The trajectories of CD4 T lymphocytes over time in patients who have defaulted on treatment for tuberculosis in a cohort of people living with HIV, Recife/PE.

BACKGROUND: The CD4 T lymphocyte count in people living with HIV (PLHIV) is a predictor for the progression of the disease (AIDS), survival and response to antiretroviral treatment (ART). A CD4 T lymphocyte count of less than 200 cells/mm3 is indicative of a greater risk for the onset of opportunistic diseases and death. Defaulting on treatment for tuberculosis (TB) may impact immune recovery in PLHIV who are taking ART. The aim of this study was to investigate an association of the CD4 lymphocyte with TB treatment Trajectory and with death. METHODS: A cohort of PLHIV over eighteen years of age and who were taking ART and who had defaulted on pulmonary TB treatment. Latent Class analysis was used to identify different trajectories of CD4 T lymphocyte counts over time. RESULTS: Latent class 1 (High CD4 trajectory) grouped individuals together who were characterized as maintaining a low probability (0 to 29%) of a CD4 count ≤ 200 cells/mm3over time, while latent class 2 (Low CD4 trajectory) grouped individuals together with a high probability (93% to 60%), and latent class 3 (Fluctuating CD4 trajectory), grouped individuals with a fluctuating probability (66% to 0%). The chance of defaulting on treatment earlier (≤ 90 days) was four times higher in latent class 2 (Low CD4 trajectory). Although there was no statistical significance, there was a higher frequency of deaths in this same latent class. CONCLUSION: Individuals with a high probability of a CD4 count ≤ 200 cells/ mm3 should be monitored in order to avoid treatment default and thereby prevent death. New studies should be conducted with a larger sample size and a longer follow-up time in PLHIV who initiated ART treatment early so as to support clinical decisions for a better understanding of immune behavior.

How do terrestrial wildlife communities respond to small-scale Acacia plantations embedded in harvested tropical forest?

To offset the declining timber supply by shifting towards more sustainable forestry practices, industrial tree plantations are expanding in tropical production forests. The conversion of natural forests to tree plantation is generally associated with loss of biodiversity and shifts towards more generalist and disturbance tolerant communities, but effects of mixed-landuse landscapes integrating natural and plantation forests remain little understood. Using camera traps, we surveyed the medium-to-large bodied terrestrial wildlife community across two mixed-landuse forest management areas in Sarawak, Malaysia Borneo which include areas dedicated to logging of natural forests and adjacent planted Acacia forests. We analyzed data from a 25-wildlife species community using a Bayesian community occupancy model to assess species richness and species-specific occurrence responses to Acacia plantations at a broad scale, and to remote-sensed local habitat conditions within the different forest landuse types. All species were estimated to occur in both landuse types, but species-level percent area occupied and predicted average local species richness were slightly higher in the natural forest management areas compared to licensed planted forest management areas. Similarly, occupancy-based species diversity profiles and defaunation indices for both a full community and only threatened and endemic species suggested the diversity and occurrence were slightly higher in the natural forest management areas. At the local scale, forest quality was the most prominent predictor of species occurrence. These associations with forest quality varied among species but were predominantly positive. Our results highlight the ability of a mixed-landuse landscape with small-scale Acacia plantations embedded in natural forests to retain terrestrial wildlife communities while providing an alternate source of timber. Nonetheless, there was a tendency towards reduced biodiversity in planted forests, which would likely be more pronounced in plantations that are larger or embedded in a less natural matrix.

The Coutinho index as a simple tool for screening patients with advanced forms of Schistosomiasis mansoni: a validation study.

BACKGROUND: Periportal fibrosis (PPF) is the major pathological consequence of Schistosoma mansoni infection. The Coutinho index-the alkaline phosphatase (ALP) to platelet ratio ([ALP/upper limit of normality {ULN}]/platelet count [106/L] x 100)-was validated. Validation consisted of modest laboratory tests to predict advanced PPF. METHODS: A total of 378 individuals from an endemic area of Brazil with a previous history of the disease and/or a positive parasitological examination were evaluated. We used ultrasound examination as the gold standard for classification of the PPF pattern and measured the biological markers of the index. RESULTS: Forty-one individuals (10.8%) without PPF, 291 (77%) with moderate PPF and 46 (12.2%) with advanced PPF, were identified. ALP and platelet count were used for the index. The cut-off point ≥0.228 predicted the presence of fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.56, sensitivity of 68.6% and specificity of 46.3%. There was an absence of PPF in 46.3% of individuals without fibrosis and the presence of PPF in 68.5% of cases with moderate and advanced ultrasound fibrosis. The identification of advanced fibrosis with a cut-off point ≥0.316 revealed an AUROC curve of 0.70, sensitivity of 67.4% and specificity of 68.3%, thus confirming the advanced phase in 65.2% of cases compared with ultrasound. CONCLUSION: The Coutinho index was able to predict advanced PPF in most individuals. It is valid as a new tool, uses routine laboratory tests and therefore is more accessible for screening patients with a severe form of the disease in endemic areas.

