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Call Transcript: Malaria Cases in the U.S. Reach 40-Year High: Information and Guidance for Clinicians

Moderators:Loretta Jackson Brown

Presenters:Mateusz (Mathew) Plucinski, PhD, MPH

Date/Time:January 28, 2013 2:00 pm ET

Coordinator:
Welcome. Thank you for standing by. At this time all participants will be on the listen-only mode until the question and answer session for today’s conference. At that time, to ask a question from the phone lines, you will press * 1 on your touchtone phone, and state your name clearly when prompted.

I would also like to inform all participants that today’s conference is being recorded. If you have any objection you may disconnect at this time. I would now like to turn today’s conference to Miss Loretta Jackson-Brown. Thank you ma'am you may begin.

Loretta Jackson-Brown:
Thank you Carol. Good afternoon. I’m Loretta Jackson-Brown and I’m representing the Clinician Outreach and Communication Activity COCA with the Emergency Communication System at the Centers for Disease Control and Prevention.

I am delighted to welcome you to today’s COCA Webinar, Malaria Cases in the U.S. Reach 40-Year High: Information and Guidance for Clinicians. We are pleased to have with us today Dr. Mathew Plucinski from the Centers for Disease Control and Prevention. He will describe malaria prevention strategies, discuss the diagnosis of malaria in patients with suspected malaria and he will explain treatment options.

You may participate in today’s presentation by audio only, via Webinar, or you may download the slides if you are unable to access the Webinar. The PowerPoint slide set and the webinar link can be found at the COCA Web site at emergency.cdc.gov/coca. Click on COCA calls. The Webinar link and slide set are located under the call-in number in call pass code.

At the conclusion of today’s session the participant will be able to explain the principal of malaria prevention strategies in travelers, describe how to diagnose malaria in the U.S., and discuss the treatment options for uncomplicated and severe malaria. In compliance with continuing education requirements, CDC, our planners, our presenters and their spouses/partners wish to disclose they have no financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supports.

Planners have reviewed content to ensure there is no bias. This presentation will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Dr. Plucinski’s discussion on malaria. He will be discussing the use of Artesunate for the treatment of severe malaria. CDC does not accept commercial support.

At the end of the presentation you will have the opportunity to ask the presenter questions. On the phone, dialing * 1 will put you into the queue for questions. You may submit questions through the Webinar system at any time during the presentation by selecting the Q&A tab at the top of the Webinar screen and typing in your questions. All questions will be addressed at the conclusion of the presentation.

Today’s presenter Dr. Mathew Plucinski is an Epidemic Intelligence Service Officer for the Malaria Branch in the Center for Global Health at CDC. Dr. Plucinski has been involved in various projects in the field of applied malaria research, including malaria surveillance, household surveys for evaluating bed net distribution campaigns, malaria case investigations and therapeutic efficacy studies.

He is a graduate from the University of California, Berkeley with a PhD in Environmental Science, Policy and Management and a Masters in Public Health in Epidemiology. Again, those PowerPoint slide set and a Webinar link are available from our COCA Web page at emergency.cdc.gov/coca. At this time, please welcome Dr. Plucinski.

Mathew Plucinski:
Good afternoon. Thanks Loretta for that introduction and thanks to those calling in. Before I start let me just give a brief outline of the talk that I will be giving. First, I will start with a very brief introduction to the biology of malaria. Next, I will discuss the epidemiology of malaria both globally and in the U.S. Finally, I will move onto the main topic of discussion: the prevention, diagnosis and treatment of malaria in a U.S. context.

First, some background information on malaria biology. Malaria is a vector-borne disease caused by parasites of the Plasmodium genus pictured here in the early erythrocitic stage. There are five species of plasmodium that could cause human disease. The parasite is transmitted by the bite of the female anopheles mosquito.

There are five species of malaria that infect humans. Plasmodium falciparum is the most common cause of malaria and is the main cause of malaria deaths worldwide. P.vivax is the most widespread malaria parasite globally, and it’s one of the two species that have dormant liver stages called hypnozoites, which can cause relapses months to years after initial infection. P.ovale is the second species that can cause relapses though it is not as prevalent as vivax.

P.malariae is a species that is notable for potentially causing infections with very long duration, up to several years. P. knowlesi is a species found in primates that can be transmitted to humans, although very rarely. Malaria is transmitted when an infected female mosquito bites a human and injects malaria sporozoites when taking her blood meal. In the human liver these sporozoites mature to merozoites, which infect red blood cells.

The parasites multiply until the red blood cell bursts releasing more merozoites and continuing the infection cycle. One to two weeks after first being bitten a person may begin to experience clinical symptoms such as fever, headache and fatigue.

