Cross-sectional assessment of prevalence and correlates of blood-borne and sexually-transmitted infections among Afghan National Army recruits.

BACKGROUND: Few data are available in Afghanistan to shape national military force health practices, particularly with regard to sexually-transmitted infections (STIs). We measured prevalence and correlates of HIV, syphilis, herpes simplex 2 virus (HSV-2), and hepatitis C virus (HCV) among Afghan National Army (ANA) recruits. METHODS: A cross-sectional sample of male ANA recruits aged 18-35 years were randomly selected at the Kabul Military Training Center between February 2010 and January 2011. Participants completed an interviewer-administered questionnaire and serum-based rapid testing for syphilis and hepatitis C virus antibody on-site; HIV and HSV-2 screening, and confirmatory testing were performed off-site. Prevalence of each infection was calculated and logistic regression analysis performed to identify correlates. RESULTS: Of 5313 recruits approached, 4750 consented to participation. Participants had a mean age of 21.8 years (SD±3.8), 65.5% had lived outside Afghanistan, and 44.3% had no formal education. Few reported prior marijuana (16.3%), alcohol (5.3%), or opiate (3.4%) use. Of sexually active recruits (58.7%, N = 2786), 21.3% reported paying women for sex and 21.3% reported sex with males. Prevalence of HIV (0.063%, 95% CI: 0.013- 0.19), syphilis (0.65%, 95% CI: 0.44 - 0.93), and HCV (0.82%, 95% CI: 0.58 - 1.12) were quite low. Prevalence of HSV-2 was 3.03% (95% CI: 2.56 - 3.57), which was independently associated with age (Adjusted Odds Ratio (AOR) = 1.04, 95% CI: 1.00 - 1.09) and having a television (socioeconomic marker) (AOR = 1.46, 95% CI: 1.03 - 2.05). CONCLUSION: Though prevalence of HIV, HCV, syphilis, and HSV-2 was low, sexual risk behaviors and intoxicant use were present among a substantial minority, indicating need for prevention programming. Formative work is needed to determine a culturally appropriate approach for prevention programming to reduce STI risk among Afghan National Army troops.

The timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and the risk of HBV infection following HIV diagnosis.

To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level ≥ 10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P < 0.01 for both compared with persons vaccinated before HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons.

Increasing rates of obesity among HIV-infected persons during the HIV epidemic.

BACKGROUND: The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown. METHODS: We evaluated prospective data from a U.S. Military HIV Natural History Study (1985-2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models. RESULTS: Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era. CONCLUSIONS: HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.

Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals.

OBJECTIVE: To assess the association of hepatitis B virus (HBV) vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees. DESIGN: Observational cohort study. METHODS: Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: During 11 632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75-2.27)/100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted hazard ratio 0.86, 95% CI 0.7-1.1; adjusted hazard ratio 1.08, 95% CI 0.8-1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (hazard ratio 0.96; 95% CI 0.56-1.64). Among 409 vaccinees with HBsAb less than 10 IU/l, 46 (11.2%) developed HBV infection compared with 11 of 217 (5.1%) vaccinees with HBsAb > or =10 IU/l (hazard ratio 0.51; 95% CI 0.3-1.0). In participants with initial HBsAb less than 10 IU/l, 16 of 46 (35%) infections were chronic, compared with none of 11 in those with initial HBsAb at least 10 IU/l (P = 0.02). CONCLUSION: Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.

Cutaneous malignancies among HIV-infected persons.

BACKGROUND: As the life expectancy of persons infected with human immunodeficiency virus (HIV) increases, cancers have become an important cause of morbidity and mortality. Although cutaneous cancers are the most common malignant neoplasms in the general population, little data exist among HIV-positive persons, especially regarding the impact of HIV-specific factors. METHODS: We evaluated the incidence rates and factors associated with the development of cutaneous malignancies among HIV-infected persons by examining data that were prospectively collected from a large HIV study that included 4490 participants (1986-2006). Poisson regression and Cox proportional hazards models were performed. RESULTS: Six percent of HIV-infected persons (n = 254) developed a cutaneous malignancy during 33 760 person-years of follow-up (mean, 7.5 years). Since the advent of highly active antiretroviral therapy (HAART), the incidence rates of cutaneous non-AIDS-defining cancers (NADCs), in particular basal cell carcinoma, have exceeded the rates of cutaneous AIDS-defining cancers such as Kaposi sarcoma. Factors associated with the development of cutaneous NADCs in the multivariate models included increasing age (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.7-2.6) and race. Compared with the white/non-Hispanic race, African Americans (HR, 0.03; 95% CI, 0.01-0.14) and other races (HR, 0.14; 95% CI, 0.03-0.57) had a lower risk of cutaneous NADCs. There were no significant associations between cutaneous NADCs and time-updated CD4 lymphocyte counts, HIV RNA levels, or receipt of HAART. CONCLUSIONS: At present, the most common cutaneous malignancies among HIV-infected persons are NADCs. Cutaneous NADCs do not appear to be significantly associated with immune function or HAART but rather are related to traditional factors such as aging and skin color.

