Infectious Diseases after Arrival in the United States
Human Immunodeficiency Virus Infection (HIV)
Many internationally adopted children come from countries with high rates of HIV infection. To date, however, very few adoptees have arrived in the United States with this disease.2 In seven studies describing a total of 1089 children adopted to the United States, Australia, and France, no child with HIV infection was identified, although three had transient antibodies to HIV.18–24 An informal multicenter survey of 7299 adopted children evaluated in 17 international adoption clinics between 1990 and 2002 found only 12 infected children (0.16%, from Panama, Russia, Cambodia, Romania, and Vietnam).25 The actual proportion of HIV-infected children is likely somewhat less, as this survey included only children who were evaluated in specialized clinics. The reason for the low rate of infection may reflect accurate preadoptive testing in the birth countries (thus only seronegative children are placed) and low risk of acquisition in orphanages or foster care. However, a recent outbreak of HIV in orphanages in Kazakhstan highlights the risks of exposure.26 Serologic testing (ELISA) for both HIV-1 and HIV-2 is recommended for all children at arrival in the United States, and again 6 (or more) months after arrival.4 Some27 but not all15 experts recommend PCR testing for HIV DNA for new arrivals younger than 6 months of age at arrival.
International adoption and other types of immigration are now the most common sources of children in the United States with hepatitis B infection.28 In a recent survey by the Centers for Disease Control and Prevention, adoptees from China, Bulgaria, Russia, Phillipines, Ukraine, and Vietnam accounted for 32% of young children reported with hepatitis B infection.29 Worldwide, about 2 billion people—one-third of the world's population—have present or past evidence of infection with hepatitis B. Nearly 75% of infected people reside in Asia.30 The 350–375 million with chronic infection have approximately 15–25% risk of dying from hepatitis B virus-related liver disease, including end-stage cirrhosis and hepatocellular carcinoma.31,32 The four serotypes (adw, ayw, adr, and ayr) and seven genotypes (A to G) of the hepatitis B virus show distinct geographic distributions; these relate to clinical outcomes and responses to drug treatments.31,33,34 Universal hepatitis B vaccination of newborns was established in only 54% of countries worldwide as of 2000, representing approximately one-third of the global birth cohort.35 By 2003, 72% of “high prevalence” nations had universal infant vaccine programs.32
Hepatitis B screening is nearly universal for children prior to placements in international adoptions. With few exceptions (sibling groups, identified special needs), only seronegative children are considered eligible for adoption. Despite negative serological tests in the country of origin, consistently about 3–5% of new arrivals have hepatitis B infection.18–24,36 Some series report slightly higher rates of 5–7%.6,37 The discrepancy between test results in the birth country and those obtained after arrival has been attributed to inaccurate laboratories or infection acquired after testing was completed. Children awaiting international adoption often receive multiple injections; infection rates in some orphanages have been high (35% or more in some orphanages in Romania in the early 1990s7,38). Unfortunately, reuse or improper disposal of needles remains a widespread practice in many parts of the world.39 A recent World Health Organization study found that nearly one-third of injections in developing countries were administered using unsterile equipment; in parts of the Middle East and Asia, this figure rose to 75%.40
Because of these risks, prospective adoptive families must be counseled on the risks of household transmission of hepatitis B41–45,46 and preferably be fully immunized before travelling to receive their new child. Adoption of a child with hepatitis B is well recognized as a source of infection within the family, with transmission rates as high as 64%.45 In a recent study of 124 unvaccinated Dutch expatriates residing in Nigeria, nearly 10% of the adults and 13% of children acquired hepatitis B infection.47 Risk of hepatitis B infection was associated with adoption of a Nigerian child and the duration of time the child had resided with the family. Extended family and community members are also at risk of acquiring infection. For example, nearly all unvaccinated parents of 31 hepatitis B-infected international adoptees in Belgium as well as a teacher, grandfather, and teenage family friend became infected, although few individuals reported blood or body fluid contact with the infected child.7
A history of vaccination in the adopted child does not insure absence of hepatitis B infection. Only approximately 70% of children who received 3 doses of hepatitis B vaccine in their birth countries had detectable antibody,37,48 while 13% of previously vaccinated adoptees had hepatitis B core antibody, reflecting prior infection.37
Because of these risks, vaccination of family members prior to adoptive placement is urgently recommended. Although most families have adequate time to receive hepatitis B vaccine using the conventional schedule (0, 1, 6 months), occasional families may need an accelerated schedule. Three vaccine doses administered over 3–4 weeks (at 0, 7, and 21 days) induces immunity in more than 75% of adults by 2 months and in 90% by 1 year; a fourth dose (administered 12 months later) for long-term immunity is usually suggested.40 If needed, this schedule is also successful in inducing immunity in children.49 Immunity appears to be long-lasting (at least 10 years) for most individuals. High-risk individuals (family members of infected children) should be tested for antibody titers at intervals and offered booster shots if the titer falls below 10 mIU/mL.31
