Cryptosporidium infection in solid organ transplantation

Table 1 Cases and case series of Cryptosporidiosis in solid organ transplant recipients

Ref.	No. of patients	Incidence	Median/mean (range/SD) age (yr)	Allograft	Immuno-suppression regimen	Symptoms	Acute renal failure	Abnormal LFTs
Abdo et al[15]	1	NA	40 (NA)	Kidney	TAC + AZA + S	Abdominal pain, D	No	Yes
Acikgoz et al[23]	1	NA	6	Kidney	TAC + MMF + S	N, V, D	Yes	No
Arslan et al[10]	43	7/43 (16.28%)	32.9 ± 12.2	Kidney (40)1 Liver (3)1	MMF, TAC, AZA, CsA, S	D	N/A	N/A
Bandin et al[8]	38	7/38 (18%)	8.93 (4.5-14)	Kidney	MMF + TAC + S (3)1 MMF + TAC (2)1 MMF + CsA + S (2)1	D (7)1, V (4)1, abdominal pain (7)1, hTN (4)1	Yes (7)	No
Bhadauria et al[3]	119	34/119 (28.5)	33.96 ± 11.13 (15-52)	Kidney	CsA + MMF + S TAC + MMF + S	D(12), F(11), malaise(25), V(18), abdominal pain (17), weight loss (9), dehydration (15), hypotension (8)	Yes (12)	N/A
Bonatti et al[5]	10	NA	51 (34-57)	Kidney (8)1 Liver (1)1 Lung (1)1	TAC + MMF + S (8)1 CsA + AZA + S (1)1 TAC + S (1)1	D (10)1, V (5)1, malaise (4)1, F (1)1	Yes	N/A
Campos et al[18]	3	NA	3.92 (1.25-7)	Liver	TAC + S (2)	V (1), D (3), F (1), abdominal pain (2)	No	Yes (2)
Chieffi et al[30]	23	17.2	N/A	Kidney	N/A	N/A	N/A	N/A
Clifford et al[21]	3	3/28 (10.7)	N/A	Kidney	CsA + AZA + S	D(2)	No	No
Delis et al[16]	4	NA	20.21 (0.83-34)	Intestine	TAC + P(3)1 TAC + MMF + S (1)1	D (4)1, abdominal pain (1)1, F (1)1	Yes (4)1	N/A
Franco et al[100]	1	NA	60	Kidney	CsA + MMF + S	D, N, V, malaise, weight loss,	Yes	NA
Frei et al[6]	1	NA	34 (NA)	Liver	MMF	D	N/A	N/A
Gerber et al[17]	1160	4/1160 (0.34%)	NA	Liver (3)1 Intestine (1)1	CsA + S (1) TAC + S (3)	D (4)1, lethargy (1)1, weight loss (1)1	No	Yes (1)1
Hong et al[9]	1	NA	7 (NA)	Kidney	TAC + MMF + S	N, V, D	Yes	No
Krause et al[4]	6	NA	3.7 (1.1-6.6)	Kidney (4)1 Liver-Kidney (1)1 Heart (1)1	TAC + MMF + S TAC + AZA + S TAC + MMF	D (6)1, F (2)1, V (1)1, abdominal pain (1)1, weight loss (4)1	Yes (5/6)1	Yes (4/6)1
Ok et al[19]	69	13/69 (18.8%)	N/A	Kidney	N/A	Asymptomatic, D	N/A	N/A
Pozio et al[14]	1	NA	13 (NA)	Intestine	TAC + S	None (1st episode) D (2nd episode)	N/A	N/A
Rodríguez Ferrero et al[7]	1	NA	78	kidney	MMF + TAC	D, hTN	Yes	No
Tran et al[12]	1	NA	59	Kidney	TAC + sirolimus + S	N, V, D, abdominal pain	No	No
Udgiri et al[13]	60	NA	35.07 ( ± 9.22)	Kidney	CsA + AZA + S (47)1 CsA + MMF + S (13)1	D (2)1	N/A	No
Vajro et al[24]	2	NA	1.49; 10	Liver	CsA + S	F	No	No
Ziring et al[11]	33	2/33 (6.06%)	2.83 (0.83-48.75)	Intestine ± liver	TAC + MMF + S	N/A	N/A	N/A

¹Number of patients; NA: Not applicable; N/A: Not available; N: Nausea; V: Vomiting; D: Diarrhea; F: Fever; hTN: Hypotension; TAC: Tacrolimus; MMF: Mycophenolate mofetil; CsA: Cyclosporine A; AZA: Azathioprine; S: Steroids.

