1 بسم الله الرحمن الرحيم epidemiology & control of infectious diseases...

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بسم الله الرحمن الرحيمبسم الله الرحمن الرحيمEpidemiology & Epidemiology &

Control of Infectious diseasesControl of Infectious diseases

MalariaMalariaShahid Beheshti University of Shahid Beheshti University of

medical sciences, 2004medical sciences, 2004By: Hatami H. MD. MPHBy: Hatami H. MD. MPH

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Definition Definition History History

Etiology Etiology

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Definition of MalariaDefinition of Malaria

• Disease caused by Disease caused by a unicellular a unicellular protozoan protozoan PlasmodiumPlasmodium

• The The most importantmost important of the parasitic of the parasitic diseases of humansdiseases of humans

• Affecting Affecting > 1 billion> 1 billion people people

• Transmission in Transmission in 103 countries103 countries

• Causing Causing 1-3 million deaths1-3 million deaths each year each year

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World's Deadliest Scourges

• Acute Respiratory Infections

• Diarrheal Diseases

• Tuberculosis

• Hepatitis B

• Malaria

• Measles

• Neonatal Tetanus

• AIDS

– 4,300,000

– 3,200,000

– 3,000,000

– 1-2,000,000

– 1,000,000

– 880,000

– 600,000

– 550,000

Infectious disease Annual deaths

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History History

500_BC500_BC HippocratesHippocrates Clinical SymptomsClinical Symptoms

18801880 LaveranLaveran Blood StageBlood Stage

18981898 RossRoss Mosquito TransmissionMosquito Transmission

19481948 GarnhamGarnham Liver StageLiver Stage

Latin: “mal aria” Latin: “mal aria” = Bad air= Bad air association with swamp and association with swamp and

marshlandmarshland

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History History • Most importantMost important of all tropical diseases of all tropical diseases

((WHOWHO))– Vast Vast morbiditymorbidity and and mortalitymortality

– 40% of world population at 40% of world population at riskrisk of of infectioninfection

– 300-500 million 300-500 million casescases >90% in sub- >90% in sub-Saharan AfricaSaharan Africa

– At least 1 million At least 1 million deathsdeaths per year per year

– Mostly Mostly African childrenAfrican children (75%) (75%)

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• WWI WWI

– Almost 5,000 cases in Almost 5,000 cases in USUS Navy and Navy and MarinesMarines

– More than 100,000 cases in More than 100,000 cases in BritishBritish and and FrenchFrench soldiers soldiers

WWII

– 500,000 cases in US Army

– More than 110,000 cases in US Navy

History History

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Resurgence of Malaria Resurgence of Malaria

• EcologicalEcological change change

• Breakdown of Breakdown of controlcontrol activities activities

• PoliticalPolitical events events

• Population Population movementmovement

• MarginalMarginal populations populations

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Etiology Etiology

• Plasmodium protozoaPlasmodium protozoa– P. vivaxP. vivax

– P. ovaleP. ovale

– P. malariaeP. malariae

– P. falciparumP. falciparum

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Plasmodium life cycle Plasmodium life cycle •Two phasesTwo phases

Extrinsic phaseExtrinsic phase In In AnophelesAnopheles – sexual – – sexual – definitivedefinitive

hosthost

Intrinsic phaseIntrinsic phase

In human –asexual – In human –asexual – intermediateintermediate hosthost

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8-30 days

7-14 days

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Severity dependent upon: Severity dependent upon: • SpeciesSpecies• ParasitaemiaParasitaemia• Health statusHealth status• Immunity Immunity

Pathogenesis Pathogenesis

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Pathogenesis Pathogenesis Fever (Febrile paroxysm)Fever (Febrile paroxysm)

Many symptoms due Many symptoms due toto

– Erythrocyte break-down Erythrocyte break-down productsproducts

– parasite proteins parasite proteins

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3 stages (paroxysm)3 stages (paroxysm)

• Pattern of fever (paroxysm):Pattern of fever (paroxysm):– 1- Cold stage1- Cold stage (shivers) (shivers)

– 2- Hot stage2- Hot stage (flush, rapid pulse) (flush, rapid pulse) severe headachesevere headache

joint pains, vomiting, diarrhoeajoint pains, vomiting, diarrhoea

– 3- Sweating stage3- Sweating stageprofuse sweating decrease in profuse sweating decrease in

Temperature exhaustionTemperature exhaustion


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AnaemiaAnaemia• Haemolytic Haemolytic • Usually most severe in Usually most severe in P. falciparumP. falciparum

