Day 2: And so it begins, malaria

Tropical diseases Malaria

Today, Monday Nov. 20th, 2017 was the first day of the Tropical disease course at the Christian Medical College. I was able to meet most of the 20 participants in the course which ranged from local Indian ID fellows, to microbiologists, ED physicians, a surgeon and even an endocrinology fellow who has an interest in tropical disease. I imagine some 10 plus countries are represented. I was also elated to find that Dr. Libman from McGill University and Dr. Rupali from CMC are here throughout the course and teaching numerous topics. Their tropical disease cases from ID week have been the highlight of the conference for me, both extremely knowledgeable.

Breakfast at the hotel is complimentary and probably contains 15 plus dishes, 90% which was awesome, including mango freakin pancakes which also tells me things will go very smoothly because I'll be well fed in the morning (shout out to Elaine Dwek).

The days have an ideal structure for learning; didactics in the morning followed with some clinical vignettes, lab work with multiple instructors to help facilitate, and then bedside teaching in the afternoon, where we are are hearing stories of patients that are admitted and actually performing physical exams.

The start of the day we discussed tropical medicine as a whole, that the tropics refers to the area between ,the Tropic of cancer and the Tropic of Capricorn and that it does not just refer to infectious causes but also malnutrition to snake bites, all of things which the course will touch on.

We started the discussion with malaria, with a reminder that parasites are divided into worms and protazoas, there are three blood protazoas; malaria, babesiosis, and trypanosomiasis. We initially heard a case of a heathy student he returned from congo that presented with confusion and dysphagia, a stroke was suspected and was admitted under neurology. Fortunately, someone was able to think of malaria, a blood smear showed schizonts, and a parasitemia of 15% - patient got IV artusunate and exchange transfusion and improved.

They discussed in detail the pathophysiology of malaria, with a specific focus on P. falciparum, how it is able to up-regulate proteins to stick to endothelial cells, to stick to each other (forming rosettes), and thus getting stuck in micro-circulation and causing end organ damage. Patient can develop immunity to malaria, and likely get less severe disease. Thus, it is the patients who have never had malaria, such as travelers visiting endemic areas, who are at risk of severe malaria. They also discussed how it does change surface proteins ~2% per cycle, thus issues with making a vaccine. Also strains of species can be different, he discussed how certain vivax species can have different relapse relates, likely related to a smart parasite ensuring it comes out from the dormant phase during wet season! So taking a year to relapse in Europe/Korea, but every 3 weeks in a tropical environment.  

Interestingly, local India students informed me that lots of patients with suspected malaria will get an exam, cbc, creatinine, liver enzymes and rapid diagnostic test, and that alone will help them decide if the patient has severe (end organ dysfunction) malaria and require admission and IV therapy, vs outpatient oral therapy.

Lots of people use rapid diagnostic tests for malaria (RDT) (finger prick to be done at the beside and can be easily read), the World Health Organization had put out a document comparing lots of them. They generally check for HRP2 (specific to P. falciparum), aldolase, and LDH – (can distinguish falciparum from non-falciparum). Generally, a pretty good test, because HRP2 stays positive for 2 weeks, not helpful to look for relapse. False negatives from very high parasitemia, prozone effect, and possible genetic variants which lack HRP2.

Finally, PCR is becoming more common, a scenario where a patient with suspected vivax no improving with chloroquine, have been found to have mixed infections (falciparum and vivax) by PCR.

Multiple pearls were dropped with regards to malaria, to name a few

1.     Anyone returning to an endemic area with fever and diarrhea, SOB, mental status, and almost any symptoms, must consider malaria.

2.     Rash, lymphadenopathy and arthritis make it less likely but co-infection can be present.

3.     Schizonts (the cell that contains multiple merozoites) often aren’t seen in periphery – usually suggests more severe disease

4.     A normal smear does not rule out malaria, incubation period (infection to symptoms) is later than prepatent period (infection to lab findings), thus it can be missed.

