Presenter :Siti Azliza Binti Yaacob030.08.304

INCOMPLETE TREATMENT OF MALARIA AND SPECIAL

CONCERNS IN PREGNANCY

INTRODUCTION• A round the world, the malaria situation is serious and getting

worse.

• Malaria threatens the lives of 40% of the world’s population – over 2 200 million people.

• Each year, there are an estimated 300-500 million clinical cases.

• Malaria is a major public health problem in Indonesia with 6 million clinical cases and 700 deaths each year (Laihad, 2000).

• It has been estimated that malaria during pregnancy is responsible for 5–12% of all low birth weight and 35% of preventable low birth weight and contributes to 75 000 to 200 000 infant deaths each year. (Steketee et al., 2001)

OUTCOMES

• Incomplete of previous treatment.• Recurrency of malaria infection. • The infecting Plasmodium species• The clinical status of the patient • The drug susceptibility of the infecting parasites as

determined by the geographic area.

PATIENT IDENTITY• Name : Mrs.H• Place/born/age :Sukabumi / 5 September 1974 /38 yo• Address :Kp. Sukamarah RT 02/01 Taman Sari Bogor • Religion :Moeslim • Occupation :Housewife• Marital status :Married• Education :SMA• MR Number : 229575• Date of admission : 23 January 2013• Date of examination :1 February 2013• Consultant :Dr. Adi Wijaya Sp PD

HISTORY TAKING

• An autoanamnesis in ward on 1 February 2013 at 20.00 pm.

Chief complaint :

Increasing fatigue since 1 weeks ago before admitted to the hospital.

Additional complaint:

History of present illness:

HISTORY OF ILLNESS

Past medical history• Varicella (+)• Measles (+)• Influenza (+)• Malaria (+)• Gastritis (+)• Appendicitis (+) • *malaria : 4 times already

Family history• Father : HT• Mother : HD + DM

History of habitual:• rarely do the excersice• Smoke (-)• drink coffee and tea (-)• routine medication or herbs.(-)

History of diet:• Present diet : frequent of meal is 2x/day, with ½ portion

and variation of food.• Apetite : loss of apetite.

NUTRITIONAL STATUS

PHYSICAL EXAMINATION

GENERAL PHYSICAL EXAMINATION

LABORATORY TEST • 23 January 2013 (In Emergency Room)

Hematology

Test performed Result Unit Recommended Interpretation

Hemoglobin 9.7 g/dl 13-18

Leukocyte 6.810 /mm3 4000-10000 N

Thrombocyte 73.000 mm3 150000-400000

Hematocrit 29 % 40-54

Serologic

Widal test Negative (-)

Chemistry blood count

SGOT 36 U/l <42 N

SGPT 26 U/l <47 N

BUN 15.0 mg/dl 10-50 N

Creatinine 0.65 mg/dl 0.67-1.36 N

Blood glucose 142 mg/dl <140 N

Laboratory test : 24 January 2013• Test / 12 hours

Hematology 1st

Test performed Result Unit Recommended Interpretation

Hemoglobin 8.7 g/dl 13-18

Leukocyte 7.620 /mm3 4000-10000 N

Thrombocyte 59.000 mm3 150000-400000

Hematocrit 27 % 40-54

Hematology 2nd

Test performed Result Unit Recommended Interpretation

Hemoglobin 8.4 g/dl 13-18

Leukocyte 6.870 /mm3 4000-10000 N

Thrombocyte 52.000 mm3 150000-400000

Hematocrit 26 % 40-54

Laboratory test : 25 January 2013Hematology 1st

Test performed Result Unit Recommended Interpretation

Hemoglobin 7.9 g/dl 13-18

Leukocyte 6.620 /mm3 4000-10000 N

Thrombocyte 64.00 mm3 150000-400000

Hematocrit 24 % 40-54

Hematology 2nd

Test performed Result Unit Recommended Interpretation

Hemoglobin 7.5 g/dl 13-18

Leukocyte 5.690 /mm3 4000-10000 N

Thrombocyte 47.000 mm3 150000-400000

Hematocrit 20 % 40-54

Hematology

Test performed Result Unit Recommended Interpretation

Malaria In a sample was found the

plasmodium Vivax in a

Early trophozoite shape

(ring form)

- - -

Laboratory test: 26 January 2013

Laboratory test: 27 January 2013.

