Recruiting a community control is not not as simple as it seems. There's many stages involved behind the scenes as community controls must be frequency matched to the cases by age, sex, seasonality and geographical area. These data are calculated by the team at LSHTM. The LOMWRU team in Laos then spends a considerable amount of time and effort travelling long distances to locate and ask healthy individuals to take part in the study as community controls. 

Dr Somvai Singha produced a video of one such trip, which took 2 hours by motorbike and boat, to a village in Viengchan province 90 km away from the capital Vientiane. This shows the lengths people will go to seek care, the same journey can take 4 hours by road. 

Watch this fascinating video of a journey to locate a control:

Read about a study participant's experience in Malawi.

Fletcher Nangupeta and Frank Mlumbe, FIEBRE fieldworkers, organised a visit to meet two FIEBRE study participants, a mother and daughter, and the village elder, at William village, in Chikwawa district. The mother explained how her daughter had been enrolled in the study when she had presented with a fever, how the daughter had recovered after treatment and subsequently, when the mother herself became ill with a fever, she had no hesitation in taking part. 

FIEBRE in practice: Malawi FIEBRE visit to William village, T/A Katunga 
Report produced by Fletcher Nangupeta and Frank Mbalume

On 8 February 2019, we received three visitors from London School of Hygiene & Tropical Medicine namely; Amit Bhasin, Ruth Lorimer and Rebecca Handley. Staff from the Malawi Liverpool Wellcome Trust Research Programme (MLW) were also in attendance: Edward Green, Kate Haigh, Fletcher Nangupeta and Frank Mlumbe
We visited William village, in the traditional authority (T/A) area of Katunga, where we went to the house of a FIEBRE study participant. The main purpose of the visit was to find out what she understood about the study and to see how people in the community perceived the FIEBRE study. On arrival at the village, we were received by the village headwoman herself, the participant and her children. The team was introduced to both the participant and the village headwoman.
When she was asked about how she feels taking part in the study, she said ‘’it is a good experience to participate in the study, this is my second time taking part in the study and two of my children also took part in study”. She appreciated that now she knows the status of her body and the general health of the children. When asked about the blood volume and blood stealing myths which can occur in Malawi, she said, ‘’The myths were circulating sometime ago but nowadays people realise the importance of being in the study”. One inquisitive neighbour had enquired about FIEBRE: a lady from a village nearby who came and asked her if any of her children became sick or were weak after participating in the study and having their blood taken. She assured the lady that the child would be fine and she should not get worried. 
The team was interested in what people in the village do when they get sick; the participant and the village headwoman explained that a few individuals buy medicine mainly painkillers from within village shops while many of them go to the hospital when they became sick.
The team asked about the demographic and ethnic composition of the village. The village headwoman said that there are about 300 households in the village mainly headed by males apart from few households which are headed by females and children, and majority of them are from the Mang’anja tribe. The majority of the inhabitants of William village rely on farming as their main economic activity almost every household has a piece of land for farming and others keep livestock such as cattle, goats and chicken. Apart from farming, a few individuals have other jobs while others have small scale businesses.
One of the visitors asked how the village had changed over the years. The participant said that in the past most of the houses were grass thatched whereas now people are able to build iron-roofed houses, and people used to drink water from the wells and river and needed to walk long distances to get water, but now water comes from taps and boreholes.
The meeting concluded after approximately one hour with friendly farewells and handshakes. 

Meeting with FIEBRE participants and village elder

All four sites, Laos, Malawi, Mozambique and Zimbabwe, are now operating fully recruiting both adult and children out- and inpatients. 

The team at Centro de Investigação em Saúde de Manhiça (CISM) in Mozambique began enrolling adult patients at Manhiça Health Research Centre in mid-March after paediatric recruitment started in December 2019.

Two sites have now recruited over 500 patients. In January, Zimbabwe became the second site following Malawi. To enable enrolment of the full cohort expansion is under way in Malawi and Zimbabwe where nurses and research assistants have been taken on to recruit participants at new sites. The plan is to train staff and be ready to open up the new sites in April. 

All sites receive regular recruitment reports tailored to their specific data requirements providing details about the participants, number of controls, 28-day follow ups etc. These updates enable the teams to chart their progress and identify any potential issues.  

  CISM team

The second FIEBRE Annual co-investigators meeting was held in Zimbabwe from 3 - 6 December 2018. World-leading fever experts were involved in the meeting contributing to the discussions and plans for the study going forward.

Over 40 team members of the partner organisations attended the meeting including London School of Hygiene & Tropical Medicine, Liverpool School of Tropical Medicine, Barcelona Institute for Global Health (ISGlobal), Universities of Oxford and Otago, Centro de Investigacao em Saude de Manhica,  Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit , Malawi-Liverpool Wellcome Trust Research Programme and the Mahidol Oxford Tropical Medicine Research Unit. 

The Biomedical Training and Research Institute (BRTI) hosted the event attended by representatives from all aspects of the study - laboratory, technical, data, clinical, microbiology and social science.

