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Consultant Microbiologist AFIP Rawalpindi
Cryptosporidiosis in a young immunocompromised patient
Dr Shams AfridiTrainee in Microbiology
SupervisorDr Nasrullah Malik
Case Presentation
Name XYZ
Age 12 years
Gender Male
Residence Peshawar
Date of admission 28 Aug 2009
Hospital AFBMTC
PATIENT’S PROFILE
● Watery diarrhoea 3 days
● Low grade fever
● Non productive cough 2 days
PRESENTING COMPLAINTS
● Known case of Fanconi’s anemia
● Allogenic bone marrow transplant at AFBMTC Rwp on 10th Aug 2009
● Discharged after two weeks
● Re-admitted on Aug 28, with symptoms of acuteGvHD
● HISTORY OF PRESENT ILLNESS
● Non-bloody, watery diarrhoea with 15-20 stools per day
● Low grade fever
● Developed non productive cough with
breathlessness
● HISTORY OF PRESENT ILLNESS
● Cyclosporine , steroids , immunoglobulins
● Antibiotic therapy including antifungal agents
● Fluid and electrolyte replacement
● Condition remained the same
● HISTORY OF PRESENT ILLNESS
● PAST HISTORY
● Frequent admissions in AFBMTC
● Fanconi's anemia diagnosed in May, 2009
at AFBMTC
● Bone marrow transplantation at AFBMTC
● Was on oral immunosuppressive therapy
● SOCIOECONOMIC HISTORY
Socioeconomic status satisfactory
● PERSONAL HISTORY
Not contributory
● FAMILY HISTORY
Not contributory
A boy of lean built lying in bed conscious and oriented
Vital signs
GENERAL PHYSICAL EXAMINATION
● Pallor +
● Jaundice +
● Dehydration + +
● Cyanosis
● Clubbing
● Edema Absent
● Lymphadenopathy
● Ascites
GENERAL PHYSICAL EXAMINATION
GIT - Hepatosplenomegaly
RESP - NAD
CNS - NAD
CVS - NAD
SYSTEMIC EXAMINATION
● Acute graft versus host disease
● Bacterial, viral and protozoal causes of watery diarrhoea
● Atypical pneumonia
● Bacteraemia/Septicaemia
PROVISIONAL DIAGNOSIS
● Blood C/P
Hb 9.5 g /dl
WBC 2.1 x 109/l
Platelets 51 x 109/l
● Urine R/E WNL
● Fasting plasma Glucose 4.8 mmol/l
LAB EVALUATION
● Renal function tests
Serum urea 2.9mmol/l
Serum creatinine 68 μmol/l
Serum Na 136mmol/l
Serum K 3.8mmol/l
Serum HCO3 23mmol/l
● Liver Function Tests
Bilirubin 70 μ mol/l
ALT 75 U/l
ALP 708 U/l
Albumin 19 g/l (reduced)
LAB EVALUATION (Cont’d)
● CXR
Normal
● USG abdomen
Mild hepatosplenomegaly
● Repeated blood cultures
No growth
LAB EVALUATION (Cont’d)
● Stool routine examination
Loose watery stools
Numerous pus cells
No ova or cysts
● Stool for culture and sensitivity
No Salmonella, Shigella or Vibrio cholerae
● Sputum for C/S and AFB
AFB not seen
Culture Non significant ( normal throat flora )
LAB EVALUATION (Cont’d)
● Stool for Clostridium difficile toxin
Negative
● Stool for Cryptosporidium
Cysts of Cryptosporidium parvum
• Sputum for Cryptosporidium
Cysts of Cryptosporidium parvum
LAB EVALUATION (Cont’d)
Cysts of Cryptosporidium parvum in stool
Cysts of Cryptosporidium parvum in sputum
Intestinal and pulmonary cryptosporidiosis
FINAL DIAGNOSIS
• Supportive therapyo I/V Fluidso Antiemeticso Antipyretics
● Syp Azithromycin (200mg/ 5ml) 1 TSF BD
● Tab Cotrimoxazole 480mg 8 hourly
● Frequency of diarrhea reduced to 5-6 stools per day● Pulmonary symptoms improved
TREATMENT
Repeat stool sample No cyst Repeat sputum sample ● Condition started to deteriorate
CMV PCR ---- Positive
o Put on Gancyclovir and I/V Immunoglobulins Oct 7, Epileptic fit with tongue bite
Bilateral bronchopneumonia
Respiratory failure and death
TREATMENT
Case Discussion
● Cryptosporidium — “hidden spores”
● Phylum Apicomplexa (the sporozoa)o Coccidian protozoan parasite
