SIVERING FEVER

STEP 3
1. Why the patient has periodic high fever preceded by shivering
Fever
Periodic fever associated with the outbreak of the mature schizont (sporolasi). In the benign
tertian malaria (P. vivax and P. ovale), schizont maturation every 48 hours, the periodicity of the
fever every 3rd day, whereas Kuartana Malaria (P. malariae) every 72 hours of maturation and
periodicity of fever every 4 days. Each attack on the mark with some periodic fever attacks.
Common symptoms (classic symptoms) is the "Trias Malaria" (malaria proxysm) respectively:

1) cold period.

Start chills, dry skin and cold, people often wrap themselves with blankets or gloves and frequent
chills when the whole body vibrates and teeth bumped each other, pale as the cold cyanosis. This
period lasts 15 minutes to 1 hour followed by rising temperatures.

2) The period of heat.

Face red, hot and dry skin, rapid pulse and remained high heat until 40oC or more, increased
respiration, headache, retroorbital pain, vomiting, shock may occur (drop in blood pressure),
awareness of delirium until seizures (children). This period is much longer than the cold phase,
can be up to 2 hours or more, followed by a sweaty state.

3) Period sweating.

Sweating sufferers from temporal, followed by the whole body, it got wet, the temperature drops,
people feel tired and often fell asleep. If the patient will wake up feeling well and can perform
normal job.

1|Page

Cycle outside of red blood cells (eksoeritrositer) takes place in the liver. This stage begins when
the female Anopheles mosquitoes bite humans and insert contained sporozoites in its saliva into
the human blood. A few minutes later (0.5-1 hours) sporozoites arrive in the liver and infect the
liver. In liver sporozoites undergo asexual reproduction (skizogoni) or the separation process and
produce child parasites (merozoites) which then will be released from the liver cells. In the
plasmodium vivax and plasmodium ovale was found in a latent form in the liver called hipnosoit,
which is a phase of the malaria parasite life that can later lead to recurrent / relapse / recurrence
(long term relapse). P. vivax can relapse several times until a period of 3-4 years, while P. Ovale
for years if not treated properly.
Relapse (relapse) is the re-emergence of the disease after a disease-free period.

Rekrudensi: fever that comes back within 8 weeks after the first symptoms disappear. This is due
to the increasing number of parasites in the blood (called short-term relapse)
Recurrence: a fever that comes back within a period of 24 weeks or more after the first attack is
lost due to the inclusion of parasites from the liver into the blood (also called long-term relapse)
Occurrence Mechanism Malaria Relapses
Marchoux in Cogswell (1992) describes the mechanism of relapse
on malaria as follows:
1) At the end of the pre-erythrocytic phase, schizont rupture, merozoites exit and enter the
bloodstream. Most of the erythrocytes that are attacking the liver sinusoid but some in
phagocytosis. On P. vivax and P. ovale, some sporozoites are being hipnozoit after some time (a
few months up to 5 years) become active again and start with skizogoni secondary eksoeritrosit.
This process is considered as a long-term relapse (long term relapse) or recurrent (recurrence).

In the development of P. falciparum and P.malariae not have eksoeritrosit secondary phase.
Parasites can remain in the blood for months or even up to several years and cause recurrent
symptoms from time to time. Caused by the proliferation of relapse and stage eritrositik known
as rekrudesensi (short term relapse). At falciparum malaria, rekrudesensi can occur within 28
days of the initial attack and this may indicate the presence of a resistance to chloroquine.
Relapse or re attack on malaria patients associated with the following conditions:
1) Not effective immune response of patients

2|Page

The fact that the disease will cause an immune response from the host to the presence of an
inflammatory reaction, it depends on the degree of infection. Relapse and disease closely
associated with low antibody titer or an increase in the ability of the antibodies against the
parasite. Immune response to malaria is species specific, someone immune to P. vivax malaria
disease will again when infected by P. falciparum (http / / www.malariasite.com, 22 November
2008).
2) The treatment is not perfect
Malaria drugs that are effective in suppressing the blood skizontisid skizogoni erythrocyte phase
and reducing clinical symptoms. Because it was already healthy patients stop taking the
medication before the entire dose of medication runs out. Another is the habit of people share
this medication with another person so that the expected dose was not reached. This resulted in
short-term relapse. In the case of P. vivax and P. ovale may occur reactivation of hipnozoit in the
liver and cause long-term relapse (http / / www.malariasite.com, November 22, 2008)
3) Reinfection or exposed to repeated mosquito bites
The cause of the most frequently repeated attacks, especially in endemic areas is a reinfection or
reinfection that occurs immediately after the patient completed treatment. Reinfection can occur
14 days after treatment. This is possible when the patient environment to support the
development of the malaria vector, so people are always exposed to infective mosquito bites
(Omunawa, 2002).
Guidelines for Case Management of Malaria in Indonesia. 2008
Fever is an elevation of body temperature that exceeds the normal daily variation
and occurs in conjunction with an increase in the hypothalamic set point (e.g., from
37C to 39C). Once the hypothalamic set point is raised, neurons in the vasomotor
center are activated and vasoconstriction commences.
The individual first notices vasoconstriction in the hands and feet. Shunting of blood away from the
periphery to the internal organs es-sentially decreases heat loss from the skin, and the person
feels cold. Shivering, which increases heat production from the muscles, may begin at this
time; however, shivering is not required if heat conservation mechanisms raise blood
temperature sufficiently. Nonshivering heat production from the liver also contributes to
increasing core temperature. In hu-mans, behavioral adjustments (e.g., putting on more clothing or
bed-ding) help raise body temperature by decreasing heat loss.
The processes of heat conservation (vasoconstriction) and heat production (shivering and
increased nonshivering thermogenesis) continue until the temperature of the blood bathing the
hypothalamic neurons matches the new thermostat setting. Once that point is reached, the
3|Page

hypothalamus maintains the temperature at the febrile level by the same mechanisms of heat
balance that function in the afebrile state. When the hypothalamic set point is again reset
downward (in response to either a reduction in the concentration of pyrogens or the use of
antipyretics), the processes of heat loss through vasodilation and sweating are initiat-ed.
Loss of heat by sweating and vasodilation continues until the blood temperature at the
hypothalamic level matches the lower setting. Behavioral changes (e.g., removal of clothing)
facilitate heat loss.

