Hepatitis C and Cardiovascular Risk

Conflicting results have been produced regarding the association between chronic hepatitis C virus (HCV) infection and coronary artery disease, including heart attacks and strokes. It was found in a study about the relationship between HCV infection and risk for incident (newly emerging) coronary artery disease. HCV-positive patients were less likely to have arterial hypertension, dyslipidemias, and diabetes than persons without HCV. HCV-positive patients were more likely to smoke cigarettes and abuse alcohol or drugs. Compared with participants without HCV, patients with HCV had lower mean plasma levels of total cholesterol , low-density lipoprotein (LDL) cholesterol, and triglycerides .

In a multivariate analysis, HCV infection was associated with a 25% higher risk for coronary artery disease. Classic risk factors (older age, hypertension, smoking, diabetes, dyslipidemias) were associated with a higher risk for coronary artery disease. In contrast, nonwhite ethnicity and female sex were associated with a lower risk. It was concluded that people infected with HCV are at increased risk for coronary artery disease despite having fewer other cardiovascular risk factors.

(Butt A, Xiaoqiang W, Budoff M, et al. Hepatitis C virus infection and the risk of coronary disease. Program and abstracts of the 48th ICAAC/46th IDSA; October 25-28, 2008; Washington, DC. Abstract V-4219)

Sleep Quality Is An Important Predictor Of Immunity And Susceptibility To The Common Cold

Poorer sleep efficiency and shorter sleep duration in the weeks before exposure to a rhinovirus are linked to greater susceptibility to the common cold. Sleep quality is an important predictor of immunity and susceptibility to the common cold. Sleep deprivation has been shown to result in poorer immune function and to attenuate antibody response to virus infections. Shorter sleep duration and lower efficiency were associated with an increased risk for development of a common cold. People who less than 7 hours of sleep were 2.94 times more likely to get a cold than those with 8 hours or more of sleep. Longer sleep duration is associated with a reduced risk for infection with the common cold. People with less than 92% sleep efficiency were 5.50 times more likely to get a cold than those with 98% or more efficiency. Higher sleep efficiency is associated with a reduced risk for infection with the common cold, and sleep efficiency lower than 85% is associated with an increased risk.
So, if you don't want to get cold, please just sleep tight... :)
(Arch Intern Med. 2009;169:62-67)

The Difficulties of Acute HCV-Infection Diagnosis

Most individuals infected with hepatitis C virus (HCV) fail to clear virus at the acute stage, becoming chronically infected, with consequent significant risks of progressive liver disease, cirrhosis and hepatocellular carcinoma. Treatment of chronic HCV with combination pegylated-interferon (PEG-IFN) and ribavirin achieves sustained virological response (SVR) rates of 42-52% of patients infected with HCV genotype 1 and 76-82% of those with genotype 2/3. In contrast, much higher SVR rates (e.g. >97%) have been reported when treating acute HCV infection with PEG-IFN, irrespective of the infecting genotype. It would thus seem preferable to treat HCV infection at the acute stage rather than waiting for the infection to become chronic.

The problem is the diagnosis of acute HCV infection is not straightforward. Detection of anti-HCV IgM does not distinguish acute from chronic infection. Genome or antigen detection techniques provide information on the current infection status of an individual, but do not indicate when infection may have taken place. One possible laboratory approach to diagnosis of acute infection would be to demonstrate sero- or genoconversion in serial samples, but practically, it is difficult to obtain regular repeat samples in high-risk individuals such as injecting drug users (IDUs). Clinical approaches to diagnosis are also flawed. Only a small minority of acute infections are symptomatic. Even in patients presenting with acute hepatitis C, the majority of whom are already anti-HCV positive, one cannot be certain that illness is due to recent infection with HCV rather than another inter-current cause in a chronically infected patient.
(J Viral Hepat. 2008;15(12):871-877)

HIV and Methicillin-resistant Staphylococcus Aureus (MRSA)

HIV-infected patients could increase the risk for Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, including bloodstream infection. A study reported that the incidence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia increased significantly in HIV-infected patients from 2000 to 2004. Injection drug use (IDU), end-stage renal disease (ESRD) and CD4 count <200 cells/μL were independent predictors for incident MRSA bacteraemia, while ESRD was more common in patients with MRSA bacteraemia than methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. IDU, ESRD and CD4 count <200 cells/μL factors may serve as important clinical markers of MRSA likelihood in decisions regarding initial antimicrobial management.

