miércoles, noviembre 18, 2009

Interferencia de rinovirus en la replicación de influenza

Common cold may hold off swine flu
A virus that causes the common cold may be saving people from swine
flu [pandemic (H1N1) 2009 influenza virus infection]. If this
intriguing idea turns out to be true, it would explain why swine
flu's autumn wave has been slow to take off in some countries and
point to new ways to fight flu.

"It is really surprising that there has not been more pandemic flu
activity in many European countries," says Arnold Monto, an
epidemiologist at the University of Michigan, Ann Arbor. In France,
flu cases rose in early September [2009], then stayed at about 160
per 100 000 people until late October, when numbers started rising again.

The delayed rise was puzzling, says Jean-Sebastien Casalegno of the
French national flu lab at the University of Lyon. He reports that
the percentage of throat swabs from French respiratory illnesses that
tested positive for swine flu fell in September, while at the same
time rhinovirus, which causes colds, rose. He told New Scientist that
in late October, rhinovirus fell -- at the same time as flu rose. He
suspects rhinovirus may have blocked the spread of swine flu via a
process called viral interference. This is thought to occur when one
virus blocks another.

"We think that when you get one infection, it turns on your antiviral
defences, and excludes the other viruses," says Ab Osterhaus at the
University of Rotterdam in the Netherlands.

How important such interference is in viral epidemics is unclear.
However, there are also cases in which there is no interference, and
people catch 2 viruses at the same time. Normally, we don't get a
chance to see how rhinovirus affects flu, because flu epidemics
usually strike in winter; whereas rhinovirus hits when schools start
(late summer in the northern hemisphere). But this year the pandemic
meant flu arrived early -- and France isn't the only country in which
rhinovirus seems to have held it at bay.

In Eurosurveillance last month [see reference below}, Mia Brytting of
the Swedish Institute for Infectious Disease Control in Solna
reported a rise in rhinovirus coupled with a swine flu lull just
after school resumed in Sweden at the end of August [2009]. She too
says rhinovirus has now fallen, as flu has climbed. Researchers in
Norway report rhinovirus rose there as flu fell in August, while Ian
Mackay at the University of Queensland found the same trend in
Australia. What's more, in March, Mackay reported that people with
rhinovirus are less likely to be infected with a 2nd virus than
people with other viruses, and are just one-third as likely to have
simultaneous seasonal flu (Journal of Clinical Virology, DOI:

So why hasn't the US, for example, seen a dip in pandemic cases
during a back-to-school rhinovirus outbreak? Mackay speculates that
interference from rhinovirus may not be enough to fend off flu if
someone is exposed repeatedly. There were far more cases of swine flu
in the US in September than in Europe. The effects of rhinovirus,
often dismissed as "only" a cold, are too poorly understood, say all
the researchers. Its seeming ability to block swine flu may already
have saved lives in France by buying the nation time before the
vaccine arrived. It may even lead to a drug that induces the
antiviral state, but without the sniffles.

[Byline: Debora MacKenzie]

[The reference for the Eurosurveillance publication cited above is
the following: Eurosurveillance, Volume 14, Issue 40, 08 October 2009
This paper by A Linde et al. is titled: Does viral interference
affect the spread of influenza. The summary reads: "This short
communication hypothesis that rhinovirus epidemics occurring after
start of school may interfere with the spread of influenza during the
period when warm and humid climate decreases the influenza spread by
aerosol. Limited laboratory data supporting this hypothesis are
included in the article, but the report is written mainly to
stimulate interest and research concerning the possibility that viral
interaction may affect influenza epidemiology."

There are many viral respiratory pathogens and it is not unreasonable
to hypothesize that some or all of these might interfere with the
replication of influenza virus, which is itself susceptible to
auto-interference by the generation defective interfering particles
during replication (Indeed such defective interfering particles may
in time be harnessed as specific therapeutic agents). The
identification of rhinoviruses as interfering agents is partly a
consequence of the surveillance activities associated with this
virus. Interference by other viral respiratory pathogens will remain
unrecognised in the absence of systematic surveillance.

FUENTE: Promedmail

lunes, octubre 05, 2009

Investigación basica

Aunque no sea una noticia de microbiología, esta noticia es un ejemplo de la importancia de la investigación básica. Si esa tan abandonada por la I+D de los políticos y encima tan recortada para el año que viene.

jueves, octubre 01, 2009

Posibles causas de mayor afectación en "jóvenes"

Residual immunity against seasonal and pandemic influenza A(H1N1) virus in people born before 1950 is probably due to the lower capacity for drift of the H1N1 subtype, combined with the wide circulation of this virus between 1918 and 1957.


martes, septiembre 29, 2009

Mutación detectada en virus de la gripe

Esta mutación previamente detectada en otras cepas de influenza A se asoció con mayor adaptación al hombre.