(Harrisons. Principles of Internal Medicine. 17th edition)

2. How is pathophysiology of fever

Mekanisme terjadinya demam secara umum

Demam terjadi karena pelepasan pirogen dari dalam leukosit yang sebelumnya telah
terangsang oleh pirogen eksogen yang dapat berasal dari mikroorganisme atau merupakan
suatu hasil reaksi imunologis yang tidak berdasarkan suatu infeksi.Pirogen diduga sebagai
suatu protein yang identik dengan interleukin-1.Di dalam Hipotalamus zat ini merangsang
penglepasan asam arakidonat serta mengakibatkan peningkatan sintesis prostalglandin E2
yang langsung dapat menyebabkan suatu pireksia.

4|Page

Pengaruh pengaturan otonomvasokonstriksi periferpengeluaran (dissipation) panas

menurundemam
Peningkatan

aktivitas

metabolismepenambahan

produksi

panaspenyaluran

ke

permukaaan tubuh inadekuatrasa demam bertambah pada pasien

IPD FKUI jilid 3 edisi 4

Fever occurs due to the release of the leukocyte pyrogen previously been stimulated by
exogenous pyrogens can be derived from microorganisms or is a result of an
immunological reaction that is not based on an alleged infeksi.Pirogen as a protein that is
identical to interleukin-1.Di these substances stimulate the hypothalamus the release of
arachidonic acid and prostaglandins E2 resulted in an increase in the direct synthesis can
lead to a pyrexia.
Effect of peripheral vasoconstriction otonomtis setting expenditure (dissipation)
decreases fever heat
Increased metabolic activity of the addition of heat production distribution of body
surface to increase inadequate sense of fever in patients

3. What causes intermitten fever

5|Page

o Demamintermittensuhubadanturunketingkatyg normal
selamabeberapa jam sajadalamsehari
2 harisekali (tersiana),terjadi 2 haribebasdemamdiantara 2
serangandemam (kuartana)
Disebabkanoleh ?
What are the kinds of plasmodium
4. What are the kinds of fever
1. Septic fever the evening once the temperature rises, the morning down
to above normal, chills and sweating. In the condition of sepsis
(infection of the entire body
can therefore bacteremia)
2. Hektik Night Fever days once the temperature rises, the morning down
to
normal. Malaria Tropica
3. Remitten fever body temperature can go down every day but never
reached normal. temperatures may reach 2 degrees but the difference is
not as big as septic fever.
4. Intermittent fever down to normal body temperature for a few hours in a
day. If fever occurred two days once called tertian and 2 day event free
of fever between 2 bouts of fever called kuartana. Malaria
5. Continuous fever temperature variations throughout the day did not
differ by more than one degree. At continuous high tingkatdemam once
called hyperpyrexia. viral infections
6. Cyclic fever rising body temperature for several days, followed by a
period bebasdemam for a few days followed by rise in temperature as
before DBD
6|Page

Sumber : Buku Ajar Ilmu Penyakit Dalam Edisi V

5. Why from the physical examination shows a pale palpebral

conjunctiva (anemia )
Guidelines for Case Management of Malaria in Indonesia. 2008
Congested spleen, blacken and become hard due to pigment deposits parasites and
erythrocytes increased connective tissue (Corwin, 2000, p. 571).

Guidelines for Case Management of Malaria in Indonesia. 2008

The degree of anemia depends on the cause of the species, is the most severe anemia due to
falciparum. Anemia caused by excessive destruction of erythrocytes normal erythrocytes can
not live long (reduced survival time). Impaired formation of erythrocytes due to depressed
erythropoiesis in the bone marrow. (Mansjoer. et al, p. 411)

Lien destroy the normal speed of 1/20 of peripheral erythrocytes

Splenomegaly destroy more of erythrocytes, even normal erythrocytes.
hemolytic jaundice
Caused by lysis (breakdown) excessive red blood cells. Jaundice can occur in red blood cell
destruction and excessive liver can conjugate all of bilirubin which is derived
hepatocellular jaundice
Presence of sporozoites that invade the liver causing decreased absorption and conjugation of
bilirubin by the liver dysfunction occurs in hepatocytes and hepatocellular call.
Overview of Clinical Examination Results, Laboratory. Ronald A. Sacher, Richard A. McPherson
Pale palpebra

7|Page

Anemia results from accelerated RBC removal by the spleen, obligatory RBC destruction
at parasite schizogony, and ineffective erythropoiesis. In severe malaria, both infected
and uninfected RBCs show reduced deformability, which correlates with prognosis and
development of anemia. Splenic clearance of all RBCs is increased.
(Harrisons. Principles of Internal Medicine. 17th edition)
Sclera icteric

(Ilmu Penyakit Hati. Ali Sulaiman)

Splenomegali
The spleen plays an important role in protection against malaria, and asplenic individuals
may be at serious risk from P. Falciparum infection. Indeed, experienced surgeons in
tropical regions take a conservative approach to management of splenic trauma in the
knowledge of increased mortality from malaria in individuals who have undergone
splenectomy. The spleen is enlarges with acute malaria, presumably as it functionsto
remove paracitised erythrocytes (recognised either because of their loss of deformity or
propessity to form clumps of sequestered cells) from the peripheral circulation, and
splenic macrophags remove dead parasites.
(Principles and Practice of Clinical Parasitology. Gillespie&Richard. 2001)
8|Page

