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Tropical Medicine:

Parasitic Diseases
Yoes Prijatna Dachlan
Faculty of Medicine
Universitas Airlangga

(KT S2 Parasitic Infection Sem I Sept 2015)

Neglected Tropical Diseases


(NTD)

Tropical Medicine:
Parasitology

Parasitic diseases

Zoonosis
(Yoes Prijatna Dachlan, 2015)

Neglected Tropical Diseases (NTD)


a

diverse group of diseases with distinct characteristics affecting an estimated


1.4 billion people worldwide
The classification of NTD is linked to their frequent neglect in public and
private sector expenditure and attention at local, national, and international
levels, and their concentration among the poor
WHO identifies 17 NTD
Protozoa: Chagas disease, Human African trypanosomiasis, Leishmaniases
Helminth: Cysticercosis/Taeniasis, Dracunculiasis, Echinococcosis, Foodborne trematodiases,
Lymphatic filariasis, Onchocerciasis, Schistosomiasis, Soil-transmitted helminthiasis
Bacteria: Buruli ulcer, Leprosy, Trachoma, Yaws
Virus : Dengue and Chikunguya, Rabies
It

is unlikely that NTDs will be able to be managed effectively without international


support to develop effective treatments, subsidies to make such treatments available for
poorer countries and support to develop environmental vector management, public
health education, and case monitoring and treatment

Neglected Tropical Diseases


(NTD)
they primarily affect hidden (relatively poor
and powerless) populations
they tend not to be transmissible beyond
such populations
It suggests that such diseases
share a number of characteristics

they are often disfiguring and


stigmatizing, as well as causing
considerable morbidity, and in some
cases, mortality
their economic costs are very substantial.

(Yoes Prijatna Dachlan, 2015)


(Bull S, Parker M, 2014)

Significant advances have been made


in the treatment of some of these diseases (new cases of dracunculiasis reported
have, for example, decreased by over 99%, between 1989 and 2009)
and relatively safe and simple treatments are available for others, such as trachoma
and lymphatic filariasis
However in 2008, only 8% of people with schistosomiasis had access to highquality medicines because donations of praziquantel from the private sector were
insufficient to meet demand and there were not enough other funds available for its
production.
(Bull S, Parker M, 2014)

(Yoes Prijatna Dachlan, 2015)

(Yoes Prijatna Dachlan, 2015)

(Yoes Prijatna Dachlan, 2015)

Global distribution of schistosomiasis due to S. hematobium and S. japonicum


(Yoes Prijatna Dachlan, 2015)

Key facts
Schistosomiasis is an acute and chronic disease caused by parasitic worms.
People are infected during routine agricultural, domestic, occupational and
recreational activities which expose them to infested water.
Lack of hygiene and certain play habits of school-aged children such as swimming
or fishing in infested water make them especially vulnerable to infection.
Schistosomiasis control focuses on reducing disease through periodic, large-scale
population treatment with praziquantel; a more comprehensive approach including
potable water, adequate sanitation and snail control would also reduce transmission.
At least 261 million people required preventive treatment for schistosomiasis in
2013.
More than 40 million people were treated for schistosomiasis in 2013
Symptoms of schistosomiasis are caused by the bodys reaction to the worms eggs

(Yoes Prijatna Dachlan, 2015)

Table: Parasite species and geographical distribution of schistosomiasis

Intestinal
schistosomiasis

(Yoes Prijatna Dachlan, 2015)

Urogenital
schistosomiasis

Species

Geographical
distribution

Schistosoma mansoni

Africa, the Middle


East, the Caribbean,
Brazil, Venezuela and
Suriname

Schistosoma
japonicum

China, Indonesia, the


Philippines

Schistosoma mekongi

Several districts of
Cambodia and the
Lao Peoples
Democratic Republic

Schistosoma
guineensis and
related S.
intercalatum

Rain forest areas of


central Africa

Schistosoma
haematobium

Africa, the Middle


East, Corsica (France)

Schistosoma species

Egg

Delayed-type hypersensitivity
An inflammatory granuloma forms with epithelial,
giant, plasma and eosinophil cells and fibroblasts.
There is subsequent fibrosis and calcification.
(Yoes Prijatna Dachlan, 2013)

(Chiodini, Moody, Manser, 2001)


Atlas of Med .Helminth. & Protozool.

