Emergency Department Management Of Mosquito-Borne Illness: Malaria, Dengue, And West Nile Virus

Table of Contents

 

1. Abstract
2. Case Presentation
3. Introduction
4. Epidemiology
   1. Malaria
   2. Dengue
   3. West Nile Virus
5. Critical Appraisal Of The Literature
6. Etiology And Pathophysiology
   1. Malaria
   2. Flaviviruses
      1. Dengue Virus
      2. West Nile Virus
7. Differential Diagnosis
8. Emergency Department Evaluation
   1. History
      1. Previous Medical History
      2. Travel History
      3. History Of Chemoprophylaxis/Vaccines
   2. Clinical Presentation And Physical Examination Findings
      1. Malaria
      2. Dengue
      3. West Nile Fever
9. Diagnostic Studies
   1. Laboratory Tests
      1. Malaria
      2. Dengue
      3. West Nile Virus
10. Treatment
    1. Treatment For Malaria
    2. Treatment Of Uncomplicated P falciparum Malaria
       1. Cerebral Malaria
    3. Treatment Of Dengue
    4. Treatment Of West Nile Virus
11. Special Considerations
    1. Prevention
12. Special Populations
    1. Pregnant Patients
       1. Malaria
       2. West Nile Virus
       3. Malaria
       4. Dengue Virus
       5. West Nile Virus
13. Controversies And Cutting Edge
    1. Vaccine Development
    2. Emergence Of Chikungunya
14. Summary
15. Clinical Pathway For Treatment Of Patients With Malaria
16. Clinical Pathway For Management Of Suspected Dengue Infections
17. Clinical Pathway For Management Of Suspected West Nile Virus
18. Risk Management Pitfalls For Mosquito-Borne Illnesses
19. Time- And Cost-Effective Strategies
20. Case Conclusions
21. Tables and Figures
    1. Table 1. Mosquito-Borne Illnesses
    2. Table 2. Acute And Life-Threatening Diseases in Western Travelers
    3. Table 3. Common Errors Seen With Diagnosis And Treatment Of Malaria
    4. Table 4. Dengue Diagnostic Process (United States)
    5. Table 5. Initial Treatment Options For Severe Malaria In Adults
    6. Table 6. Practices Not Recommended for Severe Malaria
    7. Table 7. World Health Organization Clinical Criteria For Suspected Dengue
    8. Table 8. Recommendations For Disposition-Of-Care Settings For Dengue
    9. Figure 1. Average Numbers Of Dengue Fever And Dengue Hemorrhagic Fever Cases And Countries Of Occurrence, 1995-2007
    10. Figure 2. Centers For Disease Control And Prevention Recommendations For Treatment Of Malaria In The US
22. References

Abstract

Up to 700 million people are infected and more than a million die each year from mosquito-borne illness. While the vast majority of cases occur in endemic tropical and subtropical regions, international travel and migration patterns have increased their prevalence in North America. This review discusses the diagnosis and treatment of the 3 most common mosquito-borne illnesses seen in the United States: Plasmodium falciparum malaria, dengue, and West Nile virus. With no pathognomonic findings, it is critical that emergency clinicians in nonendemic areas maintain a high index of suspicion, conduct a thorough history/travel history, and interpret indirect findings to initiate prompt and appropriate treatment. This review gathers the best evidence from international public health resources, surveillance studies, guidelines, and academic research to give emergency clinicians tools to combat these potentially lethal infections.

Case Presentation

A 50-year-old man presents with fever for 3 days. He is an immigrant from Nigeria, but has resided in the United States for a decade. Ten days ago, he visited his family in a rural part of his homeland. He complains of fever, chills, and vomiting. His only medication was chloroquine, which was prescribed by his primary care physician prior to his trip. You recall reading something about increased resistance to one of the antimalarial medications in certain countries, but you can’t remember the specifics. A nurse brings you an ominous-looking ECG from EMS, just as you’re attempting to recall where to look up that information...

A 35-year-old woman presents with fever and malaise for 1 day. While taking her blood pressure, she is noted to have petechiae on the ipsilateral arm. She says she recently returned from a trip to Puerto Rico. You have heard that there is a current outbreak of dengue on the island, but you have never seen the disease before, so you need to quickly assess whether your patient has dengue and how to manage her disease...

While on vacation, a 70-year-old man from Fort Worth, Texas who is an active gardener presents to your ED with a fever and headache that have lasted for 2 days. Twelve hours ago, he developed right-arm weakness. His wife, unsure of what to do and unable to reach their doctor, called EMS who brought the patient into the ED…

Introduction

Mosquito-borne illnesses represent an enormous burden of disease on a global level and have been a menacing threat to mankind since early civilization. Annually, nearly 700 million people are afflicted with diseases transmitted by mosquitoes. Although the majority of these cases are found outside the United States, there are more than 20 million inhabitants of the United States who travel annually to regions of the world where mosquito-borne illnesses are endemic.^1,2 Furthermore, the number of western travelers to tropical regions of the globe where mosquito-borne diseases are common is estimated to be 50 million annually.³

Malaria is a mosquito-borne protozoan illness that is a major public health concern throughout the world. The infectious Plasmodium entities can have either zoonotic or human reservoirs and are endemic mainly to the tropical and subtropical regions. Patients with these infections may present in early phases of a potentially life-threatening condition, which, if not recognized by the clinician, can lead to poor outcomes. The mosquito-borne viral illnesses with the greatest impact on humans are dengue and West Nile virus.

