Table of contents :
|
Web resources |
one of only three gastroenteritis-causing HAdVs that are equipped with two different fiber proteins, one long and one short. terminal knob domain of the long fiber (52LFK) binds to CAR, and the knob domain of the short fiber (52SFK) binds to sialylated glycoproteinsref
One strategy used by human alpha- and gammaherpesviruses to facilitate such competition is to shut off the expression of host genes located in the nuclear genome. Host shutoff involves inhibition of host gene transcription, alterations in mRNA processing, and the loss of cytoplasmic mRNAs. Altogether, these effects help redirect the cellular gene expression machinery toward the expression of viral genes. Interestingly, herpes simplex virus type 1 (HSV-1), HSV-2, and Epstein-Barr virus (EBV) have also evolved mechanisms to disrupt the expression of genes located in the host mitochondrial genome by degrading mitochondrial DNA (mtDNA)ref
There are 3 subfamilies :
|
|
|
|
18÷29 |
47.4 %
|
93.3 %
|
35.7 %
|
> 30 |
62.5 %
|
93.8 %
|
45.3 %
|
every age |
54.3 %
|
93.5 %
|
42.7 %
|
Epidemiology : regions of the Rocky Mountains area and Pacific slope of the USA and Canada, where it causes CTF, a human disease initially confused with a mild form of Rocky Mountain spotted fever, which is caused by Rickettsia rickettsii. Antibodies to CTFV antigen have been detected in sera of humans in South Korea (C. Calisher, pers. comm.).- California hare coltivirus (CTFV-Ca), identified as strain S6-14-03, was isolated from the blood of the white hare, L. californicus, black-tailed jackrabbit), in northern California (outside the range of D. andersoni)ref
- Salmon River virus (SRV), which may be a serotype of both CTFV and CTFV-Ca, isolated from a person with moderately severe CTF-like illness in Idaho
Epidemiology : isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peruref
Epidemiology : was first isolated in Nigeria in 1966 during surveys of livestock, Culicoides midges, and mosquitoes, SHUV also once was isolated from a febrile childref1, ref2. SHUV recently was identified as a previously undetected cause of neurologic disease in horses in southern Africaref and veterinarians in South Africaref and is thus of interest in comparison to WNV.
Epidemiology : in June 2009, in northwestern Missouri, United States, 2 men from 2 geographically distant farms were hospitalized for fever, fatigue, diarrhea, thrombocytopenia, and leukopenia. Both men had been bitten by ticks 5–7 days before the onset of symptoms. A virus was isolated from the leukocytes of each patient and later identified as a novel phlebovirus by next-generation sequencing. The 2 viruses were highly related (98%, 95%, and 99% sequence identity for the small, medium, and large viral genome segments, respectively), indicating that the men were independently infected with the same virusref.
Epidemiology : isolated retrospectively in 2014 during the investigation of a disease outbreak among shy albatrosses in Tasmania in 2002ref
Transmission : ticks (Ixodes eudyptidis)
Overall, 24.1% of patients with PIV-3 infection
developed virologically proven pneumonia; the
development of lower tract disease was driven
primarily by the administration of corticosteroids
for GVHD and pseudo-GVHD. Copathogens were commonly
isolated from patients with PIV pneumonia and were
highly associated with mortality from this disease.
Although therapy with aerosolized ribavirin was not
applied in a randomized fashion, this agent failed
to demonstrate any trends toward decreased viral
shedding or improved survival in those with
established pneumonia.One of the strengths of this
study was the standardized clinical protocol used.
