Blaine, R W

Prinsloo, B

Weldhagen, G F

English

South African Medical Journal (SAMJ)

SCIENTIFIC LETTERSTo the Editor: This report aims to document possibly the firstisolation of Candida famata as a cause of human central nervoussystem infection.Yeasts and other medically important fungi cause variousclinical conditions ranging from trivial infestations to seriouslife-threatening conditions. Candida species were demonstratedas being the causative agents of oral thrush from as early as18391 and thereafter recognised as causing a multitude ofinfective disorders. With the advent of widespread oncologicaltreatment in the early 1960s1 and controlled iatrogenic immunesuppression for various other reasons, Candida spp. once againarose as a formidable opportunistic human pathogen.Emerging yeast infections have been described with increasingfrequency, with at least 17 species of the genus Candida nowbeing recognised as potential human pathogens. 1 With furtherdevelopments in medical intervention and the increasingpopulation of patients with immune deficiencies, whetheriatrogenic or acquired, such as HIV infection, the list of yeaststhat can cause disease will continue to grow. The flagship ofthe genus Candida, namely C. albicans, is the most commonspecies isolated from blood cultures and blood-associatedinfections1 especially in the nosocomial setting. For newemerging yeast pathogens blood and catheter-associatedinfections are common,1 although some species may causeinfection at other sites. Yeast infections of the central nervoussystem caused by organisms other than Cryptococcus spp. areuncommon, with Candida and Aspergillus species being the onlyother noteworthy pathogens.2 The emerging yeast C. famata haspreviously been described as a human pathogen, associatedwith eye1 and intravenous catheter infections, 1 fungaemia3,4 andperitonitis5 respectively.Case reportA 29-year-old man presented to a community hospital with a 3-week collateral history of feeling generally unwell. His maincomplaint was a severe relentless headache with occasionalvomiting. At the time of admission he appeared neurologicallysuppressed, not responding well to vocal commands, but stillresponded briskly to painful stimuli. No further relevanthistory could be elicited bar that he had not travelled recently.Clinical examination revealed neck stiffness with both positiveKernig’s and Brudzinski’s signs but no other signs ofpathology.A clinical diagnosis of bacterial meningitis wasmade and treatment was commenced with cefotaxime,administered intravenously.Special investigationsA lumbar puncture performed shortly after admission revealedslightly turbid, xanthochromic cerebrospinal fluid (CSF).Biochemical investigation revealed CSF protein 28 580 mg/l(normal range 150 - 450 mg/l), CSF chloride 106 mmol/l(normal range 118 - 132 mmol/l) and CSF glucose 6.1 mmol/l(normal range 2.2 - 3.9 mmol/l). Microscopic analysis of theCSF sample revealed polymorphonuclear leucocytes (PMN)5/µl (normal range 0 - 5/µl), lymphocytes 22/µl (normal range0 - 10/µl),6 with no overt micro-organisms observed.Cryptococcal and bacterial capsular antigen tests could not beperformed due to clotting of the CSF sample. Syphilis serologywas negative in the rapid plasma reagin (RPR), Treponemapallidum haemagglutination (TPHA) and fluorescenttreponemal antibody absorption (FTA-abs) tests. HIV serologywas positive with the standard battery of one screeningenzyme-linked immunosorbent assay ELISA) and twoconfirmatory ELISAtests.Case-isolate identificationThe CSF sample was plated onto appropriate semisolid agarmedia according to standard microbiological operationalprocedures.6 Within 72 hours positive growth was observed onboth chocolate and blood agar plates. Subsequent Gramstaining of the isolate revealed yeast cells, which were kept forfurther mycological analysis and identification. This isolate wasinoculated onto the ID32C (Biomerieux SA, Marcy-l’Etoile,France) yeast identification system according to themanufacturer’s instructions. Two separate identificationsrevealed C. famata with degrees of identification (specificity) asstated by the manufacturer, of 99.9% and 99.8% respectively.The use of the ID32C system has been proved previously to bethe most accurate for the identification of infrequently isolatedCandida species.7 No other microorganisms includingmycobacteria were isolated from this specimen.Susceptibility testingThe case isolate was subjected to antifungal susceptibilitytesting employing the Fungitest micro-broth dilution kit(Biorad, Marnes la Coquette, France) according to themanufacturer’s instructions. The C. famata strain was found tobe sensitive to all antifungal agents tested including: 5-fluorocytosine, amphotericin B, miconazole, ketoconazole,itraconazole and fluconazole, which is similar to the findings ofsusceptibility studies published previously.8TreatmentThe patient’s clinical condition improved slightly duringhospitalisation to the extent that oral therapy with fluconazolecould commence 8 days after admission with a stat oral dose of400 mg fluconazole, followed by 200 mg administered twice601August 2003, Vol. 93, No. 8  SAMJCandida famata central nervous system infectionAugust 2003, Vol. 93, No. 8  SAMJSCIENTIFIC LETTERSdaily. Despite his initial recovery the patient’s conditionworsened