Medical News Blog Information

Why palm tress in the MERS-CoV acquisition model...?

Click to enlarge. See more at earlier post.
I have palm trees drawn in as a sort of focus for my hypothetical acquisition model for the Middle East respiratory syndrome coronavirus (MERS-CoV). 

I first posted this graphic back in late August. It shows ways in which humans might acquire/have acquired the (probably) occasional MERS-CoV infection from an (suspected) animal host/intermediate host.


You can probably see from that paragraph, that this is just some crazy thoughts and there are no data that link them together.


I was recently asked why the palm trees? My thinking here was that date palms, and perhaps other flowering trees, may attract insectivorous bats as well as providing shade, and perhaps water if nearby, for animals and humans. This could create a point of cross-over between species - even if they don't directly co-mingle there may be opportunity to come in contact with contaminated excreta, saliva or partially eaten fruit or bugs.

Influenza deaths amongst children...



Influenza-associated paediatric mortality data.
US CDC FluView. Click to enlarge.
I'm a little bogged down in feeling sorry for myself (no new grants in 2013), paper writing, grant planning/duck aligning just now - but I'm keep an eye on Twitter for gems like this one.

Over on his blog, Avian Flu Diary, Mike Coston has a great summary of some papers and a recent study that serve to highlight the importance of vaccinating children against influenza virus. It's a virus that can kill especially among, but not limited to, those with comorbidities. Influenza is a vaccine-preventable disease.

Have a read of the whole article at http://afludiary.blogspot.com.au/2013/10/pediatrics-influenza-associated.html.

Harare, Zimbabwe - Jessica Magidson, Postdoctoral Fellow, Chester M. Pierce, MD Division of Global Psychiatry, MGH - Improving depression and HIV medication adherence for health care workers



Greetings from Harare, Zimbabwe (or �Mhoro� in Shona� I�ve been slowly trying to learn Shona, the most commonly spoken language in Harare). I am here with Dr. Conall O�Cleirigh, a mentor of mine in the Psychiatry Department and Behavioral Medicine Service at MGH, and our gracious hosts, Dr. Melanie Abas, Dr. Frances Cowan, and Dr. Dixon Chibanda from King�s College London and University of Zimbabwe College of Health Sciences (UZ-CHS).




We are here leading a three-day training at UZ-CHS to train health care workers on brief, empirically-supported behavioral interventions for improving HIV medication adherence. Adherence in this setting is crucial, as in addition to consequences of HIV medication nonadherence that we see in the U.S. (lower levels of viral suppression, accelerated disease progression and mortality, production of medication-resistant HIV strains, and potentially greater likelihood of HIV transmission to others to name a few), there is also a reality here that when individuals fail first-line antiretroviral therapy (ART), there may be limited ART treatment options. As a behavioral intervention to improve ART adherence in this setting, we are focusing on Life-Steps, a single-session cognitive behavioral and problem-solving-based intervention for improving medication adherence. Life-Steps has been developed and tested by MGH faculty (Safren et al., 1999) and implemented in international contexts, including South Africa, although this is the first formal training and implementation in Zimbabwe, and modifications have been made for this setting.   

Day 1 of the training was a larger training � �master class� � open to a wider group of students, health care workers, and faculty as part of a capacity building initiative �Improving Mental Health Education and Research Capacity in Zimbabwe� (IMHERZ). This initiative focuses on bringing together leaders in global mental health and capacity building expertise from partnering institutions primarily in South Africa (University of Cape Town) and London (King�s College London) to increase availability of academic training in Zimbabwe as well as to offer exchange opportunities with partnering institutions. We were invited to teach a 3-hour �master class� to present the current state of the science on behavioral interventions for improving ART adherence and train the group in Life-Steps specifically. Prior to the training, we received input and feedback from local providers and faculty regarding how to culturally tailor the material to make the training as relevant as possible for the Harare context. There were over 60 people in attendance across numerous disciplines, and a few clinical psychologists in particular emerged as leaders within the group to aid in the tailoring and teaching of the material. That evening, the IMHERZ team held a dinner for us at a private home � we had a feast of Ethiopian food and the discussions continued. 

Dr. O'Cleirigh leading a role play during the IMHERZ master class


The second two full days of clinical trainings were conducted with a smaller group of health care workers (ART adherence counselors and in-training psychologists) and psychiatry department faculty. This part of the training was to provide more hands-on instruction and supervision for local providers who will be beginning to implement these interventions in local ART prescribing clinics, as well as guidance for the psychologists who will be supervising the providers. In addition to continuing a more in-depth and hands on training of Life-Steps, we discussed specifically the way in which symptoms of depression interfered with medication adherence, and how brief, empirically supported treatments for depression could be delivered alongside ART medication adherence interventions. Specifically, we trained the counselors briefly on behavioral activation (BA) for depression and problem solving therapy (PST) � although this proved to be, in my perspective, the most challenging part of the training.

