Infectious Disease Compendium

Plasmodium aka Malaria

Microbiology

P. falciparum, P. malariae, P. ovale (two species), P. vivax, P. knowlesi, P. simium.

Epidemiologic Risks

Getting bit by a mosquito, occasionally from transfusions.

And there is this weird case in Italy where roomates in the hospital spread malaria with no reason found (PubMed).

Everyone knows about sickle cell, but there are a large number of polymophisms that give resistance to malaria (PubMed). I bet no organism has left more footprints on the human genome.

P. falciparum is mostly sub Saharan Africa and SE Asia. For excellent maps of endemicity, go to A new world malaria map: Plasmodium falciparum endemicity in 2010

P. malariae: the tropics of all continents. In SE Asia there can be a severe, sometime fatal malaria that is actually P. knowlesi (PubMed, MMWR).

P. knowlesi: SE Asia, esp Malaysia where it is the most common form (PubMed). Comes from monkeys and is indistinguishable from on smear from P. malariae, but will have a higher number of parasitized red cells (PubMed). At least three different population (PubMed).

P. ovale : Africa and Asia. Turns out there are 2 types of P. ovale that are 2 distinct species that look the same P. ovale curtisi and P. ovale wallikeri (PubMed). P. ovale wallikeri my be a bit worse (PubMed).

P. vivax: Asia and South America.  Parasitaemia can be below the level of microscopic detection and need a PCR to diagnose (PubMed).

For risk of a given county go to http: //www.cdc.gov/travel/destinat.htm.

Don't let the lack of a travel history dissuade you from considering malaria in a patient with cyclic fevers: there were over 50 local outbreaks of malaria in the US in the last half of the last century (MMWR). The mosquito and/or an infected human is a plane flight away.

Cool. Your skin bacteria flora makes products that attract malaria (PubMed).

Syndromes

Fevers mostly. q 48 hours with P. vivax or P. ovale, q 72 with P. malariae, P. falciparum is usually q 48, but is more variable and the patient is sicker.

Severe P. falciparum can cause sludging and organ infarction, esp worrisome is the brain. Risks are being non black, having had prior malaria and having >2% parasitemia (PubMed). Obesity and diabetes increase the risk for severe malaria (PubMed)

If you see shizonts on the smear, expect up to a 16 fold increase in parasitemia and a bad prognostic sign.

P. knowlesi patients are a lot sicker than those infected with P. malariae.

Anyone who has a fever in a malarious region is treated for malaria, but do they have malaria when febrile? It depends on the prevalence of malaria, but in "16,903 children surveyed, 3% were febrile and infected, 9% were febrile without infection, 12% were infected but were not febrile and 76% were uninfected and not febrile...in areas where community-based infection prevalence in childhood is above 34-37%, 50% or more of fevers are likely to be associated with malaria (Ref)." Take home: just because they have a fever and got therapy for Malaria, doesn't mean they had malaria.

P. simium is in Brazil, comes from monkeys and looks like P. vivax on the smear. (PubMed).

Treatment

Given the changing resistance in malaria, always check the CDC site for up to date information. Call the CDC malaria hot line for help: 770-488-7788. And believe me, you will need help. This is a disease that can go south with remarkable rapidity.

P. falciparum:

No chloroquine resistance: chloroquine one gram, then 500 mg 6 hours later, then 500 mg at 24 and 48 hours.

Chloroquine resistance:

Mefloquine 750 mg followed by 500 mg 12 hours later OR

Quinine 650 mg q 8 hours for 3 days plus doxycycline 100 mg po bid for 7 days OR

Atovaquone plus proguanil (Comes in fixed combination tablets of 250 mg atovaquone and 100 mg proguanil Malarone®) four tablets daily for 3 days (may be administered as 2 tablets twice daily) OR

Azithromycin (750 mg twice daily) plus artesunate (100 mg twice daily) for 3 days (PubMed), OR

Azithromycin (500 mg 3 times daily) plus quinine (10 mg/kg 3 times daily) are safe and efficacious combination treatments for uncomplicated falciparum malaria OR

Artemether plus lumefantrine (Comes in fixed combination tablets of 20 mg artemether and 120 mg of lumefantrine). 6 dose regimen: 1st day: 4 tabs initially, then 4 tabs 8 hours later, 2nd day: 4 tabs twice daily, 3rd day: 4 tabs twice daily OR

6.75 of dihydroartemisinin and 54 mg/kg of and piperaquine, is more effective and better tolerated against multidrug-resistant P. falciparum and P. vivax infections (PubMed).

Pyronaridine–Artesunate daily for three days (PubMed).

Chloroquine or mefloquine resistant P. falciparum: doxycycline mg qd OR atovaquone plus proguanil 250 mg/100 mg (Malarone® one tablet) qd.

In severe disease, IV quinidine 10 mg salt/kg loading dose (max. 600 mg) in normal saline infused slowly at a constant rate over 1-2 hours, followed by continuous infusion of 0.02 mg/kg/min until oral therapy can be started. Artesunate is superior but you have to call the CDC to get it:

How to Obtain Artesunate

To enroll a patient with severe malaria in this treatment protocol, contact the CDC Malaria Hotline: 770-488-7788 (M-F, 8am-4:30pm, eastern time) or after hours, call 770-488-7100 and request to speak with a CDC Malaria Branch clinician.

Exchange transfusions doesn't help (PubMed).

P. malariae/P. knowlesi:

Chloroquine one gram, then 500 mg 6 hours later, then 500 mg at 24 and 48 hours.

P. knowlesi : Atovaquone-proguanil and primaquine has been used with success for (MMWR). Early Artesunate therapy has lower mortality (PubMed).

P. ovale: chloroquine one gram, then 500 mg 6 hours later, then 500 mg at 24 and 48 hours AND primaquine 15 mg base qd for 14 days. Check for G-6-PD deficiency before starting primaquine.

P. vivax: chloroquine one gram, then 500 mg 6 hours later, then 500 mg at 24 and 48 hours AND primaquine 15 mg base qd for 14 days. Check for G-6-PD deficiency before starting primaquine.

Chloroquine resistance is increasing in SE Asia;

Prevention: (NEJM 2008 Review)

Start 1-2 weeks before travel and continuing weekly for 4 weeks after leaving. Applies to non pregnant adults only.

P. vivax, P. ovale, P. malariae, and chloroquine susceptible P. falciparum: chloroquine phosphate 500 mg (300 mg base) once weekly.

Chloroquine resistant P. falciparum: mefloquine 250 mg once weekly.

Notes

Resistance is increasing, esp in SE Asia where mefloquine resistance occurs.

It killed King Tut. Really. And citronella with vanillin not only leads to a better smelling French car, but does prevent mosquito bites, just not as well as DEET (PubMed).

In Uganda blackwater fever, and acute intravascular hemolysis, fever, and dark or red urine, is a complication of recent or concurrent Plasmodium falciparum malaria infection in nonimmune adults Africa. Associated with chloroquine it is making a comeback perhaps due to the use of artemisinin-based combination therapies(PubMed). no good deed ever goes unpunished