STEP 1

1. Shivering fever : the condition when your shiver usually it comes when our body
need to maintance the temperature
2. Rapid test : one of the test include blood test, thick and thin blood test, additional
test to diagnostic about KLB condition, the detected malaria antigen in the blood
with immunocromatografy
3. Fever free period : our temperature increase but theres some period when our
temperature decrease to normal level.

STEP 2

1. What kind of fever?

2. Why the patient have a period high fever and preceded by shivering and
followed by spontaneous decreased in temperature with profuse sweating?
3. Why the patient show konjungtiva palpebra sclera jaundice and
splenomegaly?
4. What is the relation between patient on papua and the complient?
5. Diagnosis and dd?
6. What is the etiology of the scenario?
7. How the transmitted the mosquito bite?
8. what is another supportif examination?
9. How the procedure of rapid test and interpretation?
10. Why the pheripheral blood smear test showed an abnormal erythrocyte?
11. What kind of proper medication and preventif medication that doctor gave to
him and what kind of actvity each medication?

STEP 3

1. What kind of fever?

 Septic fever : the temperature of body increased in the night but
decreased in the morning
 Hectic fever : the temperature of body increased in the night but
decreased in the morning on normal temperature.
 Remiten fever : the fever is decreased everyday but not in the level
normal
 Intermitten fever : thefever decreased in several hour on one day.
 Continue fever : happened and the variation temperature a day and
fluctuasi 0,5derajat c.

Patofisiology fever

In our body there are pirogen endogen but in external body there are
pirogen eksogen, if pyrogen eksogen enter our body on our low immune
system pyrogen eksogen stimulate hypothalamus to increased set point
 temperature normal in our body high  (compensation)

Eksogen pyrogen  activated makrofag  sitokin  arakhidonat acid 

PGE 2  Increased the set point of thermostat  fever

Two effect : vasokontriksi  shiveringg

Vasodilatasi sweating
2. Why the patient have a period high fever and preceded by shivering and
followed by spontaneous decreased in temperature with profuse sweating?

Someone have a high fever cause by bacteri viral. Bacteri will break up on
blood cell and there are will be fagosyt by makrofag leukosit and limfosit and
all of the cell wil be digest the bacteri and the result is release IL 1 or the
pyrogen endogen and will induction PGE 2 stimulate fever on preoptic
hypothalamus anterior.
When the set point high  the body will have a compensation to make the
temperature in our body balancing.

Some disease with intermitten disease is mlaria lipoma and endocarbitis

Continues fever : demam typhoid, malignantfalciparum malaria
Remitten fever : most viral and bacterial disease
Hectic/septic fever : Kawasaki disease and piogenic infection

Spontaneous decrease?
High fever are the defense mechanism cause bacteri, shivering bcs of
balancing temperature.
Decreasing of the fever is cause by smthg infected our body doing smthg like
growing  our body doesn’t need to increased our body
3. Why the patient show pale konjungtiva palpebra sclera jaundice and
splenomegaly?
Pale konjungtiva palpebra
Cause by hb in our body decreased  eritrosit damage and hb is decreased

Sclera jaundice
Malaria can attack heoatosit  hepatosit damage cant conjugated to bilirubin
direct
Anemia hemolitik bcs of ebfected parasit  increased bilirubin I  sclera
ikterik

Splenomegali
Erythrocyte lisis  spleen will peoduced eritrocyte more.
Lien is to destruct old eritrosit and damage eritrosit  too much damage
eritrosit  damage lien
Lien is a place to destraye old eritrosit, if erittrosit contained pyrogen 
pyrogen spread on the lien  makrofag monosit release inflammation factor

4. What is the relation between patient on papua and the complient?

Parasit : parasit on papua  plasmodium falciparum and plasmoduium vivax.
Endemesitas from both of plasmodium.

Area endemic : the condition which is in area attacking one disease so if

another person come to that area must get vaccination.
5. Diagnosis and dd?
1. Malaria disease
Cause plasmodium falciparum : fever everyday
vivax, ovale : just one day
malariae : fever two day

2. Typhoid fever
 Cause salmonella tyhphi but in typhoid fever have a abdominal pain

3. Lypoma
4. endocarditis
6. What is the etiology of the scenario?
Plasmodium
p. falciparum, vivax, ovale dan malaria

7. Life cycle plasmodium?

Anopheles (vector of plasmodium)  bite human  sporozoit  enter liver
parenchyma  schizont  merozoit  enter RBC  ruptured  fagositized
by macrophage  ring form  2nd mature form  schizont ruptured 
merozoit  processing and filtrating by spleen  gametosit  mosquito wall
gut  zygot  ookinet  oocyst  migrating to salivary gland 
- Aseksual eksogen
8. How patofisiolgy and pathogenesis based on the scenario?
9. what is another supportif examination?
10. How the procedure of rapid test and interpretation?
11. Why the pheripheral blood smear test showed an abnormal erythrocyte?
12. What kind of proper medication and preventif medication that doctor gave to
him and what kind of actvity each medication?

