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Episode #47 – Bad Air

47 Cover Art OPT

Summary

Drs. Shilpa Vasishta and Courtney Coyle navigate us through fever in a returning traveler

Table of Contents

Credits

Hosts: Shilpa Vasishta, Sara Dong

Guest: Christina Coyle

Writing: Shilpa Vasishta, Christina Coyle, Sara Dong

Producing/Editing/Cover Art/Infographics: Sara Dong

Our Guests

Guest Consultant

Christina Coyle, M.D., M.S.

Christina Coyle, M.D., M.S. is a board-certified physician in Infectious Disease and has practiced Tropical Medicine for over twenty-five years in New York City (NYC). She is a Full Professor in the Department of Medicine and Pathology at the Albert Einstein College of Medicine and is recognized as an expert in Tropical Medicine. She serves as the Director of the Clinical Infectious Disease Service at Jacobi Medical Center, and oversees the largest Tropical Medicine Clinic in the Bronx, NYC. Since 2007, she has been a site director for GeoSentinel, the global surveillance network of the International Society of Travel Medicine (ISTM) and the Centers for Disease Control and Prevention (CDC). Dr. Coyle is currently serving as an associate editor for Open Forum in Infectious Diseases (OFID). From 2016 to 2021, she served as a Member of the American Board of Internal Medicine’s Infectious Disease Exam Committee. Dr. Coyle is widely recognized as an expert on larval tapeworms, neurocysticercosis, and echinococcus, serving on both national and international committees for this disease. Since 2017, she has served on the Echinococcal WHO working group. Dr. Coyle is also a content expert for the Center for Disease and Prevention Control (CDC) for all complicated cases of echinococcus. She is a co-author on “Diagnosis and Treatment of Neurocysticercosis: 2017 Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH).” She is the principal investigator for a CDC cooperative grant, “Reducing the burden of neglected parasitic infections (NPIs) in the United States through evidence-based prevention and control activities”.

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Guest Co-Host

Shilpa Vasishta, MD

Shilpa is a first-year ID fellow at the Icahn School of Medicine at Mount Sinai in New York with an interest in medical education

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Culture

Christina brought her love of ballet and dancing.  Shilpa shared a similar item by mentioning tap dancing, her son’s love of the movie Happy Feet, and Savion Glover (an American tap dancer)

Consult Notes

Consult Q

Assistance with evaluation of worsening fevers in a returning traveler

Case Summary

38 year old female who presented with fevers, headache, and nausea who was ultimately diagnosed with severe P.falciparum malaria.

Key Notes

You are called as the fellow for a patient with fever and recent travel! The next few episodes will focus on this scenario. What are the key historical points you want to learn for fever in a returning traveler?

Some key fever in a returning traveler resources mentioned on the show (plus a few others!)

Christina pointed out a few concepts or frameworks when she encounters this type of case. Here’s a quick summary of some of those:

  • She asks herself: (1) what is life threatening?  (2) what is treatable?  (3) what is transmissible?  (do I need to isolate this person)
  • The approach to the febrile traveler can be overwhelming, but consider these various schemas when building your differential diagnosis: 
      • Geographic region(s) of exposure
      • Exposure-based
      • Syndrome/symptoms-based
  • Fevers related to tropical exposures usually begin during travel or shortly after returning, but they can also be delayed.  Defining the illnesses and relevant incubation periods will help you construct the appropriate differential diagnosis
  • Risks for infections will vary by geography and season

The epidemiology of fever among travelers

The rest of these Consult Notes will focus on malaria. Let’s start with a quick overview

  • Caused by 5 species of the genus Plasmodium: falciparum, malariae, vivax, ovale, and knowlesi
  • A major cause of morbidity and mortality worldwide 
  • Originally thought to be transmitted by bad air “mala aria” (hence the name of the episode!) >> it was not until late 1800s that physicians identified parasite and demonstrated life cycle
  • Disease burden and species prevalence varies by geography and seasonality, and malaria exists year-round in tropical and subtropical regions worldwide
      • 90% of disease and death occur in Africa
      • Other areas of high incidence include Central America, South America, Southeast Asia, Indian subcontinent, Middle East
  • Risk factors for acquisition include environments conducive to the Anopheles mosquitos, such as warm and rainy seasons, shallow collections of water, lack of mosquito netting or other protective measures at home

The malaria life cycle

Image: CDC

Vector: female Anopheles mosquitoes, which prefer night-time or pre-dawn biting and transmission

Human infection begins when a malaria-infected female mosquito inoculates sporozoites into human host

  • Sporozoites infect hepatocytes, where they mature into schizonts
  • [P.vivax and P.ovale have a dormant stage (hypnozoites) which can persist in the liver and cause relapses into the bloodstream]

Schizonts rupture and release merozoites >> which next infect red blood cells (initially visible as ring or trophozoite stage) >> this human “blood stage” is where symptoms occur

  • These trophozoites will mature into schizonts, which again rupture and release more merozoites

A portion of merozoites will undergo sexual differentiation into gametocytes (rather than form schizonts) > these gametocytes are ingested by next Anopheles mosquito 

  • Inside mosquito gut, sporogonic cycle takes place where gametocytes mature and begin cycle of growth and multiplication

Clinical presentation of malaria

The clinical manifestations will vary by species, epidemiology, immunity and age!

