / Immune responses of non-infected neonates of mothers infected with Trypanosoma cruzi

We have investigated if maternal T. cruzi infection could induce in utero innate and/or adaptive immune responses in uninfected neonates by measuring specific IgM and IgA antibodies in cord blood plasma, and by performing phenotypic and functional studies of umbilical cord blood cells of their newborns (M+B- group). We detected T. cruzi-specific IgM and IgA antibodies in M+B- cord blood, indicating they had mounted in utero a strong B cell response, although they are not infected. On the other hand, circulating T cells of such uninfected neonates displayed a low level of activation, as seen bya slightly increased expression of the activation markers CD45RO on CD4+ T cells and HLA-DR on CD8+ T cells, although the proportion of CD4+ and CD8+ T cells was unmodified as compared to newborns from uninfected mothers (MB- group). This activation did not give rise to a proliferative response upon stimulation by T. cruzi antigens in vitro. However, M+B- cells produced low levels of lymphokines (IFN-gamma and IL-13) upon mitogenic stimulation, which was not the case of M-B- newborn cells. Beside this, M+B- blood cells produced higher levels of inflammatory cytokines (IL-1b, IL-6, TNF-alpha) than M-B- cells when stimulated with the T. cruzi lysate or LPS, suggesting the over-activation of the innate response in M+B- newborns. Monocytes participated in such inflammatory response since M+B- purified cord blood monocytes produced higher levels of TNF- when incubated with LPS or a T. cruzi lysate than M-B- cells. Altogether, these results show that, even in the absence of congenital infection, maternal T. cruzi infection triggers in utero both adaptive and innate immune responses in their babies. This indicates that parasite circulating antigens have been transferred from mothers to their fetuses.

Detección de la heterogeneidad molecular de Trypanosoma cruzi / Detection of molecular heterogeneity of Trypanosoma cruzi

Congenital transmission of T. cruzi in Cochabamba affects 6% of newborns from infected mothers. Only limited information is available on the type of transmitted parasites. However, it is well established that T. cruzi isolated from various vectors as well from host animals are highly heterogeneous. In our presentation we analyse aspects of molecular heterogeneity of T. cruzi and we review methods used for the molecular typing of T. cruzi lineages. Experimentally, we performed the PCR amplification of [quot ]Sequence-characterised region Markers[quot ] for typing T. cruzi isolated from umbilical blood of newborns in Cochabamba. We compared these results with those we obtained from general infected population. All 16 analysed, congenitally infected samples were of lineage IId. Our data also indicated that this lineage was found in about 80% of samples originated from general infected population in Cochabamba.

Comparación de métodos de PCR para el diagnóstico de la infección congenita por Trypanosoma cruzi / Comparison of PCR methods for the diagnosis of congenital Trypanosoma cruzi infection

PCR is a potentially interesting diagnostic tool to detect congenital T. cruzi infection. We have compared the sensitivity and capacity of a battery of T. cruzi PCR primers to detect the complete spectrum of known T. cruzi lineages, in order to improve and simplify the detection of infection in neonatal blood. We found that the primers Tcz1/Tcz2, targeting the 195 bp satellite repeat, detected all the parasitic lineages with the same sensitivity For all other tested primers (nDNA primers: BP1/BP2, 01/02, Pon1/ Pon2 and Tca1/Tca2; kDNA primers: S35VS36, 121/122), either, the intensity of amplicons varied according to T. cruzi lineages, or the assess were less sensitive. In order to better assess such PCR protocol, we assayed 311 samples of neonatal blood previously tested with parasitological methods. Reliability of our PCR test was demonstrated since all the 18 blood samples from newborns with congenital T. cruzi infection were positive, whereas the remaining samples (30 from control newborns of uninfected mothers and 262 out of 263 from babies, parasitologically negative, born from infected mothers) were negative. As our PCR method is simple, reliable, robust and cheap, it appears suitable for the detection of T. cruzi infection in neonatal blood.