Inflammatory splenomegaly
This is an acute enlargement of the spleen that develops in association with various
infections or inflammatory processes and results from an increase in the defense activities
of the organ. The demand for increased antigen clearance from the blood may lead to
increased numbers of reticuloendothelial cells in the spleen and stimulate accelerated
antibody production, with resultant lymphoid hyperplasia. Examples include
splenomegaly from lupus and Felty syndrome, and from viral infections such as Ebstein
Barr Virusinduced mononucleosis.
Hyperplastic splenomegaly
In this setting, splenomegaly is thought to reflect work hypertrophy that results from the
removal of abnormal blood cells from the circulation (either cells with intrinsic
defects or cells coated with antibody) or, in some cases, that results from
extramedullary hematopoiesis (ie, myeloproliferative disease).
Congestive splenomegaly
This condition develops as a result of cirrhosis with portal hypertension, splenic vein
occlusion (thrombosis), or congestive heart failure (CHF) with increased venous pressure.
Infiltrative splenomegaly
In this setting, splenomegaly is the result of engorgement of macrophages with
indigestible materials (eg, sarcoidosis, Gaucher disease, amyloidosis, metastatic
malignancy).
Infectious splenomegaly
Splenic filtering of blood-borne pathogens, especially encapsulated organisms, may lead
to abscess formation. Because many splenic abscesses may be indolent in presentation,
9|Page

splenic size may be increased as the abscess enlarges. This is a relatively uncommon, but
important, process to recognize and treat.

(http://emedicine.medscape.com/article/206208-overview#aw2aab6b2b2aa)
(http://www.ajronline.org/doi/full/10.2214/ajr.179.5.1791239)

6. Why the patient has icterus

Clinically visible as hyperbilirubinemia or jaundice or jaundice, which is a
yellow pigmentation of the skin and sclera. Jaundice can usually only be seen
when bilrubin serum levels exceed 34 to 43 mol / L (2.0 to 2.5 mg / dL), or
about twice the upper limit of the normal range; however, these symptoms
can be detected with higher bilirubin levels lower in patients whose skin is
white and who suffer from severe anemia. In contrast, symptoms of jaundice
are often not visible on those dark skin or who suffer from edema. Sclera
tissue is rich with elastin which has a high affinity for bilirubin, jaundice in
the sclera that is usually a sign of a more sensitive to indicate jaundice
hyperbilirubinemia than thorough. Early sign of hyperbilirubinemia was
similar to the dark color of urine, caused by bilirubin excretion through the
kidneys in the form of bilirubin glukuronid. In the striking jaundice, skin
greenish due to the partial oxidation of bilirubin to biliverdin outstanding.
This effect is often seen in conditions with prolonged conjugated
hyperbilirubinemia heavy tau as cirrhosis. Other symptoms may appear
depending on the cause, for example:
1. liver inflammation (hepatitis) can cause loss of appetite, nausea, vomiting,
10 | P a g e

and fever
2. Blockage of the bile can cause symptoms of cholestasis
Sumber : Horrison Ilmu Penyakit Dalam

7. Why the physical examination shows a splenomegaly

Guidelines for Case Management of Malaria in Indonesia. 2008
Congested spleen, blacken and become hard due to pigment deposits parasites and erythrocytes
increased connective tissue (Corwin, 2000, p. 571).

Guidelines for Case Management of Malaria in Indonesia. 2008

The degree of anemia depends on the cause of the species, is the most severe anemia due to
falciparum. Anemia caused by excessive destruction of erythrocytes normal erythrocytes can not
live long (reduced survival time). Impaired formation of erythrocytes due to depressed
erythropoiesis in the bone marrow. (Mansjoer. et al, p. 411)

Lien destroy the normal speed of 1/20 of peripheral erythrocytes

Splenomegaly destroy more of erythrocytes, even normal erythrocytes.
hemolytic jaundice
Caused by lysis (breakdown) excessive red blood cells. Jaundice can occur in red blood cell
destruction and excessive liver can conjugate all of bilirubin which is derived
hepatocellular jaundice
Presence of sporozoites that invade the liver causing decreased absorption and conjugation of
bilirubin by the liver dysfunction occurs in hepatocytes and hepatocellular call.
Overview of Clinical Examination Results, Laboratory. Ronald A. Sacher, Richard A.
McPherson

11 | P a g e

8. Why in the blood smear test shows an abnormal erythrocyte

Pedoman Penatalaksanaan Kasus Malaria di Indonesia. 2008

9. Why the mosquito bite can cause many symptom in scenario

(FEVER,menggigil,berkeringat)
Nyamukmenggigit (betinamenghisapdarah,jantan sari
makanandan buah2an)plasmodium
masukkepembuluhdarahsbgsporozoitmenginvasiselhepa
rskizonkembalikepembuluhdarahmenginvasieritrosit
(2 gambaraneritrosit 1.ring 2.knob)salah 1
eritrositpecahskizonpecahmerozoit
10.

What the prevention medication before stay inpapua

Table 2 .

Instructions for Travelers during the Pretravel Consultation.*

-

Use effective personal protection against mosquitoes.

Anopheles mosquitoes bite between dusk and dawn.

Wear long sleeves, long pants, and fully closed shoes with socks after dark.

Use permethrin-treated mosquito nets if accommodations are neither well

12 | P a g e

screened nor air-conditioned.

-

Repellent containing 30%50% DEET obtained from an outdoors store or

travel-supply vendor should be applied to exposed areas of skin every 4 to
6 hours. More frequent application is required for agents containing lower
concentrations of DEET. Agents containing 20% or higher concentrations of
picaridin (KBR 3023) are similar to those containing DEET at the
same concentration with regard to activity against anopheles mosquitoes.

Adhere to an antimalarial regimen.

Take weekly medications on the same day each week. (Sunday may be easiest
to remember.)

Take daily medications with the same meal each day.

Continue medications after the trip for the recommended duration.