All HSCT recipients with symptoms of URI had NPT
washes submitted for culture for community-acquired
respiratory viruses. More importantly, culture for
parainfluenza viruses was uniformly applied for all
BAL, biopsy, and autopsy specimens performed
throughout the study. Because virtually all patients
at our center with signs or symptoms of pneumonitis
undergo BAL (and many also undergo open lung
biopsy), an accurate measure of the frequency of
parainfluenza LRI and the prevalence of pulmonary
copathogens was possible.Progression from upper to
lower tract disease occurred in 24% of PIV-3
infections. Among those with preceding URI, the
receipt of corticosteroids for GVHD or pseudo-GVHD
appeared as the only significant risk factor for
progression in multivariable models (Table 2, Figure
2). GVHD (and the steroid therapy that accompanies
it) is well known to be associated with both
noninfectious and infectious interstitial
pneumonia.6 When steroid use was added to logistic
regression models that contained various
combinations of predictor variables (including
GVHD), however, the models were always significantly
improved. On the other hand, once steroid use was
included in a regression model, inclusion of other
variables led to models that were improved very
little (Table 2). Importantly, steroids were
associated with PIV-3 pneumonia among autologous
transplant recipients with pseudo-GVHD as well;
their use in the autologous setting effectively
raises the risk for progression to that of the
highly immunosuppressed allogeneic transplant
recipient. Thus, the correlation between GVHD and
PIV pneumonia appears to be primarily driven by the
corticosteroids patients receive for this condition.
It is likely that the "steroid effect" is related to
an acute decline in T-cell-mediated immunity that
occurs after the administration of high-dose
corticosteroids. These data suggest that tapering of
corticosteroids at the time of PIV-3 URI diagnosis
may be one strategy to prevent progression to
pneumonia.The high prevalence (53%) of pulmonary
copathogens (A fumigatus in particular) in patients
with PIV-3 pneumonia is noteworthy; a high incidence
of aspergillosis (29%) among patients with PIV-3
pneumonia was also noted in a recent report.7 This
association is reminiscent of the well-known
association between bacterial pneumonia and
influenza virus infection. PIV may predispose
patients to such infections by damaging the
respiratory epithelium and allowing other organisms
to penetrate or may exert a direct immunosuppressive
effect. Recent data have suggested that antecedent
PIV-1 infection may predispose to bacterial
pneumonia in the elderly8 and may inhibit T-cell
function in vitro,9,10 raising the possibility that
either local or global immunosuppression may be
operative. Further studies regarding the interaction
of PIV-3 with other posttransplant infections are
needed.Ribavirin has activity in vitro against a
broad spectrum of DNA and RNA viruses and reduces
PIV titers in animal models.11 Small case series
have reported clinical success with the use of
aerosolized ribavirin in the treatment of
parainfluenza pneumonia among recipients of HSCT.2
Although ours was not a randomized trial, the use of
aerosolized ribavirin with or without concomitant
IVIG did not modify the high mortality rates in
patients so treated. No differences in survival were
demonstrated in an earlier study of aerosolized
ribavirin therapy; mortality was 22% regardless of
treatment.3 Patients in that study, however, were
treated a median of 11 days after symptom onset. In
our study, all individuals who received ribavirin
did so within 48 hours of diagnosis of parainfluenza
3 infection by BAL; rapid diagnosis was achieved in
over half of these individuals via DFA staining,
allowing initiation of ribavirin a median of 2 days
after LRI was identified. Unfortunately, mortality
did not appear significantly lower in those who were
identified early, even among those without
significant copathogens isolated; early diagnosis
and therapy also failed to result in improved
mortality in another recent report.7 Furthermore,
ribavirin failed to shorten the time for viral
shedding from the nasopharynx among those treated,
arguing against a significant antiviral effect.It
remains possible that earlier diagnosis of PIV-3
pneumonia may allow for more expeditious therapy
with ribavirin, thereby potentially improving
outcome.12 Alternatively, ribavirin could be applied
to patients with parainfluenza URI to prevent
progression to LRI; this approach could have merit
in patients with GVHD on high-dose corticosteroids,
who appear to be at higher risk for progression
(Table 2). Finally, other investigators have
reported some anecdotal success with systemic
ribavirin therapy administered orally or
intravenously, though hemolysis is a notable
complication.12,13 Given the significant morbidity
and mortality associated with PIV-3 pneumonia, there
is a pressing need for systematic evaluation of
these approaches via randomized, controlled trials.
