4th GLEAN Meeting Report.pdf

4th Global Leptospirosis Environmental

Action Network (GLEAN) Meeting

18th20thNovember, 2014

Colombo - Sri Lanka

Meeting Report

Executive Summary

The Global Leptospirosis Environmental Action Network (GLEAN) was launched in 2010 and co-chaired by

World Health Organization (WHO) and the Health and Climate Foundation (HCF). Since leptospirosis

surveillance, prevention and control demand multisectoral and multidisciplinary approach, the initiative was

designed to develop a holistic multidisciplinary approach to address the leptospirosis problem by bringing

together different sectors and expertise involved in leptospirosis research and development. It provides

direction and coordination to fill many gaps in leptospirosis knowledge with the ultimate goal of translating

the research findings into operational guidance for communities and countries affected by leptospirosis

outbreaks. The first GLEAN Technical Meeting, held in France in 2011, identified existing knowledge along with

research gaps. The 2nd meeting, organized in Italy in 2012, defined short-and long-term objectives and

finalized a preliminary guideline for outbreak response. The 3rd, held in March 2013 in Brazil, hosted by the

Ministry of Health of Brazil, and organized by the Pan American Health Organization, WHO and HCF.

Formalized four working groups related to disease prediction, prevention, detection and intervention.

This 4th

GLEAN meeting, held 18-20 November 2014 in Colombo, Sri Lanka, was jointly hosted by the Ministry

of Health of Sri Lanka and WHO. Thirty international experts from 12 countries mainly from South-East Asia,

international organizations, foundations, academic institutions, research laboratories and 50 National

participants from the Ministry of Health the Department of Animal Production & Health, the Ministries of

Agriculture and Wildlife, and Universities shared their expertise and experiences through oral and poster

presentations. They reviewed the GLEAN plan of work related to Prediction, Detection, Prevention and

Intervention against Leptospirosis outbreaks taking into consideration the changing epidemiology and new

technologies

Leptospirosis remains a neglected disease globally. Large isolated outbreaks continue to be reported mainly

related to natural disasters, and have been recognized as a priority for action. Further, rural leptospirosis is

often associated with certain occupational groups especially paddy farmers. High economic loss is associated

with leptospirosis as it mainly affects the economically active population. Intersectoral collaboration especially

among human health, animal health and agricultural sectors, and community participation is observed in many

countries demonstrating One Health approach.

Participants made the following key recommendations:

- To focus the GLEAN operational agenda on countries most affected by frequent outbreaks and high incidence of cases and to develop strategies adapted to their specific realities and solutions.

- To support implementation of quality management systems for diagnosis and references laboratories. - To develop evidence-based guidelines for case management of acute febrile illnesses. - To develop predictive models for outbreaks prone areas that can inform preparedness and interventions

efforts. - To carry out studies on the influence of climate fluctuations and weather hazards on outbreak risk

Report Committee

Michel Jancloes, Health and Climate Foundation

Gyanendra Gongal, World Health Organization

Paba Palihawadana, Epidemiology Unit, Sri Lanka

Eric Bertherate, World Health Organization

Cristina Schneider, Pan American Health Organization, USA

Claudia Munoz Zanzi, University of Minnesota, USA

Rudy Hartskeerl, Royal Tropical Institute, Netherlands

Navaratnasingam Janakan, World Health Organization

Jagath Amarasekera, Epidemiology Unit, Sri Lanka

Commonly Used abbreviations AFI Acute Febrile Illness BoD Burden of Disease CDC Centers for Disease Control and Prevention DALY Disability Adjusted Life Year DG Director General ELISA - Enzyme-linked Immuno Sorbent Assay EMS Event Management System GBD Global Burden of Disease GLEAN Global Leptospirosis Environment Action Network ICU Intensive Care Unit IEDCR Institute of Epidemiological Disease Control and Research IFAT Immiuno Fluorescence Antibody Test IgM - Immunoglobulin M IHA Indirect Haem Agglutination IHR International Health Regulations LAMP - Loop Mediated Isothermal Amplification LVI Local Vulnerability Index MAT - Microscopic Agglutination test MLST Multi Locus Sequence Title MRI Medical Research Institute NTD - Neglected Tropical Disease PAHO Pan American Health Organization PCR - Polymerase Chain Reaction PhD Doctor of Philosophy PHL Public Health Laboratory PLoS Public Library of Science

QER Quarterly Epidemiology Report RDT - Rapid Diagnostic Test RMRC Regional Medical Research Center RPA - Recombinase Polymerase Amplification

SEAR South East Asia Region

SEARO South East Asia Regional Office

TEPHINET Training Programme in Epidemiology and Public Health Intervention

UBN Unsatisfied Basic Needs

UN United Nation

WBC White Blood Cells

WER Weekly Epidemiology Report

WHO World Health Organization

Contents

Introduction ............................................................................................................................................ 1

Day 1 ....................................................................................................................................................... 2

Inauguration ........................................................................................................................................ 2

Technical Session 1 ............................................................................................................................. 2

Technical Session 2 ............................................................................................................................. 6

Technical Session 3 ........................................................................................................................... 10

Day 2 ..................................................................................................................................................... 14





Day 3 ..................................................................................................................................................... 29



Conclusion and Recommendations ...................................................................................................... 34

Conclusion ......................................................................................................................................... 34

Recommendations ............................................................................................................................ 36

Annex 01: Meeting Agenda ................................................................................................................... 38

Annex 02: Meeting Participants ............................................................................................................ 41

Annex 03: Posters presented ............................................................................................................... 44

Annex 04: Photograph .......................................................................................................................... 45

GLEAN Meeting Report 2014 1

Introduction

The Global Leptospirosis Environmental Action Network (GLEAN) was initiated in 2010 and

co-chaired by World Health Organization (WHO) and the Health and Climate Foundation

(HCF). It comprises of representatives from national services, international organizations

and foundations as well as researchers. Since leptospirosis control and prevention requires a

multisectoral and a multidisciplinary approach, GLEAN initiative brings together experts

from a range of fields of expertise to fulfil this requirement. It provides direction and

coordination to fill many gaps in leptospirosis knowledge with the ultimate goal of

translating the research findings into operational guidance for countries affected by

leptospirosis.

As part of the GLEAN initiative, each year an annual meeting is held with the goal of

discussing its progress and planning for the future. Three meetings were held in 2011, 2012

and 2013 in France, Italy, and Brazil, respectively.

Leptospirosis is a high burden disease among Asian countries and this reason became a long

felt need to hold a GLEAN meeting in an Asian country. Sri Lanka was selected as the venue

for the present meeting due to its burden of leptospirosis, its experience in outbreak

management as well as its good infrastructure for organizing the meeting.

The objectives of the meeting were to make GLEAN better acquainted with experiences

from countries in Asia affected by leptospirosis outbreaks, to investigate on the different

patterns of leptospirosis transmission, to engage GLEAN in cooperation with few countries

to respond to their specific needs integrating the relevant aspects of prediction, detection,

prevention and intervention, to review the GLEAN strategic plan and to clarify next year

activities and expected deliverables.

The meeting was jointly organized by GLEAN and the Epidemiology Unit of the Ministry of

Health, Sri Lanka with support of the World Health Organization.


Day 1

Inauguration

The 4th Global Leptospirosis Environmental Action Network (GLEAN) Meeting was

inaugurated by Dr.Sarath Amunugama, Deputy Director General (Public Health Services) of

Ministry of Health Sri Lanka, Dr. Arturo Pesigan, Acting WHO Representative for Sri Lanka,

Dr. Michel Jancleos, GLEAN co chairman, Dr.Paba Palihawadana, Chief Epidemiologist, of

Ministry of Health Sri Lanka and Dr.Gyanendra Gongal, Scientist, WHO/SEARO.

Dr. Paba Palihawadana welcomed the participants from Ministry of Health and Dr. Michel

Jancloes made welcome remarks from the GLEAN perspective. Dr. Arturo Pesigan delivered

the WHO Regional Director message. The inaugural speech was made by Dr Sarath

Amunugama. Dr. Gyanendra Gongal presented the meeting background and its objectives.

