Title : Aetiology, risk factors and early outcomes of meningoencephalitis in East Africa: The role of multiplex PCR
Abstract:
Background: Meningo-encephalitis in Sub-Saharan Africa is accompanied by a mortality rate documented as high as 90%. It is linked to diverse immunosuppressive states. The etiology has remained largely undefined by traditional diagnostic tools with studies reporting an unidentifiable cause in up to 62% of patients. These studies were conducted before the era of Multiplex PCR and Gene Xpert. Globally, there is a paucity of studies on the etiology of Meningoencephalitis where these novel and older diagnostics are combined.
Objectives: To determine the etiology, risk factors and outcome of Meningoencephalitis among adult patients admitted to the Moi Teaching and Referral Hospital, western Kenya
Methods: A longitudinal study was conducted between October 2022 and January 2023 at MTRH. All consecutive participants with features of meningitis were recruited (n=94).
Ethical approval was obtained, consent received and participants recruited based on history and physical exam findings suggestive of Meningoencephalitis. Lumbar puncture and Cerebrospinal fluid analysis (CSF) were performed (Microscopy, Culture, Cryptococcal Antigen testing (CRAG), Gram Staining, GeneXpert, Multiplex PCR, Biochemistry and Cell Count). Data on a priori determined risk factors (HIV(Human immunodeficiency Virus) infection, chronic steroid use, malignancies, chronic lung diseaseand chronic alcohol use), hospital admission status and mortality of meningoencephalitis patientsby day 14 of admission was abstracted from patient records. Means and medians were calculated for categorical variables while frequency distribution for categorical variables
Results: Out of 94 participants, 49 (52.1%) were female. The mean age was 42 years. The most common presenting features were headache 70 (74.5 %), neck stiffness 59 (62.8%),
fever 57(60.6%), altered consciousness 50 (53.2%) and Seizures in 17 (18.1%). The classic triad of meningitis was present in 21 (22.3%). The most common causative organism was Cryptococcus neoformans in 40 (42.4%) of participants, followed by Mycobacterium tuberculosis 15 (16%), Cytomegalovirus 6 (6.3%), Varicella zoster virus 3 (3.2%) and Streptococcus pneumoniae 1(1.1%). The etiology was undetermined in
23.4 %. HIV seropositivity was reported in 78 (83.0 %), chronic alcohol use in 23 (24.5%) and chronic lung disease in 13 (13.8%) of the cohort. All participants with Cryptococcosis, tuberculosis, Cytomegalovirus and Varicella zoster meningitis were co- infected with HIV. By the 14th day of follow up, 55.3% of participants remained hospitalized. A mortality of 15 (16%) was observed; 7/15 had Cryptococcus neoformans infection, 4/15 Mycobacterium tuberculosis infection,1 participant had multiple organisms implicated (Cytomegalovirus, Mycobacterium tuberculosis and Human herpesvirus - 6) and 4/15 had an undetermined etiology.
Conclusion: The most common causes of Meningoencephalitis are Cryptococcus neoformans and Mycobacterium tuberculosis. HIV is the most common risk factor associated with Meningoencephalitis. Majority of patients remained hospitalized by day 14 . The aetiology of meningoencephalitis remained unidentified in nearly a quater of participants despite using multiplex PCR and GeneXpert.
