Case 28-2015: a 32-Year-Old Man with Fever, Headache, and Myalgias After Traveling from Liberia

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Case Records of the Massachusetts General Hospital

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Case 28-2015: A 32-Year-Old Man with Fever, Headache, and Myalgias after Traveling from Liberia

Paul D. Biddinger, M.D., David C. Hooper, M.D., Erica S. Shenoy, M.D., Ph.D., Ednan K. Bajwa, M.D., M.P.H., Gregory K. Robbins, M.D., M.P.H., and John A. Branda, M.D.

Presentation of Case

From the Departments of Emergency Dr. Paul D. Biddinger: In December 2014, the emergency department of this hospital Medicine (P.D.B.), Infectious Diseases received a call from a public health authority about a 32-year-old man with fever, (D.C.H., E.S.S., G.K.R.), Pulmonary and Critical Care (E.K.B.), and Pathology headache, and myalgias that had developed 8 days after he had traveled from Liberia. (J.A.B.) and the Infection Control Unit The patient had been in Liberia for 3 months, working as an administrator for (D.C.H., E.S.S.), Massachusetts General a nonprofit organization that was involved in the response to the epidemic of Hospital; and the Departments of Emer‑ gency Medicine (P.D.B.), Medicine (D.C.H., Ebola virus disease (EVD). He had not had any known direct contact with persons E.S.S., E.K.B., G.K.R.), and Pathology infected with the virus. While he was in Liberia, he did observe patients with EVD, (J.A.B.), Harvard Medical School — both as well as health care workers and funeral personnel in protective clothing, but in Boston. only from afar. He departed from Liberia 8 days before admission. He arrived in N Engl J Med 2015;373:1060-7. the United States the day after he left Liberia and immediately began participating DOI: 10.1056/NEJMcpc1503828 Copyright © 2015 Massachusetts Medical Society. in an EVD monitoring program administered by a public health authority, with plans to participate in the program for the 21-day period after his departure from Liberia. As part of this program, the patient measured his temperature twice daily, performed self-observation for other signs or symptoms of infection, and communicated each day with a public health official about his condition. He reported temperatures that were within normal limits and had felt well until the morning of the day of admission, when a headache and myalgias developed. Sev- eral hours later, his temperature rose to 39.3°C, with associated chills. The patient contacted the public health authority, who subsequently called the person who had been previously specified as the point of contact at this hospital to discuss the facts of the case and to notify the hospital about the patient’s impending arrival. The public health authority coordinated the dispatch of emergency medical services (EMS) to the patient’s home. EMS personnel performed an initial interview and assessment of the patient while maintaining a distance of greater than 6 ft (2 m) between themselves and the patient. The patient appeared to be alert, oriented, conversant, ambulatory, and well. He was provided with an impermeable jumpsuit and a face mask; EMS per-