Hematology

Test performed Result Unit Recommended Interpretation

Hemoglobin 7.2 g/dl 13-18

Leukocyte 5.740 /mm3 4000-10000 N

Thrombocyte 53.000 mm3 150000-400000

Hematocrit 22 % 40-54

Hematology

Test performed Result Unit Recommended Interpretation

Hemoglobin 7.4 g/dl 13-18

Leukocyte 4.580 mm3 4000-10000 N

Thrombocyte 64.000 mm3 150000-400000

Hematocrit 22 % 40-54

Laboratory test : 28 January 2013.

Hematology 1st

Test performed Result Unit Recommended Interpretation

Hemoglobin 10.1 g/dl 13-18

Leukocyte 9.910 /mm3 4000-10000 N

Thrombocyte 95.000 mm3 150000-400000

Hematocrit 30 % 40-54

Hematology 2nd

Test performed Result Unit Recommended Interpretation

Hemoglobin 10.2 g/dl 13-18

Leukocyte 8.890 /mm3 4000-10000 N

Thrombocyte 91.000 mm3 150000-400000

Hematocrit 31 % 40-54

Laboratory test : 29 January 2013.

Hematology

Test performed Result Unit Recommended Interpretation

Hemoglobin 10.1 g/dl 13-18

Leukocyte 8.000 /mm3 4000-10000 N

Thrombocyte 123.000 mm3 150000-400000

Hematocrit 30 % 40-54

Chemistry blood count

SGOT 25 U/l <42 N

SGPT 30 U/l <47 N

BUN 41.1 mg/dl 10-50 N

Creatinine 0.51 mg/dl 0.67-1.36

Blood glucose 143 mg/dl <140 N

Electrolyte 

Test performed Result Unit Recommended Interpretation

Natrium Na+ 139 136-146 N

Sodium K+ 4.5 3.5-5.0 N

Chloride Cl- 96 95-115 N

HEMOSTASIS

Test performed Result Unit Recommended Interpretation

APTT 26.8 Dtk 25.9-39.5 N

Protrombin time 12.2 Dtk 11.8-14.4 N

Fibrinogen 214 mg/dl 200-400 N

Laboratory test : 30 January 2013

Blood Gas Analysis

Test performed Result Unit Recommended Interpretation

Ph 7.50 7.35-7.45

PCO230 30-50 N

PO274 70-700 N

BE 0.0 -2-+3.0 N

TCO2 23.9 22-29 N

HCO323.0 18-23 N

BE act 0.7 -2.0- +3.0 N

SO297 95-98 N

O2 CT 16.6 15.0-23.0 N

Temp 35.6 N

FlO20.21

Hematology

Test performed Result Unit Interpretation

D-Dimer 6,809.36 ng/mL FEU

Laboratory test : 31 January 2013

Laboratory test : 1 February 2013.

Hematology

Test performed Result Unit Recommended Interpretation

Hemoglobin 10.1 g/dl 13-18

Leukocyte 7.580 /mm3 4000-10000 N

Thrombocyte 217.000 mm3 150000-400000 N

Hematocrit 31 % 40-54

Hematology

Test performed Result Unit Recommended Interpretation

Malaria Positive (+)

Malaria parasite was

found (Plasmodium

Vivax)

- - -

Another examination • ECG

• Normal ECG

RESUMEHISTORY TAKING :

A women, 35 years old was admitted to dr. H. Marzoeki Mahdi Hospital’s ER on 23 January that was complain increasing fatigue since a week before admitted to the hospital. She was had a history of sustained fever a long with shaking chills. The additional complaint was nausea, vomite that contain fluids, headache, loss of appetite, arthralgia and abdominal discomfort. She had instable condition with increasing fatigue, with a sudden onset of flue-like symptoms and sustained recurrent severe attacks with the highest temperature is 39.6°c with shaking chills and sometimes with sweating and arthralgia almost every day. All of this complains have become progressively worst within a last week before admitted to the

hospital.

