Speaker 1  00:00
Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. And now

Unknown Speaker  00:29
on to the show.

Dr. Sean Kane  00:31
Welcome to HelixTalk episode 28 I'm your co host, Dr. King. I'm Dr. Schuman and I'm Dr. Patel. Today we're covering a topic that is near and dear to at least Dr. Schumann's heart with a recent travel experience, and that's going to be malaria prophylaxis, yeah.

Speaker 2  00:46
And with the interest of time, I remember we were talking about prophylaxis and not really a treatment. So all the medication and the doses we're going to mention are for prophylaxis purpose, yeah.

Dr. Sean Kane  00:56
And to give you some concept of why malaria prophylaxis is so important, a recent article in The Lancet mentioned that there were 216 million with an M cases of malaria in the past year, and of those, there were 655,000 deaths. And that's worldwide. Most of those are in Sub Saharan Africa. But for people who travel from the US to other countries where malaria is more prevalent, something that we have to worry about. In the past year, based on what the CDC has reported, there was about 1500 cases of people in the US who have malaria or who acquired malaria. It's almost always due to travel outside of the US.

Speaker 2  01:37
Yeah, and I think that is a very important point to be made here that this is a travel related disease. A lot of the time when you travel in the indigenous area where malaria is very prevalent, you come back, and sometimes, because of the incubation period, you don't develop symptoms until you come back to us. And many are hospitalized, or you know, whether it be you or your relative, a lot of the times people miss telling the providers that the you are out of country. So it's really important to let your providers know as well so they can do necessary tasks to rule out this illness. I think it's

Dr. Sean Kane  02:10
kind of interesting to just note that it didn't used to be an illness of people who traveled. In actuality, in the US, we used to have malaria, but in the 1950s we actually declared it eradicated from the US because of the different measures we took, and the goal is eventually to have it eradicated everywhere. You know, there's a lot of research in terms of preventative measures, vaccinations, things like that, because it is such a prolific disease, specifically in Africa.

Speaker 2  02:38
So you wonder, what is malaria? Obviously, it's a parasite based disease. But how do these parasites, you know, come to the host body? Well, they're transmitted by female Anopheles mosquitoes. So it comes from mosquito bite. There are various different species of Plasmodium, which is the actual parasite that causes the symptoms and the condition, but most of the ones that are seen are Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale.

Speaker 3  03:06
And when we look at the areas of the world in which you're more likely to see malaria, it's based upon a certain temperature. We generally look at those warmer regions near the equator. So you know, as you get closer to the equator, moving south, you start to see an increase. And then as you continue further south, it starts to decrease again as you move back away from the equator. And the highest transmission thus is going to be in your area of Africa, South of Sahara, and then also Papua New Guinea and certain parts of Oceania.

Dr. Sean Kane  03:35
And the life cycle of this plasmodium parasite is actually incredibly complex. It goes through a number of different stages, but kind of the quick and dirty of how it becomes to be is that a mosquito has this plasmodium species that it basically injects into the host you, and at that point it isn't infectious until it goes to the liver. Hangs out in the liver for a little while it actually invades hepatocytes and it matures in the liver. From that point, it is released from the liver goes into red blood cells, and that's where most of the magic happens, right?

Speaker 2  04:11
And as the hepatocytes are bursting and all these parasites are releasing into your bloodstream, that's when you start getting most of the symptoms, so high degree fever, shivering and shaking chills, which is kind of like the hallmark symptom of malaria, fatigue, body aches, and then maybe a little bit anemia, related to, as we said, you know, it kind of invades

Dr. Sean Kane  04:34
the red blood cells as well. Dr. Patel, it sounds a lot kind of like a flu, like illness. And so I would imagine, especially in the US, it could be difficult to distinguish if you don't tell your provider. Hey, I was in Africa last week, absolutely.

Speaker 2  04:46
And, you know, growing up in India myself, you know, I've gone through episodes of malaria here and there. And so if you were talking about clinicians in India, they would never think that you have a flu. Their first suspicion will be you got bitten by a mosquito; you know you have malaria, interesting.

