ID Consult

It’s summertime, which means that pediatric and family medicine offices are filled with children who have enteroviral infections, and too many of them will receive inappropriate antibiotic prescriptions.

From June through September, children who present with fever and other flulike symptoms nearly always have a nonpolio enterovirus (NPEV) infection, with coxsackievirus groups A and B, echoviruses, and the newer numbered enteroviruses being the most common in the United States. Epidemiologic surveillance suggests that 10 million to 15 million illnesses attributable to NPEV occur in the United States each year. I tell parents that their child has a "summer flu," which helps to communicate that it is usually self-limited and that antibiotics will not work to treat it.

A sudden high fever is usually what brings the child in, and the classic blistering hand-foot-mouth presentation of enterovirus helps us nail down the diagnosis. But sometimes, especially in younger children, symptoms such as myalgia, malaise, irritability, upper respiratory symptoms, or gastrointestinal symptoms may be nonspecific. In addition, the fever can precede hand-foot-mouth blisters by several days. A 9-month-old with a sudden fever of 103° F and a mildly red-looking throat can cause panic for parents, and a physician will often be led to prescribe an antibiotic out of an abundance of caution. In fact, more than 80% of inappropriate antibiotic use in the summertime is for febrile illness related to early enteroviral infection combined with worried parents and physicians.

Obtaining a complete blood count and differential can solve this problem, but it’s often not done because typically it involves sending the patient out for the blood work and waiting 4-6 hours for the results. Depending on when the test is done, results may not be available until the following day. It’s much simpler to "cover" with an antibiotic than to order the diagnostic test.

But I believe we should be using the white blood cell (WBC) count rather than prescribing antibiotics. The WBC count will almost always be low, and if a differential is added it will show a predominance of lymphocytes, indicating a viral infection. With that, parents and physicians can be reassured it’s enterovirus, and that no antibiotic is required.

In recent years, large pediatric practices and urgent care centers have begun purchasing a point-of-care WBC test made by Hemacue. Currently, it is licensed for use only in level 3 Clinical Laboratory Improvement Amendments (CLIA) facilities. A couple of years ago, I testified before a Food and Drug Administration device panel urging broader availability for the machine in clinical practice, but the panel had concerns that physicians would overrely on the WBC – the machine doesn’t give the differential – and possibly miss a more significant illness, such as leukemia.

Of course, the current widespread practice of empirically prescribing an antibiotic with no lab testing won’t pick up leukemia, either. In my view, the point-of-care test is an aid. It’s a piece of information you add to your clinical history and physical exam that assists in your diagnosis. I believe the benefits of avoiding unnecessary antibiotic use in millions of children every summer far outweigh the theoretical possibility that pediatricians would not rely on the broader context, including the time of year, disease rates in the community, and their clinical judgment. I really believe that WBC testing constitutes better care.

My colleagues and I have published two papers regarding the use of the WBC test to aid in judicious antibiotic use. In one, a prospective, 3-year study of 1,956 patients aged 3 months to 21 years with acute upper respiratory illness and fever, 737 did not have a diagnosis established by history and physical. Of those patients, we had WBC counts done for 351 children who appeared ill, had a temperature greater than 101° F, and parents who were demanding an antibiotic or physicians who were inclined to give an antibiotic. Of those, just 14 had a WBC count of 15,000/mcL or greater, and an antibiotic was prescribed for 13 of them. With the selective use of WBC testing, no child had significant bacterial illness that was missed (Clin. Pediatr. [Phila] 2003;42:113-9).

In another study of 120 acutely ill children and potential antibiotic recipients, we found that the point-of-care Hemacue WBC device produced comparable results to the Cell-Dyn countertop machine for total WBC counts (Clin. Pediatr. [Phila] 2009;48:291-4).

I’d just like to add a few more points about enterovirus to keep in mind when you advise patients and families. There is a long-held notion that summer viruses enteroviruses in particular – are of shorter duration than are winter viruses such as influenza, parainfluenza, and respiratory syncytial virus. That’s actually not true. Several years ago, my colleagues and I prospectively studied 380 children aged 4-18 years with systemic NPEV syndromes who presented to private suburban pediatric practices. Overall, NPEV infections were virologically confirmed in 122 of 372 patients (33%). The median duration of illness was 6 days for those with rash, 7 days for those with hand-foot-mouth and viral meningitis, 8 days for those with pleurodynia, and 9 days for those with myalgia/malaise (Pediatrics 1998;102:1126-34). Many children were ill for 10 days to 2 weeks.

