MALARIA

Akmal Syaroni

DIVISION OF TROPICAL INFECTIOUS DISEASES DEPARTMENT OF INTERNAL MEDICINE SCHOOL OF MEDICINE - SRIWIJAYA UNIVERSITY MOH. HOESIN HOSPITAL PALEMBANG

MALARIA

a protozoan parasites borne disease, plasmodium genus, transmitted by the plasmodium-infected female anopheles bites a classic disease marked by periodical high fever of intermittent type fever

5 Plasmodium species infecting human : * P. falciparum * P. vivax * P. ovale * P. malariae * P. knowlesi

TRANSMISSION :
vector Anopheles mosquitoes blood transfusion organ transplant congenital

Plasmodium Falciparum picture:

Plasmodium falciparum :

Most detrimental Malaria : risk for cerebral malaria, kidney failure, Acute Respiratory Distress Syndrome , severe anemia Immediate therapy is important. Incurable infection in non immuned person may be fatal. If the patient treated and cured, no relapse risk due to P. falciparum having no liver dormant stage ( hypnozoite ).

Plasmodium Vivax picture:

Stad.ring Tropozoit Schizont Merozoit

Plasmodium Ovale picture:

Ring Trophozoite

Schizont
Gametocyte

P. vivax and P. ovale :

No life threatening, unlike Pl.falciparum.

Symptoms remain dominating ( especially fever) Treated with different drugs to eliminate the parasites in blood and liver stage.

Plasmodium Malariae picture:

Ring stage Trophozoite Schizont Gametocyte

History of Malaria :

in 3000 4000 BC happened in Nile Valley and little Asia Explained in ancient Greek era in 400 BC. In 1880 : Charles Laveran found Malaria parasites in human blood. in 1897 : Ronald Ross demonstrated malarial transmission by mosquitoes. Shortt and P.C., C. Garnham found hypnozoites in 1948.

Malaria Epidemiology :
-

300 500 millions people has malarial infection worldwide. 120 millions clinical case every year 40% of world population living in endemic transmission area, especially in Sub Saharan Africa ( 92 countries )

1,4 2,7 millions death happen every year, especially in children aged < 5 year and pregnant woman (primigravida)
The death caused by severe malaria, multiple organ failure, chronic anemia, Acute Respiratory Distress Syndrome (ARDS) and placental malaria caused by Plasmodium falciparum.

Malarial distribution :

3 STAGES OF MALARIAL PARASITES LIFESPAN :

Liver Red blood cell (erythrocyte)

Mosquito

MALARIAL PARASITES LIFESPAN :

MALARIAL INCUBATION PERIOD :

Related to liver stage from malarial parasites :

P. falciparum P. vivax P. ovale P. malariae

12 days 14 days* 14 days* 30 days

*may be 8 10 months or more in some strains

Malaria Clinical Manifestation :

Blood stage parasites account for clinical manifestation. Fever is most common symptom. Classic Cyclic Paroxysmal symptoms: * cold stage : shivering and shaking * hot stage : warm body, headache, vomiting * sweating stage: weak. Other symptoms may be: nausea, diarrhea, muscle pain, and mental state change. Feeling better in some period of time, then the cycle repeats itself.

SEVERE MALARIA

Cerebral malaria Malaria with bilirubine > 3 MG% and other organ failure Acute kidney failure < 400 ml/24 hours and creatine > 3 mg% Hypoglycemic < 40 mg% Systolic shock < 70 mmHg / children < 50 mmHg Severe anemia HB < 5 gr% / Ht < 15% Pulmonary edema / ARDS Spontaneous bleeding / DIC Repeated convulsion Acidosis pH <7.15 , Plasma Bicarbonate < 15 mmol/L HAEMOGLOBINURIA HYPERPARASITEMIA > 5 % Hyperthermia > 40 C ( rectal)

Cerebral Malaria :

syndrome defined as a comatose state caused by single factor, P. falciparum, regardless its number
1% of P. falciparum infection continue to cerebral malaria and 10-20% cases end in deaths generally happens in > 2 year old children.

Cerebral Malaria

Severe Malaria :
Anemia : caused by P. falciparum dan P. vivax erythrocytes destruction contained parasites due to its reducing oxygen transport ability. increasing the non infected erythrocytes transmission rate from circulation. erythropoiesis suppression erythrocytes immunity destruction generally happens in < 2 year old children.

Respiratory Distress Syndrome (RDS) :

a malaria feature in African children and Asian adult man. can be caused by the injury of pulmonary endothelial micro vascular and alveolar through proinflamatory mechanism. epithelia can be caused by heart failure, parasites breakage, or the increasing respiratory needs. often relates to metabolic acidosis.

ACUTE RESPIRATORY DISTRESS

HISTOPATOLOGY

Pulmonary mononuclear cell infiltration, edema

Factors related to the increasing malaria incident:

1.

Drugs resistance - anti malarial drugs misuse

- lack of anti malarial drugs development by pharmaceutical company and government.

2.

Insecticides resistance - insecticides misuse in agricultural field

- environmental influence

3. 4. 5.

6.
7.

