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COMMUNICABLE DSE :MALARIA DR. FORTUNO

DEFINITION STEPS OF LIFE CYCLE:

 Step 1: The mosquito takes a blood meal from an

 Disease caused by protozoan parasites called infective individual. Sporozoites (the sexual phase)
Plasmodium.
occurs in the gut of the mosquito.
 It is usually transmitted through the bite of an
 Step 2: preerythrocytic stage. Asexually reproduce can
infected female Anopheles mosquito.
 Malaria may also be transmitted through the be as many as 100,000 merozoites  rupture of
following: hepatic cell  attach to RBC (erythrocytic stage)
• Transfusing blood that is positive for malaria  Step 3: erythrocytic stage. Asexual stage. 1 merozoite
parasites infects 1 RBC  asexually reproduce then the RBC
• Sharing of IV needles (especially among IV bursts
drug users)  Step 4: not reproduce sexually in humans. The female
• Trans -placental (transfer of malaria parasites
and male gametocytes need to be sucked by the
from an infected mother to her unborn child)
mosquitoes
OVERVIEW  Step 5: oocyst release several sporozoites in the
abdomen
 Most important parasitic disease in humans globally.  Sexual reproduction occurs in mosquitoes (die mosquitoes
 Causes a heavy burden among tropical countries. mga bwisit )
 Poses a threat to non – endemic countries.
 Poses a danger to international and local travellers.
 Transmission of Culex us almost nil; Anopheles need large ETIOLOGY AND PATHOGENESIS
size of fresh water to survive  Human infection begins when a female anopheline mosquito
inoculatrs plasmodial sporozoites from its salivary gland
LIFECYCLE during a blood meal
 These motile forms of the malarial parasite are carried
rapidly via the bloodstream to the liver, where they invade
hepatic cells and begin asexual reproduction
 This amplification process is also known as intrahepatic or
preerythrocytic schizogony or merogony
 Swollen infected hepatic cell eventually burts discharging
motile merozoites into the bloodstream
 Merozoites invade the RBC and multiply within 48-72 hours
 When parasites reach density of 50/ul in the blood,
symptomatic stage begin
 P. vivax and ovale – portion of intrahepatic forms do not
divide immediately but remain dormant. This is the cause of
relapses. The dormant form is called hypnozoites
 Merozoites enter the RBC and become trophozoites.
 P. vivax0 receptor is Daffy group antigen Fya or Fyb.
 West Africans have FyFy phenotype – makes it resistant to P.
vivax malaria.
 During the early stage of intraerythryocytic development,
small “ring” of the different species s appear similar
 By the end of 48 intraerythrocytic stage (24 for knowlesi, 72
for malariae), the parasite has consumed two thirds of the
hemoglobin and is now called a schizont
 Multiple nuclear divsision have taken place (schizogony or
merogony) and the RBC then ruptures to release 6-30
merozoites, each can infect RBC
 the disease in humans is caused by direct effects of RBC
invasion and destruction by the asexual parasite and the
host’s reaction
***Definitive Host – it is where the sexual stage takes place  After a series of asexual cycles (p. falciparum), or
immediately after release from the liver (vivax, ovale,
Therefore, Mosquitoes – are the definitive host
malariae, knowlesi), some parasites develop into
gametocytes that can transmit the malaria
  Male and female gametocytes form zygote in the insect’s Plasmodium falciparum and Plasmodium vivax are the
midgut common species of malaria parasites in the Philippines
 Zygote then matures into ookinete which encyst in the gut where 70% of malaria cases are P. falciparum while 30% are
wall
P.Vivax cases.
 The resulting oocyst expans by asexual division untul it burts
to lierate sporozoites which then migrate to the hemolymph
 There are also P. malariae cases and contributes to
to the salivary gland of the insect
about< 1% of the total malaria cases.

 P. falciparum malaria, if not treated immediately, can

lead to severe malaria, such as cerebral malaria.
 P. vivax malaria does not lead to cerebral malaria but it
causes relapse if treatment was not completed.
 P. falciparum – in the Philippines; ovale – in Africas; Asia
– falciparum
 Incubation period P. falciparum (12 days); P. vivax (14
days) P. malariae (30 days)

Do all mosquitoes carry the malaria parasite?

