MADEX proposal

 

 

 

 

MADAGASCAR MEDICAL EXPEDITION 2016

 

RESEARCH PROPOSAL

 

Abstract

This expedition will investigate the disease morbidity of schistosomiasis in school-aged children (SAC; aged 5-14) in the Marolambo district of Madagascar.

Schistosomiasis is classified by the World Health Organisation as one of seventeen Neglected Tropical Diseases. Schistosoma mansoni is the aetiological agent for intestinal schistosomiasis, responsible for significant worldwide morbidity and mortality. It is estimated that globally 243 million people are infected.

In 2015, we lead an expedition that found an extremely high prevalence (94%) in 6 schools in the Marolambo district. We plan to return to the same schools and investigate the morbidity of schistosomiasis within this population. Through structured questionnaires, we will also collect information on local beliefs and understanding of schistosomiasis. While in the villages, we will be running a health education programme and supplying Schistosomiasis treatment.

The team consists of the founder and leader, Dr. Stephen Spencer, and two 4th year medical students James Penney and Cortland Linder. As part of the development of this project we have nurtured collaborative links with nationally and internationally recognised institutions such as the World Health Organisation, the Durrell Conservation Foundation, the Madagascar Ministry of Health and the Faculty of Medicine, University of Antananarivo. Whilst in the field we will be supported by the Durrell Foundation and will be working with counterparts from the Madagascar Ministry of Health and students from the University of Antananarivo. This contributes to a long-term objective to continue collaboration between the University of Manchester and the University of Antananarivo.

This project has received formal approval by the Madagascar Ministry of Health, and is awaiting ethical approval from the University of Manchester. We have received sponsorship from a number of organisations, including the Royal Geographical Society and the University of Manchester Learning Enrichment Fund.

We will depart for Madagascar on 20th May 2016.

  1. Aims
  • 1. Primary aim – To determine the morbidity and disease burden of schistosomiasis in school-aged children (SAC) in the Marolambo District of Madagascar.

 

  • 2. Breakdown of objectives
  1. To screen SAC for signs and symptoms of schistosomiasis in Marolambo District of Madagascar to gain up-to-date information regarding incidence and morbidity of schistosomiasis in this population.
  2. To conduct structured qualitative questionnaires with health professionals (doctors, nurses, midwives), headmasters, and senior village individuals in the Marolambo District of Madagascar to gain up-to-date information regarding understanding and beliefs around the burden of schistosomiasis in this population.
  3. To run an educational program for the school staff and parents in order to reduce reinfection rates.

 

  • 3. Long-term goals

As part of ensuring sustainability of the project we are intending to implement some long -term goals.

  1. To continue the academic collaboration between the University of Manchester and the University of Antananarivo with a view to sending recurrent teams to Madagascar for further epidemiological research with a view to tackling neglected tropical diseases.
  2. To improve local awareness of Schistosomiasis to develop an integrative approach to reducing the prevalence of schistosomiasis.
  3. Build evidence of the burden of schistosomiasis to promote regular implementation of Mass Drug Administrations in the region.
  4. To perform analyses of disease burden within the region as part of a large study assessing the effectiveness of wellbeing interventions.

 

Two of the UK members of the team (James Penney and Cortland Linder) will be using the work as part of their Applied Personal Excellence Path (Project Option) for the fourth year of their undergraduate MBChB medical degree. These independent reports will look at different aspects of the expedition project and will each contribute to a final document.

 

  1. Background and justification

 

2.1 Why Schistosomiasis?

Schistosomiasis, commonly known as Bilharzia, is a chronic, parasitic disease caused by trematodes (genus Schistosoma). Schistosomiasis is one of 17 Neglected Tropical Diseases (NTDs), of which the eradication or control is paramount to the achievement of the Millennium Development Goals[1].

