MENINGITISMENINGITIS

OUTCOMEOUTCOME VARIABLEVARIABLE

Acute Acute BenignBenign Form of Viral Form of Viral

TOTO

Rapidly Rapidly FatalFatal Bacterial Meningitis Bacterial Meningitis

WITHWITH

Local Progressive mentalLocal Progressive mental

deteriorationdeterioration and death and death

Meningitis is an inflammatory Meningitis is an inflammatory disease of the leptomeningesdisease of the leptomeninges

Defined by an abnormal Defined by an abnormal number of white blood cells in number of white blood cells in the cerebrospinal fluid (CSF).the cerebrospinal fluid (CSF).

Bacterial meningitis can be Bacterial meningitis can be community-acquired or community-acquired or healthcare-associatedhealthcare-associated

MENINGITISMENINGITIS

The possible presence of bacterial The possible presence of bacterial meningitis is suggested by the meningitis is suggested by the symptoms :symptoms :

feverfever, , altered mental statusaltered mental status,,

headache, and headache, and nuchal rigiditynuchal rigidity..

virtually all patients (99 to 100 virtually all patients (99 to 100 percent) have at least one of the percent) have at least one of the classic triad .classic triad .

S pneumoniaeS pneumoniae A gram-positive cocci, A gram-positive cocci, It is the most common bacterial It is the most common bacterial

cause of meningitis, and cause of meningitis, and in meningitis associated with basilar in meningitis associated with basilar

skull fracture and CSF leak. skull fracture and CSF leak. It may be associated with other foci It may be associated with other foci

of infection, such as:of infection, such as:

pneumonia, sinusitis, or pneumonia, sinusitis, or endocarditis endocarditis

N meningitidesN meningitides

is a gram-negative diplococcus is a gram-negative diplococcus that is carried in the nasopharynx that is carried in the nasopharynx of otherwise healthy individuals. It of otherwise healthy individuals. It initiates invasion by penetrating initiates invasion by penetrating the airway epithelial surface. the airway epithelial surface.

Most sporadic cases (95-97%) are Most sporadic cases (95-97%) are caused by serogroups B, C, and Y, caused by serogroups B, C, and Y, while the A and C strains are while the A and C strains are observed in epidemics (< 3% of observed in epidemics (< 3% of cases). cases).

N meningitidesN meningitides

Currently, it is the leading cause Currently, it is the leading cause of bacterial meningitis in children of bacterial meningitis in children and young adults, accounting for and young adults, accounting for 59% of cases.59% of cases.

APPROACHAPPROACH TOTO PATIENTPATIENTWITH POSSIBLE MENINGITISWITH POSSIBLE MENINGITIS

I) I) Maintain diagnostic Maintain diagnostic VIGILANCEVIGILANCE

a.)a.) Suspect the diseases Suspect the diseases b.)b.) Look for classical features Look for classical features

1) Headache1) Headache

2) meningeal irritation….2) meningeal irritation….HOW?HOW?

3) Obtundation3) Obtundation

c.) Confirm or exclude the diagnosisc.) Confirm or exclude the diagnosis

CASE ICASE IA 12 year old Nigerian boy who has A 12 year old Nigerian boy who has

arrived to Riyadh 2 days prior to arrived to Riyadh 2 days prior to presentation - C/O severe headache & presentation - C/O severe headache & PhotophobiaPhotophobia??

How do you approach & manage him?How do you approach & manage him?

Presence of fever & neck stiffness.Presence of fever & neck stiffness. Neurological deficit & Fundus.Neurological deficit & Fundus. SkinSkin RASH RASH CSF examination:CSF examination: Contraindications:Contraindications:

ICP reported to increase risk of ICP reported to increase risk of herniationherniation

– Cellulitis at area of tapCellulitis at area of tap– Bleeding disorBleeding disor

Opening pressure: 260 mm H20 Opening pressure: 260 mm H20 & cloudy & cloudy

WBC: 1500/ ml. 96% WBC: 1500/ ml. 96% segmentedsegmented

Glucose:Glucose: 24mg / dl 24mg / dl Protein:Protein: 200 mg. 200 mg.

