Clinical Guidelines

for Diagnosis and Management of Leptospirosis

2016

Ministry of Health
Fiji Islands
Preface
Leptospirosis is one of the key priority outbreak-prone diseases for the Fiji Ministry of Health and Medical
Services (MHMS). Endemic disease is responsible for substantial morbidity and mortality, and large
outbreaks have occurred, including two severe post-flooding outbreaks in 2012 with 576 reported cases
and 40 deaths. Inaccurate diagnosis, inconsistent clinical management and delays in referral are likely to
be responsible for progression from mild treatable disease to severe complications and deaths. High
quality clinical management can reduce disease burden and mortality, and accurate reporting will
improve public health surveillance and response. In this context, the Fiji MHMS requested WHO support
to develop national guidelines for clinical diagnosis and management of leptospirosis. The guidelines
aim to improve patient outcomes by standardising and optimising clinical assessment, diagnosis,
management, referral, and reporting of leptospirosis cases. Recommendations are based on current
scientific evidence and access to medical care and laboratory services in Fiji.

Lead author
Dr Colleen Lau, Australian National University. Email: [email protected]

The guidelines were developed after consultations with the following clinicians and public health
practitioners at Fiji Ministry of Health and Medical Services, WHO Division of Pacific Technical
Support (Suva), Colonial War Memorial Hospital, and Fiji National University (in alphabetical order):

Dr Shrish Acharya Dr Mike Kama

Dr Akuila Naqasima Dr Ravi Naidu
A/Prof Lisa Bennett Dr Devina Nand
Dr Viema Biaukula Dr Eric Nilles
A/Prof Anne Creaton Dr Gyaneshwar Rao
Dr Anne Drake Dr Vereniki Rawalui
Dr Aneley Getahun Dr Josaia Samuela
Mr Shakti Gounder Dr Laila Sauduadua
Prof Adam Jenney Dr Shahanam Venkataiya
Dr Vini Kalougivaki Dr Osea Vola Vola

Feedback on the guidelines was also sought from clinicians and public health practitioners in Suva,
Lautoka, and Labasa.

Acknowledgements
Prof Albert Ko (Yale University) for sharing Brazil’s clinical guidelines for management of leptospirosis,
and Dr Javier Cortes Ramirez (University of Queensland) for translating the Brazilian guidelines into
English.

Date submitted: Draft submitted 20th December 2015. Final version submitted 10th June 2016.
Date approved:

This guideline should be reviewed every 5 years, or earlier if there are significant changes in the
availability of diagnostic tests or access to health care.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 1
CONTENTS:
1. Introduction, epidemiology and risk factors
2. Overview of approach to the management of suspected leptospirosis
3. Clinical assessment
3.1. History and examination
3.2. Red flags - Danger signs and symptoms
3.3. Differential diagnoses
4. Case definitions: suspected, probable, and confirmed
5. Level of medical care required: criteria for hospitalisation and ICU admission
6. Investigations
6.1. General investigations
6.2. Leptospirosis diagnostic tests
7. Treatment
7.1. Antibiotics
7.2. Management of complications
7.2.1. Dehydration, hypotension, and shock
7.2.2. Respiratory complications
7.2.3. Acute renal failure
7.2.4. Cardiac arrhythmias
7.2.5. Haemorrhage and coagulopathy
7.2.6. Steroids
7.3. Convalescence and follow-up
8. Prophylactic antibiotics
9. Disease notification and public health response
10. References

Figures:
Figure 1. Leptospira IgM ELISA-positive cases reported in Fiji from 2010 to 2015
Figure 2. Seroprevalence prediction chart showing the combined effects of independent risk factors
on the estimated seroprevalence of leptospirosis
Figure 3. Case definitions for leptospirosis: suspected, probable, and confirmed
Tables:
Table 1. Levels of medical care recommended based on clinical assessment and investigations
Table 2. Common investigations and results in leptospirosis patients
Table 3. Comparison of leptospirosis diagnostic tests
Table 4. Recommended antibiotics and dosages for the treatment of leptospirosis
Appendices:
A. Overview of approach to clinical management
B. Summary wall chart for outpatient management
C. Summary wall chart for hospital inpatient management
D. Summary wall chart for intensive care unit (ICU) and emergency department (ED)
E. Leptospirosis Case Investigation Form

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 2
1. INTRODUCTION

Leptospirosis is one of the most common zoonotic diseases in the world with an estimated
1 million cases annually, and particularly high risk in tropical regions including the Pacific Islands.
Infection is caused by pathogenic leptospires that are excreted in the urine of infected animals, including
rodents, domestic pets, livestock and wildlife. Leptospires can survive in soil or water for weeks or
longer, and humans can become infected through direct contact with infected animals, or through
contact with soil or water contaminated by the urine of infected animals. Risk factors for human
infections and drivers of outbreaks depend on interactions between humans, animals, and the
environment. Environmental factors play an important role in disease transmission, and an increased
risk of leptospirosis has been linked to high rainfall, flooding, natural disasters, poor sanitation, and
population growth and urbanisation in developing countries, particularly in urban slums [1,2]. Human
activities that increase exposure to animals, soil, mud and water are also important risk factors.

In the Pacific Islands, important risk factors include the tropical climate, high rainfall, flooding, and close
contact with livestock. Many people also live a very outdoor lifestyle with close connection with the
environment, e.g. swimming, bathing, and washing in the rivers, walking barefoot, and gardening [3-9].