Technical Session 1: Leptospirosis Prevention and Control in South-East Asia

Chair: Paba Palihawadana

-GLEAN perspective

Michel Jancloes

Leptospirosis is a serious zoonosis causing an estimated 1,500,000 cases and 50,000 deaths

globally each year. Though it is a major human and animal disease with serious economic

impact, it remains neglected and under reported. The presence of nonspecific symptoms

and complex transmission is a challenge that affects implementation of control strategies.

Leptospirosis outbreaks in 2008 and 2009 in Sri Lanka and Manila respectively, highlighted

the need for technical guidance in controlling the disease. GLEAN is an inter-sectoral and

action initiative created for this purpose.

The mission of GLEAN is to reduce the impact of leptospirosis outbreaks on communities

through better understanding of the relationship between leptospirosis and various

associated factors including environmental, biological, ecological, economic and

demographic factors and providing more timely warnings of the onset of leptospirosis

outbreaks and improving the effectiveness of leptospirosis prevention and control

strategies.


Subsequently the first GLEAN meeting in 2011 in Marseille identified urban natural

catastrophes to be addressed as a priority. At the second GLEAN meeting in Ispra, Italy in

2012, decisions were made about the mission of GLEAN, its structure, its steering

committee and membership and four strategic pillars (predict, prevent, detect, intervene

including their objectives) were defined. GLEAN website www.GLEAN/lepto.org was

created. Diagnosis tests and guidelines for leptospirosis outbreak control were reviewed and

a project to review outbreak outcomes from 1970 onwards was initiated.

The third GLEAN meeting in Brazilia in 2013 worked out the plan around the four strategic

pillars. It also identified needs for guidelines on antibiotic therapy, chemoprophylaxis, early

rapid test and rodent control.

At this meeting, new partnership and new work areas will have to be explored. Such areas

include public health, veterinary and bio technology industry, economic impact of

outbreaks, detection strategies and vaccine development. It will also emphasize the needs

of public health and medical research institutions for early case detection, surveillance,

public health intelligence and public information. New partnership needs to be established

between GLEAN and countries for method comparison, knowledge sharing and

experimental strategies.

Sharing experiences from SEARO countries could help to better understand the different

patterns and dynamics of leptospirosis transmission and of outbreaks and to identify

cooperation avenues with GLEAN.

This meeting is expected to respond to the following key questions (identified in

consultation with Professor Albert Ko /Yale University)

Can surveillance and reporting be improved and made more systematic and efficient,

so as to better inform the descriptive epidemiology and provide sources of cases for

case control investigations?

Can GLEAN help in the systematic and up to date assessment of the disease burden

(morbidity, proportion of severe disease, and mortality) through passive

surveillance?

Can GLEAN help in establishing and hopefully decentralizing access to laboratory

confirmation in surveillance?

How can effective detection, diagnosis and triage of leptospirosis patients be

implemented especially since there is a high rate of severe acute febrile diseases?

Can case-control investigations be implemented in order to obtain basic information

on risk factors and at risk populations and inform risk stratification schemes?


What is the reservoir for transmission so as to inform control measures?

What are the drivers (either ecological, part being reservoir, environmental or

climactic-related) for the large emergence that happened since 2008?

The response to these questions could help update the GLEAN plan of action, based on the

four pillars identified for leptospirosis prevention and control:

Predict

To obtain baseline Incidence

To understand main drivers and their predictive value such as climate, environment,

vector demography

To develop predictive models and risk stratification to be validated at risks sites

Prevent

To evaluate the role of vectors, rodents control, chemoprophylaxis, human and

animal vaccination

Detect

To make case definition

To identify outbreak threshold

To make early diagnosis test and case confirmation (specificity and sensitivity)

To develop algorithms for outbreak detection and case management

Intervene

To inform public health decision, operational guidance for outbreak control and

outbreak investigation guidelines

-Overview in Leptospirosis in South East Asia Region

Gyanendra Gongal

Leptospirosis is an endemic disease in the SEAR countries and has been associated with

large outbreaks.

In places such as Gujarat and Tamil Nadu it is endemic with pronounced seasonality. Large

isolated outbreaks have been reported in Orissa (1999) Mumbai (2005) and Philippines

(2009). Sustained epidemics over broad geographical region have been identified in

Thailand 1990s and in Sri Lank 2008-2009.

Leptospirosis in SEARO has often occurred as an occupational hazard with epidemic

potential associated with natural disasters. Rural leptospirosis is caused as a result of

exposure of agricultural communities to contaminated wet farm land particularly during


monsoon. Leptospirosis among rice farmers in Indonesia, Thailand and India are such

examples. Urban leptospirosis is caused due to unplanned urbanization, large rodent

population infesting the sewage canals and poor drainage systems flooding the roads.

Outbreak in Mumbai following heavy rain falls is an example of this epidemiological form.

Leptospirosis is also associated with natural disasters such as cyclones and floods which

often cause outbreak of leptospirosis in Orissa in Indian following the super cyclone in 1999

is one such example. Situation in South East Asia may be underestimated due to the lack of

proper surveillance data in most countries.

Thailand has reported 10 fold increase in incidences since 1996 with some endemic pockets.

A study found the sero-prevalence in general population in Indonesia to be 11.8% and sero-

prevalence in rats to be as high as 47%. In Sri Lanka, leptospirosis has been identified as one

of the most common epidemic causing disease. Maldives and Timor-Leste too have reported

leptospirosis cases. Sero prevalence of 38.2% was observed in flood prone areas of

Bangladesh. Chukha (Bhutan) too has reported suspected leptospirosis cases after flooding

in 2008.

In addition to reporting, other areas relevant to leptospirosis are a concern. For example,

the clinical form of leptospirosis cases in India which was predominantly hepato-renal has

changed to 70% hepato-renal, 20% pulmonary and 10% multi organ failure. In Sri Lanka 19

serovars from 7 sero groups have been isolated so far with 8 reference serovars having

originated from Sri Lanka.

Technical support and capacity building for the countries in the region have been done

through WHO SEARO. Expert consultation on prevention and controlling leptospirosis was

provided in Chennai, 2010. Furthermore, technical cooperation has been provided for

diagnosis and clinical case management of leptospirosis in Member countries, for the

development of laboratory networks for better diagnosis and quality assurance of diagnostic

tests, for leptospirosis risk reduction considering country locality specific situation through

WHO Collaborating Centres and networks.

Leptospirosis, with a high case fatality rate and epidemic potential, particularly in the

aftermath of natural disasters, is a disease of high public health importance and it needs to

be kept under surveillance so that rapid response could be initiated when early warning

signals of an impending outbreak occur.


Technical Session 2: Country Presentations

Chair: Gyanendra Gongal and Yupin Suputtamongkol

-Leptospirosis Bangladesh overview

A K M Muraduzzaman

Bangladesh is a country with population of over 166 million and the density of 1237.51

persons per square kilometer making it the worlds most densely populated country.

Leptospirosis is neglected in Bangladesh and epidemiological information on leptospirosis

too is limited. However, environmental factors and statistics show that leptospirosis has

been an economically important disease in livestock sector and thereby making it a health

hazard for the people involved.

Bangladesh is a low-lying country with sub tropical monsoon climate and a wide seasonal

variation in rainfall with moderately warm temperature and high humidity. These climatic

factors favor leptospirosis spread. Sixty percent of the country is flooded annually. Over 5

million people live in slums and only 19% have access to safe sanitation. Forty five percent

of the total labor force is engaged in agriculture and uses traditional farming methods and

rodents too are great problems for farmers. These are some of the environmental factors

favoring the spread of the disease.

Surveillance for Acute Fever Infection (AFI) started in May 2014 by IEDCR (Institute of

Epidemiological Disease Control and Research) to generate data for risk analysis, to explore

the extent of the disease, to establish the national surveillance system to develop

collaborations with national, international and UN agencies and to make national policy

makers aware for decision making. It started in selected sentinel sites covering the enter

country. The samples collected from AFI cases (5 per week per sentinel site) are to be

screened and confirmed by performing laboratory tests. So far no analysis has been done.

Issues and challenges for leptospirosis control include the lack of data on animal reservoir,

climate change causing natural disasters, poor laboratory facilities, and poor coordination

between human and veterinary health sectors, limited funding and empirical use of

antibiotics.