1060 n engl j med 373;11 nejm.org September 10, 2015 The New England Journal of Medicine Downloaded from nejm.org at The University Of Illinois on January 26, 2016. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital sonnel also put on personal protective equip- department, the patient reported having increas- ment (PPE) and draped the patient compartment ing chills and feeling more tired; he had slight of the ambulance in plastic. The patient was then diaphoresis, and the temperature was 39.7°C. transported to the emergency department of this Acetaminophen was administered. hospital for further evaluation. Management decisions were made, and a di- On arrival at the emergency department, the agnostic test was performed. patient was immediately placed in a negative- pressure isolation room. He rated his headache Assessing Risk for EVD at 7 or 8 on a scale of 0 to 10 (with 10 indicating Dr. David C. Hooper: The establishment of case the most severe pain) and reported fatigue, mild definitions by public health authorities ensures nausea, and a reduced appetite. He had a history consistency and appropriateness of screening for, of a mandibular fracture that had occurred in a identification of, and response to EVD. On the sledding accident 6 years previously, and he had basis of a combination of symptoms and epide- undergone strabismus repair in early childhood miologic risk, this patient was considered to be and laser-assisted in situ keratomileusis 1 year a “person under investigation” (PUI) for EVD by before admission. He also had a history of trau- the Centers for Disease Control and Prevention matic microhyphema and partial-thickness cor- (CDC). At the time the patient presented to this neal laceration that had occurred after he was hospital, criteria for the status of a person under bitten on the face by a dog 6 years earlier, at investigation for EVD included the presence of which time the rabies vaccine and rabies immune either a fever (documented or subjective) or one globulin were administered. Before the patient or more of the following symptoms: severe head- traveled to Liberia, he had received the tetanus– ache, muscle pain, vomiting, diarrhea, abdomi- diphtheria–acellular pertussis vaccine, the live- nal pain, or unexplained hemorrhage. Fever, attenuated oral typhoid vaccine, and the yellow headache, and myalgia were present in this pa- fever vaccine. He had received doxycycline for tient. Because such symptoms are nonspecific, malaria prophylaxis during the trip, but he dis- persons under investigation for EVD must also continued taking the medication on the day he have epidemiologic risk factors — which are returned to the United States. He took no other stratified into risk categories of high, some, and medications and had no known allergies. low (but not zero) (Table 1)1 — with exposures The patient was single; he had recently ended occurring within the past 21 days, which is the a long-term monogamous relationship and had longest known incubation period for Ebola virus. no new sexual partners. He lived with room- Although this patient had had no known expo- mates, consumed alcohol in moderation, and did sure to EVD, he was considered to be in the low not smoke or use illicit drugs. During the previ- (but not zero) risk category because he had spent ous 9.5 years, he had traveled extensively in sub- time in Liberia, one of the countries (along with Saharan Africa, the Middle East, and the Cauca- Sierra Leone and Guinea) in which widespread sus. During his trip to Liberia, he had spent half transmission of Ebola virus had occurred during his time in Monrovia and the remainder divided the period of his visit. Because this patient was between two sites where there were no known considered to be a person under investigation for active cases of EVD. He had not used public EVD, he was transported to this hospital, and transportation, shared his sleeping quarters with the hospital’s Biothreat Care Unit was activated. other persons, or had exposure to animals; he had been bitten by mosquitoes. Four days before Preparations and Activation of the Biothreat admission, he had spent time with a friend who Care Unit had a resolving upper respiratory tract infection. Dr. Erica S. Shenoy: In preparation for the possible On limited examination, the patient did not need to care for a patient with suspected or con- appear to have signs that were immediately worri- firmed EVD, the hospital’s Biothreat Care Unit, some for possible sepsis. He was alert, coopera- a discrete physical space, had been created at the tive, and oriented to person, place, and time. end of an existing medical intensive care unit Extraocular-muscle movements were intact, oral (MICU) corridor, allowing for unidirectional mucous membranes were dry, and respiratory ef- flow of the care team and for isolation of the fort was normal. While he was in the emergency Biothreat Care Unit from the rest of the MICU.

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Table 1. Epidemiologic Risk Factors for Ebola Virus Disease (EVD).*

Risk Category and Associated Risk Factors Present in This Patient High Percutaneous exposure (e.g., needle stick) or exposure of mucous membranes to No blood or body fluids of a person with EVD while the person was symptomatic Exposure — without wearing the appropriate PPE — to the blood or body fluids No of a person with EVD while the person was symptomatic Processing — without wearing the appropriate PPE or taking standard biosafety No precautions — of the blood or body fluids of a person with EVD while the per‑ son was symptomatic Direct contact — without wearing the appropriate PPE — with a dead body in a No country with widespread transmission of Ebola virus Residence in the immediate household and provision of direct care to a person No with EVD while the person was symptomatic Some Direct contact — while wearing the appropriate PPE — with a person with EVD No while the person was symptomatic and while in a country with widespread transmission of Ebola virus Close contact in households, health care facilities, or community settings with a No person with EVD while the person was symptomatic† Low (but not zero) Residence in or visit to a country with widespread transmission of Ebola virus Yes within the past 21 days and no known exposures Brief direct contact (e.g., shaking hands) — without wearing the appropriate PPE No — with a person with EVD while the person was in the early stage of disease Brief proximity (i.e., being in the same room for a brief period of time) to a per‑ No son with EVD while the person was symptomatic Direct contact — while wearing the appropriate PPE — with a person with EVD No while the person was symptomatic and while in a country without widespread transmission of Ebola virus Travel on an aircraft with a person with EVD while the person was symptomatic Unknown

* Data are from the Centers for Disease Control and Prevention.1 Body fluids include but are not limited to feces, saliva, sweat, urine, vomit, and semen. PPE denotes personal protective equipment. † Close contact is defined as being, for a prolonged period of time while not wearing the appropriate PPE, within approxi‑ mately 3 ft (1 m) of a person with EVD while the person was symptomatic.

