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Cryptosporidiosis among black children in hospital in South Africa
Journalof Infectwn(I986) I3, 25-30 C r y p t o s p o r i d i o s i s a m o n g black c h i l d r e n in h o s p i t a l in S o u t h Africa G. S m i t h , J. v a n d e n E n d e
Department of Microbiology, University of Natal, Durban, South Africa Accepted for publication 5 July
I985
Summary Over a period of 3 months during the summer, 362 African children admitted to King Edward V I I I Hospital, Durban, were screened for the faecal excretion of Cryptosporidium oocysts. Of 259 children with diarrhoea, oocysts were detected in 31 (I 1.9 %), while none was found in the faeces of xo3 children without diarrhoea (controls). All those children excreting Cryptosporidium were under 2 years of age, giving a prevalence of I5 % for this group. Other potential enteric pathogens were detected in the faeces of i2 (38.7 %) of these children. The case fatality rate for patients with Cryptosporidium was 22.6 ~'o, which may reflect the selection of patients in a study concentrating on hospital inpatients. Cryptosporidium was the second most common organism detected in diarrhoeal faeces, and the only one detected in 9"2 % of diarrhoeal children aged less than two years. These findings indicate that Cryptosporidium should be regarded as a potential pathogen in children admitted to this hospital with severe diarrhoea. Such association of Cryptosporidium with diarrhoea in children accords with recent studies in other parts of the world.
Introduction T h e c o c c i d i a n p a r a s i t e C r y p t o s p o r i d i u m w a s first d e s c r i b e d in a s s o c i a t i o n w i t h h u m a n d i a r r h o e a l d i s e a s e in I976,1 h a v i n g b e e n r e c o g n i s e d p r e v i o u s l y in m a m m a l s , b i r d s a n d r e p t i l e s . 2 T h e r e f o l l o w e d r e p o r t s o f s p o r a d i c cases in h e a l t h y h u m a n c o n t a c t s o f i n f e c t e d d o m e s t i c a n i m a l s a n d s u b s e q u e n t l y c r y p t o s p o r i d i a l o o c y s t s w e r e d e t e c t e d in t h e faeces o f i m m u n o - s u p p r e s s e d p a t i e n t s w i t h i n t r a c t a b l e d i a r r h o e a . 3, 4 I n r e c e n t y e a r s t h e r e s u l t s o f s t u d i e s in W e s t e r n E u r o p e , ~-9 A u s t r a l i a , 1° C e n t r a l A m e r i c a H a n d A f r i c a ~2,~3 h a v e s u g g e s t e d a n a s s o c i a t i o n b e t w e e n C r y p t o s p o r i d i u m a n d s e l f - l i m i t i n g d i a r r h o e a l d i s e a s e , as well as s o m e t i m e s chronic diarrhoea and small bowel damage. Patients both with and without a p p a r e n t i m m u n e d e f i c i e n c y m a y b e affected. T h e h i g h e s t p r e v a l e n c e s h a v e b e e n r e p o r t e d in c h i l d r e n . T h e p r e s e n c e o f c r y p t o s p o r i d i a l o o c y s t s h a s also b e e n r e c o r d e d in t h e h u m a n b i l i a r y ~ a n d r e s p i r a t o r y t r a c t s . ~4 L i t t l e is k n o w n a b o u t t h e a s s o c i a t i o n o f c r y p t o s p o r i d i o s i s w i t h d i a r r h o e a l illness in s o u t h e r n A f r i c a , a l t h o u g h a r e c e n t s m a l l s t u d y 15 r e v e a l e d t h e p r e s e n c e o f C r y p t o s p o r i d i u m o o c y s t s in d i a r r h o e a l faeces f r o m 3 o ' 8 % o f I3 p a e d i a t r i c i n p a t i e n t s at K i n g E d w a r d V I I I H o s p i t a l , D u r b a n . T h i s article r e c o r d s t h e f i n d i n g s o f a l a r g e r s t u d y o f t h e p r e s e n c e o f C r y p t o s p o r i d i u m o o c y s t s in t h e faeces o f c h i l d r e n w i t h a n d w i t h o u t d i a r r h o e a a d m i t t e d to t h e s a m e h o s p i t a l . All correspondence should be addressed to: Dr Grace Smith, Public Health Laboratory, East Birmingham Hospital, Bordesley Green East, Birmingham B9 5ST. ox63-4453/86/o4oo25 + o6 $o2.oo/o
