Cytokine responses to Dengue Infection among Puerto Rican Patients

Recently, a strong correlation between high concentration of tumor necrosis factor (TNFalpha) in blood and severity of dengue hemorrhagic fever/dengue shock syndrome has been reported from Asia and the Pacific. We wished to determine if a similar relationship could be found in dengue patients in the Americas where adult patients with severe syndromes have been observed more frequently than in Asia where severe cases have been observed mostly among children. The concentrations of interleukin-1 (IL-1beta) in hospistalized adult groups were significantly lower than that in outpatient adults. In contrast, the levels of interleukin 6 (IL-6) were significantly higher in hospistalized adults and children than in the corresponding outpatients. Levels of TNFalpha were higher in hospistalized children than in outpatient children or hospistalized adults. There was no significant difference in the levels of these three cytokines among hospitalized patients with or without hemorrhagic manifestations. Thus, an elevated IL-6 level was positively associated with severity of dengue infection in both children and adults, but IL-1beta level was negatively associated with severity in adults.

Targeting mitochondria in the infection strategy of the hepatitis C virus.

Hepatitis C virus (HCV) infection induces a state of oxidative stress more pronounced than that observed in many other inflammatory diseases. Here, we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists of a release of Ca(2+) from the endoplasmic reticulum, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen species and a progressive metabolic adaptive response. Evidence is provided for a positive feed-back mechanism between alterations of calcium and redox homeostasis. This likely involves deregulation of the mitochondrial permeability transition and induces progressive dysfunction of cellular bioenergetics. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.

Electrocardiographic alteration among first degree relatives with serologic evidence of Trypanosoma cruzi infection: a sibship study

To analyze whether electrocardiographic alterations (ECGA) in patients with antibodies to Trypanosoma cruzi showed a patttern of familial aggregation, a sample of 379 young adults (166 men and 213 women) distributed in sibships, were assessed for the presence of anti-T.cruzi antibodies, and subjected to a complete clinical examination and a standard resting electrocardiogram (ECG). Positive T. cruzi serology was detected in 165 individuals, 48 of them showing an abnormal ECG (overall prevalence 29 por cento). One hundred and eleven seropositive individuals were distributed in 45 sibships, each of them constituted by more than one seropositive sib, with ECGA being present in 34 out of these patients. Seropositive subjects with ECGA were detected in 27 sibships. Since the index case within each sibship is counted exactly once, affected individuals selected at random as propositi were extracted to calculate the prevalence of ECGA among first degree relatives of probands. Abnormal ECGs were recorded in 7 out of 45 sibs yielding a prevalence that did not differ from estimations registered in the general population or seropositive sibs. Data from the present sample show no familial aggregation for the occurrence of ECGA in patients with T.cruzi infection.

Ultrastructural study on experimental infection of rotavirus in a murine heterologous model

Viral replication, histopathological and ultrastructural changes were observed for a period of nine days in the small intestine of suckling mice infected with a simian rotavirus (SA11). Samples taken from duodenum, jejunun and ileum were prepared for light microscopy, transmission and scanning electron microscopy analysis. Histopathologic effect could be detected within 8 hr post-infection, when only a few altered cells were observed. Damage was extensive after 16 hr post-infection, showing swollen enterocytes and reduced and irregularly oriented microvilli at intestinal villi tips. Virus particles were detected at 16 and 48 hr post-infection, budding from the viroplasm into the rough endoplasmic reticulum cisternae in ileum enterocytes. Clear evidence of viral replication, observed by electron microscopy was not described before in heterologous murine models. Regeneration of the intestinal villi began at the third day post-infection. Despite some differences observed in clinical symptoms and microscopic analysis of homologous and heterologous rotavirus infections, we concluded that mechanisms of heterologous rotavirus infection in mice follow similar patterns to those observed in the homologous models.

Eurytrema coelomaticum (Digenea, Dicrocoeliidae): the effect of infection on carbohydrate contents of its intermediate snail host, Bradybaena similaris (Gastropoda, Xanthonychidae)

The interface Eurytrema coelomaticum/Bradybaena similaris was studied by quantifying the amount of glucose on the hemolymph and the content of glycogen in the cells of the digestive gland and the cephalopedal mass of infected and uninfected snails. Samples were analyzed on days 0, 30, 90 and 150 post-infection. The infected snails had less glucose in the hemolymph, with a reduction of 67.05 por cento at 30 days, and 62.09 por cento at 90 days post-infection. The reduction in glycogen content was 86.41 por cento in the digestive gland and 79.1 por cento in the cephalopedal mass at 30 days, and 92.71 por cento and 90.89 por cento in these organs respectively at 90 days post-infection. It is proposed that the sporocysts absorb glucose directly from the hemolymph.