Some of the malaria parasites mature into gametocytes, the sexual form of the parasite. If a mosquito bites an infected human and ingests these gametocytes with her blood meal, these undergo sexual reproduction and mature in the mosquito’s gut. The mosquito can then infect another human being with sporozoites when feeding, continuing the transmission cycle.

Next I will give some background on the epidemiology of malaria. Malaria is a major global public health problem. There are roughly 207 million malaria cases worldwide every year, leading to approximately 627,000 deaths. Most deaths are cause by infection with Plasmodium falciparum. The majority of deaths occur in Sub-Saharan African children. There has been significant progress in reducing the global burden of malaria.The World Health Organization estimates that 3.3 million lives have been saved by malaria control interventions since the year 2000.

Between 1942 and 1945 the precursor agency to the CDC was established to control malaria around military training bases in the southern United States and its territories where malaria was still problematic. Malaria was interrupted in the U.S. during those years and eliminated by 1951.

While malaria transmission no longer occurs in the United States, the mosquito vector, the female Anopheles mosquito, and the ecological conditions still exist for malaria to be reintroduced via importation. This graph shows the number of cases of malaria in the U.S. from 1970 to 2011. The initial high number of cases is mostly explained by cases of malaria in returning military personnel. While there has been a significant reduction in malaria cases and deaths worldwide, there has actually been a steady increase in malaria cases in the U.S. over the past three years that is concerning to CDC.

According to the 2011 Malaria Surveillance Report for the United States, the most recent year with available data, 1,925 cases of malaria were reported in the U.S. These 1,925 cases registered in 2011 is the highest number since 1971 and represents a 14% increase since 2010. In 2011 five people in the U.S. died from malaria or associated complications.

In the vast majority of U.S. cases malaria infection is acquired abroad, primarily in individuals visiting friends and relatives in sub-Saharan Africa or South Asia. For the first time India was the country from which the most cases were reported with 13% of all reported cases. However, 69% of cases were still acquired in Africa. Malaria cases and deaths are preventable in the vast majority of U.S. cases. However, adherence to chemoprophylaxis recommendations is poor. The majority of malaria cases in the U.S. reported not taking chemoprophylaxis while traveling. Adherence was poor among those who did take chemoprophylaxis with travelers either taking the wrong drug or taking the wrong dose.

As I pointed out before, most malaria cases are preventable. In this next section I will discuss preventative measures. Clinicians play an important role in preventing malaria infection in their patients when they travel. During general patient visits, clinicians should proactively ask their patients whether they intend to travel abroad in the near future. If so, determine whether they will be traveling to a malaria endemic area.

In general, preventing malaria infection in travelers involves a few basic steps: taking an antimalarial drug if indicated, using insect repellent, sleeping in accommodations that are either air conditioned or well screened, or under insecticide treated bed nets and wearing protective clothing. The CDC malaria Web site is a good resource for information on prevention, details where malaria transmission occurs and the appropriate antimalarial drug to prescribe.

Around 70% of the U.S. malaria cases occur in travelers that are visiting friends or relatives. Winter and summer school breaks are popular times for travel to the tropics. Many travelers may choose these seasons to return to their countries of origin sometimes taking their children to meet grandparents and other family and friends. Some travelers who are born in countries where malaria is present may be under the impression they have immunity against malaria, and therefore they do not need to take an antimalarial drug.

However, without frequent exposure to malarial parasites, any immunity these persons may have had while living in their native country is quickly lost when they leave that area. They are at as much risk for malaria infection as someone who was born and raised in the United States. Often, travelers do not see their health care provider until close to their time of departure. However, even for those travelers there are antimalarial drug options.

Both atovaquone-proguanil and doxycycline can be used in the prevention of any type of malaria and don’t need to be started until one to two days before travel. Chloroquine should only be prescribed for travel to chloroquine sensitive areas and should be started one week before travel. Mefloquine can be prescribed for all areas except those with mefloquine resistance, mainly in some Southeast Asian countries. Mefloquine should be started at least two weeks before travel.

Primaquine is a good option for short trips to destinations with predominately P.vivax infection, mostly found in Central American countries. It should not be given to the patients with the G6PD deficiency, so G6PD testing is necessary. Primaquine should be started one to two days before travel.

Now, summarizing the recommendations on chemoprophylaxis and this is Slide 20, actually sorry 24: For areas with limited malaria transmission mosquito avoidance is all that is required. For areas with mainly P.vivax transmission primaquine is a good choice. Although any other prophylactic drugs are acceptable. For areas with chloroquine sensitive malaria, chloroquine, atovaquone-proguanil, doxycycline and mefloquine are recommended. For areas with chloroquine resistant malaria, atavaquone-proguanil, doxycycline and mefloquine are recommended.

