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Serological evidence for the presence of rickettsial infections in parts of Nigeria.

Weil-Felix tests using OX19 and OXK proteus antigens reveal high antibody titers to OXK and OX19 antigens in patients reporting at the University of Nigeria Teaching Hospital, Enugu with clinical diagnosis of pyrexia of unknown origin. These findings suggest the presence of either or both scrub typhus fever and Epidemic typhus fever in this community. While the advisablility of using other diagnostic techniques to support and confirm positive Weil-Felix reaction will be useful, it is felt that the above findings are strong evidences for the prevalence of these diseases in this part of Nigeria.

Antibodies, Bacterial↗

Rapid immunochromatographic diagnosis and Rolling Back Malaria--experiences from an African control program.

Malaria is a re-emerging disease in much of Africa. In response, the World Health Organization launched the Roll Back Malaria (RBM) initiative. One of six key principles adopted is the early detection of malaria cases. However, the importance of definitive diagnosis and potential value of field deployment of rapid malaria tests in RBM has been largely ignored. The Lowveld Region of Mpumalanga Province, South Africa, is home to a predominantly non-immune population, of approximately 850000 inhabitants, who are at risk of seasonal Plasmodium falciparum malaria. Malaria treatment in this area is usually only initiated on detection of malaria parasites in the peripheral bloodstream, as many other rickettsial and viral febrile illness mimic malaria. The malaria control programme traditionally relied on light microscopy of Giemsa-stained thick blood films for malaria diagnosis. This review summarizes operational research findings that led to the introduction of rapid malaria card tests for primary diagnosis of malaria throughout the Mpumalanga malaria area. Subsequent operational research and extensive experience over a four-year period since introducing the ICT Malaria Pf test appears to confirm the local appropriateness of this diagnostic modality. A laboratory is not required and clinic staff are empowered to make a prompt definitive diagnosis, limiting delays in initiating correct therapy. The simple, accurate and rapid non-microscopic means now available for diagnosing malaria could play an important role in Rolling Back Malaria in selected areas.

Communicable Disease Control↗

[Immunization recommendations for travel in the Mediterranean area].

The Mediterranean region is a popular destination for tourists during the summer. However, European tourists, who are travelers within their own continent, do not consider themselves exposed to possible, travel-associated infections, since problem awareness among tourists as well as doctors is rather weak. The objective of this consensus paper is to outline guidelines with regard to relevant travel immunizations for Mediterranean destinations. These recommendations are mainly based on risk calculations according to country-specific incidences and prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

Animals↗

Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by Rickettsia conorii- and Rickettsia rickettsii-infected cultured endothelial cells.

Hemostasis abnormalities have been described in patients with Mediterranean spotted fever and Rocky Mountain spotted fever. Evidence of the activation of the fibrinolytic system has been obtained in both diseases. After experimental Rocky Mountain spotted fever, an elevated level of fibrinogen was found in parallel with the activation of the fibrinolytic system and transient elevation of the tissue-type plasminogen activator. Later protein is mainly synthesized by endothelial cells. The ability to culture human endothelial cells in vitro provides a unique system to study the secretion of tissue-type plasminogen activator and of plasminogen activator inhibitor after rickettsial infection. Human vascular endothelial cells derived from the umbilical vein, when infected with Rickettsia conorii or Rickettsia rickettsii, secreted as much tissue-type plasminogen activator as control cells. The activity of plasminogen activator inhibitor however, was higher in the supernatants of infected cells than in those of control cells. This rickettsia-induced imbalance of the tissue-type plasminogen activator-inhibitor pair was a very early event after in vitro infection. The involvement of this system during Mediterranean spotted fever and Rocky Mountain spotted fever remains to be demonstrated.

Antibodies, Monoclonal↗

The natural history of vasculitis. What the histology tells us about pathogenesis.