Initial antimicrobial therapy for presumed sepsis in HIV-infected patients may require agents active against MRSA, including vancomycin, linezolid and, in nonpulmonary infections, daptomycin, particularly in patients with risk factors for MRSA bacteraemia.

(HIV Med. 2008;9(10):858-862)

The Role of Viral Infections in Type 1 Diabetes

A number of epidemiological studies support the hypothesis that viral infections play a causative role in type 1 diabetes. However, systematic review of control studies published between 1966 and 2002 has shown no convincing evidence for or against an association between type 1 diabetes and the prime candidate for infectious cause, Coxsackievirus B　(CVB). In animal models for type 1 diabetes, solid evidence supporting an inductive role for viruses is faced with just as solid evidence supporting a protective effect of viral infections. For example, based on mouse studies alone, there is no doubt that association between viruses and type 1 diabetes is extremely complex: while belonging to the same enteroviral group, CVB3 and CVB4 have opposing effects on type 1 diabetes in the same mouse model. Thus, the reason for current failure to associate a particular virus with induction of autoimmune diabetes likely is that such an association might be impossible to make. Certain viruses might be capable of inducing diabetes and others of preventing diabetes, and type 1 diabetes inducers might be capable of preventing disease under certain conditions. This will depend of course on the nature of the considered virus, but also on the state of advancement of autoimmunity at the time of infection. A given viral infection could thus be an essential disease precipitator once required predisposing events have occurred, but could on the other hand disrupt accumulation of these events.

Most important is the indication from animal studies that modulation of autoimmunity during viral infection does not depend merely on inherent properties of the virus, but also significantly on intrinsic factors of the host. The close interplay between the two will dictate whether enhancement or abrogation of autoimmune diabetes occurs. While molecular mimicry might activate autoreactive T-cells, it could also segregate these cells away from the islets and/or induce the activation of protective Tregs. While inflammatory cytokines might promote bystander activation of APCs and autoreactive T-cells, infection could occur at a time where inflammation will induce the relocation or demise of these cells. Whereas β-cell lysis and presentation of islet antigen might promote activation of autoreactive T-cells, it could also suppress the function of these cells by promoting Treg activity. Whereas repeated/sustained infections might lead to the accumulation of autoreactive T-cells within the memory pool, they could also induce suppressor mechanisms that will hinder autoimmunity.
(Diabetes. 2008;57(11):2863-2871)

Syphilis in Pregnancy

Syphilis in pregnancy could threatening the fetus. T. pallidum could crosses the placenta, resulting in fetal infection. Vertical transmission can occur at any time during pregnancy and at any stage of syphilis. Vertical transmission of syphilis is more common in primary (50%) and secondary syphilis (50%), compared with early latent (40%), late latent (10%), and tertiary syphilis (10%). Seventy to one hundred per cent of infants born to untreated infected mothers are infected. Pregnancies complicated by syphilis may result in intrauterine growth restriction, non-immune hydrops fetalis, stillbirth, preterm delivery, and spontaneous abortion in up to 50% of pregnancies. Women who had documented treatment for syphilis in the past do not need treatment during current or subsequent pregnancies.
Penicillin is the drug of choice for treating all stages of syphilis. Parenteral rather than oral treatment has been the route of choice as the therapy is supervised and bioavailability is guaranteed. Most women treated during pregnancy will deliver before their serological response to treatment can be assessed definitively. Neonates born to such women should be evaluated for congenital syphilis. For the treatment of early syphilis during pregnancy is procaine penicillin 750 mg daily for 10 days. If it is not possible to give daily procaine penicillin on the weekend, then either long-acting procaine penicillin in aluminium stearate, 2 million units (MU) or long-acting benethamine penicillin 1.2 MU should be given IM on the Friday. Patients with penicillin allergy: erythromycin 500 mg four times a day should be given for 14 days. Alternatively, azithromycin 500 mg should be given daily for 10 days. In addition to this, examination, tests, and treatment of all babies at birth should be carried out. Desensitization to penicillin may be considered, followed by the first-line treatment. Mothers treated with erythromycin or azithromycin may be considered for retreatment with doxycycline after delivery and when breast-feeding is stopped.
(Expert Rev Vaccines. 2008;7(10):1465-1473)

Inappropriate Antibiotic Prescribing Contributes To The Higher Bacterial Resistance

Inappropriate antibiotic prescribing contributes to the problem of higher bacterial resistance. Bacterial resistance to antibiotics is a major public health problem, increasing morbidity and mortality as well as healthcare costs.

