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1.  Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials 
Background
Vitamin D deficiency has been associated with a number of diseases, including influenza. Whether or not this reflects a causal relationship is unknown. We therefore wanted to examine if supplementation with vitamin D would affect the incidence and severity of influenza-like disease.
Methods
Questionnaires on influenza were sent to subjects participating in ongoing placebo-controlled intervention studies with vitamin D supplementation, up until the end of April 2010.
Results
Five hundred and sixty-nine subjects from 10 different clinical trials were included in the study, of whom 289 were randomized to receive vitamin D (1111–6800 IU/day) and 280 to receive placebo. Influenza-like disease during the previous fall/winter was reported in 38 subjects in the vitamin D group and 42 in the placebo group (non-significant), of whom 25 and 26 subjects, respectively, fulfilled our clinical criteria for influenza. In these latter subjects, the duration of illness was significantly longer among those in the vitamin D group than among those in the placebo group (median 7 (range 2–60) days vs median 4 (range 2–18) days; p = 0.007). However, this difference was not statistically significant if all 38 (vitamin D) and 42 (placebo) subjects who reported symptoms were included.
Conclusion
Our results do not support the hypothesis that high doses of vitamin D supplementation will have a pronounced effect on influenza-like disease in populations not targeted for high influenza risk.
doi:10.3109/00365548.2011.621446
PMCID: PMC3917712  PMID: 22026455
H1N1; influenza; randomized clinical trial; vitamin D
2.  Surgical site infection prophylaxis strategies for cardiothoracic surgery: a decision-analytic model 
Background
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of invasive surgical site infection (SSI) in the USA. Antimicrobial prophylaxis for SSI typically includes a cephalosporin. Vancomycin is used to provide MRSA coverage, but administration timing is challenging. Linezolid is an attractive agent for SSI prophylaxis, particularly for the prevention of SSI due to MRSA.
Methods
We developed a decision-analytic model to evaluate linezolid use for cardiothoracic SSI prophylaxis. A theoretical cohort of 10,000 cardiothoracic surgery patients was followed through 2 stages: 1) occurrence of SSI, and 2) mortality after SSI. All patients were administered cefuroxime, vancomycin, or linezolid between 1–180 minutes prior to surgical incision. SSIs were categorized into three pathogen categories: 1) methicillin-susceptible Gram-positive, 2) methicillin-resistant Gram-positive, and 3) other organisms. The most effective strategy resulted in the fewest SSIs. Assumptions for antibiotic effectiveness, impact of administration time, and pathogens were based on the published literature.
Results
Compared with cefuroxime, there was a 1% increase in the total number of SSIs in the linezolid group (mean SSI increase = 7), while there was a 12% increase in the vancomycin group (mean SSI increase = 86). Linezolid prophylaxis resulted in fewer SSIs due to methicillin-resistant Gram-positive infections (n=108) compared with cefuroxime (n = 200, 46% reduction in the linezolid group) and vancomycin (n = 119, 9% reduction in the linezolid group).
Conclusions
This simulation indicates that linezolid may offer benefits for SSI prophylaxis over existing prophylactic agents, particularly for the prevention of SSI due to Gram-positive methicillin-resistant pathogens.
doi:10.3109/00365548.2012.700118
PMCID: PMC3684012  PMID: 22831753
Surgical site infection; prophylaxis; decision-analytic model; linezolid; vancomycin
3.  Invasive aspergillosis among heart transplant recipients is rare but causes rapid death due to septic shock and multiple organ dysfunction syndrome 
Between 2000 and 2011, proven or probable invasive aspergillosis (IA) was diagnosed in 1.7% (8/455) of heart transplant (HTx) recipients at our center, in the absence of antifungal prophylaxis. All patients had invasive pulmonary infections and 75% (6/8) were diagnosed during 2 separate 3-month periods. Cases were notable for their association with septic shock and multiple organ dysfunction syndrome (MODS) (75%, 6/8 each), non-specific clinical and radiographic findings, and rapid mortality despite mould-active antifungal therapy (88%, 7/8; occuring at a median 11 days after diagnosis). All patients had predisposing conditions known to be risk factors for IA. For patients with early IA (within 90 days of HTx), conditions included hemodialysis, thoracic re-operation, and the presence of another case in the institution within the preceding 3 months. For late-onset IA, conditions included hemodialysis and receipt of augmented immunosuppression. Clinicians should suspect IA in HTx recipients with risk factors who present with non-specific and unexplained respiratory syndromes, including those in septic shock and MODS, and institute prompt antifungal therapy without waiting for the results of cultures or other diagnostic tests.