Interestingly, in that study we also found that in more than half of the families, there was more than one individual with NPEV illness that was often similar but sometimes had a different clinical presentation. For example, one child might have classic hand-foot-mouth while another just has upper respiratory symptoms or gastrointestinal manifestations. This creates a confusing picture for the family because it is not intuitive to attribute different clinical presentations to the same viral etiology and, as a consequence, medical care may be sought more often.

We also found that 20% of the mothers caught the illness from the child, compared with fewer than 10% of the fathers. Luckily, the mother’s illness was usually less severe.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero’s institution received a research grant in 2008 from Hemacue, and he has served as a paid consultant to testify before the FDA in 2009 for Hemacue. He said he has no other conflicts to declare.

It’s summertime, which means that pediatric and family medicine offices are filled with children who have enteroviral infections, and too many of them will receive inappropriate antibiotic prescriptions.

From June through September, children who present with fever and other flulike symptoms nearly always have a nonpolio enterovirus (NPEV) infection, with coxsackievirus groups A and B, echoviruses, and the newer numbered enteroviruses being the most common in the United States. Epidemiologic surveillance suggests that 10 million to 15 million illnesses attributable to NPEV occur in the United States each year. I tell parents that their child has a "summer flu," which helps to communicate that it is usually self-limited and that antibiotics will not work to treat it.

A sudden high fever is usually what brings the child in, and the classic blistering hand-foot-mouth presentation of enterovirus helps us nail down the diagnosis. But sometimes, especially in younger children, symptoms such as myalgia, malaise, irritability, upper respiratory symptoms, or gastrointestinal symptoms may be nonspecific. In addition, the fever can precede hand-foot-mouth blisters by several days. A 9-month-old with a sudden fever of 103° F and a mildly red-looking throat can cause panic for parents, and a physician will often be led to prescribe an antibiotic out of an abundance of caution. In fact, more than 80% of inappropriate antibiotic use in the summertime is for febrile illness related to early enteroviral infection combined with worried parents and physicians.

Obtaining a complete blood count and differential can solve this problem, but it’s often not done because typically it involves sending the patient out for the blood work and waiting 4-6 hours for the results. Depending on when the test is done, results may not be available until the following day. It’s much simpler to "cover" with an antibiotic than to order the diagnostic test.

But I believe we should be using the white blood cell (WBC) count rather than prescribing antibiotics. The WBC count will almost always be low, and if a differential is added it will show a predominance of lymphocytes, indicating a viral infection. With that, parents and physicians can be reassured it’s enterovirus, and that no antibiotic is required.

In recent years, large pediatric practices and urgent care centers have begun purchasing a point-of-care WBC test made by Hemacue. Currently, it is licensed for use only in level 3 Clinical Laboratory Improvement Amendments (CLIA) facilities. A couple of years ago, I testified before a Food and Drug Administration device panel urging broader availability for the machine in clinical practice, but the panel had concerns that physicians would overrely on the WBC – the machine doesn’t give the differential – and possibly miss a more significant illness, such as leukemia.

Of course, the current widespread practice of empirically prescribing an antibiotic with no lab testing won’t pick up leukemia, either. In my view, the point-of-care test is an aid. It’s a piece of information you add to your clinical history and physical exam that assists in your diagnosis. I believe the benefits of avoiding unnecessary antibiotic use in millions of children every summer far outweigh the theoretical possibility that pediatricians would not rely on the broader context, including the time of year, disease rates in the community, and their clinical judgment. I really believe that WBC testing constitutes better care.

My colleagues and I have published two papers regarding the use of the WBC test to aid in judicious antibiotic use. In one, a prospective, 3-year study of 1,956 patients aged 3 months to 21 years with acute upper respiratory illness and fever, 737 did not have a diagnosis established by history and physical. Of those patients, we had WBC counts done for 351 children who appeared ill, had a temperature greater than 101° F, and parents who were demanding an antibiotic or physicians who were inclined to give an antibiotic. Of those, just 14 had a WBC count of 15,000/mcL or greater, and an antibiotic was prescribed for 13 of them. With the selective use of WBC testing, no child had significant bacterial illness that was missed (Clin. Pediatr. [Phila] 2003;42:113-9).

In another study of 120 acutely ill children and potential antibiotic recipients, we found that the point-of-care Hemacue WBC device produced comparable results to the Cell-Dyn countertop machine for total WBC counts (Clin. Pediatr. [Phila] 2009;48:291-4).