An increasing interest in global health by emergency medicine residents as well as international involvement of emergency clinicians in the developing world necessitates a proficiency in identifying, diagnosing, and treating mosquito-borne illnesses both at home and abroad. Nearly 40% of Global Health Fellowshiplevel training programs in the United States stem from the specialty of emergency medicine.⁴

Emergency clinicians working in any major urban hub of global travel (such as Houston, Atlanta, New York City, or Miami) will inevitably encounter an international traveler with a fever. The risk of missed or delayed diagnosis upon return of one of these travelers “importing” a mosquito-borne illness carries the potential of death.^1,5 Equally concerning is the reemergence and translocation phenomenon of mosquito-borne illness into climactically vulnerable regions of the United States. Examples of this can be seen with dengue and West Nile viruses.

Although mosquito-borne illnesses are driving forces in morbidity and mortality on a global scale, these diseases do not represent the typical presentations encountered in emergency departments (EDs) in nonendemic areas of the United States. Despite their less-common nature, proficiency in recognizing highrisk cases and presentations of these diseases, offering the best available treatment, and recognizing indications for hospital admission will help emergency clinicians to better manage these patients.

Epidemiology

Malaria

Malaria is a leading cause of disease and death across the globe, accounting for up to 500 million febrile cases and as many as 1 million deaths per year.^1,6,7 The types of Plasmodium known to infect humans are P falciparum, P vivax, P ovale, P malariae, and P knowlesi. The most lethal is P falciparum, accounting for nearly all malaria-related deaths both globally and in the United States. Until recently, approximately 1500 cases of malaria per year were reported in the United States, according to the United States Centers for Disease Control and Prevention (CDC). However, in 2011, the highest number of cases in 40 years was reported, exceeding 1900 cases.⁸

Dengue

Dengue, the most prevalent form of viral mosquitoborne disease, is endemic in large geographic swaths of the globe, in more than 100 countries, with a staggering 2.5 billion humans at risk of exposure.² An estimated 50 million dengue infections occur annually, with about 500,000 severe dengue cases and 20,000 deaths per year.⁹ Prior to 1970, only 9 countries were known to have severe dengue outbreaks. Since 1981, the Western Hemisphere has seen the introduction of dengue hemorrhagic fever, with a concerning upsurge in the rate of cases paralleling observed trends of rapid population growth, unplanned urbanization, and poor vector control.¹⁰ Dengue is currently the most rapidly spreading viral mosquitoborne illness on a global scale, according to information from the World Health Organization (WHO) reported between 1995 and 2007.^11,12 (See Figure 1.) The United States has experienced multiple locally acquired outbreaks since 2001 (after nearly half of a century that marked the absence of indigenous dengue). ¹³ Southern areas of the United States (such as Florida and Texas) are in geographically susceptible zones.^14,15 In 2005, a rare autochthonous case of dengue hemorrhagic fever in Cameron County, Texas triggered the discovery of other local cases that were undiagnosed in south Texas. The cluster of cases coincided with an outbreak of dengue along nearby areas across the border in Tamaulipas, Mexico.¹⁶

Although uncommon in the temperate climate of North America, dengue is endemic in the United States territories of Puerto Rico, the United States Virgin Islands, and Guam. Epidemics emerge periodically (every 3 to 5 years) in Puerto Rico. In 2010, Puerto Rico experienced its historically largest dengue outbreak with > 21,000 reported cases, which coincided with a surge of United States residents diagnosed with acute dengue virus infection.^17,18

The latest CDC data on dengue, published in 2011, reported 1541 cases in the Commonwealth of Puerto Rico and 254 cases in the United States.¹⁹ Most cases of dengue in the contiguous states of the United States are travel related, most commonly from the Caribbean, Pacific Islands, Asia, and Central and South America.²⁰

West Nile Virus

In the United States, West Nile virus has become an increasing public health threat since the late 1990s, after an initial reported outbreak in New York. In 2012, more than 5000 cases of West Nile virus were reported nationwide, half of which were neuroinvasive cases. Although the vast majority of persons infected with West Nile virus (estimated to be as high as 200,000) are asymptomatic, the emergency clinician must be vigilant and aware of the neuroinvasive forms of West Nile virus infection, which carry a 10% mortality.²¹ West Nile virus is now enzootic in all 48 contiguous states of the United States. West Nile virus is a zoonotic virus, and birds serve as the amplifying reservoir, whereas humans are considered to be “dead-end” hosts. Humans are exposed when bitten by an infected mosquito, typically one from the Culex species. Transmission and infection rates are highest when the mosquito is most active, ie, summer and early fall. In warmer climates, transmission can occur year-round.