doi:10.3109/00365548.2012.705018
PMCID: PMC3686283  PMID: 22830948
Aspergillosis; septic shock; heart transplant
4.  Comparison of clinical features and immunological parameters of patients with dehydrating diarrhoea infected with Inaba or Ogawa serotypes of Vibrio cholerae O1 
Vibrio cholerae O1, Ogawa and Inaba serotypes, both cause severe cholera. We compared clinical and immunological features in patients in Bangladesh infected with these 2 serotypes. Blood was collected from hospitalized Ogawa (N = 146) or Inaba (N = 191) patients at the acute stage (day 2) and 5 and 19 days later. Ogawa patients were younger than Inaba, presented with shorter duration of diarrhoea, and had more frequent abdominal pain, vomiting and need for intravenous fluids (p < 0.05). Inaba patients more frequently had dark-field positive stools (p < 0.01). Inaba strains were more susceptible to tetracycline and erythromycin than Ogawa strains (p < 0.001). Ogawa infection produced higher plasma vibriocidal as well as IgG responses to cholera toxin B subunit, toxin-coregulated pilus subunit and lipopolysaccharide (LPS); higher IgA responses to LPS in ‘antibody in lymphocyte supernatant’ (ALS) specimens were also seen. These results suggest that a cholera vaccine based on the Ogawa serotype needs to be further investigated.
doi:10.3109/00365540903289688
PMCID: PMC3786431  PMID: 19883159
5.  Infection disclosure in the injecting dyads of Hungarian and Lithuanian injecting drug users who self-reported being infected with hepatitis C virus or human immunodeficiency virus 
The aim of this study was to assess the prevalence and correlates of disclosure to network members of being hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-infected among injecting dyads of infected injection drug users (IDUs) in Budapest, Hungary and Vilnius, Lithuania,. Multivariate generalized estimating equations (GEE) were used to assess associations. Very strong infection disclosure norms exist in Hungary, and HCV disclosure was associated with using drugs and having sex within the dyad. Non-ethnic Russian IDUs in Lithuania were more likely to disclose HCV infection to non-Roma, emotionally close and HCV-infected network members, and to those with whom they shared cookers, filters, drug solutions or rinse water or got used syringes from, and if they had fewer non-IDU or IDU network members. Ethnic Russian Lithuanian IDUs were more likely to disclose HCV if they had higher disclosure attitude and knowledge scores, ‘trusted’ network members, and had lower non-injecting network density and higher injecting network density. HIV-infected Lithuanian IDUs were more likely to disclose to ‘trusted’ network members. Disclosure norms matched disclosure behaviour in Hungary, while disclosure in Lithuania to ‘trusted’ network members suggests possible stigmatization. Ongoing free and confidential HCV/HIV testing services for IDUs are needed to emphasize and strengthen disclosure norms, and to decrease stigma.
doi:10.3109/00365548.2010.513064
PMCID: PMC3074185  PMID: 20840002
6.  Evaluation of a modified interferon gamma release assay for the diagnosis of latent tuberculosis infection in adult and pediatric populations that enables delayed processing 
The objective of the study was to evaluate the specificity of a modified interferon gamma release assay procedure that allows storage of blood samples for up to 32 hours before processing. A total of 116 subjects were enrolled for the study. Two blood samples were collected from each volunteer; one specimen was processed within 8 hours and analyzed using the T-SPOT.TB test; the second specimen was stored overnight and processed 23 to 32 hours later after addition of the T-Cell Xtend™ reagent and then analyzed using the T-SPOT.TB test. A total of 108 paired T-SPOT.TB and T-SPOT.TB plus T-Cell Xtend™ tests were analyzed on specimens from 97 adults and 11 children. The median age of the subjects was 28 years old with 68.5% female and 78.7% White. The overall agreement between the two tests was 98.2% (106/108). Specificity of the T-SPOT.TB test was 99.1% (107/108) and for T-SPOT.TB plus T-Cell Xtend was 97.2%. The two tests were comparable in results. Increasing storage time of the collected blood specimen prior to processing provides flexibility for clinicians and laboratories. Additional studies in larger and diverse patient populations including immunocompromised, pediatric, patients with active TB disease or latent tuberculosis infection are needed.