The consequences of malaria infection in pregnant women and their infants

Preliminary results are presented from this study which indicate that 84.8 of pregnant women present at first antenatal visit with anemia (Hb 11g/dl) an 8.7 of their infants (n = 230) have a hemoglobin at birth below 14g/dl. There is an association between pregnancy anemia and malaria. A case control study in pregnant women and an infant cohort study to 18 months of age, are employed to study the cause and effects of anemia and malaria on women and their infants health.

Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo.

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.

CD4+, CD8+ and CD4- CD8- T cell-subsets can confer protection against Leishmania m. mexicana infection

We studied the role of CD4+, CD8+, CD4- CD8- T cells and IgG anti-Leishmania after infection or vaccination in the CBA/ca mouse. Mice were either infected with L. m. mexicana promastigotes or vaccinated with parasite-membrane antigens incorporated into liposomes. Successfully vaccinated mice were used as cell-donors in adoptive transfer experiments. Naive, syngeneic recipients received highly-enriched CD4+, CD8+ or CD4- CD8- T cells from those two set of donors and challenged with live parasites. Our results showed that, both CD4+ and CD8+ T cells from infected or vaccinated donors conferred significant disease-resistance to naive recipients. In addition, adoptive transfer of CD4- CD8- T cells from vaccinated donors significantly delayed lesion growth in recipient mice. We concluded that vaccination of CBA mice correlates with the induction of protective CD4+, CD8+ and CD4- CD8- T cells and the synthesis of IgG anti-Leishmania.

The use and limitations of ultrasonography in the diagnosis of liver morbidity attributable to Schistosoma mansoni infection in community-based surveys

The objective of this population-based study was to estimate the liver morbidity attributable to Schistosoma mansoni infection by ultrasonography adopting the proposed standard protocols of the Cairo Meeting on Ultrasonography, 1991. We examined 2384 individuals representing 20 of the households of the rural population of the Ismailia Governorate, East of Delta, Egypt. Prevalence of S. mansoni and S. haematobium infections were 40.3 and 1.7 respectively. Portal tract thickening (PTT) grade 1, 2 and 3 considered diagnostic of schistosomal liver morbidity was detected in 35.1, 1.3 and 0.2 individuals respectively. Generally, ultrasonographically-detected pathological changes increased with age, but correlated with intensity of infection only in age group 20-59 years. Comparing individuals with and without S. mansoni infections in an endemic and a non-endemic community indicated no significant difference between the former and the latter in either case. In conclusion: ultrasonography had a limited value in estimating schistosomal liver morbidity in our population-based study where early grades of liver morbidly were prevalent. The criteria of diagnosing grade I portal fibrosis need to be revised as well as the staging system proposed by the Cairo Meeting on ultrasonography in schistosomiasis.

Methicillin-resistant Staphylococcus aureus infection after lung transplantation: 5-year review of clinical and molecular epidemiology.

BACKGROUND: Data on the epidemiology of MRSA infection in lung transplantation is limited. METHODS: We performed a 5-year retrospective study to assess the incidence and microbiologic and clinical characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infection in a cohort of 163 lung transplant recipients. RESULTS: Seventeen patients with MRSA colonization and/or infection were identified, for a calculated incidence rate of 76.1 cases per 1,000 transplanted-years. Pulsed-field gel electrophoresis identified 3 different distinct MRSA profiles, all of them consistent with hospital-associated MRSA infection. CONCLUSION: Despite negative polymerase chain reaction (PCR) for the virulence factor Panton-Valentine leukocidin, MRSA infections resulted in significant disease and morbidity.

Opportunities and constraints in schistosomiasis vaccine development: infection characteristics and industry realities

The notes provided in this article relate to two components of the development of vaccines against schistosomiasis: (1) The characteristics of schistosome infections (eg. features of the schistosome life cycle), and the parasite itself, that have implications for vaccination strategies; (2) The characteristics of the biopharmaceutical industry that have implications for product development. As will be seen, these two topic areas are not vastly disparate.