On the patient’s admission, a site manager was 1 attending physician and 4 nurses per shift. The designated from a pool of trained personnel to choice of PPE reflected a goal of no skin expo- oversee the preparation of the unit, which in- sure, in accordance with CDC guidelines.2 Clini- cluded relocating existing patients, removing cal and support staff who were required to have unnecessary supplies and equipment from the proficiency in PPE for EVD had participated in rooms, and stocking each room with materials small-group tutorials in which they were taught specific for the care of a patient with suspected how to put on and remove PPE; a checklist was EVD. The site manager was responsible for en- used in this process, with a staff member calling suring the safe and effective delivery of the pa- out each step and observing the other members tient’s treatment.2 for adherence to the protocol. Clinicians had also The Biothreat Care Unit clinical care team previously practiced performing specific manual was drawn from a group of 32 MICU nurses and medical tasks — including phlebotomy, specimen 16 attending physicians who had volunteered packaging and transport, and placement of intra- months earlier to participate in PPE training, vascular catheters — while wearing PPE. Once planning meetings, and both institution-wide the physical setup and staffing plan were in place and unit-based drills. The staffing plan included and the staff of the Biothreat Care Unit agreed

1062 n engl j med 373;11 nejm.org September 10, 2015 The New England Journal of Medicine Downloaded from nejm.org at The University Of Illinois on January 26, 2016. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital that the unit was ready to accept this patient, an onset of fever, chills, sweats, malaise, headache, attending physician and nurse donned PPE and nausea, and body aches was most consistent transported him from the emergency department. with Plasmodium falciparum malaria; the patient had reported receiving numerous mosquito bites Initial Evaluation and Management while he was in Liberia, a country in which this Dr. Ednan K. Bajwa: On the patient’s arrival in the vectorborne disease is endemic. Doxycycline had Biothreat Care Unit, a second examination was been an appropriate choice for malaria chemo- performed. The temperature was 38.5°C, the blood prophylaxis, but the patient had not recalled in- pressure 155/91 mm Hg, the pulse 99 beats per structions to continue taking the medication for minute, the respiratory rate 18 breaths per min- 28 days after leaving Liberia, and this regimen ute, and the oxygen saturation 96% while he was had been terminated prematurely. His stay in breathing ambient air. The patient appeared to Liberia had been 3 months in duration, and the be flushed and diaphoretic but otherwise well. incubation period of malaria would have been The neck was supple, the abdomen was soft and consistent with an onset of illness in this patient nontender, and the neurologic examination was 8 days after he left the country. normal. Auscultation was precluded by the hood The differential diagnosis also included other of the clinician’s PPE. There was an erythematous causes of acute febrile illness, such as enteric annular lesion (2 cm in diameter) with an over- fever, arboviral infections (e.g., dengue or chikun- lying scale between the 4th and 5th toes of the gunya virus infection), influenza, leptospirosis, left foot, without associated tenderness, edema, legionellosis, acute human immunodeficiency or warmth. virus, and rickettsial infection.3,4 However, labo- The patient was admitted to the hospital soon ratory testing was limited by the strict precau- after the onset of his symptoms and was not tions taken with this patient and his blood and critically ill. However, given the possible diagno- body-fluid specimens. He was at low risk for sis of EVD, we carefully planned for the care that EVD, but coinfection with malaria has been re- would be required if advancing disease were to ported in about 10% of patients with EVD. Be- develop. Our management strategy was guided cause the patient was still within the 21-day in- by experiences reported by EVD treatment cen- cubation period for Ebola virus and had met the ters in the United States and Europe that had criteria for a person under investigation for EVD, provided care for a moderate number of health the diagnosis could not be clinically ruled out on care workers and other travelers returning from the basis of the history and physical examina- West Africa. We were prepared to manage fluid tion alone. Therefore, we decided to test for and electrolyte abnormalities aggressively and to malaria and EVD. maintain adequate nutritional status in the patient, including through the delivery of paren- Clinical Diagnosis teral nutrition if enteral nutrition was no longer possible owing to development of severe gastro- Plasmodium falciparum malaria. intestinal symptoms. We were also prepared to use mechanical ventilation and renal-replacement Pathological Discussion therapy, both of which have been initiated suc- cessfully in patients with EVD in whom organ Dr. John A. Branda: In the months before this pa- failure has developed. As part of the initial treat- tient’s admission, the clinical laboratories (in ment of this patient, we asked the infectious consultation with hospital leaders in emergency diseases consultation service for guidance re- medicine, critical care, and infectious diseases) garding other possible causes of this patient’s developed a plan to offer needed laboratory test- illness and suggesting appropriate empirical ing for a person under investigation for EVD that antimicrobial therapy, if needed. would protect laboratory workers and minimize disruptions to routine laboratory operations. The Clinical Impression goal was to limit testing to assays that were predicted to be essential for the care of a patient Dr. Gregory K. Robbins: Although there was con- being evaluated for or with a diagnosis of EVD. cern that this patient may have EVD, the abrupt Our plan required that all specimen manipula-