STEP 7
1. What kind of fever?
• septic fever
Body temperature gradually rises to the level of eminence once at night and
fell back to levels above normal in the morning. Often accompanied by chills
and sweating complaint.
• Fever hektik
Body temperature gradually rises to the level of eminence once at night and
go back down to normal levels in the morning.
• Fever remittances
Body temperature can go down every day but never reached normal body
temperature. Which may be recorded temperature difference can reach two
degrees and not by differences of temperature recorded in septic fever.
• intermittent fever
Body temperature dropped to normal levels for several hours in a day. When
the fever like this happens every two days once called tersiana and in case of
two days free of fever between the two attacks of fever called kuartana.
• Fever continuous
Temperature variations along lebh har no different than a degree. At the level
of persistent fever that high once called hyperpyrexia.
• Fever cyclic
An increase in body temperature for several days, followed by a free period of
weeks to a few days of fever, followed by a rise in temperature as before.
((IPD medicine))

The types of fever consists of:

 Physiology Fever, fever tends to normal, and as a physiological adjustment
to the body, such as in people who are dehydrated and high body activity
(exercise). (Sherwood, 2001)
Pathological fever, fever no longer be regarded as a normal fever. Fever
that occurs as a sign of a disease. Fever pathological divided into two as
 follows:
• Fever Infection where temperatures can reach over 38 ° C. The causes
vary, the viral infection (influenza, smallpox, measles, SARS, bird flu, etc.),
fungi, and bacteria (typhoid fever, sore throat, etc.).
• Fever Non Infection, such as cancer, tumors, or autoimmune disease a
person (arthritis, lupus, etc.).
(Samuelson, 2007)

Patofisiology fever

2. Why the patient have a period high fever and preceded by shivering and
followed by spontaneous decreased in temperature with profuse
sweating?
Sumber : Essentials of Pathophysiology: Concepts of Altered Health States
Oleh Carol Porth

Spontaneous decrease?
3. Why the patient show pale konjungtiva palpebra sclera jaundice and
splenomegaly?
 Pale konjungtiva palpebra
 Anemia occurs due to rupture of red blood cells infected or not
infected. Plasmodium falciparum infects red blood cells of all types, so
that anemia can occur in acute and chronic infection. Plasmodium
vivax and ovale infect only young red blood cells which is only 2% of
the total number of red blood cells, while the plasmodium malariae
infect older red blood cells which is only 1% of the number of red blood
cells. So the anemia caused by P. vivax, P. ovale and P. malariae
generally occurs in a chronic condition.
Sumber : Pdf Pedoman penatalaksanaan kasus malaria di Indonesia

 Sclera jaundice

 Splenomegali
spleen is an Reticuloendothelial organ, which was plasmodium
destroyed by the cells - macrophages and lymphocytes. The addition
of cell - cell inflammation will cause the spleen to enlarge.
Sumber : Pdf Pedoman penatalaksanaan kasus malaria di Indonesia

4. What is the relation between patient on papua and the complient?

Sumber:
http://www.depkes.go.id/downloads/publikasi/buletin/BULETIN%20MALARIA.
pdf

Spesies Plasmodium pada manusia adalah Plasmodium falciparum, P. vivax,

P. ovale, P. malariae. Jenis Plasmodium yang banyak ditemukan di Indonesia
adalah P. falciparum dan P. vivax, sedangkan P. malariae dapat ditemukan di
beberapa provinsi antara lain: Lampung, Nusa Tenggara Timur dan Papua.
P. ovale pernah ditemukan di Nusa Tenggara Timur dan Papua.
Sumber : Direktorat Jenderal Pengendalian Penyakit dan Penyehatan
Lingkungan Departemen Kesehatan RI. Gebrak Malaria. Pedoman
Penatalaksanaan Kasus Malaria di Indonesia. Jakarta.2008. Hal: 1,3.

