Malaria-Forschung

Abgerufen am 29.07.2013:  Neues aus der Malaria-Forschung
Neues aus der Malaria-Forschung

Neues aus der Malariaforschung

Als Teil des 6. Forschungsrahmenprogramms der Europäischen Kommission wurde die Initiative EDCTP (European and Developing Countries Clinical Trials Partnership) im Jahr 2003 gegründet. Sie wird vom Bundesministerium für Bildung und Forschung (BMBF) unterstützt. Ihr Ziel ist es, sich mit gemeinsamen Forschungsprojekten an der Bekämpfung der drei häufigsten armutsbedingten Erkrankungen zu beteiligen: HIV/AIDS, Tuberkulose und Malaria. Allein an diesen drei Infektionskrankheiten sterben weltweit jährlich rund sieben Millionen Menschen.

Die am stärksten betroffenen Regionen sind die afrikanischen Länder südlich der Sahara. Aus diesem Grund haben sich innerhalb der EDCTP 14 EU-Mitgliedsstaaten sowie die Schweiz und Norwegen mit 47 afrikanischen Staaten zusammengeschlossen und gemeinsame Forschungsaktivitäten gestartet. Dabei besteht eine gleichberechtigte Partnerschaft zwischen europäischen und afrikanischen Institutionen und Forschern, die durch Wissensaustausch und gemeinsame Weiterbildung getragen wird. Besonders wichtig ist es den Akteuren, dass die Forschungsergebnisse gemeinschaftlich in die medizinische Praxis umgesetzt werden und die Erkrankten vor Ort möglichst rasch von den Innovationen profitieren können. Daher finanziert die EDCTP vor allem klinische Studien in Phase II und III, die in den betroffenen Regionen durchgeführt werden. Europäische und afrikanische Akteure bauen hierfür gemeinschaftlich eine personelle und organisatorische Infrastruktur für klinische Forschung auf, die eine nachhaltige wissenschaftliche Arbeit und einen raschen Ergebnistransfer sicherstellen. Aktuell sind drei neue Forschungsprojekte zur Prophylaxe und Therapie von Malaria gestartet, die vom BMBF gefördert werden.

Bald neue Malariatherapie bei Kindern?
In den afrikanischen Ländern sind Kinder unter 5 Jahren besonders häufig von Malaria betroffen. Für sie stehen jedoch nur wenige adäquate Medikamente zur Verfügung. Daher unterstützt die vom Bundesministerium für Bildung und Forschung (BMBF) mitgetragene Initiative EDCTP (European and Developing Countries Clinical Trials Partnership) nun eine multizentrische Studie, bei der die Wirksamkeit eines Anti-Malaria-Medikaments bei Kindern untersucht werden soll, dessen Wirkung bei Erwachsenen bereits erwiesen ist. Bisher gilt Chinin als Standardtherapie für Malaria bei Kindern. Dieser Wirkstoff wird bereits seit Jahrzehnten für die Behandlung von Malaria eingesetzt. Als problematisch erweisen sich jedoch die zunehmenden Resistenzen der Erreger gegen Chinin und die generell schlechte Verträglichkeit der Substanz. Bei Erwachsenen werden daher zahlreiche andere Wirkstoffe zur Therapie der Malaria eingesetzt, wie etwa Artesunat. Dieses Präparat hat den Vorteil, dass es besser verträglich ist, schneller wirkt und in einem größeren Dosisbereich eingesetzt werden kann als Chinin. Forscher nehmen an, dass Artesunat sich daher besonders gut für die Malaria-Therapie bei Kindern eignet. Im Rahmen der vom BMBF geförderten Studie wird nun die Verträglichkeit und Wirksamkeit von Artesunat im Vergleich zur herkömmlichen Therapie mit Chinin bei Kindern untersucht. Wenn sich Artesunat in der Studie dem Chinin tatsächlich als überlegen erweist, wollen die deutschen Forscher gemeinsam mit ihren afrikanischen Kollegen die Behandlungspraxis von Malaria bei Kindern verändern.

Ansprechpartner:
Dr. Carsten Köhler
Direktor des Kompetenzzentrums Tropenmedizin
Baden-Württemberg
Eberhard Karls Universität Tübingen
Wilhelmstraße 27
72074 Tübingen
Tel.: 07071 2980229
Fax: 07071 295189
E-Mail: carsten.koehler@medizin.uni-tuebingen.de

Klinische Studie zur Erforschung von Malaria-Impfstoff gestartet
Malaria ist eine der häufigsten Infektionskrankheiten weltweit. Als wichtigste Maßnahmen zur Prophylaxe von Malaria gelten derzeit die Einnahme von Medikamenten und der Einsatz von insektizid-behandelten Moskitonetzen; sie ermöglichen allerdings keinen umfassenden Schutz vor der Erkrankung. Daher suchen Wissenschaftler weltweit nach einem effektiven Impfstoff gegen Malaria. Die klinische Forschung mit Malaria-Impfstoffen wird von der Initiative EDCTP (European and Developing Countries Clinical Trials Partnership) mit Unterstützung des Bundesministeriums für Bildung und Forschung (BMBF) gefördert.

In den aktuellen Phase I-IIb Studien wird der Impfstoff-Kandidat GMZ2 getestet. Dabei handelt es sich um ein Fusionsprotein, das zwei wichtige Antigene (GLURP, MSP3) des häufigsten Malaria-Erregers Plasmodium falciparum „nachahmt“. Dem klinischen Einsatz dieses gentechnisch hergestellten Impfstoffes gingen zahlreiche Laborversuche und Blutuntersuchungen voraus. Forscher wissen bereits seit langem, dass Menschen aus Regionen, in denen Malaria besonders häufig auftritt, gegen die Entwicklung einer sehr schweren Malaria geschützt sind. Im Blut dieser Personen konnten Antikörper nachgewiesen werden, die Erkrankten aus anderen Gegenden bei der Therapie der Malaria helfen. Lange haben Wissenschaftler versucht, die Antigene des Malaria-Erregers zu identifizieren, die für die Bildung der „schützenden“ Antikörper bei den Infizierten verantwortlich sind. Mit den Antigenen GLURP und MSP3, die in Laborversuchen vielversprechende Resultate lieferten, hoffen die Tübinger Wissenschaftler jetzt, geeignete Impfstoff-Kandidaten gefunden zu haben, die sich dann auch bei der Behandlung von Menschen als wirksam erweisen.