© x986 The British Society for the Study of Infection
26
G. S M I T H AND J. VAN D E N ENDE
P a t i e n t s and m e t h o d s
T h e study was conducted at King Edward V I I I Hospital, Durban, South Africa, a busy teaching hospital with approximately 2000 beds. T h e hospital serves the black community in the Durban area and is a referral centre for outlying hospitals and clinics in the Natal-Kwa Zulu region which is largely coastal with a sub-tropical climate. For the period January-March I985, diarrhoeal faeces from 259 patients aged up to I2 years were examined for the presence of Cryptosporidium oocysts. Air-dried faecal smears were stained by the modified Ziehl-Neelsen technique 16 and examined microscopically by one observer (EGS): All specimens were examined also for the presence of salmonellas, shigellas, Vibrio cholerae, Yersinia enterocolitica, Campylobacter jejuni and enteropathogenic Escherichia coli by means of standard bacteriological techniques. In addition, each specimen was examined for parasitic ova, cysts and trophozoites by light microscopy of wet smears and for rotavirus antigen by enzyme immunoassay (' Rotazyme', Abbott Laboratories). Faeces from 103 children who were inpatients during the period of the study and who did not have diarrhoea or other gastrointestinal symptoms were examined as controls. When possible, further specimens were obtained from patients whose initial samples of faeces were positive for Cryptosporidium. Clinical details were recorded from inpatient notes. As a check on the observer's ability to detect and identify cryptosporidia correctly, a positive faecal specimen and a stained faecal smear were sent to D r Bruce Jackson at the Public Health Laboratory, Rhyl, North Wales, who confirmed the presence of cryptosporidial oocysts. Results
Cryptosporidial oocysts were detected in the faeces of 3I ( I I ' 9 % ) of 259 children with diarrhoea. T h e y were not detected in the faeces of I03 controls. T h e age distribution of these children is shown in Table I. All patients excreting cryptosporidial oocysts were aged less than 2 years, giving an incidence of 15 % for this group. T h e distribution of Cryptosporidium in this age group, compared with children aged between 2 and I2 years, was significantly different (X~ = 3"84; P < o . o I ) . Age and sex d i s t r i b u t i o n
T h e mean age of patients with Cryptosporidium was 6"2 months with a range of I - I 8 months. T h e male to female ratio for those less than 2 years of age was I : 2 . i for those excreting cryptosporidial oocysts; 1:o"9 for those in the Cryptosporidium negative diarrhoeal group and I :I "25 for those in the control group. T h e age distribution among males and females was similar, with a mean of 5" I months and 6"7 months respectively. O t h e r enteric p a t h o g e n s
Potential enteric pathogens were detected in the faeces of I2 (38"7 %) patients excreting Cryptosporidium; this figure did not differ significantly from the
Cryptosporidiosis Table I
27
Frequency of Cryptosporidium oocysts in the faeces of children with diarrhoea
Age
No. children
No. (%) with Cryptosporidium oocysts
No. controls*
< 6 months 6-i2 months I3-23 months
I28 53 25
I7 IO 4
47 *7 I4
Subtotal
2o6
31 (I5"o)
78
2 years 3-4 years 5-6 years 7-8 years 9--I2 years Total
7 8
0 o
II
O
3
6
o
2
0
2
2I 259
I2 6
31 (I I'9)
IO3
* Faeces of controls were all negative for Cryptosporidium oocysts. Table II
Frequency of other potential enteric pathogens in faecal specimens examined for Cryptosporidium oocysts
Patients with diarrhoea Cryptosporidium found* Cryptosporidium not found Controls
All patients
Patients < 2 years of age
38"7% 34"o% 25"o%
38"7 % 4o'6 % 25"7%
