Aetiology of meningitis at the Moi Teaching and Referral Hospital, Eldoret, Kenya. D. K. Lagat, MBChB, Mmed(Moi)

Transcription

1 Aetiology of meningitis at the Moi Teaching and Referral Hospital, Eldoret, Kenya D. K. Lagat, MBChB, Mmed(Moi)

2 Introduction Meningitis is common and important Syndromes of meningitis: Acute bacterial (Acute) viral Sub-acute and chronic Tuberculous Cryptococcal HIV has significantly impacted epidemiology

3 Global Epidemiology (USA) Acute bacterial meningitis: 2.5/100,000 annually S pneumococcus > N menengitidis > H influenzae Acute viral meningitis: 2000/yr; Only 11% definite Cryptococcal meningitis: 5-10% of AIDS TBM: less than 1% of all TB cases

4 Regional Epidemiology: Sub- Saharan Africa C. neoformans causes: 0% 45% S. pneumococcus: 13% 18 % TBM: 12% - 23% Gordon et al, J cl microbiology 2000, Malawi Campaigne et al. WHO bulletin 1999, Niger Fringpong et al. EAMJ 1998, Ghana Hakim et al. the AIDS 2000, Zimbabwe

5 Local Epidemiology Aga Khan, Kenya Cross-sectional study between 1991 and patients studied 31% Cryptococcosis 31% pyogenic organisms 23% TBM 50% HIV +ve, 31% -Ve (Healthline, Oyoo and Jowi.)

6 Study Justification New disease patterns emerging Literature is limited Most studies small, single-centre; methods variable; most early HAART era. No local data (MTRH) Needed to guide treatment & prevention Proximity to frontier districts Research AMPATH

7 Research Questions 1. What are the common causes of meningitis amongst patients admitted to the adult general medical wards of the MTRH? 2. What is the HIV sero-prevalence amongst patients with meningitis at the general adult medical wards of the MTRH?

8 2.To determine the prevalence of Human Immuno-deficiency virus (HIV) infection amongst patients with meningitis at the MTRH adult general medical wards. Objectives 1.To determine the common causes of meningitis amongst patients admitted to the adult general medical wards of the MTRH

9 Study Design and setting Cross-sectional study Consecutive patients with meningitis The adult general medical wards of the MTRH Data collection from 1 st august to 31 st October 2007

10 Patients (81) Cases were defined as any males or females 13 years or older with clinical features suggestive of meningial inflammation including: headache fever Neck pain and rigidity Confusion/altered mentation convulsion photophobia cranial nerve palsies especially in association with constitutional symptoms

11 Inclusion Criteria 1. Patients 13 years and above admitted to the adult general medical wards with suspected meningitis on clinical basis. 2. A written informed consent to participate in the study.

12 Exclusion criteria 1. Contraindication to lumbar puncture. 2. Patients already on antibiotics or anti- TB drugs.

13 Recruitment and Enrollment Patient presented to casualty staff. OPD doctor immediately informed the investigator of such patients. Patient re-evaluation: complete history and physical examination, by investigator. Enrolled if they met the inclusion criteria LP and initial treatment at casualty if acute meningitis or poor general condition; otherwise this was done in the ward.

14 Clinical Procedures Fundoscopy CT scan lumbar puncture Acute meningitis: ceftriaxone 4g iv after LP

15 Laboratory Procedures CSF studies HIV (Unigold, Bioline; ELISA if discordant) Blood sugar Other tests: CXR, Sputum, Bs for MPS, CBC etc.

16 Laboratory Procedures ZN-staining for AAFBs India ink staining for Cryptococcus neoformans Gram-staining Protein levels (colorimetric) glucose level (glucose oxidase method) Cryptococcal antigen test

17 Laboratory Procedures Bacterial culture: Blood Agar CBA Maconkey Mycobacterial culture: MGIT Lowenstein Jensen slopes Direct microscopy and serology for speciation Cryptococcal culture: Sabaraud s

18 Lab criteria for meningitis CSF cell count >5/mcL and/or, CSF protein >45mg/dL and/or, an organism known to cause meningitis was isolated and/or, a specific antigen test (e.g. CrAg) was positive.

19 Laboratory criteria Acute bacterial meningitis Positive gram-stain or culture result Probable acute bacterial meningitis CSF sugar/rbs ratio <0.5 protein mg/dl cell count >5/mcL predominantly polymorphs -Ve Gram-stain and/or cultures

20 Lab criteria TBM: ZN +Ve, and/or MGIT or LJ+ Probable TBM: CSF protein 500mg/dl cells predominantly mononuclear -Ve ZN, MGIT and/or LJ

21 Laboratory criteria Cryptococcal meningitis CrAg +, India-ink or fungal culture Meningitis of undetermined etiology CSF cell count > 5/mcL, and/or CSF protein >45mg/dL but didn t fit into any of the above categories No meningitis CSF cell count was <5/mcL and protein <45mg/dL in setting of a negative cultures & CrAg

22 Statistical Analysis Data analysis: Statistical Analysis System Institute version 9.1 Descriptive statistics e.g. mean, standard deviation, median and range used for the continuous variables frequency listings used for categorical variables Tables and a bar graph were used to depict the results.