HepatosplenomegalyHepatosplenomegaly• Begins in early acute infectionBegins in early acute infection• Spleen may be very enlarged in chronic Spleen may be very enlarged in chronic

malaria after repeated infectionsmalaria after repeated infections

JaundiceJaundiceUsually Usually mildmild but may be but may be severesevere in in P. falciparumP. falciparum due to liver damage due to liver damage


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Abiotic and Biotic Factors Abiotic and Biotic Factors influencing malariainfluencing malaria

• AbioticAbiotic• Increased Increased temperaturetemperature• An increase in An increase in greenhousegreenhouse gases gases

• BioticBiotic• An increase in An increase in parasitesparasites• An increase in An increase in mosquitoesmosquitoes• Increase in human Increase in human populationpopulation

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Movement of

People

Human / Insect

Interactions

Population

Growth

Increased

Breeding

Sites

Increased

Temperature

Increased

Precipitation

Changes in

Land Use

Increase in

Resistance

Increase in

Mortality

Spread of

Malaria

Increase in the

Dispersion of

Mosquitoes and parasite

Increased Chance

of Susceptibility

Climate

Change

Factors influencing malariaFactors influencing malaria

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Descriptive Descriptive epidemiology epidemiology

and and

occurrenceoccurrence

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1 -Incubation Period1 -Incubation Period

Prepatent period Prepatent period (I.P of parasitemia)(I.P of parasitemia)

The time from infection to the The time from infection to the appearance of parasites in the appearance of parasites in the blood (blood (usually 7-10 days)usually 7-10 days)

Incubation periodIncubation periodThe time from infection to the The time from infection to the appearance of symptoms (14 days)appearance of symptoms (14 days)

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– P. falciparumP. falciparum 7-14 days7-14 days

– P. vivax 8-14 daysP. vivax 8-14 days

– P. ovale 8-14 daysP. ovale 8-14 days

– P. malariae 7-30 daysP. malariae 7-30 days

–By blood transfusion is shorter By blood transfusion is shorter

Incubation PeriodIncubation Period

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2- Natural course 2- Natural course • RelapseRelapse

– HypnozoitesHypnozoites - dormant phase in - dormant phase in P. vivaxP. vivax and and P. ovaleP. ovale

– RelapseRelapse - reactivation of the infection - reactivation of the infection via hypnozoitesvia hypnozoites

• RecrudescenceRecrudescence – Parasitaemia falls below detectable levels and then Parasitaemia falls below detectable levels and then

later increases to a patent parasitaemia (later increases to a patent parasitaemia (P. malariae)P. malariae)

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Natural course Natural course

P. vivaxP. vivax• If untreated, usually lasts for 2-3 If untreated, usually lasts for 2-3

months with months with diminishingdiminishing frequency and intensity of frequency and intensity of paroxysmsparoxysms

• 50% experience a 50% experience a relapserelapse in a few in a few weeks to 5 years after the initial weeks to 5 years after the initial illness.illness.

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P. ovaleP. ovale• SimilarSimilar to to P vivaxP vivax infections infections

• Are usually Are usually less severeless severe

• Often Often resolvesresolves without treatment. without treatment.

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P. malariaeP. malariae• AsymptomaticAsymptomatic for a much longer for a much longer

period of time period of time

• RecrudescenceRecrudescence is common is common

• It often is associated with a It often is associated with a nephroticnephrotic syndromesyndrome

• Possibly resulting from deposition of Possibly resulting from deposition of antibody-antigen complexantibody-antigen complex upon the upon the glomeruli.glomeruli.

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P. falciparumP. falciparum• The most The most malignantmalignant form of malaria form of malaria • Not limitedNot limited to RBCs of a particular age to RBCs of a particular age• The highest level of The highest level of parasitemiaparasitemia• Vascular obstructionVascular obstruction due to its ability to due to its ability to

adhere to endothelial cell wallsadhere to endothelial cell walls• CCerebralerebral malaria, malaria, pulmonarypulmonary edema, edema,

rapidly developing rapidly developing anemiaanemia, and , and renalrenal problems.problems.

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Natural course Natural course Classic paroxysm :Classic paroxysm :• Begins with shivering and chillsBegins with shivering and chills• Lasts 1-2 hoursLasts 1-2 hours• Followed by a high feverFollowed by a high fever Finally, Finally, • The patient experiences excessive The patient experiences excessive diaphoresisdiaphoresis• Body temperature drops to normal or Body temperature drops to normal or below normal.below normal.

