Workshop Report

(1)

Workshop Report

Non-Malarial Febrile Illness Study Final Review Workshop

Cambodia and Lao People’s Democratic Republic

Vientiane, Lao People’s Democratic Republic

12 to 13 January 2011

(2)

English only

REPORT

NON-MALARIAL FEBRILE ILLNESS STUDY FINAL REVIEW WORKSOP

CAMBODIA AND LAO PEOPLE'S DEMOCRATIC REPUBLIC

Convened by:

WORLD HEALTH ORGANIZATION

REGIONAL OFFICE FOR THE WESTERN PACIFIC

Vientiane, Lao People's Democratic Republic 12 – 13 January 2011

Not for Sale

Printed and distributed by:

World Health Organization Regional Office for the Western Pacific

Manila, Philippines October 2011

(3)

NOTE

The views expressed in this report are those of the participants of the Non-Malarial Febrile Illness (NMFI) Study – Final Review Workshop and do not necessarily reflect the policies of the

Organization.

Keywords: Malaria; laboratory diagnosis; differential diagnosis; non-malarial febrile illness;

operational research; Lao People's Democratic Republic; Cambodia; leptospirosis; dengue;

influenza; rickettsia

Cover photo: Sonny Inbaraj Krishnan (WR Cambodia)

This report has been printed by the World Health Organization Regional Office for the

Western Pacific for governments of Member States in the Region and for those who participated in the Non-Malarial Febrile Illness Study – Final Review Workshop, which was held in Vientiane, Lao People's Democratic Republic from 12 to 13 January 2011.

(4)

TABLE OF CONTENTS

SUMMARY

1. INTRODUCTION... 1

1.1 Objectives ... 2

1.2 Agenda... 2

1.3 Resource persons ... 2

2. PROCEEDINGS ... 3

2.1 Workshop Objectives, Project Overview of Objectives, Protocol, Data Collection and Database ... 3

2.2 Presentation of Study Results: Lao People's Democratic Republic... 4

2.3 Presentation of Study Results: Cambodia ... 5

2.4 Updates on Diagnostic Tools Available ... 6

2.5 Introduction to Group Work ... 6

2.6 Discussion... 7

2.7 Planning on publication of results ... 8

2.8 Priorities for future research and collaboration ... 9

3. CONCLUSIONS AND RECOMMENDATIONS... 9

3.1 Conclusions ... 9

3.2 Recommendations ... 9 ANNEXES

Annex 1: PROGRAMME OF ACTIVITIES

Annex 2: LIST OF TEMPORARY ADVISERS, OBSERVERS, AND SECRETARIAT Annex 3: COUNTRY PRESENTATION: LAO PEOPLE'S DEMOCRATIC REPUBLIC Annex 4: COUNTRY PRESENTATION: CAMBODIA

Annex 5: GROUP WORK GUIDELINES Annex 6: GROUP WORK PRESENTATIONS

(5)

SUMMARY

The Non-Malaria Febrile Illness (NMFI) study was developed to better understand the causes of acute non-malarial febrile illness and to guide the management of non-malarial illness, especially among neglected rural populations in South East Asia. The study started in October 2007 in Cambodia and in January 2008 in the Lao People's Democratic Republic. The primary objectives of this study are: to develop evidence to guide the management of malaria parasite negative acute febrile cases; to determine requirements for other diagnostic tools applicable in field conditions; to guide priority setting for point of care diagnostics development to assist in such case management decisions; and, through the implementation of this study, to build capacity of the involved programmes and laboratories in conducting operational research and pathology testing within Cambodia and the Lao People's Democratic Republic.

As the NMFI study is concluding, a final review workshop was conducted with the participation of the principal investigators, Ministry of Health via representatives of involved programmes and their national staff involved in the study implementation, involved research institutes, and donor agencies who supported the study.

The objectives of the workshop were:

1. to present and discuss results of the Non-Malaria Febrile Illness Study, including a review of quality assurance of the laboratory results;

2. to discuss implications of the study on case management of NMFI relevant to Cambodia and the Lao People's Democratic Republic, and discuss critical steps that need to be taken to address issues related to NMFI which were identified in the study;

3. to plan the publication of results, and consider applying methodologies validated in this study in other settings/countries; and

4. to define priorities for future research including diagnostics and plan future collaboration.

The methodology and preliminary results of the two studies from Cambodia and Lao People's Democratic Republic were presented by the principal investigators. Discussions follow each presentation. Critical questions on the results of the study and its implications to national health programmes were carefully examined and analyzed.

Workshop participants were divided into two groups. The first group focused its discussion on the clinical implication of the study results on national health programs and on treatment guidelines. The second group, on the other hand, discussed the implication of the results on clinical trials and diagnostic development.

The analysis and report writing of the NMFI study is expected to finish sometime in May 2011. Results publication, dissemination and utilization were planned. Strategies for future directions were carefully laid, including sourcing of funds. Research needs were prioritized and the need for extensive collaboration with clinicians, other health care professionals and policy makers were emphasized.

(6)

ii

The main conclusions of the workshop were:

1. A large number of study participants (30% in Cambodia, 66% in Lao People's Democratic Republic) remained undiagnosed, suggesting further tests should be conducted to identify other NMFI pathogens.

2. The high incidence of treatable causes of NMFI opened several questions on the need for new or revised clinical guidelines and better diagnostic tools. Careful planning and further research are needed.

3. There are currently no clear algorithms in either country on how to treat patients with negative rapid diagnostic test (RDT) for malaria. This poses several problems (e.g.

treating non-malarial patients with malaria drugs or non-treatment of patients with febrile illness) and therefore improving clinical guidelines and diagnostic procedures are

important.

The recommendations of the workshop were as follows:

1. There are several considerations that should be taken into account in developing or revising clinical guidelines. The health systems in place, health care professionals and other stakeholders involved, and resources available are all equally important in developing or revising clinical guidelines and should therefore direct future steps towards better case management. It is also important to consider who will use the clinical guidelines and in what setting (such as hospitals or health centres).

2. Developing new diagnostic tools is a long-term option, requiring a number of years and considerable funding, as suitable candidate tests are not readily available for most of the pathogens isolated. Burden of the disease and cost-effectiveness of developing new diagnostic tools should be carefully studied. Similar to the clinical guidelines development, it is also important to consider who will use the diagnostic tools and in what setting.

3. A regional rickettsial diagnosis network should be developed for establishing laboratory standards and external quality assurance (EQA).

4. On research dissemination and utilization, study results should be published in parallel papers and disseminated by national partners in their countries. Organization of symposium maybe considered to present results and its implications for programmes.

5. In designing future non-malarial febrile illness studies:

5.1 Use of standardized protocol for all study sites is recommended. This includes the clinical data form, clinical database, pathology tests, use of control groups, and study setting. It will also be useful to target two levels of health care: hospitals and health centres.

