Our study is the first to systematically collate and analyze data regarding international CT notifications for TB at a nationwide level in Germany and is, to the best of our knowledge, the first of its kind for TB worldwide. Between 2010 and 2018, RKI received notifications from 23 different countries, involving 192 TB index cases and a corresponding 771 contact persons. International CT notification steadily increased in number over the study period, from 12 in 2010 to 41 in 2018; this likely corresponded to an increase in global air traffic, but perhaps also increased awareness and communication regarding TB. The majority of the notifications (N=130, 67.7%) concerned exposure to an index case with active TB during long-distance air travel, accounting for 514 (60.0%) identified contacts during the study period. However, compared to an overall LTBI prevalence of 28% among investigated contacts of active TB cases in all settings in high-income countries , the transmission risk of TB infection in aircraft, at 0.1-1.3% , is substantially lower due to the use of “High Efficiency Particulate Air” (HEPA) filters, which completely exchange air 15 to 30 times per hour .
164 (85.4%) of the 192 international CT notifications were initiated by developed countries, potentially indicating the presence of more resources to perform CTs. Indeed, CT is not a prioritized area of TB prevention in many resource-limited settings and well-defined standards of CT procedures and clear definition of roles and responsibilities are lacking . We cannot exclude the fact that our investigation, similar to a number of previously published CT investigations, is biased towards data from high-resource countries. This means that such analyses often may not reflect the true picture of potential exposures to TB during international air travel. When assessed together with the overall low risk of transmission within aircraft for TB, the resource-intensive nature of international CT following long-distance air travel, and the many potential missed occurrences of travel of infectious active TB cases on flights (occurrences that are frequently never identified), the necessity and practicality of routine CT following air travel can be brought into question.
The need for better physician and patient awareness around public travel and infectious protection measures for TB is reinforced by the fact that, in our study, 114 of the 192 index cases were considered to have been infectious during contact. Of these, 12 cases were diagnosed with drug resistant TB, which further increases the risk of spread of drug resistant TB strains. Although international guidelines state that confirmed TB cases should completely avoid air travel or, if unavoidable, wait until at least 2 weeks of treatment has been received and evidence for clinical improvement can be identified [6, 27], our analysis revealed that 7 index cases, including 2 with MDR-TB, were diagnosed with TB prior to their long-distance flights. Such events once again underline the need for physicians to better inform TB patients to either avoid commercial travel, use alternative private transportation or, if no alternative is available, to have a safety protocol established by the national public health authority and the airline, in order to decrease transmission risk of TB [3, 27]. Such events also underline the need for patients to be better informed regarding the risk public travel poses for other individuals during the infectious disease period for TB.
Our analysis revealed 32 (4.2%) children who were identified as contacts of index TB cases, the majority of whom (18, 56.3%) were exposed during private contact. Children are a vulnerable group who display unspecific symptoms of TB disease, leading to a delayed diagnosis that often occurs when the disease had already progressed to serious stages, increasing the risk of TB-associated death in children [7, 29]. As a result, timely CT plays an important role in the prevention or detection of childhood TB and the reduction of TB-associated childhood deaths. In 2017, almost 50% of all child TB cases in Germany were found through active case-finding via CT, in contrast to 4.0% of all adult TB cases . Despite this well-known impact of CT in the prevention of childhood TB, 5 children in our study could not be investigated due to lack of adequate contact information; 3 of these children had contact with a drug-resistant index case, which makes the inability to contact the children or their guardians even more serious.
A key finding of our study was the large difference in the completeness of data reported in the international CT notifications. 17.2% of all CT notifications did not contain information on microscopy smear testing for the index cases and 43.3% of all notifications were missing information on chest radiograph results. Moreover, in 38.0% of the notifications, no information on DST results was reported. All of these are key for assessing infectiousness and seriousness of TB disease, and, therefore, also important for assessing the need of CT. DST results are further important for the provision of preventive therapy or chemoprophylaxis, especially in children, should contacts who test positive for LTBI be identified during the CT procedures. When assessing the completeness of information according to RKI’s risk assessment algorithm, only 11.5% of the 130 air travel-related notifications included information on all RAGIDA criteria. For the DZK guidelines (non-flight exposure), only 16.1% had information on cumulative duration of exposure and either smear microscopy results or laboratory culture results for the index case. In addition to missing clinical information, some CT notifications contained insufficient or no information on the contact details or address of the identified contact persons.
