Silent Infection Research Articles

Systemic Inflammation Induces Endothelial Dysfunction in Peritoneal Dialysis Patients

Background. Endothelial dysfunction (ED) with atherosclerosis is a recognized complication of uremic patients. The importance of inflammation in ED pathophysiology has recently been proposed. The aim of this study was to analyze the role played by inflammation on ED in peritoneal dialysis (PD) patients. Methods: During 15 months, all the patients from our PD unit were followed-up. We determined nutritional, inflammatory (C-reactive protein (CRP), TNF-α and Vascular cell adhesion molecule-1 (VCAM)) and endothelial function markers at baseline and during systemic inflammation (SI). Seventeen patients were finally included due to elevation of CRP by various etiologies (4 suffered silent infection by Helicobacter pylori, 4 upper respiratory infections and 2 intestinal bacterial over-growth). They were compared with a control group (CG) with 12 PD patients who did not suffer SI. A venous occlusion test (VOT) was performed to stimulate the endothelium. Endothelial function was assessed by measuring: endothelial fibrinolytic capacity: tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI); endothelial damage markers: von Willebrand factor (vWF), thrombomodulin (TM) and nitric oxide (NO); cardiovascular (CV) risk markers: fibrinogen, lipoprotein(a) and homocysteine (Hcy); growth factors: VCAM-1, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF). After variable of follow-up time, CRP and TNF-α plasma levels increased. Results: We found a decrease in albumin, tPA ratio (post VOT/pre-VOT) and nitrate (NO3)-ratio. PAI, TM, Lp(a) and TGF-β Increase. A positive linear correlation between Hcy and PDGF was found, suggesting a pro-atherogenic environment. The CG did not show changes in the studied parameters. Conclusions: In PD patients, systemic inflammation induces endothelial dysfunction estimated by elevation of endothelial damage markers. Pro-inflammatory cytokines are associated with elevations in procoagulable and proatherosclerotic mediators in plasma.

A clinically silent respiratory infection withChlamydophilaspp. in calves is associated with airway obstruction and pulmonary inflammation

This study was aimed at evaluating functional and inflammatory consequences of persistent chlamydial infections on the respiratory system in clinically inconspicuous calves aged 2-7 months. Thirteen calves persistently infected with Chlamydophila (C.) abortus and/or C. pecorum (Chl+) were compared to 12 calves without chlamydial infections (Chl-). In order to evaluate lung function, 36 non-invasive impulse oscillometry tests were performed per animal within 6 months. The group of chronically infected animals was distinguished by significantly higher peripheral airway resistance (indicating peripheral airway obstruction), significantly higher respiratory rates, and significantly higher minute volumes of ventilation. At the age of seven months, all calves were necropsied, broncho-alveolar lavage fluid (BALF) was obtained ex vivo, and lungs were examined histologically. Significantly higher concentrations of total protein and 8-iso-prostane (8-IP), as well as higher activities of matrix metalloprotease 2 were measured in BALF samples of Chl+ calves. Histologically, markedly activated bronchus-associated lymphoid tissue (BALT) causing partial obstruction of bronchiolar lumina was found in the apical pulmonary lobes of Chl+ calves. Chlamydial DNA was detected in the lung tissue of 7 out of 13 Chl+ calves by real-time PCR. In conclusion, respiratory chlamydial infection appeared to be associated with chronic inflammation of the lungs and airways. Despite the lack of clinical symptoms, pulmonary dysfunctions persisted in calves until the age of seven months. Data obtained in this study provide new insight illustrating the impact of nearly ubiquitous subclinical infections on the respiratory system.