Newly adopted children should be tested at arrival and again 6 months later (HBsAg, core Ab, and sAb).2,6,15 The “hepatitis panel” (HBsAg, IgM core Ab) offered by some commercial laboratories is inadequate. Documentation of surface antibody status is useful to assess the need for additional hepatitis B vaccination (although its presence in infants may reflect maternal antibody and not denote long-lasting immunity). Children found to have HBsAg should undergo additional testing, including liver function tests (ALT, AST, bilirubin, alkaline phosphatase, albumin), HBeAg, HBeAb, α-fetoprotein, and quantitative viral HBV DNA by PCR, and be immunized against hepatitis A (if not immune). Isolated HB core Ab may indicate that the individual is recovering from acute HBV infection, distantly immune with nondetectable levels of HBsAb, has a false-positive core Ab (IgG or polyclonal core Ab may represent maternal antibody in infants), or has a false-negative HBsAg (actually a carrier). These individuals should be retested for liver transaminases, HBsAg and HBsAb (and HBV DNA by PCR) within 1–2 months. Liver ultrasound and consultation with a gastroenterologist are recommended for children with elevated transaminases and/or persistent HBsAg.
Many international adoptees acquire hepatitis B via vertical transmission. A recent study of perinatally infected children of varying ethnic groups found that ∼30% develop anti-HBe during ∼10 years of follow-up, while <5% clear hepatitis B sAg during this period.50,51
Rare circumstances associated with hepatitis B infection, including infection with viral mutants (altered S gene protein, resulting in “surface antigen negative disease”) or superinfections with >1 genotype have not yet been reported in international adoptees. However, some have speculated that early malnutrition may promote severe disease expression.52
Hepatitis C infection is rare among international adoptees (∼1%).5 However, the presence of hepatitis C antibodies is noted on many medical reports of prospective adoptees from Russia (most other countries do not screen for this infection). These usually represent maternal antibodies; some of these mothers likely acquired hepatitis C infection via injection drug use (thus indicating a possible adverse prenatal exposure for the child). Results of RNA PCR testing in Russian specialty laboratories may be offered for some of these children; results should be interpreted with caution, as reliability of these tests may be uncertain even under the best conditions. Qualitative PCR tests in the first 6 months of life have relatively poor sensitivity in identifying infection.53 Even between 9 and 15 months of age, infected children may have negative PCR tests as a result of fluctuations in viremia or technical issues related to the assay.
As with hepatitis B, long-term carriage of hepatitis C increases the risk of hepatocellular carcinoma (∼1.9–6.7% of patients after 20 years of disease54). Acquisition of infection via vertical transmission may reduce the risks of long-term carriage55 although this is controversial.56 Ethnic differences contribute to the development of hepatocellular carcinoma, with Asians, Hispanics, Native Americans, and Pacific Islanders noted to have the highest incidence.54 Coinfection with hepatitis B or HIV also increases the morbidity of HCV infection.
All newly adopted children should be screened for hepatitis C. Because false-negative tests may occur early after infection, children should be retested 6 or more months after arrival.57 Infected children should be referred to a hepatologist for consideration of drug treatment (e.g., pegylated interferon-ribavirin or other combinations) and ongoing management.
Screening for hepatitis A in new arrivals has not routinely been recommended. However, one report has highlighted the risks of hepatitis A not only in new arrivals and their household contacts, but also non-household contacts (e.g., short-term visitors to the child's home).57A Among the 27 cases of hepatitis A reported in this outbreak, 19% were adoptees, 7% were unvaccinated travelers, 48% were non-traveling contacts of the adoptees, and 26% were non-traveling contacts of the adoptees. Thus, hepatitis A screening should now be considered routinely in new arrivals.
International adoptees have multiple risk factors for infection with Mycobacterium tuberculosis, including birth in countries with high prevalence of tuberculosis, poor access to health care, residence in institutions where caregivers may not be screened for tuberculosis infection, young age, and malnutrition. Fortunately, few children arrive with active disease. In those with active disease, extrapulmonary (especially lymphadenitis Figure 68–2) is more usual than pulmonary disease. Latent tuberculosis, however, is relatively common. Most series report latent tuberculosis infection (positive tuberculin skin test [TST], no clinical disease) in approximately 5–20% of new arrivals.5 Children from Russia and Ukraine appear to be at higher risk for this infection.24,37 In a recent report of internationally adopted children in Italy, 30% of non-BCG vaccinated children had latent tuberculosis infection.37 It is vital to recognize that latent disease may activate, especially in young children, creating a public health hazard. An outbreak of tuberculosis affecting 56 people in a small town in North Dakota was traced to a child adopted from the Marshall Islands.58
Axillary lymphadenopathy in a child with tuberculosis.
