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1.  High Mycoplasma genitalium Organism Burden Is Associated with Shedding of HIV-1 DNA from the Cervix 
The Journal of infectious diseases  2008;197(5):733-736.
We assessed the relationship between infection with Mycoplasma genitalium, an emerging sexually transmitted pathogen, and cervical shedding of human immunodeficiency virus (HIV)–1 DNA among 303 HIV-1–positive Kenyan women. HIV-1 shedding was detected by qualitative polymerase chain reaction (PCR) in 154 women (51%); M. genitalium was detected by qualitative PCR in 52 (17%), and organism burden was determined by quantitative PCR. Women with high M. genitalium organism burdens (more than the median of 3195 genomes/mL) were 3-fold more likely to shed HIV-1 DNA than were M. genitalium–negative women (adjusted OR, 2.9 [95% confidence interval, 1.1–7.6]), yet this did not appear to be mediated by traditional measures of cervical inflammation (elevated polymorphonuclear leukocyte count).
doi:10.1086/526501
PMCID: PMC4090222  PMID: 18266605
2.  IFN-γ and IL-4 have contrasting effects on immunopathology and development of protective adaptive immunity against mycoplasma respiratory disease1 
For vaccine development, it is critical to understand the regulatory mechanisms determining resistance and immunopathology against mycoplasma respiratory diseases. The present study evaluated the contribution of the polarizing cytokines, IFN-γand IL-4, in the regulation of mycoplasma-specific immunity. The absence of a single cytokine, either IFN-γor IL-4, uniquely altered expression of multiple chemokines/cytokines in the lungs of uninfected mice and influenced responses to mycoplasma infection. Most importantly, prior nasal-pulmonary immunization of IFN-γ−/− mice led to exacerbated mycoplasma disease, whereas immunized IL-4−/− mice were dramatically more resistant than wild-type mice. Th2-type responses in IFN-γ−/− mice corresponded to immunopathologic reactions developed after mycoplasma infection or immunization. Thus, adaptive immunity clearly can independently promote either protection or immunopathology against mycoplasma infection, and optimal vaccination appears to be dependent on promoting protective IFN-γ-dependent network, perhaps Th1 responses, while minimizing the impact of IL-4-mediated responses that dampen generation of protective immunity.
doi:10.1086/653121
PMCID: PMC4086782  PMID: 20504237
3.  Augmented Production of Panton-Valentine Leukocidin Toxin in Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Is Associated with Worse Outcome in a Murine Skin Infection Model 
The role of Panton-Valentine leukocidin (PVL) in Staphylococcus aureus infections is controversial. We used a mouse model of skin infection to compare the virulence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) strains with different levels of PVL production. Differences in PVL production were not associated with mutations in the genes lukS-PV and lukF-PV. However, MSSA and MRSA strains that produced high levels of PVL caused larger skin abscesses, higher bacterial burdens, and more tissue inflammation than did low-PVL-producing strains. Together, these data suggest that (1) the effect of PVL on the pathogenesis of staphylococcal infection may depend on the level of toxin produced and (2) many strains of MSSA that cause soft-tissue infections produce higher levels of PVL than do MRSA strains.
doi:10.1086/648613
PMCID: PMC4084919  PMID: 19929693
4.  Sexual Role and Transmission of HIV Type 1 among Men Who Have Sex with Men, in Peru 
The Journal of infectious diseases  2005;191(0 1):S147-S158.
