MalariaH2012

Protozoan Disease

108 countries

3 billion people

1 million deaths each year

In the late twentieth : Eliminated

United States, Canada, Europe, Russia

Prevalence rose in many parts of the tropics

Resurgence

Increases in the drug resistance of the parasite

Insecticide resistance of its vectors

Human travel and migration

EtiologyFive species of the genus Plasmodium cause

nearly all malarial infections in humans.

Falciparum

Vivax

Ovale

Malariae

Knowlesi(in Southeast Asia—the monkey malaria parasite )

Almost all Deaths

Falciparum

Female Anopheline Mosquito Sporozoites

Liver

Asexual Reproduction

Single Sporozoite eventually 10,000 to >30,000 Daughter Merozoites

Liver cell eventually bursts

100 million parasites in the blood of an adult, the symptomatic stage of the infection begins

Vivax and Ovale

Intrahepatic forms

Dormant(Hypnozoites) for a period ranging from 3 weeks to a year or longer before reproduction

begins

Relapses

Duration of Erythrocytic Cycle (hours)

Falciparum 48 h

Vivax 48 h

Ovale 50 h

Malariae 72 h

Red Cell PreferenceFalciparum

Younger cells (but can invade cells of all ages)

Vivax

Reticulocytes and cells up to 2 weeks old

Ovale

Reticulocytes

Malariae

Older cells

Morphology

FalciparumUsually only ring forms; Banana-shaped gametocytes

VivaxIrregularly shaped large rings and trophozoites; enlarged

erythrocytes; Schüffner's dotsOvale

Infected erythrocytes, enlarged and oval with tufted ends; Schüffner's dots

MalariaeBand or rectangular forms of trophozoites common

Relapses

Vivax , Ovale :Yes

Falciparum , Malariae : No

Parasitemias of >2% are suggestive of Falciparum

infection

Vivax

Duffy blood-group antigen Fya or Fyb

Most West Africans and people with origins in that region carry the Duffy-

negative FyFy phenotype and are therefore resistant to P. vivax

Disease

Direct effects of RBC invasion and destruction by the asexual parasite and the host's reaction

Epidemiology

Falciparum predominates in Africa, New Guinea, and Hispaniola (i.e., the Dominican

Republic and Haiti)

Vivax is more common in Central America

Malariae is found in most endemic areas

Ovale is relatively unusual outside of Africa

Endemicity

Parasitemia rates or palpable-Spleen rates in children 2–9 years

Hypoendemic (<10%)

Mesoendemic (11–50%)

Hyperendemic (51–75%)

Holoendemic (>75%)

Holo- and Hyperendemic areas

(e.g., certain regions of tropical Africa or coastal New Guinea) where there is intense Falciparum

transmission, people may sustain more than one infectious mosquito bite per day and are

infected repeatedly throughout their lives

Morbidity and Mortality during early Childhood

Adulthood, most infections are Asymptomatic

Stable Transmission

Constant

Frequent

Year-round infection

Unstable Transmission

Transmission is low, Erratic, or Focal, full protective immunity is

not acquired, and symptomatic disease may occur at All Ages

Usually exists in Hypoendemic

An Epidemic

Changes in Environmental, Economic, or Social conditions, such as heavy rains or

migrations (usually of Refugees or Workers) from a nonmalarious region to an area of high transmission; a breakdown in malaria control

and prevention service

All Age Groups

Anophelines

>400 can transmit malaria, and the 40 considerably in their efficiency as malaria

vectors

Life cycle within the mosquito—from gametocyte ingestion to subsequent

inoculation (sporogony)—lasts 8–30 days

mosquito must survive for >7

Sporogony

Is not completed at cooler temperatures <16°C for P. vivax and < 21°C for

Falciparum;

transmission does not occur below

The most effective mosquito vectors

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

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.

