Volume 25, Number 5—May 2019
Research
Management of Central Nervous System Infections, Vientiane, Laos, 2003–2011
Table 3
Demographic and clinical data at admission of patients with suspected CNS infection, by age group and etiology, Laos, January 2003–August 2011*
Characteristic | Etiology |
|||||||
---|---|---|---|---|---|---|---|---|
Age group |
Confirmed, n = 450 | None confirmed, n = 615 | Confirmed viral, n = 172 | Confirmed bacterial, n = 175 | ||||
All, n = 1,065 | Children, n = 358 | Adults, n = 707 | ||||||
Demographic | ||||||||
M | 666 (62.5) | 207 (57.8) | 459 (64.9) | 288 (64.0) | 378 (61.5) | 111 (64.5) | 117 (66.9) | |
F | 399 (37.5) | 151 (42.2) | 248 (35.1) | 162 (36.0) | 237 (38.5) | 61 (35.5) | 58 (33.1) | |
Age, y, median (IQR) |
23 (8–38) |
3 (0.41–8) |
32 (24–47) |
23 (10–38) |
24 (6–40) |
16 (7–28) |
23 (9–45) |
|
History | ||||||||
HIV seropositive, n = 703 | 119 (16.9) | 1 (0.4) | 118 (24.8) | 75 (27.1) | 44 (10.33) | 8 (8.0) | 6 (6.2) | |
Diabetes, n = 850 | 24 (2.8) | 0 | 24 (4.2) | 12 (3.5) | 12 (2.4) | 1 (0.8) | 10 (7.5) | |
Antibiotic use before lumbar
puncture, n = 953 |
590 (61.9) |
238 (71.9) |
352 (56.6) |
252 (64.0) |
338 (60.5) |
109 (69.9) |
100 (62.5) |
|
Signs and symptoms | ||||||||
Days of fever at admission, median (IQR), n = 1,058 | 4 (2–8) | 4 (2–6) | 5 (2–10) | 5 (3–10) | 4 (1–7) | 5 (3–7) | 5 (3–8) | |
Fever, n = 1,059 | 962 (90.8) | 340 (95.2) | 622 (88.6) | 425 (94.9) | 537 (87.9) | 162 (95.3) | 171 (97.7) | |
Headache,† n = 893 | 787 (88.1) | 155 (83.3) | 632 (89.4) | 369 (92.5) | 418 (84.6) | 139 (90.9) | 135 (91.2) | |
Hearing loss,† n = 893 | 51 (5.7) | 10 (5.4) | 41 (5.8) | 20 (5.0) | 31 (6.3) | 8 (5.2) | 7 (4.7) | |
Dysuria,† n = 891 | 28 (3.1) | 4 (2.2) | 24 (3.4) | 10 (2.5) | 18 (3.7) | 3 (2.0) | 3 (2.0) | |
Visual loss,† n = 885 | 66 (7.5) | 14 (7.7) | 52 (7.4) | 23 (5.8) | 43 (8.8) | 11 (7.2) | 5 (3.4) | |
Diplopia,† n = 889 | 36 (4.1) | 4 (2.2) | 32 (4.5) | 15 (3.4) | 21 (4.3) | 6 (4.0) | 6 (4.1) | |
Photophobia, n = 850 | 52 (5.8) | 14 (7.4) | 38 (5.4) | 23 (5.8) | 29 (5.9) | 7 (4.6) | 10 (6.8) | |
Focal neurologic signs, n = 939 | 22‡ (2.3) | 5 (1.6) | 17 (2.7) | 8 (2.1) | 14 (2.5) | 1 (0.7) | 6 (4.1) | |
Neck stiffness, n = 1,064 | 683 (64.2) | 245 (68.4) | 438 (62.0) | 316 (70.2) | 367 (59.8) | 130 (75.6) | 128 (73.1) | |
Confusion, n = 1,060 | 608 (57.4) | 232 (65.5) | 376 (53.3) | 254 (56.7) | 354 (57.8) | 114 (66.3) | 103 (59.5) | |
Convulsions, n = 1,063 | 319 (30.0) | 233 (65.3) | 86 (12.2) | 119 (26.5) | 200 (32.6) | 65 (37.8) | 44 (25.3) | |
GCS score, median (IQR), n = 1,010 | 14 (11–15) | 14 (10–15) | 15 (11–15) | 15 (11–15) | 14 (10–15) | 13 (10–15) | 14 (11–15) | |
GCS score <15,§ n = 1,047 | 551 (52.6) | 220 (63.4) | 331 (47.3) | 225 (50.5) | 326 (54.2) | 101 (59.4) | 94 (54.0) | |
WHO clinical CNS infection,¶
n = 1,040 |
771 (74.1) |
313 (90.7) |
458 (65.9) |
341 (77.0) |
430 (72.0) |
143 (85.1) |
140 (80.9) |
|
Outcome | ||||||||
Days of hospitalization, n = 846, median (IQR) | 9 (5–14) | 8 (5–13) | 10 (5–15.5) | 11 (6–17) | 8 (5–13) | 10 (6–14) | 11 (7–17) | |
Death,# n = 893 | 235 (26.3) | 70 (22.5) | 165 (28.4) | 94 (25.0) | 141 (27.3) | 23 (15.7) | 43 (27.9) |
*Values are no. (%) unless indicated otherwise. We defined children as patients <15 years of age and adults >15 years of age. History or physical examination or both, were taken into account for confusion, neck stiffness, photophobia, fever (history of fever or >37.5ºC during physical examination). In total, 8 women in the patient population were pregnant; 26 (2.4%) patients had computed tomography brain scans, and 2 of these scans demonstrated brain abscesses. The confirmed viral group includes patients infected with multiple viruses, and the confirmed bacterial group includes patients infected with multiple bacteria. CNS, central nervous system; GCS, Glasgow Coma Scale; IQR, interquartile range; WHO, World Health Organization.
