**FTS-CDC-NIP**

**Moderator: Dale Babcock**

**October 11, 2007**

**11:00 am CT**

Coordinator: This is the transcriptions for the FTS conference with Mr.
Dale Babcock. The call is scheduled for Thursday, October 11, 2007 at 11
am Central Time, call ID 5259885.

Welcome and thank you all for standing by. At this time all parties will
be in a listen only mode until the question and answer portion of
today\'s' call. The call is being recorded. If anyone has an objection,
you may disconnect your line at this time. I would now like to turn the
call over to Dr. Andrew Kroger. Sir, you may begin.

Andrew Kroger: Thank you very much. Good afternoon everybody and welcome
to current issues in immunization, a CDC NetConference. This is Dr.
Andrew Kroger in the National Center for Immunization and Respiratory
Diseases, specifically the Education Information and Partnership Branch
of the Immunization Services Division. I will be the moderator for
today\'s session.

Net conference technology allows us to present material instantaneously
via the internet. To participate in today's program you will need a
telephone connection and a separate internet connection.

The learning objectives for the session are one, list a recent
immunization recommendation made by the Advisory Committee on
Immunization Practices, or ACIP, and two, describe an emerging
immunization issue.

It is October 11, 2007, and today we have Dr. Katherine Tan, a medical
officer in the malaria branch of the National Center for Vector-Borne,
Zoonotic and Enteric Disease. She will be speaking today on pre-and post
travel care for malaria.

Please make a note of the following information. If you have technical
trouble, please dial star zero on your telephone. If you would like to
ask a question, please press star one on the phone.

Continuing education credit is available only through the CDC (ATSDR)
training and continuing education online system at www.cdc.gov/T C E O N
L I N E \-- or TCE online.

You must have a verification code specific to this program to apply for
CE credit. The code will be revealed during the course of the program.
CE credit for this activity will expire on November 12, 2007.

CDC, our planners and our presenters wish to disclose they have no
financial interests or other relationships with the manufacturers of
commercial products, suppliers of commercial services or commercial
supporters.

Presentations will not include any discussion of the unlabeled use of a
product or a product under investigational use with the exception of Dr.
Tan's discussion of malaria vaccines and treatments that are still under
investigation. So now we will begin with a presentation of pre and post
travel malaria advice. Katherine?

Katherine Tan: Great. Andrew, thank you for having me on today. Here is
an overview of the talk. First we'll start with a background on
epidemiologic and clinical information on malaria. Then, the bulk of the
talk will be on pre- and post- travel care where I'll discuss practical
patient management issues related to malaria. I'll also include a brief
overview of malaria vaccines in development. Then, I'll finish the talk
by mentioning various resources on malaria.

Worldwide there are 300-500 million cases of malaria each year. Malaria
kills more than 1 million people each year, and in Africa every 30
seconds, 1 child dies of malaria. This map shows areas of malaria risk.
Countries in green have no known malaria risk, those in yellow have
varied malaria risk, and those in red have malaria risk throughout the
country. As you can see, malaria is endemic in Mexico, Central and South
America, Africa, the middle east, and Asia.

In the United States in 2005, there were 1528 cases reported of known
malaria among US and Foreign civilians. Foreign civilians are persons
from other countries who visit the US. This number does not include
individuals in the military and those with unknown status. (There were
34 individuals in the military and 258 persons with unknown status who
were reported to have malaria.) As shown in the pie chart here, a
majority, or 58% of malaria cases occurred in US civilians. 19% of cases
occurred in foreign civilians. Almost all malaria cases were imported
malaria cases, meaning that persons contracted malaria abroad and were
diagnosed with malaria after returning to the US.

This chart shows the numbers of imported malaria cases in US Civilians
by country of acquisition in 2005. Among US civilians alone, there were
780 malaria cases reported in 2005. Of these cases, the main countries
where malaria was acquired were Nigeria (26.5%), Ghana, and India.

Keeping in mind that almost all cases of malaria in the US were from
imported infections, and that most cases were in US residents traveling
aborad, let's look at the number of people at risk. This graph shows the
number of US residents who traveled abroad by year of travel. The number
of US residents traveling abroad has increased from just over 50 million
in 1995 to more than 60 million in 2005.