5.2 For quality assurance of data, EQA for all pathology should be established from the beginning of the study. Central data management and coordination should be developed to ensure standardized methods, data entry and analysis at all sites. Data collectors should also have sufficient training to perform detailed clinical

assessment.

5.3. Widen clinical questionnaire to include, for example, occupation of patients.

(7)

iii

5.4. There are limited financial resources for NMFI studies. Adequate funding should be sought from a single source to support and coordinate the whole activity. Piggy- backing on existing malaria activities in conducting the studies is recommended.

(8)

1. INTRODUCTION

The causes of acute febrile illness are largely unknown in developing countries where diagnostic facilities for infectious diseases remain limited. Malaria has long been recognized as one of the most important diseases affecting the Asia-Pacific Region. Control and prevention have been scaled up over recent years. Mortality and incidence rates have dropped significantly over time as a result of these efforts. With the shift to treatment of malaria based on the

demonstration of parasites, especially through the widespread use of rapid diagnostic tests (RDT), it is now clear that the majority of acute fever cases with suggestive clinical signs and symptoms of malaria are of non-malaria etiology. So far, it is neither known which pathogens are causing the fever nor whether the health services can offer a targeted treatment for these non- malarial febrile patients.

In an era where malaria elimination is becoming more important in the Western Pacific Region, the causes of parasitologically negative acute fever cases in malaria endemic areas should be properly explored to plan for disease-targeted management. Fever can lead to high mortality if not treated promptly and adequately. Diseases such as leptospirosis, rickettsioses (including scrub typhus), community-acquired septicaemia and dengue fever are among the important causes of fever that may mimic 'malaria-like symptoms'. Presumptive treatment of non-malarial fever with anti-malarial drugs is ineffective and a waste of resources especially if expensive artemisinin-based combination therapy is used.

The Non-Malaria Febrile Illness (NMFI) study was developed to give a better

understanding of the causes of acute non-malarial febrile illness and to guide the management of non-malarial illness, especially among neglected rural populations in South East Asia. The study started in October 2007 in Cambodia and in January 2008 in the Lao People's Democratic Republic. The primary objectives of the NMFI study are: to develop evidence to guide the management of malaria parasite negative acute febrile cases; to determine requirements for other diagnostic tools applicable in field conditions; to guide priority setting for point of care

diagnostics development to assist in such case management decisions; and, through the implementation of this study, to build capacity of the involved programmes and laboratories in conducting operational research and pathology testing within Cambodia and the Lao People's Democratic Republic.

This study is financially and technically supported by WHO, the United States Agency for International Development (USAID) and the Foundation for Innovative New Diagnostics

(FIND). It has been conducted in collaboration with researchers of Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Centre for Malariology,

Parasitology & Epidemiology and National Centre for Laboraory & Epidemiology in the Lao People's Democratic Republic and the National Centre for Parasitology, Entomology & Malaria Control of Cambodia (CNM), the Pasteur Institute of Cambodia, and the University of Munich.

The main sample collection phase was completed in June 2009 and it showed that marked geographical differences were apparent among sites in terms of incidence of major aetiological agents. Therefore, the study was extended for a second period to obtain the desired sample size and increase the data to determine whether differences in prevalence are related to seasonal variation or geographical variation linked to local epidemiological factors. The second 12-month study period was completed in 2010.

(9)

- 2 -

As the NMFI study is concluding, a final review workshop of the NMFI study was

conducted in Vientiane, Lao People's Democratic Republic, with the participation of the principal investigators, Ministry of Health via representatives of involved programmes and their national staff involved in the study implementation, involved research institutes, and donor agencies who supported the study.

1.1 Objectives

1) To present and discuss results of the Non-Malaria Febrile Illness Study, including a review of quality assurance of the laboratory results;

2) To discuss implications of the study on case management of NMFI relevant to Cambodia and the Lao People's Democratic Republic, and discuss critical steps that need to be taken to address issues related to NMFI which were identified in the study;

3) To plan the publication of results, and consider applying methodologies validated in this study in other settings/countries; and

4) To define priorities for future research, including diagnostics, and plan future collaboration.

1.2 Agenda

The workshop's agenda was organized by session. The first two sessions focused on the background of the non-malaria febrile illness studies in the two countries and then moved to the discussion of its preliminary results.

Session three was devoted to group work wherein participants were divided into two groups. One group discussed the clinical implications of the study results for national programs and for treatment algorithms/ guidelines. The other group discussed the implication of the results for further trials and diagnostics development.

In session four, results of the group work were presented in the first hour. Plans for publication of results, priorities for future research and collaboration and recommendations were also discussed in this session.

A 30- to 90-minute discussion followed every presentation to clarify and/or raise issues for each topic. See programme of activities in Annex 1.

1.3 Resource persons

Principal investigators and researchers of the NMFI studies in Cambodia and Lao People’s Democratic Republic were asked to present their preliminary results and conclusions. Health professionals from study sites (hospitals in Lao People’s Democratic Republic and health centres in Cambodia) involved in the studies since 2007 were also invited to support the investigators.

Resource persons from the Ministries of Health were also invited. One observer each from the United States Centers for Diseases Control (CDC) – Lao People’s Democratic Republic and the Fondation Merieux also attended the workshop.

Staff from WHO planned and conducted the workshop in close coordination with all principal investigators and funders of the NMFI study in Cambodia and Lao People’s Democratic Republic.

(10)

- 3 -

A full list of temporary advisers, observers and secretariat are found in Annex 2.

2. PROCEEDINGS

2.1 Workshop objectives, project overview of objectives, protocol, data collection and database

Dr Jun Nakagawa presented the background of the NMFI study. He said that the NMFI study was launched in Cambodia in 2007 and in the Lao People’s Democratic Republic in 2008 to gain a better understanding of the causes of acute non-malarial febrile illness and to guide its management, especially among neglected rural populations in South East Asia.

The primary objective of the NMFI study is to develop evidence to guide management of malaria parasite negative acute fever cases in malaria endemic areas of Cambodia and Lao People’s Democratic Republic. Specifically, the study aims to: (1) develop a prototype study design useable elsewhere; (2) determine available diagnostic tools applicable in field conditions;

(3) build capacity for operational research and pathology testing within Cambodia and Lao People’s Democratic Republic; and (4) determine needs and priorities for development or improvement of non-malaria point-of-care diagnostic tests for use at health centre and community level.

