MALARIA IN

PREGNANCY
Dr. Frank Ani
Dept. of Obstetrics and Gynecology.
PRESENTATION OUTLINE

 INTRODUCTION
 EPIDEMIOLOGY
 TERMINOLOGIES
 AETIOPATHOGENESIS
 EFFECT OF PREGNANCY ON MALARIA
 EFFECT OF MALARIA ON PREGNANCY
 MODE OF TRANSMISSION
 DIAGNOSTIC TECHNIQUES
 TREATMENT
 CONCLUSION
INTRODUCTION

 Malaria is highly endemic in Nigeria

 Is a leading cause of morbidity and mortality
 Accounts for about 60% OPD Consultations
 Most Vulnerable groups are under 5 children,
Pregnant women, HIV +ve and Non Immune Visitors
 It poses Huge economic loss due to cost of treatment
and man hour loss to the Nation
EPIDEMIOLOGY
 Over 300 million cases of malaria reported
annually globally(>90% in Africa).

 Accounts for about 2-3 million deaths

annually(>90% in Africa)

 Burden of Malaria Infestation equals TB+

AIDS+ Measles + Leprosy combined x 5

 Responsible for 11% of maternal mortality

 More amongst primigravidae and

secundigravidae
 AETIOPATHOGENESIS
 Malaria is caused by protozoa of the genus plasmodium.

 There are four species of protozoan genus plasmodium

-P. falciparum-found in Africa, south East Asia, Papua New Guinea
-P. Vivax – found in central America, Indian subcontinent and
China.
-P. Malariae – Wide spread in distribution
-P. Ovale – Mostly found in west Africa

 In Nigeria malaria infestations are caused mostly by:

- P. Falciparum- 95%
- P. malariae – 4%
- P. Ovale - 1%
 P. Vivax infestation – Not present in Nigeria b/c of the absence of
Duffy blood group.
 PATHOGENESIS OF MALARIA IN
PREGNANCY

 In pregnant women with malaria, P. falciparum in the erythrocytes is

sequestered in the intervillous space.

 Pregnancy-associated malaria variant surface antigen [VSA-PAM])

mediates adhesion of infected erythrocytes to chondroitin sulfate A
(CSA) on the syncytiotrophoblast lining the intervillous space.

 Inflammatory response is induced and The placental is thickened from

inflammation which may reduce placental transport of oxygen and
nutrients, leading to fetal growth restriction and, possibly, fetal demise.
 PATHOGENESIS CONTD.
 Antibodies formed in response to VSA-PAM (particularly
anti-VAR2CSA) correlate directly with parity in
holoendemic areas.

 Primigravid women in holoendemic areas are more prone

to complications of pregnancy-associated malaria than
multigravid women in holoendemic areas, who have
moderate-to-high VSA-PAM Immunoglobulin G levels.
 MODE OF TRANSMISSION

-Mother to child transplacental transmission, affects about

20% of neonates.

-Bite of an infected female anopheles mosquito with

transmission of the parasites( commonest mode)

-Transfusion of infected blood. Parasites remain viable in

stored blood for 2 weeks

-Use of needles shared amongst addicts infected with the

malaria parasite.
LIFE CYCLE OF MALARIA
PARASITE
 Inoculation of sporozoites by female anopheles mosquito
during blood meal

 Sporozoites circulate in blood for about 30 min then enter

liver cells

 Each sporozoite then divide thousand times to produce

merozoites in a process called pre erythrocytic schizogony
in the liver

 Swollen liver cells then burst to release merozoites in to

blood stream
LIFE CYCLE CONT.
 This begins the symptomatic stage of the disease

 In p. vivax and p. ovale the hepatic stage can remain

dormant for months and this is responsible for relapse

 While in the blood, each merozoite enters a red cell and

becomes a trophozoite (ring form). Intra-erythrocytic
(asexual) cycle

 They then mature into schizont and burst to release

merozoites
 LIFE CYCLE CONT.
 The Synchronous rupture of the ring form every 48 to 72 hours(2-3
days) in case of p. malariae corresponds to the febrile paroxysm

 After a series of intra erythrocytic cycle, some trophozoites

transform to form gametes (gametocytes), they can stay long and
relatively inert.