Epidemiology
Malaria occurs throughout most of the tropical regions of the world (Fig. 210-
2). P. falciparum predominates in Africa, New Guinea, and Hispaniola (i.e.,
the Dominican Republic and Haiti); P. vivax is more common in Central
America. The prevalence of these two species is approximately equal in
South America, the Indian subcontinent, eastern Asia, and Oceania. P.
malariae is found in most endemic areas, especially throughout sub-Saharan
Africa, but is much less common. P. ovale is relatively unusual outside of
Africa and, where it is found, comprises <1% of isolates. Patients infected
with P. knowlesi have been identified on the island of Borneo and to a lesser
extent elsewhere in Southeast Asia where the main hosts, long-tailed and pig-
tailed macaques, are found.
The epidemiology of malaria is complex and may vary considerably even
within relatively small geographic areas. Endemicity traditionally has been
defined in terms of parasitemia rates or palpable-spleen rates in children 2–9
years of age as hypoendemic (<10%), mesoendemic (11–50%),
hyperendemic (51–75%), and holoendemic (>75%); however, it is uncommon
to use these indices for planning control programs because statistically valid
national surveys are not done routinely in most endemic areas. In holo- and
hyperendemic areas (e.g., certain regions of tropical Africa or coastal New
Guinea) where there is intense P. falciparum transmission, people may
sustain more than one infectious mosquito bite per day and are infected
repeatedly throughout their lives. In such settings, rates of morbidity and
mortality due to malaria are considerable during early childhood. Immunity
against disease is hard won in these areas, and the burden of disease in
young children is high; by adulthood, however, most malarial infections are
asymptomatic. Constant, frequent, year-round infection is termed stable
transmission. In areas where transmission is low, erratic, or focal, full
protective immunity is not acquired, and symptomatic disease may occur at
all ages. This situation usually exists in hypoendemic areas and is termed
unstable transmission. Even in stable transmission areas, there is often an
increased incidence of symptomatic malaria coinciding with increased
mosquito breeding and transmission during the rainy season. Malaria can
behave like an epidemic disease in some areas, particularly those with
unstable malaria, such as northern India (the state of Rajasthan), Sri Lanka,
Iraq, Turkey, the horn of Africa, Rwanda, Burundi, southern Africa,
Madagascar, and central Asia. An epidemic can develop when there are
changes in environmental, economic, or social conditions, such as heavy
rains following drought or migrations (usually of refugees or workers) from a
nonmalarious region to an area of high transmission; a breakdown in malaria
control and prevention services can intensify epidemic conditions. This
situation usually results in considerable mortality among all age groups.
The principal determinants of the epidemiology of malaria are the number
(density), the human-biting habits, and the longevity of the anopheline
mosquito vectors. Not all of the >400 anophelines can transmit malaria, and
the 40 species that do so vary considerably in their efficiency as malaria
vectors. More specifically, the transmission of malaria is directly proportional
to the density of the vector, the square of the number of human bites per day
per mosquito, and the tenth power of the probability of the mosquito's
surviving for 1 day. Mosquito longevity is particularly important because the
portion of the parasite's life cycle that takes place within the mosquito—from
gametocyte ingestion to subsequent inoculation (sporogony)—lasts 8–30
days, depending on ambient temperature; thus, to transmit malaria, the
mosquito must survive for >7 days. Sporogony is not completed at cooler
temperatures—i.e., <16°C for P. vivax and <21°C for P. falciparum; thus
transmission does not occur below these temperatures, although malaria
outbreaks and transmission have occurred in the highlands (>1500 m) of east
Africa, which were previously free of vectors. The most effective mosquito
vectors of malaria are those, such as Anopheles gambiae in Africa, which are
long-lived, occur in high densities in tropical climates, breed readily, and bite
humans in preference to other animals. The entomologic inoculation rate
(EIR; the number of sporozoite-positive mosquito bites per person per year) is
the most common measure of malaria transmission and varies from <1 in
some parts of Latin America and Southeast Asia to >300 in parts of tropical
Africa.

Malaria terjadi di hampir seluruh daerah tropis dunia (Gambar. 210-2). P.

falciparum mendominasi di Afrika, New Guinea, dan Hispaniola (yaitu,
Republik Dominika dan Haiti); P. vivax lebih umum di Amerika Tengah.
Prevalensi kedua spesies kira-kira sama di Amerika Selatan, benua India,
Asia Timur, dan Oseania. P. malariae ditemukan di daerah yang paling
endemik, terutama di seluruh sub-Sahara Afrika, tetapi jauh kurang umum. P.
ovale luar relatif tidak biasa dari Afrika dan, di mana ia ditemukan, terdiri <1%
dari isolat. Pasien yang terinfeksi P. knowlesi telah diidentifikasi di pulau
Kalimantan dan pada tingkat lebih rendah di tempat lain di Asia Tenggara di
mana host utama, ekor panjang dan kera ekor babi, ditemukan.
Epidemiologi malaria sangat kompleks dan dapat bervariasi bahkan dalam
wilayah geografis yang relatif kecil. Endemisitas tradisional telah didefinisikan
dalam hal tingkat parasitemia atau tingkat teraba-limpa pada anak 2-9 tahun
sebagai hiperendemis (<10%), mesoendemic (11-50%), hiperendemis (51-
75%), dan holoendemic ( > 75%); Namun, hal ini jarang terjadi untuk
menggunakan indeks ini untuk perencanaan program pengendalian karena
survei nasional yang valid secara statistik tidak dilakukan secara rutin di
daerah yang paling endemik. Dalam holo- dan hiperendemis daerah
(misalnya, daerah-daerah tertentu di Afrika tropis atau pantai New Guinea) di
mana ada transmisi intens P. falciparum, orang mungkin mempertahankan
lebih dari satu gigitan nyamuk menular per hari dan terinfeksi berulang kali
sepanjang hidup mereka. Dalam pengaturan tersebut, tingkat morbiditas dan
mortalitas akibat malaria cukup besar pada anak usia dini. Kekebalan
terhadap penyakit won keras di daerah-daerah, dan beban penyakit pada
anak-anak yang tinggi; masa dewasa, namun, sebagian besar infeksi malaria
tidak menunjukkan gejala. Konstan sering, infeksi, sepanjang tahun disebut
transmisi stabil. Di daerah di mana transmisi rendah, tidak menentu, atau
focal, kekebalan protektif penuh tidak diperoleh, dan penyakit gejala dapat
terjadi pada semua usia. Situasi ini biasanya ada di daerah hypoendemic dan
disebut transmisi stabil. Bahkan di daerah transmisi stabil, sering ada
peningkatan insiden malaria gejala bertepatan dengan peningkatan
perkembangbiakan nyamuk dan transmisi selama musim hujan. Malaria
dapat berperilaku seperti penyakit epidemi di beberapa daerah, terutama
malaria tidak stabil, seperti India utara (negara bagian Rajasthan), Sri Lanka,
Irak, Turki, tanduk Afrika, Rwanda, Burundi, Afrika Selatan, Madagaskar, dan
Asia Tengah. Epidemi dapat berkembang ketika ada perubahan kondisi
lingkungan, ekonomi, atau sosial, seperti hujan lebat berikut kekeringan atau
migrasi (biasanya pengungsi atau pekerja) dari daerah nonmalarious ke area
transmisi tinggi; gangguan dalam kontrol dan pencegahan jasa malaria dapat
meningkatkan kondisi epidemi. Situasi ini biasanya menghasilkan kematian
yang cukup besar di antara semua kelompok umur.
Faktor penentu utama epidemiologi malaria adalah nomor (density),
kebiasaan manusia menggigit, dan umur panjang dari vektor nyamuk
anopheles. Tidak semua> 400 anophelines dapat mengirimkan malaria, dan
40 spesies yang melakukannya bervariasi dalam efisiensi mereka sebagai
vektor malaria. Lebih khusus, transmisi malaria berbanding lurus dengan
kepadatan vektor, kuadrat dari jumlah gigitan manusia per hari per nyamuk,
dan kekuatan sepuluh kemungkinan nyamuk yang masih hidup selama 1 hari.
Nyamuk umur panjang sangat penting karena bagian dari siklus hidup parasit
yang terjadi di dalam nyamuk-dari gametocyte konsumsi untuk inokulasi
berikutnya (sporogoni) yang -lasts 8-30 hari, tergantung pada suhu
lingkungan; dengan demikian, untuk mengirimkan malaria, nyamuk harus
bertahan selama> 7 hari. Sporogoni tidak selesai pada pendingin suhu-yaitu,
<16 ° C untuk P. vivax dan <21 ° C untuk P. falciparum; sehingga penularan
tidak terjadi di bawah suhu ini, meskipun wabah malaria dan transmisi telah
terjadi di dataran tinggi (> 1500 m) di Afrika timur, yang sebelumnya bebas
dari vektor. Vektor nyamuk yang paling efektif malaria adalah mereka, seperti
Anopheles gambiae di Afrika, yang berumur panjang, terjadi pada kepadatan
tinggi di iklim tropis, berkembang biak dengan mudah, dan menggigit
 manusia dalam preferensi untuk hewan lain. Tingkat entomologic inokulasi
(EIR, jumlah sporozoite positif gigitan nyamuk per orang per tahun) adalah
ukuran yang paling umum penularan malaria dan bervariasi dari <1 di
beberapa bagian Amerika Latin dan Asia Tenggara untuk> 300 di beberapa
bagian Afrika tropis .