 No, not all mosquitoes carry the malaria parasite.
 In the country, it is the adult female Anopheles
mosquito that can become infective and therefore
carries the malaria parasite after she bites a person
infected with malaria.
 The malaria parasite undergoes several
developmental stages inside the adult female
PLASMODIUM SPECIES mosquito until such time that the mosquito becomes
P. knowlesi infective with malaria parasites.
 This anopheles mosquito bites from dusk to dawn
 molecularly, entomologically, epidemiologically, data, (night biting) and it breeds in clear, slow flowing
indicate that human infection with P. knowlesia is not streams that are found in mountainous/forested
newly emergent areas or in brackish water where salt and fresh water
meet. This is usually found in coastal areas.
 primarily a zoonotic for reports of its emergence from
monkeys
EPIDEMIOLOGY
 isolated from Philippine macques ( maccaca fasciculus) in
 Endemicity is defined as palpable spleen rates in
1961
children 2 – 9 years old:Abdominal exam lang
 incriminated vector in Anopheles balabacerisis
 morphologically similar to P. falciparum and maybe
 < 10% - hypoendemic
mistake to be P. falciparum
 11-50% - mesoendemic
 PCR is of value in diagnosis because P.knowlesi infection  51 – 75% - hyperendemic (e.g. Cagayan,
Zambales, Rizal)
is easily misdiagnosed as less dangerous.
 > 75% - holoendemic (almost 100% has/had
OTHER NOTES FROM DOC malaria)
• Africa and New Guinea
 P. falciparum – has the shortest/ fastest hepatic phase; less
than a week  Species in the Philippines: flavisatrus, litoralis, maculatus,
 P. falciparum has the biggest release per hepatocyte mangyanus
 P. malariae has the longest duration of erythrocytic stage.
 P. falciparum – attacks ALL type of RBC PRINCIPAL DETERMINANTS ARE:
 P. malariae – attack senescent cells lang, that’s why benign  Biting habits
sya, mamamatay din naman yung mga senescent cells na yun  Density of the population
eh.  Longevity of the anopheline mosquito
 P. falciparum and P. knowlesi – sila lang may ring forms (kaya  The lifecycle that takes place inside the mosquito is
napagkakamalan) between 8 – 30 days.
 P. vivax and ovale – schuffer’s dots – the hypnozoital forms –  Low temperatures are not conducive for sporogony to
the cause for the relapse of infection because duration in
take place.
intrahepatic can be very long

 Stable transmission
What are the common species of malaria parasites in the
Philippines?
 Constant year round transmission. – regardless of weather but still
high incidence

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  By adulthood would have achieved full later.
immunity – disease of full immunity  Hypnozoite form – P. vivax and P. ovale.
 Unstable transmission  Parasite stays in the liver for months before
 Erratic transmission inducing initial infection.
 Usually in hypoendemic areas RBC CHANGES
 Full protective immunity is not acquired  Once inside the cell, it consumes and degrades
intracellular proteins (hemoglobin).
Who are at risk in getting malaria?  Alteration in RBC properties more irregular in shape and
 Children – because of immature immune system less deformable. (less deformability)- disease the
 Pregnant women- immunocompromised malleability
 Indigenous  P. falciparum – causes appearances of knobs on the cell
peoples
surface.
 Forest workers, miners,
soldiers  Mediates attachment to the capillary and
venular endothelium (cytoadherence). 
infected erythrocytes stick inside and eventually
Philippine and South East Asian Nations block capillaries and venules
 Rosette formation –infect of RBC adherence to
 P. falciparum, vivax, -responsible for new infections
uninfected RBC
 Agglutination – infect RBC adhere to other
parasitized RBC
 Cytoadherence, rosette, agglutination are
central to th pathogenesis of falciparum malaria,
the result in the equestration of RBC containing
mature forms of th parasite in vital rogans (esp.
brain) where they interfere with microciculatory
flow and metabolism
 Sequestered parasites: splenic processing and
filtration  only the younger ring forms of the
asexual parasites are seen in the circulation
 Other “benign” forms of malaria, sequestration
does not occur
 Very toxic to erythrocytic ->hemoglobin
 P. falciuparum- change internal nuclear 
degreade to Hb to heme or hemosiderin
 Falciparum prefer to survive in hemosiderin type
 After invading RBC, malarial parasite degrade
hemoglobin and is converted to inert hemozin
(malaria pigment)

