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October 6, 2015 Issue

Clinical Practice Points

Medical Knowledge
Systems-based Practice

Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use Under an Investigational New Drug Protocol

Quinidine gluconate, the only drug approved for treatment of severe malaria in the United States, has substantial adverse effects and limited availability. In a program administered by the Centers for Disease Control and Prevention, intravenous artesunate seemed to be a safe and effective alternative to quinidine for the treatment of life-threatening malaria.

Use this paper to:

  • Start a teaching session with a multiple-choice question. We've provided one below!
  • Ask your learners how malaria presents. Who is at risk? What are possible complications? Use the information in DynaMed Plus: Malaria (log on with your ACP member ID and password).
  • How is malaria diagnosed? Invite a hematologist to review the blood smear of a patient with malaria and to compare it with the smears of patients with other causes of hemolysis.
  • How is malaria treated? Artesunate has been shown to be effective and is recommended by the World Health Organization. Why is it not approved by the U.S. FDA?
  • Ask what an Investigational New Drug (IND) is. Invite a clinical investigator familiar with pharmaceutical trials to review the path a drug must follow to gain approval for use in the United States.
  • Ask who requires malaria prophylaxis for travel. What regimen should be prescribed?

Medical Knowledge
Patient Care
High Value Care

Cost-Effectiveness of Herpes Zoster Vaccine for Persons Aged 50 Years

Although herpes zoster vaccine is licensed for persons aged 50 years or older, the Advisory Committee on Immunization Practices (ACIP) recommends it be used only in persons aged 60 years or older. This analysis evaluated the cost-effectiveness of herpes zoster vaccine versus no vaccination among adults aged 50 years. The results support the ACIP recommendations.

Use this paper to:

  • Review the clinical manifestations of herpes zoster.
  • How is uncomplicated zoster managed?
  • What are the possible complications of zoster, and who is at risk? When is intravenous treatment required?
  • Ask if your learners recommend herpes zoster vaccination to their patients? Which ones? Is it available for administration in your practice? Why or why not? Use a recent study to read about the barriers to the vaccine's use in clinical practice. How is it obtained and administered when not available at your practice?

Medical Knowledge

Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia. A Systematic Review and Meta-analysis

This meta-analysis of 13 randomized trials examines the benefits and harms of adjunctive, systemic corticosteroid therapy for adults hospitalized with community-acquired pneumonia (CAP). It found that systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day.

Use this study to:

  • Ask your learners why steroids might be of benefit in CAP.
  • Review the forest plots in the paper and its appendix. Review how each study's results are displayed, how the study's “weight” relative to the others is reflected in the size of its box on the plot, and what the diamond at the bottom tells you. Ask what the diamond's peak and side edges represent (the meta-analytic estimate and its confidence interval, respectively). Be sure your learners understand the importance of the vertical line, demarcating the difference between positive and negative effects.
  • What side effects were reported with the use of steroids? Will your learners treat their hospitalized patients with CAP with steroids? Which ones? The editorialists discuss their planned approach pending additional studies.

Beyond the Guidelines

Medical Knowledge
Interpersonal / Communication Skills
High Value Care

Screening Pelvic Examinations in Adult Women. Grand Rounds Discussion From the Beth Israel Deaconess Medical Center

The American College of Physicians recommends against routine annual pelvic examination in adult, asymptomatic women at average risk; the American College of Obstetrics and Gynecology recommends in favor of routine annual pelvic examination. These engaging videos and accompanying paper summarize a discussion between an internist and a gynecologist on how they would balance recommendations in general and what they would suggest for an individual patient.

Use this program to:

  • Watch the video in which the patient describes her situation in her own words.
  • Review the summary of the ACP and ACOG guideline recommendations provided at the beginning of the article with your learners.
  • Ask your learners if they would recommend an annual pelvic examination to this patient. What are the pros and cons of performing an annual pelvic examination in this patient?
  • Watch the video of the grand rounds presentation, or review the salient points made by each of the discussants. Consider asking two members of your team to each prepare a summary to present to the rest of your team of the points made by primary care and gynecologist discussants.
  • After listening to the discussion, ask your learners what would they do.

Professionalism and Humanism


On Being a Doctor: The Tyranny of Guidelines

In his essay, Dr. Sarosi describes the path of a previously vigorous elderly man as he progressed through medications prescribed for his hypertension and diabetes.

Use this essay to:

  • Listen to an audio recording of this essay, read by Dr. Michael LaCombe.
  • Ask your learners whether treating hypertension is always a priority? How about diabetes?
  • The author decries the “bonus” a physician might have received for care that adhered to guidelines in this story. Do your learners share Dr. Sarosi's view?
  • How can we judge when to follow a guideline, and when our patient is better served otherwise? Can we only know in retrospect?

Systems-based Practice

Annals Graphic Medicine: Sign Out

Annals Graphic Medicine

In his graphic narrative, Dr. Montoya illustrates how “sign out” works and doesn't work.

Use this graphic narrative to:

  • Ask your learners whether they believe the way your program approaches “sign out” is best?
  • What makes a “sign out” good or bad?
  • How might your program improve its approach?
  • How do your learners balance the need to appear knowledgeable of all the medical details when seeing a patient they are “covering?” What do they do when it is clear they are not familiar with important information? Do they try to cover it up, hoping to avoid adding to the patient's anxiety or their own embarrassment? Should they be embarrassed? Would patients rather hear us say that we don't know but will find out?