†Data from children <3 years of age were considered not reliable and were thus excluded from analysis.
‡Of these patients, 7 had hemiplegia, 11 had limb weakness, and 1 had paraplegia; 13 patients had admission or discharge diagnoses of Guillain-Barre syndrome. Retrospective evaluation of the likelihood of this diagnosis by using the Brighton system suggested that 4 patients met level 3 criteria for Guillain-Barre syndrome diagnostic certainty (42).
§Includes confused and disoriented patients.
¶Defined as fever with GCS score <15, neck stiffness (history of or present during examination), or history of seizures or any of these signs in combination. Patients with missing data for 1 of these criteria were not counted.
#Includes patients who died at the hospital and those taken home to die.
References
- Tarantola A, Goutard F, Newton P, de Lamballerie X, Lortholary O, Cappelle J, et al. Estimating the burden of Japanese encephalitis virus and other encephalitides in countries of the mekong region. PLoS Negl Trop Dis. 2014;8:e2533. DOIPubMedGoogle Scholar
- Glaser CA, Gilliam S, Schnurr D, Forghani B, Honarmand S, Khetsuriani N, et al.; California Encephalitis Project, 1998-2000. In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis. 2003;36:731–42. DOIPubMedGoogle Scholar
- Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis. 2006;43:1565–77. DOIPubMedGoogle Scholar
- Dittrich S, Rattanavong S, Lee SJ, Panyanivong P, Craig SB, Tulsiani SM, et al. Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study. Lancet Glob Health. 2015;3:e104–12. DOIPubMedGoogle Scholar
- World Health Organization. Japanese encephalitis. 2015 Dec 31 [cited 2018 Jun 6]. https://www.who.int/en/news-room/fact-sheets/detail/japanese-encephalitis
- Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, et al. Neurological manifestations of dengue infection. Lancet. 2000;355:1053–9. DOIPubMedGoogle Scholar
- Puccioni-Sohler M, Orsini M, Soares CN. Dengue: a new challenge for neurology. Neurol Int. 2012;4:e15. DOIPubMedGoogle Scholar
- Cam BV, Fonsmark L, Hue NB, Phuong NT, Poulsen A, Heegaard ED. Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever. Am J Trop Med Hyg. 2001;65:848–51. DOIPubMedGoogle Scholar
- Hendarto SK, Hadinegoro SR. Dengue encephalopathy. Acta Paediatr Jpn. 1992;34:350–7. DOIPubMedGoogle Scholar
- Ho Dang Trung N, Le Thi Phuong T, Wolbers M, Nguyen Van Minh H, Nguyen Thanh V, Van MP, et al.; VIZIONS CNS Infection Network. Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study. PLoS One. 2012;7:e37825. DOIPubMedGoogle Scholar
- Flett KB, Rao S, Dominguez SR, Bernard T, Glode MP. Variability in the diagnosis of encephalitis by pediatric subspecialists: the need for a uniform definition. J Pediatric Infect Dis Soc. 2013;2:267–9. DOIPubMedGoogle Scholar
- Xie Y, Tan Y, Chongsuvivatwong V, Wu X, Bi F, Hadler SC, et al. A population-based acute meningitis and encephalitis syndromes surveillance in Guangxi, China, May 2007-June 2012. PLoS One. 2015;10:e0144366. DOIPubMedGoogle Scholar
- Touch S, Hills S, Sokhal B, Samnang C, Sovann L, Khieu V, et al. Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillance. Trop Med Int Health. 2009;14:1365–73. DOIPubMedGoogle Scholar
- Olsen SJ, Campbell AP, Supawat K, Liamsuwan S, Chotpitayasunondh T, Laptikulthum S, et al.; Thailand Encephalitis Surveillance Team. Infectious causes of encephalitis and meningoencephalitis in Thailand, 2003-2005. Emerg Infect Dis. 2015;21:280–9. DOIPubMedGoogle Scholar
- Dittrich S, Sunyakumthorn P, Rattanavong S, Phetsouvanh R, Panyanivong P, Sengduangphachanh A, et al. Blood-brain barrier function and biomarkers of central nervous system injury in rickettsial versus other neurological infections in Laos. Am J Trop Med Hyg. 2015;93:232–7. DOIPubMedGoogle Scholar