Future scope and planned activities are numerous. Formulating and revising ongoing

surveillance, control and prevention activities and designing an appropriate policy targeted

towards decreasing the burden of leptospirosis are such measures. Taking measures to


improve surveillance, advocacy, awareness, education, diagnosis and vaccination and

conducting further research on animal reservoirs, climate change and other environmental

factors too are identified for the future. Ensuring government policies and legal frameworks

to support surveillance, strengthening laboratory facilities and reporting systems and

increasing interaction between human and veterinary health sectors too constitute as

future scope.

-Present scenario of Leptospirosis in Bhutan

Dorji Tshering

Bhutan is a country situated between China and India. It has a land area of 38,394 square

kilometers and a population of 753,947. Though leptospirosis is a notifiable disease in

Bhutan, proper surveillance mechanism is not in place. There is lack of laboratory diagnostic

activities and surveillance in place. Limited awareness of clinical and health workers and the

community in general is another problem persisting in Bhutan with regard to leptospirosis.

Therefore, not much was known regarding leptospirosis as a public health problem until a

study was done from June 2013 onwards. The present study from June 2013 to February

2014 had 174 samples collected so far and 80 tested at RMRC Port Blair, India which yielded

7 samples positive for leptospirosis.

A first joint animal and human leptospirosis study was conducted in 2013 and laboratory

training for animal and human health personal was conducted in 2014 where some public

health action was initiated. Currently a joint work plan for human and animal health for

zoonotic disease, including leptospirosis, has been developed.

Issues and challenges for leptospirosis control in Bhutan include the need to scale up

laboratory diagnosis. There is lack of space in the current place where PHL is housed and

clinicians and health workers being unaware and not sensitized on leptospirosis. Not having

established sentinel surveillance, difficulties in sample shipment from field (health centers)

to PHL and lack of sample referral from PHL to WHO collaborating center are also some

issues that Bhutan is faced with.

Future plans include scaling of laboratory facility, establishing sentinel surveillance, training

clinicians and health workers, collaborating with livestock in research studies and

conducting health education for public.


-Leptospirosis situation in India

Paluru Vijayachari

Leptospirosis occurs mostly on the peninsular part of India which shows a strong seasonal

trend with peaks corresponding to the monsoons and post-monsoons. It is very common

among rice farmers and rice field workers. Leptospirosis also occurs as outbreaks, among

people engaged in cleaning water bodies and sewages. Pulmonary involvement has been

reported with increasing frequency and has become a common cause of death.

A case report of Acute Respiratory Disease Syndrome that occurred due to leptospirosis

reveal that the patient develop breathlessness on the fifth day of illness. Initial treatment

with oral chloroquin and amoxycilin had been given. Fever had continued and the routine

hematological test had been normal and MP negative. X-ray shows the opacities of lung to

be increased from 6th day up to the 10th day. From the 10th day, resolution of opacity was

observed progressively until day 19th, when there was complete resolution. Patient was

discharged on the 29th day.

Another case report shows a patient with a history of fever for 6 days and a cough and

severe pulmonary haemorrage syndrome. He was treated with benzyl-penicillin, ranitidine

and paracetamol. However, on the 7th day he developed breathing difficulty and the x-ray

showed bilateral mottled opacities. He developed severe haemoptysis and died on the same

day. These two case reports demonstrate the importance of identifying the respiratory

complications of leptospirosis.

Estimated incident of leptospirosis in India is around 5 per 100000 populations in 2013 with

specific mortality being 0.1 per 100000 populations. A comparison of leptospirosis cases and

deaths between 7 Indian states namely, Tamil Nadu, Karnataka, Himachal Pradesh,

Maharashtra, Gujarat, Kerala, Nicobar/Andaman was done. It revealed that although Tamil-

Nadu and Karnataka had higher cases, they did not report any deaths. On the contrary,

states such as Gujarat and Kerala reported 308 and 769 cases with 66 and 26 deaths,

respectively.

Burden of disease in the form of DALY calculated for the above mentioned Indian states for

2013 revealed the DALY per 100000 populations in states of Andaman and Nicobar and

Gujarat to be 35 and 25 respectively indicating high DALYs for leptospirosis in these states.


-Leptospirosis control in Indonesia

Tri Setyanti

Indonesia is a country with 240 million population and comprises of 34 provinces, 511

districts and 1.9 million square kilometer extent. Leptospirosis is a public health problem in

Indonesia with outbreaks reported from 2010 onwards. MAT confirmation is available only

in limited hospitals. Increasing potential risk factors such as natural disasters (floods,

volcanic eruptions) and handling of reservoir animals make it a significant public health

problem. In 2014, 411 cases and 56 deaths were reported indicating high case fatality rate.

Available information shows that majority of leptospirosis patients are males in the middle

age group. Goals of leptospirosis control in Indonesia are to decrease Case Fatality Rate, to

decrease number of leptospirosis cases (morbidity), to increase knowledge and behavior of

community in endemic areas and to make available epidemiological data and clinical data of

leptospirosis for policy decisions and control strategies.

Leptospirosis control is implemented by strengthening coordination both related to cross

programs and cross-sectoral coordination through local zoonosis commission in

Districts/Townships/Provinces and National Zoonosis Commission at National levels with

active participation of all community components. Budget for leptospirosis control comes

from District/Township, Province and Central government and community support. It also

comes from international organizations which is not binding and not against existing

regulation. Increasing source capacity especially human resource through variety of training

is also important for control. Directorate General of Disease Control and Environmental

Health holds training of trainers (TOT) for leptospirosis control. Extending leptospirosis

control network at every level of government administration with variety of stake holders,

improving technical care and monitoring to achieve optimal implementation quality and

implementing evaluation to find out program activity results too are part of leptospirosis

control activities.

Leptospirosis control strategies include building political commitment at every level of

government administration by implementing advocacy and socialization of leptospirosis

control program in endemic areas. Improving capacity of human resource and controlling

leptospirosis outbreak too are part of control strategies. Emphasis is also given to improving

epidemiological surveillance in human and for risk factor, early leptospirosis case

management, risk factor control and strengthening prevention effort. In addition the control

strategies are complemented through ensuring strong networking and monitoring and

evaluation.


Constrains and challenges for Leptospirosis include threat of zoonosis increases, close

contact between humans and animals (due to recreation, economic needs etc.), humans

increasing contact with environment and wild animals (clearing of forests, residing closer to

forests, etc.), climate change (causing rodent increases, adaptation/mutation etc.) and

change in migration pattern.

-Leptospirosis situation in Thailand

Pornpitak Panlar

Thailand is a country with 68.23 million population of which around 10 million living in

Bangkok. Its climate is warm and humid.

Number of cases has peaked just after flooding in 2013, with the morbidity rate in 2013 to

be around 5 per 100000 population and case fatality rate around 1%. Comparison of

characteristics of human leptospirosis cases between year 2002 and 2012 was taken in to

consideration. From 2001 to 2011 in North East Thailand, mean age has increased from 42

to 46 years; case fatality rate has increased from 6.3% to 19.7%. Pulmonary haemorrhage

has increased from 10% to 33%, multi organ dysfunction has increased from 27% to 50%

showing that the complications from leptospirosis has increased significantly.

A change in the infective serotype of leptospires in this area is one possible explanation for

the changing clinical manifestations. This is supported by the isolation of one new serotype

amongst the four isolates, and the new serotype was isolated from a fatal case. More effort

in the cultivation of leptospires or in the application of advance molecular techniques to

identify genotype and serotype of infective leptospires causing human leptospirosis in this

area is needed.

Technical Session 3: Experience in leptospirosis in Sri Lanka

Chair: Paluru VIjachari

-Epidemiology of leptospirosis in Sri Lanka

Jagath Amarasekera

Leptospirosis (also called as rat fever) was first described in Sri Lanka in 1953 and isolated in

1959. Leptospirosis reporting shows that the number of cases has increased fourfold from

2007 to 2008 to over 7000 cases which was a massive outbreak. From there onwards it has

remained at a higher base line level with two peaks witnessed in 2008 and 2011.