In Fiji, clinical and epidemiological studies have identified males, iTaukei, and young adults aged 20-49
years as high-risk groups [10-12], most likely related to greater occupational and recreational exposure
to animals, soil, mud and water. Other risk factors include living in rural areas or villages; poverty,
including the lack of government water supply at home; farming, working outdoors or in abattoirs;
touching rats or mongoose; raising pigs at home or the presence of pigs in the community; exposure to
flood waters; and living close to rivers or in areas of high rainfall [12]. The number of cases peak in the
wettest months from February to May.

In 2012, two large outbreaks occurred after severe flooding with 576 reported cases and 40 deaths [12].
In comparison, previous studies in Fiji reported 487 cases during a 13-year period from 1969-1981 [10],
and 576 cases during an 8-year period from 2000-2007 [11]. Figure 1 shows the number of Leptospira
ELISA IgM positive cases reported from 2010 to week 39 of 2015 by gender and division.

700 700 Not recorded

Not recorded
600 600 Northern
Female
Central
Number of cases
Number of cases

500 Male 500 Western

400 400

300 300

200 200

100 100

0 0
2010 2011 2012 2013 2014 2010 2011 2012 2013 2014
Year Year

Figure 1. Leptospira ELISA IgM positive cases reported in Fiji from 2010 to 2014, stratified by gender
and Division of residence. Note that gender and Division were not recorded in a large number of cases
in 2012. Data provided by Fiji Ministry of Health & Medical Services.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 3
 Important risk factors for leptospirosis Fiji include:
▪ Demographics: male, iTaukei, young adults
▪ Occupational risk: farmers (livestock, cane, taro, other crops), abattoir workers, outdoor workers,
cleaning streams, exposure to sewage and garbage
▪ Contact with animals: livestock (especially raising pigs), rodents, pets, wildlife
▪ Contact with freshwater, soil, or mud: floodwaters, rivers, lakes, waterfalls
▪ Household environment: live in rural area or village, no metered water at home
▪ Live or work in areas with high risk of leptospirosis (e.g. recent outbreaks)
▪ Epidemiological link to another case (e.g. household member or co-worker)

Patients with multiple risk factors are at even greater risk of infection. A recent epidemiological study of
leptospirosis in Fiji showed that the combination of multiple independent factors could significantly
increase the risk of infection [12]. Figure 2 shows a seroprevalence estimation chart for leptospirosis in
Fiji based on gender, ethnicity, community type, availability of metered water at home, and work location.
It is important to note that the numbers reported in the chart are the percentages of people who had
antibodies to leptospirosis (i.e. infected in recent years), but not all infected persons develop
symptomatic illness. Figure 2 works on the same concept as cardiovascular risk prediction charts.

Figure 2. Seroprevalence estimation chart showing the combined effects of independent risk
factors on the estimated seroprevalence of leptospirosis infection in a) females, and b) males
[12]. Seroprevalence was defined as the percentage of study participants with reactive microscopic
agglutination test (titre ≥ 1:50) to at least one Leptospira serovar.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 4
A recently published paper provides detailed information on the epidemiology of human leptospirosis in
Fiji, including environmental factors for disease transmission:

Lau CL, Watson CH, Lowry JH, David MC, Craig SB, Wynwood SJ, et al. (2016) Human Leptospirosis
Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental
Drivers for Transmission. PLoS Negl Trop Dis 10(1): e0004405. Link:
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004405

Leptospirosis is a significant public health problem in Fiji and the Pacific Islands. Although many
infections are mild or asymptomatic, severe complications can result in significant morbidity and
mortality, as well as socioeconomic losses related to health care costs, loss of working days, and
reduced productivity. Early diagnosis and treatment can reduce the risk of severe complications [13], and
this document aims to provide guidelines for clinical best practice to reduce leptospirosis-related
morbidity and mortality in Fiji. Accurate case notification by clinicians is also crucial for disease
surveillance, which helps to inform public health response as well as improve understanding of the
epidemiology of leptospirosis in Fiji.

2. OVERVIEW OF APPROACH TO MANAGEMENT OF SUSPECTED LEPTOSPIROSIS

In Fiji, diagnosis and management of leptospirosis should be based primarily on clinical

assessment – a detailed history and a thorough clinical examination is therefore crucial. For all patients
who fit the case definition of suspected leptospirosis, the following steps should be followed. An
overview of the approach is included as a summary page in Appendix A. Detailed descriptions of each
step are explained in different sections of this document, and summarised in wall charts – Appendix B
for outpatient management, Appendix C for inpatient management, and Appendix D for ICU and ED.

Step 1. Clinical assessment: history, examination, risk factors, and differential diagnoses.

Step 2. Does the patient fit the case definition for suspected leptospirosis? If yes:

Step 3. Determine initial level of care required based on clinical assessment.

Step 4. Commence treatment and arrange referral if indicated.

Step 5. Order investigations if laboratory available:

a) General investigations – FBC, UEC, LFT, CPK, CXR, ECG, urinalysis,
and others as indicated
b) Leptospirosis diagnostic tests if available:
• Rapid Diagnostic Test (RDT)
• Leptospira ELISA IgM
• PCR (molecular diagnosis)
Step 6. Classify cases as suspected, probable, or confirmed based on results of leptospirosis
diagnostic tests

Step 7. Notify all cases and deaths to public health. Cases should be notified as suspected,
probable, or confirmed using case definitions.