Gram stain Gram stain : :

Gram-negative , "diplococcal" Gram-negative , "diplococcal" arrangement of cells. Diagnosis ?arrangement of cells. Diagnosis ?

inflammatory cells and kidney-inflammatory cells and kidney-shaped, gram-negative diplococci shaped, gram-negative diplococci

EpidemiologyEpidemiology

Rates highest in infancy with Rates highest in infancy with second peak in adolescence second peak in adolescence

20% of cases occurs among 20% of cases occurs among adolescents and young adults adolescents and young adults ages 14–24 ages 14–24

Nost are sporadic cases (97%); Nost are sporadic cases (97%); Minority is associated with Minority is associated with

outbreaks (3%) outbreaks (3%) Disease is seasonal, with cases Disease is seasonal, with cases

peaking in December and January. peaking in December and January.

PREVENTIONPREVENTION ::CHEMOPROPHYLAXISCHEMOPROPHYLAXIS

Neiseria meningitidisNeiseria meningitidis Eradication of Eradication of

nasopharyngeal carriagenasopharyngeal carriage..(post exposure ) for :..(post exposure ) for :

1)house hold contact1)house hold contact 2)Treating doctor who has 2)Treating doctor who has

examined patient very closelyexamined patient very closely

Drug for prophylaxis : Drug for prophylaxis :

Penicillin does not reliably Penicillin does not reliably eliminate nasopharyngeal carriage eliminate nasopharyngeal carriage of meningococci. of meningococci. Rifampicin , ceftriaxone or Rifampicin , ceftriaxone or ciprofloxacin is used for prophylaxis ciprofloxacin is used for prophylaxis in contacts to prevent further in contacts to prevent further infection.infection.

Drug of choice :Drug of choice :

Rifampicin 600 BID FOR 2 days. Rifampicin 600 BID FOR 2 days. Ciprofloxacin 500mg stat . Ciprofloxacin 500mg stat . Ceftriaxon 125mg I.M stat . Ceftriaxon 125mg I.M stat .

Prevention : Prevention :

Meningococcal Conjugate Vaccine Meningococcal Conjugate Vaccine (MCV4)(MCV4)

A. Covers Serogroups A, C, Y and W-135 A. Covers Serogroups A, C, Y and W-135

B. B. There are two meningococcal There are two meningococcal vaccines vaccines available :available :

Meningococcal polysaccharide vaccine Meningococcal polysaccharide vaccine (MPSV4) ..1981 (MPSV4) ..1981

Meningococcal conjugate vaccine (MCV4) ..Meningococcal conjugate vaccine (MCV4) ..

CASE 2CASE 2A 26 YEAR OLD Saudi female who A 26 YEAR OLD Saudi female who has been C / O unwell & fever & has been C / O unwell & fever & cough and headache for the last 3 cough and headache for the last 3 days. Examination revealed ill – days. Examination revealed ill – looking women with sign of looking women with sign of consolidation consolidation R R Lung base.Lung base.

DIAGNOSISDIAGNOSIS::

Bacteria Pneumonia.Bacteria Pneumonia.

Organism?Organism?

Six (6) hours after admission, her Six (6) hours after admission, her headache became worse and she headache became worse and she became obstunded.became obstunded.

DIAGNOSIS:DIAGNOSIS: ?? MENINGITIS MENINGITIS CSF:CSF: WBC:WBC: 30003000 99% 99%

DMLDML Sugar:Sugar: ZeroZero Protein:Protein: 260 mg/dl. 260 mg/dl. Gram Stain: Gram Stain: Gram +Gram + DIAGNOSIS:DIAGNOSIS: Bacterial…..?Bacterial…..?

inflammatory cells and gram-positive inflammatory cells and gram-positive diplococci. Streptococcus pneumoniae diplococci. Streptococcus pneumoniae grew from this specimen. grew from this specimen.