- Moore CE, Sengduangphachanh A, Thaojaikong T, Sirisouk J, Foster D, Phetsouvanh R, et al. Enhanced determination of Streptococcus pneumoniae serotypes associated with invasive disease in Laos by using a real-time polymerase chain reaction serotyping assay with cerebrospinal fluid. Am J Trop Med Hyg. 2010;83:451–7. DOIPubMedGoogle Scholar
- Moore CE, Blacksell SD, Taojaikong T, Jarman RG, Gibbons RV, Lee SJ, et al. A prospective assessment of the accuracy of commercial IgM ELISAs in diagnosis of Japanese encephalitis virus infections in patients with suspected central nervous system infections in Laos. Am J Trop Med Hyg. 2012;87:171–8. DOIPubMedGoogle Scholar
- World Health Organization. Recommended standards for surveillance of selected vaccine-preventable diseases. 2003 [cited 2018 Jun 6]. http://www.measlesrubellainitiative.org/wp-content/uploads/2013/06/WHO-surveillance-standard.pdf
- Thaipadungpanit J, Chierakul W, Wuthiekanun V, Limmathurotsakul D, Amornchai P, Boonslip S, et al. Diagnostic accuracy of real-time PCR assays targeting 16S rRNA and lipL32 genes for human leptospirosis in Thailand: a case-control study. PLoS One. 2011;6:e16236. DOIPubMedGoogle Scholar
- Cole JR Jr, Sulzer CR, Pursell AR. Improved microtechnique for the leptospiral microscopic agglutination test. Appl Microbiol. 1973;25:976–80.PubMedGoogle Scholar
- Jiang J, Chan T-C, Temenak JJ, Dasch GA, Ching W-M, Richards AL. Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi. Am J Trop Med Hyg. 2004;70:351–6. DOIPubMedGoogle Scholar
- Jiang J, Stromdahl EY, Richards AL. Detection of Rickettsia parkeri and Candidatus Rickettsia andeanae in Amblyomma maculatum Gulf Coast ticks collected from humans in the United States. Vector Borne Zoonotic Dis. 2012;12:175–82. DOIPubMedGoogle Scholar
- Henry KM, Jiang J, Rozmajzl PJ, Azad AF, Macaluso KR, Richards AL. Development of quantitative real-time PCR assays to detect Rickettsia typhi and Rickettsia felis, the causative agents of murine typhus and flea-borne spotted fever. Mol Cell Probes. 2007;21:17–23. DOIPubMedGoogle Scholar
- Phetsouvanh R, Blacksell SD, Jenjaroen K, Day NPJ, Newton PN. Comparison of indirect immunofluorescence assays for diagnosis of scrub typhus and murine typhus using venous blood and finger prick filter paper blood spots. Am J Trop Med Hyg. 2009;80:837–40. DOIPubMedGoogle Scholar
- Carvalho MG, Tondella ML, McCaustland K, Weidlich L, McGee L, Mayer LW, et al. Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol. 2007;45:2460–6. DOIPubMedGoogle Scholar
- Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB. Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol. 2001;39:1553–8. DOIPubMedGoogle Scholar
- Mai NTH, Hoa NT, Nga TVT, Linh D, Chau TTH, Sinh DX, et al. Streptococcus suis meningitis in adults in Vietnam. Clin Infect Dis. 2008;46:659–67. DOIPubMedGoogle Scholar
- Leparc-Goffart I, Baragatti M, Temmam S, Tuiskunen A, Moureau G, Charrel R, et al. Development and validation of real-time one-step reverse transcription-PCR for the detection and typing of dengue viruses. J Clin Virol. 2009;45:61–6. DOIPubMedGoogle Scholar
- Watkins-Riedel T, Woegerbauer M, Hollemann D, Hufnagl P. Rapid diagnosis of enterovirus infections by real-time PCR on the LightCycler using the TaqMan format. Diagn Microbiol Infect Dis. 2002;42:99–105. DOIPubMedGoogle Scholar
- Lanciotti RS, Kerst AJ, Nasci RS, Godsey MS, Mitchell CJ, Savage HM, et al. Rapid detection of west nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. J Clin Microbiol. 2000;38:4066–71.PubMedGoogle Scholar