If intolerable side effects occur, make every effort to contact the health
care
provider who prescribed the medications or the covering physician by
telephone (or by e-mail if offered by the practice) for advice. Physicians at
the destination may have poor knowledge of drugs and regimens used by
travelers. (The severity of side effects must be weighed against the risk of
a potentially fatal infection with Plasmodium falciparum)

Remember that no chemoprophylactic regimen against malaria is 100%

effective.

Symptoms of malaria may be mild and may mimic influenza, gastroenteritis,

or other common infections; any fever that develops during or after travel
to an area where there is a risk of malaria infection should raise the
suspicion of malaria.

Early treatment is usually effective, whereas delay of appropriate therapy

can
have serious or even fatal consequences; therefore, if symptoms of malaria
occur, seek prompt medical attention.

If fever develops within 3 mo after return from travel, a physician should be

informed of the recent travel, and blood films or a rapid card test for
malaria with immediate reporting should be requested; waiting for next-day

13 | P a g e

results may increase the risk of death. If the blood film or card test is
negative, two additional tests (including at least one blood film) should be
performed 1224 hr apart for confirmation, and other diagnoses should
be considered at the same time.
-

Ask health care providers who need assistance with diagnosis or management
of suspected cases of malaria to call the CDC Malaria Hotline: 770-4887788.
*CDC denotes Centers for Disease Control and Prevention, and DEET
N,Ndiethyl-3-methylbenzamide.
Effective concentrations are available worldwide, but concentrations
currently available in the United States (15%) are suboptimal for
protection against malaria. Data are from Constantini et al.
Malaria Prevention in Short-Term Travelers
David O. Freedman, M.D.

11.

What does the endemic area of vector born disease mean

12.

How is the life cycle of parasite in human body

14 | P a g e

15 | P a g e

Female Anopheles

Bite human

Sporozoit enter to circulation

Liver

Schizon in hepatocyte

Replication

Hepatocyte rupture

Hipnozoit

Merozoit release

Survive in liver

RBC invasion

Relaps

Replication

Tropozoit

RBC destruction
in Spleen

Schizon imature
Anemia
Knob

Schizon mature

Toxin GPI

Rupture RBC

IL-1 , TNF

Merozoit release

Eritropoiesis depression
in Bone marrow

Anemia

13.

Fever

Hemolysis RBC

Infected other health RBC

Gametocyte

the cycle repeats

Sexual cycle in
female anopheles

DD
16 | P a g e

Jaundice

MALARIA
Alternative Names
Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever;
Tertian malaria; Plasmodium

Causes
Malaria is caused by a parasite that is passed from one human to another
by the bite of infected Anopheles mosquitoes. After infection, the
parasites (called sporozoites) travel through the bloodstream to the liver,
where they mature and release another form, the merozoites. The
parasites enter the bloodstream and infect red blood cells.
The parasites multiply inside the red blood cells, which then break open
within 48 to 72 hours, infecting more red blood cells. The first symptoms
usually occur 10 days to 4 weeks after infection, though they can appear
as early as 8 days or as long as a year after infection. The symptoms occur
in cycles of 48 to 72 hours.
Most symptoms are caused by:

The release of merozoites into the bloodstream

Anemia resulting from the destruction of the red blood cells
Large amounts of free hemoglobin being released into circulation after
red blood cells break open
Malaria can also be transmitted from a mother to her unborn baby
(congenitally) and by blood transfusions. Malaria can be carried by
mosquitoes in temperate climates, but the parasite disappears over the
winter.
The disease is a major health problem in much of the tropics and
subtropics. The CDC estimates that there are 300-500 million cases of
malaria each year, and more than 1 million people die from it. It presents a
major disease hazard for travelers to warm climates.
In some areas of the world, mosquitoes that carry malaria have developed
resistance to insecticides. In addition, the parasites have developed
17 | P a g e

resistance to some antibiotics. These conditions have led to difficulty in

controlling both the rate of infection and spread of this disease.
There are four types of common malaria parasites. Recently, a fifth type,
Plasmodium knowlesi , has been causing malaria in Malaysia and areas of
southeast Asia. Another type, falciparum malaria, affects more red blood
cells than the other types and is much more serious. It can be fatal within
a few hours of the first symptoms.

Symptoms

Anemia
Bloody stools
Chills
Coma
Convulsion
Fever
Headache
Jaundice
Muscle pain
Nausea
Sweating
Vomiting

Exams and Tests

During a physical examination, the doctor may find an enlarged liver or
enlarged spleen. Malaria blood smears taken at 6 to 12 hour intervals
confirm the diagnosis.
A complete blood count (CBC) will identify anemia if it is present.

Treatment
Malaria, especially Falciparum malaria, is a medical emergency that
requires a hospital stay. Chloroquine is often used as an anti-malarial
medication. However, chloroquine-resistant infections are common in some
parts of the world.

18 | P a g e

Possible treatments for chloroquine-resistant infections include:

The combination of quinidine or quinine plus doxycycline, tetracycline, or

clindamycin
Atovaquone plus proguanil (Malarone)
Mefloquine or artesunate
The combination of pyrimethamine and sulfadoxine (Fansidar)
The choice of medication depends in part on where you were when you
were infected.
Medical care, including fluids through a vein (IV) and other medications
and breathing (respiratory) support may be needed.

Outlook (Prognosis)
The outcome is expected to be good in most cases of malaria with
treatment, but poor in Falciparum infection with complications.

Possible Complications

Brain infection (cerebritis)

Destruction of blood cells (hemolytic anemia)
Kidney failure
Liver failure
Meningitis
Respiratory failure from fluid in the lungs (pulmonary edema)
Rupture of the spleen leading to massive internal bleeding (hemorrhage)

When to Contact a Medical Professional

Call your health care provider if you develop fever and headache after
visiting the tropics.