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Natural course Natural course Classic paroxysm :Classic paroxysm :• Many patients may have Many patients may have several small fever spikes a dayseveral small fever spikes a day

• Maintain a Maintain a high index of suspicionhigh index of suspicion for for malaria in any patient exhibiting any malaria in any patient exhibiting any malarial malarial symptomssymptoms and having a and having a history of travel to endemic areas history of travel to endemic areas

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Natural course Natural course Classic paroxysm :Classic paroxysm :

Less common symptoms Less common symptoms include the following:include the following:• Anorexia and lethargyAnorexia and lethargy• Nausea and vomitingNausea and vomiting• DiarrheaDiarrhea• HeadacheHeadache

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Natural course Natural course PhysicalPhysical: :

•TachycardiaTachycardia• FeverFever• HypotensionHypotension• Signs of anemiaSigns of anemia• SplenomegalySplenomegaly

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Natural course Natural course Laboratory finding Laboratory finding

• Normochromic, normocytic Normochromic, normocytic anemiaanemia• WBCWBC count is normal but in count is normal but in severe malaria may be raisedsevere malaria may be raised• ESRESR and and CRPCRP are high are high • the the plateletplatelet count is reduced count is reduced

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40.6

55.5

3.9

0

10

20

30

40

50

60

1001-4500 4501-10500 10501-30000

Patients with malaria admitted Patients with malaria admitted in Sina hospital Kermanshahin Sina hospital Kermanshah

WBC countWBC count

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4/7-11/938%

12-HI62%


HEMOGLOBINEHEMOGLOBINE

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99.5 99

6355.8

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28.4 24 2414.412.5 10 8.7

2.4 1.90102030405060708090

100

feve

r

chill

s

head

ache

swea

ting

vom

iting

mya

lgia

ab . pain no

sea

cons

tipat

ion

blac

k ur

ine

diar

rhea

arth

ralg

ia

ches

t pai

n

epis

taxi

a


symptomssymptoms

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82.6

57.2

37.2

26 25 21.5

7.2 4.3 0.50102030405060708090

feve

r

sple

nom

egal

ia

tach

ypne

a

pale

ness

jund

ice

tach

ycar

dia

hepa

tom

egal

ia

herp

es l

.p . o . ed

ema


signssigns

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Complications Complications • Coma (Coma (cerebral malariacerebral malaria) ) • SeizuresSeizures• Renal failureRenal failure• Hemoglobinuria (Hemoglobinuria (blackwater feverblackwater fever) ) • Noncardiogenic pulmonary edema Noncardiogenic pulmonary edema • Profound hypoglycemiaProfound hypoglycemia• Lactic acidosisLactic acidosis• HemolysisHemolysis• Bleeding (Bleeding (coagulopathycoagulopathy))

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Complications / ComaComplications / Coma• Altered Altered mental statusmental status, or multiple , or multiple seizuresseizures with with P P falciparumfalciparum• Cerebral malaria is the Cerebral malaria is the most common causemost common cause of of deathdeath in malaria patients in malaria patients• If untreated, is If untreated, is lethallethal• Even with treatment, 15% of children and 20% Even with treatment, 15% of children and 20% of adults who develop cerebral malaria dieof adults who develop cerebral malaria die• The symptoms of cerebral malaria are The symptoms of cerebral malaria are similar to those of toxic encephalopathysimilar to those of toxic encephalopathy

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Complications of Complications of P. falciparumP. falciparum

OrganOrgan SymptomsSymptoms MisdiagnosisMisdiagnosis

Stomach & Stomach & intestinesintestines

Vomiting & Vomiting & diarrhoeadiarrhoea

Gastric flu, choleraGastric flu, cholera

BrainBrain Deliria, coma, Deliria, coma, convulsionsconvulsions

Encephalitis, Encephalitis, meningitismeningitis

Kidneys Kidneys Renal failure Renal failure haemoglobinuriahaemoglobinuria

NephritisNephritis

LiverLiver Jaundice & feverJaundice & fever HepatitisHepatitis

LungsLungs Pulmonary Pulmonary oedemaoedema

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Host immune Host immune responseresponse

• In high transmission areas In high transmission areas 5-6yr 5-6yr childchild immune to lethal disease, immune to lethal disease, AdultsAdults usually mild flu-like episodesusually mild flu-like episodes

• IgGIgG limits parasitaemia limits parasitaemia

• ButBut suppressed by suppressed by pregnancypregnancy, , severe illnesssevere illness, immunosuppressive , immunosuppressive drugsdrugs

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• Both Both humoralhumoral immunity and immunity and cellularcellular immunity are necessary immunity are necessary for protectionfor protection

• The The mechanismmechanism of each are of each are incompletely understoodincompletely understood

• Premunition ??Premunition ??