 After a blood meal by the female anopheles mosquito from an

infected person, the gametes are sucked, then mature into female and
male gametocytes with in the Gastrointestinal tract of the mosquito
LIFE CYCLE CONT.
 These then undergo process of sexual reproduction
within the mosquitoes' digestive system

 This cycle produces sporozoites in about 2 weeks.

 They are then stored in the salivary gland of the

mosquito.

 These are then injected into a human being during a

bite for blood meal.
MALARIA PARASITE LIFE CYCLE

Oocyst
Sporozoites

Mosquito Salivary
Zygote Gland

Gametocyte Liver stage

s

Red Blood
Cell Cycle
EPIDEMIOLOGICAL TERMINOLOGIES OF MALARIA

 ENDEMICITY
- Risk of getting malaria is present all year round

 EPIDEMIC
-Risk of getting the disease may disappear or remain insignificant for a
long time with sudden reappearance with bouts of disease.
Transmission is intermittent.

 HOLOENDEMICITY
-There is intense all year transmission of malaria parasite with high
population immunity.

 HYPERENDEMIC
-Seasonal transmission which do not provide adequate immunity .
 TERMINOLOGIES CONT.
 Mesoendemic
-some malaria transmission with occasional epidemics providing low
immunity.
 Hypoendemic
When there is limited malaria transmission, with little or no immunity

 Gametocytes- Is the sexual stage of malaria parasite present in the host RBC

 Cure- Is the total elimination of the symptoms and asexual blood stage of the
malaria parasite that caused the patient to seek treatment
 CONT.

 Drug resistance- WHO defines drug resistance as the ability of

the parasite strain to survive or to multiply despite adequate and
effective drug treatment.

 Resistance to anti malaria could be due to parasite genetic

mutation or gene amplification that confers susceptibility
 CONT.

 Recurrence – Is the reappearance of asexual parasitaemia

following treatment. This could be caused by recrudescence,
relapse or new infection.

 Recrudescence- Is recurrence of asexual parasitaemia after

treatment of the infection with the same specie that cause the
initial illness
 CONT.
 Relapse – Is the recurrence of asexual parasitaemia in P.vivax and P. ovale
malaria from persistent liver stages.
Relapse occurs when the blood stage has been eliminated but hypnozoites persist
in the liver and mature to form hepatic schizonts

 Severe Falciparum malaria- Acute falciparum malaria with signs of

severity and evidence of vital signs dysfunction.
 CONT.

 UNCOMPLICATED MALARIA- IS SYMPTOMATIC INFECTION WITH

MALARIA PARASITEAMIA WITHOUT SIGNS OF SEVERITY OR
EVIDENCE OF VITAL ORGAN DYSFUNCTION

 MALARIA PIGMENT(HAEMOZOIN)- IS A DARK BROWN GRANULAR

PIGMENT FORMED BY MALARIA PARASITE AS A BY-PRODUCT OF
HAEMOGLOBIN CATABOLISM.
THESE MAY BE SEEN IN MATURE TROPHOZOITES, SCHIZONTS,
WBC AND PLACENTA
 INFLUENCE OF PREGNANCY
ON THE COURSE OF MALARIA
 Stress of pregnancy decrease immunity acquired in the non-
pregnant state

 Cell mediated immunity is depressed in pregnancy to reduce

graft rejection therefore susceptibility to other diseases normally
controlled by the cell mediated immunity such as TB is also
increased in pregnancy

 Result of declined immunity leads to increased severity of

parasiteamia and clinical disease in pregnancy.
Effects of Pregnancy on Malaria

 More common
Malaria is more common in pregnancy compared to the
general population probably due to Immunosuppression and
loss of acquired immunity to malaria during pregnancy.
 More atypical
In pregnancy, malaria tends to be more atypical in
presentation probably due to the hormonal immunological
and haematological changes of pregnancy.
 More severe
Probably for the same reason, the parasitaemia tends to be 10
times higher and as a result, all the complications of malaria
are more common in pregnancy compared to the non-pregnant
population.
EFFECTS OF PREGNANCY
ON MALARIA
 More fatal
P. falciparum malaria in pregnancy is more severe, the mortality is
also double (13 % ) compared to the non-pregnant population (6.5%).

