Parasitic infections in pregnancy
Parasitic infections in pregnancy: malaria, giardiasis, amoebiasis, hydatid, hookworm
Malaria, intestinal protozoa, hydatid disease and hookworm are common in rural Pakistan, and pregnancy makes several of them worse. CPSP asks the life cycle and film features of each parasite, why the placenta changes malaria, how each is diagnosed, and which antiparasitic drugs are unsafe in pregnancy.
Malaria: life cycle
- A female Anopheles mosquito injects sporozoites, which multiply in the liver (pre-erythrocytic phase) into merozoites; these invade red cells (rings, trophozoites, schizonts), and some become gametocytes taken up by the next mosquito. *P. vivax* and *P. ovale* also leave dormant liver hypnozoites.
- Synchronous schizont rupture releases pyrogens (TNF, IL-1): cold, hot and sweating stages. The anaemia is normocytic and normochromic.
- Relapse comes from hypnozoites (vivax, ovale); recrudescence from surviving blood forms after inadequate treatment.
Malaria species
| Species | Fever pattern | Key features |
|---|---|---|
| *P. falciparum* | Malignant tertian (about 48 h but irregular; may be quotidian with two broods) | Shortest liver phase (about 6 days); invades red cells of all ages; multiple small rings, banana-shaped gametocytes; cerebral malaria, blackwater fever, hypoglycaemia |
| *P. vivax* | Benign tertian (48 h) | Commonest species in Pakistan; infected cells enlarged and pale with fine red Schüffner dots, amoeboid trophozoites; enters reticulocytes via Duffy antigen; hypnozoites cause relapse; splenic rupture |
| *P. ovale* | Benign tertian | Enlarged oval cells with ragged (fimbriated) edges and Schüffner dots; hypnozoites |
| *P. malariae* | Quartan (72 h) | Longest pre-erythrocytic (liver) phase (about 2 weeks) and long incubation; band forms; nephrotic syndrome; no hypnozoites |
| *P. knowlesi* | Quotidian (24 h) | Monkey malaria of South-East Asia; can be severe |
- A long active liver phase (malariae) is different from a dormant hypnozoite (vivax, ovale).
- Diagnosis: thick film detects parasites; thin film identifies species and counts parasitaemia (Giemsa).
- Rapid diagnostic tests: falciparum tests detect histidine-rich protein 2 (HRP-2), which persists for weeks after cure, so a test stays positive after successful treatment; the film judges response. Parasites with HRP-2 gene deletions give false negatives. pLDH-based tests turn negative sooner.
- Thalassaemia, sickle trait and G6PD deficiency partly protect against falciparum; Duffy-negative red cells resist vivax.
Why malaria is worse in pregnancy
- Pregnancy lowers cell-mediated immunity, and primigravidae are most at risk. Falciparum-infected cells express VAR2CSA, which binds chondroitin sulphate A on syncytiotrophoblast, so parasites sequester in the placenta even when the blood film is scanty. Antibodies to VAR2CSA build up with each pregnancy.
- Fetal effects: low birth weight, preterm birth, miscarriage, stillbirth. Old infection leaves haemozoin pigment in placental macrophages.
- Maternal effects: severe anaemia, hypoglycaemia (worsened by quinine, which stimulates insulin), pulmonary oedema and cerebral malaria (PfEMP1 binding ICAM-1 and CD36).
- Congenital malaria presents 10–30 days after birth; it does not relapse, as there are no hypnozoites.
Antimalarials in pregnancy
| Situation | Drug |
|---|---|
| Uncomplicated falciparum | Artemether-lumefantrine (WHO allows it in all trimesters) |
| Severe malaria | IV artesunate |
| Vivax | Chloroquine, then weekly chloroquine to suppress relapse until delivery |
| Prophylaxis, chloroquine-resistant area | Mefloquine weekly (if no epilepsy or psychiatric illness), plus bed nets and repellents |
| Avoid | Primaquine, tafenoquine, doxycycline; atovaquone-proguanil only if no alternative |
- Primaquine is an oxidant that causes haemolysis in G6PD deficiency: dark (cola-coloured) urine, jaundice with unconjugated bilirubin and back pain after starting antimalarials. Even if the mother's G6PD is normal, the fetal G6PD status cannot be known, so radical cure waits until after delivery and breastfeeding (with infant testing).
- Sulfadoxine-pyrimethamine intermittent preventive treatment blocks parasite folate synthesis, so only 0.4 mg folic acid is given with it.
Giardiasis
- *Giardia lamblia*: pear-shaped flagellate with two nuclei and a ventral sucking disc. It is non-invasive: it attaches to duodenal and jejunal mucosa, blunts villi and causes foul, pale, greasy stools, bloating and lactose malabsorption, without blood or pus.
- Cysts resist chlorination. Cysts are passed intermittently, so send three stools on different days or use stool antigen or PCR. Trophozoites appear mainly in watery stools, cysts in formed stools.