> This graph shows the percentage of travelers by geographical regions.
> So, of the over 60 million US travelers, it is estimated that more
> than half traveled to malaria endemic regions such as Mexico, C or S
> America, Asia/India, Middle East, and Africa).
>
> Of these travelers, who is most at risk? Taking a look at the
> characteristics of persons who traveled to areas where most of our
> imported malaria comes from -- India, Mexico, and Africa, note that
> most are not US born as shown in the right hand column. It is thought
> that these travelers may be going to these areas to visit friends and
> relatives, whereas US born travelers may be going to these areas for
> tourism or business. In contrast, look at travel to Western Europe
> where most travelers were US born -- this might suggest that they are
> there for tourism rather than VFR. In fact, of the US civilians with
> malaria, 56% reported traveling to malarious areas for the purposes of
> visiting friends or relatives. So, a large percentage of persons
> traveling to malaria endemic regions are there visiting friends and
> relatives. Furthermore, our surveillance data has shown that persons
> traveling for the purpose of visiting friends and relatives are less
> likely to take prophylaxis and are at greater risk for contracting
> malaria during travel than persons traveling for tourism.
>
> In general, malaria is the 4th most common health problem among
> travelers. This does not include problems with malaria prophylaxis
> drugs. As you can see, the top 3 travelers health problems are
> difficult to prevent, but there are very effective preventive measures
> for malaria.
>
> Before we discuss general clinical information about malaria, let's
> look at the plasmodium parasite. There are four plasmodium species
> that cause malaria in humans: P. falciparum, P vivax, P ovale, and P
> malariae. This is important to know because determining the plasmodium
> species is very important in treatment of malaria.
>
> The plasmodium life cycle is shown here. The top half of the slide
> shows the part of the life cycle that occurs in the mosquito, and the
> bottom half of the slide shows the part of the life cycle that occurs
> in the human. Let's start with the mosquito depicted on the left of
> the slide and go clockwise around this picture. The mosquito bites a
> person infected with malaria. Plasmodium undergoes sexual reproduction
> in the mosquito's gut. Then, when a mosquito bites another person,
> sporozoites, seen on the right of the slide, get injected into that
> perosn. The sporozoites invade liver cells where two things can
> happen. Some sporozoites develop into hypnozoites, a dormant stage
> that can lead to relapses later. Some sporozoites mature into
> merozoites. Merozoites then go from the liver cells to the blood
> cells. Then, after reproducing asexually and after further
> development, the blood cell lyses, releasing more merozoites that
> invade other blood cells. Some merozoites mature into gametocytes, or
> the sexual form of plasmodium into the blood stream. Then, when a
> mosquito ingests blood from this person, it ingests the gametocytes,
> and the cycle starts again. Understanding this life cycle is important
> to understanding the rationale behind treatment and vaccine
> development.
>
> Uncomplicated malaria presents with fevers, chills, headaches, even GI
> symptoms like nausea, vomiting, or diarrhea. Of note, uncomplicated
> malaria can have very nonspecific symptoms and the typical cyclical
> fevers are only rarely seen. This is why travel history, as we'll
> discuss later, is very important in diagnosing malaria. On labs,
> anemia and thrombocytopenia can be seen.
>
> Severe malaria includes symptoms of cerebral malaria (such as
> headaches and decreased level of conciousness). severe anemia
> (hemoglobin less than 11), high parasite load (that is, greater than
> 5% of red blood cells being infected), and other signs listed here.
>
> Diagnosing malaria has three main components: a history of travel to
> an endemic area, symptoms indicative of malaria, and positive blood
> smears. Thick and thin blood smears are the diagnostic tests of
> choice. If the first smear is negative, repeat smears every 12-24 hrs
> for 48-72hrs before deciding that the patient is malaria free. If the
> blood smear is determined to be positive, the species of plasmodium
> must be identified and the level of parasitemia must be determined.
>
> Thick and thin smears help to determine the species of Plasmodium
> because different species of malaria have distinguishing
> characteristics. Smears also help determine parasitemia. Again,
> parasitemia is defined as the number of infected cells per 100 red
> cells. Shown here is a picture of P. falciparum. The large pink cells
> are red blood cells, and within these cells, you can see red nuclei
> (in this picture it looks like black dots) and blue cytoplasm of the
> plasmodium.
>
> There are several factors that guide treatment of patients with
> malaria. Determining the parasite species will help determine the type
> of drug to be used. The type of drug used for treatment will also
> depend on the risk that the person is infected by drug-resistant
> malaria. We determine the risk of drug-resistance based on which
> country the person traveled to. Then, parasite density and clinical
> status of the patient gives us an idea of the severity of malaria and
> also helps guide treatment and management decisions. Parasite density
> is also followed to guage response to treatment. Drug selection will
> also be influenced by the presence of drug allergies and the type of
> drug used during prophylaxis, if prophylaxis was used.
>
> There are many drugs available to treat malaria. However, with severe
> malaria or in patients unable to take medications orally, IV treatment
> is recommended and the only IV treatment available is IV quinidine
> used in conjunction with clindamycin, doxycycline, or tetracycline.
> However, quinidine is an old antiarrhythmic that may not be readily
> available in many hospitals. Recently, a type of artemisinin, IV
