Occurrence of cryptococcal antigenaemia among HIV- uninfected patients with stroke in Nigeria: a pilot case-control study


  • SA Fayemiwo
  • OB Makanjuola
  • F. Bongomin
  • J Nwaokenye
  • S Diala
  • M Tito-Ilori
  • R Akinyemi
  • MO Owolabi


Background: Infections have been associated with stroke occasionally, but are not considered to be a direct cause. We aimed to compare the prevalence of cryptococcal antigenaemia in stroke patients compared to stroke-free controls.

Methods: Through the Stroke Investigative Research and Education Network (SIREN) project, adults (aged >18 years) with stroke confirmed by computed tomography (CT) scan or magnetic resonance imaging (MRI) (cases) and age-matched and gender-matched stroke-free controls were recruited from the communities in catchment areas of the cases. A simple random sampling was used to select blood samples of stroke patients and controls in a 1:1 ratio. Serum cryptococcal antigen (CrAg) tests were performed using CrAg Lateral Flow Assays (BIOSYNEXR Crypto PS).

Results: Of the 100 HIV-uninfected patients (50 cases and 50 controls), majority 70 (70%) were males with a median age of 57 (range: 33-86) years. Thirty-six (72%) cases and 23 (46%) controls were hypertensive (p<0.001), while 6 (12%) cases and 14 (28%) controls were diabetic (p=0.059). Overall, CrAg was positive in 16% (n=16) of the participants; 10 (20%) among cases and 6 (12%) among controls (Odds ratio: 1.83; 95% confidence interval: 0.61-5.5; p=0.275). Overall, 13 deaths occurred, all among cases; death rates were similar between CrAg positive (2/10, 20%) and CrAg negative (11/40, 27.5%) stroke patients (p=0.628). Diabetes mellitus had a trend towards predicting a positive CrAg among cases (Odds ratios, 1.52 (95% CI: 0.97-2.4); p=0.069).

Conclusions: Cryptococcal antigenaemia appears to be more common in stroke patients compared to controls. Adequately powered studies are required to explore this observation.

Keywords: Fungal infections, Cryptococcal antigenaemia, Stroke, Diabetes, Nigeria.

Contexte: Des infections ont été associées à des accidents vasculaires cérébraux occasionnellement, mais ne sont pas considérées comme une cause directe. Nous visions à comparer la prévalence de l’antigénémie cryptococcique chez les patients victimes d’un AVC par rapport aux témoins sans AVC.

Méthodes: Dans le cadre du projet Stroke Investigative Research and Education Network (SIREN), des adultes (âgés de 18 ans ou plus) avec un AVC confirmé par tomodensitométrie (TDM) ou imagerie par résonance magnétique (IRM) (cas) et appariés selon l’âge et le sexe Des témoins sans AVC ont été recrutés dans les communautés des zones de desserte des cas. Un simple échantillonnage aléatoire a été utilisé pour sélectionner des échantillons sanguins de patients et de témoins d’AVC dans un rapport 1: 1. Des tests d’antigène cryptococcique sérique (CrAg) ont été réalisés à l’aide de tests CrAg à flux latéral (BIOSYNEXR Crypto PS).

Résultats: Sur les 100 patients non infectés par le VIH (50 cas et 50 témoins), la majorité 70 (70%) étaient des hommes avec un âge médian de 57 ans (intervalle: 33-86). Trente-six (72%) cas et 23 (46%) témoins étaient hypertendus (p <0,001), tandis que 6 (12%) cas et 14 (28%) témoins étaient diabétiques (p = 0,059). Dans l’ensemble, la CrAg était positive chez 16% (n = 16) des participants; 10 (20%) parmi les cas et 6 (12%) parmi les témoins (rapport de cotes: 1,83; intervalle de confiance à 95%: 0,61-5,5; p = 0,275). Dans l’ensemble, 13 décès sont survenus, tous parmi les cas; les taux de mortalité étaient similaires entre les patients ayant subi un AVC CrAg positif (2/10, 20%) et CrAg négatif (11/40, 27,5%) (p = 0,628). Le diabète sucré avait tendance à prédire un CrAg positif parmi les cas (odds ratios, 1,52 (IC à 95%: 0,97-2,4); p = 0,069).

Conclusions: L’antigénémie cryptococcique semble être plus fréquente chez les patients victimes d’un AVC que chez les témoins. Des études suffisamment puissantes sont nécessaires pour explorer cette observation.

Mots clés: Infections fongiques, antigénémie cryptococcique, accident vasculaire cérébral, diabète, Nigéria.

Correspondence: Dr. S. A. Fayemiwo, Department of Medical Microbiology and Parasitology, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail address: dayteet@yahoo.co


Schwartz S, Kontoyiannis DP, Harrison T and Ruhnke M. Advances in the diagnosis and treatment of fungal infections of the CNS. The Lancet Neurology. 2018;17(4):362-372.

Nguyen I, Urbanczyk K, Mtui E and Li S, editors. Intracranial CNS Infections: A Literature Review and Radiology Case Studies. Seminars in Ultrasound, CT and MRI; 2020: Elsevier.

