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5. What are the differential diagnosis related to the scenario ?

A. Leptospirosis
a. Definition
Leptospirosis is a zoonotic disease caused by a spiral-shaped bacterial
infection of the genus Leptospira which is pathogenic, transmitted directly and
indirectly from animals to humans. Leptospira bacteria are spiral-shaped with
hook-like ends, measuring 5-15 micrometers long and 0.1-0.2 micrometers
wide, flexible, thin and flexible. The disease is most commonly transmitted
from animals to humans when people with open skin sores come into contact
with water or soil that has been contaminated with animal urine. Animals that
are the source of leptospirosis transmission are rats, pigs, cows, goats, sheep,
horses, dogs, cats, insects, birds, insectivores (porcupines, bats, squirrels),
while foxes can be carriers of leptospira.
b. Epidemiology
Leptospirosis occurs in various parts of the world but generally in
tropical and subtropical areas with high rainfall. Leptospirosis is an endemic
disease in a number of countries and even in the world. Generally human cases
of Leptospirosis are reported from India, Indonesia, Thailand and Sri Lanka
during the rainy season. Major outbreaks of Leptospirosis in the Southeast
Asian region have been reported in Jakarta (2003), Mumbai (2005) and Sri
Lanka (2008). Based on reports of recent years, the global incidence of
Leptospirosis cases is estimated from 0.1-1 per 100,000 per year in temperate
climates and 10-100 per 100,000 per year in the humid tropics. The incidence
of this disease can reach more than 100 per 100,000 per year in outbreaks and
exposure is high in risk groups.
In 2007 there was an increase in cases of Leptospirosis in humans,
reported as many as 667 cases and 93% confirmed laboratory results with an
8% mortality rate. In 2010 cases of Leptospirosis in Indonesia were reported as
many as 410 cases with 46 deaths (CFR 11.2%). The number of male patients
with leptospirosis is higher than female.
 c. Etiology
Leptospirosis is caused by pathogenic organisms of the genus
Leptospira which are included in the order Spirochaeta in the
Trepanometaceae family. This bacterium is spiral-shaped with a tight twist
and the ends are shaped like hooks so that the bacteria are very active in both
rotating movements along their axis, back and forth, or curved. The size of
these bacteria is 0.1 mm x 0.6 mm to 0.1 mm x 20 mm. Leptospira can be
stained with carbolfuchsin stain. However, these bacteria can only be seen
with a dark field microscope. These bacteria are obligate aerobes with optimal
growth at a temperature of 280C-300C and a pH of 7.2 to 8.0.
The genus Leptospira is divided into two serovarians, namely L.
interrogate which is pathogenic (i.e. has the potential to cause disease in
animals and humans) and L. biflexa which is non-pathogenic/saprophytic (i.e.
free-living and generally considered not to cause disease). Pathogenic
leptospires are maintained in nature in the renal tubules and genital tracts of
certain animals.
Various animal species, especially mammals, can act as a source of
human infection, including:
1. Small mammal species, such as wild rats (including mice, porcupine
squirrels)
2. Domestic animals (cows, pigs, dogs, sheep, goats, horses, buffalo)
3. Fur-producing animals (silver fox) in captivity
4. Reptiles and amphibians may also carry leptospires
d. Clinical Manifestations
According to Widoyono (2008), clinical symptoms of leptospirosis in
humans can be divided into three stages, namely:
a. First Stage (leptospiremia)
1. Fever, chills
2. Headache
3. Red spots on the skin
4. Malaise and vomiting
Conjunctivitis and redness of the eyes
Pain in the muscles, especially the calf and back muscles.
5. These symptoms will appear between 4-9 days
b. Second Stage
1. At this stage, antibodies are usually formed in the patient's body
2. The symptoms that appear at this stage are more varied than in the first
stage, including jaundice (yellowness)
3. If the fever and other symptoms reappear, meningitis is likely
4. Usually this phase lasts for 4-30 days.
c. Third Stage
According to some clinicians, this disease can also show clinical
symptoms in the third stage (convalescent phase). Complications
Leptospirosis can cause the following symptoms:
1. In the kidneys, renal failure that can cause death
2. In the eyes, closed conjunctiva represents a septicemic phase which is
closely related to photobia and hemorrhagic conjunctiva.
3. In the liver, jaundice (yellowing) that occurs on the fourth and sixth day
with an enlarged liver and soft consistency
4. In the heart, arrhythmias, dilatation of the heart and heart failure that can
cause sudden death
5. In the lungs, hemorrhagic pneumonitis with coughing up blood, chest
pain, respiratory distress and cyanosis
6. Bleeding due to vascular damage from the respiratory tract, digestive
tract, kidneys and genital tract
Infection in pregnancy causes abortion, stillbirth, premature birth and
birth defects.
e. Supporting investigation
Diagnosis can be made by microscopic examination, as well as
by leptospira culture. The clinical sample that should be collected for
examination depends on the phase of the infection. Specimens came
from blood and cerebrospinal fluid (first week of illness) and urine
(after the first week to day 40). The specimens were grown on
Fletcher's media or EMJH media in combination with neomycin or 5-
fluorouracil. On this medium, growth will be seen within a few days to
4 weeks. The presence of leptospires in this medium can be seen using
a dark field microscope or using a fluorescent microscope
 (fluorerescent antibody stain). Immunoserological testing is also
important for the diagnosis of leptospirosis. In general, new antibodies
are found after the 7th or 10th day. The titer will increase and will peak
at the 3rd or 4th week of illness. The immunoserological tests
commonly used are: Microscopic Agglutination Test, Enzymelinked
immunosorbent assay (ELISA), polymerase chain reaction (PCR) and
dipstick assays, as well as Leptospira-specific antigen, namely
lipoprotein rLipl32 which can be the gold standard for diagnosis.