> artesunate has been made available as part of a national clinical
> trial and it's available through CDC.
>
> Now that we've gone over malaria 101, let's look at practical issues
> in pre- travel care.
>
> In the pre-travel consultation, review the patient's itinerary in
> detail to assess their malaria risk. Remember that malaria risk can
> vary within a country and even within provinces of that country. Then
> ask how long they will be traveling -- some malaria prophylaxis
> medications are easier to comply with on short versus long trips. Ask
> about the style of travel -- flying from one major city to another
> versus driving or backpacking around a country will affect malaria
> risk. Finally, ask about past medical history, allergies, and immune
> status as these also have implications for pre-travel malaria advice.
>
> After taking the history, and taking into account the patient's travel
> itinerary, assess the patient's malaria risk. You can look up malaria
> risk using several resources which I will be discussing later,
> including CDC's Yellow Book and traveler's health website available at
> www.cdc.gov/travel. Then, advise the patient on personal protection
> measures such as using insect repellants, wearing protective clothing,
> and if possible, having proper accommodations with screened windows
> and using insecticide-treated bed nets. Then, provide chemoprophylaxis
> recommendations.
>
> Before I discuss chemoprophylaxis, I'd like to briefly bring up
> repellent use. Many of us have used or heard of DEET. The lower the
> concentration of DEET, the more frequently it will need to be applied,
> but a concentration more than 50% DEET is not necessary. Picaridin is
> a repellant new to the US, but unfortunately it's available only in
> low concentrations (about 5%) and if used will need to be reapplied
> often. Ideally higher concentrations should be used (around 20%).
> Permethrin is a long lasting repellant that can be applied to clothing
> and bed nets.
>
> Travelers going to areas with malaria risk should also be prescribed a
> prophylactic medication. The prophylactic drug should be chosen
> carefully as these drugs all have different characteristics.
> Chloroquine and mefloquine are dosed weekly, 1-2 wks prior to travel,
> during travel and 4 weeks after return from travel. Some areas,
> however, have chloroquine resistance and a few limited areas have
> mefloquine resistance. Mefloquine is also contraindicated in those
> with a psychiatric and seizure history. Atovaquone/proguanil, also
> known as malarone and doxycycline are dosed daily. Malarone is quite
> useful for children requiring prophylaxis because pediatric strength
> tablets are available, and the tablets can be crushed and added to
> food. Doxycycline has the added benefit of providing protection
> against other vector borne infections, but has the unfortunate side
> effect of yeast infection in some women and GI upset in some.
> Primaquine is rarely used, and is suggested only as a last resort if
> none of the other antimalarials are options. Prior to prescribing
> primaquine, patients must be tested for glucose-6-phosphatase
> deficiency.
>
> This slide shows the various stages of the malaria lifecycle on which
> these medications work. As a reminder, the life cycle in the human
> starts with the mosquito bite, at which point plasmodium immediately
> infects the liver and is said to be in the tissue stage, or "TS" shown
> here. In the liver it can either become dormant as a hypnozoite, "H"
> shown here, or go into the blood and infect red blood cells "BS" shown
> here. From red blood cells, plasmodium can enter its gametocyte stage,
> or "G" shown here, which is what the mosquito ingests when it bites an
> infected person. So, TS stands for "tissue schizontocide," H stands
> for "hypnozoitocide," BS stands for "blood schizontocide," and G
> stands for "gametocytozide." As you can see, chloroquine, mefloquine,
> and doxycycline only work at the blood stage, and this is why they
> have a 4 week post-trip course -- the drug has to be around for a
> while to kill plasmodium that has been lying dormant in the liver.
> Malarone also known as atovaquone/proguanil, will work on the tissue
> and blood stages, so the post-trip course is much shorter. Primaquine
> does not kill the blood stage, so if primaquine fails as a
> prophylactic drug, the blood forms that cause clinical malaria will
> not be killed, and so there are concerns of the potential for severe
> P. falciparum malaria occurring while on primaquine prophylaxis.
>
> In choosing the type of prophylaxis to prescribe, one should consider
> several things. First, is there chloroquine resistance in the country
> of travel? Then, consider the length of the trip. Patients going on
> longer trips may find weekly rather than daily dosing to be more
> convenient. Patients going on shorter trips may not mind daily dosing,
> but may find a long post-trip course of medications to be
> inconvenient. Malarone, with its 1 week post-trip course may be better
> in this case. Also, determine if the patient has any history of
> adverse effects or contraindications to the antimalarial medication.
> And finally, consider cost as some prophylactic regimens vary widely
> in cost and some may not be covered by health insurance.
>
> So, for areas with no chloroquine resistance, chloroquine weekly is
> the best choice. For areas with chloroquine resistance, your options
> are atovaquone/proguanil, doxycycline, or mefloquine. Note that some
> areas of SE Asia have mefloquine resistance, so for those areas,
> atovaqoune/proguanil or doxycycline is preferred. Primaquine would
> then be your last resort if the other medications are not options.
>
> We've received a lot of questions about long term use of prophylaxis.
> In general, there is data for use of these medications for 1-2 yrs,
> but note that the absence of data does not necessarily indicate that
> the drug is unsafe beyond this period. The drug-specific details are
> listed on this slide.
>
> For patients planning extended stays in malaria-risk areas, you can
> use this information to discuss patients' options.

