Rickettsioses as causes of CNS infection in southeast Asia.

Abstract

In The Lancet Global Health, Sabine Dittrich and colleagues1Dittrich S Rattanavong S Lee SJ et al.Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study.Lancet Glob Health. 2015; 3: 104-112Summary Full Text Full Text PDF Scopus (73) Google Scholar report that scrub typhus caused by Orientia tsutsugamushi, murine typhus caused by Rickettsia typhi, and leptospirosis caused by various Leptospira species account for more than a third of CNS infections diagnosed over 8 years in Vientiane Hospital in Laos. The study is one more great contribution from this team in their investigation of undocumented syndromes, as well as in the public health challenge of rickettsial diseases in southeast Asia. The same investigators have previously reported that scrub typhus was the second most common microbial cause of fever of unknown origin in rural Laos (122 [15%] of 799 diagnosed cases).2Mayxay M Castonguay-Vanier J Chansamouth V et al.Causes of non-malarial fever in Laos: a prospective study.Lancet Glob Health. 2013; 1: e46-e54Summary Full Text Full Text PDF Scopus (164) Google Scholar In 2006, rickettsial infection was detected in 115 (27%) of 427 adults admitted to Vientiane Hospital for fever with negative blood culture.3Phongmany S Rolain J-M Phetsouvanh R et al.Rickettsial infections and fever, Vientiane, Laos.Emerg Infect Dis. 2006; 12: 256-262Crossref PubMed Scopus (178) Google Scholar The most common rickettsial agent was O tsutsugamushi followed by R typhi. Fewer data are available about the prevalence of these diseases in other southeast Asian countries. In Thailand, scrub and murine typhus has been reported4Suputtamongkol Y Suttinont C Niwatayakul K et al.Epidemiology and clinical aspects of rickettsioses in Thailand.Ann N Y Acad Sci. 2009; 1166: 172-179Crossref PubMed Scopus (46) Google Scholar in 16% and 2%, respectively, of fever of unknown origin, with mortality of 3–17% for scrub typhus. Even if epidemiological data for the whole region are unavailable, the substantial presence of rickettsial infections is shown by frequent reports in travellers returning from this area.5Jensenius M Davis X von Sonnenburg F et al.Multicenter GeoSentinel analysis of rickettsial diseases in international travelers, 1996–2008.Emerg Infect Dis. 2009; 15: 1791-1798Crossref PubMed Scopus (122) Google Scholar Because ecotourism and adventure travel are increasingly popular, the incidence of tick-borne rickettsioses among travellers is likely to continue to increase. All patients with rickettsial infections reported by Dittrich and colleagues presented with fever at admission, and few patients presented with typical eschars of inoculation (only 3·6% of patients with murine typhus and 6·7% with scrub typhus).1Dittrich S Rattanavong S Lee SJ et al.Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study.Lancet Glob Health. 2015; 3: 104-112Summary Full Text Full Text PDF Scopus (73) Google Scholar This finding might be a result of poor awareness about pathognomonic signs of rickettsioses among clinicians rather than an absence of such disease. Rickettsioses are treatable but remain underestimated. Besides murine typhus and scrub typhus, tick-borne spotted fever group rickettsioses cause much fever of unknown origin in tropical countries.6Parola P Paddock CD Socolovschi C et al.Update on tick-borne rickettsioses around the world: a geographic approach.Clin Microbiol Rev. 2013; 26: 657-702Crossref PubMed Scopus (796) Google Scholar R felis is one such rickettsia; it has been detected worldwide in arthropod hosts (mainly fleas), with the cat flea Ctenocephalides felis the only confirmed biological vector. A growing number of reports implicate R felis in human disease, particularly in the tropics. It has been detected in 3–4% of cases of fever of unknown origin in rural Mali7Mediannikov O Socolovschi C Edouard S et al.Common epidemiology of Rickettsia felis infection and malaria, Africa.Emerg Infect Dis. 2013; 19: 1775-1783Crossref PubMed Scopus (85) Google Scholar and Kenya,8Richards AL Jiang J Omulo S et al.Human infection with Rickettsia felis, Kenya.Emerg Infect Dis. 2010; 16: 1081-1086Crossref PubMed Scopus (88) Google Scholar and 6% of cases in rural Senegal.7Mediannikov O Socolovschi C Edouard S et al.Common epidemiology of Rickettsia felis infection and malaria, Africa.Emerg Infect Dis. 2013; 19: 1775-1783Crossref PubMed Scopus (85) Google Scholar R felis has also been detected in mosquitoes7Mediannikov O Socolovschi C Edouard S et al.Common epidemiology of Rickettsia felis infection and malaria, Africa.Emerg Infect Dis. 2013; 19: 1775-1783Crossref PubMed Scopus (85) Google Scholar and it is common in countries in Africa with high prevalences of malaria.7Mediannikov O Socolovschi C Edouard S et al.Common epidemiology of Rickettsia felis infection and malaria, Africa.Emerg Infect Dis. 2013; 19: 1775-1783Crossref PubMed Scopus (85) Google Scholar Cases of R felis infection in Thailand have also been reported.9Edouard S Bhengsri S Dowell SF Watt G Parola P Raoult D Two human cases of Rickettsia felis infection, Thailand.Emerg Infect Dis. 2014; 20: 1780-1781Crossref PubMed Scopus (29) Google Scholar Collaborations of investigators in the tropics combined with powerful diagnostic methods have increased the recognition of neglected pathogens in patients with acute undifferentiated fever. However, when studying the causes of fever of unknown origin, inclusion of local negative controls is essential because the incidence of many pathogens in these regions is totally different from their incidence in Europe, changing the predictive value of diagnostic tests. The lack of local negative controls causes false positives because of the commonness of asymptomatic forms of infectious diseases; therefore, European controls cannot be used to evaluate the specificity of diagnostic techniques in tropical countries. Rickettsioses are severe diseases that can be fatal, yet in Dittrich and colleagues' study few patients with scrub and murine typhus received doxycycline (55% and 39%, respectively).1Dittrich S Rattanavong S Lee SJ et al.Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study.Lancet Glob Health. 2015; 3: 104-112Summary Full Text Full Text PDF Scopus (73) Google Scholar As a consequence, the use of an empirical doxycycline treatment for patients with fever of unknown origin should be discussed, especially when empirical treatment with β-lactams has failed or in cases with severe clinical presentation. Doxycycline is used for malaria prophylaxis in travellers. Only two prospective randomised studies10Twartz JC Shirai A Selvaraju G Saunders JP Huxsoll DL Groves MG Doxycycline propylaxis for human scrub typhus.J Infect Dis. 1982; 146: 811-818Crossref PubMed Scopus (54) Google Scholar have shown the effectiveness of prophylactic doxycycline to prevent scrub typhus. Designing comparative studies to test the drug's effectiveness for preventing scrub typhus would be difficult. However, we propose that doxycycline be given as a priority for chemoprophylaxis against malaria in travellers to the tropics to thereby protect against rickettsioses and leptospirosis. Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective studyOur data suggest that R typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp infections are important causes of CNS infections in Laos. Antibiotics, such as tetracyclines, needed for the treatment of murine typhus and scrub typhus, are not routinely advised for empirical treatment of CNS infections. These severely neglected infections represent a potentially large proportion of treatable CNS disease burden across vast endemic areas and need more attention. Full-Text PDF Open Access