The most useful and most frequently collected samples are:
1. Blood with heparin for culture in the first 10 days.
2. Blood or frozen serum for serological examination is taken in
the septicemic phase. The diagnosis is based on a 4-fold
antibody seroconversion between acute and convalescent. A
negative serological result in the early stages of the disease does
not exclude the diagnosis of leptospirosis.
3. Urine for culture is taken in the immune phase.
4. Post mortem samples. It is important to collect specimens from
as many organs as possible for serology. Post mortem samples
should be collected aseptically and inoculated into the culture
medium as soon as possible after death. Samples should be
stored and transported at 4°C. In addition, crust staining,
immunostaining, and immunohisto-chemistry may be helpful.
5. CSF and dialysate for culture were taken in the septicemic
phase. In the case of an-icteric leptospirosis, normal leukocyte
counts with neutrophilia, increased erythrocyte sedimentation
rate (ESR) and protein in the CSF can be found.
f. Management
a) Medicine
Severe cases of leptospirosis should be given high doses of IV
penicillin (IV benzylpenicillin 30 mg/kg, maximum 1.2 g, 6 hours for
5-7 days). Milder cases may be treated with oral antibiotics such as
amoxicillin, ampicillin, doxycycline (2 mg/kg, maximum 100 mg,
every 12 hours for 5-7 days), or erythromycin.
 b) Supportive therapy and dialysis
Severe cases require hospitalization with aggressive supportive
care and close monitoring of fluid and electrolyte balance. Peritoneal
dialysis or hemodialysis is indicated in renal failure. Good supportive
care and dialysis have reduced the mortality of this disease in recent
years. If prothrombin is disturbed, vitamin K can be given.
g. Complications
Aseptic meningitis is the most common complication, but encephalitis,
myelitis, radiculitis, peripheral neuritis (unusual) in the second week may
occur due to a hypersensitivity reaction. Severe complications in patients with
severe leptospirosis can be in the form of shock, massive bleeding and ARDS
which is the main cause of death for severe leptospirosis. Shock occurs due to
changes in body homeostasis that play a role in the onset of tissue damage.
Renal failure, liver damage, pulmonary hemorrhage, vasculitis and cardiac
disorders in the form of myocarditis, pericarditis and arrhythmias are rarely
found although they are common causes of death. Although rare, uveitis can
be found after 2 years of symptoms of leptospira.
h. Prognosis
Mortality in severe leptospirosis is about 10%, death is most often due
to kidney failure, massive bleeding or ARDS. Liver and kidney function will
return to normal, despite severe dysfunction, even in patients on dialysis.
About a third of cases with aseptic meningitis may experience periodic
headaches. Some patients with a history of leptospirosis uveitis experience
loss of visual acuity and blurred vision.
i. Prevention
According to Rusmini (2011) in general, the prevention of leptospirosis
that can be done is as follows:
 1. Familiarize yourself with Clean and Healthy Life Behavior (PHBS)
2. Wash hands with soap before eating and drinking.
3. Use clean water for bathing and washing.
4. Vegetables and fruit should be washed with clean water.
5. Store food properly and correctly to avoid the reach of rats (closed
tightly, put in the cupboard).
6. Use footwear, especially when activities outside the home.
7. Avoid contact with sewer water or standing water, both in the home
environment and at work.
8. Avoid contact with flood waters.
9. Bathing and washing hands, feet and body parts with soap after work,
especially when in fields/gardens/trash cans/soil/sewers and other
polluted places.
10. Protecting body parts with personal protective equipment (PPE) when
working in a place where there is a risk of contamination.
11. Cover the wound on the skin with a waterproof wound dressing.
12. Avoid the presence of mice in the house or workplace.
13. Avoid pollution and improve rat control.
14. Set a mousetrap.
15. Bury or burn rat carcasses in a safe place.
16. Immediately check with the available health facilities if you experience
symptoms
sick.
Reference :
1. Setadi, B., Setiawan, A., Effendi, D. & Hadinegoro, SRS Practical Instructions for
Leptospirosis. Sari Pediatr. 3, 163–167 (2001).
2. Rampang, NH Leptospirosis Novie H. Rampengan. J. Biomedicine 8, 143–150 (2016).
3. Sitohang, RV, Burni, E., Gasem, MH & Muhadir, A. Instructions for Leptospirosis Control
Techniques. Ministry. health. RI 126 (2017).