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• Sickle cellSickle cell– Glutamic acidGlutamic acid replaced by replaced by valisevalise in in

haemoglobin (Hb)haemoglobin (Hb)– Change in Hb conformation/Change in Hb conformation/reduced reduced

oxygen carryingoxygen carrying– HeterozygotesHeterozygotes - - 80-90% protection80-90% protection

against severe malariaagainst severe malaria– HomozygotesHomozygotes – usually die before 30yrs – usually die before 30yrs

Host immune response Host immune response Non-immune protectionNon-immune protection

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• ThalassemiaThalassemia– Defective synthesis of Hb chainsDefective synthesis of Hb chains

• Duffy blood group antigensDuffy blood group antigens– Fy/Fy (Duffy negative) Fy/Fy (Duffy negative) – Erythrocyte plasma membrane Erythrocyte plasma membrane

receptor not expressedreceptor not expressed– P. P. vivaxvivax cannot enter erythrocytes cannot enter erythrocytes– Resistance to lethal Resistance to lethal P. P. falciparumfalciparum

Non-immune protectionNon-immune protection

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• Malaria occurs in over Malaria occurs in over 103 countries103 countries and territoriesand territories

• Central and South Central and South AmericaAmerica, , HispaniaHispania (Haiti and Dominican (Haiti and Dominican Republic), Republic), AfricaAfrica, the , the Indian Indian subcontinentsubcontinent, , Southeast AsiaSoutheast Asia, and , and the the Middle East. Middle East.

3 - Geographical distribution3 - Geographical distribution

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Geographical distributionGeographical distribution

p. f

p. vp. v

p. Vp. f

p. Vp. f

p. Vp. f

p. m

p. o

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12260130

5288916

105223 1123290

2000000

4000000

6000000

8000000

10000000

12000000

14000000

Africa Asia Americas Oceanis

Geographical distributionGeographical distribution

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Parasitemia rate or palpable spleen Parasitemia rate or palpable spleen rates in children 2-9 years of age :rates in children 2-9 years of age :

• HypoendemicHypoendemic < 10% < 10%• Mesoendemic 11-50%Mesoendemic 11-50%• Hyperendemic 51-75%Hyperendemic 51-75%• Holoendemic > 75%Holoendemic > 75%

Endemicity Endemicity

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Malaria in IranMalaria in Iran

• Sistan-Baluchestan, Sistan-Baluchestan, • Fars, Fars, • Boshehr, Boshehr, • Khuzestan, Khuzestan, • Ilam, Ilam, • Lorestan, Lorestan, • Charmahal, and Bakhtiari; Charmahal, and Bakhtiari; • Kerman; Kerman; • Hormozgan. Hormozgan.

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• Strong malaria control programStrong malaria control program• There has been a decreasing trend in recent yearsThere has been a decreasing trend in recent years• 16% out of the total population live in non-16% out of the total population live in non-

malarious areasmalarious areas• 66% lived in areas freed from malaria66% lived in areas freed from malaria• 12% in areas with sporadic transmission Mostly 12% in areas with sporadic transmission Mostly

P.vivaxP.vivax, , • 6% in areas of continuous transmission with a 6% in areas of continuous transmission with a

high proportion of high proportion of P.falciparumP.falciparum..

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• During 1997, During 1997, 38,76638,766 were found to were found to be positivebe positive

• 22%22% were due to were due to P. falciparumP. falciparum

• 22 22 fatalitiesfatalities were reported. were reported.

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Malaria in Iran / RegionsMalaria in Iran / Regions1.Regions to the north of the Zagros range 1.Regions to the north of the Zagros range

• Annual Parasite Incidence (Annual Parasite Incidence (APIAPI) ) in this area was in this area was 0.140.14 per 1,000 in per 1,000 in 19971997

• About About 77%77% of the malaria cases of the malaria cases were were importedimported from abroad or the from abroad or the south eastern part of the countrysouth eastern part of the country

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Malaria in Iran / RegionsMalaria in Iran / Regions2.Regions to the south of the Zagros range2.Regions to the south of the Zagros range

• API was reported to be 0.18 per API was reported to be 0.18 per 1,0001,000

• 48%48% were classified as were classified as importedimported..

