key: cord-0046181-tbes7uke authors: CECILIA DI PENTIMA, M. title: Infections in Travelers and Adoptees from Abroad date: 2020-06-22 journal: Pediatric Infectious Diseases DOI: 10.1016/b978-0-323-02041-1.50040-7 sha: e1def72f0462fb91d51d35ee013b561f2e636b11 doc_id: 46181 cord_uid: tbes7uke nan Approximately 500 million international travelers cross borders every year; among these are approximately 50 million who travel from industrialized countries to tropical or developing regions of the world. This last group includes 27 million North Americans and Canadians, 18 million Europeans, 3 million Japanese, and 1 million Australians. No less than half will become sick either while traveling or after returning to their homeland. Adoption represents the legal mechanisms that consent to full family membership and privileges to children who were not born into the family. Over the past decade, the number of families adopting children from abroad has continued to increase. Approximately 15% of the 120,000 children adopted annually in the United States are international adoptees. These children arrive to the United States mainly from countries with high rates of endemic infectious diseases such as tuberculosis, hepatitis, and intestinal parasites. Most of these children lacked adequate nutrition and lived in institutions or in crowded conditions with limited access to organized and reliable health care. Conditions such as malnutrition and emotional and physical stress, in addition to high rates of exposure, increase their vulnerability to infections. Furthermore, immunization rates and vaccine documentation among international adoptees vary greatly, creating a challenge for pediatricians who must fulfi ll the recommended U.S. immunization schedule. Between 20% and 70% of international travelers become ill during or after their travel. However, only 1% to 5% of travelers are sick enough to seek medical attention, and approximately 0.01% to 0.1% require medical intervention. The type of activities engaged in by travelers while abroad has a direct impact on their risk of acquiring a tropical or unusual infection. People visiting family and friends are at higher risk, because of increased exposure, habits, and in many cases the lack of risk perception in a familiar environment. Adventure travelers and longterm expatriates, such as Peace Corps volunteers and missionaries, also have unique risks of exposure to vectorand/or food-borne pathogens. Furthermore, patterns of International Adoptees and Immigrants International Adoptees and Immigrants International Adoptees and Immigrants International Adoptees and Immigrants International Adoptees and Immigrants International Adoptees and Immigrants International Travelers International Adoptees and Immigrants infectious diseases evolve and change based on shifts in epidemiologic factors of pathogens, drug resistance, modifi cations in popular travelers' destinations, and wide use of preventive interventions. Traveler's diarrhea (TD) is the most common infection, affecting 20% to 50% of travelers to developing countries, resulting in more than 7 million cases a year. The main risk factors for TD include point of origin and destination, host factors, and exposure to contaminated food and water. Approximately 3% of international travelers develop fever, most commonly due to malaria. However, the overall incidence of malaria in returning travelers is low, between 2% and 4%. Travelers to sub-Saharan Africa on no prophylaxis or inappropriate prophylaxis have the highest incidence, representing approximately 90% of all Plasmodium falciparum infections in returning travelers worldwide. Through the year 2000, a total of 1402 cases of malaria were reported in the United States; the majority, 827 cases, were in U.S. citizens returning from abroad. The most common factors associated with malaria in returning travelers are the lack of knowledge about appropriate chemoprophylaxis and the lack of compliance. Since 1992, seven malaria-related deaths among U.S. citizens returning from sub-Saharan Africa following inappropriate chemoprophylaxis regimens have been reported to the Centers for Disease Control and Prevention. Even when chloroquine resistance was widespread in this region, in all cases, chloroquine was the drug prescribed as prophylaxis. Among other infections, acute febrile respiratory infections develop in approximately 1% of returning travelers, followed by hepatitis A (0.5%), dengue infection (0.4%), hepatitis B (0.1%), and human immunodefi ciency virus (0.01%). Statistical data from the Department of State reveals that the number of internationally adopted children in the United States has signifi cantly increased over the past decade, from 6472 children in 1992 to 20,099 in 2002. For the past 2 years, most adopted children were born in China, Russia, South Korea, Guatemala, and Ukraine. Internationally adopted children are at high risk for infections acquired in their country of origin, representing more than 75% of all diagnoses in these children within the fi rst month of arrival to the United States. Other diseases diagnosed in these children, such as neurologic, hematologic, renal, metabolic, or congenital abnormalities are present in 5% to 15% of adoptees. Defi cient immunizations and inaccurate vaccination records represent a signifi cant problem among international adoptees, except for children adopted from Korea, where compliance with vaccinations is appropriate. According to the U.S. Immigration and Naturalization Law, foreign-born orphans adopted