-   What about costs? For a 2-week trip, including pre- and post-
    medication, it's been estimated that generic doxy costs about \$4,
    MQ about \$64, & Malarone about \$104. Note that insurance often
    does not cover atovaquone/proguanil.

> In light of these drug costs, one question that some patients bring up
> is the possibility of buying their medications for cheaper abroad.
> Unfortunately, there are many counterfeit drugs on the market in many
> countries. In fact, 36% of antimalarials abroad are counterfeit.
>
> Of the reported cases of malaria with information on prophylaxis use,
> a majority did not take prophylaxis or did not adhere to the
> prophylactic regimen, or did not take a recommended drug. These are
> some reasons why travelers fail to take chemoprophylaxis. Some
> incorrectly believe that aqcuired immunity is maintained after leaving
> a malarious area, some believe that an area isi free of malaria, when
> it isn't. Some don't realize that chloroquine resistance has developed
> in some areas. Another big reason for not taking chemoprophylaxis is
> fear of drug side-effects. If a traveler is reluctant to take
> prophylaxis, it's important to discuss their reasons and perhaps
> better inform their decision.
>
> So, after the pre-travel consultation, let's say that your patient
> goes abroad, then comes back with a fever. I'll now discuss
> malaria-related post-travel care.
>
> Fever in a returned traveler should always prompt an immediate
> evaluation for malaria. (Having said that, the work-up should also
> include other reasons for fever.)
>
> Important questions to ask when taking the history include:

1)  Travel history -- Ask about the specifics of their itinerary.
    Malaria risk varies within a country, so ask where they traveled,
    especially any travel outside of urban areas. Ask about duration of
    travel, and the date of return.

2)  Use of malaria prophylaxis -- Ask if prophylaxis was used, and if
    so, what type. Ask if they took the medications as directed.

3)  When asking about symptoms, besides asking when symptoms started,
    check for symptoms of severe malaria -- HA, stiff neck, mental
    status changes.

4)  Also ask about previous malaria history.