Assessment of a recombinant protein from Leishmania infantum as a novel tool for Visceral Leishmaniasis (VL) diagnosis in VL/HIV co-infection cases.

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.

Human leukocyte antigen-G 3' untranslated region polymorphism +3142G/C (rs1063320) and haplotypes are associated with manifestations of the American Tegumentary Leishmaniasis in a Northeastern Brazilian population.

While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.

Non-immune hydrops fetalis caused by herpes simplex virus type 2 in the setting of recurrent maternal infection.

We report a case of non-immune hydrops fetalis (NIHF) caused by herpes simplex virus type 2 (HSV-2) in an infant whose mother had recurrent HSV-2 infection. In spite of prematurity, severe disseminated infection and hydrops, the infant survived and was neurologically intact. HSV-2-induced NIHF is extremely rare, particularly in the setting of recurrent maternal infection, and this case is, to our knowledge, the first report of a surviving infant. HSV-2 should be considered in the differential diagnosis of NIHF and early initiation of empiric acyclovir therapy is recommended in this setting, pending the results of virologic diagnostic tests.

Is it better to be rich in a poor area or poor in a rich area? A multilevel analysis of a case-control study of social determinants of tuberculosis.

BACKGROUND: Tuberculosis is known to have socio-economic determinants at individual and at area levels, but it is not known whether they are independent, whether they interact and their relative contributions to the burden of tuberculosis. METHODS: A case-control study was conducted in Recife, Brazil, to investigate individual and area social determinants of tuberculosis, to explore the relationship between determinants at the two levels and to calculate their relative contribution to the burden of tuberculosis. It included 1452 cases of tuberculosis diagnosed by the tuberculosis services and 5808 controls selected at random from questionnaires completed for the demographic census. Exhaustive information on social factors was collected from cases, using the questionnaire used in the census. Socio-economic information for areas was downloaded from the census. Multilevel logistic regression investigated individual and area effects. RESULTS: There was a marked and independent influence of social variables on the risk of tuberculosis, both at individual and area levels. At individual level, being aged >or=20, being male, being illiterate, not working in the previous 7 days and possessing few goods, all increased the risk of tuberculosis. At area level, living in an area with many illiterate people and where few households own a computer also increased this risk; individual and area levels did not appear to interact. Twice as many cases were attributable to social variables at individual level than at area level. CONCLUSIONS: Although individual characteristics are the main contributor to the risk of tuberculosis, contextual characteristics make a substantial independent contribution.

Carbohydrate-deficient glycoprotein syndrome type 1 with profound thrombocytopenia and normal phosphomannomutase and phosphomannose isomerase activities.

We report siblings with a variant of carbohydrate-deficient glycoprotein syndrome, type 1 (CDGS1), characterized by normal phosphomannomutase and phosphomannose isomerase activities, severe thrombocytopenia, and respiratory compromise. Each infant died after a course of intensive care, suggesting that infants with CDGS1 and normal phosphomannomutase and phosphomannose isomerase activities may have a more severe CDGS1 phenotype.

Mechanism of all trans-retinoic acid and glucocorticoid regulation of surfactant protein mRNA.