The seasonal variation shows annual peaks to be observed during paddy cultivation and

harvesting season. There are ten traditionally high endemic districts which are all situated in

the wet zone in Sri Lanka that contribute to over 85% of caseload. However, from recent

time in addition to these districts, districts such as Anuradhapura, Moneragala, Vavuniya

and Hambantota which are in the dry zone have reported increased incidences. Majority of

leptospirosis patients are males in their middle age with paddy field exposures which have

been the most common environmental exposure. Other exposures such as marshy lands,

other water related exposures, and exposure to other agriculture lands and animal handling

too have contributed as possible sources of exposure.

Acute fever, headache, myalgia, prostration continued to be the common clinical feature of

suspected leptospirosis patients with symptoms such as prostration and jaundice too being

present in around 20% patients. The case fatality rate in Sri Lanka is currently between 1.5%

and 2%.

Letospira antibody have been identified in animal in Sri Lanka by research studies with

examples of presence of leptospirosis in domestic cattle serological confirmed by

Nityananda (1970) and Peiris and Wettimuny (1972). Gamage et al (2011) identified

leptospira antibodies in cattle (23, 20%) and rodents (13, 17.5%) in Kandy district. Study on

sero-prevalence of leptospirosis in domestic dogs in Colombo (Thammitiyagodage et al,

2013) has found 56% seroprevalence among 38% unvaccinated dogs.

-Laboratory diagnosis and common serovars in leptospirosis

Lilani Karunanayake

The National Reference Laboratory for leptospirosis of Sri Lanka has conducted 3819 MAT

tests in 3745 samples in 2013 and 2415 samples in 2014 (up to October). Culture was done

in 74 samples. Pyrogenes, Pomona, Icterohaemorrhagiae and Autumnalis were the four

common sero-groups identified in 2012 in a research done at MRI.

Comparison in serovars in humans and animals have found that in humans in 1974 common

serovars were Icterohaemorrhagiae, Autumnalis, Hebdomadis, Grypotyphosa and in 2004 it

was Pyrogenes, Icterohaemorrhagiae, Autumnalis and Pomona. In animals in 1974 it was

Icterohaemorrhagiae, Javanica, Canicola, Pomona and in 2004 it was Sejroe, Pyrogenes,

Icterohaemorrhagiae, Australis and Canicola.

Currently there have been patients who have tested positive for leptospirosis with history of

exposure due to leisure activities (white water rafting). Comparison of 3 diagnostic assays


using IgM ELISA kit, leptocheck WB and MAT test reveal that leptocheck has a 87.4 %

sensitivity and 81.7 % specificity , IgM ELISA has 90.6% of sensitivity and 96% specificity,

MAT 77.1% sensitivity and 98.5% specificity when Bayesian latent class modeling were done

in 800 patients with suspect of leptospirosis. Hence both parameters make IgM ELISA a

suitable test for early diagnosis of leptospirosis. Leptocheck may be used as a screening test

and MAT remains as a confirmatory test.

-Clinical aspects of leptospirosis; a Sri Lankan perspective

Senaka Rajapakse

Leptospirosis disease spectrum reveals that high percentages (85-90%) are asymptomatic.

Leptospirosis disease clinical features ranges from mild leptospirosis to severe leptospirosis

and Weils disease being the severest form which ultimately lead to death. Prospective data

on 232 patients admitted to National Hospital, Colombo reveals that 86% were male,68.5%

had severe leptospirosis,35.5% needed haemodialysis, and 6.9 % needed ICU care with 2.6 %

mortality.

Clinical features revealed that, over 80% patients had fever, headache and myalgia with 0 %

to 80 % having rigors, anorexia and muscle tenderness with around 20% having features of

complications such as breathlessness, oliguria, haematuria, chest pain and neck stiffness.

Acute kidney injury was observed in to 67.7%, with 2.2% having myocarditis, and 5.2% going

in to shock.

Challenges in clinical diagnosis in leptospirosis include not having a clear cut diagnosis since

many infectious diseases such as dengue, rickettsial infection, Hantavirus may present with

the similar clinical picture.

Hence a study was conducted with 450 patients with clinically suspected leptospirosis to

determine whether heamotological parameters differentiated leptospirosis from other

infections. Results show that Total WBC decline over the first 5 days of illness, and then rise

until the end of second week. It also shows the platelet counts to decline over the first six

days of illness and then gradually rise and hemoglobin levels to have a gradual decline.

Predicting severity using univariate analysis identified correlates of severe diseases as fever >

38.8 C on the day of admission (p = 0.008), age > 40 years (p = 0.033), muscle tenderness

(p= 0.04),tachycardia on admission (p = 0.05), ALT > 70 IU/L (p = 0.02), hyponatraemia<

131mEq/L (p = 0.004). Also the severity correlated with declining sodium levels and rising

serum creatinine values (correlation coefficient = 0.318, p=0.001).


It is important to have predictor of severity to identify which patients developed

complications. However, only a few predictors have been found so far and clinical

parameters are few and not robust enough to be of real clinical relevance. Hence we need

biomarkers which can predict severity. Lipid peroxide level, protein carbonyl level, anti-

oxidant capacity and nitrite level were the four biomarkers assessed. Lipid peroxide level

appeared to be high in leptospirosis and no difference between mild and severe disease

were observed. Lipid peroxide level is normal in dengue. Protein carbonyl levels were

significantly higher in severe leptospirosis and normal in dengue. Anti -oxidant capacity was

significantly lower in leptospirosis though there was no difference between severe and mild

disease. Anti-oxidant capacity was normal in dengue. Nitrite levels reveal that the severe

leptospirosis patients have the highest mean nitrite levels.

Challenges in clinical management are many. Antibiotics given generally are penicillin,

doxycycline and cephalosporins. Cochrane review has found benefit of antibiotics to be

unclear, though duration of clinical illness may be short. Management is largely supportive

and constitutes vital organ support where necessary.

-Discussion on Leptospirosis situation in Sri Lanka

Chair: Paba Palihawadena and Paluru VIjachari,

Panel members: Jagath Amerasekera, Lalani Karunanayake, Senaka Rajapakse

Facilitator: Gyanendra Gongal and Navaratnasingam Janakan

The discussion was mainly focused on leptospirosis situation in Sri Lanka, though the

regional situation and experiences too were briefly outlined mostly as a comparison.

Laboratory diagnosis was one area that was discussed. The role of rapid diagnosis tests to

complement the diagnostic capability was stressed. Currently national programme uses only

MAT test though Rapid tests are available in the private sector. However, it is important to

validate these tests with use of regional specific antigens as common leptospirosis serovars

vary between countries and geographical areas.

The role of chemoprophylaxis in leptospirosis control in Sri Lanka was discussed. In Sri Lanka

high risk farmers, as perceived by the public health staff, are given chemoprophylaxis during

the paddy cultivation season. Since there is debate and mixed results regarding the use of

chemoprophylaxis as a preventive strategy, a study is being conducted by the Epidemiology

Unit to assess the compliance and the effectiveness of chemoprophylaxis in preventing

leptospirosis. The study was discussed at this forum with participants giving the benefits and

constrains of different methods of conducting the study. Importance of linking the human


leptospirosis cases with the possible reservoir animal (rat, cattle, buffalo, dog, pig), was

discussed. A study conducted in this regard was discussed during the session.

Clinical features and severity of leptospirosis was another area of concern. It was discussed

as to whether the severity and mortality are associated with the infecting serovar. The

opinion of the forum was that it is an area worth assessing. The importance of assessing the

possible cause (e.g.: dengue, Q fever) of fever in suspected leptospirosis patients who are

negative for leptospirosis diagnosis test too was discussed.

Day 2

Technical Session 1: GLEAN Objectives and Strategic Priorities

Chair- Michel Jancloes and Maria Cristina Schneider

-GLEAN perspectives

Michel Jancloes

GLEAN is an intersectoral initiative under the aegis of WHO and HCF. It aims to reduce the

impact of leptospirosis outbreaks on communities through providing cost-effective,

implementable and sustainable solutions. Overarching objectives of GLEAN are to better

understand the relationship between leptospirosis and various associated factors including

environmental, biological, ecological, economic and demographic, to provide more timely

warnings on the onset of leptospirosis outbreaks, and to improve the efficacy of

leptospirosis prevention and control strategies.

The main institutional assets of GLEAN are its high level expertise in various disciplines, its

public health legitimacy, flexibility, autonomy and its network structure. Informed decisions

of GLEAN are made through annual technical meetings. Still, it has to develop a legal

identity, secretariat sustainability and to create incentives for collective actions.