 More selective in treatment

Some anti malarial drugs are contra-indicated in some stages of
pregnancy and therefore the treatment may become difficult,
particularly in cases of severe P. falciparum malaria.

 More problems
Management of complications of malaria may be difficult due to the
various physiological changes of pregnancy.
 EFFECTS OF MALARIA ON
PREGNANCY
MATERNAL
Worst amongst non-immune, primigravida, sickle cell disease and
Immunocompromised women.

1. Anemia: worst during the 16th-24th weeks

.Haemolysis of parasitized/non parasitized cells
.Sequestration in the spleen(hyperslenism)
.Folate deficiency/ poor nutrition
.Competing demand by the growing fetus

2. Severe infestation = Cerebral malaria

3. Gastrointestinal effects of malaria

Abdominal pains, distension, vomiting and diarrhea
EFFECTS OF MALARIA ON
PREGNANCY
4. Hypoglycemia
.Hepatic gluconeogenesis
.Increased demand for glucose utilization by mother and
fetus
.Antimalarials – Quinine stimulates insulin secretion
leading to hypoglycemia
5. Acute pulmonary oedema
6. Acute renal failure- Dehydration, shock, black water fever
7. Hyperparasitaemia
8. Hyperpyrexia
9. Premature labour
10. Prostration, acidiosis and circulatory collapse
 FETUS
Protected by three mechanisms
-Immunoglobulin G
-Placenta barrier
-Haemoglobin F
However despite these the fetus could suffer
-abortions
-intrauterine growth restriction
-intrauterine fetal death
-low birth weight
- Severe birth asphyxia
-congenital /neonatal malaria
Signs and symptoms of
malaria in pregnancy
Uncomplicated malaria
• Fever
• Chills/ Rigors
• Headaches
• Muscle/joint pains
• Nausea/vomiting
• False labor pains
• Blood film + / ++
Signs and symptoms of malaria
in pregnancy

Complicated
• Signs of uncomplicated malaria with:
• Dizziness
• Breathlessness
• Sleepy/drowsy
• Confusion/convulsion/coma
• Jaundice, dehydration
• Blood film ++ / +++
 LABORATORY DIAGNOSTIC
TECHNIQUES FOR MALARIA

 Laboratory parasitological diagnosis is required in all

suspected cases of malaria.
 Advantages of laboratory diagnosis of malaria includes
 Avoidance of unnecessary use of antimalarials
 Adequate patient care in parasite positive patient
 Identification of parasite negative patient so that further
evaluation can be carried out
 Improves case specific detection and reporting
 Confirmation of treatment failure
 INVESTIGATIONS
General Specific
 Hematocrit (FBC)  Blood smear – thick and thin film.
 Mid-stream urine for m/c/s  Blood picture – anisocytosis,
poikilocytosis, micro or
 LFT
megalocytosis, hyper/hypochromasia
 Ultrasonography
INVESTIGATION CONT.
NON-MICROSCOPIC METHOD MICROSCOPIC METHOD
 Fluorochrome staining – c acridine Blood film
orange
- Thick film – quantification of
- Positive result – differential staining parasitaemia (counting parasites
of DNA (green) and cytoplasmic relative to leucocytes)
RNA (red).
 Thin film – identification of
 Antibodies – quantification against
species.
malaria parasite.
 Using Giemsa or field stain.
 RNA or DNA polymerase chain
reaction (most sensitive) can detect
as low as 5 asexual forms/µl of
blood.
 Parasite produces specific enzyme
– pLDH (parasite lactate
dehydrogenase) which is
electrophoretically distinct from
the human LDH.
 Histidine rich protein 1 and 2.
RAPID DIAGNOSTIC TEST
 RDT is a diagnostic device that detects specific
antigens( proteins) produced by malaria Parasite. Sensitivity is
95%( New invention)