Step 8. Initiate case investigation or outbreak investigation if indicated.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 5
3. CLINICAL ASSESSMENT

3.1. HISTORY and EXAMINATION

Clinical manifestations of leptospirosis are highly variable and often difficult to distinguish from other
causes of acute febrile illnesses. After an incubation period of 5 to 14 days (range 1 to 30 days),
leptospirosis causes a biphasic illness with an early bacteraemic phase lasting 7 to 10 days, followed by
a late phase associated with immunologically mediated organ damage, severe complications and high
mortality rates. Clinical presentations range from mild non-specific febrile illnesses to severe life
threatening complications including acute renal failure, pulmonary haemorrhage, cardiac arrhythmias,
shock, liver failure, coagulopathy, and aseptic meningitis. Weil’s disease is the classic triad of jaundice,
renal failure, and haemorrhage in the late phase of severe leptospirosis, but the three manifestations do
not always occur together, and the term Weil’s disease is often used loosely refer to severe
leptospirosis.

Diagnosis of leptospirosis in Fiji should be primarily based on CLINICAL ASSESSMENT.

Patients who fit the case definition for SUSPECTED LEPTOSPIROSIS should be promptly
treated so that the risk of severe complications and death are minimised. The case
definition for suspected leptospirosis (Section 4) is based entirely on clinical assessment
– a detailed history and thorough examination is therefore crucial for early diagnosis.

ONSET OF ILLNESS: The number of days since the onset of symptoms is important for determining
which laboratory tests should be ordered, and for interpreting test results. The date of onset of illness
should also be recorded on laboratory request forms and notification forms.

EARLY PHASE: In the early phase, leptospirosis typically presents as an acute onset of fever,
myalgia, and headache. Calf tenderness and conjunctival suffusion are characteristic of
leptospirosis, but are not always present. Other symptoms include anorexia, nausea, vomiting,
abdominal pain, dizziness, lethargy, malaise, arthralgia, eye pain, and photophobia. Rashes include
macular, papular and urticariform rashes, mostly on the trunk or pre-tibial areas. Symptoms in the early
phase are non-specific and often difficult to distinguish from other causes of acute febrile illnesses.

LATE PHASE: In the late phase, symptoms relate to severe complications involving one or more organs
or systems:
Acute lung injury – Pulmonary haemorrhage and/or acute respiratory distress syndrome (ARDS) are
associated with very high mortality rates, and are major causes of leptospirosis-related deaths in Fiji.
Massive pulmonary haemorrhage can develop very quickly and result in death within hours. Warning
symptoms and signs include cough, shortness of breath, blood-stained sputum, haemoptysis, and chest
pain. Early recognition of pulmonary involvement is crucial so that referral to Division Hospital and/or ICU
can be arranged as promptly as possible.
Acute renal failure – Urine output could be normal, increased, or decreased depending on the stage of
renal failure. In the early stages, urine output is usually normal with hypokalaemia. Dialysis is required
for severe cases with acute tubular necrosis and oliguria.
Liver involvement – Jaundice can be very intense and associated with poor prognosis, but is not always
present. Hepatosplenomegaly might be present. It is important to note that severe lung injury and acute
renal failure can occur in the absence of jaundice.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 6
Haemorrhagic manifestations – Bruising or bleeding, including epistaxis, conjunctival haemorrhage,
haematemesis, melaena, and rectal bleeding.
Myocarditis – Arrhythmias (AF, supraventricular or ventricular extrasystoles), hypotension, cardiogenic
shock.
Neurological complications – Drowsiness, confusion, delirium, hallucinations, meningeal irritation,
photophobia. Leptospirosis can also cause aseptic meningitis, encephalitis, convulsions, Guillain-Barré
Syndrome, transverse myelitis, and other uncommon neurological syndromes.

3.2. RED FLAGS – DANGER SIGNS and SYMPTOMS

The following symptoms, signs, and laboratory findings in a patient with suspected leptospirosis are
associated with serious illness and a high risk of poor outcomes and death. If ANY of the following are
present, URGENT TREATMENT AND APPROPRIATE REFERRAL are required.
▪ Respiratory: Cough, blood-stained sputum, haemoptysis, shortness of breath, chest pain, or
abnormal CXR. Any symptoms and signs could signal pulmonary complications, which can progress
rapidly to massive pulmonary haemorrhage, a major cause of leptospirosis-related deaths.
▪ Bleeding or coagulopathy: petechiae, bruises, GI bleeding, platelets <100,000/mm 3, high
prothrombin time, raised INR.
▪ Abnormal urine output – oliguria or polyuria
▪ Hypotension – systolic BP <90mmHg or mean BP (MAP) <60mmHg
▪ Jaundice
▪ Cardiac arrhythmias
▪ Neurological involvement: drowsiness, meningism, seizures, focal symptoms/signs

3.3. DIFFERENTIAL DIAGNOSES

Clinical presentation of leptospirosis can be non-specific and difficult to distinguish from other causes of
acute febrile illness. A high index of clinical suspicion is therefore important. In Fiji, the most
important differential diagnoses include dengue, typhoid, and sepsis (mostly caused by staphylococcal
infections). Other differential diagnoses include influenza, pneumonia, arboviral infections (Chikungunya,
Zika), rickettsial infections, acute viral hepatitis, pyelonephritis, and meningitis. In patients with
haemorrhagic manifestations, severe dengue and meningococcal infection should be considered. Co-
infections could also occur, especially during concurrent outbreaks of multiple diseases, e.g. post-
flooding outbreaks of leptospirosis, typhoid, and dengue.

