Gatoet IsmanoeDivision of Tropical Infectious

Diseases Department of Medicine Brawijaya Medical

FacultySaiful Anwar General Hospital

Introduction (1) Malaria is an infectious disease

caused by protozoan organisms of the genus plasmodium (falciparum, ovale, vivax, malariae)

It is characterized by high fever and erythrocyte infection resulting anemia

In pregnant woman it causes a placental infection that impacts the fetus development

Introduction (2) 300 million cases each year world

wide Malaria is more frequent and

complicated during pregnancy may account for :Up to 15% of maternal anemia5-14% of low birth weight30% of preventable low birth weight3-8 % of infant death

Malaria endemic countries divided into 4 regions

In Africa , 95-100% caused by P.Falciparum.America ,Middle East P.VivaxAsia and Pacific Mixed Infection

EPIDEMIOLOGY OF MALARIA

Africa-highest mortality

Asia Pacific Mutilple Resistance to Drugs

35 countries in the world reponsible for 98 %

of total malaria deaths

30 in Africa: Nigeria,DRC,Uganda,Ethiopia,Tanzania,KenyaSudan.aniger,Burkinofaso,Ghana,Mali,Cameroon,Angola,Coted’Ivoire,Mozambique,Chand,Guinea ,Zambia,Malawi,Benin,Senegal,Sierra Leone,Burundi,Togo,Liberia,Rwanda,Congo,Central African Republic,Somalia,Guinea Bissau.

5 in Asia- Pacific:India,Myanmar,Bangladesh,Indonesia,Pap

ua New Guinea

Malaria cases in Asia -Pacific

India accounts for 45% of casesP.Vivax & P.falciparum presentIndoot and out door vectors

Population Most Affected by Malaria Children under 5 years of age Pregnant woman Unborn babies Immigrants from low-transmission

areas HIV-infected persons

Related to level of transmission and immunity of individual exposed

In areas of high transmission, endemic or stable malaria area.

In areas of low transmission or non-endemic or unstable areas

Malaria and Pregnancy

Effects of Malaria on Pregnant Women All pregnant women in malaria-

endemic areas are at risk Parasites attack and destroy red blood

cells Malaria causes up to 15% of anemia in

pregnancy Can cause severe anemia In Africa, anemia due to malaria causes

up to 10,000 maternal deaths per year

In Endemic Areas Malaria-related

anaemia Febrile illness Placental

sequestration

In Non-Endemic Areas Greater risk of severe

disease Higher risk of death Anaemia,

hypoglycemia, pulmonary oedema, renal failure

Maternal complications

Effects on Unborn Babies Parasites hide in placenta Interferes with transfer of oxygen

and nutrients to the baby, increasing risk of:Spontaneous abortionPreterm birthLow birthweight—single greatest risk

factor for death during first month of lifeStillbirth

In endemic areas Low birth weight Intra-uterine growth

retardation

In non-endemic areas Abortions Preterm delivery Congenital malaria Low birth weight

Fetal complications

Effects on Communities Causes missed work and wages Results in frequent school absences Uses scarce resources Causes preventable deaths:

increases maternal, newborn, and infant mortality rates

Recent findings – pregnant women

Pregnancy phase of immuno-Pregnancy phase of immuno-suppressionsuppression

P. falciparumP. falciparum affinity to affinity to placentaplacenta

Immune responses specific Immune responses specific to placenta physiologyto placenta physiology

Primigravidae

Secundigravidae

Multigravidae

Recent findings – pregnant women

P. falciparum malaria

Placental infection

Low birth weight

Risk of infant mortality

Maternal anemia

Acquired Immunity-high

Asymptomatic infection

Anemia

Maternal Morbidity

Low Birth Weight

Placenta sequestration Altered placental Integrity

Less nutrient transport

Higher infant Mortality

WHO 2004

STABLE TRANSMISSION

Acquired Immunity – low or none

Clinical Illness

Severe Disease

Risk to Mother Risk to Fetus

•All pregnancies are at risk•Key intervention strategies : disease recognition and case management

WHO 2004

UNSTABLE TRANSMISSION

Early diagnosis, effective treatment, manage collateral effects

Use of chemo-prophylaxis or intermittent preventive treatment (IPT)

Use of insecticide-treated bed nets Regular antenatal care and health education

about malaria

Management and Preventive Strategies

Intermittent Preventive Treatment

1. Based on the assumption that every pregnant woman living in an area of high malaria transmission has malaria parasites in her blood or placenta, whether or not she has symptoms of malaria

Although a pregnant woman with malaria may have no symptoms, malaria can still affect her and her unborn child

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Chemoprophylaxis in Pregnancy Malaria being potentially fatal to both the mother

and the foetus, this should be an important part of antenatal care in areas of high transmission. All pregnant women, who remain in the malarious area

during their pregnancy, should be protected with chemoprophylaxis.

Choice of anti malarials for chemo prophylaxis: Chloroquine being the safest drug in pregnancy, should be

the first choice. However, its use may be restricted due to the wide spread

resistance to this drug. In areas with known resistance to Chloroquine

○ Pyrimethamine + Sulpha, Mefloquine or Proguanil can be used. ○ But these drugs should be started only after 1st trimester only.

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Chemoprophylaxis in Pregnancy

Chloroquine: - 300mg base, administered once every week.

Pyrimethamine-25mg + Sulphadoxine-500mg: - One tablet once weekly.