I’d just like to add a few more points about enterovirus to keep in mind when you advise patients and families. There is a long-held notion that summer viruses enteroviruses in particular – are of shorter duration than are winter viruses such as influenza, parainfluenza, and respiratory syncytial virus. That’s actually not true. Several years ago, my colleagues and I prospectively studied 380 children aged 4-18 years with systemic NPEV syndromes who presented to private suburban pediatric practices. Overall, NPEV infections were virologically confirmed in 122 of 372 patients (33%). The median duration of illness was 6 days for those with rash, 7 days for those with hand-foot-mouth and viral meningitis, 8 days for those with pleurodynia, and 9 days for those with myalgia/malaise (Pediatrics 1998;102:1126-34). Many children were ill for 10 days to 2 weeks.

Interestingly, in that study we also found that in more than half of the families, there was more than one individual with NPEV illness that was often similar but sometimes had a different clinical presentation. For example, one child might have classic hand-foot-mouth while another just has upper respiratory symptoms or gastrointestinal manifestations. This creates a confusing picture for the family because it is not intuitive to attribute different clinical presentations to the same viral etiology and, as a consequence, medical care may be sought more often.

We also found that 20% of the mothers caught the illness from the child, compared with fewer than 10% of the fathers. Luckily, the mother’s illness was usually less severe.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero’s institution received a research grant in 2008 from Hemacue, and he has served as a paid consultant to testify before the FDA in 2009 for Hemacue. He said he has no other conflicts to declare.

It’s summertime, which means that pediatric and family medicine offices are filled with children who have enteroviral infections, and too many of them will receive inappropriate antibiotic prescriptions.

From June through September, children who present with fever and other flulike symptoms nearly always have a nonpolio enterovirus (NPEV) infection, with coxsackievirus groups A and B, echoviruses, and the newer numbered enteroviruses being the most common in the United States. Epidemiologic surveillance suggests that 10 million to 15 million illnesses attributable to NPEV occur in the United States each year. I tell parents that their child has a "summer flu," which helps to communicate that it is usually self-limited and that antibiotics will not work to treat it.

A sudden high fever is usually what brings the child in, and the classic blistering hand-foot-mouth presentation of enterovirus helps us nail down the diagnosis. But sometimes, especially in younger children, symptoms such as myalgia, malaise, irritability, upper respiratory symptoms, or gastrointestinal symptoms may be nonspecific. In addition, the fever can precede hand-foot-mouth blisters by several days. A 9-month-old with a sudden fever of 103° F and a mildly red-looking throat can cause panic for parents, and a physician will often be led to prescribe an antibiotic out of an abundance of caution. In fact, more than 80% of inappropriate antibiotic use in the summertime is for febrile illness related to early enteroviral infection combined with worried parents and physicians.

Obtaining a complete blood count and differential can solve this problem, but it’s often not done because typically it involves sending the patient out for the blood work and waiting 4-6 hours for the results. Depending on when the test is done, results may not be available until the following day. It’s much simpler to "cover" with an antibiotic than to order the diagnostic test.

But I believe we should be using the white blood cell (WBC) count rather than prescribing antibiotics. The WBC count will almost always be low, and if a differential is added it will show a predominance of lymphocytes, indicating a viral infection. With that, parents and physicians can be reassured it’s enterovirus, and that no antibiotic is required.

In recent years, large pediatric practices and urgent care centers have begun purchasing a point-of-care WBC test made by Hemacue. Currently, it is licensed for use only in level 3 Clinical Laboratory Improvement Amendments (CLIA) facilities. A couple of years ago, I testified before a Food and Drug Administration device panel urging broader availability for the machine in clinical practice, but the panel had concerns that physicians would overrely on the WBC – the machine doesn’t give the differential – and possibly miss a more significant illness, such as leukemia.

Of course, the current widespread practice of empirically prescribing an antibiotic with no lab testing won’t pick up leukemia, either. In my view, the point-of-care test is an aid. It’s a piece of information you add to your clinical history and physical exam that assists in your diagnosis. I believe the benefits of avoiding unnecessary antibiotic use in millions of children every summer far outweigh the theoretical possibility that pediatricians would not rely on the broader context, including the time of year, disease rates in the community, and their clinical judgment. I really believe that WBC testing constitutes better care.

