Abstract
The name ‘proto-zoa’ literally means ‘first animals’, and early classification systems grouped the protozoa as basal members of the animal kingdom. However, they were recognised as a discrete assemblage on the basis of their unicellularlity and were assigned to the taxon Protozoa (but still invariably figured as the trunk of the animal tree of life).
Protozoa is a parasitic single-celled organism that can divide only within a host organism. Parasites are a diverse group of organisms that account for the majority of human infections.
According to a World Health Organization (WHO) study in 2010, the prevalence was as high as 48.5 million, with 59 724 deaths annually and 8.78 million Disability Adjusted Life Years. The disability-adjusted life year (DALY) is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death). [EL 1]
Diagnosis may initially be difficult and is based largely on travel history and a variety of tests required (stool, blood tests and imaging) depending on presenting signs and symptoms.
The sequel on maternal and fetal health relies on type of infection, gestational age at presentation, patient’s own natural immunity, early diagnosis, prompt treatment and the prevention of complications.
The decision to treat parasitic infection in pregnancy should be based on risk–benefit ratio. The women should be informed of all potential risks on the fetus and should be allowed to make an informed choice.
Withholding treatment may be appropriate when infection does not pose immediate threat to the life of the mother or fetus in the presence of normal maternal haemoglobin and normal fetal growth.
Use of praziquantel (Biltricide®) medication for helminthic infections, during pregnancy and lactation was historically withheld due to concerns in 1994 of effects on the fetus. However, WHO informal consultation recommended that use of the drug would result in reduced maternal anaemia and perinatal morbidity. [EL 2]
Introduction
The name ‘proto-zoa’ literally means ‘first animals’, and early classification systems grouped the protozoa as basal members of the animal kingdom. However, they were recognised as a discrete assemblage on the basis of their unicellularlity and were assigned to the taxon Protozoa (but still invariably figured as the trunk of the animal tree of life).
Protozoa is a parasitic single-celled organism that can divide only within a host organism. Parasites are a diverse group of organisms that account for the majority of human infections.1
According to a World Health Organization (WHO) study in 2010, the prevalence was as high as 48.5 million, with 59 724 deaths annually and 8.78 million Disability Adjusted Life Years. The disability-adjusted life year (DALY) is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death).2 [EL 1]
Diagnosis may initially be difficult and is based largely on travel history and a variety of tests required (stool, blood tests and imaging) depending on presenting signs and symptoms.
The sequel on maternal and fetal health relies on type of infection, gestational age at presentation, patient’s own natural immunity, early diagnosis, prompt treatment and the prevention of complications.
The decision to treat parasitic infection in pregnancy should be based on risk–benefit ratio. The women should be informed of all potential risks on the fetus and should be allowed to make an informed choice.
Withholding treatment may be appropriate when infection does not pose immediate threat to the life of the mother or fetus in the presence of normal maternal haemoglobin and normal fetal growth.
Use of praziquantel (Biltricide®) medication for helminthic infections, during pregnancy and lactation was historically withheld due to concerns in 1994 of effects on the fetus. However, WHO informal consultation recommended that use of the drug would result in reduced maternal anaemia and perinatal morbidity. [EL 2]
General Features of Protozoa
Protozoa are single-celled micro-organisms which represent the earliest form of animal life. They have a typical tri-laminar unit membrane which encloses the cytoplasm. Various organelles present in cytoplasm play a vital role in respiration, nourishment, reproduction and regulation of osmotic pressure.
They have been classified into four groups or phyla: Sarcomastigophora, Apicomplexa, Microspora and Ciliophora.
The species traditionally collectively termed ‘protozoa’ are not closely related to each other, and have only superficial similarities (eukaryotic, unicellular and motile).
In this chapter, we will be dealing with four main protozoa that affect humans: Giardia, Trichomonas, Amoeba and Toxoplasma.
Giardia Lamblia
Introduction
Giardia intestinalis is a flagellated protozoan parasite caused by flagellate Giardia lamblia. It is the most common pathogen causing intestinal infection which may be asymptomatic or cause diarrhoea.3
Epidemiology
Giardiasis is found worldwide, with its prevalence being more common in areas of poor sanitation. Infection is more common in children due to their poor natural immunity and lack of adequate intestinal immunoglobulin A (IgA).