 Persons who are not from a malaria endemic area but travel P. FALCIPARUM
to this area  Causes severe malaria.
 Creates a high level of parasitemia and sequestration
causing end organ damage.
Can a person get malaria by drinking water in the streams with
mosquito eggs?  Sequestration is a specific property.
 Sequestration only seen in falciparum
 You need the the midgut for sexual stage stage, for you
acquire it.  Usually seen in the smears are younger forms before
 No. The malaria parasite has to undergo development sequestration takes place.
inside the adult female mosquito; therefore one SEQUESTRATION
cannot get malaria from drinking water that has  Contribute to mental changes and coma.
mosquito eggs in it.  End organs affected are:
BASIS FOR CHEMOPROPHYLAXIS  CNS, lungs and kidneys.
 Each species has a specific incubation period. OTHER THINGS NOTED IN P. FALCIPARUM INFECTION:
 P. falciparum infection typically develops within a month
of exposure. Rare cases have been reported up to a year  Hypoglycemia – check the RBS; capillary falciparum not enough, take
blood in antecubtial for RBS
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  Lactic acidosis
 Severe anemia- CBC, ABG
RESPIRATORY SYMPTOMS
 Multi - organ dysfunction secondary to hypoxia.
 Metabolic acidosis leading to respiratory distress.
 Usually occurs in travelers without immunity or young
 Can develop pulmonary edema.
children living in endemic areas.
 ROSETTE FORMATION – infected RBCs may adhere to
INNATE IMMUNITY
uninfected RBC.
 Depends on the host’s immunity.  AGGLUTINATION – infected RBCs adhere to other
 P. falciparum usually results in death. parasitized RBCs.
 A combination of all these results in…
PROTECTIVE GENETIC FACTORS: Interfere with microcirculatory circulation and
 Sickle cell disease metabolism especially in the brain.
 Hemoglobinopathies
 Polymorphisms in the host’s Tumor Necrosis Factor PHYSICAL EXAMINATION
(TNF). Most patients will have splenomegaly.

