Q fever and trench fever.
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Although trench fever appears to be endemic in many areas of the world, recognition of the disease has been handicapped by the difficulties of making a clinical diagnosis and the unavailability of a simple laboratory procedure to establish the etiology. The author describes a method for the in vitro cultivation of Rickettsia quintana that provides a relatively simple means for the laboratory diagnosis of trench fever. R. quintana can be propagated with ease from the blood of patients directly on blood agar incubated at 37 degrees C for 12-14 days under a gas tension of 5% CO(2) in air. The number of rickettsiae circulating in the patient's peripheral blood can be quantitated. The protracted rickettsiaemia in trench fever makes for a relatively long period during which blood culture can be usefully employed.In the course of studies with the method described, it was found that erythrocytes contain a factor (or, possibly, factors) essential for multiplication of R. quintana; this factor is cryostable and thermostable and may be haemoglobin. Blood serum also promotes multiplication.
Typhus and other louse-transmitted bacterial infections in Peruvian sierra communities are known to occur but have not recently been assessed. In this study, 194 of 1,280 inhabitants of four villages in Calca Province in the Urubamba Valley were included. Thirty-nine (20%) of the 194 volunteers had antibodies to Rickettsia prowazekii, whereas 24 (12%) had antibodies to Bartonella quintana and 2 against Borrelia recurrentis. There was a significant correlation between the presence of infesting ectoparasites and antibodies to R. prowazekii, as well as between antibodies to R. prowazekii and ectoparasite infestation and fever in the previous 6 months. The proportion of inhabitants infested with ectoparasites was significantly higher in the highest-altitude village than in the other three villages. Two volunteers' antibody levels suggested a recent typhus infection, but only B. quintana DNA was amplified from lice. Epidemic typhus remains extant in the area, and B. quintana infections were encountered and documented for the first time in South America.
Enzyme immunoassay (EIA) tests were used to diagnose trench fever and to determine cross-reactions of Rochalimaea quintana with other rickettsiae. The results were compared with those obtained by counterimmunoelectrophoresis (CIE). All sera from cases of primary or relapsed forms of trench fever were positive both in EIA, with serum antibody titers of 1:20-1:640, and in CIE, giving one to three precipitin lines. Sera from patients with other rickettsial infections were also tested for reactivity with R. quintana antigen: typhus group (Rickettsia prowazekii, Ricketsia mooseri), 15 sera; spotted fever group (Ricketsia ricketsii, Rickettsia akari), eight sera; and scrub typhus (Rickettsia tsutsugamushi), six sera. Strong reactions occurred with four sera from patients with scrub typhus, giving one or two lines in CIE and EIA titers of 1:40-1:160; these results were extended to guinea pig antisera to R. tsutsugamushi. About 50% of typhus group sera reacted with a single line in CIE and had antibody titers of 1:20-1:80 by EIA. The results show that EIA is accurate for the diagnosis of trench fever and, with the results obtained by CIE, suggest that R. quintana is antigenically related to R. tsutsugamushi and possibly to rickettsiae in the typhus group as well.
Rochalimaea quintana, the etiological agent of trench fever, was tested by an agar dilution method for its susceptibility to the following 14 antibiotics: penicillin G, methicillin, ampicillin, cephalothin, vancomycin, doxycycline, tetracycline, erythromycin, chloramphenicol, streptomycin, kanamycin, rifampin, colistin, and amphotericin B. The MIC of each of these antibiotics was determined. The results showed that R. quintana is susceptible in vitro to these antibiotics, with the exception of vancomycin, kanamycin, streptomycin, colistin, and amphotericin B.
A passive hemagglutination test devised for diagnosis of trench fever was easily performed and highly sensitive and specific. Tanned sheep erythrocytes were sensitized with soluble antigen from Rochalimaea quintana. The test detected antibody in six of seven cases of primary infection and in four cases of late, relapsed trench fever. Titers of antibody ranged from 1:20 to 1:640. Although both IgM and IgG antibody to R. quintana were detected by passive hemagglutination, IgG appeared to be the major reactive antibody. Antigens involved in the reaction were two types of proteins, one inactivated at 50 C and 60 C and the other at 80 C and 100 C. Of 322 control samples of sera that were tested, only one reacted positively; thus, the test had a specificity of greater than 99%. The single positive reaction was in serum from a patient with Q fever. This finding suggests that, in an area where Q fever is endemic, this disease must be ruled out in the interpretation of a positive passive hemagglutination test. Sera should be tested routinely against tanned, unsensitized erythrocytes, since an occassional sample of serum may agglutinate unsensitized cells. Because of its sensitivity and specificity, as well as its simplicity of performance, the passive hemagglutination test shows promise as a useful procedure for serologic identification of both acute and past infection with R. quintana.