Negroni R. Cryptococcosis. Clinics in dermatology. 2012;30(6):599-609.

Panackal AA, Williamson PR. Fungal infections of the central nervous system. CONTINUUM: Lifelong Learning in Neurology. 2015;21(6):1662-1678.

Williamson PR, Jarvis JN, Panackal AA, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nature Reviews Neurology. 2017;13(1):13.

Esher SK, Zaragoza O and Alspaugh JA. Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain. Memorias do Instituto Oswaldo Cruz. 2018;113(7).

Vu K, Garcia JA and Gelli A. Cryptococcal meningitis and anti-virulence therapeutic strategies. Frontiers in microbiology. 2019;10.

Del Brutto OH. Infections and stroke. Handbook of Clinical Neurology. 2008;93:851-872.

Rosario M, Song X, McCullough LD. An unusual case of stroke. The neurologist. 2012;18(4):229.

Leite AGB, Vidal JE, Bonasser Filho F, Nogueira RS and Oliveira ACPd. Cerebral infarction related to cryptococcal meningitis in an HIV-infected patient: case report and literature review. Brazilian Journal of Infectious Diseases. 2004;8(2):175-179.

Kouame-Assouan A, Cowppli-Bony P, Aka-Anghui ED, et al. Two cases of cryptococcal meningitis revealed by an ischemic stroke. Bulletin de la Societe de pathologie exotique (1990). 2007;100(1):15-16.

Mishra AK, Vanjare HA and Raj PM. Cryptococcal meningitis presenting as acute onset bilateral cerebellar infarct. Journal of neurosciences in rural practice. 2017;8(01):159-160.

Rodríguez-Quiñónez A, Schneck MJ, Biller J and Brown HG, editors. AIDS, stroke, and cryptococcus infection. Seminars in Cerebrovascular Diseases and Stroke; 2004: Elsevier.

Searls DE, Sico JJ, Omay SB, et al. Unusual presentations of nervous system infection by Cryptococcus neoformans. Clinical neurology and neurosurgery. 2009;111(7):638-642.

Akpalu A, Sarfo FS, Ovbiagele B, et al. Phenotyping stroke in sub-Saharan Africa: stroke investigative research and education network (SIREN) phenomics protocol. Neuroepidemiology. 2015;45(2):73-82.

Sarfo FS, Akassi J, Awuah D, et al. Trends in stroke admission and mortality rates from 1983 to 2013 in central Ghana. Journal of the neurological sciences. 2015;357(1-2):240-245.

Owolabi MO, Sarfo F, Akinyemi R, et al. Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study. The Lancet Global Health. 2018;6(4):e436-e46.

Odegbemi O, Dada-Adegbola H, Adeoye I and Fayemiwo S. Epidemiology of Cryptococcal antigenemia among HIV infected patients in southwestern Nigeria. Global Biosecurity. 2019;1(3).

Bratton EW, El Husseini N, Chastain CA, et al. Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant. PloS one. 2012;7(8).

Brizendine KD, Baddley JW and Pappas PG. Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PloS one. 2013;8(3).

Sharma RR. Fungal infections of the nervous system: current perspective and controversies in management. International journal of surgery. 2010;8(8):591-601.

Mfinanga S, Chanda D, Kivuyo SL, et al. Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. The Lancet. 2015;385(9983):2173-2182.

Prasad K, Agarwal J, Nag V, et al. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care center. Neurol India 2003; 51:364-366.

Lui G, Lee N, Ip M, et al. Cryptococcosis in apparently immunocompetent patients. Journal of the Association of Physicians. 2006;99(3):143-151.

Mahale K, Patil S, Ravikumar N and Mahale R. Prevalence of Cryptococcal meningitis among immunocompetent and immunocompromised Individuals in Bellary, South India—A Prospective Study. J Clin and Diagnostic Res. 2012;6(3):388-392.

Bitew A, Hassen M, Getachew T and Fentaw S. Prevalence of Crytpococcal Infection in Patients Clinically Diagnosed to Have Meningitis in Ethiopia. Clinical Medicine Research. 2016;5(4):73-76.

Datir-Rawlings W and Azeez-Akande O. Cryptococcal Antigenemia in HIV-Infected Patients Attending a Tertiary Healthcare Centre in Kano, Northwest, Nigeria. Calabar J Heal Sci. 2017;1(1):2017.

Manga N, Cisse-Diallo V, Dia-Badiane N, et al. Prevalence and Factors Associated with Positive Cryptococcal Antigenemia among HIV Infected Adult Hospitalized in Senegal. J HIV Retrovirus. 2016;2:2.

Goni B, Kida I, Saidu I, et al. Cryptococcal neorformans Antigenemia among HIV-Infected Patients in North Eastern Nigeria. J Transm Dis Immun. 2017;1:1.

Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. The Lancet infectious diseases. 2017;17(8):873-81.

Vela-Duarte D, Nyberg E, Sillau S, et al. Lacunar stroke in cryptococcal meningitis: clinical and radiographic features. Journal of Stroke and Cerebrovascular Diseases. 2019;28(6):1767-72.

Shen Y, Shi L, Nauman E, et al. Association between body mass index and stroke risk among patients with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2020;105(1):dgz032.






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