Prevention
Most people who live in areas where malaria is common have gotten some
immunity to the disease. Visitors will not have immunity, and should take
preventive medications.
19 | P a g e

It is important to see your health care provider well before your trip,
because treatment may need to begin as long as 2 weeks before travel to
the area, and continue for a month after you leave the area. In 2006, the
CDC reported that most travelers from the U.S. who contracted malaria
failed to take the right precautions.
The types of anti-malarial medications prescribed will depend on the area
you visit. According to the CDC, travelers to South America, Africa, the
Indian subcontinent, Asia, and the South Pacific should take one of the
following drugs: mefloquine, doxycycline, chloroquine, hydroxychloroquine,
or Malarone. Even pregnant women should take preventive medications
because the risk to the fetus from the medication is less than the risk of
catching this infection.
People who are taking anti-malarial medications may still become infected.
Avoid mosquito bites by wearing protective clothing over the arms and
legs, using screens on windows, and using insect repellent.
Chloroquine has been the drug of choice for protecting against malaria.
But because of resistance, it is now only suggested for use in areas where
Plasmodium vivax , P. oval , and P. malariae are present. Falciparum malaria
is becoming increasingly resistant to anti-malarial medications.
For travelers going to areas where Falciparum malaria is known to occur,
there are several options for malaria prevention, including mefloquine,
atovaquone/proguanil (Malarone), and doxycycline.
Travelers can call the CDC for information on types of malaria in a certain
area, preventive drugs, and times of the year to avoid travel.

References
Fairhurst RM, Wellems TE. Plasmodium species (Malaria). In: Mandell GL,
Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases .
7th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2009:chap 275.
Krogstad DJ. Malaria. In: Goldman L, Ausiello D, eds. Cecil Medicine . 23rd
ed. Philadelphia, Pa: Saunders Elsevier. 2007:chap 366.

20 | P a g e

MALARIA

DEFINISI
Malaria is a protozoan disease transmitted by the bite of in-fected
Anopheles mosquitoes.

ETIOLOGI
Four species of the genus Plasmodiumcause nearly all malarial infec-tions
in humans (although rare infections involve species normally affecting
other primates). These are P. falciparum, P. vivax, P. ovale, and P.
malariae. Almost all deaths are caused by falciparum malaria. Human
infection begins when a female anopheline mosquito inoculates plasmodial
sporozoitesfrom its salivary gland during a blood meal.

KLASIFIKASI

MANFEST
-

The first symptoms of malaria are nonspecific; the lack of a sense

of well-being, headache, fatigue, abdominal discomfort, and muscle
aches followed by fever are all similar to the symptoms of aminor
viral illness.

In some instances, a prominence of headache, chest pain, abdominal

pain, arthralgia, myalgia, or diarrhea may suggest another diagnosis.

The classic malarial paroxysms, in which fever spikes, chills, and

rigors occur at regular intervals, are relatively unusual and suggest
infection with P. vivaxor P. ovale.

The fever is irregular at first (that of falciparum malaria may

never become regular); the temperature of nonimmune individuals
and children often rises above 40C in conjunction with tachycardia
and sometimes delirium.

Many clinical abnormalities have been described in acute malaria,

but most patients with uncomplicated infections have few abnormal
physical findings other than fever, malaise, mild anemia, and (in
some cases) a palpable spleen. Anemia is common among young
21 | P a g e

children living in areas with stable transmission, particularly where

resistance has compromised the efficacy of antima-larial drugs. In
nonimmune individuals with acute malaria, the spleen takes several
days to become palpable, but splenic enlargement is found in a high
proportion of otherwise healthy individuals in malaria endemic
areas and reflects repeated infections. Slight enlargement of the
liver is also common, particularly among young children. Mild
jaundice is common among adults; it may develop in patients with
otherwise uncomplicated falciparum malaria and usually resolves
over 13 weeks.

PATOGENESIS

PATOFISIOLOGI

PENEGAKAN DIAGNOSIS
a. Anamnesis
Keluhan utama tersering demam >2hari, menggigil, berkeringat
trias malaria
Malaria berat gangguan kesadaran, kelemahan, kelumpuhan otot,
kejang, panas tinggi, muntah terus menerus
b. PF
Demam 37,5-40 C
Konjungtiva palpebra pucat anemia
Spleomegali
Hepatomegali
Malaria berat penurunan kesadaran, dehidrasi, perdarahan, ikterik,
gangguan ginjal, pembesaran hai dan limpa, gejala neurologi(refleks
patologis dan kaku duduk)
c. Px. Tetes darah untuk malaria
Preparat darah tebal: cara terbaik menemukan parasit malaria,
dinyatakan negatif jika setelah diperiksa dalam 200 lapang pandang
dengan pembesaran kuat 700-1000 kali tidak ditemukan parasit.
Preparat darah tipis: untuk identifikasi jenis plasmodium, bila dengan
darah tebal sulit ditemukan.
22 | P a g e

d. Tes antigen : P-F test

Mendeteksi antigen dari p. Falciparum(Histidine rich protein II)
hanya 3-5menit, sensitivitas baikDeteksi untuk p.vivax: ICT
e. Tes serologi
Indirect hemaglutination test, ELISA test, radio immunoassay,
immunoprecipitation techniques mendeteksi antibodi spesifik
malaria/ keadaan dimana parasit sangat minimal kurang bermanfaat
krn antibodi baru muncul setelah beberapa hari parasitemia.
f. PCR
Dengan teknologi amplifikasi DNA, sensitivitas dan spesifitasnya
tinggi, dapat memberikan hasil positif meskipun parasit sangat sedikit.

TERAPI

PENCEGAHAN
a. Pencegahan dari gigitan nyamuk: kelambu, obat pembunuh nyamuk
(repellent), mencegah berada di alam bebas, proteksi tempat tinggal.
b. Kemoprofiaksis
Ketahui sensitivitas plasmodium ditempat tujuan:
-

Sensitif klorokuin: 2tab klorokuin 1minggu sebelum, tiap minggu

ditujuan, 4minggu setelah tiba kembali.

