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Am. J. Trop. Med. Hyg., 78(2), 2008, pp. 321-322
Copyright © 2008 by The American Society of Tropical Medicine and Hygiene

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SHORT REPORT


Murine Typhus in Caldas, Colombia

Marylin Hidalgo, Edgar Salguero, Alberto de la Ossa, Ricardo Sánchez, Juan F. Vesga, Leonora Orejuela, AND Gustavo Valbuena*
Grupo de Microbiologia, Instituto Nacional de Salud, Bogota, Colombia; Dirección Territorial de Salud de Caldas, Manizales, Colombia; Facultad de Medicina, Universidad Nacional de Colombia; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

 

ABSTRACT

In the north of Caldas, Colombia, febrile syndromes with positive Weil-Felix reactions have been reported as Murine typhus to the national health authorities. We used indirect immunofluorescence assay (IFA) of serial paired samples to confirm the diagnosis of murine typhus in 14 of 120 patients with a compatible febrile syndrome.


Rickettsia typhi is an intracellular obligate {alpha}-proteobacteria that primarily infects the vascular endothelium and causes murine or endemic typhus. Together with the agent of epidemic typhus, R. prowazekii, they are the exclusive members of the typhus group rickettsiae. R. typhi exists in nature in an enzootic cycle involving rodents and their ectoparasites. It is transmitted to humans mainly by Xenopsylla cheopis, the Oriental rat flea, although other species of fleas, as well as lice and mites, have occasionally been implicated.1 Indeed, murine typhus is more prevalent in rat-infested locations.2 The disease presents with initial non-specific "flu-like" symptoms and, although it is rarely lethal, it is incapacitating. Murine typhus in Colombia has not been previously reported in the international literature. However, it is frequently suspected throughout the north of Caldas province, Colombia, and "confirmed" with a positive Weil Felix reaction (agglutination of Proteus vulgaris OX19), a test of low specificity and sensitivity due to the use of a non-rickettsial antigen.3

The objectives of this study were: 1) to confirm the presence of murine typhus as a cause of fever in this area of Colombia through the use of the gold standard serological test (indirect immunofluorescence assay [IFA]); and 2) to characterize the positive population. Between May and October of 2005, we collected serum samples from 120 patients that consulted the local public hospitals and met the following criteria: symptoms of headache and chills, documented evidence of fever (temperature > 39°C) with or without macular rash, and titer greater than 1:320 in the Weil-Felix test. The samples were collected at the hospitals of 6 towns (Aguadas, Aranzazu, Filadelfia, Neira, Pacora, and Salamina) of the north of Caldas that previously reported a high frequency of murine typhus to the local health authorities. This is a mountainous, coffee-growing region (height between 1,775 and 2,200 m) with temperatures between 18 and 20°C. A second sample was collected 2 to 3 weeks later. Anti-R. typhi IgG and IgM were detected through indirect immunofluorescence assay (IFA), using R. typhi, Wilmington strain, as the antigen. We defined a confirmed case of murine typhus as a febrile syndrome with initial anti-R-typhi IgM titer of 1:64 or greater, and a 4-fold or greater increase in IgG titers in the paired sera analysis. The study was performed under IRB approval and with informed consent.

Immunofluorescence assay results are shown in Table 1Go and Figure 1Go. The age range was 5 to 73 years (median age of 31.7 years). In the analysis by age groups, 29% of the pediatric population (< 14 years of age, N = 17) had a positive serologic diagnosis of murine typhus whereas only 9% of the adults (N = 101) had this confirmed diagnosis (P < 0.035 using Fisher’s exact test); the age of 2 patients was not collected. Among 96 interviewed patients (24 patients could not be interviewed), 79 (82.2%) thought that fleas were involved in the causation of the disease. Importantly, body-lice were not documented in any case and no deaths occurred (making the diagnosis of epidemic typhus extremely unlikely). After the analysis, we included 2 patients with negative IgM serology as confirmed murine typhus because the increase in IgG titers between the acute and convalescent samples was greater than 4-fold.


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TABLE 1
Demographic and serological characteristics of patients with a confirmed diagnosis of murine typhus
 

Figure 1
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    FIGURE 1. Analysis of anti-R. typhi (IgM and IgG) antibodies in paired sera of patients with a clinical syndrome compatible with murine typhus.

 
The most frequent clinical findings besides fever included headache, arthralgia, abdominal pain, cough, and nausea or vomiting. The unanticipated symptoms from the gastrointestinal and respiratory tracts, absence of rash (only 3 patients presented rash), and lack of evidence of flea bites might contribute to the fact that murine typhus is frequently misdiagnosed and not treated appropriately. In addition, the relative mildness of murine typhus (mortality of < 1%) is likely to play a role in its severe underreporting despite its widespread geographical distribution.2 In fact, in underdeveloped countries the incidence of murine typhus is probably higher than recognized given the environment of poverty that favors the conditions of transmission. Unfortunately, no thorough and well-designed prevalence studies have been reported.