  • In endemic areas, the groups at highest risk include young children under 6 and pregnant women.  In areas where malaria is transmitted throughout the year, older children and adults have some partial immunity and are at relatively low risk for severe disease
      • Travelers to malarious areas who have no previous exposure or who have lost their immunity are at very high risk for severe disease if infected with P.falciparum
  • Typical incubation periods:
      • P.falciparum: 12-14 days (range 7-30 days)
      • P.vivax and P.ovale: usually about two weeks, but illness can occur months after initial infection due to residual hepatic hypnozoites.  Relapses usually occur within 2-3 years of infection
      • P.malariae: 18 days (range 15-35), can occasionally be months to years with low grade asymptomatic infection
      • P.knowlesi: 12 days (9-12d)
  • Clinical presentation of uncomplicated malaria
      • Cardinal symptom = fever (caused by rupture of mature schizonts)
        • May follow typical fever cycles known as paroxysms, which are dependant on antibody release as erythrocytes rupture and release merozoites – but fever patterns are not reliable in early infection
        • Fever paroxysm patterns are usually described as:
              • Every other day or 48 hrs (tertian fever): P.vivax, P.ovale, P.falciparum
              • Every third day or 72 hrs (quartan fever): P.malariae
              • Every 24 hrs (quotidian fever): P.knowlesi
      • Other initial symptoms are often nonspecific: tachycardia, fatigue, headache, myalgias/arthralgias, abdominal pain, cough
      • Physical exam may be normal, but might find pallor, splenomegaly, or jaundice
      • Labs: parasitemia, anemia, thrombocytopenia, elevated AST/ALT, mild coagulopathy, elevated BUN/Cr
  • *Patients with acute falciparum malaria may have normal physical exam and no fever when first seen*
  • What about severe malaria?  See the next section!

Severe malaria

  • In clinical practice, differentiation between uncomplicated or severe malaria is of utmost importance
  • Complicated or severe malaria will have the same symptoms described in uncomplicated malaria, but patients will have evidence of end-organ damage.
  • Severe malaria features include:
      • Cerebral malaria: encephalopathy/coma, convulsions
      • Renal failure / acute tubular necrosis
      • Hypoglycemia
      • Hemorrhage/hemoglobinuria
      • Severe anemia (<=5 g/dL in children <12 yo; <7 g/dL in older children and adults)
      • Metabolic acidosis (might see rapid deep breathing on exam clinically)
      • Noncardiogenic pulmonary edema
      • Shock
      • Hyperparasitemia: >=5 % in non-immune travelers; >10% in all patients
  • Severity is often correlates with parasitemia although this is not absolute
  • P.falciparum can cause severe malaria, while the other species of malaria are much less likely to have complicated disease.  There are increasing reports of severe malaria with P.knowlesi though

Malaria Diagnostics

  • Microscopy is the standard tool for diagnosis of malaria (visualizing parasites in blood smears).  Giemsa-stained thick and thin smears are used to diagnose malaria as well as determine the species and degree of parasitemia
      • Certain features on microscopy will help identify the species, but some features might overlap.  For example, early P.knowlesi infections can look just like P.falciparum, but as infection progresses, morphology changes to resemble P.malariae.
          • You can find more on the key features in the accompanying infographics on malaria
      • One other advantage of microscopy is that it also enables diagnosis of hematologic abnormalities and other infections such as filariasis, trypanosomiasis, babesiosis, and others
      • The main drawback or limitation is lab training and expertise
      • Microscopy cannot reliably detect very low parasitemia or cases when parasite biomass is largely sequestered, as Christina mentioned on the episode.  If malaria is suspected and initial smear is negative, additional smears should be examined over the subsequent 2-3 days
  • Rapid diagnostic tests are available that can be run directly on blood samples

Malaria treatment

The first item is to determine severity of illness.  Severe malaria can lead to death within hours, so initiation of antimalarial therapy is critical and an ID emergency

 

  • Treatment of uncomplicated malaria depends on the spp and drug resistance trends
      • If chloroquine resistant P.falciparum, you really have 3 main choices:
          • Preferred >> Artemether-lumefantin x 3d
          • Atovaquone-proguanil x 3d
          • Quinine + doxycycline (or clindamycin for pregnancy) x 7d
          • (Mefloquine based regimens should only be used if above regimens are not available due to neuropsychiatric effects and resistance in some areas)
      • Chloroquine susceptible Plasmodium is only present in a handful of places

Prevention of Malaria

  •  

Other miscellaneous mentions and notes:

Episode Art & Infographics

Find all the Febrile infographics here!

Goal

Listeners will be able to diagnose and recommend management for severe malaria

Learning Objectives

After listening to this episode, listeners will be able to:

  • Identify the necessary components of the history to gather for a patient presenting with fever and recent travel
  • Describe the key diagnostics available malaria diagnosis
  • Compare and contrast available antimalarials for chemoprophylaxis and treatment

Disclosures

Our guest (Christina Coyle) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Coyle, C., Vasishta, S., Dong, S. “#47: Bad Air”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/0948e155-ec87-48a7-a08e-1cf07af6ef89

Transcript

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