Guidance

UKAP statement on risk of HTLV-1 transmission from healthcare workers to patients during exposure-prone procedures

Published 21 December 2022

Introduction

Human T-cell lymphotropic virus type 1 (HTLV-1) is a carcinogenic oncovirus discovered in 1980 (1). Once acquired HTLV-1 infection is lifelong with a long latent period until disease presents.

Until recently the lifetime risk for HTLV-1-associated diseases was considered only for the conditions most strongly associated with HTLV-1, adult T-cell leukaemia or lymphoma (ATL) in approximately 5% of all infected (2) and HTLV-1-associated myelopathy 0.25% to 3.8% (3). However, there is increasing evidence of the importance of other inflammatory disorders such as HTLV-1-associated myositis, uveitis and Sjogren’s syndrome, a range of pulmonary pathologies including bronchiectasis (4), adverse outcomes with co-infections and an unexplained 57% increase in the adjusted mortality rate (5).

Median life expectancy following presentation with ATL is 8 to 10 months despite advances in chemotherapy and transplantation (6), whilst HTLV-1–associated myelopathy (HAM) is a chronic, progressive debilitating condition lasting decades and associated with extremely poor quality of life (7) for which treatment options are limited (8).

HTLV-1 is transmitted through blood, mucocutaneous or sexual exposure to infected bodily fluids, or through vertical transmission from mother to child. HTLV-1 infection is usually identified following a diagnosis of complications associated with the virus such as ATL or inflammatory disorders, by which point onward transmission could have occurred.

In the UK, HTLV-1 is a little-known virus with care available through a small number of tertiary specialist centres. Blood and tissue donors and patients undergoing in vitro fertilization (IVF) are routinely screened for HTLV-1 infection. Among UK blood donors the prevalence of HTLV-1 infection has changed little over the last 30 years (5 per 100,000 first and repeat donors in 1991 (9) and remains the current rate among first time donors).

In the antenatal setting the prevalence is higher at 50 per 100,000 (10) whilst limited available evidence suggests that in the sexual health setting it is as high as 800 per 100,000 (11); however, screening for HTLV-1 infection is not part of standard care, nor included in any occupational health testing regimens.

The UK Advisory Panel for Healthcare Workers Living with Bloodborne Viruses (UKAP) provides expert guidance to the Department of Health and Social Care (DHSC), the NHS and local authorities on assessment and management of health care workers (HCWs) living with HIV, hepatitis B and hepatitis C who perform exposure-prone procedures (EPPs), where there is a risk of injury to the HCW and subsequent bleed-back into a patient for example, abdominal surgery. As part of annual meetings, UKAP undertakes scanning exercises of expert intelligence and research to identify potential novel risks of bloodborne virus (BBV) transmission from healthcare worker to patients in the UK.

On 17 March 2021, the World Health Organization (WHO) launched a technical report on HTLV-1 (12) recognising that the risk of nosocomial infection was unknown, and that whilst pro-viral load was associated with transmission, whether there was a level of viral load below which transmission does not occur was not known. This was accompanied by a meeting report on the public health impact and implications of HTLV-1 (13). The report recommends that further research on this issue is prioritised, and that HTLV-1 control and prevention strategies should be considered, particularly for infection control in health care settings and harm reduction for people who inject drugs.

In light of this statement and engagement from key international experts on HTLV-1, UKAP have reviewed the available evidence to assess whether any occupational health policy recommendations can be made regarding HTLV-1 infection among HCW undertaking EPP. This statement does not include human T-cell lymphotropic virus type 2 (HTLV-2) which has significantly less associated morbidity and mortality.

Prevalence of HTLV-1 among UK healthcare workers

In the general UK population, an estimated 30,000 people are infected with HTLV-1 (14, 15). Currently, the prevalence in HCWs is unknown. However, studies into key populations have been conducted and have estimated prevalence among blood donors to be 5 per 100,000 (9); among antenatal patients 50 per 100,000 (10); and among GUM clinic attendees 400 to 800 per 100,000 (11, 16), although these estimates are limited and have not been repeated recently.

The HCW population will likely differ in demographics and risk factors from these groups and so the prevalence of infection is likely to be different, however these differences have not been studied. The burden of infection in this group, and subsequent risk of onward transmission to patients, is therefore unknown but unlikely to be higher than that seen in the general UK population.

Evidence of transmission events in healthcare settings

There is no evidence in the literature of HTLV-1 transmissions from HCW to patients while undertaking an EPP. The evidence of HTLV-1 transmission from patient to healthcare workers in healthcare settings is limited to a small number of circumstantial case reports.

In 1990, a case report from Japan was published describing how a clinician dropped a needle on their foot containing blood from a patient with ATL, and the clinician was later diagnosed with HTLV-1 (17). A stored serum sample of the clinician taken before the incident was retrospectively tested and found to be negative, indicating that this was a new transmission.