● Important Specieso C. parvumo C. hominiso C. muriso C. wrairi
● Oocyst 4-6μm in dm
● 240,000 times resistant to chlorination than Giardia
INTRODUCTION
● 1907 Tyzzer, gastric mucosa of mice
● 1976 First human case — 3-year old girl rural
Tennessee, USA
● 1980s Strong association with AIDS
Most common cause of
HIV related gastroenteritis
HISTORICAL BACKGROUND
● Infection reported in six continents
● 3 days to 95 years old
● The frequency of cryptosporidiosis not well-defined o 30% of adult US population seropositive
● A local prospective study conducted at AFIP (May to September 2005)
(n=300) 8%
92%
present absent
EPIDEMIOLOGY
* Hunter PR, Nichols G. Epidemiology and clinical features ofCryptosporidium infection in immunocompromised patients.Clin Microbiol Rev 2002; 15: 145–54.
● Population at risk
o Immunocompromised individuals
o Infants and young children (day-care centres)
o Drinking unfiltered and untreated water
o Hospitalized patients & Health-care employees
o Livestock workers and farmers
o Travelers to endemic areas
EPIDEMIOLOGY (Cont’d)
Year Location Population exposed
Population infected
1984 Braun station, Texas 50900 2006
1992 Jackson county, Oregon 15000 15000
1993 Milwaukee, Wisconsin 403,000 403,000
1996 British Columbia, Canada 90,000 15000
2001 Belfast , Ireland 252,000 257
2007 Galway, Ireland 90,000 5000
2008 Northampton, UK 108,000 252
MAJOR OUTBREAKS
MacKenzie WR, Hoxie NJ, Proctor ME, Gradus MS, Blair KA, Peterson DE, Kazmierczak JJ, Addiss DG, Fox KR, Rose JB. Amassive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply. N Engl J Med 1994; 331: 161–7.
Life cycle of Cryptosporidium
● Fecal-oral
o Contaminated food and water
o Untreated groundwater, well water
o Swimming pools, water park wave pools
TRANSMISSION
● Food borne transmission
o Beverages, salads, or other foods not heated or cooked after handling.
● Day-care and Nursing centres
● Nosocomial transmission
o Patients to health care staff, patient-to-patient transmission
TRANSMISSION (Cont’d)
Guerrant R.L. Cryptosporidiosis: An emerging highly infectious threat. Emerg Infect Dis 1997;3:51-7.
● Low infectious dose
● Sporozoites adhere to the intestinal mucosa
● Cells release cytokines-activate phagocytes
● Soluble factors are released
● Increase intestinal secretion of water and chloride and inhibit absorption
PATHOGENESIS
● Epithelial cells damaged by:
o Direct parasite invasion and multiplication or
o T cell-mediated-villus atrophy
PATHOGENESIS (Cont’d)
● Incubation periodo 2 – 10 days
● Immunocompetent patients
● Acute self-limitingo Frequent, watery diarrhea o Nausea o Vomiting o Abdominal cramps o Low-grade fever
Henry MC, Alary M, Desmet P, et al. Community survey of diarrhoea in children under 5 years in Kinshasa, Zaire. Ann SocBelg Med Trop 1995;75:105–14. [PubMed: 7487197]
●
CLINICAL MANIFESTATIONS
● Immunocompromised patients- more severe illness
o Cholera-like diarrhea (up to 20 liters/day) o Severe abdominal cramps o Malaise o Low grade fever o Weight loss o Anorexia
CLINICAL MANIFESTATIONS(Cont’d)
Kumar S.S., Ananthan S., Saravanan P. Role of coccidian parasites in causation of diarrhea in HIV infected patients in Chennai. Indian J Med Res 2002;116:85-9.
● Pulmonary involvement
● Rare complication of intestinal cryptosporidiosis
o Chronic cougho Fever o Dyspnoea
Moore, J., and J. Frenkel. 2005. Respiratory and enteric cryptosporidiosis in humans. Arch. Pathol. Lab. Med. 115:1160–1162.
