Jessica Potter

The challenge of the new tuberculosis drugs

Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation. Drug-resistant regimens are long and frequently poorly tolerated due to significant toxicity. This review is an update on what is new in the treatment of drug-susceptible and drug-resistant tuberculosis, new TB drugs currently being used and studied in clinical trials are also mentioned. Fortunately, there have been many significant advances in this field in recent years. The horizon is changing with the new WHO shorter multidrug-resistant tuberculosis regimens and with the increasing availability of new or repurposed drugs like bedaquiline, delamanid, clofazimine and linezolid. These drugs pose new challenges relating to their rational use to prevent selection of resistant strains of Mycobacterium tuberculosis even before a new regimen has been studied. The availability of these new drugs is offering hope and new possibilities for saving patients who had few or no treatment options. Their use and combination into effective regimens need to be studied; trials are in progress. It is hoped that soon we will be able to treat sensitive and drug-resistant cases with a universal regimen, this would revolutionise treatment and take us another step closer towards elimination.

Moxifloxacin: An Alternative to Ethambutol for the Treatment of Presumed Ocular Tuberculosis.

Abstract Objective: To present moxifloxacin as an alternative treatment option to ethambutol in an anti-tubercular therapy (ATT) regime in patients with presumed ocular tuberculosis (TB). Methods: We identified all cases in our hospital referred for treatment of presumed ocular TB between 2009 and 2013. Age, gender, ophthalmic examination, blood tests, treatment regimens, adverse drug reactions, and outcomes were collected and analyzed for the patients who had moxifloxacin as part of their ATT. Results: Forty-three cases of presumed ocular TB were treated with moxifloxacin as a part of ATT. Mean age was 44.18 ± 12.47 years; 62.8% were male. A response to treatment, with no evidence of disease recurrence, was seen in 72.1% of cases. Shortened ATT duration was associated with increased risk of treatment failure (p = 0.02, 95% CI: −0.77 to −0.00). Conclusions: Moxifloxacin can be considered as a safe and effective alternative to ethambutol for the treatment of presumed ocular TB.

Support of vulnerable patients throughout TB treatment in the UK.

Despite well-established treatment regimens, tuberculosis (TB) remains a public health burden; it disproportionately affects poor and marginalized populations who may not have access to social support, including migrants, homeless people and those dependent on drugs or alcohol. There is a clearly demonstrated need for housing and other appropriate social support, as part of a package of integrated clinical and social care. However, TB prevention and control efforts in the UK often do not address the specific vulnerabilities of these groups and it can be a challenge to support the continued TB treatment of these underserved populations. This challenge is exacerbated by complex issues concerning funding, immigration and the law. In this paper, we have reviewed current UK guidance and legislation, discussed several case studies and highlighted examples of existing models of community support for TB patients. Finally, we lay out our recommendations for ensuring a co-ordinated, whole system approach to successful TB treatment.

A UK-based resource to support the monitoring and safe use of anti-TB drugs and second-line treatment of multidrug-resistant TB.

Using the best available evidence and expert consensus, this document provides guidance for adverse effect monitoring in multidrug-resistant TB (MDR-TB). It includes recommendations for baseline tests, routine drug and toxicity monitoring guides as well as individual drug monographs for all drugs currently available in the UK to treat TB. These recommendations provide a structure through which healthcare professionals can better manage the complex drug regimens required for the treatment of MDR-TB; minimising the risk of adverse incidents and helping to improve patients’ tolerance, compliance and treatment completion.

Providing accessible healthcare to migrants is morally right and cost effective

Keith and Van Ginneken highlight an important matter.1 Research agrees that the introduction of fees for migrants probably impedes access to healthcare, infringes on the international human rights agreement, and delays care, thereby increasing costs and threatening public health. Interviewed experts suggest the Immigration Act is a way for the government to show it is tough on immigration and is based …

An unusual presentation of miliary tuberculosis

A young Bangladeshi woman presented to the emergency department with vaginal discharge on a history of fevers and rigours. Although initially treated for pelvic inflammatory disease, the patient rapidly developed respiratory failure with acute respiratory distress syndrome. An axillary biopsy and a high-resolution CT of the chest confirmed miliary tuberculosis (TB). She was initiated on anti-TB medication and made a rapid recovery.