My colleagues and I have published two papers regarding the use of the WBC test to aid in judicious antibiotic use. In one, a prospective, 3-year study of 1,956 patients aged 3 months to 21 years with acute upper respiratory illness and fever, 737 did not have a diagnosis established by history and physical. Of those patients, we had WBC counts done for 351 children who appeared ill, had a temperature greater than 101° F, and parents who were demanding an antibiotic or physicians who were inclined to give an antibiotic. Of those, just 14 had a WBC count of 15,000/mcL or greater, and an antibiotic was prescribed for 13 of them. With the selective use of WBC testing, no child had significant bacterial illness that was missed (Clin. Pediatr. [Phila] 2003;42:113-9).

In another study of 120 acutely ill children and potential antibiotic recipients, we found that the point-of-care Hemacue WBC device produced comparable results to the Cell-Dyn countertop machine for total WBC counts (Clin. Pediatr. [Phila] 2009;48:291-4).

I’d just like to add a few more points about enterovirus to keep in mind when you advise patients and families. There is a long-held notion that summer viruses enteroviruses in particular – are of shorter duration than are winter viruses such as influenza, parainfluenza, and respiratory syncytial virus. That’s actually not true. Several years ago, my colleagues and I prospectively studied 380 children aged 4-18 years with systemic NPEV syndromes who presented to private suburban pediatric practices. Overall, NPEV infections were virologically confirmed in 122 of 372 patients (33%). The median duration of illness was 6 days for those with rash, 7 days for those with hand-foot-mouth and viral meningitis, 8 days for those with pleurodynia, and 9 days for those with myalgia/malaise (Pediatrics 1998;102:1126-34). Many children were ill for 10 days to 2 weeks.

Interestingly, in that study we also found that in more than half of the families, there was more than one individual with NPEV illness that was often similar but sometimes had a different clinical presentation. For example, one child might have classic hand-foot-mouth while another just has upper respiratory symptoms or gastrointestinal manifestations. This creates a confusing picture for the family because it is not intuitive to attribute different clinical presentations to the same viral etiology and, as a consequence, medical care may be sought more often.

We also found that 20% of the mothers caught the illness from the child, compared with fewer than 10% of the fathers. Luckily, the mother’s illness was usually less severe.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero’s institution received a research grant in 2008 from Hemacue, and he has served as a paid consultant to testify before the FDA in 2009 for Hemacue. He said he has no other conflicts to declare.

Measles is a threat that we need to take seriously, both domestically and when traveling anywhere abroad.

During 2011, the United States had more cases of measles than we have had in 15 years. There were 222 cases and 17 outbreaks of measles reported to the Centers for Disease Control and Prevention from 31 different states. This is a concern and a warning. It’s the highest number since 1996, when there were 508 cases.

Of those 222 cases, 200 were associated with importations from other countries. This includes both people who themselves traveled and became ill and/or imported the virus and those who were exposed to imported cases and themselves became ill. Most of the cases were not vaccinated against measles (65%) or didn’t know if they were vaccinated (21%). Of the 166 U.S. residents who were unvaccinated or had unknown vaccination status, 85% were eligible to get the measles-mumps-rubella (MMR) vaccine based on age and other factors. Of those 141 people, 66 (47%) were between the ages of 16 months and 19 years of age, and another 18 (11%) were under 1 year and, therefore, too young for vaccination. Of the 66 between 16 months and 19 years of age, 50 (76%) had not been vaccinated because of a philosophic, religious, or personal objection (MMWR 2012;61:253-7).

People who choose not to vaccinate themselves or their children are putting themselves and others at risk, particularly infants who are too young to receive the vaccine, and those who are immunocompromised and can’t receive the live attenuated MMR vaccine. Globally, 164,000 people die each year from measles. Nobody has died in the U.S. outbreak so far, but 70 of the 222 (32%) in 2011 were hospitalized.

Photo courtesy CDC/Cynthia S. Goldsmith; William Bellini, PhD

Nearly half of the 72 known actual importations from other countries were from Europe. We don’t typically think of Europe as a high-risk region for infectious disease, but measles has taken hold there in a big way. Of the 30,567 measles cases reported in the continent in 2011, half – 15,206 – were in France and another 5,181 in Italy, both popular destinations for U.S. travelers.

There is growing concern now about the risk of measles transmission at the Olympics, to be held in July in London. The United Kingdom reported 1,083 cases last year. This year, hundreds of thousands of visitors are
expected for the Olympics. The infectious disease community is advising all travelers to receive measles vaccination at least 2 weeks prior to traveling.