The current 4th GLEAN meeting is a timely meeting which is bringing together officials and

public health experts from highly affected countries. It is expected to recognize country

specific realities and solutions needed to guide and feed the global GLEAN Agenda. The

valuable inputs from countries would add critical information to the GLEAN Executive Board

for adequate decision making. Also by sharing experiences from South Asian countries most

affected by leptospirosis, the different transmission patterns in South Asia will be better

understood and could engage GLEAN in cooperation with countries.


-Brief review on four GLEAN strategic pillars

Predict:

Claudia Munoz- Zanzi

Goals of the Predict Pillar include identifying and understanding the main drivers of

infection in different settings and evaluating their predictive potential for outbreaks and

seasonal increases. Ultimately, improved knowledge and predictive models will be used to

support public health decisions and evidence-based intervention programs for different

applications and scales.

A systematic literature review of leptospirosis outbreaks with reported sources from 1970-

2012, show that the reported source includes floods and high rainfall (38%), water exposure

(14%), recreational (6%), occupational (28%) and others (14%). Potential source of the

outbreaks was not reported in 43% of articles. Regarding risk factors identified through

traditional epidemiological studies, recent occurrence of floods, swimming exposure,

occupational and socio-demographic factors (living conditions), and presence of rodents are

often mentioned. However, a full understanding of the mechanisms behind these risk

factors is incomplete. The living conditions, landscape features, habitat, bio diversity and

weather changes results in increase of new contacts and higher environmental

contamination load resulting in higher incident in leptospirosis. The mechanism of

transmission of infection in such circumstances leading to high incident rates needs to be

better understood which would enable us to predict increases in incidence and outbreaks. It

is recommended and necessary to integrate multiple data sources, at various ecological

setting and scales, to develop models for prediction.

Predict Pillar, through its members, had a very productive year with many publications and

presentations ranging from leptospirosis advocacy to communication of new

epidemiological knowledge.

Prevent:

Jackie Benschop

Communication, Health Education and Social Mobilization is an important area in preventing

leptospirosis. General public communication in La Runion where production of posters and

flyers for general population, for gardeners and for aquatic leisure and the small portion of

the TV programs in New Caledonia raising awareness and teaching prevention strategies

shown at the forum demonstrates the importance of clear messages in this regard.


Preparation of a Manual in Brazil for leptospirosis with three chapters (patients,

environmental surveillance and disease control) having a strong orientation on

communication, health education and social mobilization, too clearly demonstrates its

importance.

Rodent control too is another key area in prevention of leptospirosis. Currently there is an

ongoing study on impact evaluation of the continuation of Rodent Control Programs in

Brazil (Salvador, So Paulo, Curitiba and Recife). Three day National course on rodent

control to prevent leptospirosis was held in Salvador, Brazil (April, 2014). A chapter on

rodent control program (including protocols) in the MOH Brazilian manual of leptospirosis

has been included. GLEAN rodent control recommendations too are provided.

Vaccination of animal reservoirs (eg: cattle, buffalo, dog) too is a strategy to prevent

leptospirosis among the people exposed to these animals. Members of the GLEAN team

(Claudia Munoz-Zanzi) is currently evaluating the impact of animal vaccination on

leptospirosis shedding and assessing the impact of dog vaccination on decreasing

leptospirosis burden in urban settings (Claudia Munoz-Zanzi). Currently Prof Peter Wilson is

conducting a systematic literature review to assess the best practice recommendations for

the use of vaccines to prevent human exposure.

Chemoprophylaxis too is a strategy that needs to be assessed. Currently animal

experimental studies to support chemoprophylaxis pre & post exposure are conducted.

Series of studies to encompass a pre and post exposure to leptospirosis of hamster model

and treated the animals with Doxycycline by different manner are carried out. Preliminary

conclusion shows that treatment by oral route should be done for a long period of time.

Prevent pillar needs to be further strengthened. It is important to have a written protocol to

evaluate and determine preventive measures and to validate the protocol in different

epidemiological contexts. It is also important to conduct a systematic review on human

vaccines that are currently available and provide recommendation of future studies to be

conducted.

As an approach to strengthening GLEAN Pillars it is important to identify and act on

opportunities to work together. Activities such as co-supervision of PhD students and joint

grant application and linking to universities in countries where the work needs to be done

are currently being conducted. Such activities already commenced need to be built on (eg:

World Bank funded one health projects - NZ-SL vet school twinning).


It is also important to avoid isolation and promote safe sharing of ideas for better and

sustained results.

Global morbidity and mortality of leptospirosis: a systematic review

Fedrico Da Costa (Presented by Claudia Munoz- Zanzi)

Leptospirosis is a major and under recognized threat to public health which is treatable and

preventable. Therefore, establishing accurate estimates of disease burden leads to better

direction of appropriate intervention, control and prevention efforts. Hence assessing the

global burden of leptospirosis is important.

Challenges in estimating the burden of leptospirosis are multiple. The epidemiology of the

disease is highly variable and there is sparse data and lack of prospective population based

studies. Barriers to laboratory confirmation and lack of adequate studies in geographical

regions and poorest countries which are most vulnerable to the disease cause under

reporting leading to bias estimates.

A systematic review and quality assessment were done on mortality, case fatality, and

different morbidity conditions from 1970-2009 for leptospirosis. 32 electronic databases of

published literature and 9 databases from unreported population-based studies were used

as the data source. Inclusion and quality assessment criteria has been applied and the

approach approved by LERG. In order to assess the disease burden, initially a systematic

review, quality assessment and data extraction were performed. Subsequently, sources of

heterogeneity, risk stratified by age and gender, potential under-reporting was explored.

Global estimates of morbidity and mortality were obtained from country-level estimates

adjusted for age and gender distribution while addressing under-reporting due to

incomplete laboratory confirmation.

Descriptive analysis was done using ten studies with morbidity data and three studies with

case fatality data for age and gender specific risk. Under reporting between suspected and

confirmed case, in nineteen morbidity and four mortality studies was analyzed.

Morbidity estimation through modeling approach was done from country specific crude

incident available from 80 studies. Certain equations were used for the model including age

and gender specific relative risk, age and gender specific incidents for 34 countries, ratio

between clinically suspected and laboratory confirmed cases from 19 studies. It yielded,

predicted age and gender specific incidences in 220 countries and territories.


Mortality was estimated through extracting data from country specific crude incidence of 80

studies and 35 studies with case fatality.

Results of these modeling yielded Global Estimates of Morbidity and Mortality. Annual

estimated cases based on this modeling are around 1,030,000 and deaths are around 58,900.

Highest cases and deaths are estimated to be in the South East Asia and West Pacific regions.

Adult males with age 20-49 years of age accounted for 48% (95% CI, 40 61%) and 42% (95%

CI, 34 53%) of the predicted annual cases and deaths worldwide, respectively. 73% cases

occur between Tropic of Cancer and Capricorn.

As with all global burden of disease (BoD) studies, limitations include having sparse quality-

assured data, poor representative information in some regions, and data being hospital

based result in estimates not including less severe disease.

The way forward would be to complete the burden of disease study with calculations of

DALYs, validate findings with regional or national burden of disease studies, establish or

improve surveillance in regions with high predicted burden of disease. There is an urgent

need to address under-reporting and barriers to laboratory confirmation as well as

encouraging population-based studies to estimate burden at community level.

Detect:

Rudy Hartskeerl

Purpose of pillar detect is to help countries in developing and implementing policies and

tools for early outbreak detection, focusing on diagnostics and surveillance. There are

multiple areas of work or deliverables which comes under this pillar. A survey has been

initiated to assess the description of surveillance systems in South American countries with

the survey initiated in Brazil and Colombia. Though it was expected to be completed in 2014,

it would be completed at a later date. Descriptive review on diagnostics is another

component of the pillar. It has been completed and the review has been published.