CLINICAL MANIFESTATIONS(Cont’d)
● Microscopic examination
● Serological investigations
o Enzyme immunoassays
o Immunofluorescence assays
● Molecular techniques
LABORATORY DIAGNOSIS
Mehta P. Laboratory diagnosis of cryptosporidiosis. J Postgrad Med 2002;48:217
● MICROSCOPIC EXAMINATION
o Most reliable and specifico Gold standard-Modified ZN (Kinyoun) stainingo Cysts: Bright red, round to oval (4-6 µm)
LABORATORY DIAGNOSIS (Cont’d)
● MICROSCOPIC EXAMINATION
o Auramine-phenol (fluorescent stain)o Cysts appear small, round and bright yellowo False positive results
LABORATORY DIAGNOSIS (Cont’d)
● SEROLOGICAL METHODS
● ELISA o Cryptosporidium specific IgM, IgG, IgAo Sensitivity: 80-100 %o Active infection / previous exposure
LABORATORY DIAGNOSIS (Cont’d)
Marques FR, Cardoso LV, et al. Performance of an immunoenzymatic assay for Cryptosporidium diagnosis of fecal samples; Braz J Infect Dis. 2005 Feb;9(1):3-5. Epub 2005 Jun 6.
● SEROLOGICAL METHODS
● IMMUNOFLUORESCENCE ASSAYS o Sensitiveo Specifico High cost
LABORATORY DIAGNOSIS (Cont’d)
Mehta P. Laboratory diagnosis of cryptosporidiosis. J Postgrad Med 2002;48:217
● Rapid Immunochromatographic detection
o 97% sensitivityo 100% specificity
o High cost
LABORATORY DIAGNOSIS (Cont’d)
LYNNE S. GARCIA* AND ROBYN Y. SHIMIZU. Detection of Giardia lamblia and Cryptosporidium parvumAntigens in Human Fecal Specimens Using the ColorPAC Combination Rapid Solid-Phase Qualitative Immunochromatographic Assay ; JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 2000, p. 1267–1268
● MOLECULAR METHODS
● Polymerase chain reaction(PCR)
o Speciation of cryptosporidiumo Epidemiological studieso Expensiveo Not used as routine
● INTESTINAL BIOPSY SECTIONSo False negative results
LABORATORY DIAGNOSIS (Cont’d)
● No reliable effective therapy
● In immunocompetent patients
o Self limiting
o General supportive care
o Rehydration, replacement of electrolytes and antimotility agents
o Nitazoxanide, Paromomycin and Azithromycin
decrease the intensity of infection*
* De la Tribonnière X, Valette M, Alfandari S. Oral nitazoxanide and paromomycin inhalation for systemic cryptosporidiosis in a patient with AIDS. Infection 1999 May-Jun; 27(3): 232.
TREATMENT
● In immunocompromised patients
o Resolves slowly or not at all
● Spiramycin in the early stages
● Paromomycin and Azithromycin help clear the infection*
● Immunoglobulins
* Palmieri F, Cicalini S, Froio N, Rizzi EB, Goletti D, Festa A, et al. Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with paromomycin plus azithromycin. Int J STD AIDS. 2005 Jul; 16(7): 515-7.
TREATMENT(Cont’d)
● Personal hygieneo Hand washing
● Avoid water that might be contaminatedo Do not swallow recreational watero Avoid swimming when having diarrhoeao Boil water for 1 min or use 1 micron filter
● Avoid food that might be contaminated
● Take extra care when travelling
PREVENTION
Havelaar A, Boonyakarnkul T, Cunliffe D, Grabow W, Sobsey M, Giddings M, Magara Y, Ohanian E, Toft P, Chorus I, Cotruvo J, Howard G, Jackson P. Guidelines for Drinking Water Quality Water Borne Pathogens, 3rd edn. Geneva: WHO 2003.
● Stool sample for Cryptosporidium oocysts should always be sent to laboratory in cases of persistent diarrhoea
● Pulmonary cryptosporidiosis is an important but rare cause of pneumonia/mortality in immunocompromised patients
CONCLUSION
THANK YOU !