Malaria is not endemic in Fiji, but is an important differential diagnosis in patients who have travelled to
malaria-endemic areas in the previous 12 months, including India, Vanuatu, Solomon Islands, Papua
New Guinea, and sub-Saharan Africa (military personnel). Malaria should also be considered in visitors
from malaria-endemic areas, e.g. international students, foreign workers, and sailors.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 7
4. CASE DEFINITIONS

Cases are defined as suspected, probable, or confirmed (see Figure 3) based on:
▪ Clinical assessment of symptoms and signs, and
▪ Epidemiological risk factors, and
▪ Results of leptospirosis diagnostic tests

The definition of a SUSPECTED CASE is based entirely on clinical assessment. If a patient fits the
criteria for a suspected case:
▪ Treatment should be started immediately – see Section 7
▪ Treatment should not be delayed if diagnostic tests are not available
▪ Treatment should be continued even if the results of leptospirosis diagnostic tests are negative
because serological tests sometimes produce false negative results. It is also important to note
that serological tests (including the Rapid Diagnostic Test and ELISA IgM currently available
in Fiji) detect antibodies that appear from the 5th to 7th day from the onset of illness. The tests
are therefore not useful in the first 5 days of an illness.
▪ Consider referral to higher levels of medical care – see Section 5

Definitions for PROBABLE and CONFIRMED CASES are based on a combination of clinical
assessment and results of leptospirosis diagnostic tests. Suspected cases might be re-classified as
probable or confirmed once results of the diagnostic tests are available. Re-classification might therefore
need to be done after the patient has recovered, been discharged, or died. Correct classification of
cases is important for disease notification and public health surveillance of leptospirosis.

As of December 2015, diagnostic tests used to define probable cases are available in Fiji, but
none of the tests used to define confirmed cases are available. Leptospira PCR might be available
at Mataika House in the future.

The limitations of clinical case definitions should also be noted. It is not possible for a clinical case
definition to identify all cases of leptospirosis, or to exclude all cases that are not caused by
leptospirosis. The case definition is designed to help distinguish leptospirosis from other common
causes of acute febrile illnesses in Fiji, such as dengue and typhoid. In the early phase of leptospirosis,
symptoms and signs are non-specific, and it is therefore possible for a patient to have leptospirosis even
if they do not fit the case definition. If leptospirosis is considered as a likely differential diagnosis,
treatment can be started even if the patient does not fit the case definition.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 8
Figure 3. Case definitions for leptospirosis: suspected, probable, and confirm

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 9
5. CRITERIA FOR HOSPITALISATION AND ICU MANAGEMENT

The level of care required should be initially determined based on history and examination, and reviewed
regularly based on results of investigations and/or any changes in clinical status.

Table 1 shows the four levels of care recommended based on clinical assessment and investigations:

▪ Level 1: Outpatient management

▪ Level 2: Inpatient management at Sub-Divisional Hospital
▪ Level 3: Inpatient management at Divisional Hospital
▪ Level 4: Intensive care (ICU) management at Divisional Hospital

For patients who fit the case definition of leptospirosis, hospital admission is recommended for most cases
because complications can develop quickly and the patient’s condition can deteriorate rapidly. These
recommendations are particularly important for patients who live in rural and remote areas, or have difficulty
returning for re-assessment. The recommendations for level of care are based on clinical best practice, but
logistic difficulties might be encountered, e.g. arranging urgent transfers of patients from remote islands to a
Divisional Hospital.

In December 2015, there were 3 Divisional Hospitals with ICUs (CWMH, Labasa, and Lautoka), 18 Sub-
divisional Hospitals and 5 specialised/private hospitals in Fiji.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 10
Table 1. Levels of medical care recommended based on clinical assessment and investigations

DANGER SIGNS & SYMPTOMS

Increasing disease severity

LEVEL 1: LEVEL 2: LEVEL 3: LEVEL 4:

Outpatient care if Inpatient care at Inpatient care at ICU management
patient fulfills ALL of Sub-divisional Divisional Hospital if ANY if ANY of the following:
the following criteria: Hospital if: of the following:

No cough or other No cough or other ▪ Cough ▪ RR >28/min

respiratory symptoms respiratory symptoms ▪ Shortness of breath ▪ O2 sat <90% on 6L of O2 by
▪ RR >20/min mask – need non-invasive
ventilation
▪ Haemoptysis or blood-
stained sputum
▪ Abnormal CXR
Normal BP Normal BP ▪ Systolic BP <90mmHg ▪ Systolic BP <90mmHg
despite adequate fluid
replacement
No signs of bleeding No signs of bleeding ▪ Any signs of bleeding ▪ Haemoptysis or blood-
▪ Platelets stained sputum
<100,000/mm 3 ▪ Gastrointestinal bleeding
▪ Increased prothrombin ▪ Platelets <50,000/mm3
time and/or INR
Normal urine output Normal urine output ▪ Acute renal failure ▪ Haemodialysis should be
(oliguria or polyuria) considered if any of:
▪ Electrolyte imbalance • Urea >30 mmol/L
• pH <7.2
• Potassium >5.5 mmol/L
• Anuria or severe oliguria
• Volume overload with
pulmonary oedema
No jaundice No jaundice ▪ Jaundice

Normal heart rate and Normal heart rate ▪ Cardiac arrhythmias

rhythm and rhythm
Normal consciousness Normal ▪ Altered ▪ Glasgow Coma Score ≤12
consciousness consciousness ▪ Seizures
No vomiting Vomiting and needs IV
antibiotics or fluids
Ambulatory Not ambulatory

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 11
6. INVESTIGATIONS

6.1. General investigations

Investigations should include full blood count (FBC), urea, electrolytes, & creatinine (UEC), and
liver function tests (LFT). Other tests should be considered based on clinical assessment.