Erythrocyte Changes

Consumes and degrades intracellular proteins

principally hemoglobin

Alters the RBC membrane by changing its transport properties, exposing cryptic surface antigens, and inserting new parasite-derived proteins. The RBC becomes more irregular

in shape, more antigenic, and less deformable.

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 Vivax,

Ovale, and Malariae show a marked predilection for either young RBCs (Vivax, Ovale) or old cells (Malariae) and produce a

level of parasitemia that is seldom >2%, Falciparum can invade erythrocytes of all ages and may be associated with very high

levels of parasitemia.

Host ResponseInitially, nonspecific defense mechanisms

Splenic immunologic and filtrative clearance

Removal of both parasitized and uninfected erythrocytes

Strain-specific immune response then controls the infection

Exposure to sufficient strains confers protection from high-level parasitemia and disease but not from

infection

Infection without illness ,asymptomatic parasitemia is common among adults and older children living in regions with stable and intense transmission (holo- or

hyperendemic areas).

Immunity is mainly specific for both the species and the strain of infecting malarial parasite. Both humoral

immunity and cellular immunity are necessary for protection

Passively transferred IgG from immune adults has been shown to reduce levels of

parasitemia in children; although parasitemia in very young infants can

occur, passive transfer of maternal antibody contributes to the relative (but not complete) protection of infants from severe malaria in the first months of life

Immunity to disease declines when a person lives outside an endemic area for several months or longer.

Parasites may persist in the blood for months (or, in the case of P.

malariae, for many years)

Temperatures of 40°C damage mature parasites

Tertian, every 2 days; Quartan, every 3 days) are seldom seen today

Geographic Distributions

Sickle Cell disease Hemoglobins C and E

Hereditary OvalocytosisThalassemias

G6PD (glucose-6-phosphate dehydrogenas edeficiency )

closely resemble that of falciparum malaria before the introduction of control measures. This similarity

suggests that these genetic disorders confer protection against death from falciparum

Clinical FeaturesFirst symptoms of malaria are nonspecific

Lack of a sense of well-being

Headache

Fatigue

Abdominal discomfort

Muscle aches

followed by Fever

similar to the symptoms of a minor viral illness

Headache

Chest pain

Abdominal pain

Arthralgia

Myalgia

Diarrhea

Common

Nausea

Vomiting

Orthostatic hypotension

Classic malarial paroxysms

Fever spikes

Chills and rigors

occur at regular intervals, are relatively unusual and suggest

infection with P. Vivax or P. Ovale

Fever

Irregular at first (that of falciparum

malaria may never become regular); the temperature of nonimmune

individuals and children often rises above 40°C in conjunction with

Tachycardia and sometimes Delirium.

Childhood Febrile Convulsions may occur with any of the

malarias, generalized seizures are specifically associated with

falciparum malaria

Physical Findings

Fever

Malaise

Mild Anemia

Palpable Spleen (in some cases)

Anemia

Common among young children living in areas with

stable transmission

Slight enlargement of the liver

Common, particularly among Young Children

Mild jaundice

Common among adults; it may develop in patients with

otherwise uncomplicated malaria and usually resolves over 1–3

weeks

Malaria is not associated with a rash

Petechial hemorrhages in the skin or mucous develop only rarely in severe falciparum

malaria

Severe Falciparum Malaria

Appropriately and promptly treated, uncomplicated falciparum malaria (i.e., the patient can swallow medicines and

food)

Mortality rate of 0.1%

Severe Falciparum MalariaCerebral malaria/convulsion

Acidemia/acidosisSevere normochromic, normocytic anemia

Renal failurePulmonary edema/adult respiratory distress

syndromeHypoglycemia

Hypotension/shockBleeding/disseminated intravascular coagulation

Hemoglobinuria

HypoglycemiaImportant and common complication of severe

malaria, is associated with a poor prognosis and is particularly problematic in Children

and Pregnant women.