Cochrane review on serological diagnostic tests was initiated as part of a PHD study and was

not a primary GLEAN goal. The publication titled Serological laboratory tests for diagnosis

of human leptospirosis in patients presenting with clinical symptoms by Goris et al has

been accepted by Cochrane. Cochrane review on antigen detection tests titled Molecular

and antigen detection tests for leptospirosis by Yang B et al has been accepted by Cochrane

and the protocol is in the review stage. Meta analysis has been already commenced. A

future plan of this pillar is to have a global leptospirosis serum bank for validating


diagnostics (humans and animals) and it requires funds. Other actions include projects such

as TEPHINET/CDC mini-grant projects in the region and proposal submission to evaluate the

cost-effectiveness of various diagnostic strategies for early diagnosis, as well as barriers to

implementation (NIH R21). Publications on outbreak Brazil and GLEAN in leptospira and

leptospirosis (2015) are other publications carried out by different members of the GLEAN

team. Support extended by THPHINET for Brazil ministry of health to develop rapid post

flooding need assessment is another activity undertaken.

Intervene:

Michel Jancloes

The Intervene pillar is crucial for translating research findings in policy and operational

terms at country and community levels. The development of operational guidelines for

outbreak control including chemoprophylaxis is currently being carried out. A preliminary

experiment in animals has been done to test different regimens of chemoprophylactic

drugs.

Special efforts in the production of guidelines will be made to work closely with countries

and regions (within country) to be contextual.

As a long-term intervention, GLEAN is currently looking at vaccine development both in

animals and humans. This is to be designed as a 10 year investment plan. Currently few

vaccine producing companies are in discussion with GLEAN.

Other new areas for the Intervene pillar include integration into One Health approach with a

more holistic orientation.

Technical Session 2: Country Needs

Chair: Samitha Ginige

-Leptospirosis challengers in Americas region

Maria Cristina Schneider

Global alerts on leptospirosis from 2010 -2012 (total 562) show that more than half (361)

the alert were in the Americas, particularly from Brazil (158), Nicaragua (47) and Argentina

(43). Leptospirosis was the sixth top infectious hazard in the WHO Event Management

System (EMS/IHR) globally and the third top in the Americas during the period of June 2007


to Feb 2013. Possible environmental drivers in the form of natural disasters show that 69%

of the natural disasters were floods and storms from 2010- 2012.

Study titled Leptospirosis Outbreaks in Nicaragua: Identifying Critical Areas and Exploring

Drivers for Evidence-Based Planning was conducted by Schneider et al (2012) with the

objectives of documenting the known areas of outbreaks and analyzing possible drivers in

Nicaragua. It was an ecological type study using secondary sources and data available from

2004- 2010. Results show that, out of the 153 municipalities studied, 48 were hotspots and

85 were endemic areas and 20 were silent areas. The study results have to be interpreted

within the limitations of an ecological study. Exploratory analysis using regression model

found significance for type of soil, precipitation and rural population.

It can be concluded that outbreaks do not occur on a yearly basis and the risk is different

between the departments and municipalities. And this methodology used in the country

plan could be applied in other countries.

Socioeconomic factors and vulnerability to outbreaks of leptospirosis in Nicaragua was

conducted by Bacallao J et al (2014) with the objective of constructing and validating a

vulnerability index based on municipal socioeconomic indicators that could be used as

criteria to identify priority areas for intervention in the high risk departments. Relative

importance of the variables in defining the clusters found that Unsatisfied Basic Needs (UBN)

of Quality of Household was the variable with the highest (100%) relative importance,

followed by poverty (95%), UBN sanitary services (90%) and illiteracy (89%).Out of the 32

municipalities analyzed, none with a low or medium local vulnerability index (LVI) presented

with high incidence rate for leptospirosis. The municipalities with high LVI had high or

medium incidence rates for leptospirosis (with one exception). In the present study the

underlying distinction between risk (given mainly by environmental factors) and

vulnerability to risk (given mainly by socioeconomic conditions) was reinforced. The basic

components of the index were the unsatisfied basic needs in relation to the construction

material conditions of the household, access to sanitary services and extreme poverty.

The two studies mentioned above were applied in the Nicaraguan National Plans for

Neglected Infectious Disease, signifying the importance of applying research outcomes in to

practice.

Ongoing study titled Leptospirosis in Rio Grande do Sul, Brazil: An ecosystem approach in

the animal-human interface with the objective of analyzing the distribution of human cases


of leptospirosis in the State of Rio Grande do Sul and exploring possible drivers yielded

interesting preliminary results.

It was an ecological study using open access and official data. 46% of cases are rural. Over

half of the state is silent. The study looked in to possible drivers of the leptospirosis. Most

municipal councils with high incidence are under 200 feet altitude. Uruguay and Argentina

border has a lot of silent areas. Soil appears to be a possible driver. The tobacco plantations

have close proximity with high incidence areas. Though the exact reason is not known, pH

and type of soil due to tobacco plantation could be the possible reason. Also the

undergrowth may attract rodents. Further studies are needed in this regard. The animal

population too was assessed as a possible driver. Large farms with 100 and above cattle did

not appear to be associated with high leptospirosis though small farms with less than 10

cattle by property appeared to be associated. Poverty was not identified as a possible driver.

Though these results are based on GIS mapping, statistical analysis has been initiated. With

support of agriculture and UFRGS team in the bovine survey, its expected to share this

information with government at the state and national level as they are decision makers.

Further the study will be published and information will be shared with research teams.

There are few regional challenges for controlling leptospirosis. It has a complex cycle and

many species are involved in the transmission when favorable condition and several

environmental and socioeconomic drivers are in place. There is limited surveillance in

humans and animals. It is often misdiagnosed with dengue and other disease because

symptoms of leptospirosis are similar with other frequent local diseases such as dengue,

influenza, hanta virus infection, yellow fever, rickettsiosis, malaria, viral hepatitis and others.

It is not yet a tool ready disease with more options needed for rapid and early diagnosis.

However, there are regional strengths that are important for leptospirosis control.

Leptospirosis has already been recognized as a public health problem by several countries

which have already commenced control programmes. The need for multi sectorial

collaboration has been identified by several countries which have already initiated

coordinated efforts among health, agriculture and other sectors.

Activities conducted by the PAHO /CHA/IR from an outbreak perspective include identifying

priority countries in the Region related to leptospirosis outbreaks and conducting studies to

identify risk areas and drivers for leptospirosis outbreaks through a standard methodology.

Developing a tool to support countries to predict, detect, prevent and respond to outbreaks

and supporting WHO and GLEAN initiative and supporting countries in technical cooperation

too are other activities conducted by the PAHO /CHA/IR. In addition numerous forums and


meeting too were organized. Those include National Forum of Leptospirosis, International

meeting of countries that are facing outbreaks of leptospirosis in the Americas (Nicaragua,

August 2012), GLEAN Meeting (Brazil, 2013) and Simulation Exercise conducted in Choluteca,

(Honduras, 2013). The webpage on leptospirosis in the PAHO website

(www.paho.org/leptospirosis) gives more information on the leptospirosis activities

conducted in the region as well as technical details relevant to leptospirosis.

-Leptospirosis in South-East Asia Region: Issues and challenges

Navaratnasingam Janakan

Leptospirosis is a neglected disease with changing epidemiology. It has large number of

circulating serovars and different animal reservoirs. Urban and rural leptospirosis is the two

forms of leptospirosis based on the transmission of the disease. Multi-sectorial coordination

and collaboration is imperative for leptospirosis control. However, leptospirosis control is a

difficult task due to the protean nature of clinical manifestations, change in symptoms and

complications. Availability of limited diagnostic facilities and the varying opinions and results

on the effectiveness of chemoprophylaxis too is an issue that we are facing. Immunization of

dogs and livestock too is difficult to achieve.

Prevention and control activities need evidence and knowledge on exact nature of disease

transmission and dynamics including animal reservoirs & serovars responsible, environment

factors and human behavior. Obtaining this knowledge or evidence is a difficult task. Further,

the interventions implemented are sometimes done due to public demand rather than

being evidence based.

In addition to the above mentioned issues there are challenges that are faced by the South

East Asia region. Climate change is a major challenge. Frequent natural disasters such as

floods, unplanned urbanization causing constrains on drainage and waste disposal and

ground water exploitation too are challenges that we are facing. Ensuring advocacy and

community awareness regarding leptospirosis are some of the issues which still remain as a

major challenge in the region. Availability of rapid and reliable diagnostic test needs to be

improved. Nonspecific clinical features, sub-clinical infection, difficulties in diagnosis,

misdiagnosis and lack of awareness are some of the reasons which cause underreporting.