Finally, for areas with mefloquine resistant malaria the two options are atovaquone-proguanil and doxycycline. Antimalarial drugs can be safely taken at any age and by pregnant women with some drug and dosing exceptions. In general, pregnant women should be advised to avoid non-essential travel to a malaria endemic area until after delivery since malaria and pregnancy can impose health risks for both the pregnant woman and the developing fetus.

Antimalarial drugs are well tolerated by most people who take them, although some people will experience an intolerance to a particular drug. Atovaquone-proguanil is generally the best tolerated. Travelers who experience adverse reactions to their antimalarial drug should see a health care provider to be switched to another appropriate antimalarial drug rather than go unprotected.

Now, a word about the box warning on mefloquine. The FDA added a warning last year indicating that they had received rare reports of neurologic side affects to mefloquine that were permanent. Although this is not new data, the changes to the mefloquine drug label better describe the possibility of persistent neurologic and adverse events after mefloquine is discontinued and the possibility of permanent vestibular damage. However, FDA still approves mefloquine for the prevention and treatment of malaria.

Products with one of the following active ingredients: DEET, Picaridin, oil of lemon eucalyptus or PMD, or IR3535, can help prevent mosquito bites. In general, higher percentages of active ingredient provide longer protection. Another way to avoid mosquito bites is to wear protective clothing and sleep under insecticide treated bed nets. Travelers should cover exposed skin by wearing long-sleeved shirts, long pants and hats. Sleep in a screened or air conditioned room if available or sleep under a bet net if sleeping quarters are exposed to the outdoors.

Again, summarizing the key take home messages regarding prevention: first, clinicians should proactively ask patients about upcoming travel during patient visits. By understanding where malaria transmission occurs, clinicians can counsel patients on key behaviors while traveling, such as using insect repellents and protective clothing, sleeping in proper accommodations or under insecticide treated bed nets. Finally, when recommended, clinicians should also prescribe appropriate chemoprophylaxis.

In the next section I will discuss options for the diagnosis of malaria in the U.S.

Before I delve into the details of the diagnosis, let me start by passing across two very important messages and this is Slide 31. First, all patients seeking care for a febrile illness should have a travel history obtained from them, second, fever in a returned traveler should always prompt an immediate evaluation for malaria. Common symptoms of malaria include fever, chills, sweats, headaches, nausea and vomiting and body aches.

As you can see these symptoms are all very non-specific. Therefore, diagnosis of malaria on the basis of symptoms is not recommended. Laboratory diagnosis is necessary. For the diagnosis of acute infection there are two options available in the U.S.: microscopy through thick and thin smears and rapid diagnostic tests or RDTs.

To confirm a diagnosis that’s made through thick and thins smears or RDTs, polymerase chain reaction or PCR tests are available. However, they are not appropriate for diagnosis of acute infection due to the delay in receiving the results. To determine past infection with malaria, serology is available for the detection of antibodies.

Thick and thin smears where blood is smeared on a slide, dried, stained and examined under a microscope for the presence of parasites is the first choice diagnostic test for suspected malaria. If correctly read, a thick and thin smear should yield three pieces of information: the presence or absence of malaria parasites, the species of parasites, and the percent parasitemia, which is defined as a number of infected cells per 100 red blood cells. These three pieces of information are necessary when treating for malaria.

It is important to note, however, that a single negative slide does not necessarily rule out malaria. In general, three negative slides spaced 12 to 24 hours apart are necessary to truly rule out malaria. Finally, one last note about blood slides: in general the entire process of preparing a blood slide and reading it should take a maximum of one hour. It is generally not acceptable to wait more than a few hours to receive the results of a blood smear.

Rapid diagnostic tests or RDTs have recently become an alternative microscopy. They work by detecting malaria antigens in patient’s blood and return results very quickly within 15 to 20 minutes. While they can rapidly establish a diagnosis, they do not confirm the species of Plasmodium and there is no quantification of parasitemia, an important piece of information to properly treat a case of malaria. For these reasons the FDA requires confirmation of RDT results by microscopy.

There are also various PCR tests, which detect the presence of parasite DNA in patient’s blood. Often, they can be more sensitive than microscopy. However, results are not available soon enough to establish diagnosis and should not be used for the diagnosis of acute infections. They are generally more useful for species confirmation when the species cannot be easily determined by morphology.

There also exists serologic tests for malaria, which detect the presence of antibodies to species-specific antigens. Most commonly these tests are used to confirm past infection with either P.vivax or P.ovale. Remember, these are the two species that can cause relapses and confirming a past infection might lead a clinician to prescribe a treatment course to kill off the remaining dormant liver stages. This treatment course is called a radical cure. I’ll be discussing it later.

