The document outlines the biology, transmission, symptoms, diagnosis, and treatment of the apicomplexan parasites Cryptosporidium and Cyclospora, which are opportunistic pathogens particularly affecting immunocompromised individuals. It details their life cycles, with a focus on the resulting diseases, cryptosporidiosis and cyclosporiasis, including their clinical manifestations and diagnostic methods. Management strategies, prevention measures, and epidemiological insights for both parasites, especially in the context of HIV/AIDS, are also discussed.

1. PART 1
Subkingdom: Protozoa
Phylum APICOMPLEXA (OPPORTUNISTIC PARASITES)
Class SPOROZOEA
Genus: Cryptosporidium, Toxoplasma, Cystoisospora
The above being opportunistic Parasites which became very
prevalent in the advent of HIV/AIDS
Dr Chitambala-Otiono MBChB, MSc Medical
Parasitology

2. Lession Outline/Study Guide
Apicomplexas: Cryptosporidium & hominis
Able to mention Morphological stages
Habitant
Infective stage of each mode of transmission
Life cycle (in detail)
Pathogenesis in general
Mode of transmission
Symptoms diagnostic or Clinical Diagnosis
Complications
Diagnosis (at least one most recommended laboratory test that can be
performed in normal hospital setup)
Control/ preventive measure
Drug of Choice

3. • An oocyst is a thick walled cell that is present in a life cycle of a
protozoa that contains a zygote within it. Therefore the egg of an
apicomplexan parasite.
• A cyst is a dormant stage of a protozoa or even bacteria that
facilitates its survival during unfavourable environmental conditions
• Sporulation; is a process by which inmature (noninfective) coccidian
oocyst develop into a mature infective form.
• Coccidia are subclass of microscopic spore-forming, single-celled
obligate intracellular parasite of the apicomplexan class
• Coccidiosis is a generic term given to the disease caused by
infection of domestic animals with Eimeria species, these being
apicomplexan protozoa that parasitize mainaly epithelia cells,
principally those of the intestinal tract

4. Diagram of a MEROZOITE (an invasive motile form/stage of an
apicomplexa) showing the principal features seen in electron
micrographs of longitudinal section.

5. CRYPTOSPORIDIUM
• Several cryptosporidium species
• Most being host adapted
• Therefore infecting a narrow range of natural host.
• Some e.g. - specifically for birds, fish etc.

6. Cryptosporidiosis
Etiologic agents in Man; below are the following 2
that cause >90% of infection):
• Cryptosporidium hominis – generally restricted to
humans
• Cryptosporidium parvum – found in humans and
calves (infects man, cattle, sheep, goats.
deer, horses, buffaloes, - cats and other mammalian hosts
Common cause of diarrhea in both immunocompetent
and immunocompromised just that prognosis and
severity is worse in the later

7. Transmission: fecal-oral route
Water or food contaminated with faeces (in the case
of C. parvum faeces of animal reservoirs containing
their oocyst).
Habitat: (infects intestinal cells)
• Brush borders of mucosal epithelium
• Stomach
• Crypts of L.I and villi of the S.I

8. Transmission (electron micrograph) of C. parvum
trophozoites in distal duodenal mucosa. The trophozoites
occupy an intracellular but extracytoplasmic position.

9. Ultrastructure of Cryptosporidium In individuals with HIV infection, the
existence of large numbers of Cryptosporidium on the surface of the
intestinal mucosa can cause intractable. profuse, watery diarrhoea and
weight loss. 7% death rate in people with AIDS in Western countries.
The organisms in different stages of schizogony are seen surrounded by a
membrane of host-cell origin in this electron micrograph. giving the
parasites the false appearance of being extracellular. The section is from
a biopsy of rectal mucosa from one of the earliest known patients with
AIDS. The parasites can colonize any part of the intestine from the
pharynx to the rectum.