- Recurrent giardiasis suggests selective IgA deficiency. In the first trimester use poorly absorbed paromomycin; metronidazole later.
Amoebiasis
- *Entamoeba histolytica* lives in the large intestine, mainly the caecum and ascending colon. The infective cyst has four nuclei; trophozoites containing ingested red cells are diagnostic.
- Trophozoites invade with Gal/GalNAc lectin, amoebapores and cysteine proteases, making flask-shaped ulcers with undermined edges and normal mucosa between, giving bloody dysentery. Steroids given for presumed ulcerative colitis can cause fulminant colitis.
- Liver abscess: trophozoites travel by the portal vein, usually to the right lobe: single abscess with anchovy-sauce pus. Ultrasound shows it, and amoebic serology is the most sensitive test (stool is often negative). Treat with metronidazole, then a luminal agent.
- Acanthamoeba, a free-living amoeba, causes a painful ring-infiltrate keratitis in contact lens wearers who use tap water.
Hydatid disease
- *Echinococcus granulosus*: dog is the definitive host, sheep the usual intermediate host; humans are accidental intermediate (dead-end) hosts after swallowing eggs from dog faeces. Oncospheres reach the liver (60–70%) then lung; a slow-growing lung mass in a farmer may be hydatid. Humans are also intermediate hosts in cysticercosis (*Taenia solium* eggs), causing neurocysticercosis.
- Cyst wall: host pericyst, laminated membrane and germinal layer producing protoscolices (hydatid sand). Ultrasound: daughter cysts, water-lily sign, eggshell calcification.
- Anaphylaxis on puncture: the host is sensitised by leaked antigen and has specific IgE bound to mast cells. Cyst fluid spilled at surgery (even at caesarean section) cross-links this IgE, causing IgE-mediated mast cell degranulation with urticaria, bronchospasm and shock. A unilocular liver cyst in someone from a sheep-rearing area is hydatid until proven otherwise; never aspirate it blindly.
- Rupture into the bile ducts causes colic and jaundice; hydatid disease does not cause cholangiocarcinoma (liver flukes do).
- Albendazole (blocks beta-tubulin) is given around surgery but avoided in the first trimester.
Hookworm
- *Ancylostoma duodenale* and *Necator americanus*: larvae penetrate bare feet, pass through the lungs and suck blood in the small bowel, causing microcytic iron deficiency anaemia (not macrocytic) and eosinophilia, important in pregnant field workers. Albendazole is given after the first trimester. B12 deficiency comes from the fish tapeworm, not hookworm.
Remember Falciparum hides in the placenta: a scanty film does not exclude placental malaria.
Exam trap Never give primaquine in pregnancy: the fetus may be G6PD deficient.
Exam trap Do not give steroids for bloody diarrhoea before excluding amoebiasis.
How FCPS asks about this
- Malignant tertian malaria, banana-shaped gametocytes: *P. falciparum*.
- Quartan malaria and longest liver phase: *P. malariae*.
- Enlarged pale red cells with Schüffner dots: *P. vivax*.
- Dark urine after starting antimalarials: primaquine haemolysis in G6PD deficiency; not given in pregnancy.
- Rapid test still positive after cure: HRP-2 persists.
- Repeat stool tests for Giardia: cysts are passed intermittently.
- Shock after puncturing a liver cyst: IgE-mediated anaphylaxis to hydatid fluid.
Test yourself on this topic
5 of the 66 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A pregnant woman from a sheep-farming family in Balochistan is found on ultrasound to have a hydatid cyst in the liver. What role does a human play in the life cycle of Echinococcus granulosus?
Answer: Accidental dead-end intermediate host
Dogs are the definitive hosts, carrying adult tapeworms in the gut and passing eggs in their faeces. Sheep and other livestock are the normal intermediate hosts, developing hydatid cysts that dogs eat. Humans become accidental intermediate hosts by swallowing eggs, and the cysts that form are a dead end because human organs are not usually eaten by dogs. Humans never carry the adult worm or pass eggs.
Echinococcus life cycle
- Dog: definitive host
- Sheep: intermediate host
- Human: accidental, dead-end
- Humans swallow eggs
Remember Humans catch the cyst, never the worm.
Exam trap Eating meat from an infected sheep does not give a human hydatid disease; swallowing dog-passed eggs does.
Why the other options are wrong
- Definitive host releasing eggs The dog is the definitive host.
- Vector carrying larvae between animals There is no vector in this life cycle.
- Reservoir host for adult worms Adult worms live only in dogs.
- Paratenic host transmitting larvae Larvae do not pass on from humans.
In high-transmission areas of Africa, pregnant women receive monthly sulfadoxine–pyrimethamine to prevent placental malaria. They are advised to take folic acid 0.4 mg daily rather than 5 mg. Why can the higher folic acid dose reduce the benefit of the drug?