Critical Appraisal Of The Literature

A literature search from 1967 to 2013 on PubMed (with results limited to humans vs animals) using the terms malaria, West Nile virus, dengue, yellow fever, and Japanese encephalitis generated over 40,000 search results. A search of all evidence-based medicine sources on the Ovid database for the term malaria generated slightly over 3000 results. A search on www.guideline. gov and the Cochrane Database of Systematic Reviews using the same terms was also performed.

The most recent guidelines on dengue and malaria published by the WHO were also reviewed.^12,22 The 2010 WHO guidelines on malaria were developed utilizing a systematic, evidence-based approach, whereas the WHO guidelines for dengue are largely supported by empirical practices, without systematic grading of the available evidence. Available CDC guidelines regarding West Nile virus focus on surveillance, prevention, and control. They are not clinically focused, evidence-based guidelines.

A large part of the literature available regarding mosquito-borne illnesses in the United States is based on clinical epidemiology and disease surveillance documentation of outbreaks. Given the unpredictable nature of these diseases and their relatively uncommon occurrence in the Western world, there is a paucity of rigorously designed studies with direct application to nonendemic settings. Nearly all of the prospective studies were conducted in endemic regions of sub-Saharan Africa, Asia, or South America.

Risk Management Pitfalls For Mosquito-Borne Illnesses

1. “I work at a small community hospital ED, where we don’t have infectious disease specialists to consult. I had a sick-appearing patient in whom I suspected a mosquito-related illness. When I called the patient’s primary care doctor to get the patient admitted, she asked me for recommendations regarding admission orders.” When encountering a patient with suspected mosquito-borne illness, professional help is only a phone call away. The CDC has hotlines and dedicated websites for assistance with the management of malaria, dengue, and West Nile virus. There are also on-call experts who can assist in navigating your case and other conditions.
2. ”I suspected that the patient had dengue, but his fever was resolving. He just came back in severe shock.” Dengue is a multistage clinical disease. The defervescence of a patient in the first week of the disease can mark the beginning of the “critical phase” of the disease where shock and death are a risk.
3. “The tourist from Guatemala I saw 2 days ago who had fever, body aches, abdominal pain, and a rash didn’t look that sick. He just came back and is in the intensive care unit with multiorgan failure.” Be alert for any patient traveling from a dengue-endemic region with symptoms concerning for the disease. In this case, the patient had a dengue warning sign (abdominal pain) and should have been admitted for observation.
4. “The patient said he went to a picnic and was bitten by mosquitoes. Now he feels miserable, with headaches and fever.” West Nile virus is endemic to all 48 contiguous United States. Use of personal preventive measures – especially the use of DEET-containing insect repellents – is highly encouraged to prevent West Nile virus transmission.
5. “I just got a call from the local health department. They’re upset because I didn’t consider West Nile virus in that patient I admitted as having Guillain-Barré last week.” West Nile virus can cause a demyelinating process similar to Guillain-Barré. Consider West Nile virus testing in any patient with flu-like symptoms and flaccid paralysis. Appropriate monitoring and identification of new cases allows health departments to focus prevention and control efforts.
6. “The patient said that when he was in Uganda a couple of weeks ago, the hotel he stayed in didn’t provide insect nets. When he asked, they told him not to worry – their mosquitoes didn’t have malaria.” Most savvy travelers carry their own nets. Not only does this assure they are in good repair and treated with insecticide, many guesthouses and hotels don’t have nets. Advise patients not to risk a malaria infection because of the lack of nets.
7. “I thought about malaria in that patient with fever and recent travel, but he reported taking chemoprophylactic medications, so I didn’t think he could have malaria.” Even travelers prescribed prophylactic medication can be taking the incorrect regimen for resistance patterns in the areas traveled. In addition, patient nonadherence to most regimens is fairly high.
8. “I can’t believe the patient died at home 3 days after discharge. I sent the laboratory results and asked her to follow up with her primary care provider in a couple of days in case she needed to be treated. She looked well at the time of discharge.” P falciparum malaria constitutes a medical emergency and patients with a high index of suspicion for it warrant initiation of treatment either as outpatients or inpatients while tests are pending.
9. “I was proud of diagnosing complicated P falciparum malaria in a patient who had recently returned from a trip to Nigeria with vomiting, but I was confounded to find out that the patient nearly coded while receiving treatment.” Patients receiving quinidine intravenously need a baseline ECG and cardiac monitoring. Rapid infusion of the drug can cause severe hypotension as well as QT prolongation and arrhythmia.
10. “The thick and thin smears I ordered were reported negative by the lab, so malaria was ruled out.” In nonimmune populations, low-level ( < 1%) parasitemia can be clinically significant, but it can lead to false negatives with both light microscopy and rapid diagnostic tests. Diagnosis of malaria by light microscopy is technically challenging and, in nonendemic areas, most clinicians’ experience is limited. At least 3 slide preparations must be examined to definitively exclude malaria, so ensure that a sufficient amount of blood is sent to the laboratory.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.

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