10. • You can become infected with cryptosporidia by touching
anything that has come in contact with contaminated feces.
You can get infected by:
• Drinking contaminated water that contains cryptosporidium
parasites
• Swimming in contaminated water that contains
cryptosporidium parasites and accidentally swallowing
some of it
• Eating uncooked, contaminated food that contains
cryptosporidia
• Touching your mouth with your hand if your hand has been
in contact with a contaminated surface, object, person or
animal

11. TWO PHASES OF APICOMPLEXA LIFE CYCLE
1. SCHIZOGONY
2. SPOROGONY
Schizogony: A process of asexual reproduction with
end product a mature Schizont containing
Merozoites.
Sporogony: A process of sexual reproduction with
end product sporozoite or oocysts containing
sporozoites.

12. • Schizogony is the process of asexual reproduction
during which the nucleus undergoes division
preceding cell division.
• Schizogony produces daughter cells known as
merozoites which can develop into gametocytes or
enter new hosts cells and undergo another
schizogony.
• Gametocytes which are derived frm merozoites are
capable of developing into gametes

13. Morphological forms
• Schizogony:- Trophozoites, Schizonts Merozoites
• Sporogony: Microgametocytes,
Macrogametocytes, Zygote, Oocysts and
Sporozoites
• Both Asexual and Sexual phases take place in one
host in cryptosporidiosis

14. • C. parvum/hominis has a monoxenous life cycle, all stages of
development (asexual and sexual) occurring in one host.
• The entire life cycle may be completed in as few as 2 days.
• Once ingested, oocysts excyst in the GIT releasing sporozoites.
• The freed sporozoites attach to epithelial cells and become
enclosed developing attachment organelles (stages referred as
trophozoites).
• The trophozoites then undergo asexual proliferation by
merogony that form schizonts and form two types of meronts.
• Type I meronts form 8 merozoites that are liberated then invade
other epithelial cells where they undergo another cycle of type I
merogony
• or develop into type II meronts. Type II meronts form 4
merozoites which do not undergo further merogony but produce
sexual reproductive stages (called gamonts or gametocytes).

15. • Sexual reproduction occurs by gametogony and both
microgametocytes (male) and macrogametocytes (female) are
formed.
• Macrogametocytes are then fertilized by mature
microgametocytes, and the resultant zygotes undergo further
asexual development (sporogony) and form sporulated oocysts
containing 4 sporozoites.
• Most oocysts are thick-walled and are excreted from the host in
faecal material
• Some oocysts, are thin walled and can excyst within the same
host leading to a new cycle of development (internal
autoinfection).
• The presence of these auto-infective oocysts and recycling type I
meronts are the means by which persistent chronic infections
may develop in hosts without further exposure to exogenous
oocysts.

18. In these acid-fast stained fecal smears, oocysts of C. parvum stain
an intense red and the granules are characteristically black.
In acid-fast stained preparations, yeasts, which can be mistaken for
Cryptosporidium oocysts, take a green stain. Various modifications
of acid-fast stains can be used and the oocysts of Cryptosporidium may
range from light pink to intense red.

19. Cryptosporidium. Oocyst in faeces,
Zeil-Neelsen stain
Auramine stain for oocysts of
Cryptosporidium parvum.
Fluorescent staining of oocysts
with auramine

20. Symptoms
Initial signs/symptoms of cryptosporidium infection, which
usually appear within a week after infection, might include:
Watery diarrhea
Dehydration
Lack of appetite
Weight loss
Stomach cramps or pain
Fever
Nausea
Vomiting
Symptoms can last for up to two weeks, though they might
come and go for up to a month, even in people with healthy
immune systems. Some people with cryptosporidium infection
have no symptoms.

21. Pathogenesis of Cryptosporidium
1. Damage to mucosal epithelium
Acute diarrhoea: watery, secretory, bloodless
Acute diarrhoea disease, abdominal pains
nausea, weight loss
2. Asymptomatic or self-limiting, 1-2 weeks
duration the in immuno – competent
30 days the immuno-compromised
50 + stools per day, fluid loss, dehydration
3. Ectopic: Bile duct, upper respiratory and lungs

22. Diagnosis : Clinical
Diarrhoea: frequent, watery, secretory, bloodless,
abdominal Dehydration pains nausea, weight loss
Complications:-
Malnutrition resulting from poor absorption of nutrients from
your intestinal tract
Severe dehydration
Significant weight loss
Inflammation of your gall bladder, liver or pancreas
Cryptosporidium infection isn't life-threatening in
immunocompetent patients. But can be dangerous and
life threatening in immunocompromised patients.