The CDC reference laboratories offer many diagnosis services, including telediagnosis, where clinicians or technicians can take a digital picture of a blood slide and have it read within minutes by CDC laboratorians to confirm malaria or possibly a species of malaria. Health care providers can also send slides to the CDC for review and species confirmation.

The CDC also offers PCR tests for diagnosis of malaria. Blood can be evaluated for drug levels and for the presence of molecular markers of drug resistance. Finally, the CDC offers serologic testing. Details on all of these services can be found on the DPDx Web site at cdc.gov/dpdx.

As part of new molecular surveillance to characterize drug resistant patterns in isolates from confirmed malaria cases in the U.S., clinicians should send samples to CDC to confirm speciation and to test for drug resistant markers. PCR drug resistant testing or culture, please draw pretreatment whole blood in EDTA or ACD blood tubes. Instructions on how to prepare samples and send them to CDC laboratories can be found on the CDC Web site at cdc.gov/malaria/report.html.

Again, I would like to take a moment to summarize the key take home messages regarding diagnosis, and this is Slide 40. First, clinicians should obtain a travel history from all febrile patients. Next, clinicians should evaluate all returned travelers from malaria endemic areas for malaria. This includes performing a laboratory diagnostic test. Notably, diagnosis should be done within a few hours at most. Finally, clinicians should send specimens from all confirmed cases to CDC laboratories.

Finally, in this last section I will discuss treatment once a confirmed diagnosis has been made. When choosing a treatment option for malaria there are generally three important pieces of information that will guide a decision on how to treat. First, is the staging of the case, whether it is uncomplicated or severe malaria, second, the location of likely exposure or where the infection was likely acquired and finally, the species of malaria.

The first piece of information is to determine whether the patient represents a case of uncomplicated or severe malaria. Uncomplicated malaria is defined as the absence of signs of severe malaria. Signs of severe malaria include neurological involvement as in cerebral malaria, severe anemia, high parasitemia or more than 5% of red blood cells contain parasites, any end organ involvement, pulmonary edema, acute respiratory distress syndrome and a few others. Generally, the rule is that oral antimalarials are used to treat uncomplicated malaria, whereas intravenous antimalarials are used to treat severe malaria.

The next piece of information to gather is to determine where the malaria infection was likely acquired. This is typically obtained from a travel history. The reason for needing this information is the fact that there are different drug resistant patterns in different countries, which dictate different recommended treatments.

The final required piece of information is the species of malaria. This is usually determined by microscopy. It is important to know the species because there are different recommended treatments for the different species. Generally if the species is not able to be determined the standard is to assume it is P.falciparum and choose a drug that is active against all species for the acute infection. In this case, though, it is necessary to follow up to ensure the determination of species to know whether to follow up with a radical cure to remove dormant liver stages, if the species turns out to be vivax or ovale. After obtaining the treatment information, the staging, the location of likely exposure and the species, the next step is to consult the CDC malaria treatment guidelines available online at cdc.gov/malaria/diagnosis_treatment/treatment.html. Alternately, one can also search for CDC malaria treatment guidelines in any Internet search engine to find the documents.

In this slide, Slide 47, I show the treatment guidelines table. The recommendations here are broken down by species, location and stage, so uncomplicated versus severe. Next, as an example I will discuss the treatment of the two most common presentations of malaria in returning travelers. First is the treatment of uncomplicated P.falciparum malaria.

If the infection was obtained in a chloroquine resistant area, which includes the majority of malaria endemic countries treatment options are: atovaquone-proguanil which goes by the brand name of Malarone, artemether-lumefantrine, brand name Coartem, quinine with doxycycline, tetracycline or clindamycin or mefloquine, brand name Lariam. As discussed before both atovaquone-proguanil and mefloquine are commonly used for prophylaxis, so are found in many commercial pharmacies nationwide.

Artemether-lumenfantrine is one of the classes of new drugs called artemisinin-based combination therapies or ACTs, which are now the global standard of treatment for malaria, however artemether lumenfantrine can be difficult for some in the U.S. However, Novartis the manufacturer of Coartem has entered into an agreement to stock Coartem in select pharmacies across the U.S. For infections acquired in chloroquine sensitive areas, which include parts of Central America, parts of the Caribbean and the Middle East, treatment options include any of the four drugs I just mentioned, or chloroquine or hydroxychloroquine.

Next, I’ll discuss the treatment of the second most common type of infection in the U.S. or uncomplicated P.vivax. If the infection is determined to have been obtained in a chloroquine resistant area, which includes Papau New Guinea and Indonesia treatment options are atovaquone-proguanil, quinine coupled with doxycycline, tetracycline or clindamycin or mefloquine. If the infection was acquired in a chloroquine sensitive area one should treat with chloroquine or hydroxychloroquine.

