Evolution and global spread of resistance in STIs- a very useful and insightful topic and very relevant working clinically in the field of STIs. 

The session started with Dr Magnus Unemo who presented ´Evolution and global spread of resistance in Neisseria Gonorrhoeae´. Antimicrobial resistance (AMR) has mostly emerged in post- modern times due to both SNPs and recombinations. Specific linegaes are more prone to develop resistance and remain susceptible.  Extended spectrum cephalosporin (ESC) resistance has emerged from Japan as highlighted in the paper by Shimuta et. al 2015 (BMC Infectious Diseases). Genotype 1407 has accounted for most decreased susceptibility to ESCs worldwide. Most microbial resistance is due to use or misuse of antimicrobials. AMR is a global concern requiring enhanced surveillance, need for new antimicrobials and development of a vaccine is crucial.

Dr Catriona Bradshaw discussed ´Evolution and Global Spread of Resistance in Mycoplasma Genitalium´.

Mycoplasma Genitalium (MG) is a fastidious and slow growing organism making NAAT the only diagnostic solution (difficult to culture). Treatment options are limited as mycoplasma lack a cell wall and are unaffected by many antimicrobials.

Doxycyline is used as first line treatment in many areas of the world but it exhibits low overall efficacy with cure rates of 20-40%. Azithromycin however is widely recommended as first line treatment but there has been a notable decline in efficacy over the past decade. Selected macrolide resistance has been demonstrated, at least 10% of the time following 1g of azithromycin. 

Widespread use of azithromycin for syndromic management of STIs has likely contributed to resistance. Prevalence of resistance is worse in the Asia Pacific region.  Prevalence of resistance to azithromycin appears to be less in countries that preference doxycycline for 1st line treatment of MG.

Moxifloxacin is most commonly used as 2nd line treatment in NG. The recommended dose is 400mg daily for 7-10 days. However in 2007 there were the first reports of moxifloxacin treatment failures for MG.

The experience in Melbourne has been a 12-15% moxifloxacin treatment failure rate. These treatment failures have been associated with ParC mutations. ParC mutations have been observed at low rates in Europse when compared to the Asia Pacific region.

What is concerning is that dual class resistance is emerging which will have huge clinical implications. The priorities now are review of using azithromycin for STIs and syndromal management, development of new antimicrobials and evaluating the use of exiting registered antimicrobials. This particular talk was followed up later in the day with a session from Dr Jorgen Jensen and a late breaker session which I will blog about later on. 

These particular sessions I feel were extremely worthwhile and will have a huge impact on clinical practice. It reiterated the need to be mindful of antibiotic prescribing and be aware of emerging resistance.

I attended a lunch session sponsored by Cepheid regarding rapid STI diagnosis and use of point of care testing.

Working primarily in an Indigenous health setting in North Queensland I wanted to see whether a point of care testing model might be helpful with our patient cohort.

Dr Jeff Klausner started the session off presenting `Utility and applications of rapid, molecular STI testing in hard to reach populations´. The current STI statistics globally are quite staggering; over one million new STIs are acquired globally every day and each year there are 357 million new curable STIs ( CT/NG/TV and syphilis).  There is the rising risk of untreatable gonorrhoea, so much so that the WHO has listed NG as one of the top 3 infections that require immediate action. CDC reports demonstrate that STIS are increasing for the first time since 2006 and CDC STI guidelines indicate that treatment needs to be provided on the same day and directly observed.

Point of care STI testing clearly has demonstrated merit. For the patient it provides decreased anxiety and less patients are lost to follow-up. From a public health perspective there is decreased risk of forward transmission of infection, faster treatment for patients and their partners and decreased antimicrobial resistance. From an economic point of view there is scope to expand clinic capabilities, improve treatment costs and target individualized (rather than empiric) treatment. This was illustrated in the example of the Dean Street Express clinic in London. With the use of PoC testing there is quicker treatment, decreased waiting times and increased testing.

Dr Klausner discussed the rates of STIs in pregnancy and the negative consequences of STIs in pregnancy including miscarriage, stillbirth, preterm labour, low birth weights and increased MTCT of HIV. Currently only 13 countries in the world require routine chlamydia testing despite these known adverse outcomes. Point of care testing was trialled in 7 low-middle income countries and more than 2,200 pregnant women were screened for CT, NG and TV. The result of this trial showed high acceptability amongst patients and high treatment rates.

Dr Basil Donovan went on to discuss ´Implementing molecular POC testing in remote primary care in Australia´. Dr Donovan illustrated the difficulties of health care in remote Indigenous communities including the distance from laboratories, high mobility of the population, delays in time to treatment, high rates of PID and disseminated NG.