Dosificación de anticuerpos IgM e IgA anti-trypanosoma cruzi en sangre de recién nacidos de madres con serología positiva para Chagas / Serum levels for IgM and IgA antibodies to anti-trypanosoma cruzi in samples of blood from newborns from mothers with positive serology for Chagas disease

This study compares the levels of specific antibodies IgM and IgA for Chagas in samples of blood from newborns. Three groups of cord blood samples have been analysed: a group of 42 samples from newborns, displaying positive parasitemia, of seropositive mothers (M+B+), 68 samples from newborns with negative parasitemia whose mothers were seropositive (M+B-) and a group of 45 control newborns coming from mothers with negative serology for Chagas. From the 42 M+B+ samples with congenital Chagas disease, 81 and 82.9% displayed detectable levels of IgM and IgA antibodies, respectively In the M+B- group, 70.6 and 33.8% presented antibodies of IgM and IgA classes, respectively, whereas in the control group M-B-, we detected 6% and 11.1% of IgM and IgA antibodies, respectively. The calculated sensitivity of detection of congenital cases using IgM or IgA antibodies was of 82.9% and 80.9% respectively, whereas the specificity of detection was of 29.4% for IgM antibodies and of 66.1% for IgA antibodies.

Las lesiones placentarias en la infección humana por Trypanosoma cruzi / Placental lesions in human Trypanosoma cruzi infection

This histopathological study analyzes placentas of babies congenitally infected with T. cruzi (M+B+), or babies not infected but born from infected- (M+B-), or non infected-mothers (M-B-). Placentas M+B+ showed lesions of chorionitis, chorioamnionitis and cord edema with lymphocyte infiltration, whereas such lesions were infiltrated only with polymorphonuclear cells in M+B- and M-B- placentas. Parasites were found in M+B+ placentas, in fibroblasts and macrophages of chorion, membranes, chorionic plate, mainly in the area of membrane insertion, as well as in cells of Wharton jelly and myocytes of umbilical cord vessels. These results suggest that the materno-fetal transmission of parasites occurs mainly through the marginal sinus, spreading into the chorionic plate infecting fibroblasts and macrophages so far as to found a fetal vessel, inducing a fetal infection by hematogenous route.

Nivel de endemia de la infección por Trypanosoma cruzi en el lugar de residencia de la madre y desarrollo de la enfermedad de Chagas congénita en Bolivia / Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia

In Bolivia, the prevalence of infection by T. cruzi in women in fertile age can vary between 20 and 60%. The present study made in the Maternity Germin Urquidi of Cochabamba - Bolivia, it has demonstrated, that 19.9% of the mothers who go to this hospitable center to be taken care of in the childbirth, they are carrying of the infection and that 4,6% of them, they are going to transmit, by transplacentaria route, the infection to its babies. Of the 71 children born with congenital Chagas, only 47,8 % present/display some type of alteration or of development(Apgar to 1 minute low, BPN, prematuridad, pathological dismadurez) or signs (SDR, hepatomegalia, esplenomegalia, neurological signs, cardiomegalia, anasarca, petequias). When investigating the effect of the differences in the vectorial density (low, medium and high) of the zone of maternal residence, on the transmission of the infection of the mother infected to the fetus, we concluded that the rate of transmission of the congenital infection of T. cruzi is not modified by the level of endemicidad of the zone of maternal residence. By another infected new born sides whose mothers reside in zones of high endemicidad present/display, most frequently and of significant way, Apgar to 1 minute < to 7, low weight when being born and prematuridad or an association of these alterations with respiratory syndrome of distress or anasarca, when one compares them with new born of resident mothers in the zones of loss or medium endemicidad, mortality in this group is greater. These results suggest calls to account it of the mothers, in areas of high endemicidad, she is associate with a serious increase in the risk of Disease of newborn severe and mortal congenital Chagas in.