Note importantly that the areas of chloroquine resistance for falciparum and vivax parasites are different. For vivax cases treatment should also include a two-week course of primaquine to prevent relapse, referred to as a radical cure. Primaquine is the only drug active against dormant liver stages, but should not be given to patients with G6PD deficiency.

Treatment for severe malaria is very different from treatment for uncomplicated malaria. Severe malaria is traditionally caused by P.falciparum, but can occur in other species including vivax. In fact in 2011, 12% of hospitalized patients with P.vivax had severe malaria. The only FDA-approved treatment for severe malaria is IV quinidine coupled with IV doxycycline, tetracycline or clindamycin. Quinidine, however, has cardiac toxicities and continuous cardiac monitoring is necessary. Quinidine is administered through an initial loading dose and then a continuous infusion.

As I mentioned in the previous slide, quinidine is the only FDA-approved drug for the treatment of severe malaria. However, there is an alternative drug called artesunate, which is available through the CDC under an investigational new drug protocol. The drug can be released under specific criteria when the patient has severe or suspected severe malaria and one of the following four conditions is met: quinidine is not available, the patient fails quinidine treatment, defined as a less than 90% reduction in parasitemia after 48 hours, the patient has contraindications to quinidine or the patient develops some of the quinidine toxicities.

This last condition, quinidine intolerance has a specific definition, defined as either the QRS interval is widened by more than 50%, the QT interval exceeds 0.6 seconds, the QT interval is prolonged by more than 25% of the baseline value, the patient exhibits persistent hypotension unresponsive to fluid resuscitation, or the development of reaction to quinidine during therapy.

There are standard procedures for how clinicians can request artesunate from the CDC. First, the clinician treating the patient calls the CDC malaria hotline. Then the CDC malaria branch staff goes through the eligibility inclusion criteria. If the patient meets the inclusion criteria, artesunate and associate consent forms are sent to the clinician from one of nine quarantine stations located in nine airports throughout the country. The artesunate is then administered at the health facility. The entire process from calling the CDC to administration of the drug takes on average seven hours.

Again, to recap the key messages regarding treatment on Slide 54: three pieces of information are necessary to make appropriate treatment decisions. First, whether the malaria is uncomplicated or severe, next, where the infection was acquired, and third, the species of malaria. With this information the CDC malaria treatment guidelines should be consulted to make the appropriate decision.

Let me end by listing some of the resources currently available at CDC. First, there is the CDC yellow book, which has country-specific data on malaria risk, drug resistance and chemoprophylaxis guidelines. Health care professionals can call the CDC malaria hotline to inquire about any aspect of prevention, diagnosis or treatment in addition to artesunate requests. Those numbers are 770-488-7788 or after hours 770-488-7100.

The CDC malaria Web site also has extensive information including treatment guidelines, prevention and diagnosis recommendations. Finally, for more information on diagnosis services offered at CDC, one can visit the DPDx Web site. Thank you for your attention and I look forward to answering your questions.

Loretta Jackson-Brown:
Thank you Dr. Plucinski for providing our COCA audience with such a wealth of information. We will now open up the lines for the question and answer session. Using the Webinar system, again click on the Q&A tab at the top left on the Webinar, type in the white space and put your question there and click ask. On the phone, you will be assisted by the operator dialing * 1 to enter into the queue. Operator we’re ready for Q&A.

Coordinator:
As a reminder that is * 1 on your touchtone phone and please state your name clearly when prompted. We’ll give it one moment please.

Loretta Jackson-Brown:
Okay. While we’re waiting for the first question from the phone, Dr. Plucinski, talk to us about P.vivax malaria and can it cause severe disease?

Mathew Plucinski:
Thanks Loretta for that question. There is a common misconception that vivax basically results in mild disease. While it is true that falciparum does tend to cause more severe disease than the other species, vivax can cause severe malaria, as can all the other species. In fact, as I presented during this presentation, in 2011 12% of patients that were hospitalized with vivax actually had a severe case, so were treated with IV antimalarials.

Loretta Jackson-Brown:
Thank you so much. Operator do we have a question from the phone?

Coordinator:
I’m showing no questions from the phone lines at this time. As a reminder that is * 1 and you may do so at any time. Thank you.

Loretta Jackson-Brown:
Okay. So for providers who may be caring for individuals who are going to be traveling for a long period of time are anti-malaria drugs safe to use during long periods of travel?

Mathew Plucinski:
Well, that’s a common question that arises. The answer is yes. The antimalarials that I described for chemoprophylaxis can all be used for the long term, and there are people who spend years on any of these drugs without any adverse events.