Resisten klorokuin: doksisiklin 0,5 mg/kgbb/hari atau mefloquin

250 mg/minggu atau klorokuin 2tab per minggu ditambah proguanil
200mg/hari.

c. Vaksin
Masih dalam perkembangan p.falciparum 3jenis vaksin vaksin
sporozoit, vaksin asexual, vaksin transmission blocking untuk melawan
bentuk gamerosit.

PROGNOSIS

DEMAM TIPHOID
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DEFINISI
Typhoid fever is a systemic disease characterized by fever and abdominal pain and caused by dissemination of S. Typhi or S. Paratyphi. The
disease was initially called typhoid feverbecause of its clinical similarity
to typhus.

ETIOLOGI
the etiologic agents of enter-ic feverS. Typhi and S. Paratyphi
serotypes A, B, and Chave no known hosts other than humans. Most
commonly, food-borne or waterborne transmission results from fecal
contamination by ill or asymptomatic chronic carriers.
The incubation period for S. Typhi averages 1014 days but ranges from
3 to 21 days, with the duration likely reflecting the inoculum size and the
hosts health and immune status.
Bakteri ini berbentuk batang, gram negatip, tidak membentuk spora,
motil, berkapsul dan mempunyai flagella (bergerak dengan rambut getar).
Bakteri ini dapat hidup sampai beberapa minggu di alam bebas seperti di
dalam air, es, sampah dan debu. Bakteri ini dapat mati dengan pemanasan
(suhu 600C) selama 15 20 menit, pasteurisasi, pendidihan dan
khlorinisasi.

KLASIFIKASI

MANFEST
First week:
-

headache (80%)

chills (3545%),

cough (30%)

sweating (2025%)

myalgias (20%)

malaise (10%),

arthralgia (24%).

Gastrointestinal symptoms included

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anorexia (55%)

abdominal pain (3040%)

nausea (1824%)

vomiting (18%),

diarrhea (2228%) more commonly than constipation (1316%).

The most prominent symptom is prolonged fever (38.840.5C; 101.8

104.9F).
Sifat demam adalah meningkat perlahan-lahan dan terutama pada sore
hingga malam hari.
Physical findings included

hepatosplenomegaly (36%)

epistaxis

relative bradycardia at the peak of high fever

coated tongue (5156%),

abdominal tenderness (45%)

PATOGENESIS

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PATOFISIOLOGI

PENEGAKAN DIAGNOSIS
the clinical presentation of enteric fever is relatively nonspecific, the
diagnosis needs to be considered in any febrile traveler returning from a
developing country, especially the Indian subcontinent, the Philippines, or
Latin America. Other diagnoses that should be consid-ered in these
travelers include malaria, hepatitis, bacterial enteritis, dengue fever,
rickettsial infections, leptospirosis, amebic liver abscess-es, and acute
HIV infection.
Physical findings included:
-

hepatosplenomegaly (36%)

epistaxis

relative bradycardia at the peak of high fever

coated tongue (5156%),

abdominal tenderness (45%)

Px Lab
a. Pemeriksaan Rutin
Leucopenia, dapat leukosit normal atau leukositosis. Leukosotosis
dapat terjadi walaupun tanpa disertai infeksi sekunder. Selain itu
dapat pula ditemukan anemia ringan dan trombositopenia. Pada
pemeriksaan hitung jenis leukosit dapat terjadi aneosinofilia maupun
limfopenia. Laju endap darah pada demam tifoid dapat meningkat.
SGOT dan SSPT seringkali meningkat, tetapi akan kembali menjadi
meningkat setelah sembuh.
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b. Uji Widal
Uji widal adalah suatu reaksi aglutinasi antara antigen dan antibodi
(aglutinin). Aglutinin yang spesifik terhadap salmonella thypi terdapat
dalam serum klien dengan typhoid juga terdapat pada orang yang
pernah divaksinasikan. Antigen yang digunakan pada uji widal adalah
suspensi salmonella yang sudah dimatikan dan diolah di laboratorium.
Tujuan dari uji widal ini adalah untuk menentukan adanya aglutinin
dalam serum klien yang disangka menderita typhoid.

TERAPI
Sampai saat ini masih dianut trilogy penatalaksanaan demam tifoid, yaitu:
1. Istirahat dan Perawatan
Tujuannya adalah untuk mencegah komplikasi dan mempercepat
penyembuhan. Bed rest dianjurkan selama 7 hari atau sampai
demamnya hilang.
2. Diet dan Terapi Penunjang
Diet merupakan hal yang cukup penting dalam proses penyembuhan
penyakit demam tifoid, karena makanan yang kurang akan menurunkan
keadaan umum dan gizi penderita, sehingga proses penyembuhan akan
berlangsung lebih lama.
Di masa lampau penderita tifoid akan diberi diet BS-BB-NB, mula-mula
bubur saring, kemudian ditingkatkan menjadi bubur biasa, dan akhirnya
diberikan nasi, perubahan diet itu disesuaikan dengan tingkat
kesembuhan penderita. Pemberian bubur saring tersebut ditujukan
untuk menghindari komplikasi perdarahan saluran cerna dan perforasi
usus. Hal ini didasarkan pada pendapat bahwa usus harus
diistirahatkan. Beberapa peneliti menunjukkan bahwa pemberian
makanan padat dini yaitu nasi dengan lauk pauk rendah selulosa

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(menghindari sementara sayuran yang berserat) dapat diberikan

dengan aman pada pasien demam tifoid.
3. Pemberian Anti Mikroba
Pemberian anti mikroba dalam penanganan kasus demam tifoid
didasarkan pada berbagai pertimbangan. Obat-obat anti mikroba
yang sering digunakan untuk mengobati demam tifoid adalah
sebagai berikut:
a.