by U.S. citizens who are 10 years old or younger are exempted from the official immunization requirements if the new parents assure that the child would be vaccinated within 30 days of entry into the United States. Common causes of fever in returning travelers from the tropics include malaria, respiratory tract infections, diarrheal illness, hepatitis, urinary tract infection, dengue fever, typhoid fever, amebic liver abscess, rickettsial infections, mononucleosis, and pharyngitis. P. falciparum is the most common strain isolated in returning travelers diagnosed with malaria, accounting for 44% of imported and confi rmed cases of malaria reported in the United States in the year 2000 (MMWR Surveill Summ, 2002; 51:15-28) . Most of them (76%) were acquired in Africa. Plasmodium vivax, more prevalent in Latin America and Asia, represented 37% of malaria cases for the same year. Plasmodium ovale and Plasmodium malariae represented 2% and 5%, respectively. Infectious disease agents are the main cause of TD, especially bacterial pathogens, representing approximately 80% of cases with an identifi ed pathogen. The etiologic agent remains undiagnosed in 20% to 50% of travelers developing diarrhea. Among bacterial pathogens, enterotoxigenic Escherichia coli (ETEC) is the most common etiologic agent of TD in all countries. Limited data regarding other E. coli strains, such as enteroaggregative, enteroinvasive, and enteropathogenic E. coli, suggest that they represent a minor source of TD. Shigella species, well-known cause of bacillary dysentery, are responsible for 5% to 15% of TD in selected developing countries. The number of TD cases due to Salmonella species varies but is not high. Campylobacter jejuni has been increasingly recognized as the etiologic agent of TD, mainly in travelers returning from Mexico. Other pathogens implicated in TD include Vibrio parahaemolyticus, especially in Japanese travelers to Asia, Aeromonas hydrophila, Yersinia enterocolitica, and Vibrio cholerae (non-01). Nonbacterial pathogens can also cause TD, especially rotavirus and Norwalk-like virus, and parasitic infections such as Giardia lamblia, Entamoeba histolytica, Cryptosporidium, Balantidium coli, and Strongyloides stercoralis. Approximately 40% of all international adoptees develop an upper respiratory tract infection within the fi rst month after arrival to the United States. Of particular signifi cance is the newly described coronavirus responsible for the severe acute respiratory distress syndrome (SARS). In the United States, the fi rst pediatric case of SARS was diagnosed in an infant adopted from China. The rates of tuberculosis found in international adoptees are 8 to 13 times higher than in American-born children. Approximately 19% of international adoptees are diagnosed with latent tuberculosis. However, active disease is infrequently diagnosed. The prevalence of active hepatitis B in international adoptees ranges from 1% to 5%, with higher rates seen in children adopted from Asia, Africa, and countries from Central and Eastern Europe, such as Romania, Russia, and Ukraine. With the exception of Romanian-born children, the prevalence of hepatitis C virus (HCV), HIV, and congenital syphilis in international adoptees is low. Intestinal parasites are a common and frequently asymptomatic infection in international adoptees. A wide variety of pathogenic intestinal parasites can be identifi ed in their stool samples: Ascaris lumbricoides, Ancylostoma duodenalis, Necator americanus, Blastocystis hominis, E. histolytica, Giardia lamblia, Hymenolepsis nana, S. stercoralis, Schistosoma species, Taenia solium, and Trichiura trichuris. Refer to specifi c diseases, for example, malaria, typhoid and paratyphoid fever, and gastrointestinal infections, and to specifi c pathogens of interest, such as enterotoxigenic E. coli, Shigella species, C. jejuni, E. histolytica, V. cholerae (non-01), and S. stercoralis. Refer to specifi c diseases, for example, hepatitis, syphilis, HIV, and tuberculosis, and to specifi c intestinal parasites. Important aspects to consider when assessing a febrile child after returning from an international trip include the time of onset, duration and pattern of fever, and associated symptoms. For example, international travelers with P. falciparum malaria frequently develop symptoms within 30 days after their return but might be afebrile at the time of clinical evaluation. The onset of fever is usually abrupt and is commonly associated with chills; however, few children with malaria present with the classic description of tertian fever. Many infections initially present with fever and no other signs or symptoms. Children presenting with undifferentiated fever should be evaluated for the possibility of malaria, enteric fever (typhoid fever, caused by Salmonella typhi, and paratyphoid fever, caused by Salmonella paratyphi), and amebic liver abscess. If signs and symptoms of bacterial sepsis are present, such as hypotension and leukocytosis, other common pathogens should be considered. More frequently these are Staphylococcus aureus and Neisseria meningitidis. Less common infections that could manifest as an undifferentiated fever include tularemia, leptospirosis, and rickettsial diseases. Dengue fever, HIV, Epstein-Barr virus, cytomegalovirus, infl uenza virus, and hepatitis virus can commonly present with fever and nonspecifi c symptoms, such as headache and malaise. Plague, Lassa fever, anthrax, diphtheria, rabies, and African trypanosomiasis are rare tropical infections; however, because