Table 2. Common investigations and results in leptospirosis patients

Investigation Common findings in leptospirosis
FBC Leucocytosis, neutrophilia with left shift, normochromic anaemia, thrombocytopenia.
Raised urea and creatinine if renal impairment. Potassium usually normal or low.
UEC
High potassium is associated with poor outcomes. Low sodium.
Raised bilirubin (mainly direct), may take time to resolve.
LFT
Normal or raised liver enzymes. AST and ALT could be 3 to 5 times above normal.
Urinalysis Proteinuria, microscopic haematuria, pyuria, granular casts.
CPK Raised in patients with myalgia.
Coagulation Prothrombin Time (PT), partial thromboplastin time (PTT), and INR may be raised.
ABG Low PaO2, SaO2, PaO2/FiO2ratio. Metabolic acidosis (low pH, low HCO3).
ECG Atrial fibrillation (AF), supraventricular or ventricular extrasystoles, AV block, others.
Chest x-ray Variable findings, including alveolar infiltrates, nodular densities and consolidation.
Changes could be diffuse or lobar, unilateral or bilateral. Findings could represent a
range of pathology, including alveolar haemorrhage, ARDS, or pulmonary oedema.
Lumbar
Neutrophilic or lymphocytic pleocytosis. Mild elevations in protein. Normal glucose.
puncture

6.2. Diagnostic tests for leptospirosis

Table 3 provides a comparison of commonly used leptospirosis laboratory tests. As at December

2015, the only two leptospirosis diagnostic tests available in Fiji were:
1. Rapid diagnostic test (RDT) (SD Leptospira IgM) – available in laboratories across Fiji
2. Leptospira ELISA IgM (Panbio) – only available at Mataika House in Suva

Important notes about the RDT and ELISA IgM:

▪ Both tests detect Leptospira IgM antibodies, which do not appear until at least 5 days after the
onset of illness. In the first 5 days of illness, a negative test is not useful for excluding a
diagnosis of leptospirosis. If onset of illness is definitely less than 5 days, RDT and ELISA
should not be used, particularly if there are limited supplies of test kits and/or reagents.
Supplies can be quickly depleted during outbreaks, e.g. post-flooding.
▪ Because RDT and ELISA IgM are not useful in the first 5 days of illness, diagnosis and
management of suspected cases should be based on clinical assessment.
▪ If a patient fits the case definition for suspected leptospirosis, treatment should not be stopped
if results of RDT and/or ELISA IgM are negative.
▪ If initial RDT or ELISA IgM negative, the test should be repeated after 2 to 3 weeks.

Leptospira PCR might be available at Mataika House in the future. PCR has the advantages of
providing a diagnosis in the first week of illness, and for defining a confirmed case.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 12
Table 3. Comparison of leptospirosis diagnostic tests (As at December 2015, only the first two tests on the list are available in Fiji)

Laboratory Availability in Advantages Disadvantages Specimen Best time to collect Collection and transport
test Fiji in December required specimen requirements
2015
Rapid Available in Easy to perform. Sensitivity & specificity Whole blood, At least 5 days from onset Transport on ice (4oC).
diagnostic test laboratories across Result available in ~20 va riable. serum or of illness Whole blood should be stored at
(SD Leptospira Fiji minutes. plasma 2 to 8oC and used within 3 days.
IgM) Serum or plasma should be
stored at 2 to 8oC, or frozen if
stored for longer than 2 weeks.
ELISA IgM Available at Mataika Commercial kits, easy Sensitivity & specificity Serum At least 5 days from onset Transport on ice (4oC).
(Panbio) House only to perform. variable. of illness Storage at 2 to 8oC. If not used
Result available in within 2 days, serum should be
1-2 hours. frozen (-20oC).
The following leptospirosis laboratory tests were not available in Fiji in Dec 2015. PCR might be available in the future.
PCR Will possibly be Provides confirmed Requires expensive Serum or Within 1st week of illness Frozen serum (-20oC)
available at Mataika diagnosis at early equipment and plasma
House in the future. stage of illness. expertise.
Microscopic Not available in Fiji. Gold standard Complex to perform. Serum After 1st week of illness. Discuss with receiving
Agglutination Regional laboratories serological test. Laboratory needs to Ideally paired samples laboratory if sending samples
Test (MAT) where MAT available Serogroup specific. maintain panels of live collected 14 to 21 days overeas. Frozen serum
include Brisbane, High sensitivity and cultures of leptospires. apart (max 60 days) (-20oC) required.
New Caledonia, and specificity.
Massey University,
New Zealand.
Culture Not currently Provides definitive Takes weeks or months Blood or Blood and CSF: within 1st Discuss with receiving
performed in Fiji. diagnosis. to culture, therefore not CSF or urine week of illness. Urine: 2nd laboratory in if sending samples
useful for informing to 4th week of illness. overseas.
clinical management. Specimen preferably
Expertise required. collected before antibiotic
treatment.
Histopathology Not available in Fiji. Leptospires visualised Poor sensitivity and Tissue Post-mortem Discuss with receiving
and in tissue. Provides specificity. High laboratory if sending samples
immunohisto- early and confirmed concentration of overseas.
chemistry diagnosis. leptospires required for
identification by dark
field microscopy
Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 13
7. TREATMENT
If a patient fits the definition for a suspected case, treatment should be started immediately.
Treatment should not be delayed if leptospirosis diagnostic tests are not available, or while waiting
for laboratory results. All patients who fit the criteria for suspected leptospirosis should be given
antibiotics. Table 1 helps to determine the level of care required.