As the study is concluding, a final workshop is needed to: (1) present and discuss results of the NMFI study, including a review of quality assurance of the laboratory results; (2) discuss implications of the study on case management of NMFI relevant to Cambodia and the Lao People's Democratic Republic, and discuss critical steps that need to be taken to address issues related to NMFI which were identified in the study; (3) plan the publication of results, and consider applying methodologies validated in this study in other settings/countries; and (4) define priorities for future research including diagnostics and plan future collaboration.

Dr Franz-Josef von Sonnenburg of the Department of Infectious Diseases and Tropical Medicine-University of Munich presented the study’s research protocol, data collection and database. He said that the NMFI project is a cross-sectional, prospective study to identify the aetiology of acute non-malarial febrile illness without obvious causes in patients aged five years (in the Lao People’s Democratic Republic) or seven years (in Cambodia) to 49 years. The protocol had to be adjusted locally in Cambodia and Lao People’s Democratic Republic according to the facilities; ethics board committee decisions, local setting, etc. Therefore, there are differences in the study protocols.

The protocol stated that male and female subjects will be eligible for participation in the NMFI study if they: are aged five years or seven years to 49 years inclusive on the day of the recruitment; provide written informed consent; have an acute, febrile illness lasting not longer than eight days; and are eligible for a malaria test according to national guidelines.

All samples collected from the study sites were transported to the reference laboratories either by plane, bus or taxi. Samples were screened for malaria, leptospirosis, rickettsial diseases (scrub typhus, murine typhus, spotted fever group), dengue fever, influenza, Japanese

encephalitis, and community-acquired septicemia (typhoid and paratyphoid fever, meloidosis, etc). HIV infection and TB were not evaluated. If it turns out that these pathogens do not cover sufficiently the causes of the acute fever in the study subjects, the specimen will be tested for the

(11)

- 4 -

following additional infections with: Brucella spp., Coxiella burneti, Epstein-Barr-Virus, Chikungunya virus, Hepatitis A, Hepatitis E and Coxsackie virus.

Case record forms were entered into the NMFI Database using double independent data entry. Epi Info (v 3.3.2 for Windows) was used to analyze the data in Cambodia. In the Lao People’s Democratic Republic, SPSS (v10) and STATA (v10) were used.

2.2 Presentation of study results: Lao People's Democratic Republic

Dr Mayfong Mayxay, of Mahosot Hospital, introduced the Lao People’s Democratic Republic NMFI study. He described the study methodology and the different laboratory methods used to diagnose the patients. This includes microscopy, rapid diagnostic test (RDT) and

polymerase chain reaction (PCR) for malaria; blood culture for community-acquired septicaemia;

blood culture and PCR for leptospirosis; serology (ELISA) and PCR for dengue; serology (ELISA) for Japanese encephalitis virus; and serology (immunofluorescence assays IFA), blood culture and PCR for rickettsial pathogens (O. tsutsugamushi, Rickettsia typhi and SFG Rickettsia spp.).

Dr Paul Newton, of the Wellcome Trust-Mahosot-Hospital Oxford Tropical Medicine Research Collaboration at Mahosot Hospital, discussed the findings of the study. Between May 2008 to August 2010, 1595 patients were recruited (1112 from Luang Namtha and 483 from Salavan). Six patients were known to have died, one in Salavan and five in Luang Namtha.

NMFI laboratory results suggested that the causes of death for five patients were B. pseudomallei septicaemia, S. aureus septicaemia, E. coli septicaemia, Japanese encephalitis virus and dengue virus infection.

Both the recruitment to the study and the incidence of major causes varied seasonally with higher recruitment and disease incidence during the rainy season.

The study classified patient’s diagnoses in two ways. First, the more conservative, and probably accurate, methods based on culture (i.e blood culture, rickettsial culture and leptospiral culture), antigen detection (dengue NS1) and PCR (Plasmodium spp., O. tsutsugamushi, R. typhi, SFG Rickettsia spp., Leptospira spp. and dengue) plus anti-JEV IgM ELISA. Second, the study used all available tests i.e. using the above tests plus O. tsutsugamushi and R. typhi IFA and dengue IgM/IgG ELISA.

Using the conservative approach, 33.9% of patients (n=541) were diagnosed with the following diseases: scrub typhus (26%); dengue (25%); Japanese encephalitis virus infection (20.5%); leptospirosis (12%); community-acquired septicaemia (9%); multiple pathogens (4%);

malaria (3.5%); murine typhus (1%); and undetermined rickettsial infection (0.2%).

Preliminary conclusions for the Lao People’s Democratic Republic study include the following: (1) using conservative diagnostic methods about one-third of patients had aetiologies of their fever determined with scrub typhus the most common diagnosis at both study sites; (2) difference in fever aetiologies between two study sites indicate that Luang Namtha has more leptospirosis cases than Salavan and Salavan has more dengue, malaria, and evidence of multiple pathogens than Luang Namtha; and (3) Japanese encephalitis seems to be an important cause of fever in both study sites.

Current malaria treatment flow in the Lao People’s Democratic Republic was also presented as well as the treatment regimens for the infectious diseases diagnosed.

(12)

- 5 -

Lastly, Dr Darouny Phonekeo, of the National Centre of Laboratory and Epidemiology briefly presented the influenza results from June to December in Luang Namtha Province.

See Annex 3 for the country presentation of Lao People's Democratic Republic.

2.3 Presentation of study results: Cambodia

Dr Siv Sovannaroth, of CNM Cambodia, introduced the Cambodia NMFI study. He discussed the inclusion/exclusion criteria for the study subjects, study sites in Pailin and Snoul districts, and the study methodology. He said that from the three health centres (two in Pailin, one in Snoul) there were 1470 subjects recruited (1189 as cases and 281 as controls). However, as of the end of December 2010, only 1409 of the samples were tested.

Ms Tara Müller, from the University of Munich, discussed the different laboratory procedures and methodologies they used in the study. She said the samples were screened for malaria, leptospirosis, spotted fever and typhus group rickettsiosis, scrub typhus, dengue fever, Japanese encephalitis, influenza, typhoid fever, melioidosis and community-acquired

septicaemia. Ms Muller said that part of the protocol is to test the samples for additional pathogens if the above-mentioned pathogens do not cover the causes of the acute fever sufficiently. These additional tests are for the following infections: Brucella spp., Coxiella burneti, Epstein-Barr-Virus, Chikungunya-Virus, Hepatitis A-, Hepatitis E- and Coxsackie - Virus. However, the additional tests have not yet been done.

Specifically for Japanese encephalitis (JEV), only samples from subjects with more than five days of fever have been tested in Cambodia. With this inclusion criterion, there were only 10 samples tested for JEV. Comparing this with the high rate of JEV found in Lao People’s Democratic Republic, it was then suggested to do additional tests for JEV in Cambodia.