 A small drop of blood applied to an immune-chromatographic

strip which will indicate after 15 min the presence of malaria
parasite by color change

 Ideal tests for primary health care setting

 Quality assured histidine rich proteins based RDT is

recommended
COMPLICATIONS OF
MALARIA IN PREGNANCY
 What are the
effects of
malaria on the
mother and
unborn baby?
COMPLICATIONS OF MALARIA IN
PREGNANCY

 Abortion – placental sequestration

 Anaemia

 Cerebral malaria

 Low birth weight (Prematurity, IUGR)

 Stillbirth /IUFD

 Congenital infection

 Haemoglobinuria/Puerperal pyrexia

 Neonatal/Maternal Mortality

 Hypoglycaemia
Management of malaria in pregnancy
involves three aspects that are of equal
importance

1. Treatment of the malaria

2. Management of complications

3. Prevention of recurrence
TREATMENT OF MALARIA IN
PREGNANCY

• Depends on severity of the disease

- Simple / Uncomplicated
- Complicated

• Gestational age
- First trimester
- Second trimester
- Third trimester

• Aim is to achieve cure.

 TREATMENT SIMPLE/UNCOMPLICATED MALARIA

 1st Trimester = Quinine ( safe and evidence-based) WHO

recommendation.
7 days of Quinine + clindamycin

Oral Artesunate + clindamycin

 2nd and 3rd trimesters

1st Line = Artemether/Lumefantrine

(coartem)
2nd Line = Artesunate + Amodiaquine
Artesunate + fansidar
 DRUG TREATMENT OF
SEVERE
MALARIA
 ALL TRIMESTERS AND LACTATING WOMEN
1. IV or IM Artesunate for at least 24hours.
Once a patient can tolerate oral therapy, complete treatment with 3 days of
ACT. (WHO, 2015)

2. IM Artemether

3. IM or IV Quinine
SUPPORTIVE TREATMENT IN MANAGEMENT
OF MALARIA IN PREGNANCY

Correct hypoglycemia with adequate calories

 Correction of fluid and electrolyte imbalance
 Blood transfusion / EBT in acute and severe cases
 Oxygen + Diuretics in pulmonary oedema
 Anticonvulsants for Cerebral malaria
 ICU for CM
 Dialysis for ARF
Hyperpyrexia – Tepid sponge, antipyretics
 Monitoring of the fetal growth & health
 PREVENTION & CONTROL OF
MALARIA IN ENDEMIC AREAS
Available options are:
 Vector control

 Drug prophylaxis

 Vaccination
 VECTOR CONTROL
 Insecticide Treated Nets (ITNs)

-Reduces human Vs vector contact by physical barrier

-Repels or kills the vector
- Should be provided throughout pregnancy and puerperium
- Promote growth and development of fetus and newborn

 Residual house hold spraying with insecticides

 Environmental management

- Cleanliness and proper waste control

 INTERMITTENT PREVENTIVE
TREATMENT (IPT)
• It is 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 she may not have symptoms, malaria can still affect
her and the unborn child by impairing its growth

• IPT- Is the use of antimalaria drug given in treatment doses at

predefined intervals to clear presumed burden of malaria
parasites
New WHO recommendations for IPTp-SP
2015

 Started as early as possible in the second trimester,

IPTp-SP is recommended for all pregnant women at
scheduled antenatal care (ANC) visit until the time of
delivery, provided that the doses are given at least
one month apart.