Teaching Scholarship Opportunity

High Value Care

Herbert S. Waxman Clinical Skills Center Teaching Scholarship

Chief residents who are ACP members are eligible to apply for a Herbert S. Waxman Clinical Skills Center Teaching Scholarship. The Waxman Center is part of ACP's annual Internal Medicine Meeting, and it provides hands-on, small-group learning opportunities for clinical and procedural skills. Waxman Scholars help teach popular workshops under the guidance and mentorship of expert faculty. Eligible workshops include ultrasound-guided invasive procedures (central line, paracentesis, and lumbar puncture), arthrocentesis, and incision and drainage of abscesses. The scholarship includes the cost of meeting registration, travel, and accommodations for the selected chief residents to attend the ACP Internal Medicine Meeting 2016 from May 5-7, 2016, in Washington, DC.

This is an opportunity to build your CV and to gain valuable faculty workshop experience. The deadline to apply is this Friday, October 9, 2015.

Visit ACP Online to learn more.


A 54-year-old man is evaluated in the emergency department for a 2-week history of fever and chills occurring every 1 to 2 days. He also has a significant headache, muscle pain, and intermittent diarrhea. The patient is an archeology professor who returned 2 weeks ago from a 6-week “dig” in Thailand in Southeast Asia. He received pre-travel prophylactic vaccinations, including combined hepatitis A and B virus vaccines, as well as yellow fever, typhoid, and Japanese encephalitis vaccines. In addition, he completed a regimen of mefloquine for malaria chemoprophylaxis.

On physical examination, he appears ill but is awake and alert. Temperature is 39.4 °C (102.9 °F), blood pressure is 100/62 mm Hg, pulse rate is 118/min, and respiration rate is 20/min. Cardiopulmonary examination is unremarkable. There is mild splenomegaly.

A complete blood count indicates a leukocyte count of 8900/µL (8.9 × 109/L), a platelet count of 82,000/µL (82 × 109/L), and a hemoglobin level of 10 g/dL (100 g/L). He also has a mildly increased serum indirect bilirubin level and elevated serum alanine and aspartate aminotransferase levels. A peripheral blood smear is shown.


Against which of the following malaria species should treatment be initiated in this patient?

A. Plasmodium falciparum
B. Plasmodium malariae
C. Plasmodium ovale
D. Plasmodium vivax

Correct Answer
A. Plasmodium falciparum

Key Point
A diagnosis of malaria should be considered in the differential diagnosis of travelers returning from malaria-endemic areas who present with fever and a peripheral smear indicating Plasmodium organisms in the erythrocytes.

Educational Objective
Diagnose a returning traveler with malaria.

The most likely malaria species against which treatment should be directed is Plasmodium falciparum. Malaria should be considered the most likely cause of fever in any traveler returning from a malaria-endemic area of the world. After Africa, Asia is the geographic destination with the highest risk of imported malaria. P. falciparum causes most malaria cases diagnosed in the United States following travel. Although mostly all cases occur in travelers who did not take any chemoprophylaxis or who were not adherent to it, infection can still be contracted despite compliance with all medical and preventive measures. In this instance, the patient spent time in Thailand, one of the rare malaria-infested zones where mefloquine-resistant P. falciparum has been reported.

There are no pathognomonic clinical signs or symptoms of malaria. In general, the signs and symptoms of uncomplicated malaria are nonspecific and infrequently occur before 1 to 4 weeks after return from travel. Fever, present in 100% of patients, may have a recurring cyclical pattern every 48 or 72 hours, varying according to the specific Plasmodium species and corresponding to the synchrony of organism replication. However, classic periodic malarial fever is most often absent in imported cases. Other common symptoms include myalgia, headache, and gastrointestinal discomfort. The degree of anemia depends on the duration of disease and degree of parasitemia. Although leukocyte counts may be variable, thrombocytopenia is present in greater than 50% of patients. Kidney impairment may also occur, the pathogenesis of which likely relates to hemolysis and erythrocyte sequestration within the kidney circulation. The term “blackwater fever” is given to the very dark urine secondary to significant hemoglobinuria sometimes observed in patients with severe falciparum malaria. Moreover, overwhelming disease may occur in patients who have anatomic or functional asplenia. The standard for malaria diagnosis is the Giemsa-stained blood smear by light microscopy. P. falciparum can involve erythrocytes of any size and are characterized by ring forms, some of which may be multiple, positioned along the periphery of the erythrocyte against the inner surface of its membrane. Classic “banana-shaped” gametocytes, if detected, can help to distinguish falciparum malaria species from the other potential Plasmodium species.

Infection with Plasmodium malariae should be considered if the paroxysms of fever occur every 72 hours and when the parasitized erythrocytes demonstrate the characteristic band form trophozoite, neither of which is consistent with this patient's clinical scenario.

Infection with Plasmodium ovale and Plasmodium vivax may show trophozoite and schizont forms on the peripheral blood smear with Schüffner dots inside of enlarged erythrocytes, inconsistent with this patient's peripheral blood smear findings.

Taylor SM, Molyneux ME, Simel DL, et al. Does this patient have malaria? JAMA. 2010;304(18):2048-2056. PMID: 21057136

This question was derived from MKSAP® 16, the Medical Knowledge Self-Assessment Program.

From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Associate Dean of Graduate Medical Education and Affiliations, Thomas Jefferson University.


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