Speaker 3  05:02
And one thing to note is explain, explaining that symptoms usually start 10 days to four weeks after infection. And I'll probably touch on this a little more later. But having recently traveled to Honduras last year, Belize and recently for my honeymoon, as well as planning going to Honduras in the future, one of the things that's recommended with some of these medications is continuing treatment even after you get back. And a lot of that is during that period of time where it may lay dormant or you may not see symptoms. You say, Okay, I'll go ahead and stop the medication. You know, there still may be some involvement of the infection, so it's going to be important to still hang on to those medications for that extended

Dr. Sean Kane  05:39
time, as we'll talk about the plot really thickens when there's two different species that can actually lay dormant inside your liver for up to two to four years, meaning that you could have been infected while you're in let's say Sub Saharan Africa. Let's say you did or did not have clinical symptoms of disease. When you come back to the US a year later, these dormant parasites could actually kind of wake up and give you clinical signs and symptoms of malaria, if it's one of those two species, vivax and ovale. So as we'll talk about, you know, travelers who have very prolonged exposure in a certain area, it's actually recommended that they get presumptive anti relapse therapy or terminal prophylaxis, which just means that you give them a drug to kill these potentially dormant parasites that could be hanging out in the liver ready to wake up a year or two down the road. So we talked about

Speaker 2  06:31
some of the common symptoms. Now, what happens if malaria gets to its severe stage?

Speaker 3  06:37
In severe stages, you can start seeing actually neurologic issues. You can see altered mental status, some confusion. Again, we mentioned some of the shaking, but then also seizures or even even coma. And then we talked about the hemolysis from destruction of the erythrocytes. And so we can see some severe anemia there, manifested on our CBC, pulmonary edema, coagulopathy, some shock and some metabolic acidosis, acute kidney injury, hypoglycemia, even

Dr. Sean Kane  07:10
so, really, we see a host of pretty severe adverse effects in response to the malarial infection. What's interesting is that children behave very differently in terms of their typical presenting symptoms than, let's say, an adult would. So there's a lot that goes into the diagnosis in terms of risk factors, plus factors related to the patient age being probably the biggest factor in terms of how a patient will present Absolutely. So, Dr. Patel, you said that you had malaria in the past.

Speaker 2  07:38
Oh, I've had multiple bouts of malaria growing up in India, definitely.

Dr. Sean Kane  07:42
Can you tell us anything about your experience?

Speaker 2  07:45
Sure, I think you know, if I can remember far back, my parents were really good about we have distinct seasons. In India. We have monsoon season. So water kind of collects, not just flooding water, but, you know, any kind of pots and pans that are sitting out in your backyard that will collect the water. And if this water is not cleaned out, then it kind of becomes the breeding ground for these Anopheles mosquitoes, where the female can then, you know, proliferate and go ahead and infect and bite other people and then spread malaria, basically. So my parents were really careful in making sure that, you know, we didn't let the water collect, or if there was water meant to be collected that we treated the water. Also made sure that, you know, there is some sort of incense in the house that's burned to keep the mosquitoes away. There are a lot of insecticide type of creams, treated nets and stuff. So they try to do a lot of preventative measures, but sometimes, you know, those measures don't work, and you still get bitten by a mosquito or two. The illness, if I remember, kind of came very strongly for the first three days, you get this fever, shaking, chills. I remember I needed like, three, four comforters because I was that cold. And then just because you have those comforters on, and then your body kind of cools down, or kind of, you know, warms up a little bit. Then you get, like, sweaty, so then you don't you want, you don't want any of your comforters. You throw them out. And I remember then going to the doctor and stuff, and I used to get series of three injections. I do not recall what medication at that, you know, it was at that point, but I was an avid student when I was little, and I didn't want to miss any school days. So instead of preferring pills, I preferred injection so I can be up on my feet and go back to school. Typical pharmacy student.

Dr. Sean Kane  09:28
Well, speaking about non pharmacologic measures, you mentioned things like insecticides and insect repellents and things like that. What else can someone do who's in any of these areas where mosquitoes are pretty prevalent with malaria. What else can be done besides pharmacologic therapy?