The disease burden of schistosomiasis is heavily under-recognised. Schistosomiasis is one of the most widespread and economically damaging parasitic disease, surpassed only by Malaria[2]. In 2011 the World Health Organization (WHO) estimated that 243 million people across 78 endemic countries were in need of treatment for schistosomiasis[3]. In Africa alone, approximately 1.7 million DALYs (Disability adjusted life years) are lost each year, around 20 million suffer from the serious complications of schistosomiasis and over 200,000 people die each year.

 

2.2 Who gets schistosomiasis?

Schistosomiasis is a disease of poverty, affecting rural communities in remote regions of the world. It is particularly prevalent in people without access to safe drinking water and adequate sanitation and hygiene. Approximately 90% of those with schistosomiasis live in Africa[4]. Humans from resource poor environments where schistosomiasis is endemic, and who utilise streams, rivers or lakes for sanitation, drinking, cleaning and play, are particularly at risk of infection[1][2].

 

2.3 How do people get schistosomiasis?

Schistosomiasis is a disease in which the parasite, Schistosoma spp., passes through freshwater snails before infecting humans. The snails act as intermediate hosts for the parasite. Once in water, the Schistosoma leave the snails and penetrate the skin of humans entering infested waters. The small parasites tunnel into the blood stream where they circulate and reside in the venous plexus of the bladder (S. haematobium) and the mesenteric veins of the bowel (S. mansoni). They feed from nutrients in the host’s blood, and mature into adult worms, and release their eggs into the blood stream. These eggs pass out of the body via faeces or urine back into fresh water, where they penetrate host snails, thus completing the life cycle (Figure 1)[5].

However, some eggs may get trapped in other bodily organs where they stimulate immune reactions. It is not the damage directly from schistosomes but rather the immune reaction, which results in progressive damage to tissues[5].

 

2.4 Types and Symptoms of Schistosomiasis

Schistosomiasis can either infect the intestine (S. mansoni) or the urogenital tract (S. haematobium). Both intestinal and urogenital types are found in Madagsascar, but our 2015 study confirmed that villages in the Marolambo District of Madagascar had only intestinal Schistosomiasis. Therefore for this study, we will consider only the intestinal type of Schistosomiasis (S. mansoni).

Infestation with Schistosomiasis can present with varying degrees of severity. The vast majority of people are generally asymptomatic, or have largely non-specific symptoms such as tiredness and poor weight gain. Intestinal schistosomiasis can cause bleeding into the bowel, leading to blood in the stool. In addition to this chronic infection can lead to blockage of the intestines, high blood pressure in the liver blood vessels, which can cause life-threatening bleeds at other sites around the body (oesophageal varices). Furthermore, long-term infection in the liver can lead to progressive liver fibrosis.

Chronic anaemia, liver fibrosis and malaise affect children in particular. When not fatal, the lasting effects are stunting, a reduced ability to learn and increased susceptibility to other infections. Encouragingly, the effects of the disease are usually reversible with treatment [5].

 

2.5 Treatment of Schistosomiasis and impact of disease

Praziquantel is an antihelmintic drug that is excellent in treating schistosomal infections and it is currently the only drug in use for mass drug administration (MDA). It is thought to paralyse the parasite, exposing it to the host’s immune system for destruction. Only one dose is required to treat schistosomal infection meaning that there is a great potential for success with relatively few potential complications. However, there has been a reported 20% failure rate of single dose praziquantel in juvenile infections and therefore follow-up and retreatment is advised. Although re-infection may occur after treatment, the risk of developing severe disease is diminished and even reversed when treatment is initiated and repeated in childhood.  Annual or biennial reviews would hopefully show a drop in infection rates. If a second round of treatment is given at this time, incidence should continue to fall. Since humans are an integral part of the schistosome’s life cycle, regular eradication reviews will cause a decline in the overall parasite population, reducing the risk of infection for the community[10].

People suffering from schistosomiasis very rarely seek medical help due to several reasons:

  1. The most common symptoms of the disease are non-specific
  2. There is poor knowledge of disease due to lack of health education
  3. There is poor access to health care in the majority of resource-poor regions where schistosomiasis is most prevalent.