* All patients in whom Cryptosporidium oocysts were found were less than 2 years of age. d e t e c t i o n rates in the o t h e r groups, as s u m m a r i s e d in T a b l e II. Details o f organisms d e t e c t e d are given in T a b l e I I I . Salmonellas were p r e s e n t in I9"3 % o f patients excreting C r y p t o s p o r i d i u m . T h i s figure is significantly greater t h a n the 6"8% of c hi l dr en aged 2 years and less w i t h o u t C r y p t o s p o r i d i u m ( P = o'o232, according to t he test for the difference b e t w e e n p r o p o r t i o n s ) . O t h e r potential p a t h o g e n s were n o t f o u n d in 19 (61 "3 %) patients excreting c r y p t o s p o r i d i a l oocysts. Clinical details A p a r t f r o m one pat i ent excreting c r y p t o s p o r i d i a l oocysts w ho had b e e n sent h o m e after a p e r i o d o f r e h y d r a t i o n in the Paediatric Resuscitation U n i t , all others were a d m i t t e d to hospital. T h e m ai n criteria for admission were severe d e h y d r a t i o n , associated infections and fever. S y m p t o m s p r e c e d e d admission for an average of 4"6 days in patients for w h o m this i n f o r m a t i o n was available (29/3 i). R e s p i r a t o r y tract illness, ranging f r o m c o u g h to b r o n c h o p n e u m o n i a , a c c o m p a n i e d w a t e r y di ar r hoea a nd v o m i t i n g in 2~ patients (67"7%). Five
28
G. S M I T H
A N D J. V A N D E N E N D E
T a b l e I I I Potential enteric pathogens in faecal specimens examined for Cryptosporidium oocysts from children less than 2 years of age Diarrhoea specimens
Organism
Salmonella spp. Shigella spp. Enteropathogenic Escherichia coli Campylobacter jejuni Giardia lamblia cysts Rotavirus Mixed infections Pathogens not found
Cryptosporidiumnegative (Total I75)
Cryptosporidiumpositive (Total 3 I)
Controls (Total 78)
I2 (6"8%) 3 (I'7%) 27 (I 5"4 %)
6 (x9"3) i (3"2)
3 (3"8) O 4 (5"i)
3 (I-7 %)
I (3"2)
o
o
o
6 (7"7)
40 (22"8%) 14 (8"0%) Io5 (59"4%)
O
6 (I9'3) 2 (6"4) I9 (6I'3)
I4 (I7"9) 7 (I2-O) 58 (74"3)
patients (I 6.I %) had concomitant bacteraemia due to Salmonella typhimurium (one), Streptococcus pneumoniae (two), Escherichia coli (one) and Klebsiella spp. (one). Seven patients had urinary tract infections. Seven children with C r y p t o s p o r i d i u m died, t h e r e b y giving a case fatality rate of 22.6 % ; none had evidence of bacteraemia. In the remainder, the average duration of stay in hospital was 15"8 days. T w e l v e patients, 44 % of those for w h o m information was available, and including three of those w h o died, had, on admission, b o d y weights below the third percentile for their age and sex. Cryptosporidial oocysts were detected in s u b s e q u e n t faecal specimens from 29 patients and also the m o t h e r of one patient. She developed diarrhoea while caring for her child on the w a r d ; p r o b a b l y due to p e r s o n - t o - p e r s o n transfer of the parasite. 17 Discussion
T h e importance of C r y p t o s p o r i d i u m as a h u m a n intestinal pathogen in Africa has been illustrated b y the results o f previous studies of populations in northern and central regions. 12,13 T h i s study of children in southern Africa supports these findings. D u r i n g 3 m o n t h s in the s u m m e r the incidence of C r y p t o s p o r idium was I 2 ~o overall in 259 children admitted to hospital with diarrhoea, oocysts not being detected in IO3 controls without diarrhoea. F o r children less than 2 years of age the incidence was r 5 %. Both these figures are higher than the 7"9 % and IO'4% recorded in children with diarrhoea in Liberia 1~ and R w a n d a 13 respectively. Similar studies in Australia, ~° E u r o p e 5-9 and Central America 11 have revealed lower rates of b e t w e e n 2.8 % and 4"8 %. It is not clear to what extent this variation in rates reflects regional differences or efficiency in detecting cryptosporidial oocysts in faeces. Unlike other published studies, a high percentage (38"7 %) of other potential