HISTORY TAKING  Test for CBC, anemia, thrombocytopenia, MARF - adult

 Get a history of recent travel in those patients with tubular necrosis secondary to hypovolemia, ischemia,
high grade fever. intravascular coagulation
 Most patients will present with fever and (generalized)headache. Statistics
 There is no neck stiffness or photophobia  P. falciparum and P. vivax – responsible for most new
resembling meningitis. infections.
 Malarias in and near NCR: Fairview and
Antipolo DEMONSTRATION OF THE PARASITE
 Malaria free areas (Aklan, albay, batangas,  Must identify the asexual forms in the peripheral
Cavite) blood smear.
 Sickle cell disease  Negative smears do not rule out malaria if there is a
 Skin- chills –profuse sweating  release of NO high degree of suspicion. Repeat.  most erythrocytes
 Dry cough, splenomegaly , myalgia, Nausea and are sequestered
vomiting, orthostatic hypotension, headache, fever,  Use the Giemsa stains at pH – 7.2
fatigue, muscle pain, back pain  Thick blood smear provides better sensitivity.
P. VIVAX AND P. OVALE  Thin blood smear provides better specificity and
 Patient may relapse after long periods because of the allows better identification of the species involved.
hypnozoite stage in the liver.  Not so diagnostic in P. falciparum infections since
 Can remain dormant for months to years before sequestration removes the RBCs out of the peripheral
entering the blood stream to produce symptoms. circulation especially in the late stages.
 Causes the benign form of tertian fever (vivax, ovale)  Hypnozoital ) vivax and ovale)
 Diagnosis: visualization of blood smear
 (P. malariae causes the quartan fever – meaning fever o n  Thick and thin smears done 12 to 24 hours apart during
the 1st day, 2nd day and 3rd day no fever) the fever
 Falciparum – no pattern of fever • Before, blood collection is at the peak of fever, now as
long as it is febrile -> do thin and thick smear
MANIFESTATIONS Thick smear Thin smear
TYPICAL MANIFESTATIONS IN DIAGNOSING MALARIA: • More sensitive • Less sensitive
 Cerebral malaria – almost always due to P. falciparum than thin smears • Facilitate
infections. • Cant speciate speciation
• Parasitemia • Qualitative
 Coma lasts more than 30 minutes. can be calculated based test
 Fever (febrile) -> seizure -> coma cascade on the number of
 Severe anemia – usually associated with P. falciparum infected RBC
infections. • Quantitative
test
 May be secondary to RBC infection and a loss of
infected RBC.
 Uninfected RBCs are inappropriately cleared and bone marrow MALARIA SUSPECT:
suppression may also be involved.  Patients with malaria like illness
RENAL FAILURE  With thrombocytopenia
 Infected RBCs adhere to the microvasculature in the  Relative lymphopenia
renal cortex.  Atypical lymphocytes
 Oliguric renal failure. decrease blood sugar  Elevated LDH
 Usually reversible.  Anemia
 P. malariae can cause the nephrotic syndrome
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 TREATMENT
DIAGNOSIS  P. falciparum – resistant to chloroquine.
 Diagnosis of malaria rests on the demonstration of asexual forms of  P. vivax – not so resistant to chloroquine.
the parasite in stained peripheral blood smears  P. ovale and P. malariae – sensitive to chloroquine.
 Giemsa stain  Primaquine - needed to treat the hypnozoites (liver
 Thick film has advantage of concentrating the parasites and thus phase).
increasing diagnostic sensitivity Artesunate
 Both parasites and WBC are counted and the number of parasites per
unit volume is calculated from the total leukocyte count  IV anti – malarial now used in the US for severe complicated
 Before a thick smear is judged as negative, 100-200 fields should be malaria.
examined under oil immersion  Reduced mortality among children in African countries
 In high transmission areas, the presence up to 10,000 parasites /ul compared with quinine.
maybe tolerated without symptoms or signs in partially immune  Patients have less symptoms of coma, seizures, post –
individuals treatment hypoglycemia.
 Rapid simple sensitive and specific antibody based diagnostic stick  Water soluble derivative from artemisinin.
detect falciparum specific histidine rich protein 2 (pfHRP2) or lactate  Drug of choice for severe falciparum malaria.
dehydrogenase antigen  Recommendations for malaria treatment:
 Some of the rapid diagnostic test carry a second antibody which  P. falciparum malaria: Quinine plus doxycycline or
falciparum malaria to be distinguished from the less dangerous clindamycin or pyrimethamine – sulfadoxine.
malaria.  Alternative treatment: Artemether – lumefantrine, or
 PfHRP@ maybe positive for several weeks after acute infection, mefloquine
disadvantage in high transmission areas but is of value in the Artemisinin
diagnosis of severe malaria in patients who have taken antimalarial
drugs and cleared peripheral parasitemia  Approved in 2009.
 In general, >105 per ul is at risk of dying but non immune patients  Can not be used as monotherapy because of a high rate of
may die with much lower counts and partially immune patients may resistance.
tolerate higher parasitemia levels  Due to only a temporary stop in the growth of ring stage
 In severe malaria, poor prognosis is indicated by presence of parasites (dormant forms) after exposure to artemisinin.
dominance of more mature P. falciparum (>20% of parasites with Chloroquine phosphate
visible pigment) in the peripheral blood smear or by the presence of
phgocytosed malarial pigment in >5% of neutrophils  Can be used for prophylaxis and treatment.
 Drug of choice for chloroquine sensitive malaria.
 Aralen.
Quinine

 No role in prophylaxis
 Used with second agent in drug – resistant falciparum
infections.
Fansidar

 Pyrimethamine –sulfadoxine.
 Can also be used for treatment .
 Not anymore considered as a first line drug for prophylaxis
because of adverse drug reactions.