Intestinal amoebiasis
Intestinal amebiasis is caused by the protozoan Entamoeba histolytica
Most infection is asymptomatic; clinical manifestations include amebic dysentery
and extraintestinal disease. Symptoms range from mild diarrhea to severe
dysentery producing abdominal pain, diarrhea and bloody stools
Amebiasis occurs worldwide; the prevalence is disproportionately increased in
developing countries because of poor socioeconomic conditions and sanitation
levels
Extraintestinal manifestations include amebic liver abscess and other more rare
manifestations such as pulmonary, cardiac, or brain involvement
The parasite exists in two forms, a cyst stage (the infective form), and a
trophozoite stage (the form that causes invasive disease)
Pathogenesis:Lysis of target cells via a contact-dependent mechanism; lysis of
target cells via a contact-dependent mechanism; formation of amebapores, a
family
of small peptides that can form pores in lipid bilayers, resulting in cytolysis of
infected cells
Diagnosis: Diagnostic techniques include microscopy, antigen detection, serology,
molecular techniques, and colonoscopy with histological examination
(Yoes Prijatna Dachlan, 2015)

Entamoeba histolytica

(PL Chiodini; AH Moody; DW Mansor, 2001)


Atlas of Helminthology and Protozoology, 4th ed
(Yoes Prijatna Dachlan, 2015)

(Yoes Prijatna Dachlan, 2015)

Trofozoit E. histolytica mengandung


eritrosit

(Yoes Prijatna Dachlan, 2015)

Kista immature E. histolytica

Invasi trofozoit E. histolytica merusak sel epitel dan submukosa colon

(Yoes Prijatna Dachlan, 2014)

(Samie A, ElBakri A, AbuOdeh R)


Current Topics in Tropical Medicine
Amoebiasis in the Tropics: Epidemiology
and Pathogenesis

Amoebic liver abscess

(Yoes Prijatna Dachlan, 2014)

(Samie A, ElBakri A, AbuOdeh R)


Current Topics in Tropical Medicine
Amoebiasis in the Tropics: Epidemiology
and Pathogenesis

Immune reponses toward intestinal amoebiasis

(Yoes Prijatna Dachlan, 2015)

(Moonah SN, 2013)

NCD

Malnutrit
ion

AIDS

A long-term
immunosuppre
ssive therapy

IMMUNOCOMPROMIZED HOSTS
OPPORTUNISTIC INFECTIONS
Pneumocystis carini, Toxoplasma gondii,
Leishmania spp, Trypanosoma cruzi,Plasmodium
spp, Giardia lamblia, Schistosoma spp,
Cryptosporidium parvum, Cyclospora
(Yoes Prijatna Dachlan, 2015)

Malaria has a long history


The parasite and the mosquito are both ancient creatures
Throughout the written history of mankind, malaria has made
itself felt as a companion of the human race in a very wide belt
around the world
Eradication program in 1969 could not be fully implemented
~ because of the reduction in bilateral and international
assistance
~ because of lack of financial and manpower resources in
the countries affected by the disease
In the last two decades at 20th Century there were considerable
changes in the epidemiological situation
The prospects for malaria control are in the hands of the policy
makers, health administrators and malaria specialists
(Yoes Prijatna Dachlan, 2014)

(WHO, 1981; M Finkel,2010)

Six key factors appear to have


played a role in the changing
epidemiology of malaria
(emerging infection) :
1.
2.
3.
4.