- van Elden LJ, Nijhuis M, Schipper P, Schuurman R, van Loon AM. Simultaneous detection of influenza viruses A and B using real-time quantitative PCR. J Clin Microbiol. 2001;39:196–200. DOIPubMedGoogle Scholar
- Moureau G, Temmam S, Gonzalez JP, Charrel RN, Grard G, de Lamballerie X. A real-time RT-PCR method for the universal detection and identification of flaviviruses. Vector Borne Zoonotic Dis. 2007;7:467–77. DOIPubMedGoogle Scholar
- Moureau G, Ninove L, Izri A, Cook S, De Lamballerie X, Charrel RN. Flavivirus RNA in phlebotomine sandflies. Vector Borne Zoonotic Dis. 2010;10:195–7. DOIPubMedGoogle Scholar
- Kessler HH, Mühlbauer G, Rinner B, Stelzl E, Berger A, Dörr HW, et al. Detection of Herpes simplex virus DNA by real-time PCR. J Clin Microbiol. 2000;38:2638–42.PubMedGoogle Scholar
- Bousbia S, Papazian L, Saux P, Forel JM, Auffray J-P, Martin C, et al. Repertoire of intensive care unit pneumonia microbiota. PLoS One. 2012;7:e32486. DOIPubMedGoogle Scholar
- Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH. Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. J Clin Microbiol. 2001;39:4362–9. DOIPubMedGoogle Scholar
- Hummel KB, Lowe L, Bellini WJ, Rota PA. Development of quantitative gene-specific real-time RT-PCR assays for the detection of measles virus in clinical specimens. J Virol Methods. 2006;132:166–73. DOIPubMedGoogle Scholar
- Uchida K, Shinohara M, Shimada S, Segawa Y, Doi R, Gotoh A, et al. Rapid and sensitive detection of mumps virus RNA directly from clinical samples by real-time PCR. J Med Virol. 2005;75:470–4. DOIPubMedGoogle Scholar
- Phommasone K, Paris DH, Anantatat T, Castonguay-Vanier J, Keomany S, Souvannasing P, et al. Concurrent Infection with murine typhus and scrub typhus in southern Laos—the mixed and the unmixed. PLoS Negl Trop Dis. 2013;7:e2163. DOIPubMedGoogle Scholar
- White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30:377–99. DOIPubMedGoogle Scholar
- Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley and Sons; 1987.
- Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al.; Brighton Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29:599–612. DOIPubMedGoogle Scholar
- Bennett JE, Dolin R, Blaser MJ. Principles and practice of infectious diseases. 8th ed. Philadelphia: Elsevier Saunders; 2014.
- Dubot-Pérès A, Sengvilaipaseuth O, Chanthongthip A, Newton PN, de Lamballerie X. How many patients with anti-JEV IgM in cerebrospinal fluid really have Japanese encephalitis? Lancet Infect Dis. 2015;15:1376–7. DOIPubMedGoogle Scholar
- Eamsobhana P. Angiostrongyliasis in Thailand: epidemiology and laboratory investigations. Hawaii J Med Public Health. 2013;72(Suppl 2):28–32.PubMedGoogle Scholar
- Newman MP, Blum S, Wong RCW, Scott JG, Prain K, Wilson RJ, et al. Autoimmune encephalitis. Intern Med J. 2016;46:148–57. DOIPubMedGoogle Scholar
- Taylor WR, Nguyen K, Nguyen D, Nguyen H, Horby P, Nguyen HL, et al. The spectrum of central nervous system infections in an adult referral hospital in Hanoi, Vietnam. PLoS One. 2012;7:e42099. DOIPubMedGoogle Scholar
- Schut ES, Westendorp WF, de Gans J, Kruyt ND, Spanjaard L, Reitsma JB, et al. Hyperglycemia in bacterial meningitis: a prospective cohort study. BMC Infect Dis. 2009;9:57. DOIPubMedGoogle Scholar
- Erdem H, Ozturk-Engin D, Tireli H, Kilicoglu G, Defres S, Gulsun S, et al. Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study. J Neurol. 2015;262:890–8. DOIPubMedGoogle Scholar
- Blaha J, Barteczko-Grajek B, Berezowicz P, Charvat J, Chvojka J, Grau T, et al. Space GlucoseControl system for blood glucose control in intensive care patients—a European multicentre observational study. BMC Anesthesiol. 2016;16:8. DOIPubMedGoogle Scholar
1Deceased.