Cryptosporidiosis
29
enteric pathogens was f o u n d in the faeces of patients with C r y p t o s p o r i d i u m . T h e m o s t c o m m o n were Salmonella sp., f o u n d in a significantly greater p r o p o r t i o n than in those w i t h o u t C r y p t o s p o r i d i u m . A study of children with s u m m e r diarrhoea at Baragwanath Hospital in J o h a n n e s b u r g TM stressed the polymicrobial nature of diarrhoea among children in developing communities and f o u n d potential pathogens in 23"3 % o f age-matched controls, a figure similar to that of 25 % for controls in this study. A m o n g children of all ages with diarrhoea included in this study, rotavirus was detected most often (19"3 %), while C r y p t o s p o r i d i u m (I 1"9 %) was f o u n d m o r e frequently than enteropathogenic Eseherichia coli (I I "6 %). In a previous s t u d y of diarrhoea in children in K i n g E d w a r d V I I I Hospital, 19 during the winter m o n t h s , and in which the presence of C r y p t o s p o r i d i u m was not sought, rotavirus (29 % ) was also the most frequent potential intestinal pathogen detected, followed b y Campylobacter spp. (I 7 Yo) and enteropathogenic E. coli ( 1 2 % ) . In assessing the status of C r y p t o s p o r i d i u m as an intestinal pathogen, it m a y well be significant that in 9"2 % of the children less than 2 years of age with diarrhoea, C r y p t o s p o r i d i u m was the only organism detected. A striking finding in this s t u d y is the detection of C r y p t o s p o r i d i u m oocysts only in children less than 2 years of age. In spite of the significant association of C r y p t o s p o r i d i u m with diarrhoea its precise pathogenic role is n o t clear. T h e case fatality rate for children with C r y p t o s p o r i d i u m was 22.6 % which m a y reflect the severity of d e h y d r a t i o n and electrolyte disturbance at the time of admission. Patients had been s y m p t o m a t i c for a mean of 4"6 days before admission and m a n y had respiratory tract infections; 3 0 % had either bacteraemia or urinary tract infection; some were malnourished. Five t h o u s a n d children with diarrhoea and dehydration severe enough to require intravenous fluids are seen in the the D e p a r t m e n t of Paediatrics each year; a b o u t 40 0/0 of these are admitted. Since this s t u d y concentrated on inpatients, the most severely affected patients were necessarily included. In his review of cryptosporidiosis in man, domestic animals and birds, Angus 2° notes that the m o s t serious outbreaks of the disease in calves were multifactorial and that less severe outbreaks with low mortality were reported w h e n C r y p t o s p o r i d i u m was the sole pathogen identified. In this study, C r y p t o s p o r i d i u m was the only potential aetiological agent detected in 71"4 % (5) of the seven fatal cases. In order to see w h e t h e r this observation applies also in h u m a n cryptosporidiosis, it w o u l d be necessary to investigate children in the c o m m u n i t y with diarrhoea which did n o t require admission to hospital. (We are grateful to staff in the Department of Paediatrics for allowing us access to their patients and to the clinical records as well as to Dr P. Becker from the Institute for Biostatistics of the South African Medical Research Council for statistical analysis of our data. We thank Miss Colleen Dingle and Mrs Devi Sebastian for technical assistance as well as Mrs E. Koekemoer and Mrs M. Pillay for secretarial help.) References
I. Nime FA, Burek JD, Page DL, Holscher MA, Yardley JH. Acute enterocolitis in a human being infected with the protozoan Cryptosporidium. Gastroenterology 1976; 7o: 592-598. 2. Tzipori S. Cryptosporidiosis in animals and humans. Microbiol. Rev. 1983; 47: 84-96.
3°
G. S M I T H AND J. VAN DEN ENDE