In Latin America, men who have sex with men (MSM) have traditionally practiced role segregation—that is, the adoption of a fixed role (insertive or receptive) rather than a versatile role (both practices) during anal sex. Previous modeling has shown that role segregation may yield a lower incidence of human immunodeficiency virus (HIV) type 1 infection, compared with role versatility; however, the modeling assumed no risk of acquiring HIV-1 during insertive sex, which is now recognized as unlikely. We reexamine the issue by use of a deterministic model incorporating bidirectional transmission and data from a cohort study of MSM in Lima, Peru, to demonstrate the potential effects of role segregation on the trajectory of the HIV-1 epidemic. In Lima, 67% of MSM reported segregated roles in their recent male partnerships. A population of MSM with identical contact rates but complete role versatility would have twice the prevalence of HIV-1 infection throughout the epidemic’s first 3 decades. Preferential mixing among versatile MSM does not change overall prevalence but affects which individuals become infected.
doi:10.1086/425268
PMCID: PMC4063354  PMID: 15627225
5.  Immune Reconstitution of CD56dim NK Cells in Individuals with Primary HIV-1 Infection Treated with Interleukin-2 
The Journal of infectious diseases  2008;197(1):117-125.
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)–2 therapy results in an expansion of CD4+ T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NK cells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)–γ production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56dim NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-γ production were maintained over time. This reconstitution of NK cells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
doi:10.1086/524141
PMCID: PMC4061976  PMID: 18171294
6.  Detection of Taenia solium Antigens and Anti–T. solium Antibodies in Paired Serum and Cerebrospinal Fluid Samples from Patients with Intraparenchymal or Extraparenchymal Neurocysticercosis 
The Journal of infectious diseases  2009;199(9):1345-1352.
Background
Neurocysticercosis (NCC) is a frequent cause of epilepsy worldwide. Compared with the more common parenchymal brain cysts, extraparenchymal infections are difficult to manage and have a poor prognosis. Serological assays are used to detect circulating Taenia solium antigens or anti–T. solium antibodies in serum or cerebrospinal fluid (CSF) samples. There are no guidelines on whether to use serum or CSF specimens for a particular assay.
Methods
We obtained paired serum and CSF samples from 91 patients with NCC (48 had intraparenchymal NCC, and 43 had extraparenchymal NCC) for detection of antibodies, using an enzyme-linked immunotransfer blot (EITB) assay, and antigens, using a monoclonal antibody–based enzyme-linked immunosorbent assay (ELISA).
Results
For the intraparenchymal NCC group, the EITB assay yielded more true-positive results for serum samples, and the ELISA yielded slightly more true-positive results for CSF samples than for serum samples, but none of these differences were statistically significant. Most patients with calcified NCC were antibody positive but antigen negative. For extraparenchymal disease, all samples were antibody positive, and all but 2 were antigen positive, with most samples containing high antigen levels.
Conclusions
The sensitivity of antibody-detecting EITB assays is not increased through the use of CSF samples rather than serum samples. The antigen-detecting ELISA performed better for CSF samples than for serum samples, but for both specimen types it was less sensitive than the EITB assay. Active and inactive NCC are better differentiated from each other by the antigen-detecting ELISA, for both serum and CSF samples. High antigen levels suggest the presence of subarachnoid NCC.
doi:10.1086/597757
PMCID: PMC4059603  PMID: 19358669
7.  Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation 
The Journal of infectious diseases  2009;200(7):1104-1112.
Human disease caused by highly pathogenic avian influenza (H5N1) is associated with fulminant viral pneumonia and mortality rates in excess of 60%. Cytokine dysregulation is thought to contribute to its pathogenesis. In comparison with human seasonal influenza (H1N1) viruses, clade 1, 2.1, and 2.2 H5N1 viruses induced higher levels of tumor necrosis factor-α in primary human macrophages. To understand viral genetic determinants responsible for this hyperinduction of cytokines, we constructed recombinant viruses containing different combinations of genes from high-cytokine (A/Vietnam/1203/04) and low-cytokine (A/WSN/33) phenotype H1N1 viruses and tested their cytokine-inducing phenotype in human macrophages. Our results suggest that the H5N1 polymerase gene segments, and to a lesser extent the NS gene segment, contribute to cytokine hyperinduction in human macrophages and that a putative H5 pandemic virus that may arise through genetic reassortment between H5N1 and one of the current seasonal influenza viruses may have a markedly altered cytokine phenotype.
doi:10.1086/605606
PMCID: PMC4028720  PMID: 19694514
8.  Expression of Candida glabrata adhesins following exposure to chemical preservatives 
The Journal of infectious diseases  2009;199(12):1891-1898.