doi:10.3109/00365548.2010.498021
PMCID: PMC3249229  PMID: 20608764
7.  HIV and HCV discordant injecting partners and their association to drug equipment sharing 
Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR = 1.85) and negatively with discordant HCV status (OR = 0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR = 1.61) and HCV (OR = 1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners.
doi:10.1080/00365540902721376
PMCID: PMC2929251  PMID: 19172434 CAMSID: cams1471
8.  Atypical Genital Herpes: Report of Five Cases 
Manifestations of human genital herpes virus (HSV) infection are not limited to the typical cluster of genital lesions. Here we present 5 case histories suggestive to clinically atypical genital herpes (HSV detected with the polymerase chain reaction) collected in 2001 from a private outpatient clinic specializing in dermatological and venereal diseases. The clinical presentations included mucopurulent cervicitis, haemorrhagic cystitis, recurrent urethritis, and lower hack pain.
PMCID: PMC2925659  PMID: 15000557
9.  Type 2 diabetes and multi-drug resistant tuberculosis 
The association between tuberculosis (TB) and diabetes is re-emerging with the epidemic of type 2 diabetes (T2DM). We analyzed retrospective data from 2,878 TB patients across the Texas/Mexico border. Overall 161/2878 (5.6%) patients had MDR TB (resistance to rifampin and isoniazid): Texas 49/1442 (3.4%) and Mexico 112/1436 (7.8%). In Texas MDR TB was significantly associated with T2DM (OR 2.1 95% CI 1.1–4.2) when adjusted for age, gender, drug and alcohol abuse, HIV infection and history of previous episode of TB, and in Mexico (OR 1.80 95% CI 1.1–2.9) when adjusted for age and gender. Patients with T2DM were consistently more likely to be compliant with DOTS therapy (OR 2.4 95% CI 1.1–5.4) than patients without T2DM. In Texas, all but 3 of the T2DM patients with MDR TB were resistant at their first culture at the time of diagnosis. It is possible that impaired immunity in T2DM increases susceptibility to infection with resistant strains.
doi:10.1080/00365540802342372
PMCID: PMC2887603  PMID: 18728934
10.  Burden of respiratory syncytial virus in hospitalized infants and young children in Amman, Jordan 
Acute respiratory infections (ARI) play a major role in hospitalizations in the Middle East, but the specific viral causes are unknown. We conducted prospective viral surveillance in children <5 y of age admitted with ARI and/or fever at 2 dissimilar hospitals in Amman, Jordan during peak respiratory syncytial virus (RSV) season. We collected prospective clinical and demographic data and obtained nose/throat swabs for testing for RSV by real-time polymerase chain reaction (RT-PCR). We obtained clinical and laboratory data for 728/743 (98%) subjects enrolled. The children’s median age was 4.3 months, 58.4% were males, 87% were breastfed, 4% attended day care, 67% were exposed to smokers, 7% were admitted to the intensive care unit, and 0.7% died (n = 5). Out of 728 subjects, 467 (64%) tested positive by RT-PCR for RSV. Comparing RSV-positive with RSV-negative subjects, the RSV-positive subjects had lower median age (3.6 vs 6.4 months, p < 0.001) and fewer males (55% vs 64%, p = 0.02). RSV-positive children had higher rates of oxygen use (72% vs 42%, p < 0.001), a longer hospital stay (5 vs 4 days, p = 0.001), and higher hospital charges (US$538 vs US$431, p < 0.001) than RSV-negative children. In young hospitalized Jordanian infants, the medical and financial burden of RSV was found to be high. Effective preventive measures, such as an RSV vaccine, would have a significant beneficial impact.