> Other questions in a complete history include occupational exposures,
> needle exposures, and use of other medications with potential
> antimalarial effect. Some patients take medications while abroad --
> ask about those as well.
>
> If after taking the history, malaria is still suspected, consider the
> following. First, depending on the resources of your clinic, refer the
> patient because some patients with malaria need to be admitted. Labs
> that should be done include thick and thin smears to check for malaria
> parasites which should be read ASAP, CBC, and Chem 20. Most oupatient
> clinics will stop here and refer the management of malaria case.
> Otherwise, once the diagnosis is made, start treatment. Management
> then proceeds as I had discussed earlier in this talk. After the
> patient has been stabilized and his/her disposition determined, notify
> the local health department. If you have any questions on malaria case
> management, you can also call the malaria hotline at the number shown
> during business hours. After hours, call CDC's Emergency Operation's
> Center and a CDC malaria clinician on call will be paged.
>
> But, a word of caution in diagnosing malaria. All malaria is not
> malaria. There may be a mismatch between the history and the diagnosis
> of malaria. For example, incubation periods vary depending on the type
> of plasmodium but can range from 1-3 weeks. If you get a history from
> a traveler who says that their symptoms started on day 3 of their trip
> in a malaria endemic area, then it probably is not malaria. Also,
> certain species are more likely to be found in certain areas.
> Misdiagnosis often occurs, especially with babesiosis and malaria.
> Babesiosis to an inexperienced eye can look like malaria on smear and
> can present similarly. The species of malaria may be misdiagnosed. It
> is common to see a high parasite density, greater than 5% in P.
> falciparum. If you're told that it's P. vivax with 10% parasitemia,
> then suspect that either the species or the parasitemia may be
> incorrect. And finally, question the malaria diagnosis if the
> diagnosis would indicate a prophylactic or treatment failure or if the
> diagnosis would mean a mixed infection as these occurrences are very
> rare.
>
> I'd like to now briefly discuss malaria vaccines in development.
>
> The malaria vaccines in development target three main stages of the
> plasmodium life cycle. Here is a picture of the plasmodium life cycle
> again.
>
> The first type of vaccines we'll discuss are those that target the
> pre-erythrocytic stage, that is the stage that takes place shortly
> after being bitten by an infected mosquito up to and including the
> liver stage.
>
> There are two main mechanisms for how these vaccines work. The first
> is to generate antibodies against sporozoites, preventing them from
> invading the liver. The second is to prevent intra-hepatic
> multiplicaiton by killing parasite-infected hepatocytes. It is thought
> that these types of vaccines would be ideal for travelers since they
> protect against the early stages of malaria infection.
>
> The second target for vaccines is the asexual erythrocytic stage, or
> blood stage of the life cycle.
>
> These vaccines elicit antibodies to inactivate merozoites and to
> target malarial antigens expressed on red cell surfaces. This will
> inhibit the development of the parasite in RBCs. These vaccines are
> likely to be useful for reducing morbidity in endemic countries
> because many people in these countries have a baseline parasitemia.
>
> The third stage in the plasmodium life cycle targeted by vaccines is
> the sexual stage.
>
> These vaccines induce antibodies against sexual stage antigens. It
> basically prevents reproduction and maturation of plasmodium in the
> mosquito, thus preventing transmission of the parasite in to new
> hosts. While this doesn't protect the recipient of the vaccine, it
> protects those around him/her by decreasing transmission, so this type
> of vaccine will be most useful in protecting communities from
> infection.
>
> So, there are many malaria vaccines in development, and many are in
> clinical trials, however we still have a long way to go. Some
> challenges to developing a malaria vaccine include the fact that there
> are four antigenetically distinct malaria species to consider, the
> immunity in malaria is complex and not well understood, identifying
> and assessing vaccine candidates take time, and there is no clear
> "best approach" for designing the vaccine.
>
> Finally, I'd like to end will a list of resources that you can use to
> get more information about malaria.
>
> Every two years, CDC publishes "CDC Health Information for
> International Travel," also known as the "Yellow Book." This book has
> general information on malaria, chemoprophylaxis recommendations, as
> well as country-specific malaria risks. This book also has information
> on travel immunizations, and other travel related health issues. The
> Yellow Book is available online at www.cdc.gov/travel. Additional
> online resources include the CDC malaria and travelers health
> webpages. The CDC malaria webpage is
> [www.cdc.gov/malaria](http://www.cdc.gov/malaria). If you have
> questions not answered by these resources, you can also call the
> malaria hotline. General malaria inquiries not answered by available
> resources can be phoned into the malaria hotline at 770-488-7788
> during business hours. For questions about clinical management of a
> patient with suspected malaria, call the malaria hotline during
> business hours, or after hours, call 770-488-7100 to page the malaria
> clinician on call.
>
> This is the front cover of the Yellow Book that is published by the
> Travelers' Health Section of the Division of Quarantine.
>
> This is just an example of the country-specific malaria risk
> information contained in the yellow book. The list of countries are on
> the left, and the columns on the right show area of risk within the
> country, whether or not chloroquine resistance exists, and the
> recommended prophylaxis.
>
> Before I take questions, I'd like to acknowledge the contribution of
> Dr. Paul Arguin to this talk and in the development of these slides.

Andrew Kroger: Thank you very much Katherine. We'd like to invite our
listeners to call in and ask questions. And to do that, you need to dial
star one. When you call in, be sure to restrict your questions to the
contents discussed today, and please tell us your name and where you are
from. So now I\'m going to temporarily turn the mic over to our
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Coordinator: Thank you very much. Once again, if you would like to ask a
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Andrew Kroger: Okay. While we are waiting for the first question, I do
want to provide some continuing education credit information for CE
credit, please go to www.cdc.gov/T C E O N L I N E. or TCE online.

The course number for our net conference is EV0378, and the verification
code is (CR217F). And I'll repeat that. It's (CR217F). Please remember
that CE credit does expire on November 12, 2007. why don\'t we go ahead
and take our first question.

Q/A1 Yes. Thank you so much. That was a wonderful overview and it really
was so clear. It was beautifully presented and I appreciate it. I have a
question and a comment. The comment is that I use the PDF file that is
on the malaria website and give it to every patient.

It's an eight page PDF file and I just would like say that I think it's
a wonderful resource that your listeners may want to also share with
their travelers, because it kind of reiterates everything we share with
them about (CDCD).