Hepatitis B vaccine responses in a large U.S. military cohort of HIV-infected individuals: another benefit of HAART in those with preserved CD4 count.

The influence of highly active antiretroviral therapy (HAART) upon hepatitis B virus (HBV) vaccine responses in HIV-infected individuals is unclear. After classification of vaccinees as non-responders (HBsAb <10IU/L) or responders (HBsAb >or=10IU/L) in our HIV cohort, multivariate logistic regression was used to assess factors associated with subsequent vaccine response. Of 626 participants vaccinated from 1988 to 2005, 217 (35%) were vaccine responders. Receipt of >or=3 doses of vaccine (OR 1.83, 95% CI 1.24-2.70), higher CD4 count at vaccination (OR 1.09, 95% CI 1.05-1.13 per 50 cells/microl increase), and use of HAART (OR 2.37, 95% CI 1.56-3.62) were all associated with increased likelihood of developing a response. However, only 49% of those on HAART at last vaccination responded, and 62% of those on HAART, with CD4 count >or=350, and HIV RNA <400 copies/mL responded. Compared to those on HAART with CD4 count >or=350, those not on HAART with CD4 count >or=350 had significantly reduced odds of developing a vaccine response (OR 0.47, 95% CI 0.30-0.70). While HAART use concurrent with HBV immunization was associated with increased probability of responding to the vaccine, the response rate was low for those on HAART. These data provide additional evidence of HAART benefits, even in those with higher CD4 counts, but also highlight the need for improving HBV vaccine immunogenicity.

The impact of nelfinavir exposure on cancer development among a large cohort of HIV-infected patients.

BACKGROUND: Preclinical studies suggest that the antiretroviral agent, nelfinavir mesylate (NFV), may have antineoplastic properties. The relationship between NFV and cancer incidence among HIV-infected patients is unknown. METHODS: We evaluated the impact of NFV on cancer development in a large cohort of HIV-infected persons with 108 cancer events during 13,421 person-years of follow-up. Using multivariate time-updated Cox proportional hazard models, the risk of cancer among those receiving NFV were compared to those on non-NFV antiretroviral regimens. RESULTS: The risk of cancer among those receiving NFV was similar to those on non-NFV antiretroviral regimens (hazard ratio 1.0, 95% confidence interval 0.5, 1.7, P = 0.90). We also examined AIDS-defining and non-AIDS-defining cancers separately and found no significant associations between NFV use and cancer risk. Antiretroviral use, with or without a protease inhibitor (PI) component, was associated with a reduced risk of AIDS-defining cancers compared with no antiretroviral therapy; however, the risk of cancer was the same among those using PI or PI-sparing regimens. DISCUSSION: Despite reports that NFV may have tumoricidal activity, we found no significant relationship between NFV or PI use compared with other antiretrovirals and the risk of developing cancer among a large cohort of HIV-infected persons.

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism.

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models.

Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985-2007.

BACKGROUND: Whether human immunodeficiency virus (HIV) seroconverters have been presenting with progressively lower CD4 cell counts over the course of the HIV epidemic is controversial. Additional data on whether HIV might have become more virulent on a population level (measured by post-seroconversion CD4 cell counts) may provide important insights regarding HIV pathogenesis. METHODS: To determine whether post-seroconversion CD4 cell counts have changed over time, we evaluated 2174 HIV seroconverters as part of a large cohort study during the period 1985-2007. Participants were documented antiretroviral-naive HIV seroconverters who had a CD4 cell count measured within 6 months after receiving a diagnosis of HIV infection. Multiple linear regression models were used to assess trends in initial CD4 cell counts. RESULTS: The mean initial CD4 cell count decreased during the study period from 632 cells/mm(3) in 1985-1990 to 553 cells/mm(3) in 1991-1995, 493 cells/mm(3) in 1996-2001, and 514 cells/mm(3) in 2002-2007. During those periods, the percentages of seroconverters with an initial CD4 cell count <350 cells/mm(3) were 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean decrease in CD4 cell count from 1985-1990 was 65 cells/mm(3) in 1991-1995 (P < .001)), 107 cells/mm(3) in 1996-2001 (P < .001), and 102 cells/mm(3) in 2002-2007 (P < .001). Similar trends occurred with regard to CD4 cell percentage and total lymphocyte count. Similar decreases in initial CD4 cell counts were observed among African American and white persons during the epidemic. DISCUSSION: A significant decrease in initial CD4 cell counts among HIV seroconverters in the United States has occurred during the HIV epidemic. These data provide an important clinical correlate to suggestions that HIV may have adapted to the host, resulting in a more virulent infection.

Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: a 20-year cohort study.

OBJECTIVE: To describe trends in incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) during the HIV epidemic and to evaluate predictors, including the impact of antiretroviral therapy, of cancer development. DESIGN: Retrospective analysis of a multicenter, prospective natural history study including 4498 HIV-infected US military beneficiaries with 33 486 person-years of follow-up. METHODS: Predictors evaluated included demographics, clinical data, time-updated CD4 cell counts, HIV viral loads, and antiretroviral history. Time periods were classified as early pre (1984-1990), late pre (1991-1995), early post (1996-2000), and late post (2001-2006) HAART eras. Cox proportional hazard models were used to evaluate the association of specific factors with cancer. RESULTS: Ten percent of HIV-infected persons developed cancer. ADC rates increased between the early and late pre-HAART eras (7.6 and 14.2 cases per 1000 person-years) and have since declined from 5.4 to 2.7 in the early and late HAART eras, respectively (P < 0.001). Rates of NADCs have risen over the four periods (2.9, 2.8, 4.2, 6.7, P = 0.0004). During the late HAART era, 71% of cancers were NADCs. Predictors for ADCs included low CD4 cell count, noncancer AIDS diagnosis, and lack of HAART. NADCs were predicted by increasing age and white race (due to skin cancers). CONCLUSION: Although the rate of ADCs continues to fall, the rate of NADCs is rising and now accounts for the majority of cancers in HIV-infected persons. The development of NADCs is associated with increasing age among HIV patients. HAART use is protective for ADCs, but did not significantly impact NADCs.

Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer.

BACKGROUND AND AIMS: Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two orthotopic models of metastatic colon cancer (liver and lung) and in the standard subcutaneous model. METHODS: We have developed models of skin tumours, liver and pulmonary metastasis and compared the extent of tumour development between C26 colon cancer cells expressing either the native, the soluble, the membrane-bound fractalkine or none. RESULTS: The native fractalkine exhibits the strongest antitumour effect, reducing the tumour size by 93% in the skin and by 99% in the orthotopic models (p<0.0001). Its overall effect results from a critical balance between the activity of the secreted and the membrane-bound forms, balance that is itself dependent on the target tissue. In the skin, both molecular variants reduce tumour development by 66% (p<0.01). In contrast, the liver and lung metastases are only significantly reduced by the soluble form (by 96%, p<0.002) whereas the membrane-bound variant exerts a barely significant effect in the liver (p = 0.049) and promotes tumour growth in the lungs. Moreover, we show a significant difference in the contribution of the infiltrating leukocytes to the tumour-suppressive activity of fractalkine between the standard and the orthotopic models. CONCLUSIONS: Fractalkine expression by C26 tumour cells drastically reduces their metastatic potential in the two physiological target organs. Both molecular forms contribute to its antitumour potential but exhibit differential effects on tumour development depending on the target tissue.

Epidermal stem cells.

The identification of adult epidermal stem cells that are capable of self-renewal and can reconstitute not only the epidermis but also the cutaneous appendages opens new perspectives for the treatment of a variety of human skin disorders including severe burns, cutaneous cancers, alopecia and acne. However, the implementation and improvement of these novel treatment strategies require a better understanding of the biology of stem cells, in particular regarding their isolation and the maintenance of their unique characteristics in culture. In this review, we summarize the main features of epidermal stem cells and we present the most recent advances in our understanding of the development and maintenance of these cells. In addition, we discuss some of the challenges and the potential clinical applications of epidermal stem cell technology.

Tensile bond strength of composite to air-abraded dentin.

This study evaluated the influence of air abrasive treatment of dentin surfaces on the tensile bond strength between dentin and two different composite-adhesive-systems Multi-Purpose/Z100 and OptiBond FL/Herculite XR). The crowns of 200 maxillary central incisors were embedded in resin and then ground to expose a dentin surface 5 mm in diameter. The surfaces were etched or abraded by using a KCP 1000 device with different treatment conditions. Adhesive systems were applied according to the manufacturer's instructions and composite cylinders were bonded to the conditioned dentinal surface using a split mold. Tensile bond strength values and failure modes were then determined. Tensile bond strength values of the acid-etched dentin-composite-interface were significantly higher than for the interface between air-abraded dentin and composite, independent of the composite-adhesive-system used. The light microscopic evaluation showed mainly adhesive and combined adhesive-cohesive fractures. Significantly more adhesive fractures could be observed between abraded dentin and composite than between etched dentin and composite.

Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect on Brucella abortus survival.

Genetically based natural resistance to brucellosis in cattle provides for novel strategies to control zoonotic diseases. Bovine NRAMP1, the homologue of a murine gene (Bcg), has been identified as a major candidate for controlling the in vivo resistant phenotype. We developed an in vitro model for expression of resistance- and susceptibility-associated alleles of bovine NRAMP1 as stable transgenes under the regulatory control of the bovine NRAMP1 promoter in the murine RAW264.7 macrophage cell line (Bcg(s)) to analyze the regulation of the NRAMP1 gene and its role in macrophage function. We demonstrated that the 5'-flanking region of bovine NRAMP1, despite the lack of TATA and CAAT boxes, has a functional promoter capable of driving the expression of a transgene in murine macrophages. A polymorphism within a microsatellite in the 3' untranslated region critically affects the expression of bovine NRAMP1 and the control of in vitro replication of Brucella abortus but not Salmonella enterica serovar Dublin. We did not observe any differences in the production of NO by resting or gamma interferon (IFN-gamma)- and IFN-gamma-lipopolysaccharide (LPS)-treated transfected cell lines, yet the resistant transfected cell lines produced significantly less NO than other cell lines, following stimulation with LPS at 24 and 48 h.

Pathologic findings and association of Mycobacterium bovis infection with the bovine NRAMP1 gene in cattle from herds with naturally occurring tuberculosis.

OBJECTIVE: To determine necropsy and Mycobacterium bovis culture results in cattle from herds with tuberculosis, the role of the bovine NRAMP1 gene in resistance and susceptibility to infection with M bovis, and the association between magnitude of the tuberculous lesions and various types of M bovis isolates. ANIMALS: 61 cattle from herds with tuberculosis in Texas and Mexico. PROCEDURE: 61 cattle were evaluated by necropsy; 59 had positive and 2 had negative caudal fold tuberculin intradermal test (CFT) results. Thirty-three cattle with positive CFT results were genotyped to evaluate polymorphism of the 3' untranslated region of the bovine NRAMP1 gene, using single-stranded conformational analysis, 9 were resistant to M bovis with no tuberculous lesions and negative M bovis culture results, and 24 were susceptible with tuberculous lesions and positive M bovis culture results. Isolates of M bovis were analyzed by restriction fragment length polymorphism (RFLP) on the basis of IS6110 sequences and direct-repeat fingerprinting patterns. RESULTS: 21 (35.6%; 21/59) cattle with positive CFT results had tuberculous lesions or positive culture results; in addition, 1 of 2 cattle with negative CFT results had tuberculous lesions and positive culture results. Tuberculous lesions were most common in the thorax (35/63; 55.5%) and lymphoid tissues of the head (10/63; 15.9%). Tuberculous lesions varied from 1 to 11/animal; 8 of 21 (38.1%) had solitary lesions. Associations were not found between resistance or susceptibility to infection with M bovis and polymorphism in the NRAMP1 gene or between the magnitude of the lesions and various RFLP types of M bovis isolates. CONCLUSIONS AND CLINICAL RELEVANCE: The NRAMP1 gene does not determine resistance and susceptibility to infection with M bovis in cattle.

Rectal stricture in an ostrich (Struthio camelus).

Exploratory celiotomy of an 18-mo-old female ostrich (Struthio camelus) with anorexia, lethargy, and constipation of 5 days' duration showed mesenteric volvulus and a focal narrowing of the rectum approximately 28 cm cranial to the cloaca. The prognosis was poor and the animal was euthanized. Necropsy revealed a fibrinonecrotic proctitis and a 3-cm-long circumferential stricture of the rectum. Histologically, the rectal wall at the stricture was deeply effaced by fibrovascular connective tissue with vascular thrombosis and necrotizing vasculitis, and it resembled the lesions in feeder pigs with fibrinonecrotic colitis.

Ocular Halicephalobus (syn. Micronema) deletrix in a horse.

Ocular contents from a horse with a 4-week history of severe unilateral uveitis were submitted for histopathologic examination. A severe unilateral granulomatous chorioretinitis with intralesional Halicephalobus deletrix was diagnosed. The horse developed progressive neurologic signs several days following the surgery to remove ocular contents and implant a prosthesis and was subsequently euthanatized. A severe multifocal granulomatous encephalitis with intralesional H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem, was diagnosed from tissues acquired at necropsy. The other eye was not affected. This is the first report of ocular parasitism by H. deletrix and suggests possible systemic dissemination from a primary site in the eye.