Impact of a nurse‐led enhanced monitoring, management and contact tracing intervention for chronic hepatitis B in England, 2015‐2017

Around 200,000 people live with chronic hepatitis B in England. Despite national guidance on identification and management of cases and their close contacts, testing rates of close contacts is as low as 43% in high prevalence areas of London. Our study aimed to determine whether a nurse‐led enhanced management and contact tracing of chronically infected individuals improved testing uptake, vaccination and onward referral of close contacts. The study was conducted across Greater Manchester and East of England regions between October 2015 and July 2017. All HBV chronically infected individuals registered with a GP and their close contacts were eligible for recruitment. The proportion of contacts who were tested, vaccinated and referred where appropriate were compared before and after the nurse‐led intervention. Baseline and outcome information was collected using questionnaires. The intervention improved case referral rates by an additional 14% (from 86% (88/102 cases) to 99.7%; 648/650 cases). The proportion of contacts tested increased from 34% to 72%‐94% with 18 new cases of HBV diagnosed. Amongst close contacts tested, vaccination rates of at least three doses increased from 77% (43/56) to 93% (452/491) during the study. Our study has shown that nurse‐led enhanced management greatly improves identification, testing and vaccination of close contacts. The identification of new acute and chronic cases is likely to make the intervention cost effective and local health commissioners should consider providing a nurse‐led service as part of hepatitis B care pathways.


| INTRODUC TI ON
Hepatitis B is a vaccine-preventable disease caused by the bloodborne hepatitis B virus (HBV). It can cause a liver infection leading to both acute and chronic disease, cirrhosis and liver cancer. 1 Approximately 257 million people suffer from chronic HBV infection (CHB) worldwide and around 600,000 die annually because of associated liver disease. 2,3 In the UK, approximately 0.3% of the population have CHB, 4 mostly among ethnic minority groups and in large cities [5][6][7] where migrants, who acquired the infection as children in their birth country, mainly contribute to the burden. 8 The risk of CHB following acute infection is age-dependent.
Most adults (90%) clear infection and develop immunity, but <5% develop CHB. In contrast, without intervention, up to 90% of infected infants will develop CHB. 9 Around 25% of chronically infected individuals will develop liver cirrhosis or liver cancer. 10  HepB. 12 Close contacts testing has conventionally been performed on serum or dried blood spot (DBS). Oral fluid (OF) detection of anti-HBc and HBsAg has also been validated and is often a more convenient and less invasive analyte for sampling cases and has the added advantage that it can be undertaken at home by the patients Another audit conducted in Bristol in 2012 showed that only 12% of migrants for whom HBV serology testing was recommended had been tested. 14 A pilot study in two London hospitals demonstrated that nurseled enhanced follow-up of pregnant women with CHB, including home sampling by DBS, increased testing uptake among their partners from 43% to 90%. 15 Nurse-led enhanced contact tracing and management of CHB cases therefore has the potential to improve testing and management outcomes among contacts. This study aimed to determine whether a nurse-led intervention including enhanced management of cases and contacts of chronically infected individuals improves case referral and testing uptake, vaccination and onward referral of close contacts. The intervention consisted of an intervention nurse (IN) carrying out three key public health tasks: (a) tracing all close contacts of individuals diagnosed with HBV, (b) regular follow-up of contacts to ensure they are getting tested and vaccinated, and (c) appropriate referral and attendance to specialist services for contacts who test positive for HBV.

| Study design
The intervention was evaluated using a self-controlled before and after study design across two Health Protection Teams (HPTs): Greater Manchester and East of England. The INs in each HPT were in place between 1 October 2015 and 1 July 2017.
In summary, the study entailed recruiting into the baseline individuals who had a laboratory diagnosis prior to the study time period (October 2015 to July 2017) and their contacts. The outcome for baseline cases and their contacts were described retrospectively at the time of recruitment (ie prior to the intervention). Because these individuals were now prospectively being managed by the intervention nurses (giving them a 'second chance' of being followed up), they were counted in the intervention group (with an 'updated' outcome following the nurse intervention), in addition to any individuals who were first notified between 1 October 2015 and 1 July 2017.

| Recruitment
All adults registered with a GP identified as CHB cases during the study period and their close contacts were eligible for recruitment into the study as summarized in Box 1. We excluded cases below the age of one and their contacts because these cases are largely babies born to HBV-infected mothers, and are managed through a different care pathway and nationally commissioned immunization programme which is not the focus of this study.

| Intervention group
After ensuring that each case was aware of their HBV infection, the INs contacted cases to explain study objectives, invite them to participate and ask permission to communicate with their close contacts. Where this permission was declined, cases were asked for a reason and the number, ages and countries of birth of their close contacts. Phone translation services were used to consent non-English speakers. Consent for under 16 years old was obtained from a parent or legal guardian and appropriate assent from the young person.
Following case recruitment, the IN collected information on diagnosis, testing, close contacts' details, previous referrals and attendance using a patient questionnaire and confirming with the case's GP where necessary. The IN referred cases not already referred or who had missed appointments. The IN obtained GP registration details of close contacts using the NHS personal demographic system (PDS). 16 Following close contact recruitment, information on testing, number of reminders and relevant vaccination (number and dates of doses) or referral were collected using a questionnaire. The IN liaised with GPs to obtain or confirm details of previous tests, vaccinations or referrals and to arrange HBV serology testing.
Eligible contacts were offered HBsAg and anti-HBc testing either as a blood test or as a home OF test kit ( Figure 1). Individuals who did not return their OF sample were reminded one week after dispatch. The IN liaised with GP surgeries and contacts to follow-up all individuals to the conclusion of their clinical care, either vaccination or onward referral, recording the outcomes of their interaction using study questionnaires.