TSTs should be placed on all internationally adopted children after arrival and again 6 months later. There are many potential pitfalls in diagnosis. False-negative TSTs may result if the test is placed within 4–6 weeks of live virus vaccine administration (for example, MMR or varicella), if the child is malnourished, very young, immunosuppressed, has a concurrent viral or bacterial infection, or was recently exposed to tuberculosis.4 False-positives most commonly result from prior BCG vaccination or infection with nontuberculous mycobacteria.
Most international adoptees receive BCG vaccination in their birth countries. When properly administered, the BCG vaccine leaves a small scar over the deltoid muscle. Cross-reactivity between purified protein derivative and BCG usually wanes by 6–12 months of age59–61 when the vaccine is given in early infancy. TST is recommended for newly arrived adoptees regardless of the child's BCG status15,62; results are interpreted without consideration of prior BCG vaccination. Reactions ≥10 mm are considered positive. In these children, chest radiographs should be obtained, along with careful physical examination for signs of tuberculosis disease. If these investigations are negative, then the child is considered to have latent infection and prophylactic treatment with isoniazid for 9 months is recommended. Reactions in the 5–9-mm range warrant careful evaluation and follow-up, some experts recommend chest radiographs and consideration of prophylactic treatment as recent exposure cannot be excluded.6,63 Because of the prevalence of multiple-drug resistant tuberculosis in many of the countries of origin of international adoptees, consultation with an infectious disease specialist should be obtained in any child with suspicion of active disease.
A new class of diagnostic tests, interferon-γ release assays, has recently been developed to improve specificity and sensitivity over the century-old TST. To date, these tests have not been adequately studied in children, especially among high-risk populations, and their utility in the diagnosis of latent TB infection is not yet well understood.64–66 A recent report suggests this test is less sensitive than TST.67 However, such tests may aid in diagnosis in the future and may be especially valuable in BCG-vaccinated children. These tests are discussed further in Chapter 36.
Some clinicians have recommended chest radiographs for all new arrivals as a means to identify children with tuberculosis infection. A recent survey of approximately 1600 international adoptees in the Netherlands found that routine chest radiography yielded new information in only 2% of cases. Furthermore, false-positive results (findings with no clinical significance) occurred in more than 3% of children. Therefore, routine chest radiography rarely modifies management but may result in additional and unnecessary testing of children with false-positive results.68
Approximately 25% of newly arrived international adoptees have intestinal parasites. The prevalence varies depending on country of origin—infections are common in children from Eastern Europe, South Asia, and Africa but rare in children from South Korea.4,19,20,22–24,36,69,70Giardia intestinalis is the parasite most frequently identified; 8% of international adoptees in Sweden had this infection, with risk per 100,000 children ranging from 0 to 50,000.71 Some children have persistent or difficult-to-treat infections. Options for eradication include repeating treatment with metronidazole (longer duration or higher dose), or administering alternative agents such as furaxolidone, tinidazole, quinacrine, albendazole, or nitazoxanide.5 Other parasites are often found, including Entamoeba histolytica, Dientamoeba fragilis, Ascaris lumbricoides, Trichuris trichuria, Hookworms, Hymenolepsis nana, Strongyloides stercoralis, and others. Some children have multiple parasites. Organisms such as Blastocystis hominis, Entamoeba coli, Entamoeba hartmanni, Entamoeba polecki, Entamoeba dispar, Cryptosporidium, Microsporidium, Cyclospora, Isospora, Iodamoeba buetschlii, and Endolimax nana are usually considered nonpathogens and do not require treatment.