Respiratory syncytial virus infection in infants admitted to paediatric intensive care units in London, and in their families

We carried out a study in five London paediatric intensive care units (PICUs), with the objectives of describing a cohort of infants with respiratory syncytial virus (RSV) infection, comparing hospital diagnosis with PCR results and investigating the spread of RSV in families. Eligible infants were under 5 months old and admitted betweem November 1998 and October 1999 with respiratory failure, apnoea and/or bradycardia or acute life threatening episodes (ALTE). We diagnosed RSV by PCR analysis of nasopharyngeal aspirate, and in contacts by PCR of pernasal swabs. Of the 137 eligible infants, 66% (91/137) were recruited; of these, 82% (75/91) had RSV, with 47% (35/75) diagnosed by hospital laboratory tests and 93% (70/75) by PCR. The median duration of ventilation was 4.4 days, the length of stay on PICU, 8.6 days, and the length of stay in hospital, 15.9 days. In most families (62%), the parents and siblings developed symptoms of RSV infection at the same time as the infant. When the index infant was a secondary case, primary cases occurred in both older siblings (16 families) and adults (11 families). Silent RSV infection occurred frequently amongst children and adults. RSV is under-diagnosed in PICUs. PCR increases the rate of diagnosis of RSV compared to routine hospital diagnostic methods. Young infants are most often infected at the same time as or before their parents and siblings, indicating that the source may be outside the household; vaccinating family members may not prevent RSV infection in infants.

Reactivation of tuberculosis by tumor necrosis factor neutralization.

Tumor necrosis factor (TNF) is required in the control of infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. TNF is essential and non-redundant for forming microbiocidal granulomas, and cannot be replaced by other members of the TNF family. We established a model of latent Mtb infection in mice, allowing investigation of the reactivation of latent Mtb as observed in patients receiving TNF-neutralizing therapy used in rheumatoid arthritis and Crohn's disease. Antibody neutralization of TNF is able to reactivate clinically silent Mtb infection. Using mutant mice expressing solely membrane, but not soluble TNF, we demonstrated that membrane TNF is sufficient to control acute Mtb infection. Therefore, we hypothesize that TNF-neutralizing therapy, sparing membrane TNF, may have an advantage as compared to complete neutralization. In conclusion, endogenous TNF is critical for the control of tuberculosis infection. Genetic absence or pharmacological neutralization of TNF results in uncontrolled infection, while selective neutralization might retain the desired anti-inflammatory effect but reduce the infectious risk.

Prevalence of chlamydia in patients attending gynecological clinics in south eastern Nigeria.

Chlamydia infections have been reported to cause silent infections in communities which becomes endemic and could remain unnoticed for a very long time. In most parts of Nigeria these organisms are not screened for, and hence relative information about frequencies of the organisms are sparse. Five hundred and sixty five blood samples and ten umbilical cord fluids were collected from various patients attending clinics in South Eastern Nigeria and were screened for Chlamydia Complement Fixing Antibody (CCFA). Endocervical swabs and urethral discharges or swabs were collected from patients whose serum was positive and were cultured into embryonic eggs which was later observed, harvested and stained using the Romanowsky-Giemsa staining techniques. The positive sera were further confirmed by distinguishing the species of Chlamydia using the monoclonal antibody spot test kit. Of the five hundred and sixty five (565) samples collected only three hundred and forty were positive to CCFA, of which 141 were males and 204 females. From the cultured samples 230 were positive for Chlamydia trachomatis and 99 positive to Chlamydia pneumoniae. Statistical analysis using the student's t test at 95% confidence interval shows that there was no significant difference between the number of females and males that presented themselves for screening. Proper screening of patients to include Chlamydia should be encouraged at all levels of medical diagnosis in the country so as to proffer treatment. Otherwise the infection will remain a "silent epidemic", as is the case currently.

DEC-205–Mediated Internalization of HIV-1 Results in the Establishment of Silent Infection in Renal Tubular Cells

HIV-1 infection of renal cells has been proposed to play a role in HIV-1-associated nephropathy. Renal biopsy data further suggest that renal tubular cells may serve as reservoir for HIV-1. The mechanism by which HIV-1 enters these cells has not been identified. Renal tubular cells do not express any of the known HIV-1 receptors, and our results confirmed lack of the expression of CD4, CCR5, CXCR4, DC-SIGN, or mannose receptors in tubular cells. The aim of this study, therefore, was to determine the mechanism that enables viral entry into renal tubular cells. An in vitro model was used to study the HIV-1 infection of human kidney tubular (HK2) cells and to identify the receptor that enables the virus to enter these cells. Results of these studies demonstrate that the C-type lectin DEC-205 acts as an HIV-1 receptor in HK2 cells. Interaction of HIV-1 with DEC-205 results in the internalization of the virus and establishment of a nonproductive infection. HIV-1-specific strong-stop DNA is detected in the infected HK2 cells for at least 7 d, and the virus can be transmitted in trans to sensitive target cells. HIV-1 entry is blocked by pretreatment with specific anti-DEC-205 antibody. Moreover, expression of DEC-205 in cells that lack the DEC-205 receptors renders them susceptible to HIV-1 infection. These findings suggest that DEC-205 acts as an HIV-1 receptor that mediates internalization of the virus into renal tubular cells, from which the virus can be rescued and disseminated by encountering immune cells.

