International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors Few studies have described the international epidemiology of pre-existing immunity to adenoviruses We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36 Clinical trial samples were used to assess NA titers from the US and Europe The proportions of participants that were negative were 14 8%(Ad5), 31 5%(Ad6),41 2%(Ad26) and 53.6% (Ad36) Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers, participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR = 3 53,95% CI 224,557) Regardless of location. titers of Ad5NA were the highest and Ad36 NA were the lowest Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations (C) 2009 Published by Elsevier Ltd

Urogenital tuberculosis in immunocompromised patients

Compare the clinicoradiological presentation of urogenital tuberculosis (UGT) between immunocompromised and nonimmunocompromised patients. Eighty patients diagnosed with UGT were divided into two groups: eight immunocompromised patients (four with acquired immunodeficiency syndrome [AIDS], and four renal transplant patients on immunosuppressive therapy) and 72 nonimmunocompromised patients. The groups were compared as for age, signs and symptoms, diagnostic approach, pattern of urogenital organ involvement, and early specific mortality (within 6 months from diagnosis). AIDS patients were younger (median age 26 years, range 16-38 years), and renal transplant patients were older (median age 51.5 years, range 45-57 years), compared with the nonimmunocompromised subjects (median age 35 years, range 12-75 years). Immunocompromised patients had greater frequency of fever (87.5% versus 43.1%, P = 0.024), lower frequency of storage symptoms (37.5% versus 76.4%, P = 0.033), shorter length of disease (< 6 months: 87.5% versus 2.8%, P < 0.001), and larger frequency of disseminated tuberculosis (62.5% versus 18.1%, P = 0.012). Predominantly parenchymatous renal involvement was more frequent in immunocompromised patients (87.5% versus 6.2%, P < 0.001), who also had lower frequency of stenosis of the collecting system (12.5% versus 93.8%, P < 0.001) and contracted bladder (12.5% versus 65.3%, P = 0.001). UGT has a different clinicoradiological presentation in immunocompromised patients, with predominance of systemic symptoms, disseminated tuberculosis, multiple parenchymatous renal foci, and lower frequency of lesions of the collecting system. In the context of immunosuppression, UGT behaves as a severe bacterial infection, with bacteremia and visceral metastatic foci.

Epidemiology of urogenital tuberculosis worldwide

Objectives: To characterize the epidemiology of urogenital tuberculosis worldwide and to compare the features of patients from developing countries to those from developed countries. Methods: A comprehensive search of articles published up to April 2008 using a combination of the terms `tuberculosis`, `genitourinary`, `renal` and `urogenital` was performed. Results: Urogenital tuberculosis affects more men than women (2:1), with a mean age of 40.7 years (range 5-90). In 26.9% of cases there is a non-functioning unilateral kidney and in 7.4%, renal failure. Patients from developing countries are more likely to have a delayed diagnosis with a higher frequency of renal failure, unilateral non-functioning kidney, ablative surgery and contracted bladder. Conclusions: Urogenital tuberculosis is a worldwide disease with more destructive behavior in developing countries where urgent strategies for early detection are particularly warranted.

Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans

The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector -based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4(+) T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.

Neurosyphilis in HIV-infected patients: Clinical manifestations, serum venereal disease research laboratory titers, and associated factors to symptomatic neurosyphilis

Goal: To describe clinical and laboratory features of human immunodeficiency infection (HIV)-infected patients with neurosyphilis. Study Design: Retrospective study of 27 consecutive cases of HIV-infected patients with a positive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Results: Median of age was 36 years and 89% were men. Ten (37%) patients had previous nonneurologic syphilis treatment. At the time of neurosyphilis diagnosis, 10 (37%) patients had early syphilis, and 6 of them were neurologically asymptomatic. Nine (33%) patients had symptomatic neurosyphilis. Twenty-six (96%) patients were classified with early neurosyphilis. The medians of serum VDRL and CD4(+) T cell counts were 1:128 and 182 cell/mu L, respectively. Twenty five (93%) patients presented serum VDRL titers >= 1:16. Five of 6 patients with early syphilis and asymptomatic neurosyphilis, presented serum VDRL >= 1:16. Symptomatic patients showed lower CD4(+) T cell counts (59 cell/mu L vs. 208 cell/mu L, P = 0.03) and higher protein concentration on CSF (118 mg/dL vs. 39 mg/dL, P <0.001) than asymptomatic patients. Conclusions: Most patients had early and asymptomatic neurosyphilis, and more than one third had early syphilis. Patients with symptomatic neurosyphilis showed lower CD4(+) T cell counts and higher protein concentration on CSF than those asymptomatic. Most patients had serum VDRL titers >= 1:16, regardless of syphilis stage.