The preliminary results of the study were presented by Dr Didier Ménard of the Pasteur Institute of Cambodia. He said that 69% of the cases and 38% of the controls were diagnosed with a disease using different laboratory procedures. The ranking of the pathogen prevalence showed that parasitological origin accounts for 67.4%, while bacterial is 19.3% and virological is 13.3%. The most frequent pathogens observed were: P.vivax (35.7%); P. falciparum (29%);

leptospirosis (13.9%); influenza (9.1%); dengue (6.5%); scrub typhus (3.9%); bacterial

septicemia (0.9%); rickettsia (0.7%); P. knowlesi (0.2%); and P. ovale (0.1%). Leptospirosis was the most common non-malarial fever illness detected.

Dr Frank von Sonnenburg, from the University of Munich, presented the geographical differences of the study participants and the seasonal variations of each pathogen studied. He said that most of the cases are from Pailin area as the health centre in Snoul has low utilization and irregular opening hours. There were no significant differences in age and gender between the two areas in Pailin, whereas in Snoul, more men aged 15 years and above were recruited. A high percentage of asymptomatic parasite carriers was observed in control group. It is also important to note that two P. knowlesi cases were diagnosed in Pailin district.

The current algorithm for malaria suspected cases was then presented by

Dr Siv Sovannaroth. He said that symptoms of malaria are very similar to many other infections, especially in children. It is also possible to have malaria and another infection at the same time.

Dr Sovannaroth mentioned that village malaria workers refer patients to health facilities if RDT results are negative for malaria. Other public and private health providers provide treatment for malaria positives and they refer patients to a health facility if malaria results are negative especially if the case is severe and if patients are pregnant and children younger than five years old.

(13)

- 6 -

Ms Erna Fleischmann, from the University of Munich, elaborated the difficulties in diagnosing rickettsial diseases. She said that rickettsial results should be cross-checked as results from Lao People’s Democratic Republic and Cambodia are discordant. Ms Flieschmann said that real time PCR for rickettsia is difficult to establish for samples with low density of DNA.

She also mentioned that extraction method should be retested with new samples or another method should be used in conducting the re-test.

See Annex 4 for the country presentation of Cambodia.

2.4 Updates on diagnostic tools available

Dr Mark Perkins, of the Foundation for Innovative New Diagnostics (FIND), provided an update on the current diagnostic tools available. He said that patients usually comes in hospitals or health centres with fever and other clinical symptoms so it's hard to identify their illness without proper and correct diagnostic tools. However, in each level of the health system diagnostic need varies. Dr Perkins then presented the complexity and costs of the different routine technologies available today for malaria, leptospirosis, rickettsial diseases, scrub typhus, dengue, Japanese encephalitis and influenza. He concluded his presentation by saying that novel pathogen detection is very expensive and that its use should be accompanied by an extensive epidemiological background.

2.5 Introduction to group work

Dr Jun Nakagawa presented the mechanics of the group work session. A piece of paper was circulated and participants chose which group they want to join. The first group, facilitated by Dr Charles Delacollette of WHO’s South East Asia Regional Office, focused on the clinical implication of the study results on national health programs and on treatment guidelines. The second group, facilitated by Dr Mark Perkins of FIND, focused on the implication of the results on clinical trials and diagnostics development. Key questions were developed and provided to each group to focus their discussion and guide their presentation (See Annex 5). Around four hours of group work were allotted for discussion in two separate break-out rooms. The group presentations are included in Annex 6.

2.5.1 Group one presentation: Clinical implication of the study results for national programs and for treatment algorithms/guidelines

The first group's task is to discuss the treatment algorithms for management of RDT negative cases for Cambodia and Lao People’s Democratic Republic. The following questions guided their work: what would the algorithm look like; when would referral for further

investigation be recommended; should these algorithms be nationwide, regional or provincial;

what are the likely disadvantages of such algorithms; what are the likely program costs for these treatments; what other research is needed; what further research is needed to confirm

effectiveness and safety of management of these cases; and which national guidelines would be affected by any proposed changes?

The group first discussed the existing health workers and facilities available in the two countries. In Lao People’s Democratic Republic, there are about 2500 village health volunteers (VHV) working on malaria. They were trained for one week on primary health care and two days specifically on malaria. There are 700 health centres in Lao People’s Democratic Republic doing mostly clinical work with limited or no laboratory work. In Cambodia, there are 1,500 village malaria workers (VMW) who were trained for three days on malaria RDT. VHW give ACTs for malaria RDT positive patients and they refer those who are negative to the health centres. There are around 900 health centres in Cambodia, 284 of which are in malaria endemic

(14)

- 7 -

areas. Like in Lao People’s Democratic Republic, health centres in Cambodia only perform clinical work with no or limited laboratory work, except malaria detection by RDT and some by slide.

The group discussed some important considerations in developing clinical guidelines.

Some of these are: seasonality of infectious diseases; clinical condition of patients; regional disease burden; and severity of diseases. It is also important to note that the different levels of health care facilities and services available including medicines also affect the development of the guidelines. Further research is also needed to identify disease burden and laboratory gaps in each level of health care. The group stressed that in developing clinical guidelines it is

imperative to involve physicians, nurses and other health care professionals from various levels of health care and the policy makers at the Ministry of Health.

The group believes that clinical guidelines should be adopted nationwide but adapted locally at different levels of health care (village level, health centres, district/provincial/central hospitals). Clinical guidelines and intervention packages should be in line with the current clinical management efforts as well as the Ministry of Health’s master plans for human resource, facilities upgrade, laboratory strengthening among others.

2.5.2 Group two presentation: Implication of the results for further trials and diagnostics development

The second group's task is to discuss the implications of the study results on trials and diagnostic development. The following questions guided their work: how to standardize NMFI screening studies to make them more readily implementable; which will be the “gold standard”

tests for diagnosis; how to define/collect standard materials to evaluate performance of available tests and usefulness for disease diagnosis and management; what currently available diagnostic should be taken into to field trials; how do we prioritize development of diagnostic tests for:

NMFI screening and case management.

They presented the current available tests for non-malarial illness such as scrub typhus, rickettsia, leptospirosis, typhoid fever and dengue. The group then listed the requirement for sub-national clinical diagnostics and these are: use of high-sensitive tests (90-95%) for on-spot decision of clinicians; use of commercial tests and homebrew assay; staff training on laboratory equipment operation; staff supervision; and knowledge management.

The group then discussed recommendations for future NMFI studies. Further collaboration (e.g. sharing of samples and assessment of rapid tests) is needed between Cambodia and Lao People’s Democratic Republic. The two countries should discuss the advantages and disadvantages of different diagnostic tests and agree on standard techniques and protocols to be used so the results would be comparable. Study investigators should follow-up the treatment and recovery of patients as this would strengthen the analysis of results. The group also suggested that the study areas could be expanded in other provinces. For Lao People’s Democratic Republic, investigators could include district hospitals in Luang Namtha and Salavan Provinces.