In addition, newer, more active antiviral agents are
needed.Because current therapeutic options are
limited, the prevention of PIV infections is
paramount. Unfortunately, the epidemiology of PIV-3
infections makes infection control daunting. Strict
infection control practices can decrease nosocomial
or patient-to-patient transmission; these have been
in place at the FHCRC for the past 9 years. Despite
these measures, incident infections continued to
occur in outpatients, most notably in a prolonged
outbreak from September 1998 to June 1999 (Figure
1). This outbreak was coincident with a dramatic
rise in community-wide prevalence (data not shown).
In contrast to RSV infection (which is usually
symptomatic), PIV-3 can be associated with minimal
symptoms in the immunocompetent host, who may shed
the virus for up to 1 month14; the avoidance of
"symptomatic" individuals may thus be ineffective.
Peaks in community PIV-3 activity occur in parallel
with allergy season, further complicating the
interpretation of individuals with rhinorrhea. Given
the year-round distribution of cases and prolonged
shedding among those infected, constant vigilance to
staff, family, and patient symptomatology may be
needed to prevent transmission outside of the
"respiratory virus season." Vaccine or
chemoprophylaxis agents (once available) should
prove highly useful in this setting as well.In
conclusion, PIV infections occurred in approximately
7% of patients after HSCT at our center. Almost 25%
of patients with PIV-3 URI progress to pneumonia.
Corticosteroid therapy was highly associated with
pneumonia in a dose-dependent fashion, and
dramatically increased the risk for pneumonia among
autologous transplant recipients as well. Mortality
from PIV-3 pneumonia was high and driven higher by
the presence of copathogens; ribavirin with or
without IVIG did not appear to improve survival or
decrease viral shedding. New agents are sorely
needed for PIV infections in the immunocompromised
host. Until then, strict infection control measures
based on virologic surveillance of symptomatic
patients remain the cornerstone of preventive
strategy.PIV3 infections in England and Wales are
seasonal, occurring between May and September each
yearref.
Reinfection can occur throughout life, the elderly
and the immunocompromised being at greater risk of
serious complications. Infection with human
parainfluenza virus 3 is usually seasonal in
temperate climates, with outbreaks occurring
predominantly in autumn. Human parainfluenza virus 3
spreads efficiently, and, by age 5, almost all
children will show serological evidence of past
infection. Hence, firm diagnosis of human
parainfluenza virus 3 infection depends on isolation
of infectious virus. Because reinfection can occur
throughout life, despite the presence of
neutralizing antibodies, nosocomial infection is
common in both children and adults. It infects 5.3%
of HSCT recipients : while all patients with URTI
survive, 60% of patients with pneumonia die despite
early ribavirin therapyref.
=> croup in babiesref
=> bronchiolitis and acute
bronchitis
in babies
=> giant
cell
pneumonia with pulmonary alveolar
proteinosisref
and interstitial
pneumonia
in immunocompromised
adults is increasingly accepted as a cause of
serious morbidity and mortality, especially in bone
marrow transplant (BMT) patientsref1,
ref2,
ref3.
Of the parainfluenza viruses, type 3 (PIV3) seems to
have the highest virulence, since PIV3-induced
pneumonia has a mortality of about 40 to 50% in
adult BMT patientsref1,
ref2.
Transmission of PIV3 has been demonstrated
previously by Karron et al.ref,
who investigated a PIV3 outbreak on a pediatric
ward. However, our data additionally implicate
prolonged shedding of virus by an immunosuppressed
patient as a major factor in the first outbreak. In
fact, symptoms together with virus shedding were
observed for up to 4 months in several of the BMT
patients despite treatment with ribavirin. Prolonged
shedding of PIV3 may continue for many months in
immunosuppressed childrenref
and adultsref1,
ref2,
even despite ribavirin
treatment.
=> ADEM in an allogeneic HSCT recipient,
who presented with rapid onset of paraplegia and
widespread neurological deficits 6 weeks after
parainfluenza pneumonia. MRI showed typical features
of ADEM, involving the subcortical white matter,
brain steam and spinal cord. There was a rapid and
complete response to pulse high-dose corticosteriod
and intravenous immunoglobulinref.