Report of Activities from LCNTDR Travel Grant: Sorawat Sangkaew

Short term research visit on dengue modelling and clinical observations in Vietnam and Thailand

I am a second-year PhD student at the Department of Infectious Disease, the Faculty of Medicine, Imperial College London, under the supervision of Dr Sophie Yacoub, Dr Ilaria Dorigatti, and Prof Alison Holmes. I am researching the development of prognostic models for dengue severity that can be used in primary care settings to improve the triage and the clinical management of dengue patients. I am particularly interested in investigating how early signs and symptoms during the febrile phase predict disease progression and the development of severe dengue, a life-threatening condition that causes up to 20,000 deaths each year around the world.

During the first year of my PhD, I established research collaborations with the Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City, Vietnam, and Queen Sirikit National Institute of Child Health (QSNICH) in Bangkok, Thailand, as the specific geographic focus for my work is in South-East Asia where dengue is endemic. Through these collaborations, I was recently given access to two extensive datasets on the disease outcomes and clinical parameters of two prospective cohort studies comprising 7,000 and 1,000 patients in Vietnam and Thailand respectively. To strengthen these collaborations, and understand and analyse the data sets better, I undertook a 2-month research placement in late 2019 at the OUCRU and a subsequent 1-month placement at QSNICH in early 2020, with support from the London Centre of Neglected Infectious Disease Research and Dean’s Internship Award from Imperial College London. This report summarises the key contributions and learnings towards my PhD research of my time spent in Vietnam and Bangkok.

OUCRU Placement – November 4^th, 2019 to December 28^th 2019

The placement at OUCRU was timed to maximise my exposure to, the key processes of data collection from patients, data analyses, as well as clinical observations in the Hospital for Tropical Diseases in Ho Chi Minh city. After an instructive discussion with Dr Minh Tuan Nguyen, a project leader of the data analysis, I curated and analysed the data set under the supervision of clinicians on the dengue and biostatistics teams at OUCRU. My preliminary prognostic models based on the Vietnamese data set were presented to the dengue group at OUCRU. The feedback and questions from the discussion were very helpful in strengthening the robustness and validity of the model as it is developed further. Attending patient ward rounds in both paediatric and adult intensive care units was invaluable in gaining insight into current clinical practice and the value research can add to dengue patient management, particularly in the context of developing countries in endemic areas. The number of patients in the paediatric ICU was around 10 to 15 and around 30% to 40% of them at that time were severe dengue. The number of patients in the adult ICU was around 30 to 50 and the majority of the cases were tetanus infections. This proportion of tetanus cases was relatively high compared to the other hospitals in Vietnam since the Hospital for Tropical Diseases has an established expertise in this area.

It was instructive to see how in both ICUs, research and medical services complemented each other well, with both teams supporting and helping each other. In the dengue unit in OUCRU there was a culture of camaderie and open communication; it was very easy to discuss work with colleagues in the same or adjacent offices, and discussions for troubleshooting were informal but constructive and helpful, facilitating feedback and guidance in a timely manner. Problems were always solved with a variety of perspectives from the multidisciplinary expertise on the team. During my time, I also attended all seminars conducted for OUCRU research students including statistics courses (‘Introduction to R programming’ and ‘Advanced methods for data imputation’) and academic skills and professional skills workshops. In addition to the skills development I gained, the seminars were an excellent opportunity for networking with invited experts and other PhD students in a diverse range of academic fields.

By the end of my placement, the prognostic model development with the Vietnamese data set was well underway, with all the data sets required for model development ready for further analyses. Most importantly, the placement allowed me to strengthen my research collaboration with OUCRU, and establish a good working relationship for future work.

QSNICH Placement – January 1^st, 2020 to January 31^st, 2020

After my 2-month placement in OUCRU, I completed a clinical placement at the QSNICH for 1 month to gain further perspective on severe dengue case management in a different setting. The work schedule at the QSNICH involved clinical work in the mornings and data analysis and research in the afternoons. Ward rounds started at 7 am with medical students and paediatric residents. Daily patient exams and management plans were discussed before ward rounds with ward staff (i.e. infectious disease paediatricians). Although there were not many dengue cases in January as it was not the epidemic season (typically June to October), patients with complicated dengue and dengue with clinical shock were still being admitted in the ward. As case numbers were not overwhelming, the patient ward rounds provided an opportunity for comprehensive discussion and clinical guidance on cases and management. There were two cases of dengue shock syndrome and a few cases of dengue haemorrhagic fever during my placement, and it was an extremely valuable learning opportunity to be part of the team and discuss case management with real patients under the supervision of dengue experts. It was informative to see how QSNICH combines new medical evidence with their expertise in managing complicated dengue cases, as not all treatment and management practices have been documented in current guidelines. My experience with the team at the QSNICH reinforced the need for research to address gaps in clinical practice and be translatable in the real world, and I hope to address this through my research.

Outside of clinical work, my placement at QSNICH also strengthened my research network on dengue in Thailand. I presented my PhD progress to Armed Forces Research Institute of Medical Sciences (AFRIMS), a research collaboration in Thailand. I also had a chance to visit the mathematic modelling group at the Mahidol Oxford Research Unit at Mahidol University. On January 23^rd, 2020, I was invited by Professor Siripen Kalayanarooj, an infectious disease paediatrician, to attend a dengue case conference at Rayong Hospital, Rayong Province, Thailand. During the conference, dengue management and common pitfalls were presented by Professor Siripen Kalayanarooj and Assisociate Professor Vipa Thanachartwet, dengue experts in children and adults, followed by a presentation of interesting cases by medical doctors from Rayong hospital.

In conclusion, the three-month research placement gave me an invaluable opportunity to better understand the context, current needs and future use of my prognostic model for the clinical management of dengue patients. My time spent at OUCRU and the QSNICH allowed me to tailor the development of my models so that they can optimise clinical decision support systems and have a real impact on patient management, improving the quality of care in the future. In addition, the placement strengthened the existing research collaborations with Imperial College and further developed my network with other researchers and clinicians in the field that I can use in my future academic career while in the UK and back in Thailand.