Exacerbated Pathology of Viral Encephalitis in Mice with Central Nervous System-Specific Autoantibodies

We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler’s encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C′-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.

Antagonistic expression of hepatitis C virus and alpha interferon in lymphoid cells during persistent occult infection

Summary. Detection of residual HCV in individuals with SVR after treatment of CHC can be significantly heightened by analyzing ex vivo mitogen‐activated T and B lymphocytes and applying sensitive nucleic acid amplification assays. However, it remained unknown if synergistic activation of lymphocytes and monocytes would further augment HCV detection, if viral replication becomes universally upregulated in treated cells, and if examining sequential sera and lymphoid cells would improve detection of occult infection. Using paired sera and lymphoid cells collected 1 year apart from 17 individuals with normal liver enzymes for up to 72 months after SVR, it was found that simultaneous activation of lymphocytes and monocytes enhanced identification of silent HCV infection and revealed that in some cases monocytes were the principal immune cell type where HCV persisted. Testing of serial samples further increased detection of occult infection. Ultimately, by combining the above two approaches, all individuals with SVR were found to be silent carriers of HCV. Clonal sequencing revealed HCV variations in sera and lymphoid cells and evolution of viral genomes confirming ongoing virus replication. Surprisingly, similar to those with CHC, naive lymphoid cells from some individuals carried ∼103 HCV copies/μg total RNA. HCV loads in naive lymphoid cells predetermined the outcome of ex vivo stimulation with respect to upregulation or inhibition of HCV replication. HCV RNA levels in occult infection were inversely proportional to the expression of IFNα and IFN‐inducible MxA, but not to IFNγ or tumour necrosis factor α in naive and mitogen‐treated lymphoid cells.

Leprosy: what is being "eliminated"?

Leprosy: what is being "eliminated"?