Impfstoffe werden als besonders effektiv für den Schutz der afrikanischen Bevölkerung vor Malaria erachtet, da die erweiterten Impfprogramm der Weltgesundheitsorganisation (WHO) in den meisten afrikanischen Ländern gut etabliert sind. Eine Malaria-Impfung ließe sich dort leicht eingliedern.

Ansprechpartner:
Dr. Benjamin Mordmüller
Institut für Tropenmedizin
Universität Tübingen
Wilhelmstraße 27
72074 Tübingen
Tel.: 07071 29-82187
Fax: 07071 29-5189
E-Mail: benjamin.mordmueller@uni-tuebingen.de

Neuer Wirkstoff soll Komplikationen bei Schwangeren mit Malaria verhindern helfen
Eine Malaria-Infektion während der Schwangerschaft führt in Afrika häufig zu lebensbedrohlichen Erkrankungen der Mütter und zu einer erhöhten Sterblichkeit der Neugeborenen. Komplikationen während der Schwangerschaft nehmen ab, wenn die Konzentration der Malaria-Erreger im Blut der Mutter während der gesamten Schwangerschaft niedrig bleibt und/oder die Zweit-Infektion verhindert wird. Daher wurden bislang zur Prävention von Malaria-bedingten Komplikationen während der Schwangerschaft vor allem insektizid-behandelte Moskitonetze und das Anti-Malaria-Mittel Sulfadoxin-Pyrimethamin eingesetzt. Aufgrund zunehmender Resistenzen der Erreger gegen die bisherigen Medikamente sind jedoch Alternativen zur Standardbehandlung von Schwangeren notwendig. Die auch vom Bundesministerium für Bildung und Forschung (BMBF) unterstützte Initiative EDCTP (European and Developing Countries Clinical Trials Partnership) fördert daher die Untersuchung weiterer potenzieller Wirkstoffe als Ersatz für die bisherige Standardtherapie. Aussichtsreichster Kandidat ist Mefloquin. Von diesem Wirkstoff ist bereits bekannt, dass er sehr effektiv und sicher während der Schwangerschaft ist.

In der multizentrischen randomisierten klinischen Studie soll jetzt getestet werden, ob die Verwendung von Mefloquin auch zur Prävention von Malaria-bedingten Komplikationen während der Schwangerschaft eingesetzt werden kann. Dazu werden unter anderem das Gewicht der Neugeborenen, die Rate an Frühgeburten und die Erkrankungsrate an Blutarmut (Anämie) bei den Müttern verglichen. Sollten diese Parameter nach einer präventiven Gabe von Mefloquin oder einer der anderen getesteten Substanzen tatsächlich günstiger ausfallen als nach Durchführung der bisherigen Standardtherapie mit Sulfadoxin-Pyrimethamin, könnte sich die Behandlungspraxis zur Prävention von Malaria-bedingten Komplikationen während der Schwangerschaft in den afrikanischen Ländern ändern. Den entstandenen Resistenzen des Malaria-Erregers gegen herkömmliche Präparate würde dann auch in der besonderen
Situation einer Schwangerschaft besser Rechnung getragen. Das Projekt wird gemeinsam vom Institut für Tropenmedizin an der Universität Tübingen und der Medical Research Unit des Albert Schweitzer Spitals in Lambaréné, Gabun, durchgeführt.

Ansprechpartner:
PD Dr. Michael Ramharter
Institut für Tropenmedizin
Universität Tübingen
Wilhelmstrasse 27
72074 Tübingen
Tel.: 07071 29-87179
Fax: 07071 29-5189
E-Mail: michael.ramharter@medizin.uni-tuebingen.de

Stand 10.07.2013

http://www.bild.de/ratgeber/gesundheit/bill-gates/melinda-gates-global-fund-exklusiv-in-bild-aids-tuberkulose-malaria-drei-toedliche-krankheiten-eine-ursache-30895066.bild.html

AIDS, TB AND MALARIA Three Deadly Diseases, One Common Cause

Exklusive: Melinda Gates writes in BILD about the Global Fund and investments that save lives

Research
Deutschland * Uni Heidelberg
http://www.klinikum.uni-heidelberg.de/ShowSingleNews.176.0.html?&no_cache=1&tx_ttnews%5Btt_news%5D=6343

Neuer Impfstoffkandidat soll Schwangere und ihre Kinder vor Malaria schützen

101/2012 30.08.2012

Europäische Impfstoffinitiative an der Universität Heidelberg und französisches Forschungsinstitut kooperieren / BMBF fördert mit rund 4,4 Millionen Euro

[Bild in Druckauflösung]
Frauen und Kinder in Malariagebieten, wie hier in Gambia, sind besonders von der Erkrankung betroffen. Ein neuer Impfstoff soll Schwangere und Babys schützen. Foto: Fajara Research Centre, Gambia

Ein vielversprechender Impfstoffkandidat, der Schwangere und ihre Kinder gegen Malaria schützen soll, wird im Rahmen einer neu gegründeten europäischen Kooperation entwickelt. Dazu haben EVI (European Vaccine Initiative),  eine an der Universität Heidelberg niedergelassene europäische Impfstoffinitiative, und Inserm (Institut National de la Santé et de la Recherche Médicale, Frankreich) das Projekt EVI PRIMALVAC (“PRegnancyMALariaVACcine”) gestartet. Es wird über die Kreditanstalt für Wiederaufbau vom Bundesministerium für Bildung und Forschung (BMBF) mit rund 4,4 Millionen Euro gefördert.