of their associated morbidity and mortality, as well as public health implications, they should be always considered if the history is consistent with a potential exposure. When children returning from abroad develop fever and more specifi c symptoms, information provided by a detailed history and clinical assessment will guide the need for further laboratory evaluation. For example, patients with fever and hemorrhagic manifestations require prompt assessment for meningococcemia, leptospirosis, plague, and different viruses associated with hemorrhagic fever. Because bacterial infections and some viral hemorrhagic fevers are treatable and transmission should be prevented, evaluation, empirical therapy, and isolation measures should be instituted promptly. Children with altered mental status, headaches, stiff neck, and neurologic fi ndings should be evaluated accordingly. Infections associated with central nervous system involvement include pathogens with usually mild neurologic manifestations, such as malaria, dengue, and typhoid, ranging to many others that can result in serious sequelae, for example, Streptococcus pneumoniae and some of the arbovirus infections. Uncommon but treatable infections seen in returning travelers associated with neurologic manifestations include brucellosis, tuberculosis, leptospirosis, Q fever, rickettsial infections, and bartonellosis. Systemic infections such as dengue fever, malaria, and amebic liver abscess can manifest as a febrile diarrheal illness. Traveler's diarrhea, defi ned as the passage of more than three unformed stools in a 24-hour period, can present with systemic symptoms as well, including fever, chills, emesis, and abdominal pain. Refer to specifi c diseases, such as hepatitis B and C virus, tuberculosis, HIV, and syphilis, and to specifi c intestinal parasites. The differential diagnosis of fever in returned travelers is broad. A list of infectious diseases associated with each clinical syndrome is listed in Box 34-1. Statistically, a common condition is more likely than an exotic tropical disease. However, knowledge of the incubation period of endemic infectious diseases prevalent in each region can help limit the differential diagnosis and unnecessary laboratory evaluation (Box 34-2). When assessing children returning home after international travel, pediatricians should be aware of host factors and activities, as well as geographic, seasonal, and cultural factors that determine specifi c risks for acquiring particular infections. Individual host factors include the age of the patient, which determines the likelihood of independent activities and risk behaviors that could potentially increase their risk of exposure, underlying conditions, previous immunizations, and Children returning from their journeys and who are well rarely need assessment. However, when a child is sick after returning from an international trip, prompt evaluation is necessary to identify infections that could be life threatening, treatable, or transmissible. The presence of fever in returning travelers requires prompt and careful evaluation. An algorithm for the initial evaluation of fever in returning travelers is presented in Figure 34 -1. A detailed history and physical examination will determine the differential diagnosis • What is likely based on personal history and activities, as well as geographic, clinical, and laboratory information? • A complete history, physical, and laboratory evaluation is critical in the initial assessment of returning travelers. • Is this a locally acquired infection? Illness may be unrelated to exposures during travel. • Is this a rare tropical disease acquired abroad? Infections acquired abroad can include common cosmopolitan diseases. • Is malaria possible? Always consider malaria in febrile patients returning from malaria endemic areas, even in the following cases: • Patients are afebrile during your assessment. • Patients returned from the endemic area months or even years earlier. Keep in mind the incubation period for each endemic infectious disease before including them in your differential diagnosis. • What is possible based on the place of exposures? Access electronic networks to fi nd updated information regarding recent outbreaks and regional health information. • What are the public health implications of this illness? • Isolation techniques • Public health reporting • Contact prophylaxis and ultimately the appropriate steps of the workup that should be though carefully using all available information. In most cases, travelers with potentially lifethreatening and rapidly progressive infections present within a month of their return. Patients with a history of fever and/or chills must be evaluated for malaria if by history there is a potential risk of exposure, even if the patient is afebrile and well at the time of clinical evaluation and/or had received appropriate chemoprophylaxis. Breakthrough malaria infections Figure 34 -1 Algorithm for evaluation of fever in returning travelers. Consider hemorrhagic fevers based on clinical manifestations such as mucocutaneous and/or gastrointestinal bleeding, hematuria, and/or anemia. Consider malaria if epidemiologic risks are present. Antimalarial empiric therapy should be considered for acutely ill children returning from endemic areas. Common clinical manifestations of P. falciparum malaria in pediatric patients include seizures, hypoglycemia, lethargy or coma, and hyperpyrexia. Additional end organ damage can be present, such as respiratory distress, hypotension, and