The concern is not limited to travelers to Europe, of course, but extends throughout the world, as outbreaks have been reported in New Zealand, Ecuador, much of Africa, and even Canada. Montreal is currently experiencing an outbreak, with 776 cases reported in the province of Quebec between Jan. 1 and March 31 of this year.

The CDC’s Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians recommend that people of all ages receive MMR. It is given routinely to children at 1 year of age and again at kindergarten entry (4-6 years). The travelers’ recommendation is that any child aged 6-12 months who is eligible receives one MMR dose prior to travel and everyone aged 12 months or older who is eligible receives two MMR doses prior to travel, separated by 28 days.

The MMR vaccine recommendation for travelers has been the same for more than 20 years, but people never really thought about it in terms of travel to Europe or Canada. Also, many adults assume that they were vaccinated as a child. Adults born prior to 1957 are presumed to have been exposed to natural measles and are therefore generally assumed to be immune. Routine measles immunization with one dose began in the mid-1960s, and the two-dose schedule was first recommended in 1989. Since approximately 5% of people don’t respond to the first vaccine dose and many people are unsure of their vaccination history, a substantial proportion of adults are currently susceptible.

Physicians should be prepared to respond to questions regarding MMR vaccine eligibility and should look for documentation of two MMR vaccines.

Summer is travel time, and measles vaccine is now a priority for our patients who are traveling.

Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She said she has no relevant financial disclosures. 

Measles is a threat that we need to take seriously, both domestically and when traveling anywhere abroad.

During 2011, the United States had more cases of measles than we have had in 15 years. There were 222 cases and 17 outbreaks of measles reported to the Centers for Disease Control and Prevention from 31 different states. This is a concern and a warning. It’s the highest number since 1996, when there were 508 cases.

Of those 222 cases, 200 were associated with importations from other countries. This includes both people who themselves traveled and became ill and/or imported the virus and those who were exposed to imported cases and themselves became ill. Most of the cases were not vaccinated against measles (65%) or didn’t know if they were vaccinated (21%). Of the 166 U.S. residents who were unvaccinated or had unknown vaccination status, 85% were eligible to get the measles-mumps-rubella (MMR) vaccine based on age and other factors. Of those 141 people, 66 (47%) were between the ages of 16 months and 19 years of age, and another 18 (11%) were under 1 year and, therefore, too young for vaccination. Of the 66 between 16 months and 19 years of age, 50 (76%) had not been vaccinated because of a philosophic, religious, or personal objection (MMWR 2012;61:253-7).

People who choose not to vaccinate themselves or their children are putting themselves and others at risk, particularly infants who are too young to receive the vaccine, and those who are immunocompromised and can’t receive the live attenuated MMR vaccine. Globally, 164,000 people die each year from measles. Nobody has died in the U.S. outbreak so far, but 70 of the 222 (32%) in 2011 were hospitalized.

Photo courtesy CDC/Cynthia S. Goldsmith; William Bellini, PhD

Nearly half of the 72 known actual importations from other countries were from Europe. We don’t typically think of Europe as a high-risk region for infectious disease, but measles has taken hold there in a big way. Of the 30,567 measles cases reported in the continent in 2011, half – 15,206 – were in France and another 5,181 in Italy, both popular destinations for U.S. travelers.

There is growing concern now about the risk of measles transmission at the Olympics, to be held in July in London. The United Kingdom reported 1,083 cases last year. This year, hundreds of thousands of visitors are
expected for the Olympics. The infectious disease community is advising all travelers to receive measles vaccination at least 2 weeks prior to traveling.

The concern is not limited to travelers to Europe, of course, but extends throughout the world, as outbreaks have been reported in New Zealand, Ecuador, much of Africa, and even Canada. Montreal is currently experiencing an outbreak, with 776 cases reported in the province of Quebec between Jan. 1 and March 31 of this year.

The CDC’s Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians recommend that people of all ages receive MMR. It is given routinely to children at 1 year of age and again at kindergarten entry (4-6 years). The travelers’ recommendation is that any child aged 6-12 months who is eligible receives one MMR dose prior to travel and everyone aged 12 months or older who is eligible receives two MMR doses prior to travel, separated by 28 days.