Economy factor Political chaos Lack of community health infrastructure Lack of global interest Human behaviors.

Principal protection against Malaria :

1.

2.

3.

4.

To Be cautious to risk, incubation period, and main symptoms. To Avoid being bitten by mosquitoes especially from dusk till dawn. To Take anti malarial drugs as chemoprophylaxis to suppress the infection if any. To Seek for diagnosis and early therapy if presents a week or more fever after entering high risk malaria area, till a year leaving the area.

Personal protection against Malaria :

-

To avoid the endemic malaria area To live in the house from dusk till dawn in cloth covered bed or AC room To apply mosquito spray in the bedroom and cloth covered bed To put on long sleeve shirts and trousers. To apply DEET lotion to cloth uncovered skin. To use cloth covered bed .

INSECT REPELLENTS FOR SKIN AND CLOTHING

DEET lotion Permethrin
Individual Dynamic Treatment lasts for
for over 50 launderings

Absorption Kit (IDA)

NSN 6840-01-284-3982

NSN 6840-01-345-0237

Aerosol spray can Treatment lasts

through 5-6 washes

Apply a thin coat to EXPOSED skin One application lasts up to 12 hours

NSN 6840-01278-1336
US Army Center for Health Promotion and Preventive Medicine

Factors affecting the drugs choice of malaria in chemoprophylaxis: 1. Type of Malaria 2. Drugs resistance in spesific location/region. Indonesia is included as a region in which P. falciparum, P. vivax, and P. malariae has become resistant to chloroquine. 3. Allergy history or other reaction against the chosen antimalarial agents 4. Limitation related to occupation ( for instance mefloquine can not be taken by pilot and diver )

chemoprophylaxis drugs in primary Malaria :

1. 2. 3. 4.

Chloroquine Mefloquine (Lariam) Doxycycline Atovaquone-proguanil (Malarone)

First line therapy of P.FALCIPARUM in adult man :

day 1 : 4 Artesunate tabs 4 Amodiaquine tabs 2 3 Primaquine tabs 4 Artesunate tabs 4 Amodiaquine tabs 4 Artesunate tabs 4 Amodiaquine tabs

day 2 : day 3 :

Second line therapy of P.FALCIPARUM in adult man :

day 1 : Quinine Tetrasiklin / doksisiklin Primaquine Quinine Tetrasiklin / doksisiklin 3 x 2 tabs 4 x 1 capsule 2-3 tabs 3 x 2 tabs 4 x 1 capsule

day 2 7 :

Treatment of MALARIA VIVAX / MALARIA OVALE in adult man: day 1 : 3 - 4 chloroquine tabs ( 10 mg / kg BB ) 1 primaquine tab ( 0,25 mg/kgBB ) day 2 : 3 - 4 chloroquine tabs ( 10 mg / kg BB ) 1 primaquine tab ( 0,25 mg/kgBB ) day 3 : 2 chloroquine tabs ( 5 mg/kgBB ) 1 primaquine tab ( 0,25 mg/kgBB ) day 4 14 : 1 primaquine tab ( 0,25 mg/kgBB )
Treatment of MALARIA VIVAX / MALARIA OVALE resistant to chloroquine in Adult man : day 1 7 : Quinine 3 x 2 tabs / day day 1 14 : Primaquine 1 tab / day

Treatment of MALARIA VIVAX / MALARIA OVALE relapse in Adult man : CHLOROQUINE: 3 4 tabs(1 time/week) for 8-12 weeks Primaquine : 3 tabs (1 time/week) for 8-12 weeks

TREATMENT

IN SEVERE

MALARIA

Against its parasitemia Drugs type ( ARTESUNATE, ARTEMETER, QUININE ) DOSE ( ARTEMISININ, QUININE ?? ) and administration Parasites resistance/ M.I.C parasites Substitute transfusion against organs damage Kidney failure ( DIALYSIS ) Respiratory failure ( RESPIRATOR ) against general condition ( Nutrition/ fluid ) Parasites sequestration result/its metabolism OBSTRUCTION --> cerebral EDEMA (kidney ?/liver?) Hemolytic SLUDGING/ ROSETTE CYTOKINE

SPECIFIC TREATMENT SEVERE MALARIA ( ANTI MALARIA)

PARENTERAL START IMMEDIATELY DOSAGE, WEIGHT THE PATIENT MONITORING RESPONSE SWITCHED TO ORAL WHEN POSSIBLE MONITORING SIDE EFFECTS

ANTI MALARIAL THERAPY FOR S.M

ARTEMISININ :
ARTESUNATE : I.V/ I.M / ARTEMETHER : I.M ARTEMISININ SUPP

QUININE QUINIDINE CHLOROQUINE

RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR TREATMENT OF SEVERE/CEREBRAL MALARIA

DRUGS SIDE EFFECTS

ARTESUNATE i.v. 2,4 mg/kg BB in 0 hour, and

Artemeter Artemisinin

12 hours, followed 24 hours, 48 and so on until 7 days. Total dose 17 18 mg/ 7 days ( 1 Amp= 60 mg) Alternative 1,2 mg/ Kb BB with administration time as above 3.2 mg/kg im in day I divided 2 doses , followed 1.6 mg/kg/ day. NOT iv (1 amp = 80 mg) Suppositories, 10 mg/kg at 0 & 4 days followed by 7 mg/kg at 24,36,48 & 60 hours.