2.6 Discussion

A thirty-minute to ninety-minute discussion followed each presentation. Several issues were raised on the methodology, results and its implications to national programmes, clinical guidelines, and diagnostic development.

(15)

- 8 -

Methodology

There were some variations in the methodology of the Cambodia and Lao People’s Democratic Republic studies (e.g. age of recruitment, study area and use of control groups).

These variations make it difficult to compare results.

Laboratory methods used for the study were limiting in analyzing samples and this contributed to the number of undiagnosed patients. What are thought to be the main pathogens were tested but further work is needed to broaden the diagnostic net.

On patient recruitment, health-seeking behaviour of the population had an effect on the number of patients seeking health care in the health centres and hospitals. User fees, the kinds of health services offered in the health facilities, and distance of population to health facilities affect the number of patients seeking care. In the Lao People’s Democratic Republic study,

investigators should take into account the different factors that could affect the number of septicaemia cases seen. For example, since the Lao People’s Democratic Republic study is hospital-based, more patients with septicaemia are likely to go to this type of health facility compared to the Cambodia study which is health centre-based. For the Cambodia study, since there is a high burden of malaria in the country, health centres could have selection bias for malaria. Malaria infection parasite density needs to be analyzed in view of RDT/microscopy sensitivity.

Results and implications to national programmes, clinical guidelines and diagnostic tools In both study sites, there are a number of undiagnosed patients: 30% in Cambodia and 66% in Lao People’s Democratic Republic and this has clear implications on national

programmes. Currently, there is no clear algorithm on what to do with patients exhibiting febrile illness but testing negative for malaria. In the two Lao People’s Democratic Republic provinces, malaria RDT negative cases are treated based on physical examination and according to national clinical guidelines. The same is done in Cambodia where patients with RDT negative malaria are treated with chloroquine (or ACT) if they highly suspect malaria and complicated cases are referred to hospitals. It is therefore important to improve diagnostic procedure and

develop/revise clinical guidelines for better case management.

Acute, febrile illness is the entry point for patients in the study. To improve the study, participants suggested also considering the following: other symptoms/ clinical manifestations present in negative malaria patients; comparison of diagnosis with local disease endemicity and case fatality rate (with or without treatment); conducting further testing such as C-reactive protein assays to determine whether they can differentiate bacterial from viral disease; examine links between disease and patient occupation; and links between disease and seasonal variations.

Detection of diseases at the village level also should be addressed. The capacity of local (provincial and district) laboratories need to be improved especially in areas with high disease burden and/or remote areas. Laboratory technicians and/or medical technologies should be trained and/or facilitated to update their skills.

2.7 Planning on publication of results

Dr David Bell, from the Global Malaria Programme at WHO Geneva, presented the next steps and plans for result dissemination. He suggested that analysis and writing of the two reports will be finished around May 2011. Recommendations and experiences on screening and pathology testing for NMFI should be part of the report. After this, WHO, FIND and University of Munich will lead the writing of a joint final report involving all partners from both study sites.

(16)

- 9 -

All reports will be disseminated by national partners within their countries as well as to potential funding agencies. Conduct of symposium is suggested highlighting the implications of the study results on programmes.

As there is limited funding available for study expansion and collaboration in Cambodia and Lao People’s Democratic Republic, Dr Bell said that there is a need to prioritize

recommendations in the joint report. A concept note highlighting future directions could also be developed and used by both countries for dissemination and funding support. If this is agreed, someone should lead this initiative.

2.8 Priorities for future research and collaboration

Dr Mark Perkins discussed priorities for future research and collaboration. He said that developing better diagnostics is a main priority. However, he said that in doing this, one should consider who would use them and where it will be used (provincial/district hospitals or health centres). Also, disease priorities based on burden and cost-effectiveness should be considered in diagnostic development.

On developing new algorithms, researchers should first look at the existing clinical guidelines for the other febrile illnesses and decide if we still need to develop new ones or just update them. Existing health care packages and available/existing human resources in all levels of health care in countries should be considered during decision making. Extensive collaboration with clinicians, other health care professionals and policymakers are needed in this process.

3. CONCLUSIONS AND RECOMMENDATIONS

3.1 Conclusions

The main conclusions of the workshop are summarized as follows:

1. A large number of study participants (30% in Cambodia, 66% in Lao People’s Democratic Republic) remained undiagnosed, suggesting further tests should be conducted to identify other NMFI pathogens.

2. The high incidence of a number of treatable causes of NMFI opened several questions on the need for new or revised clinical guidelines and better diagnostic tools. Careful planning and further research are needed.

3. There are currently no clear algorithms in either country on how to treat patients with negative RDT for malaria. This poses several problems (e.g. treating non-malarial patients with malaria drugs or non-treatment of patients with febrile illness), therefore improving clinical guidelines and diagnostic procedures is important.

3.2 Recommendations

The recommendations of the workshop were as follows:

1. There are several considerations that should be taken into account in developing or revising clinical guidelines. The health systems in place, health care professionals and other stakeholders involved, and resources available are all equally important in

(17)

- 10 -

developing or revising clinical guidelines and should therefore direct future steps towards better case management. It is also important to consider who will use the clinical guidelines and in what setting (hospitals or health centres).

2. Developing new diagnostic tools would take a long time and is very expensive. The burden of the disease and cost-effectiveness of developing new diagnostic tools should be carefully studied. Similar to the clinical guidelines development, it is also important to consider who will use the diagnostic tools and in what setting.

3. On research dissemination and utilization, study results should be published in parallel papers and disseminated by national partners in their countries. The

organization of a symposium maybe considered to present results and its implications to programmes.

4. A regional rickettsial network can be developed for establishing laboratory standards and EQA.

5. In designing future non-malarial febrile illness studies:

5.1 Use of standardized protocol for all study sites. This includes the clinical data form, clinical database, pathology tests, use of control groups, and study setting. It will also be useful to target two levels of health care: hospital and health centres.

This approach will allow data to be compared between sites.

5.2 For quality assurance of data, external quality assurance for all pathology should be established from the beginning of the study. Central data management and coordination should be developed to ensure standardized methods, data entry and analysis at all sites. Data collectors should also have sufficient training to perform detailed clinical assessment.

5.3 The clinical questionnaire should be widened to include for example occupation of patients.

5.4 There is limited financial resource for NMFI studies. Adequate funding should be sought from a single source to support and coordinate the whole activity. Piggy- backing on existing malaria activities in conducting the studies is recommended.