Trench fever, cause by Bartonella quintana, disappeared decades ago. Between 1992 and 1994 about 20 cases were reported in industrialized countries [6, 7]. Some of these cases were associated with HIV infection [5], but most affected the homeless. The epidemiology of B. quintana is unknown in Europe, but infection and transmission are favoured by poor housing and hygiene. This paper describes the results of a seroprevalence survey among the homeless living in Marseille. The eight major non-profit organizations caring for the homeless in the city participated for the four winter months. Four of these organizations also provide health care. Each subject who came to be housed for more than one day were asked to complete a questionnaire and give a small blood sample by micropuncture. They were clearly informed about the aims of the research and were allowed to refuse participation freely. All blood samples were tested by the WHO collaborative center for ricketssiae using a previously tested and validated immunofluorescence technique. The subjects were scored positive if the IgG titer was above 1/100. Two hundred and twenty one subjects agreed to participate in the study. Most were of French origin (51.4%) and 40% under 40 years old. The seroprevalence was 1.8% (IC 95%: 0.05-3.55). None of the four positive subjects presented symptoms and clinical examination was normal. All four were over 40 years old; two were of French origin, 1 from Algeria and 1 from the Comoro Islands. One had an IgG titer above 1/3, 200, possibly reflecting recent contamination and/or severe infection. Statistical analysis revealed no significant association between seropositivity and housing or hygiene conditions. No socio-demographic data are available about the homeless in Marseille and indeed, there is no list of such individuals. It is therefore not possible to estimate the representativity of our sample. Nevertheless, we show that the homeless include infected individuals. Physicians who care for such subjects should prescribe B. quintana serological investigations, and organizations that take in these people should implement preventive action and health education programs. Any such policy must be designed so as to be acceptable to homeless people. This work should also encourage public health professionals to investigate more extensively infectious diseases among the homeless.
Some evidence is assembled to suggest that trench fever, an infection with a strain of Rochalimaea, if not quintana, then vinsonii, was present in Belfast in the first half of the nineteenth century in endemic and epidemic form. It may have amounted at times to one half or more of 'fever'. This may account for the comparatively low mortality in some years from 'fever'. The phrase 'relapsing fever' in the nineteenth and twentieth century medical literature of the United Kingdom should not be taken necessarily to mean infection with Borrelia recurrentis. Much or most may have been infection with Rochalimaea, quintana or vinsonii. The newly discovered Irish vole should be examined to see if it carries a Rickettsia or Rochalimaea infection.
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BACKGROUND: After a 12-year absence, epidemic typhus has re-emerged among the displaced population of Burundi. Following the outbreak of civil war in 1993, over 760000 people now inhabit refugee camps, under appalling conditions. A typhus outbreak occurred among prisoners in a jail in N'Gozi in 1995. At the time, the disease was not recognised, and was referred to as sutama. Reports of sutama among the civilian population date back to late 1995 and, in association with body-louse infestation, the disease has subsequently swept across the higher and colder regions of the country. METHODS: During a field study in February, 1997, 102 refugees with sutama underwent clinical examination and interview. Serum samples were collected and infesting body lice removed. Microbiological analysis included antibody estimations and specific PCRs aimed at diagnosis of Rickettsia prowezekii, Bartonella quintana, and Borrelia recurrentis. Between January and September, 1997, nationwide epidemiological data on the prevalence and distribution of sutama was obtained through liaison with local health services. A second field study in March, 1997, entailed the collection of further serum samples from suspected cases of sutama in different regions of Burundi. FINDINGS: Most of the 102 patients with sutama during initial assessment presented with manifestations similar to those previously described for typhus in Africa, though skin eruptions occurred in only 25 (25%) cases. Microbiological testing revealed evidence of R prowazeki infection in 76 (75%) patients, confirming that most cases of clinically-diagnosed sutama were epidemic typhus, and supporting the reliability of clinical diagnosis as a basis for the nationwide surveillance of the disease. Up to September, 1997, 45558 typhus cases were clinically diagnosed, most of which occurred in regions at an altitude of over 1500 m. Serological testing of 232 individuals from different regions of Burundi provided microbiological evidence to support clinical diagnoses in seven provinces, confirming the widespread nature of the outbreak. Serum from 13 of the original 102 patients and 19 (8%) of the 232 suspected cases had raised antibody titres against B quintana. A fatality rate of 15% among jail inmates fell to 0.5% after administration of a single dose of 200 mg doxycycline to suspected cases. INTERPRETATION: A gigantic outbreak of R prowazekii-induced typhus and B quintana-induced trench fever is continuing in Burundi. Transmission of both diseases to such a large number of people has followed a widespread epidemic of body-louse infestation. Diagnosis of typhus could be reliably made by means of clinical criteria, and the disease could be efficiently and easily treated by antibiotics. This epidemic highlights the appalling conditions in central-African refugee camps and the failure of public-health programmes to serve their inhabitants. Louse-associated disease remains a major health threat in this and other war-torn regions of the world.
The vole agent described by Baker in 1946 was studied as an example of a bacterium that has been mistakenly regarded a rickettsia. Unlike rickettsiae, the vole agent killed chicken embryos with great irregularity, multipled primarily at the surface of avian or mammalian cells and not intracellularly, produced colonies rather than plaques on chicken embryo monolayers under agar, and developed small colonies after 4 to 7 days of cultivation on blood plates. It was most conveniently cultivated on monolayers of irradiated L cells and was purified by minor modifications of the Renografin gradient procedure used for rickettsiae. It actively catabolized glutamate, glutamine, succinate, and pyruvate, but not glucose or glucose-6-phosphate. Enzymatic activities of cell extracts were consistent with above findings. The base ratio (molar percent guanine plus cytosine) of its deoxyribonucleic acid was shown to be 39, which was identical to the base ratio of the deoxyribonucleic acid of Rochalimaea quintana tested simultaneously. Serological studies indicated no cross-reactivity with Rickettsia tsutsugamushi, but strong cross-reaction with R. quintana was observed when a hyperimmune rabbit serum and a convalescent human serum were tested. We conclude that the vole agent is a strain of the trench fever rickettsia, R. quintana.
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