23. Diagnosis:
• Method -Stool Microscopy using Test -Modified Ziel-Neelsen stain or
Trichrome stain of stool. (Diagnosis of cryptosporidiosis is made by
examination of stool samples. Because detection of Cryptosporidium
can be difficult, patients may be asked to submit several stool samples
over several days).
• Electron microscopy of stool or biopsy specimens can also be
performed for direct visualization of oocysts
• GI biopsy instead of stool specimens; a high concentration of oocysts
is seen in the jejunum
• Serologic detection of specific anti- Cryptosporidium antibodies is
primarily used as a research or epidemiologic tool
• For research purposes and for species identification, use PCR assays

24. Other investigations
HIV testing
• Prolonged diarrhea caused by cryptosporidiosis may warrant HIV testing.
Primary immunodeficiencies
• Children with chronic diarrhea from cryptosporidiosis should be screened for
primary immunodeficiencies associated with depressed cellular immune function.
The most commonly identified immunodeficiency is hyper-IgM syndrome, which
can be identified by antibody screening. T-cell deficiencies can be identified by
examining lymphocyte numbers and subsets. [25]
Abdominal Ultrasonography
Dilated or irregular intrahepatic and extrahepatic bile ducts, along with a thickened
gallbladder, as detected with abdominal ultrasonography, indicate biliary involvement.
ERCP
Endoscopic retrograde cholangiopancreatography (ERCP) for identification of
Cryptosporidium oocysts in bile or intracellular forms on biopsy confirms the diagnosis
of biliary cryptosporidiosis.

25. Treatment: rarely successful CD4 <200 cells/mm3
No effective treatment will eradicate cryptosporidial
infection in all cases
1. Nitazoxanide is effective in HIV sero-negative (well nourished and
malnourished) children
2. Antidiarrhoeals (codeine phosphate after each loose stool)
3. Fluid and electrolyte replacement is the most important aspect of the
treatment
4. Nutritional support
5. Withdrawal of immunosuppressive therapy
6. ART- Anti Retroviral Treatment

26. Epidemiology of Cryptosporidiosis:
1. World wide, ubiquitous
2. Immunocompetent – self-limiting within
30 days, (1-2 weeks)
3. Immunocompromised – chronic
a. HIV and AIDS
b. Immunosuppressive therapy
c. Organ transplant
d. Cancer chemo, radiation therapy
e. Steroid Tx

27. f. Congenitial agamma globulinemia
or hypo gammaglobulinemia
g. Splenectomised

28. Prevention: as any other fecal/oral route
Oocyst are resistant to many disinfectant
including chlorine , but inactivated by
boiling, freezing, drying and 3% hydrogen
peroxide.
HIV –infected individuals-boil drinking water
and avoid swimming in public water

29. Lession Outline/Study Guide
Apicomplexas: Cyclospora cayetenesis
Infective stage of mode of transmission
Mode of transmission
Factors that contribute to infection/transmission or risk of infections
Symptoms diagnostic or Clinical Diagnosis
Diagnosis (at least one most recommended laboratory test that can be
performed in normal hospital setup)
Drug of Choice
Control/ preventive measure

30. Cyclosporiasis
• Caused by Cyclospora cayetenesis, this specie is human
host specific
• An emerging human pathogenic coccidian parasite,
• Sporulation, in 7–10 days, depending upon environmental
conditions. The sporulated oocysts are round, containing
two sporozoites.
• One important biological feature of C. cayetanensis is that,
unlike Cryptosporidium and Giardia, freshly excreted
oocysts are noninfectious and would require several days or
weeks under favorable environmental conditions to
sporulate and become infectious.

