Abstract
This thesis consists of 8 chapters and addresses the etiology, diagnosis, outcome and treatment of adult meningitis in Indonesia. The studies were conducted in Hasan Sadikin Hospital, Bandung, the referral hospital for West Java province, Indonesia between December 2006 and August 2012.
In a cohort of adult patients presenting with meningitis, we found that the vast majority of patients present with subacute meningitis, with high HIV prevalence. The most common diagnosis was TB meningitis, and cryptococcal meningitis was found in one-third of HIV patients. Bacterial meningitis was rare. The outcome was bad, approximately half of patients died during follow up, with HIV infection being the strongest risk factor for death.
Bacteriological confirmation of TB cases was found in 50% of cases. In-house real-time PCR (rt-PCR) targeting insertion sequence IS6110 had a higher sensitivity than microscopy and culture. In the search of other possible cause, we found that CSF PCR for Toxoplasma gondii was positive in one third of the HIV-infected population tested.
In the field of treatment, we examined if intensified antibiotic treatment containing a higher dose rifampicin intravenously and/or moxifloxacin may improve outcome. Intensified treatment regimens result in higher exposure in blood and CSF, did not result in increased toxicity, and high dose rifampicin was associated with a significant mortality reduction.
In the field of prevention, we investigated the prevalence and clinical significance of cryptococcal antigenemia in a cohort of HIV outpatient clinic. We found that 7.1% of ART-naïve patients with low CD4 count had a positive cryptococcal antigen. This cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis, early dropout, and early death. General lack of awareness of meningitis signs and symptoms was found both in laypeople and health providers. Measures to deal with this situation need to be formulated.