The limitations of clinical case definitions should also be noted (see Section 4 Case definitions). If
leptospirosis is considered as a likely differential diagnosis, treatment can be started even
if the patient does not fit the case definition.

7.1. ANTIBIOTICS
All cases of suspected leptospirosis should be treated with antibiotics. Mild cases can be treated
with oral antibiotics, but severe cases required IV antibiotics for at least 7 days.

Table 4. Recommended antibiotics and dosages for the treatment of leptospirosis

a) ORAL ANTIBIOTICS – for treatment of mild cases

ADULTS CHILDREN
1st choices ▪ Doxycycline* ▪ Amoxycillin
100mg bd for 7days 50mg/kg/day, divide into 8 hourly
doses, for 7 days
OR
▪ Amoxycillin
500mg tds for 7 days

Alternatives ▪ Erythromycin 500mg qid for 7 days ▪ Erythromycin12.5mg/kg/dose (max

500mg/dose) 8 hourly for 7 days
▪ Azithromycin 1g, followed by
500mg bd for 2 days
▪ Clarithromycin 500mg bd for 7 days
*Note: Doxycycline should not be used in pregnancy, breastfeeding, or children <9yo

b) INTRAVENOUS ANTIBIOTICS – for treatment of severe cases, at least 7 days

ADULTS CHILDREN
st
1 choices ▪ Crystalline Penicillin G ▪ Crystalline Penicillin G
1.2g (2 mega units) 6 hourly 30 to 50 mg/kg 6 hourly
Alternatives ▪ Ceftriaxone 1 to 2g daily ▪ Ceftriaxone 100mg/kg (max 2g) daily
Use 1st line in ICU, or Use 1st line in ICU, or if suspect
if suspect typhoid (2g daily) typhoid or meningococcal
▪ Ampicillin – 1 to 2g 6 hourly ▪ Ampicillin 50mg/kg (max 2g) 6 hourly
▪ Cefotaxime 1g 6 hourly ▪ Cefotaxime 25mg/kg 6 hourly
▪ Erythromycin 500mg 6 hourly (slow ▪ Erythromycin 25mg/kg 6 hourly
infusion) (slow infusion)

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 14
7.2. MANAGEMENT OF COMPLICATIONS
The following sections provide guidelines for treating complications that are commonly seen in
severe cases of leptospirosis. For management of patients with atypical complications or
comorbidities, it is important to use clinical judgement, seek advice from consultants, and refer to
higher levels of care if indicated (see Table 1). Many of the recommended treatments below are
only possible at Divisional Hospitals or ICU.

7.2.1. DEHYDRATION, HYPOTENSION, AND SHOCK

▪ Fluid replacement with IV normal saline 0.9%
➢ Assess hydration clinically and review hourly
➢ Beware of excessive rehydration in patients with respiratory complications and/or cardiac
insufficiency
▪ If systolic BP remains <90mmHg despite adequate rehydration, or deteriorating hypotension
and shock, recommend:
➢ Inotropic support as per standard guidelines, using Adrenaline or Noradrenaline or
Dopamine. Aim for systolic BP of ≥ 90mmHg, or mean BP (MAP) of 65 to 75 mmHg.
➢ ICU admission
▪ In patients with adrenal insufficiency associated with severe shock, consider adrenal
supplementation doses of Hydrocortisone: 100mg IV, then 50mg tds.
▪ Jarish-Herxheimer reactions [14] can occur from 1 to 48 hours after the first dose of
antibiotics given for leptospirosis, and has been reported with penicillins as well as
cephalosporins. It is caused by an acute inflammatory response to the release of large
amounts of cytokines when spirochetes are killed. Common features are sudden onset of
shivering or rigors, rise in temperature, and hypotension.

7.2.2. RESPIRATORY COMPLICATIONS

▪ Acute lung injury include massive pulmonary haemorrhage and ARDS
▪ Monitor O2 saturation. Arterial blood gases (ABG) should be done whenever possible. If ABG
not available, use pulse oximeter to monitor O2 saturation.
➢ If O2 saturation <90% in ambient air, provide oxygen via mask and titrate flow to maintain
O2 saturation >90%
➢ If O2 saturation <90% in 6L of O2 via mask, refer to ICU for non-invasive ventilation
▪ Respiratory complications are associated with very high mortality rates and clinical status can
deteriorate very rapidly. Need URGENT REFERRAL TO ICU if ANY of the following:
➢ RR >28/min
➢ O2 saturation <90% on 6L of O2 by mask
➢ Haemoptysis or blood-stained sputum
➢ Abnormal CXR (can range from infiltrates to consolidation of one or more lobes)

▪ Indications for intubation and protective ventilation include:

➢ No improvement in O2 saturation despite non-invasive ventilation with CPAP or BIPAP
➢ Severe ARDS: PaO2/FiO2 ratio (PF ratio) <100