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Malaria in Iran / RegionsMalaria in Iran / Regions3.The south eastern corner of Iran3.The south eastern corner of Iran

• Consists of Consists of SistanSistan and and BuluchistanBuluchistan Province, Province, HormozganHormozgan Province and the Province and the tropical part of tropical part of KermanKerman Province Province

• A combined population of approximately A combined population of approximately 3 million3 million is considered to be a is considered to be a refractoryrefractory malaria regionmalaria region

• API was reported to be API was reported to be 8.74 per 1,0008.74 per 1,000 populationpopulation

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Malaria in Iran / RegionsMalaria in Iran / Regions3.The south eastern corner of Iran (2)3.The south eastern corner of Iran (2)

• It is It is more difficult to controlmore difficult to control than than elsewhere in Iranelsewhere in Iran

• DrugDrug resistance resistance of of P.falciparumP.falciparum

• Vector resistanceVector resistance to insecticides to insecticides

• ImportationImportation of malaria, mostly of malaria, mostly P.falciparumP.falciparum, from Afghanistan , from Afghanistan

and, to a lesser extent, Pakistan. and, to a lesser extent, Pakistan.

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4 - Timeline trend4 - Timeline trend

• PandemicsPandemics

• EpidemicsEpidemics

• OutbreaksOutbreaks

• SeasonalitySeasonality

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Seasonality Seasonality • Summer,Summer,

• Autumn,Autumn,

• SpringSpring

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Spring20%

Summer57%

Automn21%

winter2%

seasonal distribution of malaria, seasonal distribution of malaria, Kermanshah 1988-99Kermanshah 1988-99

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5 – Age,5 – Age, Gender, Gender,

Occupation,Occupation, Social conditions Social conditions

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• AgeAge: :

• All ages are affected by malariaAll ages are affected by malaria

• MortalityMortality is very high in children is very high in children younger than 5 yearsyounger than 5 years

• SexSex::

• Males and females are affected Males and females are affected equally. equally.

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25.1

74.9

0

20

40

60

80

Female Male

Sex distribution of malaria, Sex distribution of malaria, Kermanshah 1988-99Kermanshah 1988-99

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6- Predisposing factors / 6- Predisposing factors / Pregnancy Pregnancy

• Especially Especially primigravidprimigravid women women

• 10 times more likely to contract 10 times more likely to contract Severe malariaSevere malaria

• Pregnant women with Pregnant women with P. P. vivaxvivax & & falciparumfalciparum are at high risk for are at high risk for severe malariasevere malaria

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• Has a Has a shorter courseshorter course, often rapidly , often rapidly progressing to progressing to severesevere malaria malaria

• HypoglycemiaHypoglycemia, , seizuresseizures, severe , severe anemiaanemia, , and and sudden deathsudden death

• Much less likely to develop Much less likely to develop renalrenal failure, failure, pulmonary edemapulmonary edema, or , or jaundicejaundice

• Commonly Commonly recoverrecover from malaria, even from malaria, even severe malaria, much faster than adultssevere malaria, much faster than adults

Predisposing factors / Pediatrics Predisposing factors / Pediatrics

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7 – Susceptibility and Resistance7 – Susceptibility and Resistance

• Tolerance in highly endemic • Duffy negatives • Sickle cell trait

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8 – Secondary attack rate8 – Secondary attack rate

Period of Period of communicabilitycommunicability

•Untreated patients may be a Untreated patients may be a source of mosquito infection source of mosquito infection for :for :

•More the 3 years in malariaeMore the 3 years in malariae• 1-2 years in vivax1-2 years in vivax• 1 year in falciparum1 year in falciparum• The mosquito remains The mosquito remains

infective for lifeinfective for life

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9 - Transmission9 - Transmission

Transmission requires complex Transmission requires complex interaction between:interaction between:

Humans, Humans,

Mosquitoes, Mosquitoes,

Parasites, and Parasites, and

Local environmentLocal environment

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TransmissionTransmission• All 4 species are transmitted All 4 species are transmitted

through the through the bitebite of an infected of an infected female female AnophelesAnopheles

• Via a blood Via a blood transfusiontransfusion, , needleneedle stick injury, stick injury, sharingsharing of needles by of needles by infected drug addicts organ infected drug addicts organ transplantationtransplantation