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tion and analysis be performed in a certified was admitted, and within approximately 1 hour, biosafety cabinet and without the use of sharp we were able to report to the clinical team that needles or other devices that could puncture the he tested positive for a P. falciparum–specific an- skin. This precluded the use of our main analyz- tigen in the blood (Fig. 1). Other values that were ers and instruments, so we focused instead on obtained on admission are shown in Table 2. point-of-care testing devices. We planned to per- Several hours after presentation, after safe pack- form testing in the mycobacteriology laboratory aging and transport of blood specimens to the because this area has a biosafety level of 2+, is state public health laboratory, a PCR assay for under negative pressure, contains an appropriate Ebola virus was performed and was negative. biosafety cabinet, and is relatively secluded, there- by ensuring that foot traffic could be controlled Discussion of Management and that the testing would have a minimal effect on routine laboratory operations. Dr. Robbins: Once the test for P. falciparum malaria We had anticipated that a person under inves- was positive, therapy with artemether and lume- tigation for EVD would be a febrile patient who fantrine was administered. Miconazole was ap- had recently been in West Africa, and thus we plied topically for the treatment of tinea pedis; thought that it would be essential to offer ma- other empirical antimicrobial agents were not laria testing, as well as to obtain routine blood prescribed. Lactated Ringer’s solution, ibuprofen, cultures to detect agents such as Salmonella typhi and enoxaparin were administered. The patient and Neisseria meningitidis, which are endemic in felt better during his first night in the hospital, that region. For blood cultures, we acquired a but the following morning, a temperature of dedicated instrument for incubation and detection and planned to use plastic rather than glass bottles to reduce the chance of breakage. In ad- dition, we anticipated the need to measure electrolyte levels and renal function in a patient with vomiting and diarrhea, to measure the hemoglobin level and hematocrit in a patient with hemorrhage or malaria, and to measure levels of blood gases in a critically ill patient. We obtained a handheld analyzer that could be used to perform these tests on venous blood. Finally, we established a procedure for prompt transport of specimens to our state public health laboratory, where a polymerase-chain-reaction (PCR) assay of the blood for Ebola virus could be performed. A small group of medical technologists was Figure 1. Microbiologic Test Results. trained on how to properly put on and remove A rapid lateral-flow immunochromatographic assay for the required PPE and to perform testing accord- the qualitative detection of plasmodium (malarial) an‑ ing to procedures clearly outlined on previously tigens in blood was performed. The appearance of a developed checklists. A rotation was established pink-to-purple line at the C (positive control) position to provide coverage by three technologists at all indicates valid performance of the assay, and the ap‑ times: one to perform testing, a second to focus pearance of the line at the T1 (test 1) position indi‑ cates the presence of a histidine-rich protein II antigen on the checklists, and a third to manage the specific to Plasmodium falciparum. No line was ob‑ transfer of specimens and supplies into and out served at the T2 (test 2) position; a line at this position of the biosafety cabinet as needed. Two laboratory would have indicated the presence of an aldolase anti‑ directors were also included in the on-call team, gen that is commonly associated with multiple species to determine an individualized testing strategy of human malarial parasites. The term mixed denotes mixed infection with P. falciparum and another plas‑ in consultation with the care teams and to man- modium species, Neg. no infection, P.f. infection with age ongoing laboratory activities with minimal P. falciparum, P.m. infection with P. malariae, P.o. in‑ disruption. fection with P. ovale, and P.v. infection with P. vivax. These plans were activated when this patient

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Table 2. Laboratory Data.*

Reference Range, Second Hospital Third Hospital Variable Adults† On Admission Day Day Hematocrit (%) 41.0–53.0 42.0 47.0 40.0 Hemoglobin (g/dl) 12.0–16.0 14.3 16.0 13.6 Sodium (mmol/liter) 135–145 134 137 139 Potassium (mmol/liter) 3.4–4.8 3.5 3.7 3.6 Chloride (mmol/liter) 100–108 96 96 98 Carbon dioxide (mmol/liter) 23–32 24 25 26 Anion gap (mmol/liter) 10–20 19 21 19 Ionized calcium (mmol/liter) 1.14–1.30 1.13 1.17 1.18 Glucose (mg/dl) 70–110 103 104 94 Urea nitrogen (mg/dl) 8–25 11 11 4 Creatinine (mg/dl) 0.60–1.50 1.20 1.10 1.00

* To convert the values for ionized calcium to milligrams per deciliter, divide by 0.250. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to micromoles per liter, multiply by 88.4. † Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may therefore not be appropriate for all patients.