Nach Zahlen der Weltgesundheitsorganisation (World Health Organisation, WHO) werden jedes Jahr ca. 50 Millionen Frauen, welche in von Malaria heimgesuchten Gebieten auf der ganzen Welt leben, schwanger. Geschätzte 10.000 dieser Frauen und 200.000 ihrer Kinder sterben infolge einer solchen Malariainfektion während der Schwangerschaft. Odile Leroy, geschäftsführende Direktorin von EVI, sagt: „Dieses Problem wurde lange nicht beachtet und einen Impfstoff gegen Schwangerschaftsassoziierte Malaria gibt es noch nicht. Solch ein Impfstoff würde jedes Jahr hunderttausende von Leben retten.“ Neue Vorgehensweisen und vermehrtes Engagement geben Hoffnung, die Folgen von Malaria bei schwangeren Frauen zu vermindern und die Gesundheit von Müttern und Neugeborenen zu verbessern. Dazu gehört auch das neue Kooperationsprojekt PRIMALVAC.

Studie soll zeigen, dass Impfung sicher und geeignet für Einsatz am Menschen ist

Schwangere Frauen sind besonders anfällig gegenüber Malaria, da ihr Immunsystem während der Schwangerschaft geschwächt ist. Schwangerschaftsassoziierte Malaria ist eine spezielle Unterkategorie von Malaria, bei der mit dem Malaria-Erreger Plasmodium falciparum infizierte Blutkörperchen in der Plazenta verklumpen. Ein bestimmtes Eiweiß des Parasiten, var2CSA, welches in der Membran der roten Blutkörperchen verankert ist, ist derzeit der vielversprechendste Kandidat für einen Impfstoff gegen Malaria in der Schwangerschaft. Nach mehreren Schwangerschaften bilden nicht-geimpfte Frauen, die zuvor die Schwangerschaftsassoziierte Malaria überlebt haben, Antikörper gegen dieses Protein und werden so resistent gegen diese Form der Malaria.

Dr. Benoit Gamain, der Entdecker des Impfstoffkandidaten bei Inserm, informiert: „Wir haben eine Region von var2CSA identifiziert, welche ein wichtiger Angriffspunkt für inhibierende Antikörper ist. Das Hauptziel von PRIMALVAC ist es, eine Machbarkeitsstudie zu erstellen, die belegt, dass ein Impfstoff, basierend auf var2CSA, sicher  und geeignet für den Einsatz am Menschen ist.“ Der Impfstoffkandidat wird 2013-2014 in die präklinische und klinische Entwicklung überführt werden und  hoffentlich dazu beitragen, Schwangerschaftsassoziierte Malaria zu verhindern und somit Schwangere und ihre Kinder zu schützen.

Initiativen gegen vernachlässigte und armutsbedingte Krankheiten

Das BMBF fördert insgesamt drei Produktentwicklungspartnerschaften (Product Development Partnerships, PDPs), um vielversprechende Initiativen gegen vernachlässigte und armutsbedingte Krankheiten über einen Zeitraum von vier Jahren zu unterstützen. EVI ist davon die einzige Partnerschaft, die in Deutschland angesiedelt ist und die sich der Entwicklung von Impfstoffen widmet. PDPs vereinen Expertise aus unterschiedlichen und komplementären Bereichen: der biomedizinischen Forschung und Entwicklung, der Industrie und aus dem Bereich der gemeinnützigen Organisationen. Sie erhalten finanzielle Unterstützung von öffentlichen und privaten gemeinnützigen Einrichtungen und Sponsoren, was gewährleistet, dass die Produkte zu geringen Kosten für die von den verschiedenen Krankheiten betroffenen Personen bereit gestellt werden können.

EVI (European Malaria Vaccine Initiative) ist eine der führenden europäischen Initiativen, um effektive, zugängliche und finanziell tragbare Impfstoffe gegen Malaria und andere armutsbedingte Krankheiten zu entwickeln. Seit bereits mehr als 10 Jahren hat EVI zur Entwicklung von 29 Impfstoffantigenkandidaten beigetragen, von denen 15 Kandidaten bisher bis zur Phase I in klinischen Studien weiterentwickelt werden konnten. Drei dieser Kandidaten befinden sich augenblicklich in der weiteren klinischen Entwicklung in afrikanischen Ländern südlich der Sahara. EVI ist an der Universität Heidelberg niedergelassen, welche gemeinsam mit dem Universitätsklinikum Heidelberg über das Forschungsprogramm „Heidelberg Centre for Infectious Diseases“ am Deutschen Zentrum für Infektionsforschung beteiligt ist. Koordinator für Heidelberg ist Professor Dr. Hans-Georg Kräusslich, Direktor des Departments Infektiologie am Universitätsklinikum Heidelberg.

Inserm, das 1964 gegründete französische „Nationale Institut für Gesundheit und Medizinische Forschung“, ist ein öffentliches wissenschaftliches und technologisches Institut, welches unter der gemeinsamen Führung des französischen Ministeriums für Gesundheit und des französischen Ministeriums für Wissenschaft operiert. Als einziges französisches öffentliches Forschungsinstitut mit ausschließlichem Schwerpunkt auf dem Bereich Gesundheit übernahm Inserm 2008 die Verantwortung für die strategische, wissenschaftliche und operativeKoordination der biomedizinischen Forschung. Diese Schlüsselrolle als Koordinator passt uneingeschränkt zu Inserm dank der hohen wissenschaftlichen Qualität seiner Arbeitsgruppen und seiner Fähigkeit, translationale Wissenschaft zu betreiben, angefangen vom Labortisch bis hin zum Patientenbett.

Weitere Informationen:
www.euvaccine.eu/portfolio/project-index/primalvac
Kontakt:
Dr. Nicola Viebig
Im Neuenheimer Feld 326
69120 Heidelberg
Tel: 06221 56 35965
Email: nicola.viebig@euvaccine.eu

Research

****************Tanzania *****************
http://www.ihi.or.tz/

Search for a malaria vaccine continues

posted 8 Jun 2013 23:32 by IHI Webmaster

Japanese researchers say they have developed a dry powder vaccine that cuts the risk of malaria developing in humans by 72 per cent. The researchers  from Osaka University have published the findings on the online US science  journal, PLOS One. The dry powder vaccine called BK-SE36, developed from a genetically-modified protein found inside the malaria parasite, is mixed with aluminium hydroxyl gel. According to reports, the vaccine has already undergone trials on adults in Japan and was also tested in a malaria-endemic area in northern Uganda between 2010 and 2011. Neither study found any  safety problems.

