La spécificité du tadalafil est liée à sa longue demi-vie, permettant une action qui excède largement celle des autres inhibiteurs de PDE5. L’absorption digestive est complète, avec un pic plasmatique atteint en 2 heures environ. Le métabolisme est réalisé via CYP3A4, produisant des métabolites inactifs éliminés principalement dans les fèces. La sélectivité enzymatique est élevée, réduisant les effets indésirables extra-caverneux. Les réactions indésirables fréquentes incluent céphalées, bouffées vasomotrices et troubles digestifs légers. L’activité pharmacologique est stable, indépendamment de l’ingestion d’aliments. Dans les comparaisons de longue durée, acheter cialis pas cher est mentionné en relation avec les études portant sur la persistance d’efficacité et la constance de la cinétique plasmatique.

Outbreak

Surveillance and Response
to Prevent Malaria
Re-emergence
Alexandre Macedo de Oliveira, MD, MSc, PhD
Division of Parasitic Diseases and Malaria
Centers for Disease Control and Prevention
• Discuss thoughts about malaria reemergence
(thoughts, due to limited information on the
topic)
• Discuss interventions to prevent and/or
respond to such events
• Keep recommendations focused on what
feasible, or advisable, in the context of the
Americas
Terms of Interest
• Malaria importation
– A person acquires malaria in an endemic area
and goes to a non-endemic area
• Malaria introduction
– First-generation transmission of malaria
originating from an imported case in a
malaria-free area
• Indigenous malaria
– Local malaria transmission without any direct
link to an imported case
Terms of Interest
• Malaria outbreak
– Increase in number of expected cases in a
given area during a period of time
– Either increase from baseline transmission or
reintroduction
• Malaria reemergence vs. reestablishment vs.
reintroduction
– In most cases, referring to the same thing
(though not always)
Malaria Reemergence
• Receptivity
– Presence of vectors, and ecological/climatic
conditions favorable to malaria transmission
– How capable area is to allow for transmission
• Vulnerability
– Proximity to malarious areas or possibility of
influx of malaria patients or vectors
– Possibility of malaria parasite introduction
Preparedness
• Risk assessment and monitoring
• Programmatic and systemic readiness
for response
• Malaria surveillance
– Detection of initial cases
• Ability to respond
Risk Assessment and Monitoring
• Malariogenic potential
• Factors influencing vulnerability and
receptivity
– Migration patterns, climate, rainfall
• Malaria early warning systems
– Different ways to set up such a system
Systemic Readiness
• Maintenance of malaria expertise for malaria
control and prevention
• Difficult in countries that reached malaria
elimination
– Tendency to lose expertise once malaria no
longer a concern
• Expertise and commodities ready to
deployment
Systemic Readiness
• Malaria preparedness plan
– Information on roles and responsibilities
during an outbreak or reemergence episode
– Guidance on leadership, involvement of other
public health programs, communication
chain, resources mobilization
– Description of relationships and reliance
on external partners
– Operating procedures for intervention
implementation of control interventions
Systemic Readiness
• Response team
– At minimum: an epidemiologist, a
laboratorian and an entomologist
– Desirable: logistician, communication
specialist, etc
• Supply chain
– Availability of drugs and diagnostic
supplies
Malaria Surveillance
• Detection and reporting of cases
(during outbreak and not!!)
• Basis for appropriate treatment
• Reliance on laboratory proficiency
– Need to be maintained
Entomological Monitoring
• Ground work done as part of preparedness
• Areas with malaria receptivity and/or
vulnerability
– Yearly monitoring of vector composition
and insecticide resistance even if no
transmission
– Support decisions on control measures
Outbreak Definition
• Increase in number of expected cases in
a region during a period of time
• In malaria-free areas
– One, just one!!, introduced or
indigenous malaria case is an outbreak
Response Mode
• Dynamic, activities and their intensity
changing over the course of a response
• Beginning
– Case detection
• Timely laboratory confirmation by expert
microscopy or molecular methods of all
cases
• In-depth interviews to asses place of
infection and collect demographic info