Endemic

Endemic is a term applied to diseases that have long existed somewhere, this
term is used also for the existence of certain living creatures such plant or
animal that has long been a place where only this earth. The size of the time
taken for a long time can mean an annual, monthly, or weekly depending on
the lifestyle and creature age or illness is endemic. If the incubation period of
the disease is very short or in a matter of a few days or a few hours, the
illness has long been said to exist if the disease in an area where there is
continued after a month or several incubation period.

Endemis adalah istilah yang dipakai pada penyakit-penyakit yang sudah lama
ada disuatu tempat, istilah ini dipakai juga untuk keberadaan mahluk hidup
tertentu misalnya tumbuhan atau binatang yang sudah lama berada disuatu
tempat dimana saja dimuka bumi ini. Ukuran tentang waktu yang dianggap
sudah lama dapat berarti sudah tahunan, bulanan, atau mingguan tergantung
dari pola hidup dan usia mahluk atau penyakit yang dianggap endemis
tersebut. Jika masa inkubasi dari penyakit sangat pendek atau dalam
hitungan beberapa hari atau beberapa jam maka penyakit dapat dikatakan
sudah lama ada jika disuatu daerah dimana penyakit itu ada terus setelah
sebulan atau beberapa masa inkubasi.
5. Diagnosis and dd?
6. What is the etiology of the scenario?
Causes of malaria infection is plasmodium, which in addition to infect humans
also infect animals such as class birds, reptiles and mammals. Including the
genus plasmodium of family plasmodidae. This Plasmodium infecting human
asexual breeding ertirosit and experience in liver tissue and in aritrosit.
Sexual Breeding occurs in the body of the female Anopheles mosquito that.
Overall there are more than 100 Plasmodium that infect animals (82 in
species of birds and reptiles and 22 in primates).
Malaria parasites found in Indonesia
Plasmodium is often encountered;
• Plasmodium vivax which causes benign tertian malaria (benign malaria)
• Plasmodium falciparum, which causes tropical malaria (malignant malaria)
• Plasmodium malariae've also seen in our case, but very rarely.
• Plasmodium ovale been reported to occur in Irian Jaya, the island of Timor,
OWI Island (North Irian Jaya)

7. Life cycle plasmodium?

 This relation based on the type of plasmodium (P. Vivax, P.ovale, P.falciform,
etc)

Sumber : Breman JG: Eradicating malaria. Sci Prog 92:1, 2009[PMID

19544698]
8. How patofisiolgy and pathogenesis based on the scenario?