As a result, international standards for the reporting of information in international CT notifications are necessary in order to streamline the process and reduce the additional time and resources required when working with CT notifications that contain insufficient information. The standards should include information on the important clinical characteristics of the index case, including laboratory diagnostics, DST results, and infectiousness and symptoms of the index case during the exposure period. They should further include any relevant information on the identified contact persons that is required to trace them and carry out the CT procedures, including full name, date of birth, passport number, residential address, email address, and telephone number. Lastly, the standards should contain information on the duration and intensity of exposure for each contact, together with any knowledge of vulnerability of contacts, i.e. children <5 years or immunosuppressed contacts. Based upon these findings, we have developed two standardized templates for international CT notification following flight and non-flight exposure, which we encourage other health authorities to utilize for their own CT notifications; both templates can be found in the Supplementary Table 1 under Additional File 1 and Additional File 2.
More recently, exposure to an active TB case following long-distance railway or bus trips, i.e. long-distance ground travel, has received increasing attention [30-32]. Beginning in 2019, which is outside the study period, RKI started to receive CT notifications specific to such incidents, a number of which concern long-distance bus travel within the border-free region of the European Union. However, CT following ground travel is associated with a variety of logistic obstacles, making follow-up of contacts very difficult or even unfeasible, as detailed passenger data is often not collected or is very incomplete [24, 30, 33]. Nevertheless, the risk of transmission during long-distance bus travel is considered to be greater than that for air travel, mainly due to the lack of standard HEPA filtration in busses and trains [24, 30, 34]. Unfortunately, scientific literature on CT following railway or bus travel is limited, making the assessment of its corresponding impact on public health difficult. The lack of high-quality evidence, in combination with the substantial amount of time and human resources needed for CT following ground travel, suggests that the decision to initiate CT should be reserved for select situations only, after careful consideration of all relevant factors [24, 30, 33, 34]. Once again, this indicates the need for a rethinking of the current conventions around CT for TB following international travel, keeping in mind that public health resources for TB might be better spent in other, more effective areas of prevention .
Our study has a number of limitations. First, the present analysis is based on CT notifications received by the German national public health institute, the RKI. Some foreign health authorities may have sent international CT notifications directly to the responsible local health authorities in Germany, in which case the local health authorities are not required to forward this information to the RKI. As a result, the total number of CT notifications reported in our study, as well as their characteristics, may not represent the full situation in Germany. Nonetheless, in our experience, RKI does receive the large majority of TB CT notifications for Germany, especially for CT following air travel. Thus, the analysis presented in this study provides the most comprehensive and complete insight to date into the international TB-related CT notifications received in Germany. Second, although RKI informally requests the final results of the CT procedures from the local health authorities, for example information such as the number of contacts reached and tested, the number of contacts who tested positive for LTBI or active TB, and the number of contacts started on preventive therapy, no information on TB-related CT is notifiable under the current disease surveillance laws in Germany. Hence, RKI does not have any information on the outcomes of the 192 CT notifications forwarded to the local health authorities during the study period, and therefore, could not estimate the yield or effectiveness of CTs following international travel. However, this study presents a very thorough inventory of other relevant data, which form a crucial aspect of international CT, and presents practical and important conclusions to improve international CT procedures, such as standardized notification templates. Lastly, our analysis was limited by the incomplete data available on the demographic and clinical characteristics of the index cases, which meant that more extensive analyses of these data other than descriptive analyses were not meaningful due to the small number of cases with available information. The lack of demographic characteristics of index cases is likely due to the minor role this information plays in the assessment of the need for CT; however, the lack of other important information, such as clinical characteristics, is in itself an important finding of this study, highlighting once again the importance of international standards for the reporting of CT information for TB.
In conclusion, CT is an important cornerstone in prevention of TB, especially among high-risk vulnerable population groups, such as children. However, the current procedures regarding CT following international travel are resource-intensive and their public health impact is not backed by strong evidence. The results of this study, which, to our knowledge, is the first of its kind to comprehensively investigate the characteristics of international CT notification for TB, add to the body of literature from around the world in questioning the efficiency and practicality of systematic TB-related CT following international travel, except in extraordinary circumstances. This is particularly true for long-distance air travel, where the described risk of transmission is very low. We instead propose that a central part of a prevention strategy should be raising awareness among physicians to diagnose TB early and encouraging them to educate their TB patients, in particular those with drug-resistant TB, regarding the importance of avoiding public travel during the infectious phase of the disease. Furthermore, the current communication, decision-making, and evidence generation regarding international CT is hampered by a lack of consistency when it comes to the information exchanged between international health authorities. Standardization of the TB-related CT notifications may thereby contribute to a more efficient and practical communication process.