Erna M. Kojic

Candida Infections of Medical Devices

SUMMARY The number of indwelling medical devices is escalating, and an increasing proportion of device-related infections are being caused by Candida spp. Candida spp. produce biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Management of device-related Candida infections can be challenging. Removal of the infected device is generally needed to establish cure of Candida infections of medical devices. However, since the pathogenesis of Candida bloodstream infection is complicated, more studies are necessary to determine the role of catheter exchange in patients with both gastrointestinal tract mucositis and indwelling catheters. The medical and economic impact of these infections is enormous.

Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in HIV-1–Infected Women

BACKGROUND Women infected with human immunodeficiency virus (HIV) are disproportionately affected by human papillomavirus (HPV)-related anogenital disease, particularly with increased immunosuppression. AIDS Clinical Trials Group protocol A5240 was a trial of 319 HIV-infected women in the United States, Brazil, and South Africa to determine immunogenicity and safety of the quadrivalent HPV vaccine in 3 strata based on screening CD4 count: >350 (stratum A), 201-350 (stratum B), and ≤200 cells/µL (stratum C). METHODS Safety and serostatus of HPV types 6, 11, 16, and 18 were examined. HPV serological testing was performed using competitive Luminex immunoassay (HPV-4 cLIA). HPV type-specific seroconversion analysis was done for participants who were seronegative for the given type at baseline. RESULTS Median age of patients was 36 years; 11% were white, 56% black, and 31% Hispanic. Median CD4 count was 310 cells/µL, and 40% had undetectable HIV-1 load. No safety issues were identified. Seroconversion proportions among women at week 28 for HPV types 6, 11,16, and 18 were 96%, 98%, 99%, and 91%, respectively, for stratum A; 100%, 98%, 98%, and 85%, respectively, for stratum B, and 84%, 92%, 93%, and 75%, respectively, for stratum C. CONCLUSIONS The quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was safe and immunogenic in HIV-infected women aged 13-45 years. Women with HIV RNA load >10 000 copies/mL and/or CD4 count <200 cells/µL had lower rates of seroconversion rates. Clinical Trials Registration. NCT00604175.

Human papillomavirus infection and cytologic abnormalities of the anus and cervix among HIV-infected women in the study to understand the natural history of HIV/AIDS in the era of effective therapy (the SUN study).

Background: Human papillomavirus (HPV) infection of the cervix and related abnormal cervical cytology in HIV-infected women has been well described. Little is known about anal HPV infection in HIV-infected women. Methods: The SUN Study is a prospective cohort study of 700 HIV-infected patients including 167 women. At baseline, patients completed a behavioral questionnaire and provided, among other samples, cervical and anal swabs for HPV detection and genotyping and for cytologic examination. Here, we present the available baseline data on the 167 women in the SUN study. Results: Baseline results were available for 120 women (median age: 38 years, 57% non-Hispanic black, median CD4 cell count 444.5 cells/mm3), of whom, 77% were taking antiretroviral therapy. The prevalences in the anus and cervix of any HPV were 90% and 83%, respectively (P = 0.039), and of high-risk (HR) types 85% and 70%, respectively, (P = 0.001). There was no significant difference in the prevalences of abnormal cytology between the anus and cervix: 38% and 33%, respectively (P = 0.217). Although the presence of abnormal cervical cytology was associated with the presence of abnormal anal cytology (relative risk: 1.7, P = 0.024), its sensitivity (52.5%) and positive predictive value positive (45.6%) for identifying women with abnormal anal cytology were poor. A history of anal sex was not associated with anal HPV infection or abnormal anal cytology. Conclusions: In this cohort of HIV-infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data support the need for studies of anal cytologic screening of HIV-infected women.

Factors associated with non-adherence to antiretroviral therapy in the SUN study

Abstract Background. Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. Methods. We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. Results. Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm3), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20–3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14–3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18–3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02–2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25–3.57). Conclusion. Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.

Detection and quantitation of HPV in genital and oral tissues and fluids by real time PCR

BackgroundHuman papillomaviruses (HPVs) remain a serious world health problem due to their association with anogenital/oral cancers and warts. While over 100 HPV types have been identified, a subset is associated with malignancy. HPV16 and 18 are the most prevalent oncogenic types, while HPV6 and 11 are most commonly responsible for anogenital warts. While other quantitative PCR (qPCR) assays detect oncogenic HPV, there is no single tube assay distinguishing the most frequent oncogenic types and the most common types found in warts.ResultsA Sybr Green-based qPCR assay was developed utilizing degenerate primers to the highly conserved HPV E1 theoretically detecting any HPV type. A single tube multiplex qPCR assay was also developed using type-specific primer pairs and TaqMan probes that allowed for detection and quantitation of HPV6,11,16,18. Each HPV type was detected over a range from 2 × 101 to 2 × 106copies/reaction providing a reliable method of quantitating type-specific HPV in 140 anogenital/cutaneous/oral benign and malignant specimens. 35 oncogenic and low risk alpha genus HPV types were detected. Concordance was detected in previously typed specimens. Comparisons to the gold standard detected an overall sensitivity of 89% (95% CI: 77% - 96%) and specificity of 90% (95%CI: 52% - 98%).ConclusionThere was good agreement between the ability of the qPCR assays described here to identify HPV types in malignancies previously typed using standard methods. These novel qPCR assays will allow rapid detection and quantitation of HPVs to assess their role in viral pathogenesis.