The Diagnosis and Management of Hepatitis C: The Role of the Physician Assistant

Hepatitis C will pose a serious challenge to the health care system during the next 2 decades. Physician assistants can play an important role in the screening, diagnosis, and management of hepatitis C infection, and in educating patients about this disease. Screening for risk factors for hepatitis C virus (HCV) can be used to identify most infected individuals, who can then be tested for the presence of anti-HCV antibodies and HCV RNA. Hepatitis C can be treated with a combination of pegylated interferon plus ribavirin, and the virus can be cleared in a significant percentage of infected individuals. HEPATITIS C: SCOPE OF THE PROBLEM The United States faces a major public health challenge over the next 2 decades from the largely silent but widespread infection of adults by HCV. This is now the most common blood-borne infection in the United States. 1 About 2% of adults in this country are infected, but only a small fraction of these individuals have been identified and are aware of their positive viral status. 123 The Centers for Disease Control and Prevention (CDC) estimated that there were approximately 30,000 new cases of HCV infection in 2003. 4 These estimates are probably conservative, because the National Health and Nutrition Examination Survey (NHANES) data on which they were based excluded people who were incarcerated or homeless, individuals known to have high rates of HCV infection. 3,4 Chronic HCV infection is defined as the persistence of HCV RNA in the blood for at least 6 months. 2 Chronic HCV is frequently asymptomatic in its early stages, and years or decades may pass before affected individuals seek treatment. 5 Even symptomatic individuals may complain of only vague feelings of tiredness or malaise, leading to delays in diagnosis if HCV is not suspected. 5 HCV-infected patients may progress to very grave illnesses, chief among them being the occurrence of silent but progressive fibrotic liver disease. 6 The rate of progression to cirrhosis varies widely in infected patients, but it is currently estimated that up to 20% of patients infected with HCV will develop cirrhosis over a 20to 25-year period. 7 Many of these patients may progress to end-stage liver disease and death unless a transplant is performed, and HCV infection has now become the most common reason for liver transplantation in the US. 7,8 Once an HCV-infected individual develops cirrhosis, the risk of hepatocellular carcinoma is also present, contributing to mortality rates. 7 Because HCV is a systemic disease, infected patients can also develop serious extrahepatic complications of immunologic origin, including rheumatoid symptoms, kidney disease, and skin disorders. 2 If HCV-infected individuals are not identified and treated, deaths due to HCV infection are expected to increase 2to 3fold by 2010 to 2020, and annual deaths from HCV infection will exceed deaths from HIV/AIDS. 9 Physician assistants (PAs) can play important roles in identifying these individuals and helping to manage their disease, with the goal of lessening the overall health care burden and reducing the risks of mortality and morbidity from this deadly but still largely silent outbreak. HEPATITIS C: A TREATABLE DISEASE The current standard of care for HCV infection is combination therapy with pegylated interferon (IFN) alfa and ribavirin. 10 Interferons are naturally occurring proteins that have antiviral, immunomodulatory, and antiinflammatory properties. 11 Interferon alfa-2a and interferon alfa-2b have been shown to inhibit HCV replication and strengthen the host immune response to the virus. 11 Pegylated interferons are interferons that have been conjugated to inert polyethylene glycol (PEG) moieties. 11 The Diagnosis and Management of Hepatitis C: The Role of the Physician Assistant 2 of 10 Interferon alfa-2b is conjugated 1:1 to an unbranched, 12kilodalton (kd) PEG moiety to form peginterferon alfa-2b, whereas interferon alfa-2a is conjugated 1:1 to a branched, 40-kd PEG moiety to form peginterferon alfa-2a. 12 Pegylation protects the molecules from enzymatic degradation and reduces their rate of renal elimination, thereby creating more desirable, longer-acting agents. 11 The combination of pegylated interferon plus ribavirin has been shown to be more effective than either pegylated interferon monotherapy or combination therapy with standard interferon plus ribavirin in inducing a sustained virologic response (SVR), defined as the complete absence of detectable HCV RNA in serum 6 months after the end of

A Conserved Subtilisin Protease Identified in Babesia divergens Merozoites

Invasion of erythrocytes is an integral part of the Babesia divergens life cycle. Serine proteases have been shown to play an important role in invasion by related Apicomplexan parasites such as the malaria parasite Plasmodium falciparum. Here we demonstrate the presence of two dominant serine proteases in asexual B. divergens using a biotinylated fluorophosphonate probe. One of these active serine proteases (p48) and its precursors were recognized by anti-PfSUB1 antibodies. These antibodies were used to clone the gene encoding a serine protease using a B. divergens cDNA library. BdSub-1 is a single copy gene with no introns. The deduced gene product (BdSUB-1) clearly belongs to the subtilisin superfamily and shows significant homology to Plasmodium subtilisins, with the highest degree of sequence identity around the four catalytic residues. Like subtilisin proteases in other Apicomplexan parasites, BdSUB-1 undergoes two steps of processing during activation in the secretory pathway being finally converted to an active form (p48). The mature protease is concentrated in merozoite dense granules, apical secretory organelles involved in erythrocyte invasion. Anti-PfSUB1 antibodies have a potent inhibitory effect on erythrocyte invasion by B. divergens merozoites in vitro. This report demonstrates conservation of the molecular machinery involved in erythrocyte invasion by these two Apicomplexan parasites and paves the way for a comparative analysis of other molecules that participate in this process in the two parasites.