renal dysfunction. When clinical manifestations are not consistent with hermorrhagic fevers and there are no epidemiologic risks for malaria, approach to differential diagnosis has to be considered based on history, physical examination, and initial laboratory testing. after receiving appropriate chemoprophylaxis occur infrequently. For nonacutely ill travelers, an initial laboratory screening is outlined in Box 34-4. The initial history and clinical assessment should guide the need for additional testing. For example, chest radiographs should be obtained in returned travelers with respiratory symptoms, or in those with unexplained and persistent fever. Occasionally, a bronchoscopy might be needed if a fi nal diagnosis cannot be achieved and symptoms persist. Tuberculosis is rare in travelers with short stay in developing countries, but is more prevalent after long-term exposure, and skin testing should be considered. Travelers with abdominal pain and/or jaundice will require liver enzymes, amylase, stool examination, and possible abdominal radiographs, or liver ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) and serologic evaluation for viral hepatitis. Fever and skin lesions might require scraping and/or biopsy. Patients with neurologic symptoms will need a head CT scan or MRI scan and lumbar puncture with opening pressure and examination of cerebrospinal fl uid for cell count, protein, and glucose measurements, as well as culture, serology, and polymerase chain reaction (PCR) for specifi c pathogens. Evaluation of TD includes stool culture for Salmonella, Shigella, Campylobacter, and E. coli 0157:H7. Giardia and cryptosporidium antigens should also be tested. For symptomatic patients with TD, fl uid management is vital to avoid dehydration. Children who develop TD associated with fever, nausea, vomiting, abdominal cramps, and/or blood in the stools may benefi t from antibiotic therapy that will effectively shorten the duration of symptoms to 1 or 1 1 ⁄ 2 days. Trimethoprimsulfamethoxazole (TMP-SMZ) is an effective antibiotic in TD, although it might not be useful in areas where resistant strains of Shigella and Salmonella species are prevalent. The recommended dose is 4 to 5 mg trimethoprim/ kg per dose, twice a day for 3 to 5 days. Azithromycin is effective against Shigella and Campylobacter and is well tolerated in children. The recommended dose is 10 mg/ kg the fi rst day, followed by 5 mg/kg on 4 subsequent days. Doxycycline and ciprofl oxacin, extensively used in adults with TD, are not approved routinely in pediatric patients. Furthermore, doxycycline can be associated with severe photosensitivity reactions and should be avoided. In children older than 12 years of age or in children with severe diarrhea who do not respond to azithromycin or TMP-SMZ, ciprofl oxacin or levofl oxacin could be considered because the risk of quinoloneassociated toxicity in children seems to be low. If symptoms persist, further consultation with an infectious disease specialist would be warranted. Internationally adopted children should have a comprehensive evaluation, including age-appropriate screening tests, for visual and hearing impairment, and growth and developmental assessments (Box 34-5). Children should be examined within 2 weeks of arrival to the United States. Testing for infectious disease pathogens should include the following: The most important routine screening test in this group of patients is the HBV profi le. These tests should consist of hepatitis B surface antigen (HBsAg) and antibodies to surface and core antigens. Some experts recommend repeating HBsAg 6 months after the initial evaluation in children with initially negative tests. Children with positive HBsAg should be tested for HBeAg, IgG core antibodies, and liver transaminases to assess the stage of the infection. Antibodies to delta hepatitis virus should be performed in children arriving from regions known to have a high incidence of co-infection, such as South America, Africa, the Middle East, and parts of Eastern Europe and Southern Italy. Hepatitis B vaccination of household contacts should be performed as soon as possible because up to 20% of unvaccinated household contacts can become infected within 5 or more years of exposure. Children with HBV infection should receive hepatitis A vaccine if they have undetectable HAV antibodies and referred to specialty care for further management (refer to hepatitis B for further information). In addition to HBV, international adoptees with risk factor for HCV infection are routinely tested for HCV by either PCR or antibody screening. Risk factors for HCV infection include a history of blood transfusion, elevated hepatic transaminases, and all adoptees arriving from China, Eastern Europe, Southeast Asia, and countries of the former Soviet Union. Routine screening for hepatitis A is not recommended unless the child present signs and symptoms of acute hepatitis. Except for children arriving from China, most internationally adoptees will have a documented HIV testing performed before their immigration to the United States. Because the reliability of these results is uncertain, it is recommended that all international adoptees have repeat HIV testing upon their arrival to the United States and 6 months later to detect seroconversion if exposure occurred before their departure. All internationally adopted children should be screened for tuberculosis using 5 TU of purifi ed protein derivative (PPD or Mantoux skin test). A consideration regarding the use of control