Epidemiological Features ofEpidemiological Features ofPneumococcal meningitisPneumococcal meningitis

The most common.The most common. CauseCause

The most killing. The most killing. 20 - 30 % 20 - 30 % DEATHDEATH

May be associated with other May be associated with other Focus:Focus:

a.a. PneumoniaPneumonia 25%25%

b.Otitis Media b.Otitis Media 30%30% c.c. SinusitisSinusitis 15 %15 % d. Head Trauma & CSF Leakd. Head Trauma & CSF Leak

10%10%.. E. splenectoy and SS disease..E. splenectoy and SS disease.. Global emergence of Penicillin – Global emergence of Penicillin –

Resistant.Resistant.

HistoryHistory Serious drug allergies Serious drug allergies Recent exposure to someone with Recent exposure to someone with

meningitis meningitis A recent infection (especially A recent infection (especially

respiratory or ear infection) respiratory or ear infection) Recent use of antibiotics Recent use of antibiotics Recent travel, particularly to areas Recent travel, particularly to areas

with endemic meningococcal with endemic meningococcal disease such as sub-Saharan Africadisease such as sub-Saharan Africa

Diagnostic tests Diagnostic tests

complete blood count with complete blood count with differential, and two sets of blood differential, and two sets of blood cultures, which are positive in 50 to cultures, which are positive in 50 to 90 percent of adults with bacterial 90 percent of adults with bacterial meningitis meningitis

lumbar puncture to determine lumbar puncture to determine whether the cerebrospinal fluid (CSF) whether the cerebrospinal fluid (CSF) findings are consistent with the findings are consistent with the diagnosis diagnosis

A history of injection drug useA history of injection drug use A progressive petechial or A progressive petechial or

ecchymotic rash, which would be ecchymotic rash, which would be most suggestive of meningococcal most suggestive of meningococcal infectioninfection

A history of recent or remote head A history of recent or remote head traumatrauma

Otorrhea or rhinorrheaOtorrhea or rhinorrhea

Management Algorithm for Management Algorithm for AdultsAdultsSuspicion of bacterial

meningitisYES

new onset seizure, papilledema, altered level of consciousness, or focal neurological deficit or delay in performance of diagnostic L.P

NO YESBlood c/s & Lumbar

punctureB/C stat

Dexamethasone + empirical Abx

Dexamethasone + empirical Abx

-ve CT-scan of the headCSF is abnormal

NO YES

YESPerform L.P+ve CSF gram stain

Dexamethasone + empirical Abx

Dexamethasone + targeted Abx

CSF should be sent for CSF should be sent for cell count and differential, cell count and differential, glucose and protein glucose and protein

concentrations, concentrations, Gram stain, and culture.Gram stain, and culture.

Characteristic findings in bacterial Characteristic findings in bacterial meningitis :meningitis :

a white blood cell count above a white blood cell count above 1000/microL, usually composed 1000/microL, usually composed primarily of neutrophils primarily of neutrophils

glucose concentration <45 mg/dL, a glucose concentration <45 mg/dL, a CSF to serum glucose ratio of <0.4, CSF to serum glucose ratio of <0.4, protein concentration of 100 to 500 protein concentration of 100 to 500 mg/dL, andmg/dL, and

GENERAL PRINCIPLES OF THERAPY GENERAL PRINCIPLES OF THERAPY Avoidance of delay Avoidance of delay Causes of delay :Causes of delay : Atypical presentation :Atypical presentation :

The most dramatic clinical predictor of The most dramatic clinical predictor of death was the absence of fever at death was the absence of fever at presentation .presentation .

Delay due to imaging Delay due to imaging

performance of a computed performance of a computed tomography (CT) scan of the head tomography (CT) scan of the head to exclude an occult mass lesion to exclude an occult mass lesion that could lead to cerebral that could lead to cerebral herniation during subsequent CSF herniation during subsequent CSF removal removal

a screening CT scan of the head a screening CT scan of the head is NOT necessary in the majority is NOT necessary in the majority of patients.of patients.

Two large series, 3 to 5 percent of Two large series, 3 to 5 percent of patients had a finding that was a patients had a finding that was a contraindication to LP .contraindication to LP .