In Candida glabrata, an opportunistic yeast pathogen, adherence to host cells is mediated in part by the Epa family of adhesins, which are encoded largely at subtelomeric loci where they are subject to transcriptional silencing. In analyzing the regulation of the subtelomeric EPA6 gene, we found that its transcription is highly induced after exposure to methylparaben, propylparaben or sorbate. These weak acid-related chemicals are widely used as antifungal preservatives in many consumer goods, including over-the-counter (OTC) vaginal products. Culture of C. glabrata in a variety of vaginal products induced expression of EPA6, leading to increased adherence to cultured human cells as well as primary human vaginal epithelial cells. We present evidence that paraben/sorbate-induction of EPA6 expression involves both preservative stress and growth under hypoxic conditions. We further show that activation of EPA6 transcription depends on the Flo8 and Mss11 transcription factors and does not require the classical weak acid transcription factors War1 or Msn2/Msn4. We conclude that exposure of C. glabrata to commonly used preservatives can alter expression of virulence-related genes.
doi:10.1086/599120
PMCID: PMC4019233  PMID: 19426114
Candida; Paraben; Adhesin; Virulence
9.  Methadone Enhances Human Immunodeficiency Virus Infection of Human Immune Cells 
The Journal of infectious diseases  2001;185(1):118-122.
Opiate abuse has been postulated to be a cofactor in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS). This study evaluated whether methadone, a drug widely prescribed for the treatment of drug abusers with opioid dependence, affects human immunodeficiency virus (HIV) infection of human immune cells. When added to human fetal microglia and blood monocyte–derived macrophage cultures, methadone significantly enhanced HIV infection of these cells. This enhancement was associated with the up-regulation of expression of CCR5, a primary coreceptor for macrophage-tropic HIV entry into macrophages. Most importantly, the addition of methadone to the cultures of latently infected peripheral blood mononuclear cells from HIV-infected patients enhanced viral activation and replication. Although the in vivo relevance of these findings remains to be determined, the data underscore the necessity of further studies to define the role of opioids, including methadone, in the immunopathogenesis of HIV infection and AIDS.
doi:10.1086/338011
PMCID: PMC4009627  PMID: 11756991
10.  Frequent Detection of Polyomaviruses in Stool Samples from Hospitalized Children 
The Journal of infectious diseases  2005;192(4):658-664.
Background
Infection with BK virus (BKV) generally occurs early during life, but its mode of transmission has not been clearly defined. We tested the hypothesis that polyomavirus shedding in stool may be a source of BKV exposure.
Methods
Pediatric stool and rectal swab samples were tested for the presence of polyomavirus DNA by a polymerase chain reaction (PCR) assay that could detect a conserved region in the large T antigen gene of BKV, JC virus (JCV), and simian virus 40 (SV40). The specific viruses detected by this assay were confirmed by DNA sequence analysis of the PCR amplicons.
Results
Of 120 samples collected from 99 patients, 54 (45.0%) were positive for polyomavirus DNA. Of the 99 patients, 46 (46.5%) had at least 1 positive sample, with 38 (38.4%) positive for BKV and 8 (8.1%) positive for SV40. JCV was not detected. There was no association between polyomavirus fecal shedding and age, sex, race/ ethnicity, immune status, or symptoms of gastrointestinal disease in the children studied. The BKV strains detected displayed polymorphisms in the T antigen sequence.
Conclusions
Polyomaviruses are frequently present in stool samples from hospitalized children. These findings suggest that fecal-oral transmission of BKV may play a role in the ubiquity of infection.
doi:10.1086/432076
PMCID: PMC4010313  PMID: 16028135
11.  Attribution of Campylobacter Infections in Northeast Scotland to Specific Sources by Use of Multilocus Sequence Typing 
The Journal of infectious diseases  2009;199(8):1205-1208.