Failure of malaria eradication


Antimalarial drug resistance
Social change
Malaria epidemics due to climatic
change
5. Breakdown of public health
infrastructure
6. Global warming
(Yoes Prijatna Dachlan 2011)

CLINICAL DISEASE
pragmatically divided into three
categories
Disease amongst children in endemic
areas
Disease in pregnant women
Disease in non-immune individuals
(English,M., & Newton, C.R.J.C., 2005)
(Yoes Prijatna Dachlan 2015)

The Relationship between Age and the


clinical Presentations of Severe Malaria at
Different levels of Malaria Transmission
(White NJ, 2009)
Severe Anemia
Cerebral Malaria

Holoendemic

Cerebral Malaria
Hyperendemic
Mesoendemic
Severe Anemia

Cerebral Malaria

Renal Failure

Hipoendemic
Unstable

Yoes Prijatna Dachlan 2015

Severe Anemia
1

3 4 5

10

20

40

60

Intensity and stability of transmission

PREGNANT WOMEN
exhibit
susceptibility
to P. falciparum infection
The
risk
of
infecti
on
ThrTTT

The level of pre-existing


immunity
(Yoes Prijatna Dachlan, 2015)

PARITY

(Beeson & Duffy, 2005)

Densitas Parasit menurut


golongan umur. Malaria Endemis
di Kabupaten Jayapura

(Petronella, Sukmawati, Dachlan YP, 2012)

Dormant forms of P. falciparum parasites at ring-form stage due to in vitro


artemisinin exposures

Kontrol
P.falciparum
sebelum terpapar
obat artemisinin

48 jam
P.falciparum
dipapar obat
artemisinin
(Lilik Maslachah, 2013)
(Yoes Prijatna Dachlan, 2013)

Malaria Control
Public health control measures are the first line of defence to
protect people living in malaria risk areas. The control
measures that are recommended depend on the level of
malaria risk in an area.
Tools for the control of malaria include:
Long lasting insecticide-treated nets
Indoor residual spraying
Intermittent presumptive treatment of malaria in infants,
young children and those attending school
Intermittent presumptive treatment for pregnant women
Access to effective treatment for children with a fever
Capacity to detect, prepare and respond to early warnings for
epidemics
Education and communication
(Yoes Prijatna Dachlan, 2015)

Indicative of partial
immunity

Asymptomatic
malaria parasitemia

examining 200 fields


of Giemsa-stained
thick blood smears

A known phenomenon
in malaria endemic areas
with high year-round
transmision

RDT

A low level of
Plasmodium parasites,
asexual
or
gametocytes
Being detectable in
the blood without the
individual being ill

(GE Strm, 2013; Tanzania)


counting 1000
nested-PCR
(S Zoghi1,2012; Iran)
red blood cells (RBCs)
in a Giemsa stained
PfMSP-119 specific
thin blood
antibodies using ELISA
film at X1,000
magnification under
immersion oil.
(Yoes Prijatna Dachlan, 2014)

(2009)

Taenia solium
(PL Chiodini, AH Moody, DW Manser, 2001
Atl Medical Helminthol & Protozool)

(Yoes Prijatna Dachlan, 2013)

EPIDEMIOLOGY
Approximately 50 million people worldwide are estimated to have
cysticercosis infection. Cysticercosis is endemic in many regions of
Central and South America, sub-Saharan Africa, India, Asia,
Indonesia (Bali, Papua, Pulau Samosir)
The prevalence of cysticercosis varies within these countries and is
often higher in rural or periurban areas where pigs are raised and
sanitary conditions are suboptimal
In some such communities the rate of epilepsy approaches 3 percent,
and 25 to 40 percent of these cases have evidence of cysticercosis
Cysticercosis is transmitted by ingestion of T. solium eggs shed in the
stool of a human tapeworm carrier (figure 1). Following ingestion,
embryos (oncospheres) hatch in the small intestine, invade the bowel
wall and disseminate hematogenously to brain, striated muscles,
liver, and/or other tissues
Over a period of three to eight weeks, tissue cysticerci develop; these
consist of membranous walls filled with fluid and an invaginated scolex
(Yoes Prijatna Dachlan, 2015)

(Clinton White, 2011- U To Date 19.3)

Invaginated scolex
T. solium

scolex T. solium

(Muller R, Wakelin D,
2002, Worms and
human disease, 2nd ed)

Cystic lesion

Cerebral cysticercosis: this 44-year-old woman from Kenya had recent-onset epilepsy(Bannister B,
Gillespie S, Jones J, 2006, Infection. Microbiol. & Management, 3rd ed)