A further report was published in 2006 describing a physician in Brazil who was injured while recapping an arterial blood gas syringe from a patient with HTLV-2, and was subsequently found to be HTLV-2 positive (18). Baseline serology in the healthcare worker was negative and follow-up serology was positive 18 months late. No other risk factors were identified.

A report was published in 1992 describing how a healthcare worker in Zaire was diagnosed with HTLV-1 associated myelopathy and occupational exposure was deemed the only likely route of infection (19). Finally, in 2014 a retrospective study reviewed 54 potential occupational HTLV-1 exposures and found no evidence of transmission to HCWs (20).

There is therefore limited evidence of the risk of HTLV transmission to HCWs through occupational exposures for example needlesticks, but no reported evidence of the risk of transmission from HCWs to patients through EPPs, and so the risk in this context remains unknown.

Likelihood of transmission and seroconversion following an exposure

It is important to consider the likelihood of HTLV-1 transmission and seroconversion following an exposure from HCW to patient in determining whether occupational screening would be of benefit. There is little evidence available on the pro-viral set point at which the risk of transmission and seroconversion of HTLV-1 becomes negligible. Based on expert opinion and applying knowledge from transmission dynamics of other viruses, it is reasonable to assume that the risk of transmission and seroconversion will be lower if the donor HCW has a low viral load.

There is evidence that the viral load stabilises quite early after HTLV-1 acquisition, certainly within 6 months (21). One cohort study demonstrated that pro-viral loads remained very stable over an 8 year period (22). It is also possible to have ‘elite controllers’ with an undetectable pro-viral load, although the natural history of infection and transmission risk in this cohort has not been studied. A cut off of above 4% (4 HTLV-1 DNA copies per 100 peripheral blood mononuclear cells) is generally considered a high pro-viral load which could lead to increased risk of disease, especially ATL (23). Patients with HAM or ATL are more likely to have a higher pro-viral load than those without these conditions. However, the median pro-viral load in asymptomatic carriers is 1.5%.

Based on this information, whilst it is reasonable to surmise that ‘healthy’ HCWs without marker conditions associated with HTLV-1 infection are likely to have a lower and relatively stable pro-viral load, a proportion of asymptomatic HCWs living with HTLV-1 will have a viral load in the same range as those with HTLV-1 associated diseases (24, 25). Furthermore, amongst those with lower pro-viral loads the risk of transmission is not known.

Morbidity, mortality and availability of treatment

As well as the likelihood of transmission and seroconversion following exposure the potential impact of a transmission on health and wellbeing of patients, including available treatment options, should also be considered. There is currently no curative treatment for HTLV-1 infection and so any transmission events will result in lifelong infection. Instead, patients are counselled and monitored for sequelae such as ATL and HAM, for which they can be offered options for management and symptom control, but not cure (8, 26).

Based on limited evidence, the overall mortality risk in people with HTLV-1 is 57% higher than compared to people without HTLV-1 (3). The impact of HTLV-1 transmission from HCW to patient is therefore likely to be significant, with associated risk of long-term morbidity and mortality with no curative treatments available.

Effectiveness of existing standard infection prevention and control in preventing transmission

There is currently no research available to determine the impact of infection prevention and control standard precautions on HTLV-1 transmission in healthcare settings. Applying what is known about the transmission of other blood borne viruses, the use of standard personal protective equipment and promoting the safe use and disposal of sharps will minimise the likelihood of HTLV-1 transmission in a healthcare setting.

It is however recognised that EPPs carry additional risk of injury and exposure of the patient’s open tissues to the blood of the HCW, in addition to what is mitigated by standard precautions. EPPs therefore present a theoretically higher chance of exposure, however this has not been studied and as highlighted above there are no case reports in the literature of transmission from HCW to patient associated with EPPs.

Conclusion

The prevalence of HTLV-1 infection among healthcare workers in the UK is unknown but is likely to be low, based on what is known about prevalence in the general population. There are several diseases associated with HTLV-1 infection that limit both quality and length of life, and there are no curative treatments available. A transmission from HCW to patient is therefore likely to have a significant impact on a patient’s health and wellbeing. There is however a lack of understanding as to the risk of HTLV-1 transmission from HCW to patient associated with EPPs, and no reports in the literature of this occurring.

UKAP recognises the developing international concern regarding HTLV-1 and will continue to review evidence and research as it becomes available in order to reassess risk and the need for further guidance. Based on the evidence available, UKAP has made the following recommendations.

Recommendations

Screening for HTLV-1

Recommendation: UKAP concludes that health clearance for HTLV-1 through occupational health services for EPP-performing HCWs should not be introduced at this time.