The question I have is you talked about Picaridin. My understanding is
that the issue is the data that showed its value against Anopheles was
at a much higher concentration.

You mentioned that the 5 or 7% concentration here in the United States
just indicated a need for more frequent reapplication. Might you clarify
that, because right now we're really encouraging a DEET product because
the Picaridin formulation in the US is not at the level of at least the
data that I\'ve seen.

Katherine Tan: Thank you very much for that question. Yes it is true
that the data that we have are for higher concentrations of Picaridin to
show its effect on Anopheles. With lower percentages, there is still
anti-mosquito effect, you just have to apply it more often to keep its
effectiveness.

Q/A1 Thanks very much.

Q/A2&3 Thank you. I have two questions. Can you please repeat - I missed
that long-term use for Malarone. How long can you prescribe the
Malarone?

Katherine Tan: The data that we have on Malarone is limited in terms of
long-term use. We do have data for the individual components of
Malarone. Malarone again is Atovaquone and Proguanil. The individual
component, Atovaquone for example has data for use for less than a year.
Proguanil maybe up to three years.

But for both Atovaquone and Proguanil, combined as it is in Malarone, we
only have data for use up to six months. So, as far as how long you can
use Malarone, based on the data from individual components, we have no
reason to suspect that it's unsafe.

So at this point I think it would have to be a discussion between the
patient and provider to make a decision as to whether or not the patient
may prefer an alternative drug, for example, like Mefloquine, where we
do have data for up to two years of long term use.

Q/A2&3 I have like, you know, several travelers that are like out for
like years \-- like two years, and they go to like almost all over the
world.

Katherine Tan: Right.

Q/A2&3 And like either there are areas that are resistant or there are
areas that are not. Could I like give them like Chloroquine in some
areas and then like switch to maybe Malarone?

Katherine Tan: It really depends on their itinerary. So for example if
they go to a place that has Chloroquine resistance, but also travel to a
place with Chloroquine sensitivity, you could conceivably switch between
mefloquine and chloroquine. But they would need to finish the four week
"post-trip" course of mefloquine once leaving the are with chloroquine
resistance prior to starting the chloroquine for the area with
chloroquine sensitivity. So, how to go about switching the drugs really
depends on the timing of that travel and exactly where they\'re going
to.

We often get a question about a patient coming back from a trip not
tolerating their Mefloquine and wanting to change over to Malarone,
because it only has a one week course.

One thing I'd like to emphasize is that these drugs act differently on
the different parts of the lifecycle, as I had shown in the talk. So
ideally, it's better to not change if you can, but if you're changing
let's say from Mefloquine to Malarone post trip and there\'s no other
choice, then they would have to do a four week course of Malarone,
because remember drugs like Chloroquine and Mefloquine do not kill the
liver stage of the malaria parasite.

Q/A2&3: Thank you.

Andrew Kroger: That - was that both of your questions?

Q/A4: Thank you. I was asking about missed doses. If we have a traveler
that returns from overseas and says that they missed a few doses or
they're worried that now they're susceptible but they're not
symptomatic, what kind of advice or reassurance can we give them?

Katherine Tan: Oftentimes we do hear about patients who will skip a dose
or who didn\'t take all of their meds, but I think at that point as long
as they\'re asymptomatic, you would have them finish their post trip
course as directed and just reassure them, give them some education
about what symptoms to look for in malaria and when to come back to you
to seek medical attention.

There have been questions like: "Well, you know, I skipped a dose last
week and I\'m on weekly Chloroquine. When should I take my next dose?"

Let's say their weekday for taking the medication is Monday. If let's
say they realize on a Tuesday or a Wednesday that they forgot their
dose, then they should just immediately take the next dose and then
continue as planned on Mondays.

If for example they skipped a dose and didn\'t realize until five days
later, then they should take it as soon as they realize and then take
their weekly dosing on the day of the week that they started up again.

So I think overall in a patient that skips a dose, it's important that
they just go ahead and continue as best they can and receive education
about malaria symptoms they should look out for in case they do develop
malaria.

Q/A4: Thank you very much.

Andrew Kroger: While we're waiting for another question, we often get
questions to our email account that kind of combine vaccinations with
malaria pre and post travel advice.

And one that we receive frequently has to do with the interaction of the
intra-dermal rabies vaccine with the malaria drug Chloroquine. Is there
any concern here, Dr. Tan?

Katherine Tan: That\'s a great question. One study did show decreased
immunogenecity of the intra-dermal rabies vaccine in Chloroquine use.
But the intra-dermal rabies vaccine is no longer recommended and has
been replaced by the inter-muscular rabies vaccine. So this should not
be an issue currently.