Arch Intern Med. 1999;159(22):2681Arch Intern Med. 1999;159(22):2681 N Engl J Med. 2001;345(24):1727N Engl J Med. 2001;345(24):1727

Risk factors Risk factors

Immunocompromised stateImmunocompromised state Seizure within the previous weekSeizure within the previous week Certain findings on neurologic Certain findings on neurologic

examination: examination: Reduced level of consciousness,Reduced level of consciousness, Focal motor or Focal motor or Cranial abnormalities, and Cranial abnormalities, and PapilledemaPapilledema

Antibiotic regimen :Antibiotic regimen :• • Bactericidal drugs effective against the Bactericidal drugs effective against the

infecting organisminfecting organism

• • Drugs that enter the CSF, since the blood-Drugs that enter the CSF, since the blood-brain barrier prevents macromolecule entry brain barrier prevents macromolecule entry into the CSFinto the CSF

• • Structuring the regimen to optimize Structuring the regimen to optimize bactericidal efficacy based on the bactericidal efficacy based on the pharmacodynamic characteristics of the pharmacodynamic characteristics of the antimicrobial agentantimicrobial agent

WHAT DETERMINE THE WHAT DETERMINE THE OUTCOME?OUTCOME?

1.1. Etiological organismEtiological organism

2.2. Speed and appropriation of the Speed and appropriation of the therapy.therapy.

MORTALITYMORTALITY

Bacterial Meningitis Bacterial Meningitis :: 40 % 40 %

Choice of regimen —Choice of regimen — Antibiotic selection must be empiric Antibiotic selection must be empiric

immediately after CSF is obtained or immediately after CSF is obtained or IF lumbar puncture is delayed: In such IF lumbar puncture is delayed: In such

patients, antibiotic therapy needs to be patients, antibiotic therapy needs to be directed at the most likely bacteria based directed at the most likely bacteria based upon patient age and underlying comorbid upon patient age and underlying comorbid disease (table 2A-B) [3]. Knowledge of local disease (table 2A-B) [3]. Knowledge of local susceptibility patterns also may be importantsusceptibility patterns also may be important

2-50 years 2-50 years

N. meningitidis, S. pneumoniae.N. meningitidis, S. pneumoniae.

Vancomycin plus a third-generation Vancomycin plus a third-generation cephalosporin.cephalosporin.

>50 years >50 years S. pneumoniae, N. meningitidis, L. S. pneumoniae, N. meningitidis, L.

monocytogenes, aerobic gram-negative bacilli.monocytogenes, aerobic gram-negative bacilli.

Vancomycin plus ampicillin plus a third-Vancomycin plus ampicillin plus a third-generation cephalosporingeneration cephalosporin

Adjunctive dexamethasone ;Adjunctive dexamethasone ; ••Dexamethasone significantly Dexamethasone significantly

reduced both mortality reduced both mortality and all unfavorable outcomes ;and all unfavorable outcomes ;

TreatmentTreatment

Bacterial meningitis is a medical Bacterial meningitis is a medical emergency.emergency.

immediate steps must be taken to : immediate steps must be taken to : 1.Establish the specific cause 1.Establish the specific cause and and

2.Initiate effective therapy. 2.Initiate effective therapy. The mortality rate of untreated The mortality rate of untreated disease approaches 100 percent and, disease approaches 100 percent and, even with optimal therapy, there is even with optimal therapy, there is a high failure ratea high failure rate

MALARIAMALARIAFebrile illness caused by Febrile illness caused by

PlasmodiumPlasmodium..200 – 300,000,000 cases.200 – 300,000,000 cases.

700,000---2.7,000,000 death/year700,000---2.7,000,000 death/year more in rural area..more in rural area.. more during rainy seasonmore during rainy season

Human Human ---- --------- ----- Another Another

MosquitoMosquito

TransmissionTransmission

BITE OF FEMALE ANOPHELESBITE OF FEMALE ANOPHELES BETWEEN DUSK AND DAWNBETWEEN DUSK AND DAWN BLOOD TRANSFUSIONBLOOD TRANSFUSION CONTAMINATED NEEDLESCONTAMINATED NEEDLES CONGENITAL.CONGENITAL.

ETIOLOGYETIOLOGY Four species. Four species.

Death is mostly due to ..? Death is mostly due to ..?