The MMR vaccine recommendation for travelers has been the same for more than 20 years, but people never really thought about it in terms of travel to Europe or Canada. Also, many adults assume that they were vaccinated as a child. Adults born prior to 1957 are presumed to have been exposed to natural measles and are therefore generally assumed to be immune. Routine measles immunization with one dose began in the mid-1960s, and the two-dose schedule was first recommended in 1989. Since approximately 5% of people don’t respond to the first vaccine dose and many people are unsure of their vaccination history, a substantial proportion of adults are currently susceptible.

Physicians should be prepared to respond to questions regarding MMR vaccine eligibility and should look for documentation of two MMR vaccines.

Summer is travel time, and measles vaccine is now a priority for our patients who are traveling.

Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She said she has no relevant financial disclosures. 

Measles is a threat that we need to take seriously, both domestically and when traveling anywhere abroad.

During 2011, the United States had more cases of measles than we have had in 15 years. There were 222 cases and 17 outbreaks of measles reported to the Centers for Disease Control and Prevention from 31 different states. This is a concern and a warning. It’s the highest number since 1996, when there were 508 cases.

Of those 222 cases, 200 were associated with importations from other countries. This includes both people who themselves traveled and became ill and/or imported the virus and those who were exposed to imported cases and themselves became ill. Most of the cases were not vaccinated against measles (65%) or didn’t know if they were vaccinated (21%). Of the 166 U.S. residents who were unvaccinated or had unknown vaccination status, 85% were eligible to get the measles-mumps-rubella (MMR) vaccine based on age and other factors. Of those 141 people, 66 (47%) were between the ages of 16 months and 19 years of age, and another 18 (11%) were under 1 year and, therefore, too young for vaccination. Of the 66 between 16 months and 19 years of age, 50 (76%) had not been vaccinated because of a philosophic, religious, or personal objection (MMWR 2012;61:253-7).

People who choose not to vaccinate themselves or their children are putting themselves and others at risk, particularly infants who are too young to receive the vaccine, and those who are immunocompromised and can’t receive the live attenuated MMR vaccine. Globally, 164,000 people die each year from measles. Nobody has died in the U.S. outbreak so far, but 70 of the 222 (32%) in 2011 were hospitalized.

Photo courtesy CDC/Cynthia S. Goldsmith; William Bellini, PhD

Nearly half of the 72 known actual importations from other countries were from Europe. We don’t typically think of Europe as a high-risk region for infectious disease, but measles has taken hold there in a big way. Of the 30,567 measles cases reported in the continent in 2011, half – 15,206 – were in France and another 5,181 in Italy, both popular destinations for U.S. travelers.

There is growing concern now about the risk of measles transmission at the Olympics, to be held in July in London. The United Kingdom reported 1,083 cases last year. This year, hundreds of thousands of visitors are
expected for the Olympics. The infectious disease community is advising all travelers to receive measles vaccination at least 2 weeks prior to traveling.

The concern is not limited to travelers to Europe, of course, but extends throughout the world, as outbreaks have been reported in New Zealand, Ecuador, much of Africa, and even Canada. Montreal is currently experiencing an outbreak, with 776 cases reported in the province of Quebec between Jan. 1 and March 31 of this year.

The CDC’s Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians recommend that people of all ages receive MMR. It is given routinely to children at 1 year of age and again at kindergarten entry (4-6 years). The travelers’ recommendation is that any child aged 6-12 months who is eligible receives one MMR dose prior to travel and everyone aged 12 months or older who is eligible receives two MMR doses prior to travel, separated by 28 days.

The MMR vaccine recommendation for travelers has been the same for more than 20 years, but people never really thought about it in terms of travel to Europe or Canada. Also, many adults assume that they were vaccinated as a child. Adults born prior to 1957 are presumed to have been exposed to natural measles and are therefore generally assumed to be immune. Routine measles immunization with one dose began in the mid-1960s, and the two-dose schedule was first recommended in 1989. Since approximately 5% of people don’t respond to the first vaccine dose and many people are unsure of their vaccination history, a substantial proportion of adults are currently susceptible.

Physicians should be prepared to respond to questions regarding MMR vaccine eligibility and should look for documentation of two MMR vaccines.

Summer is travel time, and measles vaccine is now a priority for our patients who are traveling.

Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She said she has no relevant financial disclosures. 

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

This column, "ID Consult," appears regularly in Pediatric News, a publication of Elsevier.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

This column, "ID Consult," appears regularly in Pediatric News, a publication of Elsevier.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

This column, "ID Consult," appears regularly in Pediatric News, a publication of Elsevier.

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].