doi:10.3109/00365540903496544
PMCID: PMC2854220  PMID: 20100116
11.  Severity and outcomes of Pneumocystis pneumonia in patients newly diagnosed with HIV infection: an observational cohort study 
It is unclear whether patients who are unaware of their HIV infection have different severity or outcomes of Pneumocystis pneumonia (PCP) compared to patients who have been previously diagnosed with HIV. In this retrospective observational cohort study of consecutive HIV-infected patients with microscopically diagnosed PCP at San Francisco General Hospital between 1997 and 2006, 121 of 522 patients (23%) were unaware of their HIV infection prior to their diagnosis of PCP. The proportion of patients with concurrently diagnosed HIV and PCP each year remained unchanged during the study period. Patients with newly diagnosed HIV had a significantly higher alveolar-arterial oxygen gradient at presentation (median 51 versus 45 mm Hg, p=0.03), but there were no differences in mortality, frequency of mechanical ventilation, or admission to intensive care compared to patients with previously diagnosed HIV infection. In multivariate analysis, patients who reported a sexual risk factor for HIV infection were more likely to be newly diagnosed with HIV than patients who reported injection drug use as their only HIV risk factor (odds ratio = 3.14, 95% confidence interval 1.59–6.18, p = 0.001). This study demonstrates a continued need for HIV education and earlier HIV testing, particularly in patients with high-risk sexual behavior.
doi:10.1080/00365540903051633
PMCID: PMC2806953  PMID: 19521925
12.  The platelet activating factor receptor is not required for exacerbation of bacterial pneumonia following influenza 
Pneumonia caused by Streptococcus pneumoniae is a significant cause of morbidity and mortality during influenza virus epidemics. We had previously advanced the hypothesis that interactions of pneumococcus with the receptor for platelet activating factor (PAFR) in the lung were facilitated by antecedent influenza virus infection and play a major role in the pathogenesis of bacterial super-infections. Although influenza enhanced the adherence of pneumococci to respiratory epithelial cells in vitro, chemical or antibody-mediated blockade of the PAFR did not affectt adherence. In agreement with these data, mice lacking PAFR had similar bacterial loads within the lung compartment when compared to heterozygous littermates and were not protected from secondary pneumococcal pneumonia after influenza. Lack of support for this hypothesis and the observation of enhanced inflammation during secondary pneumococcal pneumonia in mice lacking PAFR may moderate enthusiasm for treatment strategies targeting the interaction of bacteria with PAFR.
doi:10.1080/00365540701477568
PMCID: PMC2715993  PMID: 17852951
influenza virus; Streptococcus pneumoniae; pneumonia; platelet activating factor receptor
13.  HTLV-2 infection in injection drug users in King County, Washington 
Human T-cell lymphotropic virus type 2 (HTLV-2) is endemic in injection drug users (IDU), and native American populations in the Americas. Transmission is associated with high-risk injection and sexual practices. A cohort of 2561 IDU in King County, Washington completed 2 study visits over 1 y. HTLV-2 infection was detected in 190 (7.4%) of 2561 IDU, and 13 (7.8 cases per 1000 person-y) incident infections occurred during the study. Prevalent infection was associated with female gender, non-white race, longer duration as IDU, having a tattoo, combined injection of heroin and cocaine, and with serologic evidence of hepatitis B and C infection. Seroconversion was more common in women, and was associated with African American race, heterosexual identity and longer duration as IDU. In conclusion, increased risk of HTLV-2 infection was associated with non-white race, and injection drug of choice, suggesting injection networks may play an important role in transmission of HTLV-2. The high correlation of HTLV-2 infection with HCV infection suggests the major route of transmission in IDU is via injection practices. Additional studies are needed to examine the clinical manifestations of HTLV-2 infection, as well as the clinical and virological manifestations of HTLV-2/HCV coinfection.
doi:10.1080/00365540600617009
PMCID: PMC2683846  PMID: 16857611
14.  Vaccine herd effect 
Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.
doi:10.3109/00365548.2011.582247
PMCID: PMC3171704  PMID: 21604922
Vaccine herd effect; vaccine herd immunity
15.  Cerebrospinal fluid viral breakthrough in two HIV-infected subjects on darunavir/ritonavir monotherapy 
Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid viral breakthrough together with increased immunoactivation and biomarker signs of neuronal injury. These 2 cases raise concerns about the effectiveness of darunavir/ritonavir monotherapy in HIV CNS infection. Thus, we recommend caution with protease inhibitor monotherapy until CNS results have been obtained from clinical studies.
doi:10.3109/00365548.2012.690526
PMCID: PMC3507278  PMID: 22776013
HIV; cerebrospinal fluid; darunavir; monotherapy; neuronal injury

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