Another major challenge that we are faced with is linking the clinical, epidemiological and

laboratory data to ensure a holistic and a complete picture regarding leptospirosis.

Currently these three areas are not linked together in most instances, making the

information available to us on leptospirosis to be available in isolation as separate

compartments. Therefore, in order to overcome the challenges and issues relevant to


leptospirosis disease control in the region we need to carry out numerous tasks in the future.

Strengthening disease surveillance and capacity building for diagnosis & clinical case

management of leptospirosis in Member States require utmost attention. Establishment of

National Leptospirosis Reference Laboratories and networking among institutions relevant

in the field of leptospirosis (e.g. labs) too needs to be addressed. It is also equally important

that guidance for risk reduction is given considering country and locality specific situation.

Developing a Regional Strategic Framework for Prevention and Control of Leptospirosis in

the SEAR and promoting collaborative research with international partners and academia

are also tasks that we need to carry out in the future for effective control of leptospirosis

among SEAR counties.

Technical Session 3: Country Specific Strategies

Chair Vincent Herbreteau & Claudia Munoz Zanzi

-Control of interactions between animal and human leptospirosis The New Zealand

pastoral livestock example

Peter Wilson and Jackie Benschop (Presented by Peter Wilson)

In New Zealand the livestock is the primary source of human leptospirosis infection. It is also

called as dairy worker fever. In establishing New Zealands leptospirosis status and

epidemiology there is two research phases. The 1978 to 1984 phase which looked in to

mainly diary and pigs and the 2002 up to now phase involving sheep, beef, deer, humans

and diagnostics.

During the 70s and 80s the Massey University had taken steps to identify serovars by host

(humans and animals), effect of vaccination of cattle and assess the serovars of wildlife and

sheep.

By mid 90s with strong establishment of the dairy industry in New Zealand, the need to

look in to leptospirosis in dairy and humans became more important.

2002 onwards a lot of work has started at Massey University related to leptospirosis. The

diagnosis is done in these studies using MAT but with culture gold standard confirmation.

Also has quantified prevalence/incidence overall and by serovar. An ongoing longitudinal

data is currently looking at the changing patterns for at-risk human populations and also the

animal and human epidemiological associations.


These data has established relative importance to animals, humans by serovar and

identified likely sources and risk factors. They have also informed about targets for control

such as rodent and wildlife control, risk management by people and livestock vaccination.

Human cases reported from 1997 to 2012 show no reduction over the years with overall

incidence still around 2.5 per 100000. However, this may be an under estimate. A study

among risk groups indicated that the actual incidence to be 40 times higher than the

reported. The commonest serovar among notified cases continues to be Hardjo and

Pomona, though Ballum is gradually gaining importance. The commonest occupation among

the notified cases is dairy workers, abattoir workers and farmers.

A longitudinal study was done from 2009 to 2014 where leptospirosis sero-surveys were

conducted in four (meat workers, veterinarians, veterinary students and farmers) high risk

occupational groups from 2009 to 2014. It showed the meat workers to have a sero

prevalence of 12%. The farmers and veterinarians had a sero-prevalence of over 4%. The

veterinary students had a 0% sero-prevalence. Change of sero prevalence from 0 to 4 when

veterinary students become veterinarians could be due to them being more careful during

student years or them being more exposed to risk situations during work than during

student years. The sero-prevalence among livestock show that nearly 100% of cattle and

sheep farms and over 75% of deer farms to be having livestock positive for leptospirosis.

This clearly demonstrates that livestock is the major source of leptospirosis in New Zealand.

-Strategy to control leptospirosis in Thailand

Pornpitak Panlar

Leptospirosis in Thailand is mostly related to paddy farming and outbreaks occur due to

natural disasters such as flooding. Therefore most preventive and control measures are for

activities related to agriculture and floods.

Prevention and control measures need to be addressed through collaboration between

public health, livestock, and environmental sectors. Early detection of cases is done through

active case finding by village health volunteers. Then they refer suspected cases to health

center for screening and early treatment. This in return strengthens active surveillance to

detect other cases. For early diagnosis, history of exposure to contaminated source and

symptoms such as high fever, severe headache, muscle pain, particularly affecting the

muscles in the calves and lower back are taken to consideration. If this results in identifying

suspected cases the cases are quickly referred to the hospital and laboratory tests are

conducted to determine the disease.


There are two criterias for health sector recommendation. A patient who had high fever

more than 3 days, exposure to contaminated source, had severe headache and muscle pain

should be referred to the community hospital. The other criteria is a patient who had fever

less than 3 days and had not complicated symptom such as jaundice, red eyes, abdominal

pain, etc should be given the appropriate of antibiotic (eg: doxycycline). If the symptoms

have not improved in 2 days after treatment then the patient should be referred to the

hospital. Analysis of leptospirosis cases during 2008 - 2012 revealed that peoples awareness

in endemic area to be very high, resulting in them visiting the hospital within three days of

fever.

In order to achieve early control, educational efforts are to be enhanced in endemic areas

(to encourage the use of protective clothing, how to avoid the risk of factors). Strengthening

the active surveillance in the community too is important for early control. Coordination

between human health, animal health and environmental sector is important. It helps in

separating livestock areas with public water facilities and also helps to set surveillance

system in animals. Such coordination will maximize the impact of rodent management and

also develop environmental sanitation in the community. Community participation in all key

activities will strengthen the community to have intervention to prevent and control

leptospirosis. Community participation is important in deciding appropriate measures for

animal and human leptospirosis control and to improve awareness of the community.

-Sri Lanka - leptospirosis control and prevention country specific strategies

Paba Palihawadana

Sri Lanka is an Island off southern coast of India having a population around 20 million. It

has a high life expectancy (75 years) and high literacy rate (over 90%). Leptospirosis is a

public health problem in Sri Lanka with approximately over 4000 suspected cases reported

annually since 2008. Therefore having a National Leptospirosis Control and Preventive

Programme is extremely important. The objective of the National Leptospirosis Control and

Preventive Programme is to reduce the morbidity and mortality due to leptospirosis in Sri

Lanka through reducing the incidence, case fatality and preventing outbreaks of

leptospirosis. Since leptospirosis control needs multi-sectorial approach, inter-sectorial

collaboration is important. Therefore at national, district and local levels, coordination

committees and technical committees are established and are functioning with

representation from human health, animal health and agriculture sector. Strengthening

inter and intra-sectoral coordination, decision making and activity management are some of

the functions of these committees.


Surveillance is a key area for leptospirosis control. Surveillance data is routinely analyzed

and interpreted for decision making. The routine notification system and the leptospirosis

special surveillance conducted at field level and at sentinel hospitals are important in this

regard. Relevant information on leptospirosis disease situation is disseminated through

Weekly Epidemiological Report (WER), and Quarterly Epidemiology Bulletin (QEB) published

by the Epidemiology Unit of Ministry of Health of Sri Lanka. Disease situation is also updated

to the Epidemiology Unit website (www.epid.gov.lk). Disease situation, including its

prevention and control activities are periodically reviewed.

Rats are considered the major reservoir of leptospirosis in Sri Lanka. Therefore rodent

control activities such as cleaning surrounding areas, having a narrow ridge of the paddy

field, destroying rat burrows, traditional rat control measures in paddy fields and

households are implemented at field level. Increasing community awareness through

development and distribution of posters and leaflets to the field level is done by the

Epidemiology Unit. In addition, a documentary and a television film has been developed and

made available for screening at community level gatherings. Mass media campaigns are

conducted annually to coincide with paddy cultivation season. Chemoprophylaxis too is

given to selected high risk groups in Sri Lanka. One health approach is another area that is

made use of in leptospirosis control. Research projects conducted with involvement of

Ministry of Health, Ministry of livestock and rural development, WHO, World Bank and

Messy University are such examples. Identifying leptospirosis serovars and linking human

leptospirosis cases with animal reservoirs to assess which animals contribute towards the

spread of the disease is conducted through one such research project. Leptospirosis control

was also discussed during national One Health Symposium conducted in 2014.

Training of student and service personnel is a key component in leptospirosis prevention.