| Baseline population
Recruited cases who were diagnosed with CHB before October 2015 through antenatal or primary care services were eligible for inclusion in the baseline study population. Cases without complete GP records were excluded. The outcome for baseline cases and their contacts were described at the time of recruitment (ie prior to the intervention). As described above, baseline cases and their contacts were then offered the intervention and included again in the intervention group with a revised outcome following the nurse intervention ( Figure 2).
Contacts who tested negative for HBV serology were contacted by the IN to ensure appointments were booked at their GP to start or complete a HepB vaccination course. Contacts were reminded of vaccination appointments through SMS. In instances where the study ended before a vaccination course could be completed, the IN ensured appointments were booked for the remaining doses. The IN referred contacts with serology suggestive of HBV infection and followed up to attendance at the specialist service.

| Study power
The study sample size was constrained by the number of HBV cases in the study regions in the study timeframe. To ascertain the number of individuals needed in the baseline and intervention contact groups to detect a difference in testing rate, we ran several scenarios with different testing rates for contacts in the baseline and intervention groups that represented the range of what was deemed to be realistic by the intervention team. The biggest difference that was deemed realistic was 30% testing in the baseline and 85% testing in the intervention group. With a significance level of 0.05 and a power of 0.8, this difference could be detected with 6 contacts in the baseline and 17 in the intervention. The smallest expected difference was baseline testing of 45% and intervention testing of 70%, which would require identification and recruitment of 32 contacts in the baseline and 92 in the intervention group.

| Data management and Analysis
Questionnaire information from patients, contacts and GP practices was entered, managed and cleaned using Access 2010 and Excel 2010 (Microsoft). We described cases in terms of age, gender and Close contact A current and/or recent sexual partner of a case OR individual sharing the same household as case over the age of 1.

Box 1 Case and contact definitions
Close contact trace A close contact that had been tested and/ or started a course of vaccination within 60 days of the index case's date of diagnosis.

Exclusion criteria
Prisons or other places of detention CHB cases are not followed up through normal PHE HPT mechanisms.
Sexual health clinics Cases identified through sexual health clinics anonymised and unable to follow-up.
Specialist services Case already undergoing treatment for CHB as part of specialist care.
Not registered with GP No follow-up mechanisms region of birth and compared the baseline with the entire study population using chi-square tests, to asses any significant differences in the populations. To assess the impact of the intervention on cases, we compared the proportion of cases who were referred and attended their referral appointment before and after the intervention using chi-square tests. To assess the impact of the intervention on testing and subsequent management of close contacts, the proportion of contacts of cases who were contacted, tested, and appropriately referred or vaccinated (as defined in Box 1) were compared before and after the intervention, using chi-square tests. All statistical analyses were performed using Stata 14 (StataCorp, USA). NHS

Ethical approval was obtained from NRES Committee South East
Coast and management permission ('R&D approval') was obtained from the relevant NHS organizations.

| Referral of cases
We identified 1,123 eligible cases to be recruited over the study period. INs made telephone contact with 725 (65%) cases ( Figure 2). Of these, 650 (90%) consented to participate in the study. Of the 650 recruited cases, 363 had a CHB diagnosis prior to the intervention period. Of these, 102 (28%) had GP data available and were therefore included in the baseline population ( Figure 2). Compared with all cases, baseline cases were of similar age (median 33 vs 34 years), more likely to be female (77% vs 58%, P = .003) and comparable in terms of region of birth (P = .9) ( Table 1). Of the 102 baseline cases, 88 (86%) had been referred to a specialist service at the time of diagnosis (Table 1).
Among the 650 recruited cases, following the intervention, 648 (99.7%) had been referred to specialist services compared with 86% among individuals managed prior to the intervention (P < .001).
The INs checked whether referred individuals had attended their appointments and identified 53 who had not. Of these, 42 (79%) were re-referred (the others declined or could not be contacted).
Amongst those, 64% (27/42) attended their appointment. Ten cases did not attend despite two reminders from INs, a further five cases were uncontactable.

| Contact tracing
There were 183 contacts over one year of age identified for the 102 baseline cases, of which 62 (34%) had already been tested prior to the intervention. Of those 62 who were tested, 6 (10%) had evidence of CHB, of which 5 (83%) were referred to a specialist service by the GP.

F I G U R E 1 Testing of close contacts
Amongst the 56 close contacts who tested negative, 10 (18%) were completely unvaccinated and 43 (77%) had received three or more doses of hepatitis B vaccine (Table 1). Because the proportion of nontested contacts who are vaccinated is unknown, it is not possible to determine the overall proportion of contacts who were vaccinated at baseline. However, assuming that all of the nontested contacts were unvaccinated, the proportion of contacts who had received at least three doses of vaccine could be as low as 43/183 (23%) at baseline.
A total of 1,402 close contacts were identified for the 650 cases (

| DISCUSS ION
Providing nurse-based enhanced support for CHB management greatly improves the identification and testing of contacts (from 34% of contacts before the intervention to 72%-94% during the intervention), as well as contact vaccination (from potentially as low as 23% to 93%). The intervention also identified 18 new diagnoses of HBV who were referred to specialist services. The success of the Although it is difficult to estimate vaccine uptake among contacts prior to the intervention, the proportion of contacts receiving at least three doses of HepB vaccine increased by up to 70 percentage points following the intervention. Amongst the close contacts tested, vaccination rates of at least three doses of vaccine were high, suggesting vaccination was largely taking place once a close contact had been identified. Even among those tested, the proportion of vaccinated contacts increased significantly after the intervention.

F I G U R E 2 Recruitment of baseline and intervention cases
A key limitation to our findings is reflected in the difficulty in de-