Hepatic Gluconeogenesis

Increase in the consumption of glucose by both host and, to a much lesser extent, the

malaria parasites

Quinine ,Quinidine

JaundiceMild hemolytic jaundice is common in malaria

Severe jaundice is associated with P. falciparum; is more common among adults and results from:

Hemolysis

Hepatocyte injury

Cholestasis

Other

HIV/AIDS predisposes to more severe malaria in nonimmune individuals

Worsened by intestinal helminths, Hookworm in particular

Septicemia may complicate severe malaria, particularly in children(specifically

Salmonella bacteremia )

Aspiration Pneumonia

شایعتر ها بچه در

Anemia

Convulsions

Hypoglycemia

شایعتر بالغین در

Jaundice

Renal failure

Pulmonary edema

Pregnancy

Stable transmission area:

Mothers Asymptomatic

Falciparum malaria in primi- and secundigravid women is associated with Low

Birth Weight

Increased infant and childhood mortality

Maternal HIV infection predisposes newborns to congenital malarial

PregnancyUnstable Transmission

Mother:

High-level parasitemia

Anemia

Hypoglycemia

Acute pulmonary edema

Fetal distress, premature labor, and stillbirth or low birth weight are common

Pregnancy

Congenital malaria occurs in <5% of newborns

P. Vivax malaria in pregnancy is also associated with a reduction in birth weight

but, in contrast to the situation in falciparum malaria, this effect is more

pronounced in Multigravid

Transfusion Blood Transfusion

Needle-Stick Injury

IVDU

Organ Transplantation

Incubation period in these settings is often short because there is no preerythrocytic stage

Clinical features and management are the same as for naturally acquired infections.

Primaquine is unnecessary for transfusion-transmitted P. vivax and P. ovale infections.

Tropical Splenomegaly (Hyperreactive Malarial Splenomegaly)

Chronic or repeated

in some cases malarial parasites cannot be found in peripheral-blood smears

Massive Splenomegaly, Hepatomegaly

Hypergammaglobulinemia; normochromic, normocytic anemia

Antimalarial chemoprophylaxis; results usually good

Quartan Malarial Nephropathy

Chronic or repeated infections with P. Malariae (and possibly with other

malarial species

soluble immune-complex

Nephrotic Syndrome

Burkitt's Lymphoma

Strongly associated with Epstein-Barr virus

The prevalence of this childhood tumor is high in malarious areas of Africa.

Diagnosis

AsexualGiemsa (preferred)

Field's

Wright's

Leishman's stain

Both thin and thick

RDTs

Rapid, simple, sensitive, and specific antibody-based diagnostic stick or card tests that detect P.

falciparum–specific, in finger-prick blood samples are now being used widely in control programs

RDTs are replacing microscopy in many areas because of their simplicity and speed, but they are

relatively expensive and do not quantify parasitemia.

PCR

Antibody and PCR tests have NO role in the diagnosis of malaria except that PCR is increasingly

used for genotyping and speciation in mixed infections

Gametocytemia may persist for days or

weeks after clearance of asexual parasites

Phagocytosed malarial Pigment is sometimes seen inside peripheral-blood

Monocytes or Polymorphonuclear leukocytes and may provide a clue to

recent infection if malaria parasites are not detectable

Laboratory FindingsNormochromic, Normocytic Anemia is usual

WBC count is generally normal, although it may be raised in very severe infections

Monocytosis, Lymphopenia, and Eosinopenia, with reactive Lymphocytosis and Eosinophilia in the

weeks after the acute infection

ESR,CRP High

Severe infections may be accompanied by prolonged PT and partial thromboplastin times and

by more severe Thrombocytopenia

Treatment

Repeat blood smears

at least every 12–24 h for 2 days

Alternatively, a rapid antigen detection card or stick test

Any doubt about the resistance, it should be considered resistant

Antimalarial drug susceptibility testing can be performed but is

rarely available, has poor predictive value in an individual

case, and yields results too slowly to influence the choice of treatment

Chloroquine

Choice for the non-falciparum malarias

Vivax

Ovale

Malariae

Knowlesi

except in Indonesia and Papua New Guinea, where high levels of resistance in P. vivax are

prevalent.