3. Meisel JL, Perera DR, Meligro C, Rubin CE. Overwhelming watery diarrhoea associated with a Cryptosporidium in an immunosuppressed patient. Gastroenterology 1976; 70: I I56--I I60. 4" Pitlik SD, Fainstein V, Garza D, Guarda L, Bolivar R, Rios A, Hopfer RL, Mansell PA. Human cryptosporidiosis: spectrum of disease. Report of six cases and review of the literature. Arch Intern Med 1983 ; I43: 2269-2275. 5. Jokipii L, Pohjola S, Jokipii AMM. Cryptosporidium: A frequent finding in patients with gastrointestinal symptoms. Lancet 1983; ii: 358-361. 6. Casemore DP, Jackson B. Sporadic cryptosporidiosis in children. Lancet 1983; ii: 679. 7. Hart CA, Baxby D, Blundell N. Gastroenteritis due to Cryptosporidium: a prospective survey in a children's hospital..7. Infect 1984; 9:264-27 °. 8. Holten-Anderson W, Gerstoft J, Henriksen SA, Pedersen NS. Prevalence of Cryptosporidium among patients with acute enteric infection. ] Infect 1984; 9:277 -282. 9. Isaccs D, Hunt GH, Philips AD, Price EH, Raafat F, Walker-Smith JA. Cryptosporidiosis in immunocompetent children. J Clin Pathol 1983; 38: 76-8 I. lO. Tzipori S, Smith M, Birch C, Barnes G, Bishop R. Cryptosporidiosis in hospital patients with gastroenteritis. Am J Trop Med Hyg I983; 3z : 931-934. I I. Mata L, BolAnos H, Pizarro D, Vives M. Cryptosporidiosis in children from some highland Costa Rican rural and urban areas. Am ff Trop Med Hyg I984; 33: 24-29. 12. Hojlyng N, Molbak K, Jepsen S. Cryptosporidiosis in Liberia in children. Lancet I984; i: 734. I3. Bogaerts J, Lepage P, Rouvroy D, Vandepitte J. Cryptosporidium a frequent cause of diarrhoea in Central Africa. J Clin A/licrobiol 1984; zo: 874-876. 14. Ma P, Villanueva TG, Kaufman D, Gillooley JF. Respiratory cryptosporidiosis in the acquired immune deficiency syndrome JAIVIA 1984; 252: I298-I3Ol. I5. Smith G. Cryptosporidium in association with diarrhoeal disease in South Africa. S Afr M e d J 1985; 67: 442. I6. Casemore DP, Armstrong M, Jackson B. Screening for Cryptosporidium in stools. Lancet 1984; i: 734. I7. Casemore DP, Jackson FB. Hypothesis: Cryptosporidiosis in human beings is not primarily a zoonosis, ff Infect 1984; 9: 153-156. I8. Robins-Brown RM, Still CS, Miliotis MD, Richardson NJ, Koornhof HJ, Freiman I, Schoub BD, Lecatsas G, Hartman E. Summer diarrhoea in African infants and children. Arch Dis Child i98o; 55: 923--928. I9. Robins-Browne RM, Coovadia HM, Bodasing MN, Mackenjee MKR. Treatment of acute nonspecific gastroenteritis of infants and young children with erythromycin. Am J Trop Med Hyg I983; 3z: 886-89o. 2o. Angus KW. Cryptosporidiosis in man, domestic animals and birds: a review. ,7 Soc Med I983; 76: 62-70.
Department of Microbiology, University of Natal, Durban, South Africa Accepted for publication 5 July
I985
Summary Over a period of 3 months during the summer, 362 African children admitted to King Edward V I I I Hospital, Durban, were screened for the faecal excretion of Cryptosporidium oocysts. Of 259 children with diarrhoea, oocysts were detected in 31 (I 1.9 %), while none was found in the faeces of xo3 children without diarrhoea (controls). All those children excreting Cryptosporidium were under 2 years of age, giving a prevalence of I5 % for this group. Other potential enteric pathogens were detected in the faeces of i2 (38.7 %) of these children. The case fatality rate for patients with Cryptosporidium was 22.6 ~'o, which may reflect the selection of patients in a study concentrating on hospital inpatients. Cryptosporidium was the second most common organism detected in diarrhoeal faeces, and the only one detected in 9"2 % of diarrhoeal children aged less than two years. These findings indicate that Cryptosporidium should be regarded as a potential pathogen in children admitted to this hospital with severe diarrhoea. Such association of Cryptosporidium with diarrhoea in children accords with recent studies in other parts of the world.