Discussion of local barriers to ART adherence (listed on the board) with local students in attendance and our host Dr. Melanie Abas
One of the key challenges that emerged was that there did not seem to be a consensus for a term for �depression� in Shona. There is a well-documented clinical phenomenon in Zimbabwe called �kufungisisa,� which translates as �thinking too much� -- this was actually just included as a �cultural concept of distress� in DSM-5, the version of the Diagnostic and Statistical Manual of Mental Disorders released in 2013. In some cases kufungisisa has been seen as synonymous with the manifestation of depression in this culture, yet upon further discussion within our group of psychiatrists, psychologists, and health care workers during this training, it became unclear if kufungisisa always reflects a true clinical depression. We had fascinating discussions as a group as how to distinguish when kufungisisa reflects depression, or when it�s a normal human experience given the context of immense psychosocial stress, poverty, and violence. It also emerged that the ART adherence counselors who we were training (with no previous mental health experience or training) identified �stress� and their notion of �depression� as being synonymous. Although the DSM and our training in psychiatry and clinical psychology routinely and importantly make this distinction, I began to wonder how important these distinctions were in this context for our training and for the delivery of empirically supported interventions in this setting, when in fact many of the intervention techniques are effective across stress and depression, and both of which can interfere with adherence. We had to strategize at this point what would be the most efficient and effective focus for our remaining training sessions. 
With our host and the team of adherence counselors and supervisors who were trained in Life-Steps and will be implementing Life-Steps in local ART prescribing clinics
 





In addition to these challenges surrounding how to discuss and treat depression, the training in Life-Steps lasted much longer than anticipated � primarily due to challenges in re-orienting the adherence counselors from their previous approach to counseling to a more structured, cognitive-behavioral therapy (CBT) approach, which is problem-focused and time-limited. We found that the adherence counselors were trying to tackle numerous problems beyond just aiming to change adherence � how to solve their patient�s impoverished situation, lack of condom use with uninfected partners, domestic violence, etc. � leaving very little time to discuss the actual treatment goal: adherence. This approach of focusing primarily and solely on barriers to adherence was a huge shift for these providers. Additionally, adherence counseling in this setting previously was seen to be more �authoritative,� with adherence counselors often using a �wagging finger� to demand that their patients take their HIV medications, as opposed to a more non-judgmental, motivational approach typically used in CBT. Training this shift into CBT proved to be a challenging, yet doable endeavor.

In discussing with local providers, our faculty hosts, and the adherence counselors being trained, we decided to spend time conducted in-depth role plays of the treatment techniques, with myself and Conall demonstrating first and then the adherence counselors role playing the same techniques. We did role plays first all in English and then in Shona, and the supervisors in-training led this session. Interestingly, observations emerged that some of the words we had been using in the English role plays needed to be modified for Shona; for example, �why did you not take your medication� was interpreted as accusatory and blaming in Shona. The feedback was to generate other ways of asking this question without the word �why.�

We saw tremendous progress over the course of the 3 days in seeing firsthand the adherence counselors implementing these new techniques � setting agendas, discussing motivations for taking medications, supporting imperfect adherence and developing a non-judgmental context for treatment � along with structured problem solving techniques. The adherence counselors will begin implementing these techniques next week at the local ART prescribing clinics. Prior to the training, the counselors were videotaped doing role plays, and these will be re-done in one month with a supervisor coding and rating based upon a Life-Steps treatment fidelity checklist to see whether these changes are evident and sustain one month following the training. We hope to disseminate this experience and the results to the larger scientific community given the challenges often faced and the need for trainings in these types of settings.

On our final morning in Harare, we had a research meeting to guide discussions of a future randomized clinical trial to evaluate these techniques in comparison to usual care and to ultimately improve the treatment of depression and HIV medication adherence among individuals living with HIV in Zimbabwe � known as the �Treatment to improve depression and adherence to antiretroviral therapy in people living with HIV in Zimbabwe,� (the �TENDAI� study). We discussed issues related to the design, other methodological and assessment measurement issues, how to continue to implement supervision, training, and guidance in this process from the U.S., and planning for future visits to Harare.

We believe this work is truly meeting the IMHERZ initiatives through implementation of a local curriculum open to local mental health faculty, providing opportunities for training individuals to later train other providers, ongoing clinical supervision and support for research methodology, as well as to cultivate collaboration through the partnering institutions. One of the key objectives of IMHERZ is to set up ongoing collaborations with University of Cape Town (UCT). From Harare, I will be flying to Cape Town, South Africa to meet with UCT faculty involved in IMHERZ and the TENDAI study who have a specialized focus on adherence and depression in HIV. In addition to discussing the TENDAI study, we will also be discussing opportunities for collaboration for other clinical research projects to conduct during the fellowship with my global psychiatry mentor Dr. Steve Safren. More to come from Cape Town!
Our hosts insisted we see the beauty of Zimbabwe and took us to Lake Chivero just outside Harare... luckily white rhinos aren't dangerous!