• CongenitallyCongenitally between mother and between mother and fetus fetus

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TransmissionTransmission

• The mosquito must survive for The mosquito must survive for > 7 days > 7 days

• At temperature <16-18°C At temperature <16-18°C sporogony is not completed and sporogony is not completed and transmission does not occurtransmission does not occur

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Anopheles in Iran Anopheles in Iran • A. superpictusA. superpictus

• A. sacharoviA. sacharovi

• A. stephensi A. stephensi

• A. d’thaliA. d’thali

• A. fluviatilisA. fluviatilis

• A. maculipenisA. maculipenis

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Prevention Prevention andand

ControlControl

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Prevention and ControlPrevention and Control• Primary Prevention:Primary Prevention:

Prevention of disease in “well” Prevention of disease in “well” individualsindividuals

• Secondary Prevention:Secondary Prevention: Identification and intervention Identification and intervention

in early stages of diseasein early stages of disease

Tertiary Prevention:Tertiary Prevention: Prevention of further Prevention of further

deterioration, reduction in deterioration, reduction in complicationscomplications

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1 - Primary prevention 1 - Primary prevention

1)1) Personal protectionPersonal protection2)2) Chemoprophylaxis Chemoprophylaxis 3)3) VaccinationVaccination4)4) Vector controlVector control

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Primary prevention Primary prevention Personal protectionPersonal protection

• Avoidance of Avoidance of exposureexposure to to mosquitoes at their peak mosquitoes at their peak feeding timesfeeding times

• Use of insect Use of insect repellentsrepellents (DEET 10-35%)(DEET 10-35%)

• Use of Use of bed netsbed nets

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Anti malarial drugs

Drug UsageMefloquine

Atovaquone-proguanil

Doxycycline

Chloroquine

Used in areas where chloroquine resistant malaria has been reported

As alternative to mefloquine or doxycycline

As alternative to mefloquine or ato.-prog.

Used in areas where chloroquine resistant malaria has not been reported

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Primary prevention Primary prevention Chemoprophylaxis (1)Chemoprophylaxis (1)• Depends on knowledge of local Depends on knowledge of local

patterns of:patterns of:• Drug Drug sensitivitysensitivity & Resistance & Resistance• Likelihood of Likelihood of acquiringacquiring

malarial infectionmalarial infection

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• When there is uncertainty, drugs When there is uncertainty, drugs effective against resistant effective against resistant p. falciparum should be usedp. falciparum should be used

• Mefloquie Mefloquie • Atovaquone-proguanilAtovaquone-proguanil• Doxycycline Doxycycline • Primaquine Primaquine

• Chemoprophylaxis is never Chemoprophylaxis is never entirely reliableentirely reliable

Chemoprophylaxis (2) Chemoprophylaxis (2)

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Chemoprophylaxis (3) Chemoprophylaxis (3) Pregnant womenPregnant women

• If travelling to malarious areas If travelling to malarious areas should be should be warnedwarned

• In endemic areas they should In endemic areas they should receive receive prophylaxisprophylaxis : :

• ChloroquineChloroquine 300 mg weekly alone or with 300 mg weekly alone or with proguanilproguanil 200 mg daily) or . . .200 mg daily) or . . .

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Chemoprophylaxis (4) Chemoprophylaxis (4) Children Children

• Children borne to Children borne to non immune non immune mothersmothers in endemic areas in endemic areas

• Intermittent prophylaxisIntermittent prophylaxis

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Chemoprophylaxis (5) Chemoprophylaxis (5) Travelers Travelers

• Should start taking anti malarial drugs Should start taking anti malarial drugs at least at least 1 week before1 week before departure departure

• Should continue for Should continue for 4 weeks after4 weeks after has has left the endemic arealeft the endemic area

• If If atovaquone-proguanilatovaquone-proguanil or or primaquineprimaquine has been taken, only for has been taken, only for 1 week1 week after after departure departure

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Chemoprophylaxis (6) Chemoprophylaxis (6) Mefloquine Mefloquine

• 250250 mg weekly in adults mg weekly in adults • Is choice for much of the Is choice for much of the tropicstropics • Effective against Effective against MDRMDR f. malaria f. malaria• Well Well toleratedtolerated• Mild Mild nauseanausea, dizziness, . . . , dizziness, . . . • During pregnancy is uncertain During pregnancy is uncertain