We show that a higher incidence of campylobacteriosis is found in young children (age, <5 years) living in rural, compared with urban, areas. Association of this difference with particular animal sources was evaluated using multilocus sequence typing. This evaluation was achieved by comparing Campylobacter isolates originating from these children, retail poultry, and a range of animal sources by use of source attribution and phylogenetic analysis methods. The results indicate that chicken is a major source of infection in young urban children, although not in their rural counterparts, for which ruminant and other avian sources are more important.
doi:10.1086/597417
PMCID: PMC3985119  PMID: 19265482
12.  Kaposi Sarcoma–Associated Herpesvirus (KSHV) Seroprevalence in Population-Based Samples of African Children: Evidence for At Least 2 Patterns of KSHV Transmission 
The Journal of infectious diseases  2009;200(3):430-438.
Background
Kaposi sarcoma–associated herpesvirus (KSHV) infection is endemic among adult populations in Africa. A prevailing view is that childhood transmission is primarily responsible for the high seroprevalence of KSHV among adults that is observed throughout the continent. However, few studies have directly examined children, particularly in locations where KS is not commonly endemic.
Methods
Participants were children aged 1.5−8.9 years, including 427 children from a population-based sample in South Africa, 422 from a population-based sample in Uganda, and 567 from a clinic-based sample in Uganda. All serum specimens were tested by the same laboratory for KSHV antibodies with use of 2 enzyme immunoassays (against K8.1 and ORF65) and 1 immunofluorescence assay.
Results
KSHV seroprevalence was 7.5%−9.0% among South African children and was not associated with age. In contrast, in the Ugandan population-based sample, KSHV seroprevalence increased from 10% among 2-year-old children to 30.6% among 8-year-old children (Ptrend < .001). In the Ugandan clinic-based sample, seroprevalence increased from 9.3% among 2-year-old children to 36.4% among 8-year-old children (Ptrend < .001).
Conclusion
Two distinct relationships between age and KSHV infection among children imply that KSHV transmission among children is not uniform throughout Africa and is therefore not always responsible for the high seroprevalence observed in adults. There are at least 2 patterns of KSHV transmission in Africa.
doi:10.1086/600103
PMCID: PMC3975590  PMID: 19534596
13.  Candida albicans Hyr1p Confers Resistance to Neutrophil Killing and Is a Potential Vaccine Target 
The Journal of infectious diseases  2010;201(11):1718-1728.
Candida albicans is the most common cause of invasive fungal infections in humans. It is unclear how C. albicans escapes from phagocytic attack and survives in the hostile blood environment during life-threatening systemic infections. Using a conditional overexpression or suppression genetic strategy, we discovered that HYR1 gene reduced phagocytic killing activity of C. albicans in vitro and increased tissue fungal burden in vivo. Concordant with its positive regulation by the transcription factor Bcr1p, autonomous expression of HYR1 complemented the hypersusceptibility to phagocyte-mediated killing of a bcr1 null mutant of C. albicans in vitro. As for C. albicans, heterologous expression of HYR1 in Candida glabrata rendered the organism more resistant to neutrophil killing activity. Vaccination with a recombinant Hyr1p significantly protected mice against hematogenously disseminated candidiasis (P = .001). Finally, anti-rHyr1p polyclonal antibodies enhanced mouse neutrophil killing activity by directly neutralizing rHyr1p effects in vitro. Thus, Hyr1 is an important virulence factor for C. albicans, mediating resistance to phagocyte killing. Hyr1p is a promising target for vaccine or other immunological or small molecule intervention to improve the outcomes of disseminated candidiasis.
doi:10.1086/652407
PMCID: PMC3933264  PMID: 20415594
14.  Viral Commensalism in Humans? 
doi:10.1086/588705
PMCID: PMC3918959  PMID: 18544010
15.  The Optimal Anatomic Sites for Sampling Heterosexual Men for Human Papillomavirus (HPV) Detection: The HPV Detection in Men Study 
The Journal of infectious diseases  2007;196(8):1146-1152.