 SP should not be given during the first trimester of

pregnancy; however, the last dose of IPTp-SP can be
administered up to the time of delivery without safety
concerns.
New WHO recommendations for IPTp-SP
2015
 IPTp-SP should ideally be administered as directly observed
therapy (DOT) of three tablets sulfadoxine/pyrimethamine (each
tablet containing 500 mg/25 mg SP) giving the total required
dosage of 1500 mg/75 mg SP.

 SP can be given either on an empty stomach or with food.

 SP should not be administered to women receiving co-

trimoxazole prophylaxis due to a higher risk of adverse events.

 It is preferred that women take only the recommended 0.4 mg

daily dose of folic acid but in countries, 5mg of folic acid are
used, it is recommended to withhold folic acid supplementation
for 2 weeks after taking SP to ensure optimal efficacy.
 PROPHYLAXIS FOR HIV +VE
PREGNANT WOMEN
 Cotrimoxazole prophylaxis, regardless of CD4 cell count and throughout
all trimesters of pregnancy.

 Prophylaxis consists of a daily dose of sulfamethoxazole 800 mg and

trimethoprim 160 mg.

 This provides protection against malaria as well as HIV-related

opportunistic infections.

 For HIV-infected women not taking cotrimoxazole prophylaxis, monthly

SP-IPTp is recommended
Malarial vaccines
Gene responsible for the sporozoite coating has been identified and
cloned using monoclonal antibody and hybridoma techniques.

 The anti-sporozoite vaccine developed was unsuccessful in

clinical trials.

 However, a synthetic tripeptide vaccine SPf66 developed by

Pataroyo and colleagues have been found to be partially
effective, following clinical trials in Columbia

 Further clinical trials are currently going on to identify a more

efficient vaccine for malaria.
TYPES OF VACCINES

1. Antisporozoite – RTS,S/ASO2 clinical trial in Gambia (2001) –

to prevent all malarial clinical manifestation.

2. Erythrocytic stage – reduce incidence of severe malaria and

malaria mortality.

3. Transmission blocking vaccine – reduce transmission in low

endemic area.
 TYPES OF VACCINE CONT.
48
4. Pre-erythrocytic vaccine (sporozoite)
Irradiation Attenuated Sporozoite (IAS)

Circumsporozoite protein (CSP)

5. Asexual blood stage vaccine

Merozoite specific antigen (MSA-1)

Erythrocyte binding antigen (EBA)

6.Infected red cell

Schizont infected cell surface antigen (SICA)
 TYPES OF VACCINE CONTD

7. Multivalent/multistage vaccine
1. SPf66
Developed in Colombia
Made of synthetic peptide from 3 sexual blood stage MSA
Highly immunogenic & probably predominantly act by
cellular mechanism
 New recommendations for
Mefloquine use in pregnancy.
 The Centers for Disease Control and Prevention (CDC) now
recommends the antimalarial drug mefloquine for pregnant
women both as a malaria treatment option and as an option to
prevent malaria infection for all trimesters.

 Previously mefloquine was not recommended for the treatment

of malaria in pregnant women. The change in recommendations
is based on recent Food and Drug Administration (FDA)re-
categorization of mefloquine from a pregnancy category C drug
to category B, based on their review of the published data on
mefloquine use during pregnancy.
 These data showed that pregnant women
who took mefloquine at various doses for
both prevention and treatment of malaria did
not have an increased risk of teratogenic or
adverse pregnancy outcomes compared to
the background rate in the general
population.
 CONCLUSION
 Malaria in pregnancy is a recurring factor in maternal and
perinatal morbidity and mortality. It remains an important
hindrance to the attainment of the goals of safe motherhood.

 Confirmation of diagnosis of malaria by laboratory techniques

should be accessible, affordable and on the spot result if
possible to enable proper and adequate treatment of the
disease

 Advances in the development of vaccines that can break the

chain in transmission of the malaria parasite will go a long
way in tackling the scourge of the burden of malaria and its
adverse effect on mother and child.
THANK YOU
REFERENCES