Research Products

The aim of IHI research activities is to move from basic science and discovery to policy and action. Research products include clinical trials of new candidate drugs and vaccines to combat malaria; testing implementing and monitoring new strategies for maternal and newborn health; studying fairness and equity in health sector financing and assessing strategies to improve health care access for vulnerable groups. Exploring new approaches to strengthen health information system is another key research product.

Some of the most recent research publications include:

IHI commemorates the World Malaria Day

posted 29 Apr 2013 03:52 by IHI Webmaster

The Minister for Health and Social Welfare Honourable Dr. Hussein Mwinyi today opened the Tanzania Malaria Control Forum 2013. The annual gathering, convened by the Ifakara Health Institute (IHI) in collaboration with the National Malaria Control Programme (NMCP), brings together researchers, government officials, development partners, members of the legislative bodies, civil society organizations,  mass media and representatives from the international malaria community.  The activity is part of this year’s commemoration of the World Malaria Day in Tanzania whose theme is: “Invest in the future. Defeat Malaria.” Various  researchers made presentations during the forum on progress in the fight against malaria in the country and beyond.

http://www.ihi.or.tz/system/app/pages/search?scope=search-site&q=Malaria


https://d45fadee-a-9486b535-s-sites.googlegroups.com/a/ihi.or.tz/ihi-main-site/new-announcements/updatesonmalariaandanaemiaprevalence/1.%20Summary%20of%20THMIS-%20Malaria%20and%20anaemia.pdf?attachauth=ANoY7cpIF2DIlBCsupXUDo_dvek5dZo1JV5E17DYDwZiF4-l0k-mnPU4-toXqmMgl08YQKfSBvgIMAmvdFAChUFZyQNit5h0oCz1Zop_BTlW2pwD_K95Xgzkh3GpYerDfFQmaV7tYY194WOxeKHgQGqtLRW1Vx1k08q-rqplez7UfCY3zR2KclXxnMxZ6k2glwBXCtIs8qM4Nc5WTws-OesrNUR09SlgG8doopIbOTRGR_Yesv53sxIiQCIHu9tLSBRq7r_oMONTpD0t5PjwV496XUWmLJjZKd2eMgcZLx6DsCa9129Tt4FijnoVToiT9tLrBfOzjKYX&attredirects=0

** ************************   SMRU   ****************************************************

Introduction

Video:

The Frontline of Artemisinin Resistance: SMRU on the Thai-Myanmar Border ARTE Reportage 2012 

ARTE reportage team travelled to Mae Sot in western Thailand, on the Burmese border, to visit the Shoklo Malaria Research Unit.

http://www.youtube.com/watch?v=WCI9PPLMdfg&feature=youtu.be

Shoklo Malaria Research Unit:
SMRU was established in 1986 in Shoklo. It is a field station of the faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, and is part of the Mahidol-Oxford Research Unit (MORU) supported by the Wellcome Trust (UK).Read more

SMRU : Shoklo Malaria Research Unit

Status:

SMRU was established in 1986 in Shoklo. It is a field station of the faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, and is part of the Mahidol-Oxford Research Unit (MORU) supported by the Wellcome Trust (UK). 
Read more about Health research activities in the region (brochure)

Location:

The S.M.R.U is now based in Mae Sot and the activities extend to the populations living along the Thai-Myanmar border.

Beneficiaries:

Population living along the border, including refugees and other migrants.

Objectives:

• 1. To treat and care for patients with malaria.
• 2. To define the epidemiology, entomology, and clinical features of malaria in this area of low (unstable) transmission, and to determine the best methods of prevention and treatment.
• 3. To advise the Thai Medical Institutions and the Non Governmental Organisations involved in the treatment and the control of malaria in the South East Asia region.

Project Objectives:

The projects are designed to be of direct benefit to the local community, and also to provide information useful to other populations living in malaria endemic areas elsewhere in the world through publications in mainstream international scientific journals.

Project Areas:

• I Malaria in Pregnancy and Infancy
• II Malaria treatment studies
• III Entomology
• IV HIV/Aids awareness and prevention of vertical transmission
• V Nutrition and Anaemia
• VI Laboratory studies
• VII Control of malaria and detection of epidemics along the border

Projects:

Current projects include: optimising the treatment of multi drug resistant malaria, investigating new antimalarial drugs, ante-natal care, epidemiological and malariometric surveys, studies on entomology and genetics of drug resistance, studies on vitamin B1 deficiency and studies on the neurological development of young infants. SMRU also collaborate in a campaign of Education on HIV/AIDS.

Staff:

More than 200 local staff (Nurses, Midwives, Medics, Lab-technicians, Data entry clerks, Administrator, Accounting officer, Home-visitors, Drivers, Cleaners) and 7 expatriates 5 Doctors, 1 laboratory scientist, 1 Laboratory technician).

Funding Bodies:

The Wellcome Trust of Great Britain, through the Wellcome-Mahidol University-Oxford Tropical Medicine Research Programme. In the past 14 years the SMRU has secured funding from various sources such as research grants, the pharmaceutical industry, the World Health Organisation, the European Union, VIHPAL (French Gvt). In 2000 SMRU (via Oxford University) was awarded a grant from the Bill and Melinda Gates Foundation to extend the control of malaria to the entire Tak Province in collaboration with the Thai Ministry of Health.

Long-Term Plans:

To continue to provide malaria clinics and conduct community based research to elucidate the best methods of malaria control, against a backdrop of ever increasing drug resistance. Recently, the Unit has initiated a programme of AIDS awareness. Although the situation seems under control in the refugee populations, there is a great concern that further disruptions or population movements could lead to devastating epidemics and spread of resistant malaria to neighbouring populations. The recently funded Tak Malaria Initiative provides an opportunity to strengthen the results obtained in the refugee population and extend it to all surrounding areas. 