Table 2 Risk factors, diagnosis and co-morbidities in Cryptosporidium Infections

Ref.	Exposure	Cryptosporidium spp.	Diagnosis	Co-infection	Tacrolimus levels (early on admission)
Abdo et al[15]	N/A	C. parvum	N/A	No	No
Acikgoz et al[23]	Petting animals	N/A	ELISA Modified acid fast staining	No	Increased
Arslan et al[10]	N/A	N/A	Modified acid fast staining	N/A	N/A
Bandin et al[8]	Swimming pool (3) Traveler diarrhea (1)1	N/A	Zielh-Nielsen staining Auramine staining Microscopy Biopsy	No	N/A
Bhadauria et al[3]	N/A	N/A	Modified acid fast staining	CMV (8)	Increased
Bonatti et al[5]	Travel (water exposure) (4)1 Camping (1)1 Restaurant (1)1 Well water/farm animals (1)1	C. jejuni (1/10)1	Microscopy Enzyme immunoassay	N/A	Increased
Campos et al[18]	N/A	N/A	N/A	No	N/A
Chieffi et al[30]	N/A	C. parvum	Carbol-fuchsin staining	N/A	N/A
Clifford et al[21]	Public water supply	N/A	N/A	No	No
Delis et al[16]	N/A	N/A	Microscopy Biopsy	No	Increased
Franco et al[100]	N/A	N/A	Gastric and small bowel biopsies and hematoxillin staining	No	N/A
Frei et al[6]	N/A	N/A	Modified Ziehl-Neelsen staining	No	N/A
Gerber et al[17]	N/A	N/A	Micriscopy (2)1 Biopsy (3)1	No	N/A
Hong et al[9]	Swimming pool	N/A	Modified acid-fast staining DFA	N/A	Increased
Krause et al[4]	None	N/A	Immunochromatographic test	No	Increased (5/6)
Ok et al[19]	N/A	N/A	N/A	Blastomycsis hominis, Giardia intestinalis, Dientamoeba fragilis, Entamoeba coli	N/A
Pozio et al[14]	Allograft	C. hominis	Microscopy	No	N/A
	N/A	C. parvum	Biopsy
Rodríguez Ferrero et al[7]	N/A	N/A	Modified Kinyoun stain	No	No
Tran et al[12]	N/A	N/A	Modified acid fast staining Microscopy Biopsy	No	No
Udgiri et al[13]	N/A	N/A	Modified acid fast stain	Giardia spp. (7)1Entamoeba butschili (1)1	N/A
Vajro et al[24]	N/A	N/A	Monoclonal antibody fluorescein-conjugated stain	No	NA
Ziring et al[11]	Nosocomial (1)1	N/A	Direct immunofluorescent assay	N/A	N/A

¹Number of patients; DFA: Direct fluorescent antibody; N/A: Not available. C. hominis: Cryptosporidium hominis; C. parvum: Cryptosporidium parvum ; C. jejuni: Cryptosporidium jejuni.

Table 3 Management of Cryptosporidium infections

Ref.	Treatment regimen (length)	Changes in immunosuppression	Resolution of symptoms	Graft loss	Death
Abdo et al[15]	Rifampin (3 wk)	Temporary lower level of TAC	Resolved	No	No
Acikgoz et al[23]	Spiramycin + NTZ + PAR (4 wk)	Switch from MMF to AZA	Resolved	No	No
Arslan et al[10]	N/A	N/A	N/A	N/A	N/A
Bandin et al[8]	NTZ (4 wk) (2) NTZ (2 wk) (5)1	MMF switched to AZA (3)1 MMF reduced (3)1 TAC switched to sirolimus (1)1	Resolved	No	No
Bhadauria et al[3]	NTZ (13) (16-60 d) NTZ + fluoroquinolone (21) (16-60 d)	MMF → AZA (3) TAC → CsA (8) Reduction of immunosuppression (11)	Resolved microbiologically (83%)	Yes (3)
Bonatti et al[5]	AZM (14-21 d) (2)1 AZM + NTZ (6-18 d) (2)1 NTZ (14-16 d) (2)1 AZM (5 d) + NTZ + TMP/SMX (14 d) (1)1 AZM + PAR(14d) (1)1	MMF stopped (4)1 MMF reduced (1)1	Resolved	No	No
Campos et al[18]	Spiramycin → PAR (6 mo) PAR(2)	N/A	Resolved	No	No
Chieffi et al[30]	N/A	N/A	N/A	N/A	N/A
Clifford et al[21]	N/A	N/A	Resolved	No	No
Delis et al[16]	AZM (7 d) + PAR (21 d) (2)1 PAR (14 d) (1)1 PAR (21 d) (1)1	Stopped (1/4)1 TAC reduced (1/4)1	Resolved	No	No
Franco et al[100]	Spiramicin 10 d	MMF → Aza Stopped Aza	Resolved	No	No
Frei et al[6]	PAR (4 wk)	No	Resolved	No	No
Gerber et al[17]	AZM (3 wk) (1)1 PAR (2-3 wk) (2)1	No	Resolved	No	No
Hong et al[9]	NTZ (4 wk) PAR + AZM (5 wk), oral human immunoglobulin (5 d)	TAC reduced MMF stopped and AZT started	Resolved	No	No
Krause et al[4]	NTZ (5-24 d)	No	Resolved	No	No
Ok et al[19]	N/A	N/A	N/A	N/A	N/A
Pozio et al[14]	AZM (1 wk) + PAR (3 wk) AZM + PAR (1 yr 7 mo)	N/A	Resolved	No	No
Rodríguez Ferrero et al[7]	AZM + PAR (14 d) NTZ (6 d)	MMF and TAC reduced	Resolved	No	No
Tran et al[12]	PAR (4 wk)	Sirolimus discontinued	Resolved	No	No
Udgiri et al[13]	Spiramycin (10 d) (2)1	No	Resolved	No	No
Vajro et al[24]	None	No	Resolved	No	No
Ziring et al[11]	PAR + AZM	N/A	Resolved	No	No

¹The number of patients; TAC: Tactolimus; MMF: Mycophenolate mofetil; AZT: Azathioprine; S: Steroids; AZM: Azithromycin; NTZ: Nitazoxanide; PAR: Paromomycin; N/A: Not available; TMP/SMX: Trimethoprim/sulphamethoxazole.