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 15
▪ Special notes on protective ventilation of leptospirosis patients:
➢ Use low tidal volumes (6 mL/kg) and plateau pressure <30cm of water to reduce the risk of
barotrauma
➢ Use an initial PEEP of 5 cm of water, and increase as required to maintain PaO2
>60mmHg, SatO2 >90% and PaO2/FiO2 ratio >200.
➢ Use intermittent inline suctioning to minimise bleeding
➢ Ensure that heat and moisture exchanger (HME) is not blocked with blood

7.2.3. ACUTE RENAL FAILURE

▪ Maintain hydration and electrolyte balance. Give fluid replacement with IV normal saline
0.9%, and assess hydration based on clinical examination and urine output. Continue to
monitor and reassess hourly regarding the need for haemodialysis. If needed, haemodialysis
should be commenced as soon as possible, especially in patients with pulmonary
complications.
▪ Haemodialysis is indicated if one or more of the following:
➢ Urea >30 mmol/L
➢ pH <7.2
➢ Potassium >5.5 mmol/L
➢ No urine output for 12 hours or severe oliguria (<400mL/day or <0.5mL/kg/hour)
➢ Volume overload with pulmonary oedema
▪ Adjust dosages of medications based on creatinine clearance

7.2.4. CARDIAC ARRHYTHMIAS

▪ Myocarditis can cause a range of arrhythmias including atrial fibrillation (AF), supraventricular,
and ventricular extrasystoles, and others
▪ Important to correct electrolyte imbalances to avoid exacerbation of arrhythmias
▪ Treat specific arrhythmias according to standard protocols

7.2.5. HAEMORRHAGE & COAGULOPATHY

▪ ICU admission recommended if haemoptysis, blood-stained sputum, GI bleeding, or platelet
count <50,000/mm3
▪ Platelet transfusion recommended if platelet count <50,000/mm3, particularly if any of the
following:
➢ Evidence of bleeding (pulmonary, gastrointestinal, or other)
➢ Abnormal CXR
➢ Invasive procedures are required, e.g. insertion of central venous catheter
Aim for platelet count of ≥100,000/mm 3
▪ Fresh frozen plasma (FFP) and cryoprecipitate should be considered if INR >2 or
Prothrombin time >16 sec
▪ If not eating, give prophylaxis for GI haemorrhage: Ranitidine 50 mg IV 8 hourly

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 16
7.2.6. STEROIDS
▪ A recent systematic review [15] found no robust scientific evidence to support the use of
high (immunosuppressive) doses of corticosteroids in the treatment of severe leptospirosis
▪ One randomised controlled trial found that high dose steroids were ineffective for severe
leptospirosis, and increased the risk of nosocomial infections [16]
▪ A small number of studies reported benefit in using high dose steriods for severe cases, but all
had significant methodological limitations (small sample sizes, lack of control group,
retrospective studies, diagnostic criteria, unvalidated clinical scoring systems, young patients,
and other biases) [15]
▪ In patients with adrenal insufficiency associated with severe shock, consider adrenal
supplementation doses of Hydrocortisone: 100mg IV, then 50mg tds

7.3. CONVALESCENCE and FOLLOW-UP

▪ Patients should not be discharged until all complications and danger signs have resolved.
▪ Jaundice can persist for many weeks – it is not necessary to wait until jaundice is resolved
before discharging a patient if all else is satisfactory.
▪ Chronic uveitis (iritis, iridocyclitis and chorioretinitis) is a complication of leptospirosis, and can
occur up to 18 months after an acute infection.
▪ If Leptospira IgM negative on latest blood sample, arrange for patient to have repeat serology
in 2-3 weeks.
▪ Advise patients to return for review if any deterioration in clinical condition or development of
complications and danger signs or symptoms.
▪ Advise close contacts (e.g. household members, co-workers) to seek early medical attention
for any febrile illness.

8. PROPHYLACTIC ANTIBIOTICS
▪ Currently, there is little evidence on the effectiveness of prophylactic antibiotics [17]. Routine
use of prophylactic antibiotics is not recommended, but might be used in special situations
based on clinical decision on a case-by-case basis.
▪ Pre-exposure prophylaxis for short-term intense exposures, e.g. soldiers, outbreak response
personnel, occupational/recreational exposures: Doxycycline 200mg weekly starting 1-2 days
before exposure and continue during exposure.
▪ Post-exposure prophylaxis after high-risk exposure, e.g. contact with floodwaters with open
cuts/wounds in a high risk area: Doxycycline 200mg daily for 3 to 5 days
▪ Doxycycline is contraindicated in pregnancy, breastfeeding, and children <9 years old.
Gastrointestinal side effects are common.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 17
9. DISEASE NOTIFICATION and PUBLIC HEALTH RESPONSE