Cestoda Tape Worm

Cysticercosis (Pork Tape Worm) (1)

Cysticercosis is caused by the larval stage of the tapeworm Taenia solium;


clinical syndromes include neurocysticercosis (NCC) and extraneural
cysticercosis. Neurocysticercosis is divided into parenchymal and
extraparenchymal forms. Extraparenchymal forms include intraventricular,
subarachnoid, intraocular, and spinal disease
CLINICAL MANIFESTATIONS
In general, parenchymal cysts are associated with seizures and headache,
while extraparenchymal cysts are associated with symptoms of elevated
intracranial pressure (eg, headache, nausea, and vomiting) and may be
accompanied by altered mental status
Pathophysiology :Taenia parasites have sophisticated means of evading
destruction, and a number of mechanisms for host immune tolerance have
been postulated
~ Metacestodes elaborate a variety of substances, including taeniaestatin
(a parasite serine proteinase inhibitor), paramyosin, sulfated
polysaccharides, and secretory proteases, that inhibit or divert host
inflammatory response

(Yoes Prijatna Dachlan, 2015)

Clinton White, 2011- U To Date 19.3)

Cestoda Tape Worm

Cysticercosis (Pork Tape Worm) (2)


Pathophysiology :
~ Taeniaestatin may also interfere with lymphocyte proliferation and
macrophage function, thereby inhibiting normal cellular immune defenses
Secreted proteases degrade host molecules including cytokines. In
addition, humoral antibodies do not kill the mature metacestode
~ After a variable number of years, the cysts degenerate and lose their
ability to modulate the host immune response
~ Host immune and inflammatory cells attack the cysticercus, which leads
to the appearance of edema and/or contrast enhancement on imaging
studies This inflammatory response is associated with onset
of seizures. Host inflammatory molecules such as
Substance P may be key mediators of seizures
~ Ultimately, the cystic lesions either resolve or form a calcified
granuloma. When present, the calcifications are associated with recurrent
seizures

(Yoes Prijatna Dachlan, 2015)

(Clinton White, 2011- U To Date 19.3)

Clinical Diagnosis
In general, parenchymal cysts are associated with
seizures and headache, while extraparenchymal cysts
are associated with symptoms of elevated intracranial
pressure (eg, headache, nausea, and vomiting) and
may be accompanied by altered mental status

(Yoes Prijatna Dachlan, 2015)

DIAGNOSIS

CLINIC
IMAGING
IMMUNOLOGIC DATA
EPIDEMIOLOGIC DATA

Radiographic imaging :
Computed tomographic (CT) scan
MRI (magnetic resonance imaging)

Deteksi cysticercus :
NCC dan extraNCC
cerebral cortex atau brainstem

(Yoes Prijatna Dachlan, 2015)

SEROLOGY
ELISA
CFT
RIA
HEMMAGLUTANITION
IMMUNOBLOT

Deteksi anti-cysticercal antibody


Unfractionated antigens of T. solium
Specificity dan sensitivity rendah
EITB (CDC USA)
Enzyme immunoelectrotransfer blot
assay
affinity-purified glycoprotein antigens
fractionated by electrophoresis
Specificity dan sensitivity tinggi

Toxoplasma gondii
Toxoplasma gondii is a protozoan parasite that can infect many animals,
including humans. Most infections are silent and have no ill effect on the patient
The acute phase of this infection lasts for less than around ten days. The parasite
causes a very strong type-1 response focused on the interferon-gamma secreted
by the T lymphocytes. This immune response limits the tissue extension of the
parasite, ensuring the survival of the host, but, paradoxically, also aiding the
survival of the parasite by converting it into a bradyzoite, an intracellular
quiescent resistant form persisting in the muscle and brain tissues

(Yoes Prijatna Dachlan, 2015)

(Guerrant RL, Walker DH, Weller PF, 2004)

Protozoa: Toxoplasma
gondii

tachyzoite

(Yoes Prijatna Dachlan, 2015)

(Gerald D. schmidt & Larry S. Roberts


Foundation of Parasitology, 2009)

Siklus hidup dan penularan T. gondii

Tissue cyst mengandung sejumlah


bradyzoite intra seluler pada uvea mata
penderita
(Hematoxylin and eosin, 1000.)
(Guerrant RL, Walker DH, Weller PF, 2004)
(Yoes Prijatna Dachlan, 2015)

Definitive host (DH) Toxoplasma gondii : domestic cats and their relatives).