While histopathologic analysis may offer some clues as to the pathogenesis of vasculitis, observations must be interpreted with caution, as there is considerable overlap in the histologic pattern. In most cases, a predominantly neutrophilic vasculitis affecting small dermal venules suggests a relatively acute, immune complex-mediated reaction. Less commonly, this histologic pattern may be seen in non-immunologically mediated processes, such as in the presence of bacterial toxins or malignant hypertension, or in more chronic disease states, such as granuloma faciale or erythema elevatum diutinum. A predominantly lymphocytic vasculitis may represent several pathogenetic mechanisms. In lesions more than 24 to 48 hours old, a lymphocytic vasculitis may represent a resolving phase of an immune complex-mediated neutrophilic vasculitis. Alternatively, this histologic pattern may be seen de novo in conditions with a presumed cell-mediated immunologic pathogenesis. Lymphocytic vasculitis may also be seen in rickettsial infections such as Rocky Mountain spotted fever. The pathogenesis of granulomatous vasculitis remains poorly understood and is thought to be induced by a combination of circulating immune complexes and a cell-mediated immune response.

Granuloma↗

A msp1alpha polymerase chain reaction assay for specific detection and differentiation of Anaplasma marginale isolates.

Anaplasma marginale is the causative agent of bovine anaplasmosis, a disease which can be protected by vaccination with the less pathogenic Anaplasma species, A. centrale. Currently, there is no polymerase chain reaction (PCR) assay available which differentiates between different species of Anaplasma or which can differentiate isolates of A. marginale within outbreaks and between different countries. A molecular test specific for A. marginale would be ideal for the identification of Anaplasma species in wild ruminants, as possible reservoirs of anaplasmosis, and to differentiate between A. marginale from A. centrale. A PCR assay was designed to amplify the major surface protein 1alpha gene of the rickettsial bovine pathogen, A. marginale both as an inter- and intra-specific test. The test did not amplify A. centrale or A. ovis, and discriminated A. marginale by amplifying repeat regions within the msp1alpha gene which vary in number between many isolates. The nested A. marginale amplicons varied in size from 630 to 1190bp representing one to eight internal repeats. All 22 Australian isolates tested amplified a 630bp product (one repeat) in contrast to all 19 non-Australian isolates tested. Eight sequences from Australian isolates from different geographical regions confirmed the conserved nature of the Australian A. marginale msp1alpha genes. The Australian 'repeat unit' MSP1a deduced amino acid sequence has been designated as Australian type 1. The msp1alpha PCR method developed here enabled the amplification and comparison of A. marginale isolates originating from North and South America, Africa, Israel and Australia. The method is sensitive and specific for A. marginale. Although additional msp1alpha products were amplified from at least two Australian isolates, the results suggest limited introduction of A. marginale into Australia.

Amino Acid Sequence↗

[Rift valley fever and rickettsial retinitis including fluorescein angiography (author's transl)].

Three cases of Rift Valley fever retinitis and one case of Tick Bite fever retinitis are presented. The clinical features are indistinguishable, manifesting as localised areas of retinal ischaemia and soft exudate formation. Fluorescein angiography shows that there is primary involvement of the retinal circulation without involvement of the choroidal circulation. Vascular occlusion is a feature of the retinal pathology. These patients were treated with steroids and immunosuppressives as their maculae were threatened and they all regained normal to near normal vision except in one case in whom old macula scarring from previous episodes of the disease prevented visual improvement.

Angiography↗

Comparison of two dosage schedules of doxycycline in children with rickettsial spotted fever.

We carried out a randomized clinical trial with oral doxycycline in children with Israel rickettsial spotted fever. Our purpose was to investigate whether an abbreviated course of therapy with this drug (until the patient was afebrile plus one day) would be as effective as a one-week regimen of therapy. Results with 50 pediatric patients during this three-year study indicated that the abbreviated treatment regimen was as effective. This clinical trial may serve as a model for determining shorter durations of therapy for other diseases.

Child↗

[Imported tsutsugamushi fever].

Scrub typhus rarely figures among the imported tropical diseases in western Europe. Rickettsia tsutsugamushi is transmitted by larval mites. A typical eschar develops at the site of the mite bite during the incubation period, after which systemic symptoms (remittent or continuous high fever, severe headache, tender lymphatic glands and symptoms of bronchitis) develop with sudden onset. Antibodies appear during the second week and can be shown by a positive and increasing titer against Prot. OXK (Weil-Felix) or by specific rickettsial agglutination. The Weil-Felix reaction is neither very sensitive nor very specific. Therefore, treatment should be started as soon as suspicion arises whether a positive serology is available or not. Tetracycline drugs are effective treatment and fever subsides in less than 24 hours in most patients. - We report the rare observation of a tourist who imported tsutsugamushi fever from India.