Leptospirosis is a notifiable disease in Fiji, and reported through the Notifiable Diseases
Surveillance System (NDSS). All SUSPECTED, PROBABLE, and CONFIRMED cases and deaths
need to be reported as per the Fiji National Notifiable Disease Protocols. Accurate reporting of
cases is important for surveillance, identification of hotspots and outbreaks, and initiation of public
health responses if indicated.
▪ Single cases of leptospirosis should be notified weekly using routine procedures
▪ Clusters of cases or an outbreak should be reported urgently by telephone to the respective
Divisional Medical Officer
▪ When notifying a case, it is important to include the following information:
➢ Classification of the case as suspected, probable, or confirmed (based on case
definitions in Section 4, Figure 3)
➢ Date of onset of illness
➢ Date of presentation
➢ Date of collection of blood sample for leptospirosis diagnostic tests
➢ Epidemiological links to other cases, e.g. household member, another person from the
same community, co-worker
▪ Laboratories are required to report cases with positive leptospirosis diagnostic tests
▪ For cases diagnosed at hospitals, Medical Officers should also notify the Infection Control
Nurse, who will then notify the Divisional Medical Officer (DMO) or Sub-divisional Medical
Officer (SDMO). If indicated, the DMO or SDMO will initiate a case investigation by the
Divisional or Sub-divisional Outbreak Response Team (DORT or SORT). The teams consist of
a Medical Officer, Health Inspector (Environmental Health Officers), and Risk Manager (DORT)
or Health Sister (SORT).
▪ Case investigations should include details on patient demographics, history of the illness,
type of community where the patient lives, household environment, occupational exposures,
contact with animals, and exposure to fresh water and/or flood waters. In hospitalised patients,
case investigations should be commenced while the patient is still in hospital. Some patients
will be very difficult to contact after discharge, especially those who live in rural and remote
areas.
▪ A standardised case investigation form has been developed for leptospirosis (Appendix E).
Completed forms should be submitted to SDMOs and DMOs.

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 18
10. REFERENCES

1. Mwachui MA, Crump L, Hartskeerl R, Zinsstag J, Hattendorf J. Environmental and Behavioural

Determinants of Leptospirosis Transmission: A Systematic Review. PLoS Negl Trop Dis. 2015;9:
e0003843.

2. Lau CL, Smythe LD, Craig SB, Weinstein P. Climate Change, Flooding, Urbanisation and Leptospirosis:
Fuelling the Fire? Trans R Soc Trop Med Hyg. 2010;104: 631-638.

3. Colt S, Pavlin BI, Kool JL, Johnson E, McCool JP, et al. Human Leptospirosis in the Federated States of
Micronesia: A Hospital-Based Febrile Illness Survey. BMC Infect Dis. 2014;14: 186.

4. Berlioz-Arthaud A, Kiedrzynski T, Singh N, Yvon JF, Roualen G, et al. Multicentre Survey of Incidence and
Public Health Impact of Leptospirosis in the Western Pacific. Trans R Soc Trop Med Hyg. 2007;101: 714-
721.

5. Goarant C, Laumond-Barny S, Perez J, Vernel-Pauillac F, Chanteau S, et al. Outbreak of Leptospirosis in

New Caledonia: Diagnosis Issues and Burden of Disease. Trop Med Int Health. 2009;14: 926-929.

6. Lau C, Dobson A, Smythe L, Fearnley E, Skelly C, et al. Leptospirosis in American Samoa 2010 —
Epidemiology, Environmental Drivers, and the Management of Emergence. Am J Trop Med Hyg.
2012;86: 309-319.

7. Lau C, Clements A, Skelly C, Dobson A, Smythe L, et al. Leptospirosis in American Samoa — Estimating
and Mapping Risk Using Environmental Data. PLoS Negl Trop Dis. 2012;6: e1669.

8. Massenet D, Yvon JF, Couteaux C, Goarant C. An Unprecedented High Incidence of Leptospirosis in

Futuna, South Pacific, 2004 - 2014, Evidenced by Retrospective Analysis of Surveillance Data. PLoS
One. 2015;10: e0142063.

9. Perrocheau A, Perolat P. Epidemiology of Leptospirosis in New Caledonia (South Pacific): A One-Year

Survey. Eur J Epidemiol. 1997;13: 161-167.

10. Ram P, Collings DF. Further Observations on the Epidemiology of Leptospirosis in Fiji. Fiji Medical
Journal. 1982;10: 71-75.

11. Ghosh A, Khan S, Kishore K. Leptospirosis in Fiji: Incidence between 2000 to 2007 and Review of
Literature. Fiji Medical Journal. 2010;29: 8-14.

12. Lau C, Watson C, Lowry J, David M, Craig S, et al. Human Leptospirosis Infection in Fiji: An Eco-
Epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.
PLoS Negl Trop Dis. 2016;10: e0004405.

13. Tubiana S, Mikulski M, Becam J, Lacassin F, Lefevre P, et al. Risk Factors and Predictors of Severe
Leptospirosis in New Caledonia. PLoS Negl Trop Dis. 2013;7: e1991.

14. Guerrier G, D'Ortenzio E. The Jarisch-Herxheimer Reaction in Leptospirosis: A Systematic Review.

PLoS ONE. 2013;8: e59266.

15. Rodrigo C, Lakshitha de Silva N, Goonaratne R, Samarasekara K, Wijesinghe I, et al. High Dose
Corticosteroids in Severe Leptospirosis: A Systematic Review. Trans R Soc Trop Med Hyg. 2014;108:
743-750.

16. Niwattayakul K, Kaewtasi S, Chueasuwanchai S, Hoontrakul S, Chareonwat S, et al. An Open

Randomized Controlled Trial of Desmopressin and Pulse Dexamethasone as Adjunct Therapy in
Patients with Pulmonary Involvement Associated with Severe Leptospirosis. Clin Microbiol Infect.
2009;16: 1207-1212.

17. Brett-Major DM, Lipnick RJ. Antibiotic Prophylaxis for Leptospirosis. Cochrane Database Syst Rev. 2009:
Issue 3. Art. No.: CD007342. DOI: 007310.001002/14651858.CD14007342.pub14651852.

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Appendix A

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 20
Appendix B

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 21
Appendix C

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 22
Appendix D

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 23
Appendix E

Fiji National Guidelines for Clinical Diagnosis & Management of Leptospirosis, 2016 24