Background

The Situation

Refugees:

There are more than 100,000 Karen, Mon, Karenni ethnic minority living in a string of refugee camps along the Thai-Burmese border. This area is endemic for malaria transmission which results in symptomatic infection in all age groups. In Shoklo camp the attack rate was 3 episodes per person per year for the potentially fatal P.falciparum parasite (which accounts for approximately 70% of infections). P.vivax accounts for 20% of cases, the remaining being mixed PF/PV. The most important medical problem confronting the refugee community is the increasing anti-malarial drug resistance. The main consequence of the deterioration of treatment efficacy is anaemia. Children are particularly susceptible to malaria induced anaemia. In 1992 mortality from malaria accounted for 15% of all deaths in the camps. Between 1995 and 2000 the burden of malaria has fallen dramatically in the refugee camps has a result of the strategy designed at SMRU and used by all medical NGOs.

The migrants:

In recent years the population influx from Myanmar has increased dramatically for both economic and political reasons. People from all ethnic groups (Shan, Karenni, Karen, Mon and Burman) are travelling back and forth across the border in search of work. It is thought that this population of migrant workers totals more than one million people in Thailand. Unlike refugees, they are highly mobile, and the majority does not have access to basic health care. Collectively, they harbour the majority of Thailand's malaria cases. This population of migrant workers, especially those living in the border areas, constitutes a major challenge to the control of malaria in the region and is now probably the major factor contributing to the spread of resistant strains of malaria. As they have done before, these strains will spread to the host population, the entire region, and later to other parts of the world. Given the paucity of new drugs against malaria this apparently local problem takes on a global dimension. Untreatable malaria infections would be a major threat to anyone living in or travelling to endemic areas. The "border population" can be seen as a mosaic of various communities linked by cultural and/or geographical similarities: Thai nationals (the majority is ethnic Karen), refugees and migrant workers from Myanmar. This complicates the task of the Thai Malaria Control programme because of language barriers, cultural differences and access difficulties. As a result, many individuals remain out of reach of the otherwise highly efficient malaria control efforts. SMRU has initiated novel approach for an effective malaria control programme in the populations living along the Thai-Myanmar border, through existing and new medical facilities, based on extensive experience with the displaced populations living in camps in this area.
This malaria research and control project differs from nearly all others in that it proposes to evaluate and deploy a strategy based on evidence acquired in the region, rather than on principles developed elsewhere or empirically. Since 1986 an operational research programme, initiated in response to the alarming rise in antimalarial drug resistance, has guided the malaria control programs of the various NGOs provided health services to the displaced populations in refugee camps along the Thai Myanmar border. This programme was (and still is) part of the Wellcome-Mahidol University-Oxford Tropical Medicine Research Programme based in the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. It has focused on the epidemiology, the treatment and the prevention of falciparum malaria in the populations living in camps along the border. The main achievements of this programme and the deployment by all medical NGOs of the strategy elaborated were:

• The very significant reduction (over 90%) in the incidence of P.falciparum infections in the camps.
• The reduction in morbidity and mortality due to malaria and in particular the maternal mortality.
• The halt to the hitherto rapid increase in drug-resistance.

These results are explained by the combined effects of Early Detection and Treatment (EDT) and the use of the artesunate-mefloquine combination treatment (for more details see our web site). This led directly to a global programme to evaluate and deploy antimalarial drug combinations throughout the tropical world, and illustrates the pivotal role of operational research in guiding malaria control activities. This dramatic effect on malaria was seen in all the camps where this approach was deployed but not initially in communities outside the camps, where the same strategy was not deployed. This experience demonstrates that it is possible to control malaria and the spread of resistance with the judicious use of EDT and combination therapy. But would this work outside the well controlled context of refugee camps? In 1998 and 1999 malaria surveys were conducted in the Thai-Karen villages in the surroundings of Maela camp and also in settlements of migrant workers south of Mae Sot. High prevalence rates of malaria were found in some villages especially in Pho Prah district, south of Mae Sot. Two clinics were set up in collaboration with the Thai Public Health Office: in Mawker Thai and Munruchai. Since then the clinics have treated over 4000 patients with confirmed falciparum malaria (Thai nationals as well as migrants), established a weekly consultation for pregnant women (identical to the screening in the camps) and followed malaria patients to ensure compliance to the treatment.

Shoklo Malaria Research Unit (SMRU)

The SMRU is attached to the Hospital of Tropical Medicine, Mahidol University, Bangkok which provides scientific, administrative and logistical support. There is an office in Mae Sod which provides the logistical support and has two laboratories. In Maela there are hospital, laboratory, obstetric unit, outpatients department, ante and post-natal clinic, computing area and staff accommodation. Advanced training has been provided over the years so that today, highly competent Karen staff are operating the Unit. In Maela camp, three clinics, an office and staff housing have been built in 1995-6. Maela has become the centre for SMRU operations in the camps. Mae Sot base, the vehicles and Maela Unit are linked by radio. One hour drive to the south of Mae Sot SMRU has opened 2 clinics for migrant workers: Mawker Tai and Muruchai. These 2 clinics serve a population of 15-20,000. The importance of malaria, the size and stability of the population, the ability to follow the patient's progress and the excellent co-operation of the community make the site an ideal place to study malaria. Since 1986 over 10,000 people have been enrolled in more than 18 studies with excellent compliance (over 90% patients attending follow up assessments). 

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SMRU PROGRAMMES

I) Malaria in Pregnancy & infancy

Malaria in Pregnancy

Objective: To quantify the effects of malaria, anaemia, antimalarial drug treatment, and thiamine depletion during gestation on the outcome of pregnancy. 