Chemoprophylaxis

 Doxycycline 100 mg daily for 2 – 3 days before going to an

endemic area, continue while in the endemic area and
continue for 4 more weeks after leaving the endemic area.
Primaquine

 Prevents drug resistant falciparum and vivax malaria in

adults
Alternative tests  Contraindicated in pregnant patients or new born babies
 Quantitative buffy coat – as sensitive as a thick smear but  (x) G6PD deficiency à hemolysis à death
must still do a thin smear.  testing ofr antibody
 (PfHRP2)Histidine rich protein - 2 ( the only approved
rapid test in the US. Protection
 Rapid diagnostic testing
 for epidiomolgical test  Reduce the frequency of mosquito bites.
 10 to 15mins  Avoid the mosquito’s peak feeding hours.
 Detect malarial parasite Ag in the blood  DEET and picaridin
 Insecticide impregnated mosquito nets.

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 dobutamine, epinephrine
UNCOMPLICATED MALARIA

 febrile, parasite in the blood, absence of severe malaria and

MDR
 Day 0 to 2 – Co Artem (artemisin + lumefantrin); taken after
fatty meals; Contraindicated in pregnant and lactating
 Day 3 – Primaquine
 Falciparum  gametocidal
 Vivax  hypnozoiticidal
 Discharge If asexual forms not seen in day 7 then
monitor once a week for 1 month
How to assess

 Day 0, 3,7 -> do blood smear, if parasite not seen in day 7

it means the patient is getting well. If still present, label as
treatment failure

P. malariae: Chloroquine on day 0, 1,2,3. Day 3: Primaquine

SEVERE MALARIA

 Dysfunction of the brain/lung/ kidney

 Seizures, impaired consciousness

TREATMENTS
 Philippines: Co Artem. If it fails, quinine plus tetracycline or
clindamcine or doxycycline
 WHO: parenteral or recal atemisin
 US FDA: don’t give Co Artem
 falciparum + either vivax or malariae : Coartem
(falciparum) + primaquine (vivax; not quinine because
benign lang naman siya)
P vivax

 Day 0 to 2: Chloroquine
 Day 3 to 17: Primaquine
 Treatment failure: falciparum malaria: quinine +
doxycycline, tetracycline or clindamycin
MALARIA SITUATION ON THE PHILIPPINES
TREATMENT UNDER SPECIAL CONDITIONS (pregnant) Malaria situation in the Philippines

Falciparum  Malaria is a rural disease

 oral quinine (insulin secreting drug – monitor  one of the important mosquito-borne diseases affecting
blood sugar) far-flung barangays of the countr
 Out of the 79 provinces nationwide, 57 are malaria
 Don’t give co artem
endemic
 Vivax: give chloroquine Malaria Control Program
 Treatment of severe falciparum
 tetracycline, doxycycline, clindamycin  Vision: malaria-free Philippines by 2020.
 SE: tetra ( yellow stain teeth), doxy (gastric Strategies:
irritation); Clinda (diarrhea)
SUPPORTIVE MANAGEMENT 1) Early diagnosis and prompt treatment;

 Cerebral malaria (unarousable coma not attributed to any 2) Vector control – insecticide-treated mosquito net as main
other cause and persist for >30mins)
vector control strategy, complemented by indoor residual
 Give air
spraying;
 Correct hyperpyrexia
 Control seizure
3) early management and disease surveillance;
 No mannitol, osmotic diuretics
 Pulmonary edema
4) monitoring and evaluation
 Hypoglycemia
 Circulation collapse : give dopamine,
Current Treatment Policy in the Philippines
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  Uncomplicated Plasmodium falciparum:

 Combination therapy of chloroquine and

sulfadoxine/pyrimethamine as the 1st line treatment
of uncomplicated P. falciparum.
 Artemisinin-based combination (Coartem®) is the 2nd
line treatment of uncomplicated P. falciparum and is
used if 1st line drugs are not available or if there is
treatment failure from 1st line drugs.
 Primaqine is given on the 4th day of treatment

 Treatment of severe P. falciparum

 combination therapy of quinine ampule/tablet
plus any of the following antibiotics:
Tetracycline, Doxycycline or Clindamycin.
 Plasmodium vivax treatment with Chloroquine
for 3 days and Primaquine for 14 days

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