In the past history patient often frequently travel from Papua to Java since September 2011.She was 3 times diagnosed of malaria in Papua.

• 1st diagnosed on Disember 2011• malaria tertian (P.Vivax and P.Ovale).

• she was in pregnancy, G3 P2 A0 (aborted on February 2012.)

• Admitted in the Hospital Totally recovered• 2nd diagnosed on November 2012

• Admitted in the hospital not sure recovered• 3rd diagnosed on Disember 2012

• She had a 4 weeks gestation in pregnancy. (G4 P2 A1).

• admitted discharged instable condition. • Then she was decided to going back to Java.

PHYSICAL EXAMINATION

General condition : Mrs. H appears alert, oriented and cooperative.

Consciousness: conscious

Vital signs:

Blood pressure :100/70 mmHg

Pulse rate :90x/m

Respiration rate:20x/m

Temperature :39.3°c

Eyes :conjunctival pallor (+/+)

Abdomen: palpitation : tenderness (+).

LABORATORY TEST (23 Jan 2013)• Hemoglobin 9.7g/dl • Thrombocyte 73.000mm3

• Hematocrit 29%

• Anemia • Thrombocytopenia

24 Jan 25 Jan 26 Jan

27 Jan

28 Jan

29 Jan 30 Jan

31 Jan 1 Feb

Hemoglobin (g/dl)

-8.7-8.4

-7.9-7.5

-7.2 -7.4 -10.1-10.2

10.1 - 10.1 -

Hematocrit %

-29-26

-24-20

-22 -22 -30-31

39 - 31 -

Thrombocyte (mm3)

-59.000-52.000

-64.000-47

53.000

64.000

91.000

123.000

- 217.000

-

Microscopic of malaria

P.vivax in a Early trophozoite Shape (ring form)

- - - - - - (+) P.vivax

Chemistry blood count

- - - - N - - -

Electrolyte - - - - N - - -

Hemostasis - - - - N - - -

Blood gas analysis

- - - - - N - -

D-Dimer (ng/ml FEU)

- - - - - 6,809.36

- -

PROBLEMS• Sustained recurrent high fever• Fatigue • Dyspepsia (Nausea,vomit,abdominal

discomfort), Loss of apetite• Arthralgia• Anemia , Thrombositopenia• Recurrent malaria infection. • Pregnancy• Most probably she was infected from the

high transmission area that is Papua New Guinea.

Differential diagnosis :• Relapse of malaria.• Thyphoid fever• Dengue hemorrhagic fever.

THERAPY

Medicamentosa• IVFD RL /8hrs• Oxygen canul 2L/m• Antipyretic : Paracetamol 3x1g

• H2 Blocker : Ranitidine 2x1

• Planning for transfusion of PRC 200cc.• Planning for giving of anti-malaria drugs.

DISCUSSION

RESOLUTION AND THERAPY

In 9th hospitalization On 1 February 2013 patient was ask to discharge by her on dicision and there is no provided any anti-malarial drugs during she was discharged.

Condition :

• Conscious, mild illness.

• Mild headache

• Nausea (+),vomit(-), Apetite is good

• Arthralgia(+).

• BP: 110/60mmHg Pulse: 80x/m

• RR: 20x/m Temp: 36 °c

• Hb : 10.1 g/dl

• Ht : 31%

Throm : 217,000 mm3

DEFINITION AND EPIDEMIOLOGY

• Malaria is caused by infection of red blood cells with protozoan parasites of the genus Plasmodium .