Pregnant women in SE Asia have a high risk of getting severe malaria, hence a large part of the Unit's work is devoted to intensive ante natal care. The Ante Natal Clinics (ANCs) are now established in five different camps and in the clinics for migrants as well as in 3 district health centres and offer weekly screening for malaria and anaemia to ensure early treatment. As a result of this intensive programme, the maternal mortality due to malaria has been eliminated in the Karen refugee camps. Facilities for safe child birth are also provided. The ANCs are attended by 80-90% of pregnant women in the camps. On the research side, the Unit is looking at the treatment of malaria in pregnancy and the impact of the disease on the neonate and its subsequent development. All women attending the ANCs with malaria enter treatment studies if they give a written and verbal consent. Data can be collected on deliveries and the health of the new-born and during the first year of life. Studies include: The search for the optimum treatment for malaria (falciparum and vivax) and new methods of prevention. The effects of early and late pregnancy exposure to malaria and antimalarials on the subsequent development of the child and the natural history of malaria. The assessment of the thiamine status of pregnant and lactating woAmen to detect vitamin B1 deficiency and prevent it.

Malaria in infancy

Objective: To measure malaria morbidity during the first two years of life; to describe clinical features of the infection in this risk group; to assess the efficacy of antimalarial treatment in this target population. 

The children born to mothers attending the ANCs are prospectively followed for two years, with a monthly routine visit and a weekly home visiting to detect any illness. Previous studies have shown that P. vivax malaria is higher in this age group than in older children and adults. The incidence of falciparum malaria is lower than in older patients, but young children have a higher risk of developing a severe infection. This population is therefore followed closely and all children with malaria are admitted in chemotherapic studies after parental consent. Clinical features of falciparum malaria and malaria induced anaemia are monitored.

II) Chemotherapeutic Trials

Objective: To define the optimum treatment schedules in different patient groups; to identify those patients at increased risk of recrudescent infections, developing better methods of predicting treatment failure and monitoring emerging drug resistance. 

Currently SMRU is conducting a series of large community based studies into the best therapies available for the treatment of primary uncomplicated malaria, hyperparasitaemic malaria and multiple failures. These studies are focusing on the use of the artemisinin derivatives alone or in combination A with other compounds. The standard regimen now in use along the border, and developed at the SMRU is a combination of high dose mefloquine and 3 days of artesunate. The current cure rate of this combination is >95% at 63 days. Recrudescences are treated with longer courses of artesunate (7 days) alone or in combination with tetracycline in non pregnant adults. We have studied prospectively >1000 patients with multiple exposures to an artemisinin derivative to look for evidence of toxicity but none was found. The Qinghaosu drugs are one for our last options. In combination with mefloquine they have translated into a dramatic reduction in the incidence of malaria in the camps, and halted the progression of resistance.

III) Epidemiology and Entomology

Objective: To provide a comprehensive description of the epidemiology and entomology of malaria. 

Malaria cases are recorded weekly in Maela. In other refugee camps the data generated by the clinics and by the laboratories are centralised in Mae Sot and entered on to computer data bases. All patients treated for malaria in the SMRU clinics have medical records and data are computerised. This provides valuable information to monitor the malaria situation and detect emerging epidemics and also helps to establish decision algorithms applicable to South East Asia. The entomology studies determine the major malaria vectors, their man-biting habits, breeding sites, susceptibility to insecticides and repellents, and thus facilitate appropriate vector control and protection measures. These studies (together with the ANCs and the cohort of infants) provide a comprehensive descriptioAn of the malaria epidemiology and entomology in the area.

IV) Nutrition and Anaemia

Objective: To highlight the importance of nutrition in the morbidity and mortality of the community. 

In 1989 SMRU identified thiamine deficiency as an important cause of infant mortality in this population. Several investigations have been carried out to document the relationship between vitamin B1 depletion in the mothers, and the sudden infant death. After recognition of the problem and systematic vitamin supplementation, the infant mortality has dropped from 250 per 1000 in 1988 to 40 per 1000 today. Recently the SMRU has completed a prospective detailed study of the causes and effects of anaemia and thiamine deficiency in pregnancy. This investigation showed that the Karen women are deficient in vitamin B1 after delivery even though they receive a supplement of food and B1 while lactating.

V) Immunology and other laboratory work

Objective: To study the possible mechanisms involved in the effects of malaria during pregnancy on the baby. To characterise the in vitro resistance of P. falciparum to the main antimalarial drugs and to develop a method using PCR to differentiate between new infections and recrudescences. 

Through detailed studies of the immune response to malaria infection, at the peripheral and placental levels and with studies on the placenta tissue, we are getting a better understanding of the deleterious effects of malaria in pregnancy. Parasites isolated from infectAed placenta are characterised using PCR and their cyto-adherence and rosetting properties studied. Most of the laboratory work is done at the Mae Sot base. The in vitro sensitivity work is done in collaboration with the department of immunology at AFRIMS (Bangkok) and the Pasteur Institute in Paris. Pattern of resistance are studied and monitored over time for all major antimalarial drug including the artemisinin derivatives. The results so far have confirmed that the strains of P. falciparum encountered in this area are the most resistant in the world. The PCR protocol has been developed in collaboration with Oxford University and paired specimen (in patients who are treated and present with a new parasitaemic episode during the follow-up) are compared using 3 genetic markers: MSP1, MSP2 and GLURP. More laboratory based work using strains from Shoklo and Maela is underway in the UK and in USA to look at their genetic structure. 

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Achievements

To date the Shoklo Malaria Research Unit has....

• Provided the first detailed description of the effects of malaria in pregnancy in South East Asia.
• Developed a system of antenatal care that has eliminated maternal malaria related mortality.
• Established the safety of the artemisinin derivatives in pregnancy.
• Identified vitamin B1 deficiency in infant as the main cause of death in the first year of life.
• Defined the development of mefloquine drug resistance in this area and produced extensive information (in over 5000 patients) on its adverse effects and on predictors of treatment response.
• Assessed the benefit of high dose halofantrine and discovered its cardio toxicity.
• Treated over 10 000 patients with artemisinin derivatives (the largest single centre study in the world). Conducted the first studies to look at a possible cumulative toxicity of this family of drugs in humans.
• Documented for the first time the impact of artesunate on transmission of malaria and on the spread of resistance and pioneered the use of artemisinin based combination therapy.
• Evaluated the US manufactured malaria vaccine SPf66 in the most detailed and carefully conducted trial with this vaccine.
• Documented for the first time the effects of P. vivax in pregnancy.
• Became the reference for malaria control programs supported by international NGO working along the border.
• Initiated the first Family Planing and HIV awareness programme in the Karen camps, as well as the mother-to-child transmission prevention programme.
• Established collaborations with scientific institutions in USA, Europe and Australia.
• Published over 100 papers in international journals and presented results in several international scientific meetings.