Infectious diseases in paediatric pathology: experience from a developing country

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas` disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

Histoplasma capsulatum Cell Wall beta-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B(4) Generation and Role in HIV-1 Infection

Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B(4) plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B(4) and PGE(2). Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly beta-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that beta-glucan plays a signaling role in LB formation. In agreement with this hypothesis, beta-glucan-elicited LB formation was inhibited in leukocytes from 5-LO(-/-), CD18(low) and TLR2(-/-) mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after beta-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection. The Journal of Immunology, 2009, 182: 4025-4035.

Comparison of bioelectrical impedance with skinfold thickness and x-ray absorptiometry to measure body composition in HIV-infected with lipodistrophy

Introduction: Human immunodeficiency virus (HIV)associated lipodystrophy syndrome (LS) includes body composition and metabolic alterations. Lack of validated criteria and tools make difficult to evaluate body composition in this group. Objective: The aim of the study was to compare different methods to evaluate body composition between Brazilians HIV subjects with (HIV+LIPO+) or without LS (HIV+LIPO-) and healthy subjects (Control). Methods: in a cross-sectional analyses, body composition was measured by bioelectrical impedance analysis (BIA), skinfold thickness (SF) and dual-energy x-ray absorptiometry (DXA) in 10 subjects from HIV+LIPO+ group; 22 subjects from HIV+LIPO- group and 12 from Control group. Results: There were no differences in age and body mass index (BMI) between groups. The fat mass (FM) (%) estimated by SF did not correlate with DXA in HIV+LIPO+ group (r = 0,46/p >0,05) and had fair agreement in both HIV groups (HIV+LIPO+ =0,35/ HIV+ LIPO- = 0,40). BIA had significant correlation in all groups (p < 0,05) and strong agreement, meanly in HIV groups, for FM (HIV+LIPO+ = 0,79/ HIV+LIPO- = 0,85/Control = 0,60) and for fat free mass (FFM) (HIV+LIPO+ = 0,93/ HIV+LIPO- = 0,92 / Control = 0,73). Discussion: Total fat mass can be measured by BIA with good precision, but not by SF in HIV-infected patients with LS. Segmental BIA, triciptal SF, circumferences of arms, waist and legs maybe alternatives that need more studies.

Oral lesions in HIV infected individuals from Ribeirao Preto, Brazil

Objectives: The aim of this study was to diagnosis oral lesions related to HIV infection in individuals followed in the General Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. The presence of oral lesions was correlated with gender, age, smoking habit, levels of CD4 lymphocytes, HIV load, time of HIV seropositivity, AIDS condition, use of removable dental prosthesis, and use of HAART. Materials and Methods: 340 HIV infected individuals were selected for this study, all participants of the study were examined by only one practiced dentist which performed anamnesis, peribuccal and oral examination. Results: Oral lesions were observed in 113 of 340 (33.2%) HIV infected individuals. These oral lesions included: oral candidiasis (17.7%) of pseudomembranous (10.8%) and of erythematous types (6.9%), angular cheilitis (13.9%), hairy leukoplakia (11.8%), and oral ulcers (2.1%). Oral candidiasis lesions were more frequently observed in women (p. 033). Smoking addict participants presented a high frequency of tongue hairy leukoplakia (p. 038) and a reduced frequency of oral ulcers (p. 018). Hairy leukoplakia and pseudomembranous candidiasis were inversely correlated to CD4+ L levels and directly correlated with HIV load, behaving as immune depression markers. Hairy leukoplakia and pseudomembranous candidiasis also showed an inverse correlation with HAART use (p < .0001). Patients using mobile dental prosthesis presented a high frequency of erythematous candidiasis (p. 003). Conclusion: The inverse correlation with CD4+ L level and the direct correlation with HIV load suggest that oral lesions could be used as alternative clinical markers for poor immune condition in HIV infected individuals.

Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population

OBJECTIVE: To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. STUDY DESIGN: In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. RESULTS: All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P=.009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P=.002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P<.0001). CONCLUSION: Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Paracoccidioidomycosis Epidemiological Features of a 1,000-Cases Series from a Hyperendemic Area on the Southeast of Brazil

Paracoccidioidomycosis has been known for over 100 years, and until now, there were only few estimates of the disease`s incidence. We aim to analyze 1,000 cases treated between 1960 and 1999 at Ribeirao Preto city, Sao Paulo, Brazil, where the disease`s incidence range detected was 1.6 to 3.7 cases per 100,000 habitants per year (mean = 2.7 cases/year). We observed a male to female ratio of 6:1 and an age distribution from 3 to 85 years. The acute/subacute form of the disease accounted for 25.4% of cases. Most of the patients (93.5%) had lived or worked in rural areas before the disease development. Smoking and alcoholism were reported by 64.7% and 37.2% of patients, respectively. Comorbidities identified included tuberculosis (8.3%), Chagas` disease (8.6%), and human immunodeficiency virus/acquired immunodeficiency syndrome (4.2%). The present study revealed an area in Brazil where paracoccidioidomycosis is hyperendemic (has the highest reported incidence of this disease); this endemic area is probably caused by geological and climatic conditions as well as intensive agriculture.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Herpes viruses in periodontal compromised sites: comparison between HIV-positive and -negative patients

Aims: The objective of this study was to compare the frequency of herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in subgingival plaque, saliva and peripheral blood of HIV-positive and-negative patients with periodontal disease. Materials and Methods: Fifty HIV-positive subjects (23 with gingivitis, 27 with periodontitis) and 50 healthy HIV-negative patients with chronic periodontitis were included in the study. Parameters of probing depth (PD), clinical attachment level (CAL), gingival index and plaque index were recorded. The samples were processed for viral identification by the nested polymerase chain reaction technique. Results: HCMV was the most prevalent virus in HIV-positive (82%) and-negative patients (84%), and the detection in the three samples was similar (p > 0.05). HSV-1 was the least prevalent virus in both groups, being detected in similar frequencies in oral sites and in peripheral blood. EBV-1 was found more frequently in saliva and subgingival plaque of HIV-positive patients than in HIV-negative patients (p <= 0.05). Conclusions: EBV-1 was more frequently recovered in oral sites of HIV-positive patients than in HIV-negative patients.

Impact of PI and NNRTI HAART-based therapy on oral lesions of Brazilian HIV-infected patients

Background: The incidence of oral lesions related to human immunodeficiency virus (HIV) infection have been investigated after treatment with highly active antiretroviral therapy (HAART) including protease inhibitors (PI) but no data are available on the effect of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy on incidence of acquired immunodeficiency syndrome (AIDS) oral manifestations or impact of HAART on oral manifestations of HIV infection in Brazil. The aim of this study was to describe the effects of anti-HIV therapy on the incidence of oral lesions during 17 years of AIDS epidemics in a Brazilian population. Methods: From 1989 to 2006, we collected data from 1595 consecutive HIV patients at the Special Care Dentistry Center, Sao Paulo, Brazil. We compared the effect of PI- and NNRTI-based antiretroviral therapy (ARVT) on the annual incidence of Kaposi sarcoma (KS), oral candidiasis (OC) and hairy leukoplakia (HL). The chi-squared test was used to test the association between oral lesions and therapeutic regimen (P < 0.05). Results: None of patients on ARVT presented with KS. Patients who used (nucleoside reverse transcriptase inhibitors) NRTI + PI were 0.9 times as likely to present with HL as those who used NRTI + NNRTI. This finding, however, was not statistically significant (P = 0.5). The relative risk for OC was 0.8 in patients with PI-based HAART. The increased risk among those on PIs was statistically significant (P = 0.004). Conclusions: The superiority of NNRTI regimens in decreasing OC incidence is consistent with current therapeutic guidelines which recommend NNRTI-based therapy as the treatment of choice for initial ARVT.