To the best of our knowledge, only 3 reports of murine typhus and/or murine typhus serological studies have been produced from Latin America during the past 4 decades. None of them used paired samples in the analyses. One from Brazil reports a seroprevalence of antibodies against R. typhi of 1.1% among healthy individuals.4 Another one, also from Brazil, reports the analysis of one case and discusses earlier local medical literature that suggests probable (but not confirmed) cases of murine typhus.5 The third one, from Mexico City, reports a seroprevalence of ~14% among blood donors.6 Thus, it will be important to characterize the epidemiology of murine typhus in Colombia and the rest of Latin America. Descriptive and epidemiologic studies will hopefully bring awareness of the importance and frequency of this antibiotic-treatable disease and the necessity for laboratory testing with sensitive and specific tests.


Received August 30, 2007. Accepted for publication October 31, 2007.

Financial support: This research was supported by Direccion Territorial de Salud de Caldas and grant 1204-04-16332 from Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología Francisco José de Caldas, Colciencias to G.Valbuena.

Disclaimers: We do not have conflicts of interest related to this article.

* Address correspondence to Gustavo Valbuena, Department of Pathology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609. E-mail: gvalbuen{at}utmb.edu Back

Authors’ addresses: Marylin Hidalgo, Instituto Nacional de Salud, Grupo de Microbiología, AV Cll 26 No. 51-60, Bogotá, Colombia, Tel: 57+1+2207700+446, E-mail: mhidalgo{at}ins.gov.co. Edgar Salguero, Dirección Territorial de Salud de Caldas, Calle 49 numero 26-46, Manizales, Colombia, Tel: 57+68+783033+110, E-mail: edgalsalguero4{at}hotmail.com. Alberto de la Ossa, Dirección Territorial de Salud de Caldas, Calle 49 numero 26-46, Manizales, Colombia, Tel: 57+68+783033+110, E-mail: tomasossa{at}hotmail.com. Ricardo Sánchez, Universidad Nacional de Colombia, Facultad de Medicina, Ciudad Universitaria, Cra 30 No 45-03 Facultad de Medicina, Edificio 471 Oficina 202 Bogotá, Colombia, Tel: 57+1+ 3165000 +15117, E-mail: rsanchez{at}unal.edu.co. Juan F. Vesga, Instituto Nacional de Salud, Grupo de Microbiología, AV Cll 26 No. 51-60, Bogotá, Colombia, Tel: 57+1+2207700+446, E-mail: jfvesga{at}cable.net.co. Leonora Orejuela, Department of Pathology, The University of Texas Medical Branch, 301 University Boulevard Galveston, TX 77555-0609, Tel: (409) 747-2464, Fax: (409) 7470762, E-mail: leorejue{at}utmb.edu. Gustavo Valbuena, Department of Pathology, The University of Texas Medical Branch, 301 University Boulevard Galveston, TX 77555-0609, Tel: (409) 747-0763, Fax: (409) 747-2429, E-mail: gvalbuen{at}utmb.edu

Reprint requests: Gustavo Valbuena, Department of Pathology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, Tel: (409) 747-0763, Fax: (409) 747-2429, E-mail: gvalbuen{at}utmb.edu

 

REFERENCES

  1. Azad AF, Radulovic S, Higgins JA, Noden BH, Troyer JM, 1997. Flea-borne rickettsioses: ecologic considerations. Emerg Infect Dis 3: 319–327.[Web of Science][Medline]
  2. Azad AF, 1990. Epidemiology of murine typhus. Annu Rev Entomol 35: 553–569.[Web of Science][Medline]
  3. La SB, Raoult D, 1997. Laboratory diagnosis of rickettsioses: current approaches to diagnosis of old and new rickettsial diseases. J Clin Microbiol 35: 2715–2727.[Web of Science][Medline]
  4. Costa PS, Brigatte ME, Greco DB, 2005. Antibodies to Rickettsia rickettsii, Rickettsia typhi, Coxiella burnetii, Bartonella henselae, Bartonella quintana, and Ehrlichia chaffeensis among healthy population in Minas Gerais, Brazil. Mem Inst Oswaldo Cruz 100: 853–859.[Web of Science][Medline]
  5. Silva LJ, Papaiordanou PM, 2004. Murine (endemic) typhus in Brazil: case report and review. Rev Inst Med Trop Sao Paulo 46: 283–285.[Medline]
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This Article
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