Speaker 3  09:44
I know bed nets can be something important to use, and you may or may not be able to treat them with insecticides, but making sure that you have a net that's got a fine enough mesh, then it's actually able to hold out. We're not talking about a, you know, a very big mesh. You know, if it's big enough to fit a spider through it, it's probably not going to. Be enough. But if you can use those nets, especially during during those hours, you know, if you are going to be outside, if there is access to the outside from where you're staying, you can have that net available. And I think with insect repellents, one thing you know, regardless of one's opinion on DEET, it's generally shown to be appropriate, and they usually recommend at least 20 to 25% in the insect repellent if you're going to use it for mosquitoes.

Speaker 2  10:24
And the city, you know, again, going back to India, not sure, in Africa, if they're following the same practices, but the city was pretty good about making sure that large water reservoirs were treated, so then these mosquitoes don't breed. In general, my parents used to tell, you know, after seven o'clock, after the dusk, you know, that's when the mosquitoes come out, so try to be indoors those after those times. And then I think you alluded to the fact that there are no preventative measures in terms of vaccines available yet. But just because we know that in Sub Saharan Africa, the mortality rate from malarial disease is so high that who has invested a lot of money for the past 20 years looking for a vaccine, and we hope that in the near future we accomplish that.

Dr. Sean Kane  11:09
So unfortunately, no matter how good you are at preventative measures, it's not a 100% that you're going to be protected against malaria. So kind of another line option is to basically take medication to prevent malaria from infecting you, basically killing it before it gets into your hepatocytes. So as I understand it, we have a couple different options in terms of chemical prophylaxis that we can administer to a patient who's going into an endemic area with malaria. Is that right?

Speaker 2  11:38
That is correct. And these medications are actually recommended based on the geographical region, and the reason being is that the resistant pattern is different. The species are prevalent in certain regions are different too. So we want to make sure that we give you the proper prophylaxis. And actually, CDC has a good list, actually a table, alphabetical table of different countries. What are the risk of malaria, what species and what medications they recommend travelers to be using in those regions.

Speaker 3  12:09
And as always, make sure to seek out the most recent or most comprehensive source of information for your country. But in general, Papua, New Guinea and Indonesia are two of the areas which are more likely to have some of the resistance strains, although they've also been documented in South America, Central America as well.

Dr. Sean Kane  12:29
And we'll talk about the fact that you have to start your therapy before you leave. Sometimes it can be a couple days or even a couple weeks in advance of your trip. But with that in mind, the CDC recommends that you purchase those medications in the United States before you leave, because there's plenty of issues in terms of counterfeit drugs, drugs that have things that shouldn't be in there, drugs that are supposed to have your prophylactic agent in it that doesn't have it. So for safety and efficacy reasons, you really should get it from an FDA approved source from the someone in the United States.

Speaker 2  13:03
Yeah, and sometimes it is pain in the rear, because these medications, because they're prophylactic, sometimes they're not covered through your insurance. So be more lean towards getting something from your, you know, grandparent in South America or India or Indonesia or anywhere. But as Dr. Kane said, we would recommend you finding your source through FDA approved medication.

Dr. Sean Kane  13:25
So Dr. Schuman to kind of kick it off in terms of what agents are available to us. Congratulations on your recent honeymoon in marriage. Maybe you can tell us what you took for your trip to Belize, to prophylax yourself, and maybe your wife against malaria.

Speaker 3  13:40
Sure. So what I did, and again, also did the same thing going to Honduras last year is looked at at the nice CDC chart, and saw that both Honduras and Belize have a pretty much non existent amount of the resistance there. So you can both safely take chloroquine or hydroxychloroquine in those areas. So I know for myself, always keeping in mind things such as compliance and cost, I went ahead and stuck with the chloroquine so I could go ahead and take something that was weekly. And so what I started with was 300 milligram tablet once a week. You start one to two weeks before you travel. So we started taking it every Sunday, starting the week before the wedding. And then you can, you want to, again, as I mentioned before, continue to take it after you get back, due to the fact that there can sometimes be that delay in terms of the presentation of the infection and whether or not and when you notice symptoms.

Dr. Sean Kane  14:35
So I assume you didn't elope in the sense that you had at least one to two weeks in advance notice of your wedding.