Animals↗

Mechanisms of immunity in typhus infection: some characteristics of Rickettsia mooseri infection of guinea pigs.

Rickettsia mooseri infection has been studied in syngeneic guinea pigs inoculated intradermally with the objective of developing a model for the study of immune mechanisms. Characterization of infection included the following: a study of replication, dissemination, and clearance of rickettsiae; measurement of the antibody response with different rickettsial antigens and tests; and attempts to measure the cell-mediated immune response using the correlate of delayed-type hypersensitivity skin reactions. Following intradermal inoculation, rickettsiae replicate locally and then spread to the draining lymph nodes and subsequently cause systemic infection. Spread to draining lymph nodes occurred before the appearance of circulating antibody, whereas systemic infection occurred afterwards. Two distinct patterns of acquired resistance developed. The first was marked by a cessation of rickettsial growth within a given organ and the second by a clearance of rickettsiae. The duration of each of these phases differed markedly from one organ to another. Delayed-type hypersensitivity was not demonstrated by skin testing.

Animals↗

Blood parasites of mammals from Papua New Guinea.

Thin blood smears were collected from 126 mammals representing four genera of marsupials and six genera of murid rodents. A species of Hepatozoon was discovered in the New Guinea spiny bandicoot (Echymipera kalubu), trypanosome infections were found in three genera of rodent hosts and the prevalence of a rickettsial parasite of the genus Grahamella was recorded in rodents from the genera Rattus and Melomys. Dried blood samples also were taken and screened serologically for antibodies to arenavirus infection but with negative results.

Animals↗

[Diagnostic measures on the occasion of a Q-fever epidemic in a sheep flock in Berlin].

This report gives an account of a Q-fever infection in flocks of sheep, taking into consideration the epidemiological aspects. In the inner organs, and particularly in the central nervous system of affected animals, rickettsial as well as chlamydial agents were directly demonstrated by immunofluorescence and specific staining methods, as well as by isolation via cell culture. Serological examination showed antibodies against both agents in sheep from flocks where the outbreak occurred.

Animals↗

[Mediterranean spotted fever. Apropos of a case].

We report the case of a patient who presented an engigmatic chorioretinopathy. The rickettsial etiology was confirmed late. This case recalls the general ophthalmological features of Mediterranean spotted fever. The serology pattern and different clinical arguments led to diagnosis.

Adult↗

[In vitro susceptibility of a strain of Rickettsia recently isolated from a case of Japanese spotted fever to chemotherapeutic agents].

The in vitro susceptibilities to five chemotherapeutic agents against a rickettsial strain which was isolated from a case of Japanese spotted fever were determined by cell culture system. Minocycline was the most effective (MIC, 0.15 micrograms/ml) followed by Tetracycline and Demethylchlor tetracycline (0.31 micrograms/ml 0.16 micrograms/ml). Chloramphenicol was less effective (5 micrograms/ml) and Aminobenzyl-penicillin was not effective with the MIC of 10 micrograms/ml or less. Thus, the earlier administration of Minocycline is recommended to clinically suspicious cases of Japanese spotted fever as well as Tsutsugamushi disease.

Anti-Bacterial Agents↗

Serologic diagnosis of epidemic typhus fever.

Microagglutination (MA), microcomplement-fixation (CF), indirect microimmunofluorescence (micro-IF) and Weil-Felix (WF) tests were compared for sensitivity and specificity in detection of antibodies against Rickettsia prowazekii and for serologic diagnosis of epidemic typhus fever. Paired sera from hospitalized Ethiopian patients suffering from febrile illness were examined. Purified particulate rickettsial antigens used in MA, CF and micro-IF tests were made from infected yolk sacs by differential centrifugation from molar NaCl and from NaCl-sucrose, D20=1.1491, pH 5.5. In sensitivity the tests ranked micro-IF greater than MA greater than CF greater than WF. Use of specific anti-IgG and anti-IgM sera in parallel micro-IF tests made it possible to differentiate cases of recrudescent epidemic typhus (Brill-Zinsser disease) from primary epidemic typhus cases. Antibodies reacting in high titer with R. canada were produced by 86% of patients with rising antibody titers against R. prowazekii.