While ingestion of contaminated food and water is a more common mode of transmission, direct person-to-person transmission may also occur in children and homosexual men.3
Morphology and Life Cycle
Giardia lives in the duodenum and upper jejunum and is the only protozoa found in the lumen of the human small intestine.1 It occurs in vegetative and cystic forms. Infections occur by ingestion of cysts in contaminated food and water. As few as 10 cysts are capable of initiating an infection. Within an hour of ingestion, the cyst hatches out into two trophozoites which multiply by binary fission and colonise the duodenum.
Pathogenesis and Clinical Features
The incubation period is about one to two weeks. The organisms are typically seen in the crypts of the duodenum or the ileum.1, 2 The villous architecture is damaged, causing atrophy resulting in malabroption of fat, nutrients and vitamins particularly A and B12. The mechanism causing alteration of mucosal architecture is possibly immune-mediated.6
Occasionally, Giardia may colonise the gall bladder, causing biliary colic and jaundice.
The acute stage lasts for three to four days and is characterised by sudden onset of watery diarrhoea, abdominal distension, flatulence, nausea, anorexia and abdominal cramps. The stools are malodorous and loose, but with no blood. If untreated, it may progress to chronic infection resulting in malabroption and steatorrhoea. Bacterial overgrowth is responsible for fat malabsorption.
Maternal Implications
Complications and Symptoms
Chronic intestinal upset, flatulence, diarrhoea, reflux acidity
Malnutrition, signs of anaemia
Poor weight gain
Pregnant women may also suffer from an exaggerated form of hyperemesis gravidarum
The effects in pregnancy are mainly related to associated diarrhoea, malabsorption, fluid and electrolyte disturbances.
Maternal-to-fetal transmission has not been documented.
Fetal Implications
Fetal implications are usually secondary to maternal anaemia rather than a direct effect on the fetus.
1. Low birthweight.
2. Intrauterine growth restriction (IUGR). Late-onset IUGR is more frequently seen in women presenting with symptoms of Giardia infection and subsequent anaemia. [EL 1]
3. Preterm deliveries. Preterm delivery more frequently occurs in second and third trimesters. [EL 2]
4. Fetal anaemia.
Diagnosis4
1. Stool examination (microscopy) commonly reveals cysts and occasionally trophozoites.
Concentration, centrifugal and flotation is useful when cysts are sparse. The stools usually do not show any red blood cells or pus cells.
2. Duodenal aspiration, when stool samples have negative results and there is strong suspicion of the disease, may be done to confirm diagnosis.
3. Immunodiagnostic tests such as enzyme-linked immunoassay (ELISA) and immunochromatographic strip tests have also been developed for detection of Giardia antigens in faeces, but not for routine use. Antibody demonstration is not useful in diagnosis.
Treatment5
The pregnant woman should be treated only if symptomatic, and the mainstay of the treatment is maintaining adequate hydration.
1. Metronidazole (pregnancy category B) with a cure rate of 85–90 per cent is the most commonly prescribed first-line antibiotic used in the treatment.
The recommended dose is 250 mg orally three times a day for five to seven days. However, its use has been associated with significant failure rates in clearing parasites from the gut and is associated with poor compliance.
2. Tinidazole (TNZ) either as an oral single dose of 2 g or 500 mg twice daily for three to five days. It causes minor side effects of bitter or metallic taste. Major side effects may include change in consciousness, difficult or noisy breathing, wheezing or tightness in chest.
In countries such as the United States where tinidazole is not licensed for use in pregnant women (pregnancy category C), metronidazole 250 mg three times daily for five days can be used.
Breastfeeding
In breastfeeding women, it is advisable to stop breastfeeding for 12–24 hours after metronidazole therapy, especially after single high dose has been used.
Metronidazole is FDA pregnancy category B. (Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.) It is best avoided in the first trimester.
The US Food and Drug Administration does not recommend furazolidone use in pregnancy. It is recommended only if benefits outweigh the risks and no other alternative is available (category C).
Trichomonas Vaginalis (Tv)
Introduction and Epidemiology6
Trichomonas vaginalis is an anaerobic, flagellated protozoan parasite.
Trichomonas is a facultative anaerobe, unable to survive outside the body, therefore infection is transmitted directly from person to person.
It is a sexually transmitted infection commonly found in the human genitourinary tract.
T. vaginalis selectively infects the squamous epithelium.6
Approximately more than 250 million people get infected by this parasite annually.
The incidence is more than 3.5 million in the United States, whereas in the UK it is relatively uncommon, and tends to be clustered in specific urban areas among black ethnic minorities.
The incidence ranges from 5 to 10 per cent in healthy women to as high as 50–70 per cent amongst sex workers and female prison inmates.