Cycle In Humans
At the time of infective Anopheles mosquitoes suck human blood, which is sporozoites in
the salivary glands of mosquitoes would enter the blood circulation dsalam for
approximately 30 minutes. After that sporozoites will go into liver cells and become
tropozoit heart. Then develop into liver schizonts which consists of 10,000 to 30,000
merozoites heart. This cycle is called eksoeritrositer cycle that lasts for approximately 2
weeks. In P. and P. ovale vivak, partly tropozoit indirect hearts develop into schizonts, but
there are memjadi dormant form called hipnozoit. Hipnozoit can stay in liver cells for
months to years. At a time when the body's immunity decreases, will be active so that it can
lead to relapse (relapse).
Merozoites from liver schizonts rupture will enter into the bloodstream and infect red blood
sidelines. In the red blood cells,
The parasite develops from tropozoit until schizont stage (8-30 merozoites). Asexual
development process is called skizogoni. The Next
schizont-infected erythrocytes) broke out and merozoites that will infect other red blood
cells. The cycle is called the cycle eritrositer. After 2-3 cycles skizogoni blood, some
merozoites which meninfeksi red blood cells and form the sexual stage is gametocytes
male and female.

In the cycle of female Anopheles mosquitoes

When the female Anopheles mosquito sucks blood containing gametocytes, in the
mosquito's body, male and female gamete gametes do
fertilization becomes a zygote. This zygote will develop into ookinet then penetrate the
mosquito stomach wall. In the mosquito stomach wall area ookinet will be oocysts and
sporozoites which subsequently become infective and will be ready to be transmitted to
humans.
The incubation period or the time span required from sporozoites
into the human body until the onset of clinical symptoms characterized by fever varies,
depending on the species of Plasmodium. While prepaten period or periods ranging from
sporozoites enter until the parasites in the blood can be detected by microscopic
examination.

Pathogenesis MALARIA
The pathogenesis of malaria as a result of complex interactions between the parasite, host
and
the environment. Pathogenesis more emphasis on the increase in vascular permeability
than intravascular coagulation. Oeleh because
skizogoni damage will occur anemia erythrocytes. Severity of anemia is not comparable with
parasitaemia showed abnormalities of erythrocytes in addition to containing the parasite.
This is presumably due to malaria toxin that causes malfunctioning of erythrocytes and
erythrocyte partially broke through the spleen so that the parasite out. Other factors that
cause anemia may be due to the formation of antibodies to erythrocytes.
Have an enlarged spleen and damming and pigmentation so easily broken. In many
parasites found in the spleen macrophages and often occurs phagocytosis of erythrocytes
infected or not infected. In chronic malaria occur hyperplasia of reticulocytes and
accompanied by an increase in macrophages.
In beratm malaria pathogenesis mechanisms associated with the invasion of merozoites into
erythrocytes causing erythrocytes containing
parasites undergo structural changes and biomolecular cell to maintain the parasite's life.
These changes include a mechanism,
including cell membrane transport, sitoadherensi, sequestration and resetting.
Sitoadherensi an attachment events that have been infected erythrocytes
P. falciparum to receptors on the endothelial venules and capillaries. Besides
erythrocytes can also be attached to uninfected erythrocytes, forming a rosette.
Resetting is a phenomenon of attachment between a mature erythrocytes containing
merozoites shrouded by about 10 or more erythrocytes non parasites, so berbentu like
flowers. One of the factors that
affect the resetting is where the presence of blood group antigens A and B blood group that
acts as a receptor on the surface of uninfected erythrocytes.
In the opinion of another expert, malaria pathogenesis is multifactorial and related to the
following matters:
1. The destruction of erythrocytes
Phagocytosis not only in erythrocytes containing parasites but also against erythrocytes that
do not contain parasites, causing anemia and tissue hypoxemia. In severe intravascular
hemolysis can occur hemoglobinuria (black white fever) and can lead to kidney failure
2. The mediator of endotoxin-macrophage
At the time skizogoni, erythrocytes containing parasites trigger macrophages
endotoxin sensitive to release a variety of mediators. Endotoxin
may originate from the gastrointestinal tract and the malaria parasite itself can release
tumor necrosis factor (TNF), which is a monokin, found in human blood circulation and the
malaria parasite infected animals. Cytokines TNF and can cause fever, hypoglycemia, and
sndrom respiratory diseases in adults
3. sequestration of erythrocytes were injured
Erythrocytes infected by Plasmodium can form protrusions (knobs) on its surface. The bulge-
containing antigens and antibodies react with malaria and is associated with an affine
ated erythrocytes containing parasites of the capillary endothelium in the tool, so skizogoni
take place in circulation in the appliance. Infected erythrocytes attached to the endothelium
and forming clots containing capillary leak and cause anoxia and tissue edema.
Source: https://yayanakhyar.com/2010/03/doctors-files_diagnosis_malaria.pdf