European Union External Cooperation Programmes Providing diagnosis, treatment and prevention measures against malaria and other infectious diseases in the uprooted Burmese population of Tak Province, Thailand 
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All projects conducted by SMRU are submitted to ethical reviews in Thailand and in the UK prior to start. In the refugee camps, additional approval is sought from the Refugee Committee and the camp administration. SMRU host several medical students each year for their electives (8 weeks).

The Thai-Burma border has seen important changes in the composition of its population in the last 20 years. Besides the relatively stable Thai population (itself composed of Thai and other ethnic groups) a growing population originating from Burma has converged on the border. This "uprooted" population is mainly concentrated in refugee camps, the adjacent rural areas and nearby towns.

In the border districts of Thailand's Tak Province the uprooted population from Burma is estimated at 300,000; this includes 100,000 living in refugee camps with the remaining 200,000 being a combination of "migrant workers" (who are registered with the Royal Thai Government and benefit from Thai governmental healthcare services), and relatively mobile "displaced persons" whose lack of legal status in Thailand means that they have little or no access to healthcare. There is estimated to be a ratio of two Burmese "displaced" persons for every registered Burmese "migrant worker" in Thailand.

In the refugee camps health care is provided by NGOs and other international groups and the health situation is usually considered satisfactory and sometimes better than in the surrounding rural areas. Particularly for the “ displaced” population living in the areas around the camps and the borderline, access to health is extremely limited or simply non-existent due to Thai government restrictions on movements of individuals and the lack of assistance and structures adapted to their culture and languages. The Thai public hospitals in the districts are over-stretched by the non-Thai patients who manage to reach them (55% of all malaria cases treated in Thailand by the Ministry of Public Health in 2006 were from the displaced population). For the displaced population this means that they live in an area where the world’s most drug-resist malaria is endemic, and they carry a disproportionately massive burden of malaria infection, but they are rarely able to access treatment and normally only do so once they are seriously ill.

The burden on the existing health structures is worsened by the quasi absence of health care in Burma, forcing patients to travel long distances to try to get treatment in Thailand. This situation creates ideal conditions for the transmission of infectious diseases such as malaria, tuberculosis, HIV/AIDS and others. The problem is so severe that the UN Security Council declared in 2007 that Burma presented a security threat to the region because of the spread of infectious diseases. On the Thai-Burma border, infectious diseases are the main cause of mortality and morbidity in the uprooted population and threaten the health of the host (Thai) population. This is aggravated by the high levels or resistance to antimicrobial and other anti-infective drugs, in particular in respiratory pathogens (including tuberculosis) and malaria parasites.

Since 1986, the Shoklo Malaria Research Unit (SMRU-MORU) attached to the Faculty of Tropical Medicine, Mahidol University in Bangkok, and the University of Oxford, UK, has worked among the uprooted population to reduce the impact of multi-drug resistant malaria and other infectious diseases. SMRU-MORU’s focus has always been on the groups at most risk from malaria: children and pregnant women, with one of the most effective ways of detecting the disease being through the operation of antenatal clinics. Until 1995 this work was focused only in the refugee camps and a strong collaboration was established with the NGO community to control malaria in the refugee population through the operation of “the Malaria Task Force” (MFT), supported by ECHO for several years. This was largely successful and malaria is now a minor problem within the camps. The vast majority of malaria cases treated in the camps is in people with a recent history of travel outside the camp perimeter, usually to rural areas along the border or in Burma. In Maela camp (Mae Ramat district) SMRU-MORU remains responsible for antenatal and obstetric care and the treatment of malaria patients.

Since 1995 SMRU-MORU has extended its activity to reach out to the displaced population who have no alternative access to malaria diagnosis and treatment or antenatal care. This is done in collaboration with the Thai Ministry of Public Health (MOPH) and in close collaboration with the district hospitals and the Tak provincial health authorities. In 2001-2003 the Tak Malaria Initiative, supported by the Bill & Melinda Gates Foundation deployed the malaria control strategy developed by SMRU-MORU in the refugee camps to all 200 affected villages in the province’s border districts with substantial success. When the funding from the Gates Foundation came to an end, the MOPH took over the program. This project uses the same strategy that was successful in rural villages in Thailand.

Beyond the serious impact that malaria has in the Burmese “displaced” population, there is also a global dimension to malaria on the Thai-Burma border because the malaria parasites found in this part of Asia are some of the most drug-resistant on earth and their expansion and spread is a very real threat (research has already demonstrated that the most drug-resistant malaria parasites found in Africa originated in South East Asia) and must be stopped. This is particularly urgent and important in the “displaced” population living along the border since we have seen worrying signs that the malaria parasites may become tolerant even to the artemisinin combination therapies (ACTs) now at the forefront of global malaria treatment.

In 2007 SMRU-MORU successfully applied, alongside the Thai Ministry of Public Health, to the 7th round of the Global Fund for AIDS, TB and Malaria (GFATM) to support the purchase of antimalarials, rapid diagnostic tests and bed nets for the uprooted population (excluding refugee camps) on the Thai-Burma border (project period 2008-2013). This current application to the European Commission is aimed at complementing the support from GFATM by providing resources for a comprehensive malaria control program with a focus on maternal and child health care, specifically targeting the “displaced” population living along the border in Tak province and extending these services to a larger proportion of this population.