5.     Patient coming from endemic place, felt chills yesterday but feels fine today can be concerning, NOW would be the time to check peripheral smear for malaria!

6.     Knowlesi and falciparum infect at all stages, vivax and ovale affect reticulocytes

7.     Think about bacterial coinfection, one doctor notes at their hospital, with un-differentiated fever, the cocktail of ceftriaxone, doxycycline + artusunate if malaria rapid test comes back positive.

8.     Other drugs with anti-malarial activity, doxy, clindamycin, quinolones, sulfas, azithromycin – may partially treat malaria and so may cause atypical presentations.

We then went to the micro lab and looked at a bunch of different malaria smears. I felt this was pretty challenging but felt quite confident to identify falciparum, and decent at picking up vivax. In India, often they will send PCR to confirm what species this is.

Clinical Vignettes were presented in the afternoon, perhaps the most interesting case was a male from the Congo, who presented with several months of confusion, depression and was in the psych ward for nearly a year. Ended up being diagnosed with African sleeping sickness,  T. Brucei gambiense. I found it really interesting that patient was able to have this for so long. A very interesting phenomenon Dr. Libman brought up is generally parasites which mainly infect humans, which are older and better adapted, often can co-exist for some time, as it would not be ideal to kill its host for its own survival, this is the case with T. Brucie Gambiense (in West Africa), vs rhodesiense which game animals are the reservoir. The best to diagnosis this is CATT (a serum antibody test) as it is very sensitive. High IgM, polyclonal immunoglobulin and positive antibodies is common. Also has fluctuating parasitemia. All patients need an LP – Morula cell of Mott can be present, a plasma cell packed with immunoglobulin.

Patient also had a feature of kerandel’s hyperesthesias, which classically was a sign of African sleeping sickness.

Patient got treated with Eflornithine x 2 weeks

Finally, the clinical bedside portion was great! We saw three patients with my group of 5.

1.     A 28 year lady, home maker with hydatid disease – presenting with 6 months of abdo pain. Given the size of her lesions, she was planned for surgery. Serology not often done in India as difficult to interpret (false negatives?).

2.     50 year old man with uncontrolled diabetes, presenting with fever and LUQ pain x 6 weeks, found to have splenic abscess that ruptures and this was due to meliodosis – apparently it’s a top differential for splenic abscess in the tropics. Looks like a safety been, but often need to warn lab about suspecting it with a non-fermenter gram negative bacilli.

3.     55 yo male who had weight loss, myalgias and was found have massive hepato-spleno megaly, being classic for Kala Azar, (visceral leishmaniosis), was given one dose of IV ampho (which cures 90% of cases), but failed. He was being seen in follow up. Amastigotes were seen on bone marrow biopsy.. They do a serology test RK39 which is a pretty good test and only needs a finger prick, thus used in the community to diagnose and treat quite easily. It detects antibodies to recombinant K39antigen, a kinesin gene product with 39 amino acid repeat seen in the viscerotropic species L. donovani, L infantum, and L chagasi.


For my own notes:

Life cycle of echinococcus:

1.  adult tapeworm inhabits intestine of definitive host (i.e. dogs).

2. eggs in dog stool ingested by humans/or sheep (they are highly resistant!) - can last months

3. eggs/oncospheres hatch when ingested in humans or sheep, migrate to liver and become fluid filled cysts - become metacestode, protocolices develop in cyst.

4. In definitive host - that ingest sheep visceral organs containing cysts, protoscolices evaginate, attach to intestinal mucosa and develop into adult worms - this happens over 4-7 weeks.

CE lesions can be staged by means of US. Today, it is largely agreed to use the WHO classification of five stages: stages 1 and 2 of which are regarded as ‘active’; stage 3 ‘transitional’ and stages 4 and 5 ‘inactive’. MRI and CT can substitute for US if cysts are not accessible by US. CT scans, however, miss important stage-defining features, leading to misclassification.