Introduction T h e c o c c i d i a n p a r a s i t e C r y p t o s p o r i d i u m w a s first d e s c r i b e d in a s s o c i a t i o n w i t h h u m a n d i a r r h o e a l d i s e a s e in I976,1 h a v i n g b e e n r e c o g n i s e d p r e v i o u s l y in m a m m a l s , b i r d s a n d r e p t i l e s . 2 T h e r e f o l l o w e d r e p o r t s o f s p o r a d i c cases in h e a l t h y h u m a n c o n t a c t s o f i n f e c t e d d o m e s t i c a n i m a l s a n d s u b s e q u e n t l y c r y p t o s p o r i d i a l o o c y s t s w e r e d e t e c t e d in t h e faeces o f i m m u n o - s u p p r e s s e d p a t i e n t s w i t h i n t r a c t a b l e d i a r r h o e a . 3, 4 I n r e c e n t y e a r s t h e r e s u l t s o f s t u d i e s in W e s t e r n E u r o p e , ~-9 A u s t r a l i a , 1° C e n t r a l A m e r i c a H a n d A f r i c a ~2,~3 h a v e s u g g e s t e d a n a s s o c i a t i o n b e t w e e n C r y p t o s p o r i d i u m a n d s e l f - l i m i t i n g d i a r r h o e a l d i s e a s e , as well as s o m e t i m e s chronic diarrhoea and small bowel damage. Patients both with and without a p p a r e n t i m m u n e d e f i c i e n c y m a y b e affected. T h e h i g h e s t p r e v a l e n c e s h a v e b e e n r e p o r t e d in c h i l d r e n . T h e p r e s e n c e o f c r y p t o s p o r i d i a l o o c y s t s h a s also b e e n r e c o r d e d in t h e h u m a n b i l i a r y ~ a n d r e s p i r a t o r y t r a c t s . ~4 L i t t l e is k n o w n a b o u t t h e a s s o c i a t i o n o f c r y p t o s p o r i d i o s i s w i t h d i a r r h o e a l illness in s o u t h e r n A f r i c a , a l t h o u g h a r e c e n t s m a l l s t u d y 15 r e v e a l e d t h e p r e s e n c e o f C r y p t o s p o r i d i u m o o c y s t s in d i a r r h o e a l faeces f r o m 3 o ' 8 % o f I3 p a e d i a t r i c i n p a t i e n t s at K i n g E d w a r d V I I I H o s p i t a l , D u r b a n . T h i s article r e c o r d s t h e f i n d i n g s o f a l a r g e r s t u d y o f t h e p r e s e n c e o f C r y p t o s p o r i d i u m o o c y s t s in t h e faeces o f c h i l d r e n w i t h a n d w i t h o u t d i a r r h o e a a d m i t t e d to t h e s a m e h o s p i t a l . All correspondence should be addressed to: Dr Grace Smith, Public Health Laboratory, East Birmingham Hospital, Bordesley Green East, Birmingham B9 5ST. ox63-4453/86/o4oo25 + o6 $o2.oo/o
© x986 The British Society for the Study of Infection
26
G. S M I T H AND J. VAN D E N ENDE
P a t i e n t s and m e t h o d s
T h e study was conducted at King Edward V I I I Hospital, Durban, South Africa, a busy teaching hospital with approximately 2000 beds. T h e hospital serves the black community in the Durban area and is a referral centre for outlying hospitals and clinics in the Natal-Kwa Zulu region which is largely coastal with a sub-tropical climate. For the period January-March I985, diarrhoeal faeces from 259 patients aged up to I2 years were examined for the presence of Cryptosporidium oocysts. Air-dried faecal smears were stained by the modified Ziehl-Neelsen technique 16 and examined microscopically by one observer (EGS): All specimens were examined also for the presence of salmonellas, shigellas, Vibrio cholerae, Yersinia enterocolitica, Campylobacter jejuni and enteropathogenic Escherichia coli by means of standard bacteriological techniques. In addition, each specimen was examined for parasitic ova, cysts and trophozoites by light microscopy of wet smears and for rotavirus antigen by enzyme immunoassay (' Rotazyme', Abbott Laboratories). Faeces from 103 children who were inpatients during the period of the study and who did not have diarrhoea or other gastrointestinal symptoms were examined as controls. When possible, further specimens were obtained from patients whose initial samples of faeces were positive for Cryptosporidium. Clinical details were recorded from inpatient notes. As a check on the observer's ability to detect and identify cryptosporidia correctly, a positive faecal specimen and a stained faecal smear were sent to D r Bruce Jackson at the Public Health Laboratory, Rhyl, North Wales, who confirmed the presence of cryptosporidial oocysts. Results
Cryptosporidial oocysts were detected in the faeces of 3I ( I I ' 9 % ) of 259 children with diarrhoea. T h e y were not detected in the faeces of I03 controls. T h e age distribution of these children is shown in Table I. All patients excreting cryptosporidial oocysts were aged less than 2 years, giving an incidence of 15 % for this group. T h e distribution of Cryptosporidium in this age group, compared with children aged between 2 and I2 years, was significantly different (X~ = 3"84; P < o . o I ) . Age and sex d i s t r i b u t i o n