It is essential that large scale screening and treatment programmes are developed in these populations to control disease and to educate communities of the disease risk factors and symptoms[9]. Furthermore, treatment programmes must be adapted to the specific communities, to ensure maximum efficiency.

The Malagasy government will be using this as an opportunity to extend their mass treatment programme into this remote area of Madagascar. This may also offer the opportunity to future students to return and re-assess the success of the programme comparing with our original prevalence study data.

 

  1. Why Madagascar?

In 2012 the WHO estimated that 16 million people in Madagascar required preventative chemotherapy (PC) for schistosomiasis. The current population of Madagascar is 20 million. In 2009, less than 20% of those needing PC for schistosomiasis received treatment. A great deal of information is required to determine the re-infection rates in treated communities as well as trend information from treatment-naive communities. This will demonstrate whether or not widespread treatment in Madagascar is lowering the prevalence amongst communities that have never specifically received treatment. Without this essential data it is impossible to determine which areas are in greatest need of treatment and should be a focus for control of the disease.

 

 

  1. Methodology

4.1 Site selection

From a base in Marolambo village in the centre of the Nosivolo watershed, we will survey 6 villages along the Nosivolo river. These villages were all found to have extremely high prevalence of schistosomiasis in the 2015 expedition. The villages are selected from those which Durrell Madagascar has been working with over the last decade. This will allow us to continue good relations with the villages, and to have access to Centres de Sante de Base (CSB) health centres and village primary schools.

 

4.2 Overview of programme

The research is a cross-sectional research field project, looking to assess the infection intensity of schistosomiasis, as well as the clinical morbidity of the disease.

In total we will spend 3 weeks collecting data. We will spend 3 days in each village, including time for travelling between villages and making introductions. We will stay in and work from the CSBs in each village, and children will come to the CSB for testing.

The team will consist of 3 British team-members (Dr Stephen Spencer, Mr James Penney and Mr Cortland Linder) and 4 Malagasy team-members. The Malagasy team will comprise Dr Alain Rahetilahy (Head of Infectious Disease Control, MoH Madagascar) and colleagues from the University of Antananarivo.

 

4.3 Itinerary

Before our arrival in each village, local healthcare professionals, headteachers, and village chiefs will have been made aware of our project and arrival dates (through our collaboration with Durrell). Lists of children to be surveyed will be drawn up by headteachers of each school.

Our itinerary for each village is as follows:

Day 1

  • Morning – children will progress through the following stations:
    • o Questionnaire
    • o Utrasound scan
    • o Anthropometrics
    • o Finger prick blood (anaemia/malaria)
    • o Distribute stool sample containers
    • o Distribute urine sample containers
  • Afternoon:
    • o Collect stool sample containers
    • o Collect urine sample containers
    • o Malagasy team – interview local leaders/headteachers
    • o Manchester team – prepare Kato-Katz slies
    • o Manchester team – perform faecal occult blood test and CCA test

Day 2

  • Morning:
    • o Malagasy team – conduct 20 metre shuttle-run test (10 children per test)
    • o Manchester team – prepare/analyse Kato-Katz slides
  • Afternoon:
    • o Malagasy team – conduct educational programme
    • o Manchester team – analyse Kato-Katz slides

Day 3

  • Morning:
    • o Wrap up – clean and dry all equipment, pack up kit
    • o Praziquantal administration
    • o Journey to next village
  • Afternoon:
    • o Introductions made at next village

 

4.4 Details of methods

Questionnaire

Each child will be interviewed by Malagasy members of the team. Symptomatic history of schistosomiasis will be assessed, as this offers good indication of schistosomiasis morbidity. We will also investigate the social understanding of schistosomiasis, including knowledge of transmission factors and treatment practices. Water contact behaviour will be investigated to determine main source of infection. Finally, Quality of Life will be assessed using the PedQL assessment questionnaire. Full questionnaire can be seen in Appendix 5.