1 Unsporulated oocysts are shed in the cats feces. Oocysts take 1-5 days to sporulate in the
environment and become infective

2 Intermediate hosts in nature (including birds and rodents) become infected after ingesting soil,
water or plant material contaminated with oocysts

3 Oocysts transform into tachyzoites shortly after ingestion. These tachyzoites localize in neural
and muscle tissue and develop into tissue cyst bradyzoites

4 Cats become infected after consuming intermediate hosts harboring tissue cysts
5

may also become infected with tissue cysts after ingestion of sporulated oocysts in the
environment
Humans can become infected by:

6 eating undercooked meat of animals harboring tissue cysts


7 consuming food or water contaminated with cat feces
8 blood transfusion or organ transplantation
9 transplacentally from mother to fetus
1
0
1
1

In the human host, the parasites form tissue cysts, most commonly in skeletal
muscle, myocardium, brain, and eyes
Diagnosis of congenital infections can be achieved by detecting T. gondii DNA in amniotic fluid

Acute toksoplasmosis

The symptoms may manifest and are often influenza-like:


swollen lymphnodes, headaches, fever, and fatigue,]or muscle
aches and pains that last for a month or more
Rarely will a human with a fully functioning immune system
develop severe symptoms following infection
Young children and immunocompromized people, such as
those with HIV/AIDS, those taking certain types of
chemotherapy, or those who have recently received an organt
transplant, may develop severe toxoplasmosis
The toxoplasmic trophozoites causing acute toxoplasmosis are
referred to as tachyzoites

Latent toksoplasmosis

Due to its asymptomatic nature, it is easy for a host to become


infected with Toxoplasma gondii and develop toxoplasmosis
without knowing it
In most immunocompetent people, the infection enters a
latent phase, during which only bradyzoites are present,
forming cysts in nervous and muscle tissue

Cutaneous toxoplasmosis

Skin lesions may occur (rarely): roseola, erythema multiformelike eruption, prurigo-like nodule, urticaria, maculopapula

EMERGING ZOONOSES
Indirect transmission : the infection of animal require
the presence of an intervening vector, or a specific
arthropod vector, and to carry it to human
vertebrate animals

Indirect transmission :
e.g.
West Nile,
Trypanosomiasis,
Plague

(Yoes Prijatna Dachlan,2012)

Vecto
r

Vecto
r
vertebrate animals

(Mims, 2000; McMichael,


Woodruff, 2008; Shakespeare
M., 2009)

ZOONOSES : those diseases and infections which are naturally


transmitted between vertebrate animals and man (WHO)
(Yoes Prijatna Dachlan,2012)
Direct transmission : an organism capable
of transferring from the vertebrate animal
source directly to human

Direct transmission

Direct transmission
e.g. Lassa
Once across the species barrier,
some Lassa virus (Arenavirus) may
spread by human to human

(Mims, 2000; McMichael, Woodruff,


2008; Shakespeare M., 2009)

EMERGING ZOONOSES (1) :


the pathogens that responsible for
zoonotic disease
The process of the spread of the
disease or pathogen into another
species (e.g. human) is known as
crossing or jumping the species gap
The pathogen must have the ability
to cross between an animal an
human
host
under
suitable
circumstances or conditions
Any disease that can cross the
(Yoesspecies
Prijatna Dachlan,gap
2012) is described as having a

EMERGING ZOONOSES (2):


the pathogens that responsible for
zoonotic disease
Two important points : must have the
ability
and
must
have
the
opportunity to cross the species
barrier
The term opportunity is often related
to a variety
of other external
factors :
~ A change of the ecosystem
~ the meteorological pattern
~ global warming
~ farming practice

(Yoes Prijatna Dachlan,2012)

