Management of Central Nervous System Infections, Vientiane, Laos, 2003–2011

Dubot‐Pérès, Audrey; Mayxay, Mayfong; Phetsouvanh, Rattanaphone; Lee, Sue J.; Rattanavong, Sayaphet; Vongsouvath, Manivanh; Davong, Viengmon; Chansamouth, Vilada; Phommasone, Koukeo; Moore, Catrin E.; Dittrich, Sabine; Lattana, Olay; Sirisouk, Joy; Phoumin, Phonelavanh; Panyanivong, Phonepasith; Sengduangphachanh, Amphonesavanh; Sibounheuang, Bountoy; Chanthongthip, Anisone; Simmalavong, Manivone; Sengdatka, Davanh; Seubsanith, Amphaivanh; Keoluangkot, Valy; Phimmasone, Prasith; Sisout, Kongkham; Detleuxay, Khamsai; Luangxay, Khonesavanh; Phouangsouvanh, Inpanh; Craig, Scott B.; Tulsiani, Suhella M.; Burns, Mary‐Anne; Dance, David A.B.; Blacksell, Stuart D.; Lamballerie, Xavier de; Newton, Paul N.

doi:10.3201/eid2505.180914

Cited by 36 publications

(51 citation statements)

References 46 publications

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“…The first report of acute JEV infection in Laos was by Moore et al, 7 through detection of anti-JEV IgM in cerebrospinal fluid (CSF) among patients with suspected central nervous system (CNS) infections at Mahosot Hospital, Vientiane. Recent studies have confirmed JEV infection across Laos, [8][9][10] more commonly in the north than in the south. Aubry et al 11 described JEV genotype 1 from the CSF of a patient from Vientiane Province.…”

Section: Introductionmentioning

confidence: 97%

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR

Mayxay

Douangdala²,

Vilayhong

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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Although Japanese encephalitis virus (JEV) infection is an important cause of acute febrile illness in Lao PDR (Laos), patient outcome has not been evaluated. We prospectively followed up 123 JEV-infected patients (70 children < 15 years and 53 adults ≥ 15 years) admitted at Mahosot Hospital, Vientiane, from 2003 to 2013. Japanese encephalitis virus infection was diagnosed by the detection of anti-JEV IgM in cerebrospinal fluid and/or IgM seroconversion. Neurological sequelae were assessed using the Liverpool Outcome Score (LOS), total (maximum score = 75), and final (maximum score = 5). The median (interquartile range [IQR]) age of the patients was 12.0 (7.5–18.8) years, and 57% were male. The median (IQR) duration of patients’ follow-up was 4.5 (3.2–7.3) years. Of all patients, 10/123 (8.1%) died during hospitalization, and 13/123 (10.6%) died at home after discharge, giving a mortality of 18.7% (23/123) (33 [26.8%] patients were lost to follow-up). The frequency of neurological sequelae at the last follow-up was 61.2% (48.4% in adults and 69.4% in children, P = 0.135). The proportion of patients with severe and moderate functional impairment at the last follow-up was significantly higher in children (25%) than in adults (6.5%), P = 0.042. Half of the patients who were still alive at the last follow-up (67) and for whom LOS data were available (22) had improvements in their total and final LOS between discharge and the last follow-up. The total and final LOS at discharge were not significantly different between children and adults, but total LOS at the last follow-up was significantly higher in adults than in children (median [IQR]: 74.5 [73–75] versus 73.0 [73–75], P = 0.019).

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Section: Introductionmentioning

confidence: 97%

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR

Mayxay

Douangdala²,

Vilayhong

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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“…Neurological manifestations and sequelae of scrub typhus and SFR have been overlooked. Numerous reports indicate that both Orientia and Rickettsia are significant causes of encephalitis and meningitis in the Asia-Pacific region [ 10 – 13 ]. O .…”

Section: Introductionmentioning

confidence: 99%

“…O . tsutsugamushi accounts for 17.9% of all bacterial central nervous system (CNS) infections in Laos and up to 25% of all encephalitic infections in India [ 10 , 13 ]. Rickettsia spp .…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses

2020

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Scrub typhus and spotted fever rickettsioses (SFR) are understudied, vector-borne diseases of global significance. Over 1 billion individuals are at risk for scrub typhus alone in an endemic region, spanning across eastern and southern Asia to Northern Australia. While highly treatable, diagnostic challenges make timely antibiotic intervention difficult for these diseases. Delayed therapy may lead to severe outcomes affecting multiple organs, including the central nervous system (CNS), where infection and associated neuroinflammation may be lethal or lead to lasting sequelae. Meningitis and encephalitis are prevalent in both scrub typhus and SFR. Additionally, case reports detailing focal neurological deficits have come to light, with attention to both acute and chronic sequelae of infection. Despite the increasing number of clinical reports outlining neurologic consequences of these diseases, relatively little research has examined underlying mechanisms of neuroinflammation. Animal models of scrub typhus have identified cerebral T-cell infiltration and vascular damage associated with endothelial infection and neuropathogenesis. Differential gene expression analysis of brain tissues during murine scrub typhus have revealed selective increases in CXCR3 ligands, proinflammatory and type-1 cytokines and chemokines, and cytotoxicity molecules, as well as alterations in the complement pathway. In SFR, microglial expansion and macrophage infiltration contribute to neurological disease progression. This narrative Review highlights clinical neurologic features of scrub typhus and SFR and evaluates our current understanding of basic research into neuroinflammation for both diseases in animal models. Further investigation into key mediators of neuropathogenesis may yield prognostic markers and treatment regimens for severe patients.

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“…Central nervous system (CNS) infections cause significant mortality and morbidity worldwide, but especially in low- and middle-income countries (1). Common CNS infections include bacterial meningitis (BM), viral encephalitis, tuberculous meningitis (TBM) and cryptococcal meningitis (2), but there are >100 documented infectious causes of CNS infections (3). Additionally, over the last decade, antibody-mediated causes of encephalitis (e.g.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections

Thanh

Casals-Pascual

Nth.

et al. 2020

Preprint

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Word counts: Abstract: 245, text: 2760 2 7 Keywords: Meningitis, central nervous system infections, mass-spectrometry, lipocalin 2, 2 8 biomarkers 2 9Running title: Diagnostic biomarker discovery in central nervous system infected patients 3 0 ABSTRACT 1 Background: Central nervous system (CNS) infections are common causes of morbidity and 2 mortality worldwide. Rapid, accurate identification of the likely cause is essential for clinical 3 management and the early initiation of antimicrobial therapy, which potentially improves clinical 4 outcome. 5Methods: We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal 6 fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential 7 diagnostic protein biomarkers. We then validated the diagnostic performance of a selected 8 biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS 9 infections admitted to a referral hospital in southern Vietnam. 0Results: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of 1 1 bacterial meningitis. The analysis of the validation cohort showed that LCN2 could discriminate 1 2 bacterial meningitis from other CNS infections, including tuberculous meningitis, cryptococcal 1 3 meningitis and viral/antibody-mediated encephalitis (sensitivity: 0.88 (95% confident interval 1 4 (CI): 0.77-0.94), specificity: 0.91 (95%CI: 0.88-0.94) and diagnostic odd ratio: 73.8 (95%CI: 1 5 31.8-171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) 1 6 commonly used in routine care worldwide. The combination of LCN2 and these four routine 1 7 CSF markers resulted in the highest diagnostic performance for bacterial meningitis (area under 1 8 receiver-operating-characteristic-curve 0.96; 95%CI: 0.93-0.99).1 9Conclusions: Our results suggest that LCN2 is a sensitive and specific biomarker for 2 0 discriminating bacterial meningitis from a broad spectrum of CNS infections. A prospective 2 1 study is needed to further assess the diagnostic utility of LCN2 in the diagnosis and management 2 2 of CNS infections. 2 3 1 Central nervous system (CNS) infections cause significant mortality and morbidity worldwide, 2 but especially in low-and middle-income countries (1). Common CNS infections include 3 bacterial meningitis (BM), viral encephalitis, tuberculous meningitis (TBM) and cryptococcal 4 meningitis (2), but there are >100 documented infectious causes of CNS infections (3). 5 Additionally, over the last decade, antibody-mediated causes of encephalitis (e.g. anti-N-methyl-6 D-aspartate receptor (anti-NMDAR) encephalitis) have been recognized (4), which further 7 challenges routine diagnostics. 8 Clinical features are often insufficient to discriminate the likely cause and standard laboratory 9 investigations identify the causative agent in <60% of cases (5, 6). Critically, the clinical We thank Le 1 logistic support, and Dr Nguyen Thi Hoang Mai for her help with material collection. We are 2 indebted to patients for the...

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Management of Central Nervous System Infections, Vientiane, Laos, 2003–2011

Cited by 36 publications

References 46 publications

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR

Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses

Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections

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