Prevalence of human papillomavirus infection in the genital tract determined by hybrid capture assay

Human Papillomavirus (HPV) infection is the most prevalent sexually-transmitted virus worldwide. It is known to be the etiological agent of cervical cancer and cervical intraepithelial neoplasia (CIN). Consequently, there is strong motivation to evaluate HPV testing in cervical cancer screening. Recently developed, the second generation of the hybrid capture test (HCA II) is a non-radioactive, relatively rapid, hybridization assay, designed to detect 18 HPV types divided into high and low-risk groups. We evaluated 7,314 patients (5,833 women and 1,481 men) for HPV infection by HCA II. Among them, 3,008 (41.1%) presented HPV infection: 430 (14.2%) had HPV DNA of low risk for cancer, 1,631 (54.2%) had high risk HPV types and 947 (31.5%) had both types. The prevalence in females was 44.9%. The prevalence of HPV DNA in the group for which cytological results were available was slightly higher: 55.3% (1007/1824). Significant differences were detected in the frequency of HPV infection of the cervix between normal cases and those with high-grade squamous-intraepithelial lesions (HSIL)(P<0.0001). Among males, the prevalence was 26.2%, composed of 9.1% in Group A, 9.7% in Group B and 7.4% with multiple infections. We observed that male prevalence was lower and that low-risk types were more frequent than in females. HPV viral load was significantly greater in SILs than in normal or inflammatory cases (P<0.0001), suggesting an association between high viral load values and risk of SIL. Because of high costs, the HCA II test cannot be recommended for routine mass screening for cervical infection in poor countries. Nevertheless, it was found to be a useful tool, when combined with cytology, discovering high-risk infections in apparently normal tissues and revealing silent infections that may be responsible for the maintenance of HPV in the general population. These findings point to the need for close and careful management of patients, thereby reducing overtreatment, allowing analysis of both sexual partners and finally contributing to the control of genital infections associated with a risk for cancer.

The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV‐2) infection

It is not known why some individuals infected with herpes simplex virus type 2 (HSV-2), experience frequent recurrences, while most of those infected have a completely silent infection. We wanted to study if local factors in the skin could explain this difference. DESIGn 21 HSV-2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as transepidermal water loss (TEWL) and skin capacitance, were measured on labium majus and perineum. Culture for bacteria was performed from the same regions. No significant differences in terms of pH and skin barrier function were registered between symptomatic and asymptomatic patients. Asymptomatic patients had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus than symptomatic patients.

Human Immunodeficiency Virus type 1 in seronegative infants born to HIV-1-infected mothers

BackgroundSome individuals repeatedly exposed to Human Immunodeficiency Virus do not seroconvert and are resistant to HIV infection. Here, in a pediatric cohort of HIV seronegative infants born of HIV-infected mothers, we have studied eight non-breastfed children in whom viral DNA was detected in their PBMC. Our objective was to assess whether silent infection in these children can be explained by the presence of integrated viral DNA.MethodsThe presence of viral DNA was corroborated by nested PCR with primers for gag and the nef/LTR regions of HIV-1. Integration of HIV DNA into the host genome was assessed by an Alu-LTR PCR. Amplicons were sequenced and phylogenetic analyzes were done.ResultsHIV-1 DNA was detected in the earliest available PBMC sample from all eight infants, and two of them tested positive for HIV DNA at 2 years of age. Nested PCR resulted in the amplification of gag, nef/LTR and Alu-LTR fragments, which demostrated that HIV-1 DNA was integrated in the host cell genome. Each individual has a characteristic sequence pattern and is different from the LTR sequence of HXB2 prototype virus and other Mexican isolates.ConclusionHIV-1 DNA was observed in PBMC from HIV exposed seronegative children in this pediatric cohort.