Siklus Pada Manusia

Pada waktu nyamuk anopheles infektif mengisap darah manusia, sporozoit
yang berada dalam kelenjar liur nyamuk akan masuk ke dsalam peredaran
darah selama kurang lebih 30 menit. Setelah itu sporozoit akan masuk ke
dalam sel hati dan menjadi tropozoit hati. Kemudian berkembang menjadi
skizon hati yang terdiri dari 10.000 sampai 30.000 merozoit hati. Siklus ini
disebut siklus eksoeritrositer yang berlangsung selama kurang lebih 2
minggu. Pada P. vivak dan P. ovale, sebagian tropozoit hati tidak langsung
berkembang menjadi skizon, tetapi ada yang memjadi bentuk dorman yang
disebut hipnozoit. Hipnozoit tersebut dapat tinggal di dalam sel hati selama
berbulan-bulan sampai bertahun-tahun. Pada suatu saat bila imunitas tubuh
menurun, akan menjadi aktif sehingga dapat menimbulkan relaps (kambuh).
Merozoit yang berasal dari skizon hati yang pecah akan masuk ke dalam
peredaran darah dan menginfeksi sela darah merah. Di dalam sel darah
merah,
parasit tersebut berkembang dari stadium tropozoit sampai skizon (8-30
merozoit). Proses perkembangan aseksual ini disebut skizogoni. Selanjutnya
eritrosit yang terinfeksi skizon) pecah dan merozoit yang keluar akan
menginfeksi sel darah merah lainnya. Siklus inilah yang disebut dengan siklus
eritrositer. Setelah 2-3 siklus skizogoni darah, sebagian merozoit yang
meninfeksi sel darah merah dan membentuk stadium seksual yaitu gametosit
jantan dan betina.

Siklus Pada Nyamuk Anopheles Betina

Apabila nyamuk Anopheles betina menghisap darah yang mengandung
gametosit, di dalam tubuh nyamuk, gamet jantan dan gamet betina
melakukan
pembuahan menjadi zigot. Zigot ini akan berkembang menjadi ookinet
kemudian menembus dinding lambung nyamuk. Di luas dinding lambung
nyamuk ookinet akan menjadi ookista dan selanjutnya menjadi sporozoit
yang nantinya akan bersifat infektif dan siap ditularkan ke manusia.
Masa inkubasi atau rentang waktu yang diperlukan mulai dari sporozoit
masuk ke tubuh manusia sampai timbulnya gejala klinis yang ditandai dengan
demam bervariasi, tergantung dari spesies Plasmodium. Sedangkan masa
prepaten atau rentang waktu mulai dari sporozoit masuk sampai parasit dapat
dideteksi dalam darah dengan pemeriksaan mikroskopik.

PATOGENESIS MALARIA
Patogenesis malaria akibat dari interaksi kompleks antara parasit, inang dan
lingkungan. Patogenesis lebih ditekankan pada terjadinya peningkatan
permeabilitas pembuluh darah daripada koagulasi intravaskuler. Oeleh
karena
skizogoni menyebabkan kerusakan eritrosit maka akan terjadi anemia.
Beratnya anemi tidak sebanding dengan parasitemia menunjukkan adanya
kelainan eritrosit selain yang mengandung parasit. Hal ini diduga akibat
adanya toksin malaria yang menyebabkan gangguan fungsi eritrosit dan
sebagian eritrosit pecah melalui limpa sehingga parasit keluar. Faktor lain
yang menyebabkan terjadinya anemia mungkin karena terbentuknya antibodi
terhadap eritrosit.
 Limpa mengalami pembesaran dan pembendungan serta pigmentasi
sehingga mudah pecah. Dalam limpa dijumpai banyak parasit dalam
makrofag dan sering terjadi fagositosis dari eritrosit yang terinfeksi maupun
yang tidak terinfeksi. Pada malaria kronis terjadi hyperplasia dari retikulosit
diserta peningkatan makrofag.
Pada malaria beratm mekanisme patogenesisnya berkaitan dengan invasi
merozoit ke dalam eritrosit sehingga menyebabkan eritrosit yang
mengandung
parasit mengalami perubahan struktur dan biomolekular sel untuk
mempertahankan kehidupan parasit. Perubahan tersebut meliputi
mekanisme,
diantaranya transport membran sel, sitoadherensi, sekuestrasi dan resetting.
Sitoadherensi merupakan peristiwa perlekatan eritrosit yang telah
terinfeksi
P. falciparum pada reseptor di bagian endotelium venule dan kapiler. Selain
itu
eritrosit juga dapat melekat pada eritrosit yang tidak terinfeksi sehingga
terbentuk roset.
Resetting adalah suatu fenomena perlekatan antara sebuah eritrosit yang
mengandung merozoit matang yang diselubungi oleh sekitar 10 atau lebih
eritrosit non parasit, sehingga berbentu seperti bunga. Salah satu faktor yang
mempengaruhi terjadinya resetting adalah golongan darah dimana
terdapatnya antigen golongan darah A dan B yang bertindak sebagai reseptor
pada permukaan eritrosit yang tidak terinfeksi.
Menurut pendapat ahli lain, patogenesis malaria adalah multifaktorial dan
berhubungan dengan hal-hal sebagai berikut:
1. Penghancuran eritrosit
Fagositosis tidak hanya pada eritrosit yang mengandung parasit tetapi
juga terhadap eritrosit yang tidak mengandung parasit sehingga
menimbulkan anemia dan hipoksemia jaringan. Pada hemolisis
intravascular yang berat dapat terjadi hemoglobinuria (black white fever)
dan dapat menyebabkan gagal ginjal
2. Mediator endotoksin-makrofag
Pada saat skizogoni, eritrosit yang mengandung parasit memicu makrofag
yang sensitive endotoksin untuk melepaskan berbagai mediator.
Endotoksin
mungkin berasal dari saluran cerna dan parasit malaria sendiri dapat
melepaskan faktor nekrosis tumor (TNF) yang merupakan suatu monokin,
ditemukan dalam peredaran darah manusia dan hewan yang terinfeksi
parasit malaria. TNF dan sitokin dapat menimbulkan demam,
hipoglikemia, dan sndrom penyakit pernapasan pada orang dewasa
3. Sekuestrasi eritrosit yang terluka
Eritrosit yang terinfeksi oleh Plasmodium dapat membentuk tonjolan-
tonjolan (knobs) pada permukaannya. Tonjolan tersebut mengandung
antigen dan bereaksi dengan antibodi malaria dan berhubungan dengan
afin
itas eritrosit yang mengandung parasit terhadap endothelium kapiler alat
dalam, sehingga skizogoni berlangsung di sirkulasi alat dalam. Eritrosit
yang terinfeksi menempel pada endothelium dan membentuk gumpalan
yang mengandung kapiler yang bocor dan menimbulkan anoksia dan
edema jaringan.
Sumber : https://yayanakhyar.com/2010/03/doctors-
files_diagnosis_malaria.pdf