39.8°C developed; he reported diaphoresis and reported by another U.S. hospital highlighted worsening headaches and myalgias. Additional the importance of considering the diagnosis of laboratory test results are shown in Table 2. The EVD and planning a strategy to safely evaluate patient’s fever abated on the third hospital day, the patient once this possibility is considered.6 and by the fourth hospital day, headaches and Prompt recognition of the possibility of EVD al- myalgias had resolved; a decision was made to lows for early and aggressive care, which is impor- forgo repeat PCR testing for Ebola virus. Isolation tant for survival.7 Furthermore, rapid isolation of precautions were removed, and the patient was the patient and implementation of personal pro- embraced by many members of the care team. tective measures decrease the chance of nosoco- Dr. Biddinger: As the strategy for the care of mial transmission of disease. Second, a patient this patient shows, an extensive amount of plan- such as this one, for whom EVD is included in ning and other preparation is required for medi- the differential diagnosis, may also face the some- cal providers, hospitals, and health systems to what unusual danger of a delay or failure in the safely provide high-quality care for patients with recognition and treatment of alternative diagno- suspected EVD or infection with another rare ses because of the limitations placed on labora- but highly infectious pathogen. It is unlikely that tory testing, imaging studies, and other diagnos- most clinicians in the United States will care for tic services for patients who require the highest a patient with a confirmed diagnosis of EVD, but levels of isolation.8 At this hospital, the tests with the ease of global travel, it is certainly pos- available under these circumstances allowed us sible that many clinicians could encounter pa- to rapidly make a diagnosis of malaria and to tients, such as this one, for whom the diagnosis initiate treatment. of EVD is considered but an alternative diagnosis Finally, the development of procedures for ob- is ultimately made. Despite this possibility, recent taining an appropriate travel history from pa- research has shown that very few clinicians have tients who present with symptoms of emerging felt adequately prepared to handle this scenario.5 infectious diseases will expedite early recogni- We learned several lessons in our preparation tion. Websites that list diseases of concern, the for and care of this patient. First, the recent ex- countries in which such diseases are active, and perience of nosocomial transmission of EVD links to current case definitions — such as sites

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maintained by the CDC, the Department of fection with a non–P. falciparum plasmodium spe- Health and Human Services Office of the As- cies represented reactivation of a dormant infec- sistant Secretary for Preparedness and Response, tion that had been acquired during an earlier trip and other appropriate expert organizations — to Kenya; some reports suggest that treatment of are important resources. The establishment of a P. falciparum may increase the risk of reactivation robust plan for the management of suspected of P. vivax.12,13 cases, including provisions for patient transfer The patient is here today, and I would like to to a specified safe location of care delivery, will ask him to say a few words about his experience. benefit both the patient and the health care pro- The Patient: When I woke up feeling sick that viders. morning, I knew rationally that it wasn’t Ebola. Modifying a hospital’s physical plant to safely I had not had direct contact with anyone who house a person who is under investigation for was symptomatic during my time in Liberia, so EVD, as was done at this hospital, can be very I was at very low risk. But as the day progressed, costly and may not be necessary for all hospi- and the number of resources at the disposal of tals.9,10 The establishment of a rational, sustain- the state and hospital that were being used be- able plan at each level of the health care system came apparent to me, I started to think, “Wow, and of a network of institutions to which per- they are building an isolation unit for me, they sons under investigation for EVD can be sent for are wearing space suits, and the media are inter- evaluation and treatment will enhance the abil- ested. Maybe I do have Ebola.” ity to safely consider the diagnosis of EVD while As that day went on, it was helpful that the limiting risks to the public, medical providers, extra precautions and extraordinary circum- and individual patients. stances were explained to me as they unfolded and that Dr. Robbins called my mother before Follow-up the malaria test came back positive and talked her through the hysteria she was feeling. In gen- Dr. Robbins: After discharge, the patient contin- eral, everyone who participated in my care pro- ued to participate in the EVD monitoring pro- jected an effective bedside manner, even while gram for the full 21-day period after his depar- they were wearing space suits, which was pretty ture from Liberia; he did not have recrudescence remarkable. of fever during that time. However, 6 weeks after Something that struck me as I was lying there admission, he called to report that fevers, rigors, was the contrast between the deployment of re- and headaches had recurred. He was seen in a sources here and what I had seen in Liberia. clinic at this hospital, and diagnostic tests were There were only 50 doctors to serve Liberia before performed. the outbreak, and of the more than 300 health Dr. Branda: Repeat testing for malaria with the care workers who have died of Ebola in West use of a rapid antigen-detection assay was nega- Africa, 180 have been in Liberia. All the factors tive for the P. falciparum–specific antigen but was that made this experience as pleasant as possible positive for a common plasmodium-specific an- for me — like getting to the hospital right away, tigen. Examination of thick and thin peripheral- receiving a rapid diagnosis, and having great blood smears revealed malarial parasites in ap- supportive care and reassurance — have been proximately 0.1% of the red cells; these parasites lacking for so many people affected by this epi- were morphologically incompatible with P. falci- demic in West Africa. parum, but their species could not be determined One other thing that hasn’t yet been men- with certainty. tioned is the lengths to which the hospital ad- Dr. Robbins: A second course of artemether ministration went to protect my identity. I didn’t and lumefantrine was administered, and prima- fully realize the importance of this at the time, quine phosphate was prescribed to reduce the but in retrospect, it was really important. risk of future relapses.11 Primaquine phosphate I’ve told a lot of people since my hospitaliza- had not been given initially because the plasmo- tion that although I was stuck in the same room dium species that creates latent hypnozoites is for 3 days, the experience was about as positive uncommon in Liberia. It is possible that the in- as I could expect.