Andrew Kroger: Okay, thank you for that clarification. What about the
issue of pregnancy? This is another question that we receive all the
time. Is it safe to travel to areas high risk for malaria while
pregnant?

Katherine Tan: Well usually we try to advise women who are pregnant or
likely to become pregnant to not travel to areas of malaria risk if it's
possible. Malaria in pregnant women can be more severe than in women who
are not pregnant.

It can also increase the risk of serious pregnancy outcomes such as
prematurity, miscarriage, and stillbirth. But if you cannot defer travel
to a malarious area, it's of utmost important that these women start
chemo prophylaxis regimens.

No drugs are completely effective, but we have shown that Chloroquine is
quite safe during pregnancy. Mefloquine prophylaxis during the second or
third trimester are also considered safe during pregnancy.

Malarone and Doxycycline are not drugs that we suggest in pregnancy, as
we don\'t have enough information on Malarone use in pregnant women, and
Doxycycline may affect the developing fetal skeleton and teeth.

There have also been questions from women who return from travel and are
planning to become pregnant after traveling. They're worried about the
anti-malarial drug in their bodies and if they should wait to become
pregnant until the drugs clear.

But there really is no evidence that Chloroquine and Mefloquine are
associated with congenital defects. We don\'t have a recommendation for
women planning pregnancy to delay or to wait specific period of time
after their use of these drugs before becoming pregnant.

However, if women or the health care providers want to decrease the
amount of anti-malarial drug in the body before conception, we do have
in the Yellow Book a table that shows the half lives of select
anti-malarial drugs.

So you can wait, two half lives, at which point 25% of the drug is still
in the body, four half lives at which point 6% of the drug is in the
body and so on. And that will be the choice between the woman and her
care provider.

Q/A5: Hi. I have a question \-- the 2008 Yellow Book says for India that
risk exists in all areas throughout the country except above 2000
meters.

Katherine Tan: Right.

Q/A5: But the shoreland recommendation states that the risk is
negligible for typical short stay business travelers to major cities.
And I wonder what your recommendation would be for such travelers.

Katherine Tan: Our risk assessment shows that there's still risk in the
low altitude big cities. So our recommendation would be to take malaria
prophylaxis, even for business travelers in these cities.

Q/A5: Okay, great. Thank you.

Katherine Tan: Yes.

Q/A6&7: Yes. I actually have two questions. One is how long do you need
to wait after you return from a malarious area before you can donate
blood at the Red Cross?

Katherine Tan: Yes,

Q/A6&7: And secondly, if you would make comments about the concerns that
have been in the lay literature about the psychological side effects of
Mefloquine, even in people who have not had previous psychological
problems.

Katherine Tan: Great questions. I\'ll take your first one about how long
you have to wait before you donate blood after you return from a trip.
The guidelines state that after a short trip, in general travelers have
to wait for about a year. If you used to live in a malaria risk area and
let's say you immigrated here, you have to wait for three years.

If you've been previously diagnosed with malaria you can\'t donate blood
for three years. And these guidelines are FDA guidelines as well as the
American Association of Blood Banks guidelines. And incidentally we will
actually be releasing early next week a blood donor page on the malaria
website, so look for that for more information.

And your second question about the psychiatric side effects with
Mefloquine, studies have actually shown that these psychiatric side
effects are only very, very slightly increased compared to placebo.

People with a history of psychiatric diagnosis are at higher risk for
that happening, which is why we have it as a contraindication for those
persons.

But with no previous psychiatric problems, the occurrence of psychiatric
side effects from Mefloquine is actually quite rare.

Q/A8: If you have a child who is unable to swallow pills, do you
recommend giving them Mefloquine, which can be crushed?

Katherine Tan: It really depends on where they\'re going because both
malarone and mefloquine can be crushed and mixed with food or formula.
So Malarone and Mefloquine are both two good options, depending on
travel destination.

Q/A8: Okay, thank you. I didn\'t realize Malarone could be crushed.

Katherine Tan: Yes, yes. And Malarone actually comes in pediatric doses
as well.

Q/A8: Thanks.

Q/A9: Does previous history of malaria confer any immunity future
infection?

Katherine Tan: Actually it does not. There are some people who are born
and live in these malaria endemic areas who have repeated malaria
infections may walk around with a parasitemia and not have any symptoms
and feel okay.

But if let's say a traveler or someone who immigrated years ago has a
history of malaria in the past, then they will still have susceptibility
to malaria. Does that answer your question?

Q/A9: Yes. Thank you.

Q/A10: Yes, do people with sickle cell traits have some resistance
against malaria if they travel to foreign countries, for example?

Katherine Tan: There are some studies that show that there is some
protection from sickle cell, but it's not an absolute protection.
Persons with sickle cell are not immune from malaria.