Kloramfenikol.
Kloramfenikol merupakan kristal putih yang sukar larut dalam
air dan rasanya sangat pahit.
Kloramfenikol bekerja dengan menghambat sintesis protein
kuman. Obat ini terikat pada ribosom subunit 50s dna
menghambat enzim peptidil transferase sehingga ikatan
peptide tidak terbentuk pada proses sintesis protein kuman.
Efek toksik kloramfenikol pada system hemopoietik sel mamalia
diduga berhubungan dengan mekanisme kerja obat ini.
Kloramfenikol
umumnya
bersifat
bakteriostatik.
Pada
konsentrasi tinggi kloramfenikol kadang-kadang bersifat
bakterisid bagi kuman-kuman tertentu.
Spektrum antimikroba kloramfenikol meliputi D. pneumonia,

S.pyogenes, S.viridans, Neisseria, Haemophilus, Bacillus spp,

Listeria, Bartonella, Brucella, P. multocida, C. diphteriae,
Clamidia, Mycoplasma, Rickettsia, Treponema, dan kebanyakan
kuman an aerob.

Setelah pemberian oral, kloramfenikol diserap dengan cepat.

Kadar puncak dalam darah tercapai dalam dua jam. Masa paruh
eliminasinya pada orang dewasa kurang lebih 3 jam. Kira-kira
50% kloramfenikol dalam darah berikatan dengan albumin.
Obat ini didistribusikan secara baik ke berbagai jaringan
tubuh, termasuk jaringan otak, cairan serebrospinal, dan mata.
Dalam waktu 24 jam, 80-90% kloramfenikol yang diberikan oral
telah diekskresikan melalui ginjal.
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Kloramfenikol dikontraindikasikan unutk neonates, pasien

dengan gangguan faal hati, dan pasien yang hipersensitif
terhadapnya.
Efek samping dari kloramfenikol terutama berupa reaksi
hematologik, reaksi saluran cerna, dan sindrom Gray.
Reaksi hematologik ini terdapat dalam dua bentuk. Yang
pertama ialah reaksi toksik dengan manifestasi depresi sumsum
tulang. Kelainan darah yang terlihat ialah anemia,
retikulositopenia, peningkatan serum iron dan iron binding
capacity serta vakuolisasi seri eritrosit bentuk muda. Bentuk
yang kedua adalah anemia aplastik.
Reaksi saluran cerna sebagai efek samping dari penggunaan
kloramfenikol bermanofestasi dalam bentuk mual, muntah,
glositis, diare, dan enterokolitis.
Pada neonates, terutama bayi premature yang mendapat dosis
tinggi (200mg/kgBB) dapat timbul sindrom Gray. Mula-mula
bayi muntah, tidak mau menyusu, pernafasan cepat dan tidak
teratur, perut kembung, sianosis dan diare dengan tinja
berwarna hijau dan bayi tampak sakit berat. Pada hari
berikutnya tubuh bayi menjadi lemas dan berwarna keabuabuan; terjadi pula hipotermia. Angka kematian kira-kira 40%,
sisanya sembuh sempurna.
Di Indonesia, kloramfenikol masih merupakan obat pilihan
pertama untuk mengobati demam tifoid. Dosis yang diberikan
adalah 4x 500 mg per hari dan dapat diberikan secara oral
maupun intravena. Diberikan sampai dengan 7 hari bebas panas.
Dari pengalaman penggunaan obat ini dapat menurunkan ratarata 7,2 hari. Penulis lain menyebutkan penurunan demam dapat
terjadi rata-rata setelah hari ke-5.
b. Tiamfenikol

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Rumus molekul tiamfenikol berbeda dengan kloramfenikol pada

rantai-R, dimana rantai-R pada kloramfenikol adalah NO2,
sedangkan rantai-R pada tiamfenikol adalah CH3SO2.
Tiamfenikol digunakan untuk indikasi yang sama dengan
kloramfenikol,. Selain itu dapat juga doberikan pada kasus
infeksi saluran empedu.
Efek samping yang timbul ialah depresi sumsum tulang yang
reversible dan berhubungan dengan dosis yang diberikan. Efek
samping lain yang sering dijumpai ialah depresi eritropoiesis,
leucopenia, trombositopenia, dan peningkatan kadar serum iron.
Dosis dan efektifitas tiamfenikol pada penderita demam tifoid
hampir sama dengan kloramfenikol, akan tetapi komplikasi
hematologik yang diakibatkan oleh tiamfenikol lebih rendah.
Demam rata-rata menurun pada hari ke-5 sampai ke-6.
c. Kotrimoksazol
Kotrimoksazol merupakan kombinasi antara sulfametoksazol
dengan trimetoprim.
Sulfametoksazol termasuk golongan sulfonamide. Sulfonamid
berbentuk kristal putih yang umumnya sukar larut dalam air.
Sulfonamid memiliki spectrum anti bakteri yang luas, meskipun
kurang kuat dibandingkan dengan antibiotic dan strain mikroba
yang resisten makin meningkat. Golongan obat ini umumnya
hanya bersifat bakteriostatik, namun pada kadar yang tinggi
dalam urin , sulfonamide dapat bersifat bakterisid.
Kuman memerlukan PABA (p-aminobenzoic acid) untuk
membentuk asam folat yang digunakan untuk sintesis purin dan
asam-asam nukleat. Sulfonamid merupakan penghambat
kompetitif PABA.
Dalam proses sintesis asam folat, bila PABA digantikan oleh
sulfonamide, maka akan terbentuk analog asam folat yang nonfungsional.
30 | P a g e