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Final Diagnosis This case was presented at Emergency Medicine Grand Rounds, hosted by Brigham and Women’s Hospital. Disclosure forms provided by the authors are available with Malaria due to Plasmodium falciparum and non– the full text of this article at NEJM.org. P. falciparum plasmodium species.

References 1. Centers for Disease Control and Pre- 4. Ryan ET, Wilson ME, Kain KC. Illness 9. Hladky GB. Hospitals have spent vention. Case definition for Ebola virus dis- after international travel. N Engl J Med $5 million to prepare for Ebola. Hartford ease (EVD). 2015 (http://www.cdc.gov/vhf/ 2002;347: 505-16. Courant. December 1, 2014. ebola/healthcare-us/ evaluating-patients/ 5. APIC Ebola readiness poll: results of 10. Firgir J. Ebola in the U.S.: who pays the case-definition.html). an online poll of infection preventionists. bills? CBS News. October 31, 2014 (http:// 2. Centers for Disease Control and Pre- Washington, DC: Association for Profes- www.cbsnews .com/ news/ ebola-in-the-us vention. Guidance on personal protec- sionals in Infection Control and Epidemiol- -who-pays-the-bills). tive equipment to be used by healthcare ogy, 2014 (http://www.apic.org/Resource_/ 11. Baird JK, Hoffman SL. Primaquine workers during management of patients TinyMceFileManager/Topic-specific/ Ebola therapy for malaria. Clin Infect Dis 2004; with Ebola virus disease in U.S. hospi- _Readiness_Poll_Results_FINAL.pdf). 39:1336-45. tals, including procedures for putting on 6. Weber EJ. A man walks into an ED . . . . 12. Douglas NM, Nosten F, Ashley EA, et al. (donning) and removing (doffing). 2014 Emerg Med J 2014;31:950. Plasmodium vivax recurrence following fal- (http://www.cdc .gov/ vhf/ ebola/ healthcare 7. West TE, von Saint André-von Arnim A. ciparum and mixed species malaria: risk -us/ppe/ guidance .html). Clinical presentation and management of factors and effect of antimalarial kinet- 3. Boggild AK, Esposito DH, Kozarsky severe Ebola virus disease. Ann Am Thorac ics. Clin Infect Dis 2011;52:612-20. PE, et al. Differential diagnosis of illness Soc 2014;11:1341-50. 13. White NJ. Determinants of relapse in travelers arriving from Sierra Leone, 8. Clinical inquiries regarding Ebola vi- periodicity in Plasmodium vivax malaria. Liberia, or Guinea: a cross-sectional study rus disease received by CDC — United Malar J 2011;10:297. from the GeoSentinel Surveillance Net- States, July 9–November 15, 2014. MMWR Copyright © 2015 Massachusetts Medical Society. work. Ann Intern Med 2015;162:757-64. Morb Mortal Wkly Rep 2014;63:1175-9.

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