Ultrasound Markers of Fetal Infection, Part 2

Up to 1% of all pregnancies have clinically overt intra-amniotic bacterial infections, and an even larger percentage of pregnant women may be affected by silent infections. Although most pregnant women with overt intra-amniotic bacterial infection have experienced prolonged rupture of membranes (PROM), symptomatic and most silent nonviral intra-amniotic infections may occur with intact membranes. The etiology of intra-amniotic infection after PROM is almost always polymicrobial and consists of genital tract pathogens, such as group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, mycoplasmas, aerobic Gram-negative bacilli, such as the coliforms, and facultative and anaerobic endogenous organisms, such as peptococci, peptostreptococci, and Bacteroides species. These organisms gain access to the uterine cavity by the ascending route. Organisms such as Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii, trypanosomes, and plasmodia are capable of gaining access to the amniotic cavity by transplacental hematogenous spread, and cause devastating fetal infections. Symptomatic intra-amniotic infection is usually a diagnosis of exclusion. Diagnostic criteria based on both clinical and laboratory findings lack sensitivity and are nonspecific. It is difficult to obtain uncontaminated intra-amniotic samples, especially when there is PROM. The problem is even greater with silent infections. In most cases, fetal infection is suspected after an unexplained and unexpected adverse outcome. Maternal morbidity is increased with intra-amniotic infection; although maternal mortality is extremely rare in developed countries, this is not the case in societies where pregnant women have limited or no access to medical care. Although infected women who are treated early and aggressively with wide-spectrum antibiotics do well, more than 10% of these women develop bacteremia and up to half of them will require cesarean delivery because of poor uterine contractions and arrest of labor. The overwhelming majority of term neonates exposed to intrauterine infection after PROM do well, but up to 30% of these neonates require treatment of neonatal pneumonia or bacteremia. Outcomes for preterm neonates or for neonates who experienced silent fetal infections are more severe. Morbidity and mortality rates in these cases are high, and survivors may have long-term devastating sequelae. The ability to identify ultrasound markers of fetal infection will help clinicians identify etiologic agents with greater accuracy and correlate these infections with specific antepartum and postpartum syndromes. The recognition of markers of intrauterine infection will also reduce unexpected adverse outcomes that result from undiagnosed fetal infections.

Ultrasound Markers of Fetal Infection, Part 2

Up to 1% of all pregnancies have clinically overt intra-amniotic bacterial infections, and an even larger percentage of pregnant women may be affected by silent infections. Although most pregnant women with overt intra-amniotic bacterial infection have experienced prolonged rupture of membranes (PROM), symptomatic and most silent nonviral intra-amniotic infections may occur with intact membranes. The etiology of intra-amniotic infection after PROM is almost always polymicrobial and consists of genital tract pathogens, such as group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, mycoplasmas, aerobic Gram-negative bacilli, such as the coliforms, and facultative and anaerobic endogenous organisms, such as peptococci, peptostreptococci, and Bacteroides species. These organisms gain access to the uterine cavity by the ascending route. Organisms such as Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii, trypanosomes, and plasmodia are capable of gaining access to the amniotic cavity by transplacental hematogenous spread, and cause devastating fetal infections. Symptomatic intra-amniotic infection is usually a diagnosis of exclusion. Diagnostic criteria based on both clinical and laboratory findings lack sensitivity and are nonspecific. It is difficult to obtain uncontaminated intra-amniotic samples, especially when there is PROM. The problem is even greater with silent infections. In most cases, fetal infection is suspected after an unexplained and unexpected adverse outcome. Maternal morbidity is increased with intra-amniotic infection; although maternal mortality is extremely rare in developed countries, this is not the case in societies where pregnant women have limited or no access to medical care. Although infected women who are treated early and aggressively with wide-spectrum antibiotics do well, more than 10% of these women develop bacteremia and up to half of them will require cesarean delivery because of poor uterine contractions and arrest of labor. The overwhelming majority of term neonates exposed to intrauterine infection after PROM do well, but up to 30% of these neonates require treatment of neonatal pneumonia or bacteremia. Outcomes for preterm neonates or for neonates who experienced silent fetal infections are more severe. Morbidity and mortality rates in these cases are high, and survivors may have long-term devastating sequelae. The ability to identify ultrasound markers of fetal infection will help clinicians identify etiologic agents with greater accuracy and correlate these infections with specific antepartum and postpartum syndromes. The recognition of markers of intrauterine infection will also reduce unexpected adverse outcomes that result from undiagnosed fetal infections.

Persistent brain infection and disease reactivation in relapsing fever borreliosis

Relapsing fever, an infection caused by Borrelia spirochetes, is generally considered a transient, self-limiting disease in humans. The present study reveals that murine infection by Borrelia duttonii can be reactivated after an extended time as a silent infection in the brain, with no bacteria appearing in the blood and spirochete load comparable to the numbers in an infected tick. The host cerebral gene expression pattern is indistinguishable from that of uninfected animals, indicating that persistent bacteria are not recognized by the immune system nor cause noticeable tissue damage. Silent infection can be reactivated by immunosuppression, inducing spirochetemia comparable to that of initial densities. B. duttonii has never been found in any host except man and the tick vector. We therefore propose the brain to be a possible natural reservoir of the spirochete. The view of relapsing fever as an acute disease should be extended to include in some cases prolonged persistence, a feature characteristic of the related spirochetal infections Lyme disease and syphilis.

