This large comprehensive study with country-specific data examined protective antibody levels to vaccine antigens to determine whether internationally adopted children had serologic evidence of protection against vaccine preventable diseases and to determine if documentation of immunization was associated with protective antibody levels. summarizes previously published studies examining immunization verification in internationally adopted children (5–15). The countries evaluated, ages of children studied and laboratory methods used may account for some of the differences seen between studies. Some studies presented data for children with ≥3 doses, without indicating how many additional doses were given [5
]. In order to make direct comparisons with the existing literature, we have presented our data by the specific number of doses as well as by ≥3 doses of vaccine for diphtheria, tetanus, polio, and HBV and ≥1 dose for measles, mumps, rubella, and varicella.
Review of literature of serologic studies to assess protective antibody levels in internationally adopted children.
For diphtheria, the Verla-Tebit
] study found a higher proportion of children (from Russia, China, & Guatemala) with ≥3 doses of vaccine to be protected (95%) compared to 85% in our study. For tetanus, they reported a lower proportion protected (87%) compared to ours (95%) which may be due to the different definitions of protection that were used (>0.50 IU/mL compared to ours >0.10 IU/mL). Similar to our data, two previous studies [11
] detected an increase in protective antibody with additional number of doses for diphtheria and tetanus.
There were major differences in our polio results compared to other published studies. We found high levels of the proportion protected overall (90%) and by each serotype (93–95%) using a definition of protection of ≥1:8. The overall proportion protected ranged from 50% to 86% in other studies [6
]. When we analyzed our data using a titer of ≥1:32 to compare to the Verla-Tebit
] which used ≥1:40, we still had higher levels of overall protection (84%) and to serotypes 1–3 (87%, 93%, and 90%, respectively) compared to their study which had 58%, 82% and 52% with protective antibody for serotypes 1–3, respectively. One possible explanation for the lower immunity in other studies is that complement fixation testing may have been inadvertently performed in some studies. This may have occurred without the knowledge of investigators since most commercial laboratories offer both tests.
The results of HBV testing are difficult to compare to other studies since many did not provide dose-specific data. For children with ≥3 doses of vaccine, we found the proportion protected in our study was slightly higher (77%) compared to Saiman
]. Without regard to number of doses, our population had lower rates of protection (60%) compared to the children in the Cilleruelo
study (76%) that took place during similar time periods as ours [11
]. In the Verla-Tebit
study, 94% of children with ≥2 doses of vaccine were protected [12
]. One explanation may be that many children in that study may have had 3 or more doses of vaccine. While it is not entirely clear why our study and others have reported a lower than expected proportion of children with protective antibody compared to vaccine trials, one explanation may be due to waning immunity as evidenced by the difference we saw in children with longer intervals from the last vaccine dose to testing and boosting seen in those children who received an additional dose and repeat testing. Also in our study, we found no association with lack of protection and receipt of the third dose prior to 6 months of age.
To our knowledge, our study provides the first data on Hib antibody in internationally adopted children. While there is controversy over the serologic value that should be used as a cut-off to define protection, we included this vaccine antigen in our study to better understand whether internationally adopted children had adequate levels of protection. Only 24% of children evaluated had documentation of Hib vaccination. Using the two different proposed definitions of protection (≥1.0 and ≥0.15 IU/mL), 66% and 74% of children with 3 doses had protection, respectively while 20% and 43% without documentation had protection. The reason for a lower than expected level of protection with three doses could not be determined in our study, however studies have shown that children with different ethnic backgrounds, such as Native Americans may have a decreased immune response to Hib vaccine [27
]. Given a large proportion of children immunized with Hib were Guatemalan children, this may have played a role in the decreased immune response. In children ≥5 years of age with no history of immunization, 85% had evidence of Hib protection using the ≥0.15 value. Currently, it is not recommended that children ≥5 years of age be vaccinated, since it is assumed most children are immune and there is widespread vaccination in the US [2
]. However, with recent outbreaks in the US, children without documentation of Hib immunization or immunity may benefit from receiving one dose of Hib vaccine upon arrival to the US [36
In our study, most children had documentation of measles immunization, and in contrast to other studies, we found that the majority of children with one or two doses of vaccine were protected [6
]. In addition, measles protection increased with age regardless of vaccine history, suggesting that many children had prior infection with wild-type measles or had undocumented immunizations. Thus, the higher protection seen in our study could be due to age differences between the study populations or in other studies, the inclusion of children tested <12 months of age. Even though only a small proportion of children had documentation of mumps or rubella vaccine, many children had evidence of immunity and even in those with documentation, immunity increased with age.
Very few children had documentation of varicella immunization. Even in those who did, few had evidence of immunity. The lack of protective antibody may be due to problems with difficulty in maintaining cold chain vaccine storage. A history of varicella disease was associated with protective antibody, and that protection increased with age.
Some limitations should be considered in interpreting our findings. While our study had a large sample size, there were still small numbers for many countries and regions. In addition, in recent years the demographics of international adoption have changed with more children adopted from Ethiopia and other African countries. It will be important for future studies to assess whether children from countries not included in large numbers in our study have similar findings. We also could not determine whether protective levels of antibody were due to immunization, infection with wild-type disease or boosting from natural disease. Also, for polio, children with protective antibody, regardless of immunization documentation, could have been infected or boosted their immune response with vaccine-type polio virus exposure.
Our study found serology to be a useful tool for verifying a child’s protection against vaccine-preventable diseases. In our population of internationally adopted children, the proportion of children with protective antibody in our study was fairly comparable to expected protective antibody levels after a primary series for tetanus [20
] (96% versus 100%) and polio [22
] (91% versus 100%) and after one dose of measles [30
] (94% versus 95%) and rubella [37
] (94% versus >90%) vaccines. Children in our study had slightly lower levels of protection compared to expected levels with a primary series for diphtheria [17
] (87% versus 96%), hepatitis B [25
] (77% versus 95%) and one dose of mumps [32
] (77% versus >95%). Protective antibody levels were much lower than expected for a primary series of Hib vaccine [27
] (67% versus >95%) and one dose of varicella vaccine [35
] (38% versus >95%). There are several reasons why lower than expected levels of protection were seen in our study. These expected levels of protection result from vaccine trials, under ideal, controlled conditions with a specific interval for testing from the last documented dose of vaccine. Antibody levels in these conditions would be optimal, and it would be expected that in field conditions the antibody levels would be somewhat lower. For varicella, the most likely explanation for the very low levels of protection is due to the inability to keep the vaccine at the appropriate temperature [35
Administering unnecessary vaccines to internationally adopted children increases the number of visits and may negatively impact the transition for these children [38
]. Since screening tests are recommended for all internationally adopted children, serologic testing for vaccine antibodies can be performed at the initial visit to guide immunization decisions for those without a complete immunization record. However, given the high proportion of protective antibody levels in children with documentation of immunizations, a reasonable approach would be to consider birth country vaccine doses to be valid, similar to the recommendations for other immigrants [2
] and to complete the series as appropriate for the child’s age. If serologic testing is done and protective antibody levels are found for diphtheria, tetanus, polio, Hib or HBV, children should still complete the immunization series for that vaccine according to their age if additional doses of vaccine are recommended. Given the high proportion of protection in children without vaccine documentation, serologic testing to verify immunity should be done to determine which immunizations, if any, are needed. Additional studies to examine the cost-effectiveness of different strategies for immunization decisions in internationally adopted children should be considered while taking into account the medical and psychological affects of administering unnecessary immunizations.