SYPMTOMSSYPMTOMS------ Non-specific Non-specific

Headache & Headache & fatigue & fatigue &

muscle painmuscle pain

FeverFeverDXDX:: Viral infection..? Viral infection..?

The clinical manifestations of malaria The clinical manifestations of malaria vary with vary with

geography, epidemiology, immunity, geography, epidemiology, immunity, and ageand age

Groups at highest risk include Groups at highest risk include young children (6 to 36 months), who young children (6 to 36 months), who

can develop severe illness, and can develop severe illness, and pregnant women, who are at risk for pregnant women, who are at risk for

delivering low birth weight newbornsdelivering low birth weight newborns

older children and adults develop older children and adults develop partial immunity after repeated partial immunity after repeated infections and are at relatively infections and are at relatively low risk for severe diseaselow risk for severe disease

Travelers to malarious areas generally Travelers to malarious areas generally have had have had

1) No previous exposure to malaria 1) No previous exposure to malaria parasites orparasites or

2) have lost their immunity if they left 2) have lost their immunity if they left the endemic area;the endemic area;

They are at very high risk for severe They are at very high risk for severe disease if infected with Plasmodium disease if infected with Plasmodium falciparum falciparum

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS Uncomplicated malaria (0.1 Uncomplicated malaria (0.1

percent parasitized RBCs)percent parasitized RBCs)

Malaria should be suspected in Malaria should be suspected in patients with any febrile illness if patients with any febrile illness if they have had exposure to a they have had exposure to a region where malaria is endemic .region where malaria is endemic .

Nonspecific symptomes: Nonspecific symptomes:

chills, malaise, fatigue, diaphoresis, chills, malaise, fatigue, diaphoresis, headache, cough, anorexia, nausea, headache, cough, anorexia, nausea, vomiting, abdominal pain, diarrhea, vomiting, abdominal pain, diarrhea, arthralgias, and myalgias .arthralgias, and myalgias .

Physical exam :Physical exam :

anemia and a palpable spleenanemia and a palpable spleen

Laboratory evaluation may Laboratory evaluation may demonstrate: parasitemia demonstrate: parasitemia (usually <5000 parasites/microL (usually <5000 parasites/microL of blood, <0.1 percent parasitized of blood, <0.1 percent parasitized RBCs), anemia, RBCs), anemia, thrombocytopenia, elevated thrombocytopenia, elevated transaminasestransaminases

Complicated malaria Complicated malaria Patients with complicated or severe Patients with complicated or severe

malaria may have hyperparasitemia (≥5 malaria may have hyperparasitemia (≥5 to 10 percent of parasitized RBCs)to 10 percent of parasitized RBCs)

The clinical findings are the result of the The clinical findings are the result of the parasitized (and non-parasitized) RBCs parasitized (and non-parasitized) RBCs adhering to small blood vessels adhering to small blood vessels ("cytoadherence") causing small ("cytoadherence") causing small infarcts, capillary leakage, and organ infarcts, capillary leakage, and organ dysfunctiondysfunction

••Altered consciousness with or without seizuresAltered consciousness with or without seizures ••Respiratory distress or acute respiratory distress Respiratory distress or acute respiratory distress

syndrome (ARDS)syndrome (ARDS) ••Circulatory collapseCirculatory collapse ••Metabolic acidosisMetabolic acidosis ••Renal failure, hemoglobinuria ("blackwater fever")Renal failure, hemoglobinuria ("blackwater fever") ••Hepatic failureHepatic failure ••Coagulopathy with or without disseminated Coagulopathy with or without disseminated

intravascular coagulationintravascular coagulation ••Severe anemia or massive intravascular hemolysisSevere anemia or massive intravascular hemolysis ••HypoglycemiaHypoglycemia

Cerebral malaria — Cerebral malaria — Cerebral malaria is an Cerebral malaria is an

encephalopathy that presents with encephalopathy that presents with impaired consciousness, delirium, impaired consciousness, delirium, and/or seizures.and/or seizures.