Loretta Jackson-Brown:
Okay. Excellent. We do have a question through or Webinar system. The participant is interested in learning about CDC has addressing delayed diagnosis and whether or not infectious disease docs from other countries use CDC malaria expertise?

Mathew Plucinski:
Okay. Thanks for that two-part question. Let me first address the first question. So, as I discussed in the slides, you know, suspect malaria is a medical emergency and it is very important to get a proper malaria diagnosis within an hour or within a few hours to quickly treat the patient. Like I said, and several of the laboratory-confirmed diagnosis is necessary to actually make the correct decision. So having a prompt laboratory confirmation is very important.

Like I said, a blood slide should or can be read within one hour. So in theory any hospital laboratory is capable of providing that service. It’s as easy as spreading blood on a slide, staining it and then looking under the microscope to see whether there are parasites in the red blood cells; all of those steps can be done by a laboratory technician.

We also offer the telediagnosis services where if the laboratory technician can take a picture of that slide, basically they can send an email to the folks at DPDx and the CDC laboratorians will look at it. If there are parasites in the blood they can actually identify them as possibly malaria and potentially the species. So that’s one way in which the CDC is working at increasing the speed of diagnosis.

Another option is RDTs, which as I mentioned have results back within 15 to 20 minutes. The availability of RDTs is increasing in the United States. Then globally RDTs are becoming a more and more useful alternative to microscopy. So I expect to see the role of RDTs also increasing in the U.S. The second question if I remember correctly was whether there are international calls or whether the CDC...

Loretta Jackson-Brown:
Okay let me stop there. You were asked if ID, infectious disease docs in the U.S. are using CDC malaria resources and expertise?

Mathew Plucinski:
Oh, that was the question? Okay. The answer is yes. The malaria hotline, which is staffed by myself and several other CDC malaria branch staff does get calls from ID physicians in the U.S. on a regular basis.

Loretta Jackson-Brown:
Okay. Thank you. Operator do we have anyone on the phone?

Coordinator:
Actually, we do have quite a few questions, one moment. (Dave Warshauer) your line is open.

(Dave Warshauer):
Hi. How often do you see mixed infections?

Mathew Plucinski:
So, the question is how often do you see mixed infections in the U.S. with regarding species? I would have to look at the surveillance data from 2011, but the majority of infections are mono infections, most commonly with falciparum. I’m actually looking at the data now and in 2011 it was 1%. So 21 cases out of those 1900 were mixed infections.

Although there are some caveats with diagnosis in the U.S. Mixed infections are often not picked up using microscopy, so that is likely, or that could potentially be, an underestimate of the true number of mixed infections.

(Dave Warshauer):
Yeah because in our laboratory we use PCR for confirmation. We do pick up mixed infections that we don’t detect on microscopy.

Mathew Plucinski:
Yes, that’s true. Like I said PCR is good for species confirmation. It’s particularly good for picking up those mixed infections because it is common to find one infection that is responsible for the majority of the parasitemia with a much lower level of parasitemia for another species.

(Dave):
Okay. With the RDTs, how do you feel about their performance in a low-prevalence population like the U.S.?

Mathew Plucinski:
So, in general RDTs are about as specific and sensitive as microscopy. While it is true that if they’re used indiscriminately in a population that has low risk for malaria, you could potentially see a large number of false positives. If they’re used in patients that are returning from malaria endemic areas, so are already at some risk of malaria, I would expect the predictive value positive to be quite high and to there not be that many false positives.

(Dave):
Okay. Thank you.

Coordinator:
Next question? (Gale Wesalow). Your line is open.

(Gail Wesalow):
Yes. Thank you very much for this presentation. Could you expand on the mefloquine issue? We have historically used that particular drug for a long stay because of the weekly dosing and improved compliance for some individuals, but that new FDA warning really has put a chill.

Mathew Plucinski:
Yeah. The warning has I guess changed patients’ perspectives on mefloquine. Nevertheless, it continues to be recommended by FDA. Most people do fine with mefloquine and both CDC and WHO still recommend mefloquine for prophylaxis.

(Gail Wesalow):
As a follow up question, are you tracking adverse affects now more for that?

Mathew Plucinski:
Tracking adverse events is the responsibility of FDA.

(Gail Wesalow):
Thank you.

Coordinator:
Question? Dr. (Norman Castile). Your line is open.

(Norman Castile):
Yes. Thank you. I have two questions. One, I just tried looking up the dosage for doxycycline as a preventative and I looked it up on the CDC sites, and I don’t see a recommended dosage. The other question was, can you use serology to determine if someone had malaria decades earlier?

Mathew Plucinski:
Let me tackle that first question. So, the dose for doxycycline is 100 mg per day. That’s daily.

(Norman Castile):
Okay.