antigens such as Candida or tetanus depends on the age and nutrition status of the child. The tuberculin skin test (TST) should be read by a health care professional 48 to 72 hours after inoculation. For children living abroad, the American Academy of Pediatrics indicates that an induration of more than 10 mm should be considered positive, and in children with a household contact with tuberculosis (e.g., orphanages), an induration of greater than 5 mm. International adoptees with a positive TST should have a thorough examination and chest radiograph. Children with latent tuberculosis (positive TST and negative chest radiograph) should complete a 9-month course of isoniazid. Children with evidence of tuberculosis disease should be referred to an infectious disease specialist. Diagnostic and management of intestinal parasites differ in the clinical practice. Although one stool sample for ova and parasites could be suffi cient in the hands of an experienced technician, an appropriate screening should include three stool samples obtained 2 to 3 days apart. Repeat testing is controversial; some experts recommend repeating it if the child has persistent symptoms after appropriate treatment or if other parasites not identifi ed in the fi rst sample are suspected based on clinical and epidemiologic information. Some others recommend performing repeat testing several weeks after treatment to ensure that the infection has cleared. Some immigrant health clinics, using a more cost-effective approach, treat all patients with a single dose of albendazole. Adoptees with diarrhea should also have a stool specimen submitted for bacterial enteropathogens, including Salmonella, Shigella, Yersinia, and Campylobacter. However, bacterial enteric pathogens are seldom isolated in these children, except for adoptees arriving from orphanages in India or Romania. Serologic evaluation for syphilis is mandatory for all immigrants to the United States. Most countries accurately identifi ed children with congenital syphilis, unfortunately, evaluation and management of these patients in many of these countries is inappropriate. International adoptees with a positive Venereal Disease Research Laboratory (VDRL) test result or rapid plasma reagin (RPR) test require prompt and aggressive evaluation to assess the extent of the disease and to provide appropriate antibiotic treatment. Evaluation of international adoptees should include a careful examination of the skin, because a wide variety of common skin infections, such as lice, scabies, and molluscum contagiosum are very common, especially among children living in orphanages. When vaccination records are not available or explicitly documented, antibody titers can be measured to determine whether the child has immunity either through immunization or by infection. When immunization records are available and the source or the information provided is not reliable, there are two possible options to determine the appropriate vaccine schedule. One is to measure antibody titers to immunizing antigens, such as diphtheria, tetanus, polio, hepatitis B surface antigen, measles, mumps, rubella, and varicella. A second approach is to reimmunize independently of the immunization record. Age is an important factor when considering the most appropriate and cost-effective management. In young infants, maternal antibodies to measles and varicella can be present, and thus testing for these should not be performed in children younger than 12 months of age. Measuring antibody titers is more cost effective in older children, who will otherwise require multiple doses of vaccine. Age and the time of the last vaccine are also important to consider when interpreting antibody titer results. Older children could have low titers if they are due for booster immunizations. Children with a history of poliomyelitis should receive complete IPV series, because infection provides protection only against the serotype causing the infection. Parents traveling with children should seek medical advice at least 4 weeks in advance to determine the need for specifi c immunizations and chemoprophylaxis. Preadoption counseling allows parents to clarify misconceptions about potential infectious diseases and feel comfortable regarding subsequent evaluations that the international adoptee will need after arrival to the new family. Between 20% and 70% of international travelers become ill during or after their travel. However, only 1% to 5% of travelers are sick enough to seek medical attention. Traveler's diarrhea (TD) is most common, affecting 20% to 50% of travelers to developing countries. Internationally adopted children are at high risk for infections acquired in their country of origin, representing more than 75% of all diagnoses in these children within the fi rst month of arrival to the United States. Common causes of fever in returning travelers from the tropics include malaria, respiratory tract infections, diarrheal illness, hepatitis, urinary tract infection, dengue fever, typhoid fever, amebic liver abscess, rickettsial infections, mononucleosis, and pharyngitis. Medical evaluation of internationally adopted children for infectious diseases Centers for Disease Control and Prevention: Health Information for International Travel Textbook of Travel Medicine and Health Infectious diseases in immigrant and internationally adopted children Fever in the returned traveler Illness after international travel Hunter's Tropical Medicine and Emerging Infectious Diseases Health information for international travel