Answer: It lets the parasite bypass the block
Sulfadoxine inhibits dihydropteroate synthase and pyrimethamine inhibits dihydrofolate reductase, so together they block two steps of folate synthesis that the parasite needs for DNA replication. High-dose folic acid can be taken up and used by the parasite, partly bypassing this block and reducing the drug's antimalarial effect. The standard 0.4 mg dose does not cause this problem. The interaction is pharmacodynamic, not a change in absorption or metabolism.
SP and folic acid
- Sulfadoxine: dihydropteroate synthase
- Pyrimethamine: dihydrofolate reductase
- High-dose folate bypasses the block
- Use 0.4 mg folic acid with SP
Remember Too much folate feeds the parasite past the block.
Exam trap Women on SP who are also on co-trimoxazole for HIV should not take SP, because both block the same pathway.
Why the other options are wrong
- It speeds the liver breakdown of the drug Not a recognised interaction.
- It blocks absorption of the drug Absorption is unaffected.
- It binds the drug in the plasma Not the mechanism.
- It raises parasite chloroquine resistance Unrelated to chloroquine resistance.
A 3-week-old baby has fever, poor feeding, pallor, jaundice and hepatosplenomegaly. His mother had untreated fever with rigors in the last month of pregnancy in rural Balochistan. The baby has had no mosquito exposure since birth because he has been kept indoors under a net. What is the most likely diagnosis?
Answer: Congenital malaria
Congenital malaria results from parasites crossing the placenta, usually around delivery, from a mother with malaria in late pregnancy. Symptoms typically start 10–30 days after birth with fever, anaemia, jaundice and hepatosplenomegaly. Because transmission is through the placenta, there are no hypnozoites, so even vivax does not relapse. Haemolytic disease presents in the first days, and biliary atresia gives pale stools without fever or anaemia.
Congenital malaria
- Transplacental spread
- Onset 10–30 days after birth
- Fever, anaemia, jaundice, splenomegaly
- No hypnozoites: no relapse
Remember Feverish, anaemic 3-week-old of a mother with late malaria: check a blood film.
Exam trap Congenital vivax malaria does not need primaquine, because no liver hypnozoites form.
Why the other options are wrong
- Neonatal sepsis from group B streptococcus Usually presents in the first days with respiratory distress or shock.
- Haemolytic disease of the newborn Presents within the first days with jaundice and anaemia.
- Congenital toxoplasmosis Chorioretinitis, hydrocephalus and calcification are typical.
- Biliary atresia Pale stools and dark urine without fever or anaemia.
A woman at 24 weeks was treated for Plasmodium falciparum malaria with a drug of uncertain quality from a market stall. She has not left her home, which is fully screened, and has had no new mosquito exposure. Three weeks later she again has fever and ring forms of P. falciparum on her film. What is the most likely explanation?
Answer: Recrudescence from blood stages
P. falciparum does not form hypnozoites, so it cannot relapse from the liver. Return of falciparum parasitaemia within weeks of treatment, without new exposure, is recrudescence: blood-stage parasites that survived inadequate or failed treatment multiply again. Poor-quality drugs, incomplete courses, vomiting and drug resistance are common causes. Relapse from hypnozoites is a feature of P. vivax and P. ovale.
Recrudescence vs relapse
- Recrudescence: surviving blood forms
- Falciparum and malariae
- Relapse: liver hypnozoites
- Vivax and ovale
Remember Falciparum comes back from the blood, vivax from the liver.
Exam trap Recrudescence after treatment should raise concern about drug quality, adherence or resistance.
Why the other options are wrong
- Relapse from liver hypnozoites P. falciparum has no hypnozoites.
- New infection from a mosquito bite She has had no new exposure.
- Activation of placental gametocytes Gametocytes do not cause clinical relapse.
- Malaria acquired by transfusion No transfusion was given.
Entamoeba histolytica trophozoites must first attach to colonic epithelial cells before they can kill them and invade. Antibodies that block one parasite surface molecule prevent this attachment and protect animals from amoebic colitis. Which molecule mediates attachment?
Answer: Gal/GalNAc lectin
Entamoeba histolytica binds to galactose and N-acetylgalactosamine residues on colonic mucins and epithelial cells using its Gal/GalNAc lectin. Attachment is followed by contact-dependent killing using pore-forming amoebapores and cysteine proteases, which also degrade the extracellular matrix and allow invasion. Secretory IgA against the lectin protects against infection. Amoebae lack lipopolysaccharide, capsules and pili, which are bacterial structures.
E. histolytica virulence
- Gal/GalNAc lectin: attachment
- Amoebapores: kill cells
- Cysteine proteases: invasion
- Ingests red cells and debris
Remember Lectin to stick, amoebapore to kill.
Exam trap Pores and proteases cause the damage only after the lectin has attached the amoeba.
Why the other options are wrong
- Lipopolysaccharide endotoxin A Gram-negative bacterial component.
- Hyaluronidase Not the main amoebic virulence factor.
- Polysaccharide capsule A bacterial and fungal structure.
- Fimbrial pili A bacterial structure.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Infection in obstetrics and gynaecology, Parasitic infestations in pregnancy: malaria, giardiasis, amoebiasis, hydatid disease
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