cerebral malaria can progress cerebral malaria can progress rapidly to coma and death.100%rapidly to coma and death.100%

mortality is 15 to 20 percent mortality is 15 to 20 percent

PREGNANCYPREGNANCY In areas of low unstable In areas of low unstable

transmission are prone to severe transmission are prone to severe infection; they are vulnerable to infection; they are vulnerable to high-level parasitemia with high-level parasitemia with anemia, hypoglycemia, and acute anemia, hypoglycemia, and acute pulmonary edemapulmonary edema

Clinical Features:Clinical Features: Symptoms:Symptoms: 7 – 10 days7 – 10 days

Malaria Malaria Paroxysms.Paroxysms.Cold Cold Chills & Rigor & cold skinChills & Rigor & cold skin

HotHot Fever, warm skin Fever, warm skin

3-63-6hourshours deprevescencedeprevescence Marked Marked

sweating sweating

Between Paroxyms Between Paroxyms Well Well DX ?DX ?

SIGNSSIGNS

Spleen EnlargementSpleen Enlargement JaundiceJaundice FeverFever AnemiaAnemia

CASE 4CASE 4

An 18 years old Saudi An 18 years old Saudi pregnant young women pregnant young women originally from Jazan came C/O originally from Jazan came C/O Fever and headache.Fever and headache.

Exam: Exam: Pale, jaundiced, Pale, jaundiced,

Temp. - 39°CTemp. - 39°C

Spleen enlarged Spleen enlarged NEXT?NEXT?

CBC:CBC: WBC - 8000 WBC - 8000

Hb - 9.0Hb - 9.0

Platelets: Platelets: 90 90 MCU : 98MCU : 98

CXR:CXR: NormalNormal

DIAGNOSISDIAGNOSIS1.1. Index of suspicionIndex of suspicion

Travel hist.Travel hist. Incubation PeriodIncubation Period 2 WKS2 WKS Prophylaxis Prophylaxis -- Longer Longer

2.2. ? Malaria? Malaria 3.3. Blood smear :Thin & thickBlood smear :Thin & thick 4.4. Special DrugSpecial Drug

COMPLICATION:COMPLICATION: 1.1. CerebralCerebral MalariaMalaria encephalopathyencephalopathy SeizureSeizure Death 20%Death 20% 2.2. Black. Water FeverBlack. Water Fever non immunenon immune High degree High degree

of F.M.of F.M. HemolysisHemolysis

Malaria & Pregnancy:Malaria & Pregnancy:

1.1. Risk of low birth & abortion. Risk of low birth & abortion. 2.2. Risk of glucose , pulm. Risk of glucose , pulm.

oedemaoedema

TREATMENTTREATMENT

1.1. HistoryHistory 2.2. SmearSmear 3.3. SpeciesSpecies

4.4. Severity Severity CBC CBC HibHib Coagulation Coagulation

5.5. Drugs:Drugs:

PREGNANCYPREGNANCY The antimalarials considered safe The antimalarials considered safe

in the first trimester of pregnancy in the first trimester of pregnancy are Quinine,are Quinine,

chloroquine,chloroquine,

proguanil, pyrimethamine, proguanil, pyrimethamine, sulfadoxine- pyrimethamine and sulfadoxine- pyrimethamine and clindamycinclindamycin

WHO recommendations ;WHO recommendations ; ••First trimester: quinine and First trimester: quinine and

clindamycinclindamycin ••Second and third trimesters: Second and third trimesters:

: artesunate and clindamycin, or : artesunate and clindamycin, or

quinine and clindamycinquinine and clindamycin

TREATMENTTREATMENT 1.1. Uncontrolled airway Uncontrolled airway 2.2. I.V . infusion I.V . infusion

3.3. Blood glucose test, Blood glucose test, parasitemia, Hct.parasitemia, Hct. 4.4. Antimalaria. Antimalaria. a.a. Chloroquine p.o.Chloroquine p.o. b.b. MefloquineMefloquine C .C . Quinine AND DOXYCYCLINE Quinine AND DOXYCYCLINE D. ARTEMISININSD. ARTEMISININS E . ATOVAQUONE PLUS E . ATOVAQUONE PLUS