(18)

ANNEX 1

NON-MALARIA FEBRILE ILLNESS PROJECT IN LAOS AND CAMBODIA

Vientiane, the Lao People's Democratic Republic 12 to 13 January 2011

WPR/DCC/MVP(01)/2011/IB/2 5 January 2011

ENGLISH ONLY

DAY 1 (Jan 12)

08:00 Registration WHO LAO

08:30 Opening remarks MoH, FIND, WHO Lao

08:45 Group Photo All participants

Session 1 (9:00-12:00) Chairperson : Dr. Chanphomma Co-chair: Dr. M. Mayxay 09:00 Introduction

- Objectives

- Overview of the NMFI project

E. Christophel/ J. Nakagawa

09:20 Research protocol, data collection and data base F. von Sonnenburg 09:40 Presentation of the study results: Lao PDR

- Data collection and pathology results - Difference between study sites

-Geographical, seasonal, demographic and clinical association with the results from all sites

P. Newton M. Mayxay

10:30 Discussion 11:00 BREAK

11:15 Presentation of the study results: Cambodia - Data collection and pathology results - Difference between study sites

-Geographical, seasonal, demographic and clinical association with the results from all sites

S. Sovannaroth D. Menard

F. von Sonnenburg

12:00 Discussion 12:30 LUNCH

Session 2 (13:30-17:15) Chairperson: Dr. S. Sovannaroth, Co-chair: Dr. M. Perkins 13:30 Discussion (continuation)

14:30 Clinical implications of the study results

(19)

- Cambodia - Lao PDR

P. Newton/ M Mayxay S. Sovannaroth/ D. Menard 15:00 Discussion

15:30 BREAK

16:00 Updates on diagnostic tools available - What is possible,

- Where we go with new diagnosis?

M. Perkins

16:30 Discussion 17:00 Closure

19:00 Social Dinner FIND

DAY 2 (Jan 13)

Session 3 (8:30 – 14:00) Chairperson: Dr. R. Phetsouvanh Co-chair: Dr. F. von Sonnenburg 8:15 Introduction to Group Work (14^th Floor)

8:30 Working Group (1^st Floor)

Group 1: Clinical implication of the results for national programs and for treatment

algorithms/guidelines

Group 2: Implication of the results for further trials and diagnostics development

Group 1

Facilitator: C. Delacollette Chairperson: TBD

Rapporteur: TBD Group2

Facilitator: M. Perkins Chairperson: TBD Rapporteur: TBD 10:30 BREAK

11:00 Working Group (continuation)

12:00 Presentation of the group work: Group 1 (14^th Floor)

Group 1 Rapporteur 12:30 Discussion

13:00 LUNCH

Session 4 (14:00-17:40) Chairperson: Dr. K. Sim, Co-Chair: Dr. D. Bell

14:00 Presentation of the group work: Group 2 Group 2 Rapporteur 14:30 Discussion

15:00 Planning on publication of results, and the development of a module/tools based on the methodology of the study

Plenary discussion facilitated by co-chair

15:30 Priorities for future research and collaboration Plenary discussion facilitated by M. Perkins

16:00 BREAK

16:30 Recommendations Plenary discussion facilitated by

co-chair

17:30 Concluding remarks B. Hongvanthong

17:40 Closure

(20)

ANNEX 2

NON-MALARIA FEBRILE ILLNESS PROJECT IN LAOS AND CAMBODIA

Vientiane, the Lao People's Democratic Republic 12 to 13 January 2011

WPR/DCC/MVP(01)/2011/IB/2 5 January 2011

ENGLISH ONLY

INFORMATION BULLETIN NO. 2

LIST OF TEMPORARY ADVISERS,

REPRESENTATIVES/OBSERVERS AND SECRETARIAT

1. TEMPORARY ADVISERS Ms Phatsana Basy Laboratory Head

Luang Nam Tha Provincial Hospital Nongbouvien Village,

Luang Nam Tha Province

Lao People's Democratic Republic Tel No. : +856 20 9998 7858 Fax No. : +856 86 211 752

E-mail : [email protected] Dr Phouvieng Douangdala

Head of Pediatrics

Luang Nam Tha Provincial Hospital Nongbouavieng Village,

Luang Nam Tha Province

Lao People's Democratic Republic

Tel No. : +856 20 2428 120 / +856 20 5631 8122 Fax No. : +856 86 211 752

E-mail : [email protected]

(21)

Ms Erna Fleischmann Chief laboratory Technician

Department of Infectious Diseases and Tropical Medicine University of Munich

Georgenstr. 5, 80799 Munich, Germany Tel No. : +49 89 2180 17600 Fax No. : +49 89 336038

Dr Iveth J. Gonzalez * Scientific Officer – Malaria

Foundation for Innovative New Diagnostics (FIND) Avenue de Budé 16

1202 Geneva, Switzerland

Tel No. : + 41 (22) 710 05 90 Fax No. : + 41 (22) 710 05 99

E-mail : [email protected] Dr Bouasy Hongvanthong

Acting Director

Centre of National, Parasitology and Entomology Ministry of Health

Vientiane, Lao People's Democratic Republic Tel No. : (856) 21 21 4040

Fax No. : (856) 21 21 8131 E-mail : [email protected] Dr Saythong Inthilath

Coordinator

Luang Namtha study site and team in Vientiane Luang Namtha Hospital

Nongbouavieng Village, Luang Nam Tha Lao People's Democratic Republic Tel No. : +856 20 5560 2456 Fax No. : +856 86 211 752 E-mail : [email protected]

Dr Mayfong Mayxay

Head, Field Research

Wellcome Trust–Mahosot-Oxford Tropical Medicine Research Collaboration,

Mahosot Hospital

Vientiane, Lao People's Democratic Republic Tel No. : +856 21 250 752

Fax No. : +856 21 242 168

(22)

Dr Didier Ménard

Molecular Epidemiologist Molecular Epidemiology Unit Pasteur Institute of Cambodia

5 Boulevard Monivong - PO Box 983

Phnom Penh, Cambodia

Tel No. : +855 23 426 009 Fax No. : +855 23 725 606

E-mail : [email protected] Ms Tara Muller

Medical Student

Georgenstr. 5, 80799 Munich, Germany Tel No. : +49 176 64370551 Fax No. : +49 89 336038

E-mail : [email protected] Dr Leng Naren

Provincial Malaria Supervisor Ministry of Health

Kratie Province, Cambodia

Tel No. : Mobile Phone: 855(0)11907626 Fax No. :

Dr Paul Newton

Director

Microbiology Laboratory

Wellcome Trust–Mahosot-Oxford Tropical Medicine Research Vientiane, Lao People's Democratic Republic

Tel No. : +856 21 250 752 Fax No. : +856 21 242 168 E-mail : [email protected] Dr Daniel Paris ***

Head of Microbiology

Mahidol-Oxford Tropical Medicine Research Unit (MORU) Faculty of Tropical Medicine, Mahidol University