The Test, Treat and Go Trial was discussed (TTANGO). This was a cross over randomised controlled trial that compared traditional laboratory testing with point of care testing in a number of remote locations across Australia. Median time to treatment was 0 days for POC testing versus 7 days for laboratory testing. Patients reported that they liked getting their result on the same day, that they could be treated on the same day and that they didnt have to return for follow-up. The patient reported dislikes were that they didnt like ´waiting around´. Staff were also interviewed and expressed that they ´felt like a scientist at times´. The staff reported that the point of care tests were easy to use and interpret and they felt increased job satisfaction. Of course there are challenges to report which included high staff turnover in these communities, the need for ongoing public health surveillance and adapting clinical practice.

The session in my opinion was very useful and insightful and very relevant to my current clinical practice. At the particular indigenous health clinic I work at we have high rates of STIs, high rates of treating emperically and difficulty with follow-up. Point of care testing (if costs are appropriate) may be an option for our clinic to improve treatment rates and appropriate use of antimicrobials.

During lunch I attended a Roche sponsored integrated symposium titled ´Syphilis, Chlamydia, Gonorrhoea-Oh My: Diagnostic Advances, Hurdles and Considerations.

I used this opportunity to get a refresher on syphilis considering the rates we are experiencing in North Queensland and to see whether trends/testing/management vary in other parts of the world. It was a very informative talk and definitely made me consider other presentations of syphilis i.e chancres in non-genital sites ( fingers, tonsils etc).

Dr Marco Cusini of the University of Milan, Italy presented ´Current Trends in Syphilis Testing´. The landscape of syphilis in 2017 is that it is well and truly still present and a major public health problem. Late syphilis is rare in Europe but early syphilis still very prominent. Thankfully it is still highly sensitive to penicillin G. In terms of clinical diagnosis, syphilis can be difficult as it is `the great imitator´. Sites of the primary lesion can be extra-genital (and unusual locations), the morphology of lesions can be challenging and there may be a number of primary lesions. Occular involvement also needs to be remembered! 

The diagnosis of syphilis can be achieved through direct methods if lesions are present. This is a quick and in-expensive method but only useful if used under expert eyes. NAATs have the highest sensitivity and specificity. Serology needs always to be performed to confirm the diagnosis and for ongoing disease follow-up. 

Point of care testing are useful in developing countries and there is one FDA approved test. POC testing for syphilis shows good specificity and sensitivity but Dr Cusini stated that they were not really a substitute for serological testing if laboratory facilities are available.

Lumbar punctures need to be considered in anyone demonstrating signs or symptoms of neurosyphilis or demonstrating occular involvement.

Adequate response after treatment was discusssed. Generally an adequate response after treatment for active syphilis is considered a 4 titre decrease at six months. It was good to hear that at our clinic we follow similar guidelines.

Dr Cusini referred to the 2014 European Guidelines for the Management of Syphilis (Janier. et al, 2014) for further information regarding diagnosis and management. It is easily found on the web should anyone wish to read it.

Definitely a good refresher on syphilis and an interesting lecture.

Dr Sinead Delany-Moretlwe presented a plenary regaring the implications of implementation of PrEP.

In November 2015 the World Health Organization recommended that PrEP be offered to high risk individuals. This was based on key evidence of 12 randomized controlled trials of oral PrEP effectiveness. PrEP was found to be effective at reducing HIV across age, gender or mode of HIV acquisition. The caveat to this was the effectiveness of PrEP depended on the level of adherence.

The greatest impact and cost effectiveness of PrEP will be in populations where HIV incidence is >3 per 1000 person years.

As a result of the WHO recommendations truvada as PrEP has been approved in more than 17 countries and just recently has been approved in Belgium, Portugal, Brazil and now the UK. US data of retail pharmacies has shown a dramatic increase in the rates of PrEP prescribing. There has been a 738% increase in prescribing since PrEP was recommended. UNAIDS has estimated that >160,000 people globally are currently on PrEP. However the targets set for those on PrEP by 2020 is 3 million people.

So what does PrEP offer for the patient? Decreased anxiety, increased disclosure amongst partners, increased intimacy and trust and increased self efficacy.

However there are significant barriers to PrEP use and these involve stigma surrounding its use. Other perceived barriers include:

1.) Safety in terms of side effects and effects on bone/renal health

2.) Resistance

3.) Longer term follow-up

4.) Development of safer drugs

5.) Potential effects in pregnancy and breast-feeding

6.) Cost especially if public funding is involved

The key questions to implementation include- how do you create demand? How do you supply demand? How do you support effective use?

Certainly many of the challenges can be seen as opportunities to strengthen and revitalize sexual health services for those most in need.

Dr Kevin De Cock delivered an insightful keynote lecture which has set the tone for what should be a very valuable conference. 