Background
Human papillomavirus (HPV) infection in men contributes to infection and cervical disease in women as well as to disease in men. This study aimed to determine the optimal anatomic site(s) for HPV detection in heterosexual men.
Methods
A cross-sectional study of HPV infection was conducted in 463 men from 2003 to 2006. Urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples were obtained. Samples were analyzed for sample adequacy and HPV DNA by polymerase chain reaction and genotyping. To determine the optimal sites for estimating HPV prevalence, site-specific prevalences were calculated and compared with the overall prevalence. Sites and combinations of sites were excluded until a recalculated prevalence was reduced by <5% from the overall prevalence.
Results
The overall prevalence of HPV was 65.4%. HPV detection was highest at the penile shaft (49.9% for the full cohort and 47.9% for the subcohort of men with complete sampling), followed by the glans penis/coronal sulcus (35.8% and 32.8%) and scrotum (34.2% and 32.8%). Detection was lowest in urethra (10.1% and 10.2%) and semen (5.3% and 4.8%) samples. Exclusion of urethra, semen, and either perianal, scrotal, or anal samples resulted in a <5% reduction in prevalence.
Conclusions
At a minimum, the penile shaft and the glans penis/coronal sulcus should be sampled in heterosexual men. A scrotal, perianal, or anal sample should also be included for optimal HPV detection.
doi:10.1086/521629
PMCID: PMC3904649  PMID: 17955432
16.  Helicobacter pylori colonization is inversely associated with childhood asthma 
The Journal of infectious diseases  2008;198(4):553-560.
Background
Asthma, a serious health problem worldwide, is growing more common. The colonization of Helicobacter pylori, a major human indigenous (commensal) microbe that is present early in life may be relevant to childhood asthma risk.
Methods
We conducted cross-sectional analyses using data from 7,412 participants in the National Health and Nutrition Survey (NHANES) 1999–2000 to assess the association between H. pylori and childhood asthma.
Results
H. pylori seropositivity was inversely associated with early-onset asthma (onset age < 5 years) and current asthma in children 3–13 years. Among participants 3–19 years of age, the presence of H. pylori was inversely related to ever having asthma (OR = 0.69; 95% CI = 0.45–1.06), and the inverse association with early childhood-onset (
Conclusions
This study is the first to report an inverse association of H. pylori with asthma in children. The findings indicate new directions for research and asthma prevention.
doi:10.1086/590158
PMCID: PMC3902975  PMID: 18598192
Helicobacter pylori; epidemiology; asthma; cross-sectional study
The Journal of infectious diseases  2008;198(8):1123-1130.
Background
We studied whether severely immunocompromised, human immunodeficiency virus (HIV)–infected children who were beginning highly active antiretroviral therapy (HAART) or changing HAART regimens could spontaneously respond to a recall antigen (tetanus toxoid [TT] vaccine) or respond to a recall antigen and neoantigen (hepatitis A virus [HAV] vaccine) after 3 vaccinations.
Methods
A total of 46 children who had CD4 cell percentages <15% and who demonstrated a >0.75-log reduction in plasma HIV RNA levels within 4 weeks of starting HAART were randomized to receive vaccinations with either TT or HAV vaccines during the first 6 months of HAART. Study subjects then received the alternate vaccine during the next 6 months of HAART.
Results
Despite the early decline in viremia and the later increase in the percentage of CD4 T cells, spontaneous recovery of cell-mediated immunity (CMI) was not seen for TT. Serologic responses to TT required 3 vaccinations and were comparable in both groups. Serologic responses to HAV were infrequent and of low titer, although the group that received HAV vaccine after receiving TT vaccine performed somewhat better. CMI to HAV was virtually absent.
Conclusions
Severely immunocompromised children who are receiving HAART develop CMI and antibody to a recall antigen independent of the timing of vaccination, but they require a primary series of vaccinations. Antibodies to a neoantigen, HAV, developed when vaccination was delayed after initiation of HAART. CMI to a neoantigen was difficult to establish.