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Chemoprophylaxis (7) Chemoprophylaxis (7) Atovaquone-proguanil Atovaquone-proguanil • 250/100250/100 mg once daily mg once daily• Very well Very well toleratedtolerated• Fewer adverseFewer adverse effects effects • Effective against all types of malaria Effective against all types of malaria • May be discontinued May be discontinued 1 week1 week after after

departuredeparture• Insufficient data on safety in Insufficient data on safety in pregnancypregnancy

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Chemoprophylaxis (8) Chemoprophylaxis (8) Doxycycline Doxycycline

• 100 mg daily100 mg daily• Effective alternative to mefloquine Effective alternative to mefloquine • Well tolerated Well tolerated • May cause May cause vulvovaginal thrushvulvovaginal thrush, ,

diarrhoeadiarrhoea, , photosensitivityphotosensitivity• Can not be used by Can not be used by childrenchildren < 8 years < 8 years• Can not be used by Can not be used by pregnantpregnant women women

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Chemoprophylaxis (9) Chemoprophylaxis (9) Chloroquine Chloroquine

• Drug of choice for drug-sensitive p. f. Drug of choice for drug-sensitive p. f. and the other human species and the other human species

• Resistant p. vivax in :Resistant p. vivax in :• Eastern AsiaEastern Asia• OceaniaOceania• Central and South AmericaCentral and South America

Resistant p. falciparum in :Resistant p. falciparum in :• Many parts of the worldMany parts of the world

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Chemoprophylaxis (10) Chemoprophylaxis (10) Chloroquine Chloroquine

• Safe in Safe in pregnancypregnancy • RetinopathyRetinopathy if for more than 5 years if for more than 5 years• AmodiaquineAmodiaquine is associated with a is associated with a

high risk of agranulocytosis high risk of agranulocytosis

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Chemoprophylaxis (11) Chemoprophylaxis (11) Primaquine Primaquine

• 30 mg30 mg daily daily• Effective in prevention of Effective in prevention of DR malariaDR malaria• Abdominal painAbdominal pain• Oxidant hemolysisOxidant hemolysis • Should not give to Should not give to G6PDDG6PDD persons persons• Should not give to Should not give to pregnantpregnant & & neonateneonate

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Current programmesCurrent programmes

• Roll Back Malaria global partnership (Roll Back Malaria global partnership (WHOWHO))• Mosquito breeding sites: Mosquito breeding sites: Draining, Draining,

insecticide against larvaeinsecticide against larvae• House spraying:House spraying: Newer insecticides Newer insecticides• Insecticide-treated bed netsInsecticide-treated bed nets: : AnophelesAnopheles

bite at nightbite at night• Chemotherapy:Chemotherapy: Artemisinin-based Artemisinin-based

combination therapies (ACTs)combination therapies (ACTs)• VaccinesVaccines: Poor results to date: Poor results to date

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2 - 2 - Secondary Prevention:Secondary Prevention:

IdentificationIdentification

AndAnd

interventionintervention

in early stages of in early stages of diseasedisease

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DiagnosisDiagnosis

• Blood smearsBlood smears – Most common methodMost common method– Giemsa stainGiemsa stain

SerodiagnosisSerodiagnosis Immune response for years after Immune response for years after

disappearance of the parasitedisappearance of the parasite Used mostly for returning western Used mostly for returning western

travellers.travellers.

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Specific treatmentSpecific treatment

P. vivax, P. ovale, P. malariae P. vivax, P. ovale, P. malariae and chloroquine-susceptible P. and chloroquine-susceptible P. falciparum :falciparum :

• 600 mg base chloroquine PO initially, 600 mg base chloroquine PO initially,

• followed by an additional 300 mg base followed by an additional 300 mg base 6 hr later, and again 6 hr later, and again

• On days 2 and 3 On days 2 and 3

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Chloroquine-resistant P. falciparum Chloroquine-resistant P. falciparum Drugs of choice Drugs of choice

QuinineQuinine sulfate 650 mg every 8 hr × 3–7 d sulfate 650 mg every 8 hr × 3–7 dplusplusDoxycyclineDoxycycline 100 mg bid × 7 d 100 mg bid × 7 dororQuinineQuinine followed by followed by FancidarFancidar, 3 tablets on , 3 tablets on the last day of quinine treatment the last day of quinine treatment