At each village, local leaders will be interviewed to determine socio-economic status of villages. Occupations, educational status and living arrangements of villagers will be investigated.

Liver Ultrasound Scan

Using a portable ultrasound scanner, trained Malagasy technicians will scan the liver of each child, following WHO recommendations. Scarring of the liver (peri-portal liver fibrosis) will be measured by the quantity of artery wall thickening compared to the patterns A, B, C, D, E and F, in accordance with the Niamey Protocol. This is a sensitive, non-invasive method of assessing schistosomiasis-related morbidity.

Anthropometrics

All children will be measured according to proper procedures. Weight will be obtained by digital weight scale, and rounded to the nearest 0.1kg. Height will be measured using a statiometer and rounded to the nearest 1.0cm. Each measurement will be performed twice and the mean values used for analysis. Height-for-age and body-mass index for age will be calculated, and compared against reference populations using reference growth standards from WHO/CDC.

Rapid-diagnostic-test for Anaemia and Malaria

Finger-prick blood will be used to obtain red blood cell measurement (using Hemacue point-of-care tests). Anaemia will be categorised according to WHO criteria by age and sex. As anaemia and other symptoms are also caused by malaria, we will use finger prick blood to also test for P. falciparum for malaria. Any children testing positive for malaria will be sent for treatment at the local health centre.

Urine-CCA cassette testing

To assess schistosomiasis infection, mid-morning urine samples (1000-1200 hours – peak time for egg levels) will be collected from all children. Presence of schistosomiasis infection will be tested using CCA cassette tests. A drop of urine will be placed onto the cassette, with a buffer added. The result is read exactly 20 minutes after the Buffer is added, the result is recorded as negative (0) or positive (1+, 2+ or 3+). Any results read outside 25 minutes will be considered invalid and must be repeated. Used test cassettes will be disposed of into a medical waste bag.

Faecal occult blood test

Stool samples will be collected from each child, and tested using Instalert Onestop Faecal Occult blood test device (innovacon, Inc. San Diego, Ca). A stick is used to collect 3 samples in the faeces, which are mixed with buffer and suspended. After 5 minutes, results show absence or graded severity of blood in the stool.

Kato-Katz examination

Stool samples will then be processed using the Kato-Katz method to quantify infection intensity.

Material needed to perform the Kato-Katz cellophane faecal thick smear technique:

  1. Wooden applicator sticks
  2. Stainless steel screen (60 mesh)
  3. Plastic template (41.7 mg a hole of 6 mm on a 1.5mm thick template in line with standard Madagascar protocol)
  4. Plastic spatula
  5. Newspaper
  6. Microscope slides (75 x 25 mm)
  7. Hydrophilic cellophane (40-50 μm thick, strips 25 x 30 mm) soaked in glycerol-malachite green solution
    1. To prepare these cellophane strips, 1ml of 3% aqueous malachite green is added to 100ml glycerol and 100ml distilled water and well mixed. This solution is poured onto the cellophane strips and left in a jar for at least 24 hrs prior to use.

A small amount of faeces will be placed on the sheet of newspaper using an applicator stick. A screen will be pressed on top so that some of the faeces filters through, the filtered faeces will be collected by scraping a plastic spatula across the upper surface. The collected faeces will be added to the template so that the hole is completely filled. The template will be removed carefully, leaving a cylinder of faeces on the slide. The faecal material will be covered with a pre-soaked cellophane strip, and the material spread evenly. The slide will be labelled, and left in direct sunlight for several minutes or at an ambient temperature for one or more hours. This allows the glycerol to clear the faecal material prior to examination. The slide will be observed under a light microscope. Quantity of schistosoma mansoni eggs will be recorded on the form. The eggs-per-gram will be classified as a mild, moderate or heavy level of infection, according to WHO guidelines.