Chloroquine-Sensitive

Vivax

Malariae

Ovale,

Knowlesi

Falciparuma

Chloroquine (10 mg of base/kg stat followed by 5 mg/kg at 12, 24, and 36 h or by

10 mg/kg at 24 h and 5 mg/kg at 48 h)

or

Amodiaquine (10–12 mg of base/kg qd for 3 days)

Radical Treatment Vivax or Ovale

Primaquine (0.5 mg of base/kg qd) should be given for

14 days to prevent relapse.

In mild G6PD deficiency, 0.75 mg of base/kg should be given once weekly for 6–8

weeks.

Not be given in severe G6PD deficiency

FalciparumArtesunatec (3 days)

+

Sulfadoxine/Pyrimethamine as a single dose

or

Artesunatec (3 days) +

Amodiaquine (3 days)

Multidrug-resistant Falciparum

Artemether-Lumefantrinec (bid for 3 days with food)

or

Artesunatec (3 days)

+

Mefloquine (3 days )

Second-line treatment/treatment of imported

Artesunatec (7 days) or Quinine (tid for 7 days)

plus 1 of the following 3:

1. Tetracycline (qid for 7 days)

2. Doxycycline (qd for 7 days)

3. Clindamycin (bid for 7 days)

or

Atovaquone-Proguanil (qd for 3 days with food)

Severe Falciparum Artesunatec (IV followed by at 12 and 24 h and then daily if necessary)

or, if unavailable, one of the following:

Artemetherc (IM followed by qd)

or

Quinine dihydrochloride (infused over 4 h, followed infused over 2–8 h q8h)

or

Quinidine (infused over 1–2 h, followed by houriwith electrocardiographic monitoring)

Very few areas now have chloroquine-sensitive P. falciparum

Tetracycline and Doxycycline should not be given to pregnant women or to children <8 years of age

Oral treatment should be substituted as soon as the patient recovers sufficiently to take fluids by mouth

WHO now recommends Artemisinin-based

combinations as first-line treatment for uncomplicated

Falciparum

Quinine, Quinidine

Common: Hypoglycemia

Chloroquine

Acute: Hypotensive shock (parenteral), cardiac arrhythmias, neuropsychiatric

reactions

Chronic: Retinopathy (cumulative dose, >100 g), skeletal and cardiac myopathy

Primaquine

Massive hemolysis in subjects with severe G6PD deficiency

Severe Malaria

Uncomplicated Malaria

…..If there is any doubt as to the identity of the

infecting malarial species, treatment for falciparum malaria should be given

Nonimmune patients receiving treatment ,daily parasite counts performed until the thick films are negative. If the level of parasitemia does not fall below 25% of the admission value in

48 h or if parasitemia has not cleared by 7 days (and adherence is assured), drug resistance is

likely and the regimen should be changed

Radical Treatment

Primaquine (0.5 mg of base/kg, adult dose) should be given daily for 14 days to patients

with P. vivax or P. ovale infections after laboratory tests for G6PD deficiency have

proved negative. If the patient has a mild variant of G6PD deficiency, primaquine can be given in a dose of 0.75 mg of base/kg (45 mg maximum)

once weekly for 6 weeks.

Radical Treatment

Pregnant women with vivax or ovale malaria should not be given

Primaquine but should receive suppressive prophylaxis with

Chloroquine (5 mg of base/kg per week) until delivery, after which radical treatment can be given.