Symptoms of infestation include diarrhea, flatulence, odoriferous stools, abdominal pain, failure to thrive, and anemia. However many children are asymptomatic.4 Impaired neuropsychiatric function (unrelated to anemia) has been attributed to parasitic infection, with improved cognition after treatment.72–75
All newly arrived children should be screened for intestinal parasites. Three samples are recommended to improve detection rate4; immunoassay of giardia antigen alone is inadequate. Follow-up samples should be obtained after treatment to verify eradication and to screen for additional parasites. Parasites are sometimes missed in initial stool screening; retesting is advisable if later symptoms appear.2 A recent survey of intestinal parasites in immigrant children included serologic tests for Strongyloides (positive in 1%, equivocal in 10%) and Schistosoma (positive in 2%).76
Only some parasites induce eosinophilia (especially hookworm, Strongyloides, Ascaris, and Toxocara). Children with unexplained eosinophilia after initial stool screening should be reevaluated, and less common parasitic causes of eosinophilia considered (filariasis, schistosomiasis, cutaneous larva migrans).77 Specific serological testing is available for schistosomiasis, strongyloidiasis, filariasis, echinococcosis, and toxocariasis. Even mild eosinophilia may indicate a pathogenic parasite: evaluation of Southeast Asian immigrants with eosinophilia and negative stool examinations eventually revealed a pathogenic parasite in 95%, most commonly hookworm, Strongyloides, or E. histolytica.78 In children with persistent eosinophilia and no obvious diagnosis, empirical treatment with a broad-spectrum antihelminthic is reasonable.77 Options include mebendazole, pyrantel, or albendazole,79 although the first two are not effective for strongyloidiasis, tapeworm, or schistosomiasis. Other explanations should be sought if the eosinophil count does not return to normal.79 Current treatment guidelines for parasites are available in the Red Book15 and other sources.80,81
Bacterial Enteric Pathogens and Helicobacter Pylori
Bacterial enteropathogens (Salmonella, Shigella, Enteropathogenic E. coli, or Campylobacter) are relatively uncommon in newly arrived adoptees, but children with diarrhea, flatulence, and abdominal pain should be tested for these infections and treatment given to prevent disease transmission.
Some children arriving from orphanages are infected with H. pylori.82 This organism can cause diarrhea, growth faltering, anemia, dyspepsia, and malnutrition.83 Stool antigen testing for H. pylori in young children is both sensitive and specific.83,84 Some strains acquired in the developing world are resistant to usual drug therapies (e.g., amoxicillin and clarithromycin).85
Most—but not all—internationally adopted children are screened for congenital syphilis in their birth countries.5 Medical records provided at the time of adoption indicate that approximately 15% of children adopted from Russia have a history of congenital syphilis. Details of treatment are rarely provided, however, these children virtually all have negative rapid plasma reagin (RPR) tests on arrival in the United States. Characteristic dental malformations are sometimes seen even when adequate treatment has been provided. Other medical or neurologic complications have not yet been reported in this group of children. Rarely, children arrive with unrecognized, untreated congenital syphilis, or even more uncommonly, with syphilis resulting from sexual abuse. Thus, all children should be tested upon arrival with a nonspecific treponemal test, such as RPR. If this is negative and the child is asymptomatic (and sexual abuse is not suspected), then no additional testing is needed. Children with prior treated congenital syphilis should have careful clinical evaluation and follow-up RPR testing at 1, 2, 4, 6, and 12 months of age. Ophthalmologic and audiologic evaluations should be obtained, as well as screening for neurologic and developmental disorders.5,6
Children with positive RPR tests or physical findings consistent with syphilis should have confirmatory treponemal tests (MHA-TP or FTA-ABS), lumbar puncture (if there is consideration of neurosyphilis86), dark-field examination of body fluids (such as nasal discharge), long-bone X-rays, as well as vision and hearing tests. After successful treatment, nontreponemal antibody titers become nonreactive over time, while treponemal tests remain positive for life.6 Detailed recommendations for management of children with positive screening serology on arrival may be found in the Red Book.15
Skin infections such as scabies, pediculosis, ringworm, impetigo, and molluscum contagiosum are relatively common in new arrivals, and may spread readily within the new household. Scabies should be suspected in almost any pruritic rash appearing within several weeks of arrival; response to treatment is often diagnostic.
Malaria and Unusual Infections
As the number of adoptions from Africa has increased (>3000 in past 10 years), concerns about malaria and other tropical diseases has risen. Splenomegaly, anemia, and thrombocytopenia at arrival should prompt consideration of malaria. Some experts suggest routine malaria screens (thick and thin blood smears) for any child adopted from an endemic area. Maps showing malaria risks are readily available online.13,30,87,88 In a survey of Liberian children immigrating to Minnesota, 65% had positive malaria smears, one-third were completely asymptomatic, and one-third had splenomegaly only.78 Children from India and South Asia may also be at risk for this infection.36
The global epidemic of SARS (severe acute respiratory syndrome) in 2003 serves as a vivid reminder of the potential role of newly arrived adoptees as vectors for transmissible diseases. Although none was laboratory-confirmed, 17 adoptees from China and their family members were investigated as “suspect” or “probable” cases.
Other tropical diseases remain rare (e.g., tungiasis,89 leprosy,36 gnathostomiasis90). Several cases of Pneumocystis jiroveci (formerly P. carinii) pneumonia5,91,92 and one case of fatal measles-related subacute sclerosing panencephalitis have been reported.93 Recently, international adoptees were found to be a source for methicillin-resistant Staphlyococcus aureus.94