Rates of antimicrobial resistance were higher in countries with the highest consumption of antibiotics. In countries with the highest use of antibiotics, prescription rates peaked during cold and flu seasons. The antibiotics were prescribed for sore throat during 73% of visits although the prevalence of sore throat caused by bacterial infection among adults is between 5% and 17%. Moreover, most of these patients received antibiotics that were not recommended for pharyngitis, with a high number of prescriptions being for extended-spectrum antibiotics. More than half of children with sore throats received antibiotics, a rate significantly higher than the regular prevalence of bacterial pharyngitis. Furthermore, more than one quarter of these children received an inappropriate antibiotic.
In a study it was found that the rates of resistance of S. pneumoniae to penicillin, amoxicillin-clavulanate, and cefdinir were 16%, 6.4%, and 19.2%, respectively. The least effective agents against S. pneumoniae were trimethoprim-sulfamethoxazole and azithromycin, with resistance rates of 23.5% and 34%, respectively. In a study of resistance in urinary tract infections in one health maintenance organization in the United States, the prevalence of resistance among isolates of Escherichia coli to ampicillin, cephalothin, and sulfamethoxazole exceeded 20% in each of the study years 1992 to 1996. The overall prevalence of resistance to trimethoprim-sulfamethoxazole doubled between 1992 and 1996.

Rotavirus among Children Worldwide

A hospital-based surveillance reports indicate that during 2001-2008, rotavirus accounted for approximately 40% of hospitalizations for diarrhea among children aged <5>85% of these deaths occurring in low-income countries of Africa and Asia. Two licensed rotavirus vaccines have shown efficacy of 85%-98% against severe rotavirus diarrhea in trials conducted in the Americas and Europe and they have been introduced into routine immunization programs in 11 countries in these regions and in Australia. Although the two licensed rotavirus vaccines differ in strain composition (i.e., one is monovalent, and one is pentavalent), both appear to provide protection against a variety of strains, including some strains not included in either of the licensed vaccines.
(MMWR. 2008;57(46):1255-1257)

CD4 Cell Count and AIDS-Defining Malignancies (ADM)

CD4 cell count is strongly associated with the risk of death from both AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM). Non-AIDS events have become an important cause of mortality as individuals with HIV infection survive to older ages and have started to suffer from similar age-related diseases to the HIV-uninfected population.
Rate of death of nADM is higher than from ADM in all patients other than those with very low CD4 cell counts. Lung cancer is the most common fatal nADM, concordance with the high prevalence of smoking among the HIV-infected population.
Age is also a strong predictor of death from malignancies, suggesting that, at similar CD4 cell counts, older patients are at greater risk of dying from malignancy. This may be a consequence of the higher incidence of cancers in older individuals, as well as an increased likelihood of death in older individuals, irrespective of the cause. However, this may also reflect reduced immune system activity in the elderly. Interestingly, the HIV RNA level was only weakly associated with ADM mortality and was not independently associated with nADM mortality.
Non-AIDS-defining malignancies was related to combination antiretroviral (cART) exposure. The individuals taking effective cART are less likely to die from ADM and, as a result, may be more likely to die from nADM. In contrast, patients dying from ADM may be more likely to have stopped or never received cART.
(AIDS. 2008;22(16):2143-2153)

The Immunologic Cascade of Kawasaki Syndrom Trigerred by An Infectious Agent?