Mathew Plucinski:
I believe it is actually on; it should be on the malaria Web site. The second question is regarding the diagnosis or I guess the confirmation of past malaria infection (unintelligible). It works best during infection. It may not last decades. There is little data to show how sensitive it is in picking up infections from decades ago. In general, immunity from malaria works… It’s not that long lasting. It’s not necessarily as sensitive as immediately after infection.

(Norman Castile):
Okay. Thank you.

Loretta Jackson-Brown:
Okay we’re going to take one of the questions from the Webinar. This individual wants to know, they want you to repeat when they should give artesunate alone? Did I say that right?

Mathew Plucinski:
Is it artesunate?

Loretta Jackson-Brown:
Artesunate? Okay. It could be. I’m going to take your word on that one. Yes.

Mathew Plucinski:
Let me go to that slide on this, on the presentation very quickly. Basically, there are four conditions when artesunate can actually be given to cases of severe malaria. Although, let me first correct that the person asking the question, the artesunate should never be given alone. Artesunate should be coupled, given and then followed up with either atovaquone-proguanil, doxycycline, clindamycin or mefloquine.

The other part of the question was when it can be given? Let me first turn to that slide. So, the four conditions are quinidine not being available, so not being available in the hospital and so these are situations where the artesunate basically can get to the patient more quickly than quinidine. Please keep in mind that usually it’s about seven hours to get artesunate to the patient.

There is quinidine treatment failure, which is basically when the patient doesn’t respond to the initial quinidine treatment course. Then when there is any contraindications or allergies to quinidine. Then finally, there is the situation, which the patient develops some of the cardiac toxicities associated with quinidine.

Sorry, let me just clarify that. So, its artesunate is given. Then it’s followed up with another round of doxycycline and clindamycin or mefloquine sequentially, not at the same time.

Loretta Jackson-Brown:
So with that our anti-malarial purchase in Central and South America and Africa as reliable, and if someone stops their chemoprophylaxis, should they start it when they return to the U.S.?

Mathew Plucinski:
Sorry, I’m not sure I understood the question. The question is … are anti-malarials purchased abroad?

Loretta Jackson-Brown:
Yeah. Are they as reliable?

Mathew Plucinski:
I really can’t comment on the drug quality of drugs purchased abroad. I think that is a question for the FDA, but -- I’m sorry, what was the second part of the question?

Loretta Jackson-Brown:
If the provider does start an individual on anti-malarial chemoprophylaxis and the individual stops for whatever reason, should they recommend that the individual resumes the treatment once they return to the U.S.?

Mathew Plucinski:
Yes. Sometimes. That’s generally on a case-by-case basis. The best resource for that is to call the hotline because those patients should be counseled on like a case-by-case basis. Let me first clarify my initial answer to that question, which is that although I can’t comment on the quality of drugs purchased abroad, counterfeit drugs and particularly counterfeit antimalarials is a serious problem worldwide. That should be kept in mind when purchasing anti-malarials abroad.

Loretta Jackson-Brown:
Okay. Thank you. Operator do we have anymore questions on the phone?

Coordinator:
Yes. We still have a question from before. One moment. (Suzanne) your line is open.

(Suzanne):
Yes. Can you hear me?

Coordinator:
Yes. We can.

(Suzanne):
Okay. Good afternoon. Thank you for the presentation. I’m (Suzanne) (Unintelligible) from Health Canada in Ottawa. I’m a travel health nurse. I have three questions to you regarding prophylaxis. The first one regarding Chloroquine. If I was to give a loading dose of Chloroquine, up to how many days before they arrive in the area would I be able to do that?

Mathew Plucinski:
Sorry, maybe can you ask all three questions first? Then I’ll address them all.

(Suzanne):
Yes. Mefloquine, do you -- again prophylaxis do we give it one or two weeks prior to entering the area? The third question is regarding the thick and thin smear. We just want to know the interval time between the three slides?

Mathew Plucinski:
Okay. So to tackle the first question, in general we don’t really do loading doses for Chloroquine for prophylaxis. Generally, the recommendations are just to start Chloroquine one week before travel. For mefloquine, it’s actually at least two weeks. So start mefloquine at least two weeks before the patient begins travel. To address the final question, which is the spacing between the three thick and thin smears. As I said during the talk to truly rule out malaria you need three negative blood slides. Typically, those should be spaced between 12 to 24 hours apart.

(Suzanne):
Okay. Okay. Thank you.

Coordinator:
I’m showing no other questions from the phone lines at this time.

Loretta Jackson-Brown:
Okay. We have another question from the Webinar system. This has to do with how is CDC soliciting samples for molecular surveillance? They are saying that they -- they heard that CDC would like to receive these samples for every confirmed case?