PROGUANELPROGUANEL 5.5. Fluid balanceFluid balance P. EdemaP. Edema Dehydration & ShockDehydration & Shock 6. Convulsion6. Convulsion DiazepamDiazepam 7.7. Blood C/ S……8) LP Blood C/ S……8) LP

CHLOROQUINE SENSITIVE CHLOROQUINE SENSITIVE MALARIA :MALARIA :

Treatment with chloroquine may Treatment with chloroquine may be administered to patients for be administered to patients for whom chloroquine sensitive P. whom chloroquine sensitive P. falciparum malaria can be falciparum malaria can be predicted with certaintypredicted with certainty

CHLOROQUINE RESISTANT CHLOROQUINE RESISTANT MALARIA :MALARIA :

••Artemisinin derivative combinationsArtemisinin derivative combinations ••Atovaquone-proguanil (Malarone)Atovaquone-proguanil (Malarone) ••Quinine-based regimen (in combination with Quinine-based regimen (in combination with

doxycycline or clindamycin)doxycycline or clindamycin) ••Mefloquine (Lariam) (in combination with Mefloquine (Lariam) (in combination with

artesunate or doxycycline)artesunate or doxycycline)

Artemisinin combination therapiesArtemisinin combination therapies

(ACTs) are recommended by the WHO (ACTs) are recommended by the WHO as the first line treatment of as the first line treatment of uncomplicated falciparum malariauncomplicated falciparum malaria

They are potent against all developmental They are potent against all developmental stages of the asexual forms of malaria, stages of the asexual forms of malaria, resulting in the most rapid clearance time resulting in the most rapid clearance time relative to other agents. In addition, ACTs relative to other agents. In addition, ACTs also have activity against gametocytes, the also have activity against gametocytes, the stage responsible for continued stage responsible for continued transmission transmission

EXAMPLE: a short half lifeEXAMPLE: a short half life artesunate and artemetherartesunate and artemether Artemisinins should be given in Artemisinins should be given in

combination to forestall combination to forestall resistanceresistance

DRUG TOXICITYDRUG TOXICITY

MEFLOQUINE : neuropsychiatric MEFLOQUINE : neuropsychiatric symptoms : mood symptoms : mood changes .encephalopathy…changes .encephalopathy…transienttransient

QUININE : Bitter taste , GIT upset QUININE : Bitter taste , GIT upset , cinchonism ( nausea, vomiting , , cinchonism ( nausea, vomiting , tinnitus , high tone deafness )tinnitus , high tone deafness )

Doxycycline ..GIT upset, vaginal Doxycycline ..GIT upset, vaginal candidiasis..( use antifungal ) candidiasis..( use antifungal )

PREVENTIONPREVENTION

Avoid mosquitoAvoid mosquito Wear long sleeved clothingWear long sleeved clothing Sleep in well – screened roomsSleep in well – screened rooms Use mosquito nettingUse mosquito netting Use insect repellents (e.g. Use insect repellents (e.g.

DEET)DEET) Chemoprophylaxis..Chemoprophylaxis..

1) CHLOROQUINE1) CHLOROQUINE ONE TABLET EVERY WK..ONE TABLET EVERY WK.. DAILY WILL LEED TO DAILY WILL LEED TO

RETINOPATHYRETINOPATHY Consider resistant plasmodiumConsider resistant plasmodium

Chloroquine-sensitive areas Chloroquine-sensitive areas Drug of choice Drug of choice Chloroquine 500 mg (300 mg base)Chloroquine 500 mg (300 mg base) : :

once/wk once/wk Atovaquone/ proguanil (Malarone) : 1 tab/d Atovaquone/ proguanil (Malarone) : 1 tab/d ( 250 mg atovaquone( 250 mg atovaquone /100 mg proguanil)/100 mg proguanil) Mefloquine 250 mg once/wk Mefloquine 250 mg once/wk

Doxycycline 100 mg dailyDoxycycline 100 mg daily Alternatives Alternatives Primaquine 30 mg base dailyPrimaquine 30 mg base daily Chloroquine plus proguanil 500 mg (300 Chloroquine plus proguanil 500 mg (300

mg base) oncemg base) once / wk + 200 mg / wk + 200 mg