Trimetoprim dan sulfametoksazol (yang termasuk golongan

sulfonamide) menghambat reaksi enzimatik obligat pada dua
tahap yang berurutan pada mikroba, sehingga kombinasi kedua
obat member efek sinergi. Sulfonamid menghambat masuknya
molekul PABA ke dalam molekul asam folat dan trimetoprim
menghambat terjadinya reaksi reduksi dari dihidrofolat
menjadi tetrahidrofolat.
Pada dosis yang dianjurkan tidak terbukti bahwa kotrimoksazol
menimbulkan defisiensi folat pada orang normal. Namun batas
antara toksisitas untuk bakteri dan manusia relative sempit bila
sel tubuh mengalami defisiensi folat. Dalam keadaan demikian
obat ini mungkin menimbulkan megaloblastosis, leucopenia, atau
trombositopenia. Kira-kira 75% efek samping obat terjadi pada
kulit, berupa reaksi yang khas yang ditimbulkan oleh
sulfonamide. Gejala-gejala saluran cerna terutama berupa mual
dan muntah, diare jarang terjadi. Glositis dan stomatitis
relative sering. Reaksi susunan saraf pusat berupa sakit kepala,
depresi, dan halusinasi, disebabkan oleh sulfonamide.
Reaksi hematologik lainnya adalah berbagai macam anemia,
gangguan koagulasi, granulositopenia, agranulositosis, purpura,
purpura Henoch-Schonlein dan sulfehemoglobinemia.
Efektifitas kotrimoksazol pada demam tifoid dilaporkan hampir
sama dengan kloramfenikol. Dosis untuk orang dewasa adalah
2x2 tablet (1 tablet mengandung sulfametoksazol 400 mg dan
80 mg trimetoprim) diberikan selama dua minggu.
d. Ampisilin dan Amoksisilin
Ampisilin dan amoksisilin merupakan penisilin golongan spectrum
luas. Penisilin merupakan salah satu antibiotika beta laktam,
karena pada struktur kimianya terdapat cincin beta laktam.
Mekanisme kerjanya dengan menghambat sintesis mukopeptida
yang diperlukan untuk pembentukan dinding sel bakteri
(inhibitor sintesis dinding sel).

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Kemampuan kedua obat ini untuk menurunkan demam lebih

rendah dibandingkan dengan kloramfenikol. Dosis yang
dianjurkan berkisar antara 50-150 mg/kgBB dan digunakan
selama dua minggu.
e. Sefalosporin Generasi Ketiga
Sefalosporin dibagi menjadi 4 generasi berdasarkan aktifitas
anti mikrobanya yang secara tidak langsung juga sesuai dengan
urutan masa pembuatannya.
Seperti halnya antibiotic beta laktam lain, mekanisme kerja anti
mikroba sefalosporin ialah menghambat sintesis dinding sel
mikroba. Yang dihambat ialah reaksi transpeptidase tahap
ketiga dalam rangkaian reaksi pembentukan dinding sel.
Sefalosporin generasi ketiga umumnya kurang aktif
dibandingkan generasi pertama terhadap kokus gram-positif,
tetapi jauh lebih aktif terhadap Enterobacteriaceae, termasuk
strain penghasil penisilinase.
Efek samping yang sering terjadi dalam penggunaan
sefalosporin adalah reaksi alergi, dengan gejala yang mirip
dengan reaksi alergi yang ditimbulkan oleh penisilin. Reaksi
mendadak yaitu anafilaksis dengan spasme bronkus dan
urtikaria dapat terjadi. Reaksi coombs sering timbul pada
penggunaan sefalosporin dosis tinggi. Depresi sumsum tulang
terutama granulositopenia dapat timbul meskipun jarang.
Hingga saat ini golongan sefalosporin generasi ketiga yang
terbukti efektif untuk demam tifoid adalah seftriakson,
dengan dosis yang dianjurkan adalah 3-4 gram dalam dextrose
100cc diberikan selama jam perinfus sekali sehari, diberikan
selama 3 hingga 5 hari.
f. Fluoroquinolon
Merupakan golongan kuinolon yang memiliki atom fluor pada
posisi 6 dalam struktur molekulnya. Daya anti bakteri
fluorokuinolon jauh lebih kuat dibandingkan dengan kelompok
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kuinolon lama. Selain itu kelompok obat ini diserap dengan baik
pada pemberian oral, dan beberapa derivatnya juga tersedia
dalam bentuk parerental sehingga dapat digunakan untuk
penanggulangan infeksi berat, khusunya yang disebabkan oleh
kuman Gram-negatif.
Bentuk double-helix DNA harus dipisahkan menjadi dua rantai
DNA pada saat akan berlangsungnya replikasi dan transkripsi.
Pemisahan ini selalu akan mengakibatkan terjadinya puntiran
berlebihan (overwinding) pada double helix DNA sebelum titik
pisah. Hambatan mekanik ini dapat diatasi kuman dengan
bangtuan enzim DNA girase (topomeirase II) yang kerjanya
menimbulkan
negative supercoiling. Golongan kuinolon
menghambat kerja enzim DNA girase pada kuman dan bersifat
bakterisidal. Fluorokuinolon bekerja dengan mekanisme yang
sama dengan kelompok kuinolon terdahulu.
Beberapa efek samping yang dapat ditimbulkan akibat
pemakaian obat kuinolon dan fluorokuinolon antara lain efek
samping pada saluran cerna, susunan saraf pusat,
hepatotoksisitas, kardiotoksisitas, disglikemua, fototoksisitas,
dan lain sebagainya.
Beberapa obat golongan fluorokuinolon yang dapat digunakan
dalam pengobatan demam tifoid:
Norfloksasin. Dosis 2 x 400 mg/hari selama 14 hari
Siprofloksasin. Dosis 2 x 500 mg/hari selama 6 hari
Ofloksasin. Dosis 2 x 400 mg/ hari selama 7 hari
Perfloksasin. Dosis 400 mg/hari selama 7 hari
Fleroksasin. Dosis 400 mg/hari selama 7 hari.
Demam pada umumnya mengalami lisis pada hari ke-3 atau
menjelang hari ke-4.
g. Kombinasi Obat Antimikroba
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Kombinasi dua antibiotic atau lebih diindikasikan hanya pada

keadaan tertentu saja antara lain toksik tifoid, peritonitis atau
perforasi, serta syok septic, yang pernah terbukti ditemukan
dua macam organism dalam kultur darah selain kuman
Salmonella.
h. Kortikosteroid
Penggunaan steroid hanya diindikasikan pada toksik tifoid atau
demam tifoid yang mengalami syok septic dengan dosis 3 x 5
mg.

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