Mathew Plucinski:
Yes. So, that last part is true. The CDC does request that all confirmed cases of malaria in the U.S. have whole blood specimens sent to the CDC so that we can test all cases for molecular markers of resistance to anti-malarials. So the specimen submissions forms are, like I said, available on the CDC malaria Web site.

Loretta Jackson-Brown:
Okay. Great.

Coordinator:
You have another question from the phone line.

Loretta Jackson-Brown:
Okay. Go ahead.

Coordinator:
(Unintelligible) your line is open.

Woman:
Okay. How quickly does a person lose their ability to fight malaria? For example, a student coming from Africa, if they go back -- come in August and go back in December, do they need it at that point, or is it only after they’ve been here for perhaps say nine months or a year?

Mathew Plucinski:
Okay before tackling that question let me also clarify my previous response, which is regarding the submission of specimens. The specimens can also be routed through the state health departments as they make their way to CDC. You can also send the whole blood to state laboratories and they will send them to CDC for the molecular resistance testing.

As I said before to tackle this first question, the actual current question, so in general, immunity from malaria is poorly understood. It’s hard to say really how the level of protecting immunity. So it does seem to wane quickly, but it’s really -- I can’t really make any statement as to say, you know, that there is a specific threshold that which the student is considered to be non-immune.

Woman:
Okay. Thank you.

Loretta Jackson-Brown:
Now, another question from the Webinar is what are the U.S. health care settings which CDC encourages use of RDTs and does that include in emergency department settings?

Mathew Plucinski:
So RDTs, as I mentioned in the presentation, are an alternative to microscopy. If for example, microscopy is not available then definitely RDTs should be done, but they should be done in laboratories. It’s not a point-of-care test. It’s important that they be followed up with microscopy. Again, because an RDT is not going to tell you, it can’t really determine between the other species of malaria. Also, you can’t quantify the level of parasitemia.

Like I mentioned in the presentation both the species and the parasitemia are important when making a treatment decision. When prescribing treatment solely on the basis of an RDT you might be making a suboptimal treatment decision. Let me also say that although they are sensitive and specific, they are not as sensitive specific as microscopy. So microscopy does remain the gold standard in labs throughout the country.

Loretta Jackson-Brown:
Wonderful. Thank you for that response. Operator do we have any last questions on the phone?

Coordinator:
Yes. We just got one. One moment I’ll get their name. Ma'am your line is open. Please state your name.

(Ellen Lee):
It’s (Ellen Lee) in New York City.

Coordinator:
Thank you. Your line is open.

Loretta Jackson-Brown:
Go ahead (Ellen).

(Ellen Lee):
Hi. We’re just curious about the slide that had information about the most frequent countries for the source of malaria for people returning to the U.S. I think there was something about India being the most frequent country reported, but then there was something about Africa. We’re just wondering if you could just review that again?

Mathew Plucinski:
Sure. Let me find the slide quickly. When looking at countries India does have, as a single country, have the most number of imported cases. However, most cases, around 70% are still acquired in Africa, principally, in West Africa; although that’s spread across multiple countries. Most of the ones from West Africa come out of Nigeria.

(Ellen Lee):
Thank you.

Loretta Jackson-Brown:
All right. We have time for one more question. Operator do we have another question on the phone?

Coordinator:
I’m showing no other questions at this time.

Loretta Jackson-Brown:
Okay. Thank you operator. On behalf of COCA I would like to thank everyone for joining us today. With a special thank you to Dr. Plucinski. We invite you to communicate to our presenter after the Webinar. If you have additional questions for today’s presenter, please email us at coca@cdc.gov. Put January 28 COCA call in this subject line of your email and we will ensure that your question is forwarded to Dr. Plucinski for a response. Again, the email address is coca@cdc.gov.

The recording of this call and the transcript will be posted to the COCA Web site at emergency.cdc.gov/coca within the next few days. Free continuing education is available for this call. Those who participated in today’s COCA conference call and would like to receive continuing education should complete the online evaluation by March 1, 2014 using course code WC2286(SC).

For those who will complete the online evaluation between March 2, 2014 and January 27, 2015, that’s an entire year folks, use course code WD2286(SC). All continuing education credits and contact hours for COCA conference calls are issued online through TCEOnline, CDCs training and continuing education online system at www.cdc.gov/tceonline. To receive information on upcoming COCA calls, please subscribe to COCA by sending us an email at coca@cdc.gov and write subscribe in the subject line.

Also, CDC COCA is on social media. We launched a Facebook page for our health partners. Like our page today Facebook.com/CDCHealthPartnersOutreach at  to receive COCA updates. Thank you again for being a part of today’s COCA Webinar. Have a great day.

Coordinator:
This does concludes the conference for today. All participants may disconnect at this time. Thank you.

END

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