Slide examination must be done on the same day, but a delay of several hours is acceptable. The cellophane and faecal material will be disposed of into a medical waste bag. The slide, screen, template and plastic spatula will be disinfected and re-used.

20 metre shuttle-run test

All children will perform a 20 metre-shuttle-run test. This is a standardised, easy-to-perform, low-technology test of physical fitness, and should be enjoyable for the children. A flat area of ground will be chosen (potentially football fields, which are in all villages). A group of 5-10 children will be instructed to run back and forth on a 20 metre track, reaching the other end in time with bleep played from a portable CD-player. The bleeps will become progressively closer together as the levels progress. When children can no longer follow the pace, he/she will be asked to stop, and their highest level obtained will be recorded as a fitness score. Higher scores correlate with better fitness.

Education programme

An education programme on basic hygiene and infection control, to improve schistosomiasis understanding and health behaviours of the population, with be delivered, using resources donated by Manchester Immunology Group.

Overseeing Praziquantel distribution

The treatment for schistosomiasis is Praziquantel (one dose of 40mg/kg).  We will work with Dr Alain Rahetilahy, of the Madagascar Ministry of Health, to supervise the distribution of this medication by local doctors in local health centres, to the population.  The rationale behind distributing Praziquantel via a Mass-Drug-Administration approach is as follows: in 2015, we found a 94% prevalence in this area.  The WHO guidance on prophylaxis for schistosomiasis recommends Mass-Drug-Administration to any population that has a prevalence of greater than 50% of schistosomiasis.

 

  1. Personnel

 

5.1 UK Team

Founder and Expedition Lead – Dr. Stephen Spencer FRGS (British)

Stephen led the 2015 expedition to Marolambo, to investigate the prevalence of schistosomiasis. Stephen graduated with a BSc in Zoology from Edinburgh University in 2008 and is currently working as a Foundation Year 2 Doctor in the North West Deanery, Stephen has co-organised and been Medical Officer for three previous expeditions and has worked as an instructor for Wilderness Medical Training™. His first expedition involved two months in the Bornean primary rainforest in 2007, researching the effects of logging on reptiles, amphibians and birds. In 2008 he led a reconnaissance to Sulawesi in order to set up a coral reef conservation centre; a project that went to the final round of the Rolex Young Laureate Award. In 2010 he organised a research expedition to the Sea of Cortez to search for and photograph the world’s rarest marine mammal, the Vaquita porpoise. Stephen is a Fellow of the Royal Geographical Society (RGS), has been awarded the Zochonis Award for his work in Mexico and has spoken widely on the field of ‘Expedition Medicine’, including at the RGS annual conference ‘Explore’ on ‘Student-Led Expeditions’. With a strong interest in Tropical Medicine and Global Health, Stephen has carried out work placements in hospitals in Kuala Lumpur and Kota Kinabalu, Malaysia and Mansoura University Hospitals. In June 2014 Stephen completed a diving research expedition in Mexico looking at barotrauma.

Research Coordinator and Treasurer – Mr Cortland Linder (British)

Cortland is a 4th year medical student from the University of Manchester. He is on the committee of Manchester University Expedition Society. In 2015, Cortland completed a Masters in Genetic Medicine as an intercalated degree, which has given him experience in laboratory work and academic writing. Cortland has done work experience with the media company Seeper, and has some experience in filming. In 2012, Cortland taught outdoor skills and climbing to children in Camp Equinunk, PA, USA. He is also an avid cycler and climber, and has done multiple small expeditions with the University of Manchester climbing society.

International Communications Lead – Mr. James Penney (British)

James was Research Lead for the 2015 expedition to Marolambo. James is a 4th year medical student from the University of Manchester. Last year he undertook an intercalated BSc (Hons) in Physiology, which provided him with vital experience in laboratory methodology. James has a wealth of experience in logistics from the planning and execution of unsupported hikes across Corsica, French/Italian Alps, and cycles twice through France, and from Barcelona to Dubrovnik. Further Wilderness Medical Training is arranged for May 2016. James is also a conversational French speaker.