T h e mean age of patients with Cryptosporidium was 6"2 months with a range of I - I 8 months. T h e male to female ratio for those less than 2 years of age was I : 2 . i for those excreting cryptosporidial oocysts; 1:o"9 for those in the Cryptosporidium negative diarrhoeal group and I :I "25 for those in the control group. T h e age distribution among males and females was similar, with a mean of 5" I months and 6"7 months respectively. O t h e r enteric p a t h o g e n s
Potential enteric pathogens were detected in the faeces of I2 (38"7 %) patients excreting Cryptosporidium; this figure did not differ significantly from the
Cryptosporidiosis Table I
27
Frequency of Cryptosporidium oocysts in the faeces of children with diarrhoea
Age
No. children
No. (%) with Cryptosporidium oocysts
No. controls*
< 6 months 6-i2 months I3-23 months
I28 53 25
I7 IO 4
47 *7 I4
Subtotal
2o6
31 (I5"o)
78
2 years 3-4 years 5-6 years 7-8 years 9--I2 years Total
7 8
0 o
II
O
3
6
o
2
0
2
2I 259
I2 6
31 (I I'9)
IO3
* Faeces of controls were all negative for Cryptosporidium oocysts. Table II
Frequency of other potential enteric pathogens in faecal specimens examined for Cryptosporidium oocysts
Patients with diarrhoea Cryptosporidium found* Cryptosporidium not found Controls
All patients
Patients < 2 years of age
38"7% 34"o% 25"o%
38"7 % 4o'6 % 25"7%
* All patients in whom Cryptosporidium oocysts were found were less than 2 years of age. d e t e c t i o n rates in the o t h e r groups, as s u m m a r i s e d in T a b l e II. Details o f organisms d e t e c t e d are given in T a b l e I I I . Salmonellas were p r e s e n t in I9"3 % o f patients excreting C r y p t o s p o r i d i u m . T h i s figure is significantly greater t h a n the 6"8% of c hi l dr en aged 2 years and less w i t h o u t C r y p t o s p o r i d i u m ( P = o'o232, according to t he test for the difference b e t w e e n p r o p o r t i o n s ) . O t h e r potential p a t h o g e n s were n o t f o u n d in 19 (61 "3 %) patients excreting c r y p t o s p o r i d i a l oocysts. Clinical details A p a r t f r o m one pat i ent excreting c r y p t o s p o r i d i a l oocysts w ho had b e e n sent h o m e after a p e r i o d o f r e h y d r a t i o n in the Paediatric Resuscitation U n i t , all others were a d m i t t e d to hospital. T h e m ai n criteria for admission were severe d e h y d r a t i o n , associated infections and fever. S y m p t o m s p r e c e d e d admission for an average of 4"6 days in patients for w h o m this i n f o r m a t i o n was available (29/3 i). R e s p i r a t o r y tract illness, ranging f r o m c o u g h to b r o n c h o p n e u m o n i a , a c c o m p a n i e d w a t e r y di ar r hoea a nd v o m i t i n g in 2~ patients (67"7%). Five
28
G. S M I T H
A N D J. V A N D E N E N D E
T a b l e I I I Potential enteric pathogens in faecal specimens examined for Cryptosporidium oocysts from children less than 2 years of age Diarrhoea specimens
Organism
Salmonella spp. Shigella spp. Enteropathogenic Escherichia coli Campylobacter jejuni Giardia lamblia cysts Rotavirus Mixed infections Pathogens not found
Cryptosporidiumnegative (Total I75)
Cryptosporidiumpositive (Total 3 I)
Controls (Total 78)
I2 (6"8%) 3 (I'7%) 27 (I 5"4 %)
6 (x9"3) i (3"2)
3 (3"8) O 4 (5"i)
3 (I-7 %)
I (3"2)
o
o
o
6 (7"7)
40 (22"8%) 14 (8"0%) Io5 (59"4%)
O
6 (I9'3) 2 (6"4) I9 (6I'3)
I4 (I7"9) 7 (I2-O) 58 (74"3)
patients (I 6.I %) had concomitant bacteraemia due to Salmonella typhimurium (one), Streptococcus pneumoniae (two), Escherichia coli (one) and Klebsiella spp. (one). Seven patients had urinary tract infections. Seven children with C r y p t o s p o r i d i u m died, t h e r e b y giving a case fatality rate of 22.6 % ; none had evidence of bacteraemia. In the remainder, the average duration of stay in hospital was 15"8 days. T w e l v e patients, 44 % of those for w h o m information was available, and including three of those w h o died, had, on admission, b o d y weights below the third percentile for their age and sex. Cryptosporidial oocysts were detected in s u b s e q u e n t faecal specimens from 29 patients and also the m o t h e r of one patient. She developed diarrhoea while caring for her child on the w a r d ; p r o b a b l y due to p e r s o n - t o - p e r s o n transfer of the parasite. 17 Discussion