Administration of Protein-Conjugate Pneumococcal Vaccine to Patients Who Have Invasive Disease after Splenectomy Despite Their Having Received 23-Valent Pneumococcal Polysaccharide Vaccine

Patients who undergo splenectomy are at greatly increased risk for overwhelming pneumococcal bacteremia and death. Twenty-three-valent pneumococcal polysaccharide vaccine (PPV-23), which contains capsular polysaccharides (PSs) from 23 common serotypes of Streptococcus pneumoniae, is strongly recommended for such patients. The capacity to respond to PPV-23 by producing immunoglobulin (Ig) G is genetically regulated. Some proportion of adults do not respond and, despite postsplenectomy administration of PPV-23, may remain susceptible to recurrent pneumococcal sepsis. Here, we describe 2 patients who had recurring pneumococcal bacteremia after undergoing splenectomy despite having received numerous doses of PPV-23. Heptavalent protein-conjugate pneumococcal vaccine (PCPV-7) was then administered, and it induced high levels of IgG to all 7 PSs; in one of the patients, functional activity against 5 of the 7 PSs was demonstrable, both in vitro and in vivo. Recurrent pneumococcal bacteremia in patients who have undergone splenectomy may indicate a genetically regulated failure to respond to PPV-23; PCPV-7 may stimulate production of IgG to PSs in such patients.

Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature

In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by anatomical site. Among women, prevalence was found to be 0.6–35.8% for rectal gonorrhea (median reported prevalence 1.9%), 0–29.6% for pharyngeal gonorrhea (median 2.1%), 2.0–77.3% for rectal chlamydia (median 8.7%), and 0.2–3.2% for pharyngeal chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.2–24.0% for rectal gonorrhea (median 5.9%), 0.5–16.5% for pharyngeal gonorrhea (median 4.6%), 2.1–23.0% for rectal chlamydia (median 8.9%), and 0–3.6% for pharyngeal chlamydia (median 1.7%). Among MSW, the prevalence was found to be 0–5.7% for rectal gonorrhea (median 3.4%), 0.4–15.5% for pharyngeal gonorrhea (median 2.2%), 0–11.8% for rectal chlamydia (median 7.7%), and 0–22.0% for pharyngeal chlamydia (median 1.6%). Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse. We discuss current clinical recommendations and future directions for research.

Update: human papillomavirus infection remains highly prevalent and persistent among HIV-infected individuals

Purpose of review Human papillomavirus infections and human papillomavirus-associated anogenital tumors are more prevalent in HIV-infected than HIV-uninfected individuals. This review focuses on recent developments related to human papillomavirus burden in HIV-infected individuals; anogenital human papillomavirus types and type-specific differences in the natural history of human papillomavirus infections; the effect of highly active antiretroviral therapy on human papillomavirus infection; and novel human papillomavirus therapeutic interventions. Recent findings There is a paucity of recent data on the effect of highly active antiretroviral therapy on human papillomavirus infection and its related anogenital abnormalities/cancer. Review articles on the molecular biology of human papillomavirus in HIV infection outline why, despite highly active antiretroviral therapy, anogenital tumors may continue to increase in this population. Studies continue to confirm the high prevalence of human papillomavirus infection and to define the different human papillomavirus types correlated with anogenital cytologic abnormalities, an important area in light of the development of an effective type-specific human papillomavirus vaccine. Summary Anogenital human papillomavirus infection remains highly prevalent and persistent in HIV-infected individuals. HIV is associated with a wide diversity of human papillomavirus types and a high prevalence of anogenital cytologic abnormalities. The incidence of anogenital human papillomavirus-related cancers remains high in the highly active antiretroviral therapy era, raising concerns of human papillomavirus infections as a rising health burden among HIV-infected individuals. Interventions aimed at preventing human papillomavirus infections with vaccinations need to be evaluated in HIV-infected individuals.

A Positive Enzyme-Linked Immunoelectrotransfer Blot Assay Result for a Patient without Evidence of Cysticercosis

The enzyme-linked immunoelectrotransfer blot (EITB) has been considered diagnostic of cysticercosis when the results are positive. We describe a patient with a single band at 50 kDa on EITB and neuroimaging abnormalities suggestive of neurocysticercosis but no evidence of exposure to Taenium solium. Autopsy findings excluded neurocysticercosis. We suggest that a single band at 50 kDa on an EITB be considered an equivocal finding rather than diagnostic of cysticercosis.

HIV-2 diagnosis and quantification in high-risk patients

Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States.