Agglutination Tests↗

Seroepidemiology of spotted fever group and typhus group rickettsioses in humans, South Korea.

The prevalence of spotted fever group (SFG) and typhus group (TG) rickettsioses was investigated in 3,362 sera by immunofluorescence assay. The serum samples were obtained from patients with acute febrile episodes in South Korea from December 1992 to November 1993. The number of polyvalent positive sera against SFG rickettsial agents at the level of 1: 40 dilution was 269 (8%) in Rickettsia sibirica, 482 (14.34%) in R. conorii, and 546 (16.24%) in R. akari. Many of the positive sera contained immunoglobulin (Ig) M antibodies rather than IgG antibodies. These results strongly suggest that SFG rickettsioses are prevalent in Korea. For TG rickettsial agents, the number of positive sera was 1,096 (32.60%) in R. typhi and 951 (28.29%) in R. prowazekii. Only a few epidemic typhus positive sera contained IgM antibodies. The result suggests that recent and/or primary infections of epidemic typhus were very rare in Korea during the said period. Among seven patients who had high titers (1:5,120) of IgG antibody to R. prowazekii, six were over 50 years old. The result suggests that Brill-Zinsser disease was prevalent in Korea.

Adolescent↗

Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas.

Application of molecular diagnostic technology in the past 10 years has resulted in the discovery of several new species of pathogenic rickettsiae, including Rickettsia felis. As more sequence information for rickettsial genes has become available, the data have been used to reclassify rickettsial species and to develop new diagnostic tools for analysis of mixed rickettsial pathogens. R. felis has been associated with opossums and their fleas in Texas and California. Because R. felis can cause human illness, we investigated the distribution dynamics in the murine typhus-endemic areas of these two states. The geographic distribution of R. felis-infected opossum populations in two well-established endemic foci overlaps with that of the reported human cases of murine typhus. Descriptive epidemiologic analysis of 1998 human cases in Corpus Christi, Texas, identified disease patterns consistent with studies done in the 1980s. A close geographic association of seropositive opossums (22% R. felis; 8% R. typhi) with human murine typhus cases was also observed.

Adolescent↗

Transmission of Rickettsia tsutsugamushi strains among humans, wild rodents, and trombiculid mites in an area of Japan in which tsutsugamushi disease is newly endemic.

Thirty-two newly isolated strains of Rickettsia tsutsugamushi, 14 from patients with tsutsugamushi disease, 12 from wild rodents, and 6 from trombiculid mites parasitizing rodents in Gifu Prefecture, Japan, were examined for reactivities to 12 monoclonal antibodies by an indirect fluorescent-antibody test to classify their antigenicities. All of the isolates could be classified into one of six groups (KN-1, KN-2, KN-3, GJ-1, R158, and R161) according to their reactivities to the monoclonal antibodies. The KN-1 and GJ-1 strains that are prevalent among patients from Gifu Prefecture had the same reactivities as the Kawasaki and Kuroki strains, respectively, which have been isolated and are prevalent in the Miyazaki and Kagoshima prefectures in southwest Japan. The isolates from patients were different in serotype from those from rodents and mites (Leptotrombidium pallidum). The KN-2 and KN-3 strains were most prevalent among patients and among rodents and mites, respectively. No close similarity between KN-2 and other strains tested was observed. KN-3 is only a minor contributor to diseases in patients in Gifu Prefecture; however, it was proven that the same strain was prevalent in Niigata Prefecture in northern Japan. Thus, Gifu Prefecture is an area where southern, northern, and local strains are found. We hypothesize that humans are prone to infection with KN-2, GJ-1 (very similar to Kuroki), and KN-1 (very similar to Kawasaki), probably by infestation with Leptotrombidium scutellare. While both L. scutellare and L. pallidum parasitize wild rodents and may carry any rickettsial strain, the most virulent strain, KN-3, is predominant among wild rodents. Antigenic analysis using monoclonal antibodies to R. tsutsugamushi should be useful for epidemiological studies of infection with this organism.

Animals↗