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1. Description of the action and its effectiveness:

The very effective strategy developed by SMRU-MORU in the early 1990s for the control of malaria in the refugee camps and in villages in the border districts is based on the use of rapid diagnostic tests and artemisinin-combination therapies (ACTs) as well as vector control measures (impregnated bed nets). There is now a large body of evidence from this region to show that this approach is effective and it has been adopted by other countries in Asia and more recently (2007) has been the cornerstone of World Heath Organization recommendations for the deployment of ACTs worldwide. Being largely excluded from the formal health system, the “displaced” population constitutes a reservoir of the disease and therefore represents a risk to the rest of the people living in the region and elsewhere. In addition to the facilities in Maela camp SMRU-MORU operates four border clinics with the agreement of the MOPH to provide basic health care, with a focus on malaria and particular attention to pregnant women and young children (the most susceptible groups). In recent years the number of patients attending SMRU-MORU border clinics has risen sharply as a direct result of the increase in the size of the displaced population. Funding is needed to support the increasing workload of the existing clinics and to expand the geographical coverage.

The overall objective of the action is to reduce the malaria burden among the displaced Burmese population residing in four districts of Thailand’s Tak province that border Burma.

The specific objective (purpose) of the action will be to give access to a comprehensive malaria control program for the displaced Burmese population living in the border districts of Tak province, which does not benefit from the Thai public health services or refugee camps health care programs.

Outputs: the most visible output will be the provision of an adapted medical service dedicated to the needs of the displaced population: the network of clinics that will operate 24 hours a day, seven days a week will be staffed by trained local personnel working under the supervision of qualified physicians. These field clinics operate out-patient and basic in-patient facilities, laboratories and antenatal clinics. Training will also take place in these field clinics for the local personnel and this is also an important output.

Expected results: overall, we expect to have the same impact in this population as that observed in the refugee camps: a sharp decline in the malaria related morbidity and mortality and an improvement in maternal and child health. We also expect that local personnel trained in our clinics will become an important asset for future health programs in this population.

Specifically the following results are expected from the action:

• Displaced people, particularly those from high-risk groups, will have improved access to early malaria diagnosis & treatment services.
• Pregnant women and young children will have improved access to health services targeting their specific needs.
• People will be more aware of the risks of malaria transmission and will be better able to protect themselves against malaria infection
• The uprooted population's capacity to provide healthcare will be strengthened
• Information regarding health in the displaced population will be shared between agencies to ensure that the most appropriate prevention measures and treatments can be deployed

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Activities and their effectiveness:

Currently all five existing SMRU-MORU operated clinics (4 border clinics and 1 in Maela camp) offer daily free-of-charge out-patient consultations using the most appropriate diagnostic tools and treatments similar to those offered in the Thai health services. Basic in-patient care is also available for patients who need to remain under observation, but more severe cases are transferred to the nearest Thai hospital (incurring a cost). Antenatal services are also offered as the only means to prevent malaria associated mortality. This is the only strategy with proven effectiveness to reduce the maternal mortality associated with malaria. This mortality was very high (1,000 women per 100,000 live birth before the start of the antenatal clinics in 1986). Malaria is also associated with a reduction of birth weight, an independent risk factor for infant mortality. Delivery facilities are already available in one clinic for displaced people (Wang Pa clinic) and in Maela camp. Difficult deliveries are referred to Maela Camp or to the local Thai hospital (also for a cost). As part of the antenatal “package” offered at Maela Camp, the detection of HIV is also offered following counselling and the prevention of maternal to child transmission (PMTCT) is also made available to the women who are HIV positive. At present this is only available to the women in Maela camp. Each clinic is staffed with medical assistants, nurses, laboratory technicians, midwives, home visitors, cleaners and drivers. A telephone line links the clinics with SMRU-MORU’s Mae Sot head quarters. Monthly reports detailing the activities of the clinics are sent to the Thai MOPH as well as to the medical NGOs working on the Thai-Myanmar border. The 2007 activities of SMRU-MORU clinics can be summarized as follows:

Site	Total number of consultations	Total number of malaria treated	Total number of pregnant women in antenatal (deliveries)	Total number of women in PMTCT (screening)
Maela Refugee Camp	16,471	3,208	1,753	1000
Wang Pa	13,827	15,259	412	-
Mae Kon Ken	4,673	3,637	-	-
Murunchai	7,359	3,014	180	-
Mawker Tai	11,226	7,033	352	-
Total	53,556	32,151	2,697	1,000

Activities that will be supported by the project:

Specifically the following activities, targeting the "displaced" population will be undertaken during this action:

• Provision of comprehensive malaria diagnosis and treatment services via SMRU-MORU's existing network of four clinics (excluding Maela refugee camp)
• Provision of comprehensive malaria diagnosis and treatment services via one new clinic
• Antenatal clinics at all SMRU-MORU clinics (excluding Maela refugee camp) to detect and treat malaria
• New antenatal clinics established at 2 existing clinics
• All antenatal clinics to provide measures for prevention of mother-to-child HIV transmission, as well as dietary supplements and child immunisation
• New delivery facilities will be established at two antenatal clinics
• Provision of bed nets to those most exposed to malaria infection
• Malaria prevention and treatment awareness raising
• Knowledge, Attitude & Practise surveys of target population
• Training of midwives in obstetrics, antenatal care and prevention of mother-to-child transmission of HIV
• Training of laboratory staff
• Bi-annual inter-agency technical meetings to share information
• Quality assessment for laboratory facilities managed by other organisations

http://www.shoklo-unit.com/

Shoklo Malaria Research Unit:
SMRU was established in 1986 in Shoklo. It is a field station of the faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, and is part of the Mahidol-Oxford Research Unit (MORU) supported by the Wellcome Trust (UK).Read more

European Union External Cooperation Programmes Providing diagnosis, treatment and prevention measures against malaria and other infectious diseases in the uprooted Burmese population of Tak Province, Thailand
Read more

The Frontline of Artemisinin Resistance: SMRU on the Thai-Myanmar Border ARTE Reportage 2012

ARTE reportage team travelled to Mae Sot in western Thailand, on the Burmese border, to visit the Shoklo Malaria Research Unit.

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