Speaker 3  14:40
Then, oh no, this is, this is was nice enough that I, you know, was, if you're able to plan it, you know, I was able to go look at the list of what my insurance covered, go to my primary care provider, talk about it with her. And so, yeah, this is not the best one for for that last minute. You know, we're going to Vegas, except in an area with endemic mosquito infections. But. You know, if you do have long travels, and you don't want to take a whole huge number of pills, if you restrict it in the volume, especially that that weekly tablet can be very advantageous. And once again, to be clear, not a lot of areas you can still get by with using Chloroquine or hydroxychloroquine.

Dr. Sean Kane  15:16
So, Dr. Patel, in the past, when you've traveled to India, have you used Chloroquine or hydroxychloroquine.

Speaker 2  15:23
So no, I couldn't use Chloroquine. I had to resort to mefloquine, because Chloroquine is resistant to a lot of species of Plasmodium out in India. Got it.

Speaker 3  15:34
And then the one thing with them is another reason why I chose it is this is one that doesn't have a huge amount of side effects. You could have some itching, some GI upset, headaches and insomnia. And again, personally, didn't have any issues with it. And it can be used throughout pregnancy. And again, that wasn't something where, you know, just in case that somehow became a factor. It is something that can be used throughout

Dr. Sean Kane  15:57
Well, Dr. Patel, you said that in your experience going to India, you weren't able to use Chloroquine or hydroxychloroquine because of resistance patterns there. What was your go to agent when you traveled back to India?

Speaker 2  16:08
That was mefloquine. And it's very similar in schedule. So it is also once a week. You have to start one to two weeks before and then continue four weeks thereafter. The interesting thing is the long list of side effects that comes with mefloquine. So as you mentioned, Dr. Schuman, some of the side effects are gi issue, headache, insomnia, but adding to the list on mefloquine Is depression, anxiety, vivid, abnormal dreams, which actually, I can attest to, I had a dream about zombie apocalypse, and which wasn't fun, but then rare side effects associated are also some psychiatric issues such as psychosis, even seizures. And so we recommend choosing an alternative agent for patients who already have some psychiatric conditions such as depression, anxiety, schizophrenia, seizures and this medication also can be used throughout the pregnancy. So just like Chloroquine, the profile is a little bit similar, differs in terms of the list of side effects.

Dr. Sean Kane  17:11
Then one more thing that I know about mefloquine is, if you have a history of any cardiac abnormalities, specifically conduction problems, this is definitely not the agent for you. So in addition to the neuropsychiatric issues that you may experience, you know anyone with those a background in, as you said, depression, things like that, probably not a great agent, also the cardiovascular issues with it as well. So as I understand it, then we have Chloroquine or hydroxychloroquine that you take once a week that has a very favorable adverse effect profile, but can only be used in certain geographic areas, whereas mefloquine basically has the same dosing schedule, the same issues or the same benefit, where it can be used in pregnancy, but has a lot more adverse effects associated with it, but is able to be used throughout the world, as opposed to more just Central America. Then so is it really just those two that we're picking from? Are there other options that either of you considered at the time that you went for prophylaxis?

Speaker 3  18:08
I know for myself, I was actually giving doxycycline a little bit, a little bit of a thought, you know, and all the an oldie but a goodie in terms of use for some of those, you know, for MRSA, or for any a lot of different kinds of unusual infections. This is when we covers a lot of atypicals. You can actually use it here too new one dose daily, starting here again, one to two days before travel, and continuing up to four weeks afterward. But the one thing, at least for me, was one of the some of the additional counseling coins and side effects with the the issue with photosensitivity, given as somebody who's fairly fair skinned, and I, at times, can be not so good about putting on my sunscreen, and I was concerned about that as well as you know, just in general, getting some some sunburn. And so avoiding sun exposure to me sounded like potential little bit of a deal breaker on a honeymoon excursion. You also want to take it with a full glass of water. Probably don't want to take it at bedtime. Some of the risk of esophagitis. Can see vaginal yeast infections due to knocking out some of the microflora with bacteria, like any other antibiotics you've got the GI issues, some potential for drug out, drug interactions, and that specifically, you know, as we know about things like, like milk, and wanted to be aware of that, but it's any real food or mineral tank product that has divalent and trivalent cations, which I found pretty interesting. So it's your your ions and your magnesium and your calcium, not necessarily your sodium or for example, and it's course not for pregnancy of children less than eight years due to some chelations and some issues with with with bone and calcium, for example.