Kawasaki syndrome (KS) is the most common cause of acquired heart disease in children. This acute, self-limited vasculitis results in permanent coronary artery damage in up to 25% of untreated children. High dose intravenous gamma globulin reduces the risk of coronary artery aneurysm to 3-5% if administered early in the course of disease. However, without a specific diagnostic test, affected children may be difficult to recognize, and delayed diagnosis and treatment continue to result in potentially preventable morbidity and mortality. The etiology of Kawasaki syndrome (KS) remains unknown despite 30 years of intensive search for an agent.
Associations have been observed between antecedent respiratory illness and KS. It is proposed that an agent causing KS could first infect the upper respiratory tract before triggering a systemic immunologic response. Researchers found an increased IgA plasma cell infiltration of the upper respiratory tract and coronary arteries in KS patients, therefore, further support the respiratory route as a potential portal of entry for the causative agent. The presence of IgA-secreting plasma cells in the upper respiratory tract mimics the response seen in autopsies of children who died of known viral respiratory infection such as respiratory syncytial virus.
(Pediatr Infect Dis J. 2008;27(11):981-985)

Maraviroc, The CCR5 antagonists

Maraviroc (Celsentri or Selzentry; Pfizer Ltd., Sandwich, UK) belongs to a new class of anti-HIV drugs named CCR5 antagonists, which block HIV entry into cells. Viral entry is an attractive step for the development of new agents against HIV variants resistant to current antiretroviral drugs. HIV gains entry into CD4-expressing cells through a series of sequential interactions between the envelope glycoprotein gp120 and the CD4 receptor and one of two coreceptor molecules, chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4), which are expressed on the surface of target cells. Maraviroc specifically inhibits the replication of R5-tropic HIV variants by an allosteric mechanism after binding to the transmembrane CCR5 coreceptor cavity. Because of its exclusive activity against CCR5 tropic strains, viral tropism testing is mandatory before using CCR5 antagonists in the clinic.

Maraviroc is a substrate for the P-glycoprotein and the cytochrome P450 (3A4), both of which are involved in the metabolism of multiple other agents, including several antiretroviral drugs. Therefore, drug interactions using maraviroc should be kept in mind. Briefly, the standard 300 mg twice daily dose of maraviroc does not require changes when the drug is given concomitantly with methadone, statins, nevirapine, cotrimoxazole, etinilestradiol nor pegylated interferon and ribavirin. However, dose adjustments have to be made when maraviroc is used along with some potent inhibitors or inducers of CYP3A4.
(AIDS. 2008;22(17):2231-2240).

Beware for Prolonged Initial Antibiotic Therapy for Extremely-Low-Birth-Weight Infants

In extremely-low-birth-weight (ELBW, birth weight of <1000 g) infants, prolonged initial empiric antibiotic therapy should be used with caution. It could cause an increased risk for necrotizing enterocolitis (NEC) or death. Although cultures from normally sterile sites usually do not yield any bacterial agents and the incidence of culture-proven bacterial sepsis is low in this population, ELBW infants admitted to intensive care nurseries usually receive empirical antibiotic treatment in the first postnatal days. A study suggested that cefotaxime for the first 3 postnatal days is associated with higher mortality risk, even for the most preterm infants.
(Pediatrics. 2009;123;58-66).

Acquired Vancomycin Resistance Pathogens

Acquired vancomycin resistance appears to be a serious and growing therapeutic challenge among various Gram-positive pathogens worldwide. In Enterococcus, different types of gene clusters encoding vancomycin (and teicoplanin) resistance have been identified; the vanA and, to a lesser extent, the vanB types are the most prevalent. Occasionally, the vanA cluster spread to S. aureus, constituting the first seven cases of VRSA (vancomycin-resistant S. aureus) that all emerged independently. Vancomycin treatment failure can be associated with van-independent mechanisms of (intermediate) resistance to vancomycin and seems to be an increasing problem in S. aureus and the CNS (coagulase-negative staphylococci).
(Future Microbiol. 2008;3(5):547-562)