Mefloquine: -250mg weekly.Dose may have to be increased in the last

trimester, in view of the accelerated clearance of the drug.

Proguanil: - 150-200mg / day.

Intermittent Preventive Treatment: WHO RecommendationAll pregnant women should receive at least two doses of IPT after quickening, during routinely scheduled ANC visits (WHO recommends a schedule of four visits, three after quickening)Presently, the most effective drug for IPT is sulfadoxine-pyrimethamine (SP) Women should receive at least two doses of IPT with SP at ANC visits after quickening, but no more frequently than monthly

IPTp can be given during regularly scheduled antenatal care visits

Intermittent Preventive Treatment: Dose and Timing A single dose is three tablets of

sulfadoxine 500 mg + pyrimethamine 25 mg

Healthcare provider should dispense dose and directly observe client taking dose

Instructions for Giving Intermittent Preventive Treatment Ensure woman is at least 16 weeks

pregnant and that quickening has occurred

Inquire about use of SP in last 4 weeks Inquire about allergies to SP or other

sulfa drugs (especially severe rashes) Explain what you will do; address the

woman’s questions Provide cup and clean water

Instructions for Giving Intermittent Preventive Treatment (cont’d.) Directly observe woman swallow three

tablets of SP Record SP dose on ANC and clinic card Advise the woman when to return:

For her next scheduled visitIf she has signs of malariaIf she has other danger signs

Reinforce the importance of using ITNs

Intermittent Preventive Treatment: Contraindications to Using SP Do NOT give during first trimester: Be sure

quickening has occurred and woman is at least 16 weeks pregnant

Do NOT give to women with reported allergy to SP or other sulfa drugs: Ask about sulfa drug allergies before giving SP

Do NOT give to women taking co-trimoxazole, or other sulfa-containing drugs: Ask about use of these medicines before giving SP

Do not give SP more frequently than monthly: Be sure at least 1 month has passed since the last dose of SP

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All trimesters: First line - Chloroquine; Quinine; Second line - Artesunate / Artemether /

Arteether 2nd / 3rd trimester: with caution

Pyrimethamine + sulphadoxine; Mefloquine Contra indicated:

Primaquine; Tetracycline; Doxycycline; Halofantrine

Choice of Anti malarials in pregnancyTreatment of Malaria in Pregnancy

Treatment of Falciparum Malaria in pregnancy without complications 1st trimester

Quinine + Clindamycine Failure :

- Quinine + Clindamycine- ACT- Artesunate + Clindamycine

2nd / 3rd trimester ACT Artesunate + Clindamycine Failure :

○ Artesunate + Clindamycine○ Quinine + Clindamycine

Treatment of Severe Falciparum Malaria in Pregnancy Initial : Artesunate

2,4 mg/kg BW hour 0,12,24-every 24-hour

Followed : Artesunate + Clindamycine Alternative

Initial : Quinine20mg/kgBW loading dose 4-hour

10mg/kgBW/8-hourFollowed : Quinine + Clindamycine

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Chloroquine: 600mg (base) start, 300mg after 6 hours, 24 hours & 48 hours

Quinine: IV - 20mg/kg infusion over 4 hours, repeat 8 hourly.

Maintenance: 10mg over 4 hours, 8 hourly. Follow with oral medication after clinically stable.

Oral – 600mg 8hourly ( maximum 2 gm / day) for 7 days. Artesunate:

Oral-100mg BD on day 1, then 50mg BD for 4-6 days (Total dose 10mg/kg).

IM / IV-120mg on Day 1 followed by 60mg daily for 4 days. In severe cases an additional dose of 60mg after 6 hours on Day 1.

Dose of Anti malarialsTreatment of Malaria in Pregnancy

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Artemether: Six amp (480mg) IM in 5 / 3 days. 1x2x1+1x1x4 OR 1x2x3.

Arteether: One amp (150mg) IM / day for3 consecutive days.

Pyrimethamine 25mg+sulphadoxine 500mg tablets: Three tablets single dose.

Mefloquine: 15mg / kg body wt., up to 1 Gm in a single dose. OR Tablets of 250mg, 3 tab start, then 2 tab after 6-8 hours.

With body wt >60kg, a third dose of 1 tab after 6-8 hours.

Dose of Anti malarialsTreatment of Malaria in Pregnancy

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Treatment of Vivax Malaria in Pregnancy Use of Primaquine & Proguanil are not safe in

pregnancy and also in lactating mothers. Therefore to prevent the relapse of vivax malaria,

suppressive chemoprophylaxis with Chloroquine is recommended.

Tablet Chloroquine 300 mg (base) weekly should be administered to all such patients until stoppage of lactation.

At that point, a complete treatment with full therapeutic dose of Chloroquine and Primaquine (7.5mg b.I.d. or 15mg daily, for 14 days) should be administered.

However in case of resistance, Primaquine or Proguanil may be given with caution in 2nd half of pregnancy.

Radical cure

Conclusion Malaria is more common in pregnancy

compared to the general population probably due to immuno supression and loss of acquired immunity to malaria

Intermittent preventive treatment of pregnant women has a benefecial impact on maternal and infant health

Choice of antimalarials in pregnancy especially falciparum malaria : all trimesters first line : chloroquine, quinine. Second line : artesunate / artemether / arteether. 2nd / 3rd trimester : pyrimetamine + sulphadoxine, mefloquine.