MERS-CoV antibodies not found in children in 2010-11 or adults from 2012

Gierer and colleagues from the German primate center and the University of Dammam in Saudi Arabia, have presented the findings of their study of antibodies to the Middle East respiratory syndrome coronavirus (MERS-CoV).

The publication, in Emerging Infectious Diseases (ahead of print - you can find it here, at least until it's other link here starts working), measured the antibodies capable of blocking infection by MERS-CoV, called "neutralising antibodies" with a method they have described before. The assay was not validated with multiple MERS-CoV-positive patient sera, but appeared specific in the testing completed. None of the sera stopped the MERS-CoV Spike protein coated virus-like particles (VLP) from entering the Caco-2 cell line. Entry of the lentivirus/Spike hybrids was measured by enzyme activity inside the cells if infection is successful. Less or no activity if the VLP could not enter the cell because the VLP's Spike proteins were bound after pre-incubation with anti-MERS-CoV-containing patient sample. 

Patient samples from the area served by King Fahd Hospital were obtained from:

  1. Children (158 sera, 77 female, mean age 12 months) admitted to hospital with lower respiratory tract infections during 12-months form May 2010. 
  2. Adult (110 plasma samples, all males, mean age 28-years, upper limit of 52-years) blood donors 
No sera or plasma had neutralising MERS-CoV antibodies.

The authors conclude that <2.3% of children and <3.3% pod adults were seropositive though, because that accounts for the upper limit of the confidence intervals. They also note that their sampling of hospitalized children could have missed an antibody response (because it takes time to develop) if they had only just been admitted to hospital for MERS-CoV. 

Additionally, its a pretty small sample on which to be base too many conclusions when considering a virus that is spread across a 2,100,000kms2 and reportedly caused notable disease in <200 of 28,000,000 people.



MERS case-control study during the Hajj

Dr Ziad Memish, Deputy Minister of Health, Kingdom of Saudi Arabia, has made a welcome comment about some analysis of ill cases that went on during the Hajj. In the Saudi Gazette..


He added that in addition to detailed investigations of every suspected case, case-control studies for index cases and intensive follow-up of contacts with serological testing to improve understanding of the critical features of MERS-CoV infection were carried out.

I'm not clear on whether that indicates there were MERS-CoV cases during the Hajj, or if he is referring to probable cases that were not confirmed (no contacts then?) or to respiratory illnesses in general. He unfortunately wasn't quoted as saying whether any of those results were positive for MERS-CoV infection. 

Given that 997,3709 pilgrims apparently partook in some degree of medical healthcare service while in the KSA for Hajj, this study should provide some very useful information about what MERS-CoV was doing both in the ill and the healthy in mid-October. I might even be able to stop whingeing about lack of testing of all but those who are severely ill (or their contacts)!

The case-control study protocol is likely to follow that defined by the WHO in July - which can be found here.

The controls (best if >1 per case) will be randomly selected people of equal age (leeway varies with age band) and sex ("matched"), living in the same neighbourhood (to ensure try and capture the same environmental exposures; difficult for visiting pilgrims so general are of pilgrimage might suffice) that are not presenting with the same illness as the confirmed "case" at the time of sampling. Sampling (described in the lab testing WHO document here) which is recommended to include material from the lower respiratory tract - which may prove difficult from otherwise well controls. Informed consent is recommended as part of the (any such) study so controls will know what they are in for ahead do time.

Interestingly the WHO document comments that...


Currently, circulation of this virus in the community is thought to be nonexistent or minimal at most and the numbers of infections low. For that reason, prospective controls who have not had recent respiratory illness can be enrolled without laboratory

This study will address whether this is an accurate premise.

MERS cases swell by 3, information scant...

Middle East respiratory (MERS) coronavirus cases in the Kingdom of Saudi Arabia have increased by 3 according to the latest Ministry of Health update. This brings the tally 147 with 62 deaths, a PFC of 42%. With the data we have, the median age of all cases is at 53-years and that of fatal cases sits at 60-years.

  • FT#147. 83-year old female. Contact of previous case. Comorbidities. Stable.
  • FT#148. 54y. Healthcare worker. Comorbidity. Stable.
  • FT#149. 49-year old. Stable.

Since the update doesn't have much detail to speak of, I'll focus on what the release does not have based on my earlier updated wishlist of useful details from the MOH:

  • Sex of cases (subsequently identified via Twitter)
  • Dates of onset
  • Dates of hospitalisation
  • Details of contacts
  • Type of comorbidities
  • Healthcare worker's role
  • Location of acquisition (just town)
  • Type of laboratory testing
  • Treatments/management
  • English translation
  • History of contact with animals, types (not detailed) of places visited or other possible exposures that may shed light on acquisition

None of these things would identify the cases (a justifiable concern of Dr Ziad Memish) but would be useful for researchers seeking to better understand the nature and track the spread of MERS. 

There may be clues within those details that alert researchers to a nugget that helps explain spread or acquisition or change in disease.

Thanks to Crawford Kilian's @Crof initial tweet and @HelenBranswell and @azizalhinde for clarifying sex of cases. 

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