Rationale: owing to the lack of evidence as to the likely prevalence of HTLV-1 among EPP-performing HCWs, the unknown risk of transmission to patients in this context, and the lack of treatment or monitoring criteria to facilitate HCWs to continue in their EPP-performing role following diagnosis, testing and health clearance in HCWs who wish to perform EPP for HTLV-1 is not deemed a proportionate or appropriate occupational health intervention.

However, UKAP notes that although high viral load is associated with the occurrence of marker conditions such as ATL or HAM, the majority of high viral load carriers do not have either condition, or do not develop such conditions until after years of living with a high viral load. Indeed, based on the ratio of estimated to diagnosed infections in the England 90% of infections are undiagnosed and so it is unreasonable to assume that a HCW would be tested for HTLV as a consequence of such a diagnosis.

Restrictions to EPP practice

Recommendation: UKAP does not currently advise any restriction from EPP practice for HCWs with a known HTLV-1 infection. Under existing occupational health and ethical duties, HCWs should disclose their HTLV-1 status to occupational health, for risk assessment at the point of diagnosis. Occupational health should consider recording the HCWs pro-viral load, which could be used to inform any future risk assessments.

Rationale: currently there is a lack of evidence that restriction of EPP practice would improve patient safety and there is an unknown risk of transmission from HCWs to patients. Therefore, it would not be appropriate to restrict HCWs practice at this time.

Restriction to EPP practice for HCWs with HTLV-1 could have significant implications for individual HCW careers, without there being sufficient evidence that this is necessary on patient safety grounds, it is unlikely that it could be successfully embedded into practice or accepted by HCW groups.

Pro-viral load will have an impact on the risk of transmission and seroconversion, however there is insufficient evidence available to be able to infer the likelihood of healthcare workers having a high viral load, and therefore a subsequent higher risk of transmission. The variable risk of transmission associated with different viral loads in this context has not been quantified and so no ‘cut off’ level can be determined, below which a HCW living with HTLV-1 could be allowed to perform EPPs.

Monitoring HCWs with HTLV-1 infection

Recommendation: UKAP does not currently recommend routine occupational health monitoring of HCWs infected with HTLV-1.

Rationale: As above, there is a lack of evidence around risk of transmission of HTLV-1 from HCWs to patients. Pro-viral load will have an impact on the risk of transmission and seroconversion, however there is insufficient evidence available to be able to infer the likelihood of healthcare workers having a high viral load, and therefore a subsequent higher risk of transmission. As a ‘cut off’ pro-viral load cannot currently be determined, no action would be taken from regular monitoring of HCW pro-viral load.

Exposure to patients from HCW infected with HTLV-1

Recommendation: if occupational health or other services require support or advice regarding HTLV-1 exposures, for instance if there is an incident where bleed back occurs, they should seek advice from a local virologist, local health protection teams and national experts on HTLV on a case by case basis in the first instance. A risk assessment may also be considered.

Rationale: contacting local virology and national experts on HTLV in the first instance, will allow for advice on whether the exposed patient requires post-exposure prophylaxis (PEP). The administration of PEP is time limited so virology or national experts should be contacted urgently.

Further research and training

Recommendation: further training of HCWs about HTLV-1 risk and exposure is recommended in routine BBV training, as well as training HCWs on their duties regarding HTLV-1 diagnosis. Further research is required to improve the understanding of prevalence of HTLV-1 among HCW and the general population and transmission risk in healthcare settings. National guidance on the management of HTLV-1 is needed.

Rationale: UKAP recommends that EPP-performing HCWs keep themselves updated and informed on HTLV-1, so that they are aware of the risks regarding HTLV-1 and so that they are aware of their responsibility to inform occupational health (OH) of any HTLV-1 diagnosis. UKAP recommends that occupational health services should include information on HTLV-1 in training materials alongside information on other BBVs and that occupational health should remind all HCWs beginning an EPP role that they have a duty to inform occupational health of a HTLV-1 diagnosis.

UKAP has noted that there is a gap in guidance on the investigation and management of HTLV-1 exposures for both patients and HCWs, and treatment recommendations. It would be beneficial for guidance to be developed by professional bodies in order to standardise clinical practice and improve reporting.

Testing for HTLV-1 infection in the event of a needlestick injury to HCWs may be one way of gathering such evidence for this cohort. Further research is required to better understand the prevalence of HTLV-1 infection in the general population and key risk groups including HCWs and those at risk of other BBVs for example, people who inject drugs or engage in other behaviours that are associated with BBV transmission risk. In particular, longitudinal studies into disease progression should be instigated to establish the risk of long-term morbidity and mortality.

References

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Authors

Laura Coughlan, Sophie Nash, Ali Hashtroudi, Matthew Donati, Kirsty Roy, Divya Dhasmana, Vanessa MacGregor, Graham Taylor, Emily Phipps *, Monica Desai *, on behalf of the UKAP Panel.

*Joint last authors