• The four Plasmodium species that infect humans are P. falciparum, P. vivax, P. ovale and P. malariae.

• Increasingly, human infections with the monkey malaria parasite, P. knowlesi, have also been reported from the forested regions of South-East Asia.(1)

• The World Health Organization estimates that malaria caused approximately 655,000 deaths in 2010.

• Most are in young children in sub-Saharan Africa.• Malaria can also cause dangerously low birth weights and

permanent disability

LIFE CYCLE OF MALARIA PARASITES

The incubation period : • Malaria bite until

clinical symptoms appear 7 days (1-2 weeks).

• Symptom due to the cycling parasitemia in the bloodstreams.

• symptoms every 2 to 3 days depending on the type of Plasmodium with which they are infected.

PHATOFISIOLOGY

Blood stage

BODY’S INFLAMMATORY RESPONSE

• Repeated malarial infections lead to some immunity. “learned immunity”

• In fact, in areas where malaria incidence is episodic rather than endemic, patients will present with more severe forms of the disease, as their previously “learned immunity” appears to fade over time.

• It is not surprising, therefore, that malaria-naive and immunocompromised patients are prone to more severe infection.

• This puts pregnant women, children, travelers to endemic regions, and persons with coexisting HIV infection at highest risk for morbidity and mortality secondary to malarial infection.(9)

CLINICAL DISEASE• Caused by the asexual erythrocytic or blood stage parasites. • When the parasite develops in the erythrocyte, substances such as :• hemozoin pigment and other toxic factors accumulate in the infected red

blood cell. • These are dumped into the bloodstream when the infected cells lyse

and release invasive merozoites. • The hemozoin and other toxic factors such as glucose phosphate

isomerase (GPI) stimulate macrophages and other cells to produce cytokines and other soluble factors which act to produce fever and rigors and probably influence other severe pathophysiology associated with malaria.

Pregnancy-malaria and intensity of transmission: 

Complication High Transmission Low transmission

Hypoglycemia - ++

Severe Anemia +++ +++

Pulmonary oedema - ++

ARF - ++

Hyperpyrexia + +++

Placental malaria +++ +++

LBW babies +++ +++

Abortions - +++

Congenital malaria - +++

PATENT PARASITEMIA FOR MALARIA CAUSED BY P.VIVAX

When a parasitemia reappears after blood schizonticidal therapy, it may be a relapse from the liver, a reinfection by a mosquito, or a recrudescence originating from asexual blood-stage parasites that survived therapy. The emergence of CQ-resistant P. vivax favors the last possibility.

DIAGNOSIS

• The diagnosis of malaria is based on :

• - clinical suspicion • -the detection of

parasites in the blood ( parasitological or confirmatory diagnosis).

CLINICAL DIAGNOSIS

• Ring-form trophozoites of P. vivax in thin blood smears

• Trophozoite of P. vivax in a thick blood smear

TREATMENT OF MALARIA INFECTION

Treatment should be guided by three main factors :

TREATMENT OF MALARIA CAUSED BY P.VIVAX

Classes and representative antimalarial drugs

Type of drug TargetClinical

application Prophylaxis Licensed drug(s)Experimental

drug(s)

Blood schizontocide

Trophozoite in blood

Treatment of acute malaria

Suppressive Chloroquine, quinine, mefloquine, doxycycline, AV-PG, DH-PP

Tafenoquine, ACTs

Primary tissue schizontocide

Active schizont in liver

None Causal Primaquine Tafenoquine

Hypnozoitocide Dormant hypnozoite in liver

Prevention of relapse

None Primaquine Tafenoquine, elubaquine

Gametocytocide Gametocyte in blood

Prevention of transmission

None Primaquine Tafenoquine, artesunate, artemether

Sporontocide Forms in mosquito including sporozoite

Prevention of transmission

Causal prophylaxis

Primaquine Tafenoquine

• Deterioration of chloroquine (CQ) efficacy between 1945 (green line) and 1995 (red line) among tropical Asian strains of P. vivax relative to natural relapse of the same strains following quinine (QN) therapy (blue line). The suppression of relapse by chloroquine in 1945 is due to lingering levels of drug in blood up to day 35, and the 1995 data suggest not only failure to suppress relapse but also failure to clear primary asexual parasitemia. Data were derived from various sources