23 Summary of methods Patients re-evaluated for eligibility CSF studies HIV test on all patients

24 Results Screening and Enrollment Screened: 102 Eligible: 81 Completed study: 81

25 Basic demographics Characteristic Frequency (%) N = 81 Age (years) Mean (SD) Median (range) Gender Female Male:Female Marital status Married Single Widowed Educational level Nil Primary level At least H/School Occupation: Self employed Employed 34 (9.2) 32(14-62) 50 1: (59) 27 (33) 6 (7) 9 (11) 21 (26) 51 (63) 36 (44) 14 (17) Residence Urban Rural Aware of HIV status: Yes No 28 (35) 53 (65) 25 (31) 56 (69)

26 HIV infection and meningitis Diagnosis HIV-infected (%) Cryptococcal Meningitis (N=34) 34 (100) T B M (N=6) 5 (83.3) Pneumococcal Meningitis (N=3) 2 (66.7) Meningitis of Unconfirmed Etiology (N=31) 26 (83.9) No Meningitis (N=7) 4 (57.1) Total ( N=81) 71 (87.7)

27 Figure 1:A bar graph showing relative frequency of the various aetiologic types of meningitis in the study group (n=81) 42% 38% percentage of patients % 7% 0 1st Qtr 4% 2nd Qtr 3rd Qtr 4th Qtr cryptococcal East tuberculous West pneumococcal North unknown aetiology No meningitis Aetiologic category of meningitis

28 Clinical variables Symptom/ Sign Cryptococcal (N=34) Pneumococcal (N=3) T B M (N=6) Headache( N=35) 28 (82%) 3 (100%) 4 (67%) Fever (N=31) 22 (65%) 3 (100%) 6 (100%) Weight loss (N=20) 17 (50%) 2(67%) 1 (17%) Cough (N=6) 5 (15%) 0(0.00%) 1 (17%) Night Sweats (N=3) 2 (6%) 0(0.00%) 1 (17%) Night Stiffness=28) 21 (62%) 3 (100%) 4 (67%) Kerning s Sign (N=20) 13 (38%) 3 (100%) 4 (67%) Brudzinski s (N=5) 4 (12%) 0 (0.00%) 1 (17%) Reduced Consciousness (N=14) 9 (26%) 1 (33%) 4 (67%) Cranial nerve palsies (N=0) 0(0.00%) 0(0.00%) 0(0.00%) Convulsions (N=1) 1 (3%) 0(0.00%) 0(0.00%) Others (N=3) 3 (9%) 0(0.00%) 0(0.00%)

29 Laboratory characteristics Variable Cryptococcocal Meningitis (N=34) T B M (N=6) Pneumococcal (N=3) Mean Cell Count per Microlitre Mean CSF Protein in mg/dl Median (mg/dl) 198 ( ) 653.5( ) ( ) 225 Mean CSF :Serum glucose ratio Microbiological/immunological Findings (absolute figures) CRAG positive: 34 India ink positive: 19 Culture positive: 20 ZN positive: 1 LJ positive: 2 MGIT positive: 6 (All Mtb) Gram Stain positive:3 Culture positive:3

30 Discussion Meningitis common: 6.6% of admissions Gordon et al in Blantyre Malawi: 5.2% of all medical admissions KNH: 1.7% of medical cases seen, and 22.6% of neurologic diseases Nairobi Hospital: CM 22% of neurologic HIV complications )

31 Discussion Meningitis associated with high HIV sero-prevalence; 71(88%) HIV positive (100% cryptococcosis, 83% TBM, 67% pneumococcal Similar results: Zimbabwe, 84% 61% in Nairobi Kenya

32 Discussion C. neoformans commonest cause of meningitis identified (42%) Similar results: Blantyre Malawi: CM28%, S. Pneu. 18%, N.meneng. 13% Harare Zimbabwe: CM45%, 27%MM, PM16%, TBM12% Dissimilar results: Kumasi Ghana: no CM in 314 meningitis patients (

33 Discussion No confirmed co-infections None described in the studies reviewed

34 Discussion Headache in 91% of the patients Other common symptoms: fever (82%), weight loss (49%) 6% of the patients had history of convulsions Neck stiffness: 65%; kerning s sign: 45% Similar findings: Braingana et al at the Mulago

35 Limitations The sample size probably not large enough to detect uncommon aetiologies Some exclusion criteria based on selfreporting Possibility that patients were missed Lab Limitations

36 Conclusion and recommendations Meningitis is associated with high HIV coinfection C. neoformans a leading cause identifiable Investment on cryptococcosis research prudent: primary chemoprophylaxis, emerging therapy challenges Laboratory capacity building to facilitate improved definitive diagnosis of meningitis

37 Acknowledgements Supervisors Colleagues and faculty Ward, OPD, Lab and AMPATH staff Family