9. what is another supportif examination?

10. How the procedure of rapid test and interpretation?

Tes diagnosis cepat

1. Antigen HRP-2 (histidine rich protein-2) yang di produksi oleh trofozoit

dan gametosit muda dari P. falciparum, di kenal di pasaran sebagai PF
test, ICT test, Paracheck, dll
2. Antigen enzim parasit lactate dehidrogenase (p-LDH) yang di produksi
oleh parasit bentuk aseksual / seksual dari 4 spesies. Dipasaran
dikenal sebagai test OPTIMAL
3. Mendeteksi antigen HRP-2 dari P. falcifarum dan antigen “pan-
malarial” dari 4 spesies plasmodium

Sumber : Sudoyo A. W. dkk, 2007. Buku Ajar – Ilmu Penyakit Dalam Jilid I
Edisi IV. Jakarta : EGC
11. Why the pheripheral blood smear test showed an abnormal erythrocyte?

After invading an erythrocyte, the growing malarial parasite progressively

consumes and degrades intracellular proteins, principally hemoglobin. The
potentially toxic heme is detoxified by lipidmediated crystallization to
biologically inert hemozoin (malaria pigment). The parasite also alters the
RBC membrane by changing its transport properties, exposing cryptic surface
antigens, andinserting new parasite-derived proteins. The RBC becomes
more irregular in shape, more antigenic, and less deformable. In P. falciparum
infections, membrane protuberances appear on the erythrocyte’s surface 12–
15 h after the cell’s invasion.
These “knobs” extrude a high-molecular-weight, antigenically variant, strain-
specific erythrocyte membrane adhesive protein (PfEMP1) that mediates
attachment to receptors on venular and capillary endothelium—an event
termed cytoadherence . Several vascular receptors have been identified, of
which intercellular adhesion molecule 1 (ICAM-1) is probably the most
important in the brain, chondroitin sulfate B in the placenta, and CD36 in most
other organs. Thus, the infected erythrocytes stick inside and eventually block
capillaries and venules. At the same stage, these P. falciparum –infected
RBCs may also adhere to uninfected RBCs (to form rosettes) and to other
parasitized erythrocytes (agglutination).
The processes of cytoadherence, rosetting, and agglutination are central to
the pathogenesis of falciparum malaria. They result in the sequestration of
RBCs containing mature forms of the parasite in vital organs (particularly the
 brain), where they interfere with microcirculatory flow and metabolism.
Sequestered parasites continue to develop out of reach of the principal host
defense mechanism: splenic processing and filtration. As a consequence,
only the younger ring forms of the asexual parasites are seen circulating in
the peripheral blood in falciparum malaria, and the level of peripheral
parasitemia underestimates the true number of parasites
within the body. Severe malaria is also associated with reduced deformability
of the uninfected erythrocytes, which compromises their passage through the
partially obstructed capillaries and venules and shortens RBC survival.
In the other three (“benign”) human malarias, sequestration does not occur,
and all stages of the parasite’s development are evident on peripheral-blood
smears. Whereas P. vivax , P. ovale , and P. malariae show a marked
predilection for either young RBCs ( P. vivax , P. ovale ) or old cells ( P.
malariae ) and produce a level of parasitemia that is seldom >2%, P.
falciparum can invade erythrocytes of all agesand may be associated with
very high levels of parasitemia.
Harrisons principle of internal medicine 17th edition hal 1691

12. What kind of proper medication and preventif medication that doctor
gave to him and what kind of actvity each medication?

7.2.2 Chemoprophylaxis
The most appropriate chemoprophylactic antimalarial drug for the destination
should be prescribed in the correct dosage (see Country list and Table 7.2).