Neurotoxicity in animal not human

RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR TREATMENT OF SEVERE/CEREBRAL MALARIA

DRUGS Quinine
20 mg of dihydrochloride salt/kg by iv infusion over 4 hr, then after loading, followed by 10 mg/kg over 4 hr every 8 hr. Patients should not received quinine or mefloquine within last 24 hr
Alternatively, 7 mg of salt/kg can be infused over a period of 30 min, followed by 10 mg salt/kg over a period of 4 hr, or

SIDE EFFECTS Hypoglycemia, chinchonism, tinnitus, hearing impairment, nausea, dysphoria, vomiting, prolonged QT interval, dysrhythmias, hypotension

10 mg of salt/kg (500 mg for adult) by i.v infusion over 8 hr continously 3 x a day

Dextrose 5%

Maintenance fluid

Piggy Back

QUININE
Microdrips 100-200 cc

Administration methods

QUININE in severe
Malaria

TREATMENT OF ORGAN FAILURE

ENCEPHALOPATHY/ RENAL

CONVULSION

FAILURE ACIDOSIS HYPOGLYCAEMIA HYPERBILIRUBINAEMIA RESPIRATORY FAILURE HYPOTENSION SEPSIS SEVERE ANAEMIA

Cerebral Insufficiency Management

Oxygenation
Convulsion prevention: diazepam, luminal, largactil Trauma/falling prevention Anxiety management, delirium state

ICTERIC MANAGEMENT
No special treatment Be cautious to hypoglycemic Be cautious against bleeding Vit K administration in deep icteric/ bleeding sign: 10 mg/ day for 3 days. Bilirubine repeating , SGOT/ SGPT at day 3

HYPOGLYCAEMIA ( BL. SUGAR < 40 MG% ) 20 -50 ml 50% dextrose i.v. 5 10 minutes ( routine is not recommended ) Infusion 10 % dextrose ( children 5% dextrose) beware hyponatremia Hypoglycemia may developed Day 1 --- 7 Pushed 50% dextrose if necessary Glucagons injection Via nasogastric , beware gastric distension In peritoneal dialysis, add glucose in dialysis fluid Somatostatin analogue octreotide (Sandostatin)
Coma,

MANAGEMENT ACUTE RENAL FAILURE

Exclude

pre-renal/ hypovolemic Dopamine /& dobutamine or diuretic Dialysis early

MANAGEMENT OF RESPIRATORY FAILURE

PRINCIPLES : *Consider severity & cause. *Correct pH, if < 7.1 *Maintain PaO2 : 50 - 60 torr * Rapid Rx anti-malarial * Consider aggravating factors : - secreting obstructing airways - pneumothorax

MEOLIC ACIDOSIS
Occur

in : - acute renal failure - hypovolemic - shock - pulmonary edema - hyperparasitemia Management : * Dialysis * Sod.bicarbonate if pH< 7.15, beware of sodium overload Pulmonary edema * Preferable THAM tris (hydroxymethyl)- amino methan, no sodium * Pyruvate dehydrogenase activator dichloro acetate

HYPOTENSION (ALGID MALARIA)

Causes: gram - ve bacteriaemia, MOF Management : 1. CVP : 0 -- 5 cm H2O with crystalloid/ colloid infusion 2. I.V. Dopamine +/ dobutamine 3. Blood culture 4.Antibiotic ( Cephalosporin III)

GENERAL SUPPORTIVE MEASURES

Urinary catheterization should be used to monitor output Patients should be observed for vomiting. To ensure patients safety, cot-sides may be required Regular re-positioning of patient is necessary to prevent development of pressure sores Nasogastric tube should be avoided because of the risk of aspiration

SUPPORTIVE MANAGEMENT C.M.

AIRWAY FLUID REQUIREMENT : HYDRATION / OVERHYDRATION CONVULSION : DIAZEPAM MONITORING GCS & VITAL SIGN LAB : FBC, GLUCOSE, PAR.COUNT, CREATININE, UREUM, BLOOD GAS, URINE S.G, SODIUM, POTASSIUM. PREVENT : SHOCK, SEPTICAEMIA, ACIDOSIS, ARDS, HYPOGLYCAEMIA, ASPIRATION, BEDSORES. TREAT HYPERPYREXIA VOLUME URINE & CATHETERIZATION

INITIAL MANAGEMENT OF SEVERE MALARIA

Clear & maintain airway Position semi prone or on side Weight patient, calculate dosage Start antimalarial chemotherapy Make rapid clinical assessment Exclude or treat hypoglycemia Asses state of dehydration Measure & monitor urine output, if nes. Catheter, S.G Diagnostic smear, rapid test, other lab test Plan first 8 hrs i.v. fluid, including anti malarial, glucose, blood transfusion Consider CVP line If temp. rectal > 39 C, r. clothes, tepid sp., fan, cooling Lumbal puncture, to exclude meningitis Anti convulsion, anti-microbial, VIT.K