He presented the lecture titled " HIV, STIs and evolution in global health". Global health involves a a complex interplay of many different facets and although gains have been made in some areas, there is still unfinished business to contend with. These include finding a cure for HIV, vaccine development for HIV, TB and malaria and shorter answer simpler treatments for TB. 

In terms of STIs there are changes and goals to be achieved. This was highlighted with the numbers of cases of syphilis, rising in the US since 2001.  Of these increased numbers the majority of those affected are men, particularly MSM. Rate of congenital syphilis have risen by 35% ( did I hear that right?!) since 2013. What are we doing to decrease this burden? How did this happen? Is screening for syphilis occurring where the burden is highest?

Clearly there is no easy solution to these issues however it was concluded the forging alliances, stronger networks, deeper epidemiology and stronger science are part of the answer.

A very thought provoking keynote lecture....

Blood Pressure Targets IN HIV+ patients

Again another very interesting session from a GP perspective. 

Dr Shanti Narayanasamy discussed the challenge of meeting BP targets in HIV positive outpatients.

The background to the problem is concerning; high BP accounts for 45% of heart disease mortality and 51% of stroke deaths. Rates of hypertension in people living with HIV in Australia is approximately 20-25% and those affected have higher rates of myocardial infarction than the general population.

This cross sectional, retrospective study examined whether HIV positive patients attending an outpatient clinic who were diagnosed and treated for hypertension were meeting blood pressure targets as per the Heart Foundation guidelines.  Please see below:

People with proteinuria >1 g/day (with or without diabetes) < 125/75

People with associated condition/s or end-organ damage:* • Coronary heart disease • Diabetes • Chronic kidney disease • Proteinuria (> 300 mg/day) • Stroke/TIA < 130/80

People with none of the following: • Coronary heart disease • Diabetes • Chronic kidney disease • Proteinuria (> 300 mg/day) • Stroke/TIA < 140/90 or lower if tolerated

Of the 69 patients studied, 97% studied were male. Of these 48% met the target BP and 59% had end organ disease from hypertension. Most of these patients were treated with ACE-i medications (no: 39). Most patients were treated with monotherapy (70%) and 30% were taking more than 1 anti-hypertensive. Of the patients that had end organ disease only 68% had seen either a cardiac or renal specialist as per the guidelines. Of those that had seen a specialist; this was correlated with better BP control.

Those patients that were virologically suppressed had better BP control. This could be attributed to overall better medication compliance. Older patients also had better BP control.

This raised the question of whether there was some reluctance/inexperience of the ID physicians or general practitioners involved in these patients care to up-titrate hypertensive management when necessary.

Certainly this appears to be an issue that is likely faced in a number of different settings and was a great way to raise the awareness of meeting BP targets and involving specialist opinion when required.

I really enjoyed the sessions today on co-morbidities and as a S100 general practitioner found this very useful. The discussion re bone health was especially interesting to me given a number of my patients have low BMD.

Professor Jennifer Hoy outlined practical management and screening of bone disease in HIV. Osteoporosis is a silent disease until fracture occurs and people living with HIV have a higher risk of low BMD and fragility fractures than the general population. This is likely due to lifestyle risk factors, low vitamin D levels, HIV induced inflammation and the effect of ART.  The question is who should be screened? Which tool should be used? When should we start screening and how often should we be screening our patients?

Who should be screened? All HIV positive individuals over the age of 40years, those with a history of fragility fractures, those taking corticosteroids for more than 3 months at doses of greater than 5mg per day and prior to ART initiation.

Which tool do we use ?Using the FRAX calculator ( https://www.shef.ac.uk/FRAX/tool.aspx?country=31) calculates the ten year probability of fracture with BMD. However the FRAX calculator while useful has not been validated in the HIV population. High risk patients should have a DEXA scan. However DEXA scan can only be accessed if there is a history of previous low BMD or previous fragility fracture/fracture with minimal trauma, if there is a history of chronic liver or renal disease, proven malabsorptive disorder, history of rheumatoid arthritis, thyroid excess states and in patients over 70 years of age. It does make it difficult if your patient does not fall into this category and alternatives to DEXA include the 'Measure Up Mobile Dexa Bone Health'unit, quantitative CT scan and heel ultrasound.

DEXA screening intervals are based on the baseline screening result. For normal-mild osteopenia this would be every 5 years and for more advanced osteopenia every 1-2 years. Professor Hoy mentioned that there was insufficient evidence for more frequent screening for those on certain ART regimens i.e. tenofovir.

In terms of treatment for those with fragility fracture or low BMD this includes:

- adequate dietary calcium

- ensure they are vitamin D replete

- lifestyle modifications ie smoking cessation/alcohol reduction

- exclude secondary cause of low BMD

- discontinue or change ART regimen if appropriate

- initiate bisphosphonates under the same criteria as general population

This was a very informative session and information that will be very useful in my position as a GP