T h e importance of C r y p t o s p o r i d i u m as a h u m a n intestinal pathogen in Africa has been illustrated b y the results o f previous studies of populations in northern and central regions. 12,13 T h i s study of children in southern Africa supports these findings. D u r i n g 3 m o n t h s in the s u m m e r the incidence of C r y p t o s p o r idium was I 2 ~o overall in 259 children admitted to hospital with diarrhoea, oocysts not being detected in IO3 controls without diarrhoea. F o r children less than 2 years of age the incidence was r 5 %. Both these figures are higher than the 7"9 % and IO'4% recorded in children with diarrhoea in Liberia 1~ and R w a n d a 13 respectively. Similar studies in Australia, ~° E u r o p e 5-9 and Central America 11 have revealed lower rates of b e t w e e n 2.8 % and 4"8 %. It is not clear to what extent this variation in rates reflects regional differences or efficiency in detecting cryptosporidial oocysts in faeces. Unlike other published studies, a high percentage (38"7 %) of other potential
Cryptosporidiosis
29
enteric pathogens was f o u n d in the faeces of patients with C r y p t o s p o r i d i u m . T h e m o s t c o m m o n were Salmonella sp., f o u n d in a significantly greater p r o p o r t i o n than in those w i t h o u t C r y p t o s p o r i d i u m . A study of children with s u m m e r diarrhoea at Baragwanath Hospital in J o h a n n e s b u r g TM stressed the polymicrobial nature of diarrhoea among children in developing communities and f o u n d potential pathogens in 23"3 % o f age-matched controls, a figure similar to that of 25 % for controls in this study. A m o n g children of all ages with diarrhoea included in this study, rotavirus was detected most often (19"3 %), while C r y p t o s p o r i d i u m (I 1"9 %) was f o u n d m o r e frequently than enteropathogenic Eseherichia coli (I I "6 %). In a previous s t u d y of diarrhoea in children in K i n g E d w a r d V I I I Hospital, 19 during the winter m o n t h s , and in which the presence of C r y p t o s p o r i d i u m was not sought, rotavirus (29 % ) was also the most frequent potential intestinal pathogen detected, followed b y Campylobacter spp. (I 7 Yo) and enteropathogenic E. coli ( 1 2 % ) . In assessing the status of C r y p t o s p o r i d i u m as an intestinal pathogen, it m a y well be significant that in 9"2 % of the children less than 2 years of age with diarrhoea, C r y p t o s p o r i d i u m was the only organism detected. A striking finding in this s t u d y is the detection of C r y p t o s p o r i d i u m oocysts only in children less than 2 years of age. In spite of the significant association of C r y p t o s p o r i d i u m with diarrhoea its precise pathogenic role is n o t clear. T h e case fatality rate for children with C r y p t o s p o r i d i u m was 22.6 % which m a y reflect the severity of d e h y d r a t i o n and electrolyte disturbance at the time of admission. Patients had been s y m p t o m a t i c for a mean of 4"6 days before admission and m a n y had respiratory tract infections; 3 0 % had either bacteraemia or urinary tract infection; some were malnourished. Five t h o u s a n d children with diarrhoea and dehydration severe enough to require intravenous fluids are seen in the the D e p a r t m e n t of Paediatrics each year; a b o u t 40 0/0 of these are admitted. Since this s t u d y concentrated on inpatients, the most severely affected patients were necessarily included. In his review of cryptosporidiosis in man, domestic animals and birds, Angus 2° notes that the m o s t serious outbreaks of the disease in calves were multifactorial and that less severe outbreaks with low mortality were reported w h e n C r y p t o s p o r i d i u m was the sole pathogen identified. In this study, C r y p t o s p o r i d i u m was the only potential aetiological agent detected in 71"4 % (5) of the seven fatal cases. In order to see w h e t h e r this observation applies also in h u m a n cryptosporidiosis, it w o u l d be necessary to investigate children in the c o m m u n i t y with diarrhoea which did n o t require admission to hospital. (We are grateful to staff in the Department of Paediatrics for allowing us access to their patients and to the clinical records as well as to Dr P. Becker from the Institute for Biostatistics of the South African Medical Research Council for statistical analysis of our data. We thank Miss Colleen Dingle and Mrs Devi Sebastian for technical assistance as well as Mrs E. Koekemoer and Mrs M. Pillay for secretarial help.) References
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3°
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