The surfactant proteins (SPs) are required for the normal function of pulmonary surfactant, a lipoprotein substance that prevents alveolar collapse at end expiration. We characterized the effects of cortisol and all trans-retinoic acid (RA) on SP-A and SP-B gene expression in H441 cells, a human pulmonary adenocarcinoma cell line. Cortisol, at 10(-6) M, caused a significant inhibition of SP-A mRNA to levels that were 60-70% of controls and a five- to sixfold increase in the levels of SP-B mRNA. RA alone (10(-6) M) had no effect on SP-A mRNA levels and modestly reduced the inhibitory effect of cortisol. RA alone and the combination of cortisol and RA both significantly increased SP-B mRNA levels. RA had no effect on the rate of SP-A gene transcription or on SP-A mRNA stability. Cortisol alone and the combination of cortisol and RA significantly inhibited the rate of SP-A gene transcription but had no effect on SP-A mRNA half-life. RA at 10(-6) M had no effect on the rate of SP-B gene transcription but prolonged SP-B mRNA half-life. Cortisol alone and the combination of cortisol and RA caused a significant increase in the rate of SP-B gene transcription and also caused a significant increase in SP-B mRNA stability. We conclude that RA has no effect on SP-A gene expression and increases SP-B mRNA levels by an effect on SP-B mRNA stability and not on the rate of SP-B gene transcription. In addition, the effects of the combination of RA and cortisol were generally similar to those of cortisol alone.

The effect of inhaled nitric oxide therapy on bleeding time and platelet aggregation in neonates.

The effect of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation was studied in nine newborn infants with resolving pulmonary hypertension. Infants treated with iNO at 40 ppm for 30 minutes had bleeding times that were nearly twofold longer than those obtained 24 hours after iNO was discontinued. iNO had no effect on in vitro platelet aggregation studies.

Transient surfactant protein B deficiency in a term infant with severe respiratory failure.

A 38-day-old male infant with persistent pulmonary hypertension and respiratory failure since birth was found to have a complete absence of surfactant protein B (SP-B) along with an aberrant form of SP-C in his tracheal aspirate fluid, findings consistent with the diagnosis of hereditary SP-B deficiency. Surprisingly, SP-B and SP-B messenger ribonucleic acid were present in lung biopsy tissue. However, DNA sequence analysis demonstrated a point mutation in exon 5 of one of the SP-B gene alleles. The infant's mother was found to be a carrier of this mutation. The infant's other SP-B allele did not differ from the published DNA sequence for the SP-B gene. We conclude that this patient had a transient deficiency of SP-B, in contrast to that of previously described infants with irreversible respiratory failure caused by hereditary SP-B deficiency. We recommend that infants with suspected SP-B deficiency have serial analysis of tracheal fluid samples for both SP-B and SP-C before lung biopsy, along with genetic analysis for the known SP-B mutations. We speculate that the new mutation found in one of this patient's SP-B genes was in part responsible for the transient deficiency of SP-B.

Regulation of surfactant protein gene expression by retinoic acid metabolites.

Surfactant-associated proteins (SP) play an important role in the function of pulmonary surfactant. We have previously shown that SP-B mRNA is increased whereas SP-A and SP-C mRNA are decreased by all-trans-retinoic acid (RA) in a dose-dependent manner in human fetal lung explants. All-trans-RA binds primarily to the retinoic acid receptors (RARs) and 9-cis-RA binds primarily to the retinoid X receptors (RXRs). Because the fetal lung contains RXRs, we hypothesized that 9-cis-RA regulates surfactant protein gene expression in lung epithelial cells. H441 human lung adenocarcinoma cells, which synthesize SP-A and SP-B mRNA and protein, were treated with either all-trans-RA or 9-cis-RA (10(-10) to 10(-6) M) for 24 h. Neither all-trans-RA nor 9-cis-RA had an effect on SP-A mRNA levels in the H441 cells. All-trans-RA (10(-6) M) significantly increased SP-B mRNA levels in the H441 cells and 9-cis-RA had a smaller, not statistically significant effect. Human fetal lung explants were treated with 9-cis-RA for 6 d. 9-cis-RA did not significantly increase SP-B mRNA levels, significantly inhibited SP-A mRNA levels at all concentrations tested, and significantly inhibited SP-C mRNA levels at 10(-6) M in the human fetal lung explants. Both all-trans-RA (10(-6) M) and 9-cis-RA (10(-6) M) significantly increased SP-B protein levels in the human fetal lung explants. Together, these results are suggestive that all-trans-RA directly regulates SP-B gene expression in human pulmonary epithelial cells. In addition, the inhibitory effect of all-trans-RA and 9-cis-RA on SP-A mRNA levels in pulmonary epithelial cells is probably an indirect effect mediated by other cell types present in fetal lung tissue.