~ genetic modification

The emergence of a new


zoonosis

External factors
(Shakespeare, M., 2009)

ling
d
n
a
h
Food

Farming practice

Global

ern
att
Mt
p

Ec
os

A
change

Warmi
ng

Closer
and
prolon
ged
contact
with
species
carrier

The
pathogen
must have
the
opportunity
to cross the
barrier
ys
te
m

The ability
of the
causative
agent to
cross
species
barrier

Pathogen
transmission

The pathogen
may adapt to
human
physiology
and
immunology

(Yoes Prijatna Dachlan,2012)

MODE of
TRANSMISSION
AEROSOL INHALATION

Inhalation of infected aerosol (direct


transmission)

BLOOD, SALIVA

Direct transmission may be contact with infected


body fluids

FAECES, URINE

Indirect spread may also involve animalassociated organic residues - Psittacosis in human

FOMITE CONTACT

Touching an object or surface that has been in


physical contact with an infected animal can also
lead to infection. The inoculum on the fomites
may consist of active organism, spores or
encysted forms. e.g. Anthrax

FOOD AND WATER

Toxocara spp., Toxoplasma gondii, Weils disease


(Leptospira)

ORAL OR PHYSICAL
CONTACT

People who handle animals in the course of their


work, e.g. agricultural workers, abbatoir workers,
veterinary surgeon

PARASITIC VECTORS

Plague (Yersinia pestis, rat & flea); Transmission of


P. knowlesi
from the long-tailed monkey
to
humans follows the bite of Anopheles mosquitoes

(fleas, mosquitoes, lice,


ticks)

SCRATCHES, BITES,
(Yoes Prijatna Dachlan PBL 30-3-

Bartonella henselae (cat);(Shakespeare


Rabies (dog);M., 2009)

Children in rural Assammese communities share a close relationship with


semidomesticated dogs. Photographs taken by Rebecca J. Traub (TRENDS in
PARASITOLOGY vol.21 No 1 january 2005 )

Canine gastrointestinalis parasitic


zoonoses in developing countries
Uncontrolled populations of stray and
CLM= cutaneous larval
semi-domesticated dogs
migrans
Humans often share a close relationship
(Traub,
EE = eosinophilic enteritis
Robertson, Irwin,
with semi-domesticated dogs
VLM= visceral larval migrans
Mencke,
Socioeconomically disadvantaged
OLM=occular larval migrans
Thompson, 2005)
CV= covert toxocariasis
communities
The poor levels of hygiene and
overcrowding
Zoonotic
Giardiasis
A lack of veterinary attention and
ancylostomia
Giardia in dogs
zoonotic awareness
sis
Giardia in
CLM & EE in
humans
humans
Echinococcosis
E. multilocularis in
humans
E. granulosus in dogs

Toxocariasis
canis
VLM, OLM,CT

Malaria and Zoonoses


HOST-SWITCH EVENTS
Drove the evolution of
the extant Plasmodium
species and highlights
the parasites ability to
switch between host
A PCR-confirmedspecies (Hayakawa, A PCR-confirmed
case of P. knowlesi
case of P. knowlesi Tanabe, 2008)
infection that was
infection
acquired in South
In a migrant
Kalimantan
worker from
Indonesia and
Malaysia Serawak
imported to
The P. knowlesi
Borneo in the
Australia
parasites was
Netherlands
(van Hellemond, identified in DNA (Figtree, et al.,
2010)
et l., 2009) samples among oil
palm workers
(mostly migrants)
in Central
Kalimantan
Indonesia
(Kasmijati, et al.,

Humans acquire
knowlesi malaria
P. knowlesi is derived from ancestral parasite
population that existed prior to human settlement
in Southeast Asia, and underwent significant
population approximately 30,000 40,000 years
ago
Knowlesi malaria is primarily a zoonosis with wild
macaques as the reservoir hosts
On going ecological changes due to the
destruction of natural forests, may alter the
parasite, macaque and mosquito population
dynamics and lead the parasites to switch to
human as the preferred
hosts
(Lee K-S,
2011; Kakilaya, B.S., 2011)

TERIMAKASIH

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