A ProMED-mail post

Date: Mon 28 Sep 2009
From: Marion Koopmans

We would like to report 2 patients in The Netherlands, diagnosed with
influenza pandemic A(H1N1) 2009 virus infection that had a mutation (E627K)
in the basic polymerase 2 (PB2) protein. This mutation has previously been
associated with increased efficiency of replication and possible virulence
changes in other influenza A viruses.

The investigation identified a specific geographic region in the north of
The Netherlands as the place where viruses with the same genetic background
have circulated between mid July and mid August [2009]. No other cases
carrying the PB2 mutation have been identified.

On 15 Sep 2009, the 1st influenza A(H1N1)v virus with a glutamic acid to
lysine mutation at position 627 (E627K) in PB2 was identified through
routine sequence analysis of clinical samples from a diabetic patient
infected with A(H1N1)v virus. The 1st day of illness was on 9 Aug 2009,
when the patient was vacationing on one of the West Frisian Islands in the
wetlands north of The Netherlands (Waddenzee). He had a relatively mild
course of illness. Subsequent retrospective tracing of geographically
linked A(H1N1)v cases from the national databases led to the identification
of 24 additional A(H1N1)v confirmed cases throughout the country that had
stayed on the same popular holiday island during July and August. Sequence
analysis of 12/24 clinical specimen available at the institute identified
10 A(H1N1)v viruses that clustered with the virus obtained from the
diabetic index patient based on unique mutations in the NA gene and PB2
gene. Only one of these had the PB2 E627K mutation. This virus was isolated
from a family contact of an adolescent girl who returned from a one-week
stay on the same island on Mon 20 Jul 2009 with high fever and coughing.
This girl had been camping with a group of 16 boys and 8 girls that shared
2 tents. Almost all members of this group reportedly had been ill, and
influenza A(H1N1)v infection had been diagnosed in 2 other persons
belonging to the same camp. The girl was ill for a week, with full recovery
after 2 weeks. Our 2nd case with a virus shedding carrying the PB2 mutation
is the younger sister and became ill on Thu 23 Jul 2009. She was treated
with oseltamivir and recovered fully after one week. Both parents remained
free from symptoms.

As the mutations were identified more than one month after initial
detection, no further contact investigations were done. Municipal health
services were informed about the local disease activity. Since 15 Aug 2009,
mild influenza cases are no longer notifiable in The Netherlands, so we
have no information on possible onward transmission. No clusters of illness
(for example, from schools) were reported in the health regions involved
(including the island), and surveillance data from a national
physician-based sentinel network showed low ILI activity for the
Netherlands. Samples from 22 patients hospitalized with influenza A(H1N1)
in July and August did not have the PB2 mutation.

PB2 627K is consistently found in human influenza A viruses, but rarely in
avian-derived viruses. The E627K mutation may result in enhanced virus
replication efficiency in humans, possibly by adjustment to host body
temperature or cellular cofactors, and has previously been shown to be
associated with fatal cases of HPAI H5N1 and H7N7 virus infection in
humans. Until now, A(H1N1)v viruses with Influenza pandemic (H1N1) 2009
(57): in PB2 have not been reported, and the clinical and epidemiological
relevance of our finding remains unclear.

Preliminary experiments in ferrets using reverse genetics-derived new
influenza A(H1N1)v viruses with the E267K mutation in PB2 did not indicate
increased shedding, virulence or transmissibility. Further experiments as
well as increased molecular surveillance to monitor the situation are ongoing.

communicated by:
Marion Koopmans
Chief of Virology
Laboratory for Infectious Diseases and Screening, Center for Infectious
Disease Control
National Institute of Public Health
The Netherlands

[ProMED-mail thanks Dr Koopmans and colleagues for providing this
interesting information recording the detection of the same E267K mutation
in the basic polymerase 2 (PB2) protein of 2 independent isolates of
A(H1N1)v in the north of The Netherlands. The functional relevance of this
mutation remains to be determined. - Mod.CP]"

lunes, septiembre 28, 2009

Nuevas cepas de C. difficile.

En brote padecido en Canadá se ha demostrado que C. difficile ha evolucionado hacia una cepa con mayor facilidad de diseminacion y màs poder patogènico. ha sido mediante la comparaciòn del genoma de cepas aisladas hace varios años con cepas actualmente aisladas.

Estas cepas " hipervirulentas" pertenecen al PCR-ribotipo 027.


presenta 5 nuevas regiones, que no aparecen en cepas anteriores del mismo PCR-ribotipo, donde se encuentran genes que regulan motilidad, toxicidad, regulación de la transcripción y resistencia a fármacos.

jueves, septiembre 24, 2009

Hay que estudiar HPV en cancer orofaringeo

El motivo no es otro que condiciona el tratamiento a seguir así como el pronóstico. Si es HPV positivo, mejor pronóstico y solo con quioterápia y radioterapia. Si es HPV negativo responde peor a quimio y radioterapia necesitando tratamiento quirurgico. Publicado este mes de Septiembre en: Cancer Prevention Research.

martes, septiembre 01, 2009

Evolución de la gripe en Invierno

Muy recomendable este artículo de como ha evolucionado la estación de la gripe en Nueva Zelanda durante el invierno.