Trial registration
Clinicaltrials.gov identifier: NCT00004735/PACTG P1006.
doi:10.1086/592050
PMCID: PMC3895909  PMID: 18752430
The Journal of infectious diseases  2009;200(2):273-278.
estD encodes a carboxylic ester hydrolase and is part of the NmlR regulon in Neisseria gonorrhoeae. An estD mutant was found to be susceptible to nitrite and to S-nitrosoglutathione. This mutant was also unable to infect and survive within human cervical epithelial cells, and it showed reduced ability to form a biofilm on these cells. We conclude that esterase D is an integral part of the nitrosative stress defense system of N. gonorrhoeae and that it has potential importance in pathogenesis.
doi:10.1086/599987
PMCID: PMC3889162  PMID: 19527171
The Journal of infectious diseases  2009;200(2):10.1086/599795.
Background
The morbidity and mortality resulting from dengue hemorrhagic fever (DHF) are largely caused by endothelial barrier dysfunction and a unique vascular leakage syndrome. The mechanisms that lead to the location and timing of vascular leakage in DHF are poorly understood. We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome.
Methods
We used an in vitro model of human endothelium to study the combined effects of dengue virus (DENV) type 2 (DENV2) infection and inflammatory mediators on paracellular macromolecule permeability over time.
Results
Over the initial 72 h after infection, DENV2 suppressed tumor necrosis factor (TNF)–α–mediated hyperpermeability in human umbilical vein endothelial cell (HUVEC) monolayers. This suppressive effect was mediated by type I interferon (IFN). By 1 week, TNF-α stimulation of DENV2-infected HUVECs synergistically increased cell cycling, angiogenic changes, and macromolecule permeability. This late effect could be prevented by the addition of exogenous type I IFN.
Conclusions
DENV infection of primary human endothelial cells differentially modulates TNF-α–driven angiogenesis and hyperpermeability over time. Type I IFN plays a central role in this process. Our findings suggest a rational model for the DHF vascular leakage syndrome.
doi:10.1086/599795
PMCID: PMC3881588  PMID: 19530939
The Journal of infectious diseases  2007;196(8):10.1086/521632.
Background
Human papillomavirus (HPV) is strongly associated with cervical and other anogenital cancers. Identification of risk factors for HPV infection in men may improve our understanding of HPV transmission and prevention.
Methods
HPV testing for 37 types was conducted in 463 men 18–40 years old recruited from 2 US cities. The entire anogenital region and semen were sampled. A self-administered questionnaire was completed. Multivariate logistic regression aided the identification of independent risk factors for any HPV type, oncogenic HPV types, and nononcogenic HPV types.
Results
Prevalence was 65.4% for any HPV, 29.2% for oncogenic HPV, and 36.3% for nononcogenic HPV. Factors significantly associated with any HPV were smoking ≥10 cigarettes per day (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0–5.3]) and lifetime number of female sex partners (FSPs) (OR for ≥21, 2.5 [95% CI, 1.3–4.6]), and factors significantly associated with oncogenic HPV were lifetime number of FSPs (OR for ≥21, 7.4 [95% CI, 3.4–16.3]) and condom use during the past 3 months (OR for more than half the time, 0.5 [95% CI, 0.3–0.8]). For nononcogenic HPV, a significant association was found for number of FSPs during the past 3 months (OR for ≥2, 2.9 [95% CI, 1.4–6.3]).
Conclusions
Lifetime and recent number of FSPs, condom use, and smoking were modifiable risk factors associated with HPV infection in men.
doi:10.1086/521632
PMCID: PMC3877918  PMID: 17955431
The Journal of infectious diseases  2009;199(11):10.1086/598524.
Background
Capsule expression may be important during ascending Escherichia coli urinary tract infections (UTIs).