31. • Infection by C. cayetanensis is remarkably seasonal
worldwide, although it varies by geographical regions.
However, infection is more prevalent in the absence of rain,
during the drier and hotter months of the year in Peru and
Turkey. In Haiti, infections occur during the driest and
coolest times of the year, or during the cooler wet season in
Indonesia. In India, clinical cases were more frequent in the
summer before the rainfall period.
• Therefore, it is difficult to explain a common factor for
the differences observed in seasonality
• Most susceptible populations are children, foreigners,
and immunocompromised patients in endemic countries,
while in industrialized countries, C. cayetanensis affects
people of any age.

32. • After an initial episode of cyclosporiasis, the likelihood of
diarrhea and the duration of symptoms decreases significantly
with each subsequent infection
• High percentages of asymptomatic carriers have been
noted in endemic areas, suggesting that persistent contact
with oocysts during the first years of age induces protective
immunity against disease that will last into adulthood in
endemic areas
• However, some outbreaks have been reported among local
populations, such as naval recruits in Peru, which challenge
this theory. An explanation to these results would be that the
acquired immunity is not long lasting and either diminishes
over time or that the geographic distribution of C. cayetanensis
is unequal, leaving some populations unprotected. It seems
clear that the persistent contact with oocyst confers some
resistance against the disease.

33. • The average duration of diarrhea for HIV-infected patients is longer than that for
HIV-negative patients (199 days vs. 57.2 days)
• A coccidian protozoan responsible for syndromes of acute and chronic
diarrhea,
• The main symptoms of C. cayetanensis infection are voluminous watery
diarrhea, abdominal cramps, nausea, low grade fever, fatigue and weight loss
. Although the disease is self-limiting in most of the immunocompetent patients, it
may present as a severe, protracted or chronic diarrhea in immunocompromised
patients .
• The clinical presentation in endemic settings shows differences by age, with
elderly persons and young children having more severe clinical symptoms, while
infections are milder in older children and adults . In addition, asymptomatic
infections are frequent in endemic areas. The severity and duration of infection
tend to become milder after repeated episodes.
• The organism produces a recognizable syndrome of profound fatigue and anorexia
in addition to watery diarrhea and other gastrointestinal symptoms. Untreated
cyclosporiasis may last for weeks or longer; may be cyclic or relapsing; and may
result in significant dehydration and weight loss. In patients with AIDS, chronic
enteritis and biliary tract disease may develop. Similar to cryptosporidiosis, the
detection of Cyclospora oocysts in stool samples requires specific staining
methods

34. • The disease is self-limiting in most immunocompetent
patients, but it may present as a severe, protracted or
chronic diarrhea in some cases, and may colonize extra-
intestinal organs in immunocompromised patients.
• Infective stage/Form: - A sporulated oocyst contains two
sporocysts, each with two sporozoites.
• The life cycle of C. cayetanensis has not been fully
described.

35. • The pathogenesis underlying these symptoms has not been defined
• Risk assessments for waterborne cyclosporiasis are hampered by
the lack of data about the sporulation, survival, fate and transport of
oocysts, human infectivity and susceptibility.
• Unsporulated oocysts have been reported in human sputum .
Cholecystitis and biliary involvement have been confirmed
histologically in HIV-infected patients.
• Trimetoprim-sulfamethoxazole (TMP-SMX) is the antibiotic of
choice used for the treatment of cyclosporiasis and is effective for
both immunocompetent and immunocompromised patients .
Ciprofloxacin can be used as an alternative therapy in patients with
sulfonamide allergies, although is not considered as effective as
TMP-SMX
• A new thazolide treatment, nitazoxanide, was used in a patient who
did not respond to ciprofloxacin and was allergic to sulfonamides

36. Diagnosis
• Stool Microscopy using Modified Ziel-Neelsen
stain or Trichrome stain of stool
• Microorganisms. 2019 Sep; 7(9): 317.
• Published online 2019 Sep 4. doi: 10.3390/microorganisms7090317
• Cyclospora cayetanensis and Cyclosporiasis: An Update
• Sonia Almeria,1 Hediye N. Cinar,1 and Jitender P. Dubey2,*
• Author information Article notes Copyright and License information
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• This article has been cited by other articles in PMC.