3rd Floor, 60th Anniversary Chalermprakiat Building 420/6 Ratchawithi Rd., Ratchathewi District

Bangkok 10400, Thailand Tel No. : +66 (0) 2 203 6304 Fax No. :

(23)

Dr Mark Perkins Chief Scientific Officer

Foundation for Innovative New Diagnostics (FIND) Avenue de Budé 16

1202 Geneva, Switzerland

Tel No. : + 41 (22) 710 05 90 Fax No. : + 41 (22) 710 05 99

E-mail : [email protected] Dr Rattanaphone Phetsouvanh

Head of Microbiology Laboratory

Mahosot Tropical Medicine Research Unit Vientiane, Lao People's Democratic Republic Tel No. : +856 21 250 752

Fax No. : +856 21 242 168

E-mail : [email protected] Dr Rattanaxay Phetsouvanh

Head

Administration and Technical Office

Center of Malariology, Parasitology and Entomology Ministry of Health

Vientiane, Lao People's Democratic Republic Tel No. : +856 21 242980

Fax No. : +856-21 242981

E-mail : [email protected] Dr Chanthavone Phimmavongsa

Chief of Laboratory Ward Saravane Provincial Hospital Ban Phonkeo, Saravane District,

Saravane Province , Lao People's Democratic Republic Tel No. : +856 20 574 9338

Fax No. : +856 34 211 106 E-mail :

Dr Sok Po Deputy Director

Hospital Services Department Ministry of Health

#151-153, Kampuchea Krom Avenue Phnom Penh, Cambodia

Tel No. : Mobile Phone: 855 12 985 126 Fax No. : 855 23 428 221

(24)

Dr Kheng Sim Deputy Director

National Centre for Parasitology, Entomology and Malaria Control

Ministry of Health 372 Prah Monivong Blvd.

Tel No. : +855 12 926 266 Fax No. : +855 23 426 841 E-mail : [email protected] Dr Thongchanh Sisouk

Chief of Laboratory

National Center for Laboratory and Epidemiology, Km. 6, Thadeua Road

Vientiane, Lao People's Democratic Republic Tel No. : +856 21 315347

Fax No. : +856 21 350209 E-mail : [email protected] Dr Duong Socheat *

Director

National Centre for Parasitology, Entomology and Malaria Control

372 Monivong Blvd.

Tel No. : +855-12-926 266

Fax No. : +855-23 426 034/426 841 E-mail : [email protected]

Dr Franz-Josef V. Sonnenburg

Professor/Head

Section of International Medicine and Public Health Section,

Georgenstr. 5, 80799 Munich, Germany Tel No. : +49 89 2180 17600 Fax No. : +49 89 336038

Dr Phouthalavanh Souvannasing Chief of Pediatric Ward

Saravane Provincial Hospital Ban Phonkeo, Saravane District, Saravane Province

Lao People's Democratic Republic Tel No. : +856 20 5693 9539 Fax No. : +856 34 211 106 E-mail : [email protected]

(25)

Dr Siv Sovannaroath Chief of Technical Bureau

Chief of M&E CNM, Vector Control Coordinator National Centre for Parasitology, Entomology and Malaria Control

372 Monivong Blvd.

Tel No. : +855 12 335 029

Fax No. : +855-23 426034/426841 E-mail : [email protected] Dr Yok Sovann

Vice Director of Provincial Health Department and Provincial Malaria Coordinator

National Road # 57 Phum Wat, Sangkat Pailin, Krung Pailin, Pailin Province

Cambodia

Tel No. : +855 16 811 912 Fax No. : +(855) 55 956 033 E-mail : [email protected] Ms Jarasporn Tangkhabuanbutra

Scientist

Wellcome Trust – Mahosot Hospital Oxford Tropical Medicine Research Collaboration

Microbiology Laboratory, Mahosot Hospital Vientiane, Lao People's Democratic Republic Tel No. : +856 21 250 752

Fax No. : +856 21 242 168

E-mail : [email protected] Dr Viengxay Vanisaveth

Chief of Laboratory and Treatment Unit

Center of Malariology, Parasitology and Entomology Ministry of Health

Fax No. : +856 21 218 132 E-mail : [email protected] Dr Chanphomma Vongsamphanh

Deputy Director General Health Care Department Ministry of Health

Simuong Road, Sisattanak District

Fax No. : +856 21 217 848

(26)

2. OBSERVERS

USAID REGIONAL

DEVELOPMENT MISSION FOR ASIA

Dr Chansuda Wongsrichanalai*

Infectious Diseases, USAID/RDMA GPF Withhayu Tower A, 3rd Floor 93/1 Wireless Road.

Bangkok 10330 Thailand

Tel No. : +66 2 263 7411 Fax No. : +66 2 263 7499

E-mail : [email protected] Dr Rosanna Peeling

Clinical Research Unit, ITD

London School of Hygiene & Tropical Medicine Keppel St., London SC1E

7HT United Kingdom

Tel No. : +44 20 7927 2529 Fax No. : +44 20 7637 4314

E-mail : [email protected] USAID/MALARIA CONTROL

IN CAMBODIA

Dr Kheang Soy Ty * Chief of Party

USAID/Malaria Control in Cambodia Tel No. : +855 23 22 24 20 Fax No. : +855 23 221 433 E-mail : [email protected]

LAO, PDR

Dr Andrew Corwin US CDC Country Director U.S. Embassy

Vientiane, Lao People's Democratic Republic Tel No. : +856 21-26 7000

Fax No. : +856 21-267190

E-mail : [email protected]; [email protected] BILL AND MELINDA GATES

FOUNDATION

Dr Debbie Burgess * Senior Program Officer Global Health Technologies Bill & Melinda Gates Foundation P.O.Box 23350

Seattle, WA 98102, USA

Tel No. : +1 206 709 1672 Fax No. : +1 206 709 3170

(27)

FONDATION MERIEUX Mr Nicolas Steenkeste South East Asia Manager Fondation Merieux 73 Bd Monivong

Tel No. : +855 77 555 185/ +855 23 986 729 Fax No. : +855 23 98 67 29

E-mail : [email protected] MINISTRY OF HEALTH Dr Douangchanh KeoAsa**

Director of Department of Hygiene and Prevention Ministry of Health

Vientiane

Tel No. : +856-21 216364, 251619 Fax No. : +856-21 216365

E-mail : Ms Nancy Knapp **

Evaluation and Monitoring Technical Adviser (EMA) Global Fund Office

Ministry of Health Vientiane

Tel No. : +856 5680 0208 Fax No. : +856 21 242981

E-mail : [email protected] NATIONAL CENTER FOR

LABORATORY AND EPIDEMIOLOGY

Dr Onechank Keosavanh **

Deputy Director

National Center for Laboratory and Epidemiology Ministry of Health

Vientiane

Tel No. : +856 020 5589 7320 Fax No. : +856 21 350 209

E-mail : [email protected] Dr Daroumy Phonekeo **

Deputy Chief of Laboratory

National Center for Laboratory and Epidemiology, Ministry of Health

Vientiane

Tel No. : +856 020 5552 6255

Fax No. : [email protected] E-mail : +856 21 350 209

(28)