 

5.2 International Collaboration

Madagascar Ministry of Health: Dr Alain Rahetilahy, Lead of Preventative Chemotherapy, Head of Department of Epidemic Diseases and Tropical Neglected Diseases, National Coordinator for the Control of Schistosomiasis/Helminthiasis, Ministry of Public Health, Madagascar. Dr Rahetilahy has provided us with invaluable information of in-country schistosomiasis epidemiological data. Dr Alain provided in-country supervision to the 2015 expedition, and will accompany us in the field for the duration of the 2016 expedition.

University of Antananarivo: Dr Luc Samison, Acting Dean of the Medical Faculty. We have formed a formal collaboration with the University of Antananarivo. This collaboration will enable Malagasy medical students with an interest in Preventative Chemotherapy/Neglected Tropical Disease research the opportunity to join us in location in rural Madagascar.

Durrell Wildlife Foundation Madagascar. Herizo Andrianandrasana. A collaboration with Mr. Andrianandrasana, a representative of Durrell Foundation Madagascar and DPhil Candidate at the Univeristy of Oxford has allowed us to develop a project plan which will use well established research sites in the Marolambo region, as well as access on-the-ground contacts to gain permission from local village representatives/leaders.

 

5.3 Key Advisors

Dr Lester Chitsulo, Head of Preventive Chemotherapy and Transmission Control Unit Control of Neglected Tropical Diseases, World Health Organization http://www.who.int/neglected_diseases/preventive_chemotherapy/en/

Dr. Alain Rahetilahy, Lead of Preventative Chemotherapy, Head of Department of Epidemic Diseases and
Tropical Neglected Diseases, National Coordinator for the Control of Schistosomiasis/Helminthiasis, Ministry of Public Health, Madagascar. Dr Rahetilahy has been critical in developing the expedition with particular focus on Schistosomiasis epidemiological fieldwork.

Professor Anthony Freemont, Dean of Undergraduate Department, University of Manchester Medical School. Professor Freemont has provided us advice how to seek University and Ethical approval.

Dr. Peter Long, James Martin Fellow, Biodiversity Institute, Department of Zoology, University of Oxford. Dr. Long has provided advice and guidance regarding fieldwork aspects whilst out in Madagascar, as well as establishing contacts with on the ground organisations in the Nosivolo region.

Professor Russell Stothard & Professor Bertie Squires (Liverpool School of Tropical Medicine and Hygiene) and Dr Amaya Bustinduy (St. George’s, University of London), have provided extensive advice on methodology.

Dr Jane Wilson-Howarth, Expedition Leader, GP, Zoologist and Author. Jane designed and led a schistosomiasiasis research expedition to Madagascar in the 1980s.  She provided advice during the initial planning stages in 2013 and put Stephen in contact with the necessary people to kick-start the expedition.

Drs. Mark Lewis and Kate Millichamp. Both Dr. Lewis and Dr. Millichamp are 2014 medical graduates of the University of Manchester. They designed and set up the foundations of this research/clinical expedition with Dr. Stephen Spencer, and were fundamental to the organisation of the project.

Dr Ian Stanley (consultant anaesthetist and ICU) and Dr Chris Kosmidis (consultant in infectious diseases) will be providing medical advisory roles in case of medical emergencies in the field.

 

  1. Visas and Permits

Research permits are being sought from the Madagascar Ministry of Health.

 

  1. Ethical approval

The project has obtained ethical approval from the University of Manchester Research Ethics Committee.

 

  1. Health and Safety

The risk analysis and safety management plan has been reviewed and approved by The University of Manchester (Manchester Medical School) with any suggested amendments made.

 

  1. Financial Information

Funding has been obtained from various sources, including the University of Manchester, the Royal Society of Medicine, the Royal Geographical Society, and other independent funding bodies.

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