New Guidelines for HIV Treatment

In AIDS 2008-XVII International AIDS Conference, the International AIDS Society–USA recommends new guidelines for HIV treatment. This recommendation is simplified and strengthened. One change in the recommendations is a greater emphasis on full virologic suppression. In this recommendation, deciding whether to start treatment in patients with a CD4 cell count of 350 cells/μL or more should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient willingness to begin treatment. Individuals with incomplete virologic suppression have greater morbidity and mortality than those who more completely suppress it.
The guidelines move aggressively toward earlier initiation of antiretroviral therapy. Treatment should be started before CD4 cell count decreases to less than 350/μL if there are correlates of faster HIV disease progression such as high plasma viral load (>100,000 copies/mL), rapidly decreasing CD4 cell count (>100/μL per year), active hepatitis B or C virus coinfection (resulting in faster progression of liver disease), cardiovascular disease risk, and HIV-associated nephropathy. Initiation of therapy in patients within the 200 to 350/μL CD4 cell count range should be strongly considered and individualized. The recommendations to start therapy in any patient with symptomatic HIV disease, regardless of CD4 count or viral load, and asymptomatic patients with less than 200/μL CD4 cell count.
Clinicians are encouraged to evaluate the whole patient, not just the status of HIV disease, but all coexisting conditions. Resistance testing should be conducted in all patients as part of their baseline workup. There is a little change in recommendations for an initial regimen in patients who are not infected with resistant virus. The first-line choice is a backbone of either an NNRTI or a ritonavir-boosted protease inhibitor (PI), combined with a dual nucleoside reverse transcriptase inhibitor (NRTI) component. The initial treatment regimen for HIV infection must be individualized, particularly in patients with comorbid conditions, but typically includes efavirenz or a ritonavir-boosted PI plus 2 NRTIs (tenofovir or emtricitabine or abacavir or lamivudine). Better not using darunavir as part of an initial regimen but holding it in reserve to use with patients who develop resistance to other PIs. Current first-line regimens are good and simple to use, and there is still concern about holding some drugs in reserve for patients who develop resistance to existing drugs. Even in heavily pretreated patients, the goal of treatment is an HIV-1 RNA level below assay detection limits. Treatment failure should be promptly identified and managed.

Depending on the NRTI mutations present, one might want to consider use of etravirine. Failure of a PI-based regimen can be more complicated, depending upon the genetic barriers. If caught early, changing the NRTI component to 2 active drugs might be sufficient to save the regimen. But as resistance points accumulate, one should consider use of darunavir or tipranavir.

The 3 drugs approved since the last version of the guidelines in 2006 are maraviroc, the first drug to target the CCR5 co-receptor on the surface of the cell; raltegravir, the first drug in the integrase inhibitor class; and etravirine, a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with clear activity against some NNRTI-resistant viruses. Enfurvitide remains an important option for the heavily treatment experienced population, but problems associated with daily injections and the emergence of other therapeutic alternatives such as raltegravir or maraviroc have reduced its use.

(AIDS 2008: XVII International AIDS Conference. Antiretroviral Treatment of Adult HIV Infection, 2008 Recommendations of the International AIDS Society–USA Panel. Presented August 3, 2008. JAMA. 2008;300:555-570)

Clostridium difficile-associated disease (CDAD)

Clostridium difficile-associated disease (CDAD) is an important nosocomial infection associated with healthcare, and it may recur in 15% to 30% of patients. The agent, Clostridium difficile, is a Gram-positive, anaerobic spore-forming bacillus. C. difficile was first identified as an aetiological agent of antibiotic-associated pseudomembranous colitis in the late 1970s. Approximately 15% to 20% of antibiotic-associated cases of diarrhea and nearly all cases of pseudomembranous colitis have been attributed to this bacteri. The incidence of CDAD has steadily climbed in the past decade, and it is an important cause of morbidity both in North America and in Europe.

Rapid diagnosis of CDAD further allows implementation of infection control measures and timely treatment. Stool assays is not a good strategy for rapid diagnostic since the false-negative rates is very significant. The best methods for rapid identification of C. difficile–associated pseudomembranous colitis is sigmoidoscopy.
Control of C difficile infection requires prudent use of antimicrobial agents, prevention of cross-infection, and ongoing surveillance. For patients with mild CDAD, discontinuation of the causative antibiotics without further treatment may be sufficient. Many guidelines recommend the use of metronidazole, an imidazole derivative, in patients thought to need antibiotic treatment, however it has a high failure rates and and resistance to metronidazole has been reported. Controlled clinical trials have shown efficacy for CDAD treatment with vancomycin, a glycopeptide. The mean duration of symptoms was also significantly shorter with vancomycin comparing with that of metronidazole. For patients with severe CDAD, intensive care unit (ICU) admission may be needed. A combined medical and surgical approach is recommended, with surgical resection of the inflamed colon as a therapeutic option.

Universal Screening at Hospital Admission to Reduce Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) Infection?

A study reported in the March 12 issue of the Journal of the American Medical Association (JAMA. 2008;299:1149-1157, 1190-1192.) concluded that universal screening on hospital admission for methicillin-resistant Staphylococcus aureus (MRSA) infection may not reduce the rate of hospital-acquired infections in surgical patients.