Mr Sinakhone **

Laboratory technician

Vientiane

Tel No. : +856 020 2233 6196 Fax No. : +856 21 350 209 E-mail : [email protected] Ms Phoutsamay **

Laboratory technician

Vientiane

Tel No. : +856 020 77004932 Fax No. : +856 21 350 209

3. SECRETARIAT

WHO/HQ Dr David Bell

Medical Officer

The Global Malaria Programme Avenue Appia 20

1211 Geneva 27, Switzerland Tel No. : +41 22 79 13236

Fax No. : +41 22 791 0746 E-mail : [email protected] Ms Amy Louise Cawthorne*

Alert and Response Operations World Health Organization Avenue Appia 20

1211 Geneva 27, Switzerland Tel No. : +41 22 79 11963 Fax No. : (+41 22) 791 0746 E-mail : [email protected] WHO/SEARO Dr Charles Delacollette

Coordinator

WHO Mekong Malaria Programme

Faculty of Tropical Medicine, Mahidol University 420/6, 7th Floor, New Charlermprakiat Building Ratchawithi Road,

10400 Bangkok, Thailand Tel No. : +66 2 643 5860 Fax No. : +66 2 643 5870

(29)

WHO/WPRO Dr Eva Maria Christophel ***

Medical Officer

Malaria, Other Vectorborne and Parasitic Diseases WHO Regional Office for the Western Pacific 1000 Manila, Philippines

Tel No. : +63 252 89723 Fax No. : +63 252 11036

E-mail : [email protected] Dr Jun Nakagawa

Technical Officer

Malaria, Other Vectorborne and Parasitic Diseases WHO Regional Office for the Western Pacific Manila, Philippines

Tel No. : +63 252 89721 Fax No. : +63 252 11036

Ms Glenda Gonzales Fellow

Malaria, Other Vectorborne and Parasitic Diseases WHO Regional Office for the Western Pacific 1000 Manila,

Philippines

Tel. : (632) 5288001 Fax : (632) 5211036

WHO/WPR Country Offices

CAMBODIA Dr Stephen Bjorge*

Scientist

Malaria, Other Vectorborne and Parasitic Diseases WHO Country Office in Cambodia

P.O. Box 1217, Sangkat Chaktomouk Khan Daun Penh

Phnom Penh

Tel No. : +855 23 216 610 Fax No. : +855 23 216 211 E-mail : [email protected] Dr Md. Abdur Rashid

Medical Officer

Malaria, Other Vectorborne and Parasitic Diseases WHO Country Office in Cambodia

P.O. Box 1217, Sangkat Chaktomouk Khan Daun Penh,

Phnom Penh

Tel No. : +855 23 216 610 Fax No. : +855 23 216 211 E-mail : [email protected]

(30)

LAO PEOPLE'S

DEMOCRATIC REPUBLIC

Dr Reiko Tsuyuoka Epidemiologist

Communicable Disease Surveillance and Response WHO Country Office in Laos

125 Saphanthong Road, Unit 5

Ban Saphanthongtai, Sisattanak District Vientiane

Tel No. : +856 21 353 902 Fax No. : +856 21 353 905

Dr Deyer Gopinath

Medical Officer

Malaria, Other Vectorborne and Parasitic Diseases WHO Country Office in Laos

Tel No. : +856 21 353 902 Fax No. : +856 21 353 905

E-mail : [email protected] Ms Hannah Catherine Lewis

Epidemiologist

Tel No. : +856 21 353 902 Fax No. : +856 21 353 905 E-mail : [email protected] Ms Mathida Thongseng

Temporary Secretary

Malaria, Other Vectorborne and Parasitic Diseases WHO Country Office in Laos

Tel No. : +856 21 353 902 Fax No. : +856 21 353 905

Dr Christian Winter **

Consultant for infection Control and Case management Communicable Disease and Response

Tel No. : +856 20 7783 0077 Fax No. :

(31)

Ms Pakapak Ketmayoon **

Consultant for Influenza Virology

Vientiane

Tel No. : +856 020 5630 2219 Fax No. : +856 21 353 905 E-mail : [email protected]

LEGEND:

* Invited but unable to attend.

** Additional secretariat/observers

*** Unable to attend

(32)

ANNEX 3

Country Presentation: Lao People's Democratic Republic

(33)

(34)

(35)

(36)

(37)

(38)

(39)

(40)

(41)

(42)

(43)

(44)

(45)

(46)

(47)

(48)

(49)

(50)

(51)

(52)

(53)

(54)

(55)

(56)

(57)

(58)

(59)

(60)

(61)

ANNEX 4

Country Presentation: Cambodia

(62)

(63)

(64)

(65)

(66)

(67)

(68)

(69)

(70)

(71)

(72)

(73)

(74)

(75)

(76)

(77)

(78)

(79)

(80)

(81)

(82)

(83)

(84)

(85)

(86)

(87)

(88)

(89)

(90)

(91)

(92)

(93)

(94)

(95)

ANNEX 5

Group Work Guidelines

Group 1: Clinical implication of the results for national programs and for treatment algorithms/guidelines

Tasks: Discuss the treatment algorithms for management of RDT negative cases for Laos and Cambodia

Key questions:

1. What would the algorithms look like?

2. When would referral for further investigation be recommended?

3. Should these algorithms be nationwide, regional or provincial?

4. What are the likely disadvantages of such algorithms?

5. What are the likely program costs for these treatments?

6. What other research is needed?

7. What further research is needed to confirm effectiveness and safety of management of these cases?

8. Which national guidelines would be affected by any proposed changes?

Group 2: Implication of the results for further trials and diagnostics development

Tasks: Review available laboratory diagnostic methods and define priorities for future developments.

Key questions:

1. How do we standardize NMFI screening studies to make them more readily implementable?

2. Which will be the “gold standard” tests for diagnosis?

3. How to define/collect standard materials to evaluate performance of available tests and usefulness for disease diagnosis and management?

4. What currently available diagnostic should be taken into to field trials?

5. How do we prioritize development of diagnostic tests for:

NMFI screening?

Case management?

(96)

ANNEX 6

Group work Presentations

(97)

(98)

(99)

(100)

(101)

(102)

(103)

(104)

(105)

(106)

(107)

(108)