- Varias cepas de virus de la influenza han circulado, con predominio de la nueva cepa A H1N1 09
- Mayor número de casos notificados entre los menores de un año (a prepararse los pediatras)
- Pico muy ligero de casos coincidente con la vuelta a clase, menor de lo esperado.
- La tasa de fatalidad está en el rango habitual de la influenza estacional para los menores de 65 años (Los avances médicos actuales es una posible causa a que los datos no sean similares a los de 1918: antibióticos, antivirales, cuidados intensivos).
- La tasa de notificación de gripe entre los mayores de 70 años es la más baja entre todos los grupos de edad.
- Estimación de infección sintomática en 7,5 % de la población.

martes, mayo 05, 2009

¿reactividad cruzada?

El que la media de edad de los afectados por la cepa causal de estos casos tan publicitado de influenza puede ser por varios motivos.
Se apunta que es la población más joven la que más viaja y que en este brote se contagia más. Sin embargo ya en sus inicios, lo que en Mexico llamó más la atención, era precisamente eso, que afectaba más a la población joven del punto origen.

Otra posibilidad no muy comentada es que quizás haya inmunidad cruzada con otros virus H1N1 que remotamente en el tiempo haya circulado por el globo, hace unos 40 años. Esto puede apuntar que si en la vacuna que está en producción este año hay alguna cepa H1N1 pueda ofrecer alguna inmunidad aunque especificamente no se introduzca el virus causal del brote.

sábado, mayo 02, 2009

¿Vacuna para el virus influenza A H1N1?

Dentro de unos días este virus desaparacerá. Pero en la nueva temporada de la gripe puede aparecer de nuevo y ser uno de los dominantes. Para protegernos, una posibilidad sería la inclusión en la vacuna de la procima estación gripal. El problema es que la vacuna para la proxima estacion está ya en produccion y para Agosto se comienza a distribuir.

Hasta final de Mayo no pondrá el CDC a disposición de las companias la cepa patrón de este brote de influenza. Una vez con ella, las companias tardarán en adaptar el proceso a la nueva cepa, así como establecer su eficacia respecto a concentracion de antigeno y seguridad. Añadimos la dificultad de necesitar dos dosis para lograr una buena inmunidad para una cepa nueva.

La posibilidad barajada por algunas firmas es la de elaborar dos vacunas, la estacional de la gripe, que ya esta en proceso y que frenarla supondría un gran retraso, y la este brote de gripe.

Las pocas firmas que pueden desarrollar una vacuna a su tiempo, como Novavax, usarían metodología y protocolos no habituales de los que no tenemos pruebas de su eficacia. (en el proceso actual ya tenemos experiencia y conocemos su eficacia).

En resumén, que parece que esta cepa de influenza no será incluida en la vacuna del año que viene.

jueves, abril 23, 2009

La evolución bacteriana

No me digáis que no es precioso como Chlamydia trachomatis está mutando. Tenemos muchos ejemplos de como las bacterias evolucionan bajo la presión de los antibióticos por aparecer mutaciones en las dianas de los antibióticos o por difundirse en un ambiente unos genes que confieren esta resistencia de unas bacterias a otras. Las bacterias con estos genes se encuentran privilegiadas en un medio con la presencia de antibióticos pudiendo diseminarse para ocupar todo el nicho ecológico que ocupaba previamente la cepa carente de estos genes antes de aparecer estos antibióticos en el medio.

La variación detectada en Chlamydia trachomatis no se debe a la presión antibiótica. Se debe, aquí lo novedoso, a la presión diagnóstica. Chlamydia trachomatis presenta una delección de 377 pares de bases en el plasmido usado como diana para su detección mediante técnicas moleculares. Así la detección de la secuencia diana en el plásmido en una muestra clínica motiva la administración de un antibiótico anti-clamidia al paciente. Pero los pacientes infectados por la cepa con la variación en la secuencia diana empleada en la detección no reciben tratamiento anticlamidia, favoreciendo su diseminación y permitiendo a esta cepa variante ocupar el nicho que ocupaba la cepa salvaje.

Cuando nos creíamos que con técnicas moleculares podríamos detectar todos los gérmenes que tuvieramos secuenciados ahora resultan que se nos escapan. ¿No suena esto igual a cuando creíamos que con los antibióticos podríamos controlar a todos los gérmenes y estos gérmenes se nos escaparon?