P6 Ocular tuberculosis: a survey of uk clinical practice

Background Ophthalmic manifestations of tuberculosis (TB) are described as inflammatory events in one or both eyes involving the uvea, optic nerve or orbit. The diagnosis is almost always presumptive as mycobacterium are rarely cultured from ocular/periocular tissues. Ocular TB is rare in the developed world and there is a general lack of consensus regarding diagnosis and treatment duration. We surveyed UK specialists involved in the diagnosis and treatment of tuberculous uveitis to examine current clinical practice. Method A previously validated survey based on two clinical cases (one more likely to have TB, one less likely to have TB) was used to examine diagnostic and treatment practices amongst consultants from three different specialities across different institutions in the UK: ophthalmologists with an interest in uveitis, respiratory, and infectious disease (ID) physicians with a TB interest. Results Ten ophthalmologists, 24 ID and 29 respiratory physicians completed the survey. Responses varied greatly within the same specialty as well as between different specialities. For example, in a patient with chronic granulomatous panuveitis and a known TB risk factor, the pre-test likelihood of having ocular TB varied significantly within the groups: ophthalmologists (range 5%–95%), respiratory (range 20%–99%), ID (range 9%–90%). Similarly, for the same scenario, there was disagreement in the optimal duration of treatment. Whilst the majority of clinicians would treat for 6 months, 17 clinicians (24%) – ophthalmologists [3], respiratory [5], ID [9] – would treat for longer than 6 months. All 10 ophthalmologists (100%) would defer antibiotic treatment decisions to a TB specialist rather than initiate treatment themselves. All ID and respiratory physicians would screen for HIV if ocular TB was suspected, whereas only 6 (60%) of ophthalmologists would. Conclusion Diagnosis of ocular TB is challenging due to lack of a gold standard test. Expert consensus is therefore important to ensure the right patients are treated appropriately. This is the first multidisciplinary survey within the UK capturing a spectrum of opinions regarding ocular TB. The Results highlight a lack of consensus both within and between different specialties in the field. An open dialogue between relevant stakeholders is key to harmonising diagnostic and treatment strategies.

S27 Have recent changes to health policies increased diagnostic delay amongst migrant patients with active tb

Background In April 2014 the UK government launched the ‘Migrant and Visitor Cost Recovery Programme’ (MVCRP): a series of policy changes to recoup costs from ‘chargeable’ (largely non-UK born) patients. In England approximately 75% of tuberculosis (TB) cases occur in those born abroad. Delays in treatment increase the risk of morbidity and mortality and threaten public health. We considered whether time between symptom onset and starting treatment for TB has increased since the introduction of the MVCRP. Methods Adult TB cases notified on the London TB Register across Barts Health NHS Trust between 2011 and 2016 were identified. Incomplete data sets were excluded. We examined time to treatment between UK born and Non-UK born patients before and after the policy change using a student paired t-test. To further evaluate non-UK born patients, we labelled a delayed diagnosis as ≥median time to treatment for all patients (79 days). We used a chi-squared test to look for an association before developing a logistic regression model adjusting for age, sex, occupation, time in the UK and social risk factors. Other potential confounders were not included in the final model if they had no effect on the original association. Analyses were performed using Stata15. Results 2237 cases were identified (for summary statistics see Table 1). Pre-MVCRP there was no difference in the mean time to treatment between the UK born and non-UK born (p=0.559) but post MVCRP there was a non-significant increase for the non-UK born (p=0.076). Amongst non-UK born patients only, time to treatment increased following introduction of MVCRP (p=0.0008) and they were more likely to have a delayed diagnosis (p<0.001). A logistic regression model adjusting for confounders found that the non-UK born were 37% more likely to have a delay in diagnosis post introduction of the MVCRP (aOR 1.37, 95% CI 1.13–1.66, p=0.001). Conclusion Our findings suggest an association between the introduction of the MVCRP and risk of a delayed TB diagnosis amongst migrants. We cannot exclude the possibility of unknown confounders. However, further investigation into the effect of policies restricting access to healthcare for migrants is urgently needed. Abstract 27 Table 1 Pre-MVCRP Post-MVCRP UK born Non-UK born UK born Non-UK born Total cases 178 1037 158 864 Mean age (years) 36.4 36.8 37.6 41.2 Proportion female sex 0.42 0.37 0.34 0.38 Mean time to diagnosis 133.2 122.1 120.3 163.9

Intestinal tuberculosis. A diagnostic challenge

To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low‐burden country.

S39 Preliminary Results of a Latent Tuberculosis Screening and Treatment Project and the Role of TB Services in Secondary Care

Introduction Since July 2014, the London Borough of Newham has offered latent tuberculosis (TB) screening to all recent migrants (residing in the UK less than 5 years), aged 16–50 years, from countries with a TB incidence of greater than 150/100 000 cases/year. All migrants are offered an interferon gamma-release assay (IGRA) when registering with a general practitioner. Active TB is excluded by the GP using chest radiography, blood tests and clinical examination. All IGRA positive patients are tested for HIV, Hepatitis B and C. All patients without underlying liver disease, Hepatitis B, C or HIV infection and those who are not immunosuppressed are offered treatment for LTBI with Rifampicin and Isoniazid for 3 months in primary care. Patients with positive results not meeting the above exclusion criteria are referred to the local secondary care service using a standardised referral protocol. We conducted a retrospective study reviewing records of all patients referred to secondary care from the LTBI screening programme. Results From July 2014 to March 2015, a total of 5683 patients were offered screening. 3272 proceeded to IGRA testing of which 866 were positive. Of these patients, 138 were referred to the TB clinic. The most common reasons for referral were symptoms suggestive of active TB (26%), abnormal liver function tests (19%) before and after initiation of treatment, an abnormal chest radiograph (CXR) (10%), Pregnancy or breastfeeding (9%), Hepatitis B or C infection (7%) or previously treated latent or active TB (7%). Of those referred, 11 patients were found to have active disease. 6 patients had mediastinal lymphnode TB, 4 pulmonary and one patient had TB of the knee. Conclusion Screening for latent tuberculosis in primary care has identified a significant of number of cases of active Tuberculosis, particularly mediastinal TB.