There was a packed agenda covering:

• Country updates - site and personnel details, number of patients and controls recruited, logistical recruitment challenges
• Solutions to ethical and operational issues
• Open Data Kit
• Laboratory activities
• Update on protocol amendments and implications of the changes
• Reference laboratories
• Microbiology data and interim analysis
• Social science update on overall research questions and initial findings from fieldwork
• Complementary studies
• Dissemination of results
• Way forward, follow-on studies and future plans 

A visit to the Harare sites, Budiriro polyclinic, Chitungwiza General Hospital and Harare Central Hospital, and to the BRTI facilities, illustrated how the study proceeds from the initial recruitment of patients through data input to the samples being tested at the laboratory. 

The social science team held a subsequent meeting from 7-8 December to look at their progress and analyse the data collected so far.

The meetings were successful and resulted in detailed plans for the study's future.   

FIEBRE will be at the 67th Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) which takes place from 28 October to 1 November 2018 in New Orleans.

Several FIEBRE colleagues are participating in a symposium:

100,000 papers later: Reviewing and mapping the etiology of non-malarial febrile illnesses globally

Session 39, 29 October 2018, 16:00-17:45 h

Organizer: Philippe J. Guerin, Infectious Diseases Data Observatory (IDDO)

More details available on the ASTMH website. 

A co-investigators meeting will also be held with representatives from many of the partners and organisations involved in the study taking the opportunity to discuss progress so far.

FIEBRE is progressing well with three sites now enrolling participants and one prepared, ready to start.

October is a busy month with the London School of Hygiene & Tropical Medicine team travelling from Asia to Africa to hold training first in Laos then Mozambique.

The LOMWRU team in Laos, led by Dr Vilada Chansamouth, enrolled their first patient at the Vientiane Provincial Hospital on 11 October 2018.

The background to this was several weeks' of training in all aspects of the study at the MORU office in Laos and at CISM Manhica, Mozambique. This includes reviewing SOPs, data input with ODK, sample taking with colleagues, consent procedures and laboratory management. A range of clinical, technical, data and laboratory staff are all involved.   

After gaining experience from previous training and pilot sessions in Zimbabwe and Malawi the activities were adapted to meet the needs of the teams, as all the facilities and personnel involved have different specialisms and knowledge.

Issues have arisen as enrolment is ongoing. Analysis has shown that excluding children with symptoms of cough/fast breathing (only outpatients) has significantly limited recruitment in Zimbabwe, with the potential to do so in Laos and Myanmar. Therefore amendments to the selection criteria have been made to address this.

Questions have also arisen over the definition of fever and methods used by staff (axillary or tympanic measurement of temperatures) for study enrolment, as a result, the SOP is being adjusted to aid enrolment.   

The quick access to data through OpenDataKit from all sites enables such issues to be picked up swiftly, discussed and addressed to ensure the study continues to run smoothly, efficiently with consistency from country to country.

FIEBRE is holding a symposium during LSHTM week.

Fever, diagnosis and antimicrobials: the multi-disciplinary FIEBRE study 

Date: Monday, 17 September 2018    Time: 14.00–16.30 h
Where: Manson Theatre, London School of Hygiene & Tropical Medicine

The symposium will look at the challenges facing a large multi-disciplinary study taking place across sub-Saharan Africa and South East Asia.

The topics under discussion will be anthropology, paediatric and adult clinical care, antimicrobial resistance, standard and novel diagnostics, approaches to database management, project management and statistical issues.

This will be an opportunity to come along and find out about the latest data emerging from FIEBRE on the causes of fever, antimicrobial resistance, treatment seeking, case management and the roles of antibiotics.

Representatives from the Malaria Centre, AMR Centre and MARCH Centre will be presenting on several aspects of the study including: social science; clinical value of biomarkers; use of and experience of ODK to enable real-time data access; and recruitment of controls.

Speakers include: Shunmay Yeung; Heidi Hopkins; Clare Chandler; Sham Lal; John Bradley; Ioana Olaru and David Mabey. 

A recording of the event is available online. 

The first patient was enrolled in the study on 22 June 2018 by the team at Biomedical Research and Training Institute (BRTI) in Harare.

The plan is to enrol 2400 febrile patients at each of five sites, over a 12-month period at each site to account for possible seasonal variation. The patients will include children and adults, both inpatients and outpatients. 

On the day of enrolment a venous blood sample is taken, a nasopharyngeal swab (to test for respiratory viruses) and in addition a urine sample from young children and patients of any age who have possible urinary tract infection symptoms. At the initial assessment stage, the team will, also undertake diagnostic tests (such as malaria tests and blood culture) that are of immediate clinical benefit to the patient, and for research purposes.

The focus of the study is on infections that are treatable and/or preventable. Participants will also be asked to return in 28 days’ time when a further blood sample will be taken for serology. Community control participants are also recruited to provide additional data for interpretation of diagnostic tests, and information on antimicrobial use in the surrounding communities.

Although fever is one of the most common presenting symptoms there have been few studies on its potential causes. FIEBRE will provide valuable data to help identify the causes of fever in settings where diagnosis is not usually available in real time, thus enhancing the quality of local care.

Recruitment of patients at the Malawi site in Chikwawa is due to begin in the coming weeks, following training sessions and collaborative work to refine data collection tools and to address site-specific logistical aspects.