Such trainings are done as in- service training, under graduate training and post graduated

training. Currently there are new challenges for controlling leptospirosis in Sri Lanka.

Changes in weather pattern causing heavy rains and floods during harvesting season and

rains affecting the dry zone is such a challenge. Increase in disease incidence in non high

endemic areas and variability in clinical management of leptospirosis too are such new

challenges. Strengthening one health activities through formation and implementing of One

Health hub in Sri Lanka too is currently being carried out to improve the inter-sectoral

coordination.


-Capacity building and referral services in countries of the South East Asia region

Paluru Vijayachari

Regional Medical Research Centre (RMRC) Port Blair, Indian is an institution designated by

the WHO to form part of an international collaborative network in support of programmes

at the country, regional and global levels for leptospirosis. The functions include collection,

collation and dissemination of information, standardization of technology of diagnostic,

therapeutic and prophylactic substances and also development and application of

appropriate technology. Conducting collaborative research, promotion of the application of

research results and training are few more of its functions. Terms of reference of this

institute include estimating the burden of leptospirosis in India and other countries,

studying the ecology of leptospirosis, developing control strategies (environmental control)

and developing vaccines for the prevention of leptospirosis in human and animals. It also

serves as a referral and training centre on leptospirosis and coordinates network of

leptospirosis reference laboratories in countries of the South-East Asia region. Developing,

standardizing and evaluating diagnostic test kits too are part of its terms of reference. RMRC

also provides training on laboratory methods in leptospirosis throughout the year. Hands-on

training workshops on laboratory methods in leptospirosis too are being conducted on

alternate years at national level. International level workshops were conducted in 2010 and

2013.

Leptospirosis laboratory network in India consist of the RMRC Port Blair which is the

national reference laboratory and five regional and eight referral laboratories. RMRC also

plays a key role in leptospirosis diagnostic tests development. Since RMRC is situated in Port

Blair in Andaman and Nicobar Islands, it has contributed towards the improvement of the

leptospirosis situation in those two Islands. It has resulted in a sharp decrease in the

leptospirosis sero-prevalence in humans (decreased from 30% to 13%) and animals

(decreased from 38% to 16%). Specific mortality due to leptospirosis has decreased from 7.5

/100000 population to about 1/100000 population. Overall leptospirosis burden too has

dropped from 618 to 117 DALY.


Technical Session 4

-Update on diagnostics and vaccine development

Rudy Hartskeerl

There are conventional test such as DFM, MAT, ELISA, IFAT, IHA, and MSAT for leptospirosis

diagnosis. These tests have many draw backs. Being slow and unreliable, having a low

detection threshold, difficulties in standardization are some of the draw backs. In addition

these may require well trained person and expensive media or equipments. Isolation of the

spirochete confirms leptospirosis but this test is too slow for individual diagnosis. Hence its

mainly of epidemiological value. Serological tests such as MAT are considered gold or

reference standards and it may provide indication of the infecting sero group. However it

requires panels of locally representative serovars.

ELISA is another serological test which detects IgM antibodies against leptospires. Its genus

specific. Although rapid diagnostic tests are available they have their own draw backs.

Relatively low and varying diagnostic accuracy, requiring repeated local evaluations and

confirmation by conventional test too is a drawback. Rapid diagnosis is different from early

diagnosis since it is done based on serology. Therefore it does not help in early diagnosis

and initiate early antibiotic treatments. There is an early diagnostic gap encountered when

serology tests are used for diagnosis. Since leptospires circulate in the blood notably first 4-7

days after onset of disease, several NA amplification techniques on blood samples like PCR

can fill in this gap.

The future leptospirosis diagnostic tests should look at providing antigen detection based

early and rapid test. Development of clinical and laboratory algorithm by validation through

globally representative sample banks globally or locally, assessment of epidemic thresholds

by collecting base-line data (surveillance) are areas that need to be considered for the

future. Antigen test can be improved by using nano/biosensors.


Day 3

Technical Session 1

Chair: Jackie Benschop

-Prediction and modeling in leptospirosis research and action

Claudia Munoz-Zanzi

Leptospirosis can occur in different epidemiological patterns resulting in some areas with

sporadic cases and other areas with high incidence and outbreaks. Furthermore, in a specific

area or region, there is often a strong seasonality component and various levels of

endemicity. When thinking of options for risk reduction and interventions, we should

understand if we are trying to minimize or prevent outbreaks or reduce the existing level of

endemicity or reduce both. A different strategy is required if, for example, the goal is

reducing case fatality. These different needs call a different set of epidemiological

approaches and methods.

It is important to separate statistical prediction from mathematical prediction. Statistical

analysis of empirical data from various studies is producing vast amount of knowledge about

leptospirosis burden, epidemiology and ecology. Examples of such studies being carried out

by GLEAN members is the epidemiology of leptospirosis in rodents (Brazil) and in dogs

(Chile). Analysis of prospectively collected data improves the predictive potential of findings

(e.g. cohort studies in slum of Brazil); however, there is still uncertainty and challenges in

the best way to measure exposures that would lead to infection. At a different scale, a study

on El Nino Southern Oscillation and Leptospirosis outbreaks in New Caledonia (Daniel

Weinberger et al) was conducted using cases from surveillance data. El Nino Southern

Oscillation (ENSO) and other climate variables were used in this study and predictive

(multivariable) model was developed. Goal was to forecast the number of leptospirosis

cases four months into the future using a simple model that included the SST (sea surface

temp) anomaly variable (one of the best predictors) which is available nearly in real-time.

Mathematical modeling integrates the knowledge about leptospirosis biology, epidemiology,

ecology, as well as specific population characteristics through mathematical equations and

assumptions. These systems help to understand the mechanism of transmission of

leptospirosis in the various host populations and generate hypothesis. Models can also be

used to assess impact of leptospirosis in humans and animals and value of interventions (eg:


vaccination, chemoprophylaxis, rodent control programs). In terms of healthcare

administration and planning, models can be used to identify cost effective interventions and

also predict public health needs such as how much money needs to be allocated for an

intervention.

Models help us understand reality because they simplify it. Consequently all models are by

definition wrong. A model should only be as complex as needed, depending on the

question of interest.

A Workshop on leptospirosis modeling sponsored by the National Institute of Mathematical

and Biological Synthesis (NIMBioS) was conducted in June 2014 at the University of

Tennessee in Knoxville, where an interdisciplinary group of experts discussed uses of

modeling at different scales and applications. A follow up NIMBioS Working Group was

approved to work on various modeling projects during the next two years. Collaborations

with stakeholders to generate critical questions and needs as well as access to data for cases

studies are needed.

-Leptospirosis: addressing the public health challenge for this neglected disease

Albert Ko and Federico Da Costa (Presented by Mathieu Picardeau)

Leptospirosis was considered traditionally to be an occupational disease among subsistence

farmers and other groups. Hence, it was identified as Milkmaid Fever and Fort Bragg Fever.

However with current increase recreation, travelling and globalization, it is emerging as a

disease in recreational activities, water sports and in global events such eco challengers.

Although leptospirosis has an endemic transmission in tropics, large outbreaks following

disasters such as floods, have been witness in Nicaragua (1995, 2000s), Mumbai, 2005 and

Philippines 2009. Urbanization coupled with poverty resulting in expansion of slums give rise

to increased leptospirosis in the urban population as witnessed in Brazil. Therefore

leptospirosis is an emerging public health problem. The epidemiological pattern among the

slum dwellers shows it to be a rat-borne transmission, single sero-group agent with annual

epidemics. The exposures occur during rain fall and it attacks the same slum communities

each year. Leptospirosis is a neglected disease with limited data to guide resource allocation

and policy. There is lack of an adequate diagnostic test and safe vaccines are not available.

There are major knowledge gaps on pathogenesis, natural history and transmission resulting

in absence of effective control measures.


Recent advances in leptospirosis has resulted in over 300 geno sequence improved MLST

methods (PLoS NTD 2013) and basis to address basic questions on diversity, pathogenesis

and vaccines.

Leptospirosis is a treatable yet an under recognized cause of acute fever and life treating

illness as demonstrated in global systematic AFI surveys. There are barriers to diagnosis and

treatment of leptospirosis. Although Antibiotic therapy affords greatest

Documents

4th GLEAN Meeting Report.pdf