Q/A10: Thank you.

Q/A11: Yes. I have a question about how do you advise or how do you dose
somebody who is going from a country where Chloroquine is the drug of
choice into where is Chloroquine resistance within their same trip?

Katherine Tan: Actually there are a couple of options that you can do.
You could start them off on Mefloquine. And that way they\'re covered
for their whole trip and they don\'t have to switch drugs.

But if let's say you have a patient who would rather not be on
Mefloquine for the whole time, you can have them start out with
Chloroquine and then maybe the week before their trip to the area with
Chloroquine resistance they can start Mefloquine and then finish off
their post-trip course with Mefloquine. So that's another option.

Another option is to also just start them on Malarone which is one of
the drugs suggested for areas with Mefloquine resistance. Another option
is also Doxycycline. So you do have a lot of options in that case.

Q/A11: Okay. So at no time they should ever be on two drugs.

Katherine Tan: At the same time? No.

Q/A11: Okay. Thank you.

Katherine Tan: Yes.

Andrew Kroger: Another question that we frequently get, Katherine, is
the issue of breastfeeding. Is it considered safe to breastfeed while
taking an anti-malarial drug?

Katherine Tan: Yes, there's limited data available about the safety of
anti-malarial drugs and breastfeeding. And the amount of anti-malarial
drug transferred from the nursing mother to the infant is really not
thought to be very harmful, because only very, very small amounts pass
into breastmilk. So for example, only small amounts of Chloroquine and
Mefloquine are excreted in the breast milk of women who are
breastfeeding.

There's also limited information about Doxycycline, but most experts
consider it unlikely to cause any harm. There's no information on
Primaquine, but the mother and the infant should be tested for glucose-6
phosphatase deficiency before Primaquine is given to women who\'s
breastfeeding.

For Malarone it's not known whether the Atovaquone component is excreted
in the human milk and Proguanil is excreted in small quantities.

So our recommendation for Malarone is that women breastfeeding infants
less than 5 kilograms should not be on Malarone.

Andrew Kroger: Okay. Thank you. Any more questions in the queue?

Coordinator: I\'m showing no questions, sir.

Andrew Kroger: Why don\'t we conclude with one last question. It's one
that's been addressed already I guess, but it bears repeating, because
it's one we receive a lot. How long after returning from an area with
malaria can a person develop malaria?

Katherine Tan: You know, that's a great question. I\'m glad you asked
that, because we also do get calls on our clinical hotline from
clinicians that say, "Well, you know, this patient traveled eight months
ago. Could it still be malaria, because that was eight months ago?"

But, travelers can become ill even a year after returning home. There
are situations where you have travelers that may have forgotten a
prophylaxis pill who developed malaria.. Malaria could have been
partially treated while on the rest of their prophylaxis, but then comes
back much later.

And actually in the literature, relapses of malaria have been shown up
to as much as three years after travel.

Andrew Kroger: Okay, thank you very much Dr. Tan. These were very
thorough answers to some very difficult questions. Since we have no
further questions in the queue, I\'m going to move on now to our closing
information \-- housekeeping. For continuing education credits, please
go to [www.cdc.gov/T](http://www.cdc.gov/T) C E O N L I N E or TCE
online.

The course number for our net conference is EV0378, and the verification
code is (CR217F). And I will repeat that \-- (CR217F). And please keep
in mind that CE credit will expire on November 12, 2007.

Once you become familiar with the online system, you will find it easy
to use and a great way to keep track of CE credit earned from CDC
training programs.

If you are having any difficulty or are new to the system, you can get
assistance by phoning 1-800-41-TRAIN or 404-639-1292, and that's during
business hours from 8 am to 4:30 pm Eastern Time. To get help by way of
email you can contact <CE@CDC.gov>.

If you have further questions based on today's net conference or if you
have questions in general, you can contact us at our email question and
answer service at the address N I P I N F O \-- NIP Info \-- at CDC.gov.

If the question is related to the net conference, please write the word
net conference in the subject line. And of course we do definitely look
forward to receiving feedback as well on this training product.

Another way that you can ask us a question is to call the CDC hotline.
And that's at 1-800-CDCINFO \-- C D C I N F O. This is a general hotline
service that handles immunization related questions in addition to other
public health related questions. The hotline is staffed 24 hours a day 7
days a week.

I would really like to thank everyone for joining us today with special
thanks to our subject matter expert, Dr. Katherine Tan. And thank you
very much everybody from Atlanta. Goodbye and have a great day.

Coordinator: That does conclude today's call. Thank you all for joining.
You may disconnect your lines at this time.

END