Post-eradication poliovirus facility-associated community risks

Minimizing the risk of poliovirus transmission from the poliovirus facility to an increasingly susceptible community is crucial when global poliovirus transmission and OPV use stops. Community risks of exposure to wild poliovirus as well as Sabin strains are highest from facility personnel who are unknowingly contaminated or infected. Immunization with OPV or IPV prevents poliomyelitis, but neither vaccine fully inhibits silent infection of the gut. Facility environments maintained at low relative humidity (<50%) may reduce poliovirus survival and inhalation risk. Circulating antibodies reduce personnel infection risks from injection or virus entry through breaks in skin or mucous membranes. Community exposure risk through inhalation of contaminated air effluent is likely low in most modern facilities. Community risks through ingestion of liquid effluents are facility-specific and may range from high to low. This assessment of community risks, when combined with assessments of facility-specific hazards and the consequences of wild or Sabin poliovirus transmission, provides the foundation for effective risk management.

A Mouse Model for Polyomavirus-Associated Nephropathy of Kidney Transplants

Polyomavirus-associated nephropathy is an important cause of dysfunction and failure of renal transplants. BK virus is an ubiquitous human polyoma virus that persistently infects the kidney. This otherwise silent infection can reactivate in immunosuppressed individuals, resulting in renal complications. Because polyoma viruses are highly species-specific, we developed a mouse polyoma virus-renal transplant model in order to investigate the pathogenesis of polyomavirus-associated nephropathy. Using this model, we found that polyoma virus preferentially replicates in the allogeneic kidney grafts, accelerating graft failure; thus, this animal model is able to mimic the polyomavirus-associated nephropathy seen in human renal transplant patients. Acute polyoma virus infection of mouse allograft recipients augmented the alloreactive CD8+ T-cell response, while maintaining the anti-viral CD8+ T-cell response. In addition to the known virus-induced cytopathology, these findings demonstrate a potential role for an enhanced anti-donor T-cell response in the pathogenesis of polyomavirus-associated nephropathy.

Impact of hepatitis B vaccination on hepatitis B disease and nucleic acid testing in high-prevalence populations

Hepatitis B virus (HBV) infection is highly prevalent in Asia, Africa, southern Europe and Latin America, HBV vaccination has effectively reduced the acute and chronic infection rates as well as related complications in the vaccinated children. The incidence of hepatocellular carcinoma in children has been reduced to approximately 25% of the incidence before the vaccination program, and fulminant hepatitis in children has also been reduced after universal hepatitis B vaccination. HBV DNA sero-positive rate was 98–100% in HBsAg positive vaccinated children, while the positive rate was only 11–20% in those vaccinees with a negative HBsAg but positive anti-HBc reaction. Hepatitis B surface gene mutants in HBV DNA positive children increased gradually from 7.8% before the vaccination program, to 19.6%, 28.1% and 23.1% at 5, 10 and 15 years after the vaccination program. Long-term follow-up of vaccinated children has confirmed that universal HBV vaccination in infancy has produced adequate protection up to 14 years of age. The annual decay rate of hepatitis B surface antibody (anti-HBs) was 10.2% in children who did not receive a booster dose. The new HBV infection rate was not different between those who did and those who did not receive a booster dose of HBV vaccine. During a follow-up period of seven years for 1200 vaccinated 7-year-old children in Taiwan, the mean annual hepatitis B core antibody sero-conversion rate was 0.2%. All were negative for HBV DNA. No new chronic HBV infections developed. A booster dose of HBV vaccine is not recommended in children under 15 years of age. Systematic HBV DNA screening of a large population such as blood donors may be instrumental in following the long-term effect of the universal vaccination program on the incidence of silent HBV infection and vaccine escape mutants.