The peak incidence is about 16–35 years. Trichomonas vaginalis lives in the vagina and cervix and may also be found in the Bartholin’s gland, urethra and urinary bladder.
Trichomonas often coexists with other sexually transmitted infections (candidiasis, gonorrhoea, syphilis and HIV). The pH of the vagina is a critical growth-limiting factor, and the favourable pH is usually 5.5–7.
Signs and Symptoms
The incubation period may vary from four days to four weeks.
Symptoms of severe vulvo vaginitis, irritation of the genital area, itching, an increased, strong-smelling frothy vaginal discharge, discomfort while urinating and or dyspareunia.
The vulva may be erythematous, with the presence of fresh red spots and excoriations.
The cervix and vagina may demonstrate characteristic red punctuate haemorrhages, giving it a classical ‘strawberry cervix’ appearance.
Regional lymphadenopathy and endometritis and pyosalpinx are infrequent complications due to early diagnosis and treatment.
Fetal Implications
Colonisation of the lower genital tract with trichomonas has been shown to increase the risk of:
1. Premature rupture of membranes (PROM)
2. Preterm labour
3. Small for gestational age
Evidence that treatment of colonised patients prevents PROM is lacking.
Neonatal Implications
Neonatal effects occur due to contact with the organism during the process of childbirth. [EL 2]
Rarely, neonatal pneumonia and conjunctivitis have been reported in infants born to infected mothers.9
Vaginal infection in the female neonate incidence is 2–17 per cent. The infection site is vaginal epithelium as neonatal vaginal epithelium is relatively mature due to maternal oestrogen making it susceptible to trichomonas.
Within three to four weeks the maternal oestrogen is metabolised and thus the epithelium becomes resistant to trichomonas.
Diagnosis
Trichomonas may be isolated from urine sediment and vaginal secretions by
1. Wet mount preparations of the vaginal discharge (placing a small amount of vaginal discharge on a microscope slide and mixing with a few drops of saline solution). T. vaginalis can be identified by its characteristic jerky movements. The sensitivity ranges between 38 and 82 per cent). It is a reliable and simple method and treatment can thus be initiated immediately.
2. Cultures – trichomonas can be grown in a variety of solid and liquid media, in tissue culture and in egg cysteine, peptone, liver, maltose (CPLM).
3. Papanicolaou test smears and special stains. High vaginal swab (HVS) collected on cotton swabs left for some time in a tube containing 5 per cent glucose saline shows better shape and motility of the organism.
4. Serological tests like indirect haemagglutin and gel diffusion are available for antibody detection.
5. Nucleic acid amplification tests (NAATs) to offer the highest sensitivity, up to 75–90 per cent for detection of T. vaginalis.
A combination of wet mount and culture increases the sensitivity of detecting trichomonas to 98 per cent, as reported by several studies.
Screening
Evidence does not support routine screening for trichomoniasis in asymptomatic pregnant women.
Treatment7,8
1. Metronidazole is the drug of choice. [EL 1]
More than 98 per cent of the strains are sensitive to the drug, although some resistance has been demonstrated both in vivo and in vitro studies.
The recommended dose for initial treatment is 2 g orally, although in pregnancy a five-day course is recommended. Both the partners should be treated simultaneously, and sexual intercourse should be avoided until the completion of treatment.
Meta-analyses and more recent studies have concluded that there is no evidence of teratogenicity from the use of metronidazole [EL 1] and it can be used in all stages of pregnancy and during breastfeeding.
The British National Formulary advises against high-dose regimens in pregnancy, i.e. 2 g stat dose, and instead low-dose regimen 400 mg eight-hourly for five to seven days is recommended.
2. Tinidazole is an alternative drug of choice.
In the United States, tinidazole in pregnancy is category C and its safety in pregnant women has not been well evaluated. The manufacturer states that the use of tinidazole in the first trimester is contraindicated.
Failed Treatment
Failure of treatment may be due to inadequate therapy, resistance, reinfection, or low patient compliance.
A history should be taken to try to find any of the above reasons for failure of treatment.
In case of non-response, initial regime should be repeated with a higher-dose course of metronidazole (800 mg three times daily for seven days. [EL 3]
If there is further failing, of this third regime, resistance testing should be performed (if available).
Breastfeeding and metronidazole: metronidazole is secreted in breastmilk and may affect its taste. The manufacturers recommend avoiding high doses if breastfeeding, or if using a single dose of metronidazole, breastfeeding should be discontinued for 12–24 hours to reduce infant exposure.
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