Travellers and their doctors should be aware that no antimalarial prophylactic

regimen gives complete protection, but good chemoprophylaxis (adherence to
the recommended drug regimen) significantly reduces the risk of fatal
disease. The following should also be taken into account:
-Dosing schedules for children should be based on body weight.
-Weekly chloroquine should be started 1 week before arrival.
-Weekly mefloquine should preferably be started 2–3 weeks before departure,
to achieve adequate drug blood levels and to detect possible side-effects
before travel so that possible alternatives can be considered.
-Daily prophylaxis with doxycycline or atovaquone–proguanil should be
started 1-2 days before arrival (or earlier if drug tolerability needs to be
checked before departure).
-All prophylactic drugs should be taken with unfailing regularity for the
duration of the stay in the malaria risk area, and should be continued for 4
weeks after the last possible exposure to infection, since parasites may still
emerge from the liver during this period. The single exception is atovaquone–
proguanil, which can be stopped 1 week after return because it is effective
against early liver-stage parasites (liver schizonts). However, in case daily
doses have been skipped while the traveller is exposed to malaria risk,
atovaquone–proguanil prophylaxis should also be taken for 4 weeks after
return.
-Depending on the type of malaria at the destination, travellers should be
advised about possible late-onset malaria caused by P. vivax and P. ovale,
due to persistent hepatic forms of these parasites.

Depending on the type of malaria risk in the specific area of the

country/territory visited (see Country list), the recommended prevention
method may be mosquito bite prevention only, or mosquito bite prevention in
combination with chemoprophylaxis and/or stand-by emergency treatment, as
shown in Table 7.1 (see also Table 7.2 for details of individual drugs).

There are specific contraindications and possible side-effects for all

antimalarial drugs. Adverse reactions attributed to malaria chemoprophylaxis
are common, but most are minor and do not affect the activities of the
traveller. Serious adverse events – defined as constituting an apparent threat
to life, requiring or prolonging hospitalization, or resulting inpersistent or
significant disability or incapacity – are rare and normally identified in post-
marketing surveillance once a drug has been in use for sometime. Severe
neuropsychiatric disturbances (seizures, psychosis, encephalopathy) occur in
approximately 1 in 10 000 travellers receiving mefloquine prophylaxis, and
have also been reported for chloroquine at a similar rate. The risk of drug-
associated adverse events should be weighed against the risk of malaria,
especially P. Falciparum malaria, and local drug-resistance patterns.

Each of the antimalarial drugs is contraindicated in certain groups and

individuals, and the contraindications should be carefully observed (see Table
7.2) to reduce the risk of serious adverse reactions. Pregnant women, people
travelling with young children, and people with chronic illnesses should seek
individual medical advice. Any traveller who develops severe adverse effects
while using an antimalarial should stop taking the drug and seek immediate
medical attention. This applies particularly to neurological or psychological
disturbances experienced with mefloquine prophylaxis. Mild nausea,
occasional vomiting or loose stools should notprompt discontinuation of
prophylaxis, but medical advice should be sought if symptoms persist.

Long-term chemoprophylaxis
Adherence and tolerability are important aspects of chemoprophylaxis for
people with long-term exposure to risk of malaria infection. There are few
studies on chemoprophylaxis use for more than 6 months.
 The risk of serious side-effects associated with long-term prophylactic
use of chloroquine is low, but retinal toxicity is of concern when a
cumulative dose of 100 g of chloroquine is reached. Anyone who has
taken 300 mg of chloroquine weekly for more than 5 years and
requires further prophylaxis should be screened twice yearly for early
retinal changes. If daily doses of 100 mg chloroquine have been taken,
screening should start after 3 years.
 Data indicate no increased risk of serious side-effects with long-term
use of mefloquine if the drug is tolerated in the short-term.
Pharmacokinetic data indicate that mefloquine does not accumulate
during long-term intake.
 Available data on long-term chemoprophylaxis with doxycycline (i.e.
more than 12 months) are limited but reassuring. There are few data
on long-term use of doxycycline in women, but use of this drug is
associated with an increased frequency of vaginitis due to Candida.
 Atovaquone–proguanil is registered in European countries with a
restriction on duration of use (varying from 5 weeks to 1 year); such
restrictions do not apply in the United States
Sumber : http://www.who.int/ith/ITH_chapter_7.pdf
 Sumber : Pdf Pedoman penatalaksanaan kasus malaria di Indonesia

The goal of these malaria prevention guidelines is to prevent malaria caused by

all species, not only P. falciparum. These guidelines apply to both short-term and
long-term travelers. Malaria prevention consists of a combination of mosquito
avoidance measures and chemoprophylaxis. Although efficacious, the
recommended interventions are not 100% effective.
Sumber :Leder K, Black J, O’Brien D, Greenwood Z, Kain KC, Schwartz E, et al.
Malaria in travelers: a review of the GeoSentinel surveillance network. Clin Infect
Dis. 2004 Oct 15;39(8):1104–12.
Chapter 3Infectious Diseases Related To Travel
Paul M. Arguin, Kathrine R. Tan
First line treatment for uncomplicated infection, regardless of species, is chloroquine
phosphate: second line alternative for therapy is
hydroxychloroquine (for P. vivax or P. ovale add primaquine phosphate). In the
presence of chloroquine resistant species, quinine sulfate plus doxycycline, tetracycline,
or clindamycin is recommended. Depending upon the region and species, other choices
include mefloquine, primaquine, or atovaquone-proguanil. For dosing and selection see
http://www.cdc.gov/malaria/pdf/treatmenttable.pdf.
http://www.unicef.org/prescriber/eng_p18.pdf