Mycoplasma pulmonis-host relationships in a breeding colony of Sprague-Dawley rats with enzootic murine respiratory mycoplasmosis

The longitudinal Mycoplasma pulmonis-host relationships in rats 1 to 72 weeks of age were investigated in a conventional breeding colony of Sprague-Dawley rats with enzootic murine respiratory mycoplasmosis (MRM). Mean intracage ammonia (NH3) concentrations of 52 +/- 21 micrograms/1 and active Sendai virus infections during the first month of life were associated with important early events in MRM. There was rapid colonization of proximal airways by large numbers of M. pulmonis in most rats by 2 weeks of age and the lungs by 6 weeks. The prevalence of lesions of MRM peaked by 3 weeks in nasal passages, later in middle ears, larynx and trachea, and not until 8 weeks in lungs. Approximately 10% of rats 8 weeks of age and older had bronchiectasis and/or bronchiolectasis, usually restricted to a few airways. Despite continued high NH3 concentrations (42 +/- 14 micrograms/1 in cages of weanlings and 86 +/- 45 micrograms/1 in cages of adults), M. pulmonis populations declined dramatically by 8 weeks of age. Nevertheless, in older rats lesions continued to be extremely prevalent in proximal airways. Mycoplasma pulmonis infection and disease persisted in respiratory tracts of most rats through 72 weeks of age, despite high serum concentrations of mycoplasma-specific IgM and IgG antibodies. These interrelationships of M. pulmonis, host, and environment may be representative of many breeding colonies of rats that have enzootic MRM.     

Antimicrobial susceptibility patterns,emm type distribution and genetic diversity of Streptococcus pyogenes recovered in Brazil

Streptococcus pyogenes is responsible for a variety of infectious diseases and immunological complications. In this study, 91 isolates of S. pyogenes recovered from oropharynx secretions were submitted to antimicrobial susceptibility testing, emm typing and pulsed-field gel electrophoresis (PFGE) analysis. All isolates were susceptible to ceftriaxone, levofloxacin, penicillin G and vancomycin. Resistance to erythromycin and clindamycin was 15.4%, which is higher than previous reports from this area, while 20.9% of the isolates were not susceptible to tetracycline. The macrolide resistance phenotypes were cMLSB (10) and iMLSB (4). The ermB gene was predominant, followed by the ermA gene. Thirty-two emm types and subtypes were found, but five (emm1, emm4, emm12, emm22, emm81) were detected in 48% of the isolates. Three new emm subtypes were identified (emm1.74, emm58.14, emm76.7). There was a strong association between emm type and PFGE clustering. A variety of PFGE profiles as well as emm types were found among tetracycline and erythromycin-resistant isolates, demonstrating that antimicrobial resistant strains do not result from the expansion of one or a few clones. This study provides epidemiological data that contribute to the development of suitable strategies for the prevention and treatment of such infections in a poorly studied area.     

Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence

Background

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.

Methods

We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.

Results

Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55–5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).

Conclusions

In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed.     

Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009

Background

In 2009, an outbreak of dengue caused high fatality in Sri Lanka. We conducted 5 autopsies of clinically suspected myocarditis cases at the General Hospital, Peradeniya to describe the histopathology of the heart and other organs.

Methods

The diagnosis of dengue was confirmed with specific IgM and IgG ELISA, HAI and RT-PCR techniques. The histology was done in tissue sections stained with hematoxylin and eosin.

Results

Of the 319 cases of dengue fever, 166(52%) had severe infection. Of them, 149 patients (90%) had secondary dengue infection and in 5 patients, DEN-1 was identified as the causative serotype. The clinical diagnosis of myocarditis was considered in 45(27%) patients. The autopsies were done in 5 patients who succumbed to shock (3 females and 2 males) aged 13- 31 years. All had pleural effusions, ascites, bleeding patches in tissue planes and histological evidence of myocarditis. The main histological findings of the heart were interstitial oedema with inflammatory cell infiltration and necrosis of myocardial fibers. One patient had pericarditis. The concurrent pulmonary abnormalities were septal congestion, pulmonary haemorrhage and diffuse alveolar damage; one case showed massive necrosis of liver.

Conclusions

The histology supports occurrence of myocarditis in dengue infection.

     

Induction of class II MHC antigen expression in macrophages by Mycoplasma species

Several different Mycoplasma species have been shown to act as mitogens for either T or B cells and as stimulators of macrophage tumoricidal activity. In this report, we show that at least five different species of Mycoplasma are capable of inducing class II MHC expression on macrophages. We have observed significant induction of class II MHC surface expression on the myelomonocytic cell line, WEHI-3, as early as 24 h after deliberate infection of cultures, reaching maximal levels by 4 days. This induction was also apparent at the mRNA level as assessed by Northern blot analysis by using A alpha, E alpha, and A beta probes. However, unlike many other previously described MHC-inducing agents, mycoplasmas failed to induce class I MHC expression at either the cell surface or mRNA levels. Kinetic analysis revealed that induction of class II mRNA by mycoplasmas was slower than induction by IFN-gamma requiring 24 h rather than 8 h for significant increases to be noted. Induction by mycoplasmas does not require the presence of live organisms and remains active after heat treatment of 90 degrees C for 30 min. We have also demonstrated that mycoplasma infection of primary bone marrow macrophage cultures leads to the induction of both class I and class II genes and, as in the case of WEHI-3, this induction does not require the presence of live organisms. These data indicate that several Mycoplasma species have the capacity to induce class II MHC expression in WEHI-3 and both class I and class II MHC expression in bone marrow macrophage cultures in the absence of any T cell products.     

Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2

Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.     

Degeneration of the intervertebral disc

The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.