ComplicationsAcute Renal Failure

Acute Pulmonary Edema (Acute Respiratory Distress Syndrome)

Hypoglycemia

Spontaneous Bleeding

Convulsions

Aspiration pneumonia

Bacterial Sepsis

Prevention

no safe, effective, long-lasting vaccine is likely to be available

for general use in the near future

Personal Protection Against Avoidance of exposure to mosquitoes at their peak

feeding times (usually dusk to dawn)

Insect repellents containing 10–35% DEET (or, if DEET is unacceptable, 7% Picaridin),

Suitable Clothing

Insecticide-impregnated bed nets or other materials. Widespread use of bed nets treated with residual

Pyrethroids reduces the incidence of malaria in areas where vectors bite indoors at night

Chemoprophylaxis

Chemoprophylaxis is never entirely reliable

Chloroquine phosphate

Atovaquone-Proguanil (Malarone)

Doxycycline

Mefloquine

است قديمي بسيار انگلي بيماري يك ماالريا بيماريدر مسيح ميالد از قبل سال هفتصد هزارو در كه

. نيز سقراط است شده ياد آن از ها چيني هاي نوشته . آن در است داده توضيح را بيماري اين خود آثار درمي هوائي و آب بد شرايط را بيماري علت زمان

( باتالق ( بد هواي ماالريا نام به دليل همين به دانستندبا . كه بودند قومي اولين باستان مصريان شد ناميده

كردند كنترل را بيماري راكد آبهاي كردن .خشك

نوبه تب به متناوب لرز و تب علت به قديم ايران دراست بوده معروف نيز . هم

فالسیپاروم پالسمودیومبدخیم یک سه ماالریای عامل

ویواکس پالسمودیومیکخوش سه ماالریای عامل

خیمماالریه پالسمودیوم

یک چهار ماالریای عاملاوال پالسمودیوم

اوال ماالریای عامل

:) لرز ) اول لرز مرحلهحتي كه است شديد بحدي

ميخورد . تكان هم بيمار تختخوابپوست انتهاي وخشكي كبودي

اين اختصاصات از پاها و دست . ولي نبضسريع است مرحله . است ممكن نيست پر چندان

و تهوع حالت سردرد دچار بيمار . مرحله اين شود Vاستفراغ معموال

طول 15 به يكساعت تا دقيقهانجامد .

كالسيك ماالریا حمله(Paroxysm)

91

كالسيك ماالریا حمله(Paroxysm)

:) تب ) دوم تب مرحله دچار بيمار لرز، قطع پسازتا . است ممكن تب مينمايد احساسحرارت و 41شدهآن با همراه و يابد افزايش باالتر يا سانتيگراد درجهتند، نبض ، پوست خشكي چشم، و صورت سرخي

. اين ميشود ديده استفراغ گاه و ،تهوع عطش سردرد،حدود .6تا 2مرحله انجامد مي طول به ساعت

92

سوم مرحله :) به تعریق) بيمار

تعريق دچار سرعت . تعريق ميگردد شديد

دستها و صورت از ابتدااز سپس و ميشود شروع

انجام بدن منافذ كليهبه كه روطميگيرد، ي

خيسو ملحفه و لباسها . اين ميشود مرطوبمعمول بطور تا 2مرحله

مي 4 بطول ساعتانجامد .

كالسيك ماالریا حمله(Paroxysm)

93

حمالت بين ماالریا عالئمو كم بيمار مرحله اين در

عادي حالت به بيشو و برگشته كار به ميل

. مينمايد عادي زندگي انجامپريده رنگ تاحدي بيماربنظر ناراحت و ضعيف

او . اشتهاي شده ميرسد كم. است

94

بدخيم ماالرياي عالئم

در ناتوانيو نشستنو ايستادندر ناتوانيو خوردنآشاميدن

استفراغ مكرر

رنگ تيره در ادرار مشكلتنفس

باالي ) ل ركتا باال 40تبباالي بغل زير يا و درجه

5/39)

و عروقي كالپسشوك

95

پیشگیری های روشماالریا

•: آنوفل الرو با مبارزهها – باتالق خشکاندنراکد – های آب کردن جارینفت – مثل کشها الرو از استفاده– : باکتری از استفاده بیولوژیک روشهای

خاص های ماهی و ها

96

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