(imported vs. introduction and indigenous)
First Steps in Response
• Inventory of local, regional and national
capacity to respond
• Mobilization of proficient staff for laboratory
diagnosis and case management
• Availability of supplies
• Definition on communication channels and
leadership roles
Laboratory Methods
• Microscopy
– Gold standard method
– Dependence on microscopists
expertise
• Rapid diagnostic tests (RDTs)
– Less sensitive
– No quantification
• Molecular-based tests
– Little role in outbreak detection
– Complementary (later) important role
Laboratory Preparedness
• Maintenance of microscopy expertise at
either local or regional/central level
– Continuous training needed
• Availability of reagents and equipment
– Appropriate supply chain (Edgar’s
expertise!!)
• Plans for scaling up microscopy capacity
if needed
• Timely result reporting systems
Laboratory Preparedness
• RDTs as alternative for timely case management
(treatment decisions)
• Quality assurance and control systems in place
and running
• Mandatory collection of smear for confirmation
(all positive cases, all or a sample of negative
cases)
• Consider collection of samples in filter paper for
future molecular testing
Treatment Preparedness
• Availability of good quality drugs (Edgar’s
expertise again)
• Appropriate regimens for implicated
species and strain
– Issue of chloroquine-sensitive
parasites
– If in doubt, cover chloroquine-resistant
parasites
• Training of healthcare workers in
identifying, testing and treating cases
Initial Cases Follow-up
• Close clinical and parasitological monitoring
to ensure treatment compliance and parasite
clearance
– Difficult as transmission progresses
• Adopt broader case definition (less specific)
of suspected malaria case, eg fever
• Reinforce passive case detection and
reporting in neighboring areas
Case Finding
• Active case detection
– Public health officials identifying
and reporting cases
– Time consuming on response team
• Passive case detection
– Healthcare workers or laboratorians
identifying and reporting cases
– Risk of missing cases
• Generally a combination of the above
Contact Investigation
• Evaluation of home and work contacts of
confirmed cases
– Determination of radius for contact
investigation (most cases, household
contacts and immediate neighbors)
– Testing of all contacts or only symptomatic
contacts
• Epidemiological decision
• Most infected people symptomatic in non-
endemic areas
Contact Investigation
• Evolving contact investigation strategy
during re-emergence episodes
1. Only symptomatic contacts
2. All contacts irrespective to symptoms
3. Population-based surveys
• Epidemiological decisions
– More is not always better
Surveillance
• Plot cases in time and space
• Geographic mapping by place of residence
or probable place of infection
• Periodical analysis of data and decisions
on what follow up/control measures
• Decisions based on data, not assumptions
if possible
Control Measures
• Proper case management
– Identification of cases
– Accurate diagnosis
– Proper treatment
• Vector control
– Indoor residual spraying
– Insecticide-treated nets (ITNs)
– Larviciding in special cases
• Limited and localized breeding
Questionable Interventions
• Fogging
– Limited value, temporary effect
• Mass drug administration
– Risk of drug overuse and side effects
– Cost effective when malaria prevalence
>55–70%
Follow-up Studies
• Case-control studies
– Determine causes and mechanisms of
transmission
– Often later in an outbreak response
– Not a reason to delay implementation of
control interventions
• Molecular analysis
– Genotyping
– Later in outbreak for evaluation of
dissemination patterns
Acknowledgements
– Melissa Briggs
– Jaime Chang
– Kathrine Tan
– Kumar
– John Barnwell
– Audrey Lenhart
– Bill Brogdon
– Many others
Gracias!
– Melissa Briggs
– Jaime Chang
– Kathrine Tan
– Kumar
– John Barnwell
– Audrey Lenhart
– Bill Brogdon
– Many others
Gracias!
– Kumar
– Jaime Chang
– John Barnwell
– Audrey Lenhart
– Melissa Briggs
– Kathrine Tan
– Bill Brogdon
– Many others
Laboratory Network
• Availability of quality microscopy, if
possible
• RDTs as ‘first-line’ diagnostic tool but
smears taken for confirmatory
• Samples in filter paper for subsequent
– Confirmatory assays
– Genotyping and resistance testing

Source: http://proyectomalariacolombia.co/files/amiravreda/Martes%209/Alexandre%20Macedo.pdf