Methods
An isogenic ksl(k2)ABCDE mutant of extraintestinal pathogenic E. coli (ExPEC) strain CFT073 that could not synthesize the K2 capsule was compared with wild-type CFT073, to determine virulence in a murine model of ascending UTI and in vitro killing assays.
Results
No significant differences were observed regarding the abilities of the mutant and the wild-type CFT073 strains to colonize the murine urinary tract in single-challenge infection experiments. However, in competitive-colonization experiments, the mutant was significantly outcompeted by the wild-type strain in urine and the kidneys. The mutant strain was also more susceptible to human serum. Complementation of the mutant with a plasmid containing the ksl(k2)ABCDE genes restored capsule expression, enhanced survival in the murine urinary tract, and restored serum resistance.
Conclusion
These results indicate that expression of the K2 capsule is important for the pathogenesis of UTI and provides protection against complement-mediated killing. To our knowledge, this is the first study in which the E. coli capsule has been proven to play a role in infection by use of isogenic mutants and genetic complementation.
doi:10.1086/598524
PMCID: PMC3872369  PMID: 19432551
The Journal of infectious diseases  2008;197(7):10.1086/528806.
Nasopharyngeal colonization precedes invasive pneumococcal disease. HIV infection increases rates of invasive disease; its effect on colonization is unknown. In a longitudinal cohort of HIV-positive/negative Zambian mothers, HIV increased the risk of colonization (RR 1.9, 95% CI 1.3–2.8) and repeated colonizations (RR 2.4, 95% CI 1.1–5.3), and reduced time to new colonization (p=0.01). Repeated colonizations with homologous sero/factor-types occurred only among HIV-positive mothers. Pediatric serotypes 6, 19 and 23 accounted for the excess colonization in the HIV-positive mothers. HIV significantly increases the risk of pneumococcal colonization. Increased colonization by pediatric serotypes suggests a potential role for the 7-valent pneumococcal vaccine.
doi:10.1086/528806
PMCID: PMC3869545  PMID: 18419536
The Journal of infectious diseases  2009;200(7):10.1086/605645.
Background
A herpes simplex virus (HSV) 2 candidate vaccine consisting of glycoprotein D (gD2) in alum and monophosphoryl lipid A (MPL) reduced genital herpes disease in HSV-1 seronegative women, but not in men or HSV-1 seropositive women.
Methods
To determine the effect of HSV-1 serostatus on effectiveness of different vaccines, we tested gD2 in alum/MPL, gD2 in Freund's adjuvant, and dl5-29 (a replication-defective HSV-2 mutant) in seropositive or seronegative guinea pigs.
Results
In HSV-1 seronegative animals, dl5-29 induced the highest titers of neutralizing antibody, and after vaginal challenge with wild-type virus, dl5-29 resulted in lower rates of vaginal shedding, lower levels of HSV DNA in ganglia, and a trend for less acute and recurrent genital herpes than the gD2 vaccines. In HSV-1 seropositive animals, all three vaccines induced similar titers of neutralizing antibodies and showed similar levels of protection against acute and recurrent genital herpes after vaginal challenge with wild-type virus, but dl5-29 reduced vaginal shedding after challenge more than the gD2 vaccines.
Conclusions
dl5-29 is an effective vaccine in both HSV-1 seropositive and seronegative guinea pigs, and was superior to gD2 vaccines in reducing virus shedding after challenge in both groups of animals which might reduce transmission of HSV-2.
doi:10.1086/605645
PMCID: PMC3826825  PMID: 19702506
Herpes simplex virus 1; Herpes simplex virus 2; Vaccine; Replication-Defective Virus; Glycoprotein D
The Journal of infectious diseases  2007;196(6):876-883.
Background
A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear.
Methods
We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples—from the lesion and from healthy skin from the same patient—were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models.
Results
Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44–8.11]) and for the healthy skin samples (OR, 3.65 [95% CI 1.79–7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92–10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72–6.99]).
Conclusions
Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma.
doi:10.1086/521031
PMCID: PMC3795387  PMID: 17703418

Results 1-25 (682)