Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality. Methods We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40). Results Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.
References
[1]
Molyneux E (2005) Human immunodeficiency virus infection and pediatric bacterial meningitis in developing countries. J Neurovirol 11 Suppl 36–10.
[2]
Schutte CM, Van der Meyden CH, Magazi DS (2000) The impact of HIV on meningitis as seen at a South African Academic Hospital (1994 to 1998). Infection 28: 3–7.
[3]
de Gans J, van de Beek D (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347: 1549–1556.
[4]
Auburtin M, Wolff M, Charpentier J, Varon E, Le Tulzo Y, et al. (2006) Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 34: 2758–2765.
[5]
Georges H, Chiche A, Alfandari S, Devos P, Boussekey N, et al. (2009) Adult community-acquired bacterial meningitis requiring ICU admission: epidemiological data, prognosis factors and adherence to IDSA guidelines. Eur J Clin Microbiol Infect Dis 28: 1317–1325.
[6]
Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, et al. (1993) Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 328: 21–28.
[7]
Swartz MN (2004) Bacterial meningitis–a view of the past 90 years. N Engl J Med 351: 1826–1828.
[8]
Gjini AB, Stuart JM, Cartwright K, Cohen J, Jacobs M, et al. (2006) Quality of in-hospital care for adults with acute bacterial meningitis: a national retrospective survey. QJM 99: 761–769.
[9]
Gordon SB, Walsh AL, Chaponda M, Gordon MA, Soko D, et al. (2000) Bacterial meningitis in Malawian adults: pneumococcal disease is common, severe, and seasonal. Clin Infect Dis 31: 53–57.
[10]
Manga NM, Ndour CT, Diop SA, Ka-Sall R, Dia NM, et al. (2008) Adult purulent meningitis caused by Streptococcus pneumoniae in Dakar, Senegal. Med Trop (Mars) 68: 625–628.
[11]
Scarborough M, Gordon SB, Whitty CJ, French N, Njalale Y, et al. (2007) Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 357: 2441–2450.
[12]
Hakim JG, Gangaidzo IT, Heyderman RS, Mielke J, Mushangi E, et al. (2000) Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS 14: 1401–1407.
[13]
Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, et al. (2010) Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis 10: 317–328.
[14]
van de Beek D, de Gans J, McIntyre P, Prasad K (2003) Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev: CD004405.
[15]
Ajdukiewicz KM, Cartwright KE, Scarborough M, Mwambene JB, Goodson P, et al.. (2011) Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial. Lancet Infect Dis.
[16]
van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, et al. (2004) Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 351: 1849–1859.
[17]
Schut ES, Westendorp WF, de Gans J, Kruyt ND, Spanjaard L, et al. (2009) Hyperglycemia in bacterial meningitis: a prospective cohort study. BMC Infect Dis 9: 57.
[18]
Jarvis JN, Meintjes G, Williams A, Brown Y, Crede T, et al. (2010) Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis 10: 67.
[19]
Brouwer MC, van de Beek D, Heckenberg SG, Spanjaard L, de Gans J (2007) Hyponatraemia in adults with community-acquired bacterial meningitis. QJM 100: 37–40.
[20]
Everett DB, Mukaka M, Denis B, Gordon SB, Carrol ED, et al. (2011) Ten years of surveillance for invasive Streptococcus pneumoniae during the era of antiretroviral scale-up and cotrimoxazole prophylaxis in Malawi. PLoS One 6: e17765.
[21]
French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, et al. (2010) A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med 362: 812–822.
[22]
Nyasulu P, Cohen C, De Gouveia L, Feldman C, Klugman KP, et al. (2011) Increased risk of death in human immunodeficiency virus-infected children with pneumococcal meningitis in South Africa, 2003–2005. Pediatr Infect Dis J 30: 1075–1080.
[23]
Domingo P, Suarez-Lozano I, Torres F, Pomar V, Ribera E, et al. (2009) Bacterial meningitis in HIV-1-infected patients in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 51: 582–587.
[24]
Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, et al. (2011) Bacterial meningitis in the United States, 1998–2007. N Engl J Med 364: 2016–2025.
[25]
Sanjoaquin MA, Allain TJ, Molyneux ME, Benjamin L, Everett DB, et al. (2013) Surveillance Programme of IN-patients and Epidemiology (SPINE): Implementation of an Electronic Data Collection Tool within a Large Hospital in Malawi. PLoS Med 10: e1001400.
[26]
Cohen C, Singh E, Wu HM, Martin S, de Gouveia L, et al. (2010) Increased incidence of meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South Africa. AIDS 24: 1351–1360.
[27]
Grau I, Pallares R, Tubau F, Schulze MH, Llopis F, et al. (2005) Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med 165: 1533–1540.
[28]
Glennie SJ, Banda D, Gould K, Hinds J, Kamngona A, et al. (2013) Defective pneumococcal-specific Th1 responses in HIV-infected adults precedes a loss of control of pneumococcal colonization. Clin Infect Dis 56: 291–299.
[29]
Flannery B, Heffernan RT, Harrison LH, Ray SM, Reingold AL, et al. (2006) Changes in invasive Pneumococcal disease among HIV-infected adults living in the era of childhood pneumococcal immunization. Ann Intern Med 144: 1–9.
[30]
McCormick DW, Wilson ML, Mankhambo L, Phiri A, Chimalizeni Y, et al.. (2012) Risk Factors for Death and Severe Sequelae in Malawian Children with Bacterial Meningitis, 1997–2010. Pediatr Infect Dis J.
[31]
Koster-Rasmussen R, Korshin A, Meyer CN (2008) Antibiotic treatment delay and outcome in acute bacterial meningitis. J Infect 57: 449–454.
[32]
Harnden A, Ninis N, Thompson M, Perera R, Levin M, et al. (2006) Parenteral penicillin for children with meningococcal disease before hospital admission: case-control study. BMJ 332: 1295–1298.
[33]
Booy R, Habibi P, Nadel S, de Munter C, Britto J, et al. (2001) Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Arch Dis Child 85: 386–390.
[34]
Nadel S, Britto J, Booy R, Maconochie I, Habibi P, et al. (1998) Avoidable deficiencies in the delivery of health care to children with meningococcal disease. J Accid Emerg Med 15: 298–303.
[35]
Mugisha JO, Shafer LA, Van der Paal L, Mayanja BN, Eotu H, et al. (2008) Anaemia in a rural Ugandan HIV cohort: prevalence at enrolment, incidence, diagnosis and associated factors. Trop Med Int Health 13: 788–794.
[36]
Lewis DK, Whitty CJ, Walsh AL, Epino H, Broek NR, et al. (2005) Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence. Trans R Soc Trop Med Hyg 99: 561–567.
[37]
Burgos J, Penaranda M, Payeras A, Villoslada A, Curran A, et al. (2012) Invasive pneumococcal disease in HIV-infected adults: clinical changes after the introduction of the pneumococcal conjugate vaccine in children. J Acquir Immune Defic Syndr 59: 31–38.
[38]
Cornick JE, Everett DB, Broughton C, Denis BB, Banda DL, et al. (2011) Invasive Streptococcus pneumoniae in Children, Malawi, 2004–2006. Emerg Infect Dis 17: 1107–1109.
[39]
Prokesch RC, Rimland D, Petrini JL Jr, Fein AB (1983) Cerebrospinal fluid pleocytosis after seizures. South Med J 76: 322–327.
[40]
Cohen DB, Zijlstra EE, Mukaka M, Reiss M, Kamphambale S, et al. (2010) Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Trop Med Int Health 15: 910–917.
[41]
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, et al. (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34: 17–60.