and he died 12 days after admission.DiscussionThis case demonstrates that C. famata may act as a centralnervous system pathogen in immune-compromisedindividuals.A study conducted on mice previously treated withcortisone9 demonstrated the organism’s potential to invade thecentral nervous system under immune-compromisingconditions. Of these infected animals, 50% were killed whilethis species proved non-pathogenic to normal mice with nogross pathology, microscopic lesions or positive tissue culturesat the end of the experiment.9Our patient demonstrated a chronic clinical picture, withCSF special investigations supporting the diagnosis ofmeningitis caused by a fungal pathogen, with increased CSFlymphocytes, elevated CSF-protein and positive fungal culturebeing most suggestive. Fluconazole treatment for C. famatainfections has reported mixed success, 4,5 with one case ofsuccessful treatment of catheter-associated fungaemia afteradministration of amphotericin B.1 Successful therapy withfluconazole for yeast infections usually requires intravenousdosing, early commencement of therapy and an adequatedosage, this patient being a case in point, with delayedtreatment and ineffective oral dosing probably leading to hisdeath. The role of HIV as an immunosuppressive conditionand possible co-factor for C. famata infection of the centralnervous system could not be further investigated due to thedeath of the patient. C. famata is an uncommon humanpathogen with few documented infectious conditions. The casepresented shows the organism to be a possible novel pathogenin the human central nervous system. Failure to identify andrecognise C. famata as a pathogen, combined with delayedtherapy, especially when occurring in immune-compromisedpatients, may lead to unnecessary fatalities.We thank R Lindeque-Kolver for supplying the clinicalinformation.B PrinslooG F WeldhagenDepartment of Medical MicrobiologyUniversity of PretoriaNationalHealth Laboratory ServicePretoriaR W BlaineNational Health Laboratory ServicePretoria1. Hazen KC. New and emerging yeast pathogens. Clin Microbiol Rev 1995; 8: 462-478.2. Gripshover B, Ellner JJ. Chronic meningitis. In: Mandell GL, ed. Mandell, Douglas andBennett’s Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: ChurchillLivingstone, 1999.3. Krcmery V, Kunova A. Candida famata fungemia in a cancer patient: case report. J Chemother2000; 12: 189-190.4. Carrega G, Riccio G, Santoriello L, Pasqualini M, Pellicci R. Candida famata fungemia in asurgical patient successfully treated with fluconazole. Eur JClin Microbiol Infect Dis 1997; 16:698-699.5. Quindos G, Cabrera F, Arilla MC, et al. Fatal Candida famata peritonitis in a patientundergoing continuous ambulatory peritoneal dialysis who was treated with fluconazole.Clin Infect Dis 1994; 18: 658-660.6. Gray LD, Fedorko DP. Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 1992;5: 130-145.7. Michel-Nguyen A, Favel A, Chastin C, Selva M, Regli P. Comparative evaluation of acommercial system for identification of Candida lusitaniae. Eur J Clin Microbiol Infect Dis 2000;19: 393-395.8. Barchiesi F, Tortorano AM, Di Francesco LF, Cogliati M, Scalise G, Viviani MA. In-vitroactivity of five antifungal agents against uncommon clinical isolates of Candida spp. JAntimicrob Chemother 1999; 43: 295-299.9. Khan ZU, Mizra VC, Rhandhawa HS, Damodaran VN. Pathogenicity of some ordinarilyharmless yeasts for cortisone-treated mice. Sabouraudia 1980; 18: 319-327.602To the Editor: In South Africa there is scepticism about thefeasibility of exclusive breast-feeding (EBF) — despite successstories from Mexico, Bangladesh and Belarus. 1-3 We report onthe steps taken to develop a breast-feeding counselling andsupport strategy, which supports EBF, in a rural subdistrict inKwaZulu-Natal, where mixed feeding was the norm. Priorresearch showed that traditional beliefs and concerns aboutmilk sufficiency or infant satiety/health were the main reasonsfor mixed feeding.4Between May and September 2000 we recruited matriculatedwomen, living in the subdistrict, as breast-feeding counsellors(BCs). They were trained using the WHO/UNICEF breast-feeding counselling training course, 5 a 40-hour course with astrong counselling component. Knowledge before and aftertraining was assessed using a tool developed by the studyteam. A field guide, containing information from the courseand appropriate suggestions addressing traditional beliefs thathinder EBF, was developed as an aide-mémoire to facilitatequality, consistent breast-feeding counselling. All BCs weretrained to use the field guide. BCs recruited pregnant or breast-feeding women at clinics, and visited them at home atleast once a week. The involvement of influential familymembers during home visits was encouraged. During eachhome visit, using the listening and learning skills from thecourse,5 BCs asked how feeding was going, whether additionalfeeds or fluids were given to the infant and reasons for these,and about breast health. They observed a breast feed, and thencounselled the mother (and often the family) using ‘buildingExclusive breast-feeding — a pipe dream?

Candida famata central nervous system infection

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Candida famata central nervous system infection

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