Speaker 2  19:43
Yeah. So it is a little pain again to take this medication once a day, but it comes in handy for those who have unplanned travel, because they can do, you know what? They can start taking this one to two days before. The issue is, you know, you have to take it every day, so when you're out on your vacation and trying to do leisure activities, sometimes people forget to get in that routine. So scheduling, again, is really important, not just for daily prophylaxis, but the other ones that we mentioned, like Chloroquine and mefloquine,

Dr. Sean Kane  20:12
just to drive home the dosing. Again, typically when I think of doxycycline, I think of a twice a day dose, but in this case, it can actually be taken once a day, which is convenient in terms of avoiding certain foods like dairy products and acids and things like that. So in that sense, it is nice, but it is still daily, as opposed to weekly, with mefloquine or Chloroquine, hydroxychloroquine, okay. Are there any other options available to us?

Speaker 2  20:36
Yeah, so you mentioned doxycycline, which is a daily and it's good for the unplanned travels. We have couple more that are also good for unplanned travels due to the fact that they're taken daily. So one of those ones once a daily dosing is atovaquone-proguanil. The brand name is Malarone, which is a very good brand name to sell the point that this is for malaria. It's also dosed once a day, like I mentioned, and you can start one to two days prior to the travel and only seven days after returning, as opposed to for

Dr. Sean Kane  21:06
four weeks with doxycycline. Correct? Got it okay? So that seems a little bit more convenient anything that we have to worry about in terms of adverse effects with malaria.

Speaker 2  21:15
Yeah, the adverse effects are actually pretty similar to the Chloroquine side effects. So you got some GI issues. You got some abdominal pain, nausea, vomiting, and then perhaps the headache, not so much the insomnia. So what we suggest is to reduce some of these gi discomfort, to take the medication with food, although, unlike the Chloroquine and mefloquine, this is not meant for patients who are pregnant, or children who are less than weighing less than 11 pounds, or patients who have renal issues where their creatinine clearance is less than 30.

Dr. Sean Kane  21:49
So I'm actually seeing a lot of similarities then with doxycycline, in the sense that it's once a day, and it can be started one to two days before travel starts. And also it cannot be used in pregnancy. So with doxycycline, it definitely should not be used because of the chelation problems. And with Malarone, it's not recommended for pregnancy just because of lack of data. And we have better data with the other agents like Chloroquine and mefloquine.

Speaker 3  22:13
Alright, so I believe we have one last agent that can that can be used that we haven't covered, and that's going to be primaquine. And this one is another one that we're going to go back and forth. This is another once a day dose that you can do for one to two days before travel, and you do have to continue it after you return. But in this case, it's actually seven days. So maybe that kind of in between, we have the two to three days on one hand, four weeks on the other, we've got a seven day here. And this is one that can also be used for that presumptive anti relapse therapy or the terminal prophylaxis that Dr. Kane you alluded to before. Take this one for two weeks at the end of a long trip, and you can use that pretty much to wipe out whatever dormant species is hidden in the liver. And it's usually done for those individuals who really spend a whole long time there. You know, if you're spending three days there, it's not really any need to go ahead and start this, this huge dose. But if you spent months and months over over for what, for various reasons, you want to go ahead and wipe it out on the way back, this may be your option. And that's the drug of toys for the the vivax infected ears for that particular species. This is, this is one that you want to go ahead and use.

Speaker 2  23:18
So I believe the some of the minor side effects are very similar to the other agents, gi discomfort, so again, taken with food. But there is actually a very interesting side effect that you can actually remember this medication by that is very important for clinicians to know, and also the patients to know, patients who have deficiency of glucose, six phosphate dehydrogenase enzyme. It can this medication can cause fatal hemolysis, so obviously we don't want that happening on the trip. So what they suggest, or what the manufacturer suggests, is to actually do a test for checking this deficiency prior to giving the prescription.