• Plot of the cumulative incidence of recurrent parasitemia after chloroquine therapy of vivax malaria in western Indonesian Borneo and eastern Indonesian New Guinea

A regimen recommended for chloroquine-resistant P. vivax infections.

Artemisinin-based combination therapy (ACTs)

• Recent studies have also demonstrated the efficacy of the recommended ACTs in the treatment of vivax malaria.

• ACTs based on either amodiaquine, mefloquine or piperaquine, rather than monotherapy, are the recommended treatment of choice.

• The exception to this is artesunate plus sulfadoxine-pyrimethamine.

• P. vivax has developed resistance to sulfadoxine-pyrimethamine. (study from Afghanistan reported)

TREATMENT DURING PREGNANCY

• Parenteral artesunate is preferred over quinine in the second and third trimesters, because quinine is associated with recurrent hypoglycaemia.

• In the first trimester, the risk of hypoglycaemia is lower and the uncertainties over the safety of the artemisinin derivatives are greater.

• However, weighing these risks against the evidence that artesunate reduces the risk of death from severe malaria, both artesunate and quinine may be considered as options until more evidence becomes available. Treatment must not be delayed; so if only one of the drugs artesunate, artemether or quinine is available, then it should be started immediately

• ????????????

PRIMAQUINE IN PREGNANCY

• For P. vivax or P. ovale infections, primaquine phosphate for radical treatment of hypnozoites should not be given during pregnancy.

• Pregnant patients with P. vivax or P. ovale infections should be maintained on chloroquine prophylaxis for the duration of their pregnancy.

• The chemoprophylactic dose of chloroquine phosphate is 300mg base (=500 mg salt) orally once per week.

• After delivery, pregnant patients with P. vivax or P. ovale infections should be treated with primaquine.

• Pregnant women di agnosed with severe malaria should be treated aggressively with parenteral anti malarial therapy .(10)

Prevention and Control of Malaria during Pregnancy

78

Facts about Malaria and Pregnancy

• 30 million African women are pregnant yearly

• Malaria is more frequent and complicated during pregnancy

• In malaria-endemic areas, malaria during pregnancy may account for:• Up to 15% of maternal anemia • 5–14% of low birthweight• 30% of “preventable” low birthweight

Chemoprophylaxis

• Remind women that there is no malaria prophylaxis regimen that is 100% protective.

Chemoprophylaxis for long-term travellers

• Long-term travellers are defined as those travelling through or visiting malaria-endemic countries for over six months.

• Chloroquine and proguanil are the only drugs licensed for long-term use but there effectiveness is reduced in some areas, due to resistance.

• Mefloquine is licensed for up to one year (although it has been used for up to three years without problems).

• Doxycycline can be used for up to two years.

• Malarone® is licensed for up to 28 days but can be safely used for up to three months (and possibly six months or longer).

CLONCLUSIONMalaria in a pregnant woman increases the risk of maternal death, miscarriage, stillbirth and low birth weight with associated risk of neonatal death. Pregnant women should be advised to avoid travelling to areas where malaria transmission occurs. When travel cannot be avoided, it is very important to take effective preventive measures against malaria, even when travelling to areas with transmission only of vivax malaria. Pregnant women should seek medical help immediately if malaria is suspected. There is very limited information on the safety and efficacy of most antimalarials in pregnancy, particularly during the first trimester. However, inadvertent exposure to antima -larials is not an indication for termination of the pregnancy.