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Specific treatmentSpecific treatmentChloroquine-resistant P. falciparum Chloroquine-resistant P. falciparum AlternativesAlternativesQuinineQuinine followed by followed by clindamycinclindamycin 900 mg tid × 5 days 900 mg tid × 5 days

ororMefloquineMefloquine 1250 single dose 1250 single doseororHalofantrineHalofantrine 500 mg every 6 hr × 3 doses, repeat 1 500 mg every 6 hr × 3 doses, repeat 1 wk laterwk laterororAtovaquoneAtovaquone 1000 mg daily × 3 d plus proguanil 1000 mg daily × 3 d plus proguanil 400 mg daily × 3 d 400 mg daily × 3 d

89

Specific treatmentSpecific treatmentChloroquine-resistant P. falciparum Chloroquine-resistant P. falciparum AlternativesAlternativesoror

AtovaquoneAtovaquone 1000 mg daily × 3 d plus 1000 mg daily × 3 d plus doxycyclinedoxycycline 100 mg bid × 3 days100 mg bid × 3 days

oror

ArtesunateArtesunate 4 mg/kg daily × 3 d plus 4 mg/kg daily × 3 d plus mefloquinemefloquine 1250 single dose (750 mg followed 12 hr later by 1250 single dose (750 mg followed 12 hr later by 500 mg) 500 mg)

90


Parenteral regimensParenteral regimens• Quinidine gluconate 10 mg /kg loading Quinidine gluconate 10 mg /kg loading

dose (max 600 mg) in normal saline dose (max 600 mg) in normal saline infused slowly over 1–2 hr, followed by infused slowly over 1–2 hr, followed by

• Continuous infusion of 0.02 mg/kg/min Continuous infusion of 0.02 mg/kg/min until patient is able to begin oral until patient is able to begin oral treatment treatment

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OrOr

QuinineQuinine dihydrochloride 20 mg salt/kg dihydrochloride 20 mg salt/kg loading dose in 5% dextrose over 4 hr, loading dose in 5% dextrose over 4 hr, followed by 10 mg salt/kg over 2–4 hr followed by 10 mg salt/kg over 2–4 hr every 8 hr (max 1800 mg/d) until every 8 hr (max 1800 mg/d) until patient is able to begin oral treatment patient is able to begin oral treatment

ArtemetherArtemether 3.2 mg/kg intramuscularly, 3.2 mg/kg intramuscularly, then 1.6 mg/kg daily × 3 d then 1.6 mg/kg daily × 3 d

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Prevention of Relapse Due to Prevention of Relapse Due to P. Vivax or P. Ovale P. Vivax or P. Ovale

Primaquine phosphate 15.3 mg Primaquine phosphate 15.3 mg base per day PO for 14 daysbase per day PO for 14 days

oror

45 mg base per week × 8 wk 45 mg base per week × 8 wk

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Drug resistanceDrug resistance

• Particular to Particular to P. falciparumP. falciparum but spreading to other but spreading to other speciesspecies

• Resistance to Resistance to chloroquinechloroquine most widespread but also most widespread but also newer drugsnewer drugs

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Chloroquine-resistant P. falciparumChloroquine-sensitive malaria

Chloroquine-resistant Chloroquine-resistant P. falciparumP. falciparum, 1995, 1995

CDC

200 million clinical cases annually

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Artemisinin Artemisinin or Qinghaosu ("ching-how-soo")or Qinghaosu ("ching-how-soo")

• Active principal of Chinese medicinal Active principal of Chinese medicinal herb herb Artemisia annua. - Artemisia annua. - used to treat used to treat fevers in China for more than 1000 fevers in China for more than 1000 years.years.

– Terpinoid active anti-malarial Terpinoid active anti-malarial constituents isolated in 1971. constituents isolated in 1971.

- artesunate artemether and arteether- artesunate artemether and arteether

– Activated by parasite-digested haem – Activated by parasite-digested haem – free radical formed that kills free radical formed that kills PlasmodiumPlasmodium..

– Short half-life.Short half-life.

– Used in combination with other drugs. Used in combination with other drugs.

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3 - 3 - Tertiary Prevention:Tertiary Prevention:

• Treatment of complications Treatment of complications

97

Sources :

• Control of communicable diseases, 2000• Nicholas J. White, Joel G. Breman, Malaria and Babesiosis in Harrison’s principles of internal medicine, 16th ed. 2005• Mandell 2000• BSL 2014, Parasites and Pathogens of Man, Dr Ron Stanley• Nicole T. McCadie, The Impact of Global The Impact of Global Change on the Spread of MalariaChange on the Spread of Malaria

1 بسم الله الرحمن الرحيم epidemiology & control of infectious diseases...

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