Dr. Sean Kane  23:56
That's actually also the reason why it should not be used in pregnancy is that you can't test the fetus if it has this g6 PD deficiency or not. So to prevent potential hemolysis for the fetus, it's just not recommended that you use it at all. And if you kind of go back again seeing the forest through the trees here, it makes sense that you would want to do the testing in advance, because this is a preventative, prophylactic therapy. You don't want to cause harm, given that a patient has a very small chance of getting malaria if they're going to be in Belize for a few days, and they do the non chemo prophylactic therapy, it's not worth the risk to have potentially fatal Hemolytic Anemia because they took a preventative medicine. So it makes sense to do the testing in advance. So just to kind of review and kind of classify some of these medications to help the listener remember them when we're thinking about pregnant women, the CDC does recommend that you defer travel, meaning that you don't travel to endemic malaria areas if you can avoid it, if you can't avoid it, though, the preferred agent is Chloroquine. If you're in a susceptible area, which is pretty much just Central America, or if you're anywhere else, they suggest mefloquine. We don't have very good data for Malarone, which is a combination of atovaquone and proguanil, and we cannot use doxycycline because it inhibits bone growth and chelates to calcium in teeth and bone, and because of the risk of G6PD deficiency, we should not use primaquine either for preventative therapy in pregnant women.

Speaker 3  25:27
And then in children, we kind of we have the options of Chloroquine or mefloquine, and that's for all children of all ages or weights. And then, based upon weight restrictions, we can use the other options. So if they're greater than five kilos, which is 11 pounds, we can consider the atovaquone and proguanil combination, and then we can also look at doxycycline, but really it's only going to be if they're greater than eight years of age, although, you know, within the UK, they'd actually say greater than 12 years of age. So use your discretion. But again, if you meet those options, you can, you can use atovaquone-proguanil or doxycycline. But in general, we're looking at Chloroquine or mefloquine for children.

Speaker 2  26:06
And if you kind of take a look at the side effects, you know, if you want to choose the agent based on the side effect, besides the GI issues and some headache type side effects, the main three ones to remember are doxycycline, which gives photosensitivity. This could be huge for vacation travelers sunbathing and whatnot. Mefloquine has additional side effects for neuropsychiatric issue as well as cardiac conduction issues, and then primaquine, as we talked about, the G6PD deficiency patients can be put at risk for hemolytic anemia,

Dr. Sean Kane  26:39
for those last minute travelers who are either eloping or have that last minute travel plan for one to two days prior to the travel, you can get away with atovaquone-proguanil (Malarone), doxycycline or primaquine, but for Chloroquine and mefloquine, you have to start it at least a week, if not two weeks, in advance of your travel, before you enter the endemic area.

Speaker 3  27:00
And lastly, when, if you are concerned about not wanting to take medications long term, when you get back, there are the few that you can stop after seven days once you return home, and that's going to be your atovaquone and proguanil and your primaquine. And then there are a couple others you want to continue for four weeks, the chloroquine, the doxycycline and the mefloquine, yeah.

Speaker 2  27:18
And in general, the tips we would like to suggest you is, you know, be on top of your toes. You know, look, consult the CDC website, because they get the most updated data in terms of the prevalence of the species and prevalence of the resistant patterns too. CDC is a great source, but if you it's a little bit too much information for a common person, you can also visit travel clinics like there is an example of Passport Health usa.com, there is a website you can actually consult the clinic too, because you might be needing some other prophylaxis in addition to malaria prophylaxis as well. And again, timing and schedule of the prophylaxis is really important, so we recommend that you plan ahead and while you are enjoying your vacation that you don't forget about your medication schedule.

Dr. Sean Kane  28:04
So that concludes our episode 28 talking about malaria prophylaxis, if you haven't done so already. We really love the five star reviews in iTunes. The biggest reason is right now we're trying to climb as high as we can on the medicine category in iTunes for the podcast, so five star reviews help us climb that ladder so that other listeners are able to find us easier in iTunes. So we really appreciate that five star review. We're available at HelixTalk.com we're searching for HelixTalk and iTunes. With that, I'm Dr. King, I'm

Unknown Speaker  28:33
Dr. Schuman, and

Speaker 2  28:34
I'm Dr. Patel, and this time, instead of saying study hard, I'm going to say vacation hard. Thank you.

Narrator - Dr. Abel  28:40
Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at HelixTalk.com you.