Ned Tijdschr Geneeskd, 2004 Dec 25, 148(52), 2602 - 6 {The private society 'Utrechtsch Geneeskundig Gezelschap Matthias van Geuns' as a source of history and inspiration}; Haneveld GT; The Utrechtsch Geneeskundig Gezelschap {Utrecht Medical Society} Matthias van Geuns (1793 to the present) is the oldest still active local medical society in the Netherlands . Membership is select and limited to only one local representative from every medical specialty . Proceedings of the medical meetings have never been published, neither was a prize offered for a best essay . The minutes of the meetings, however, have been preserved . They give a fascinating insight into the way this small society reacted to the developments in medicine during two centuries . Infectious diseases, for example cholera, abdominal typhus and tuberculosis, and newly introduced surgical procedures like anaesthesia and antisepsis or asepsis were discussed . The lectures had to be attended by all members and were meant to be aimed at a general medical audience . The society members were expected to prepare themselves and take part in the discussion afterwards, everyone from his own point of view . This procedure was both instructive and stimulating . The minutes of the Utrechtsch Geneeskundig Gezelschap Matthias van Geuns are a valuable source for scientific research on medical developments in the Netherlands, particularly in Utrecht. Verh K Acad Geneeskd Belg, 2004, 66(5-6), 384 - 405; discussion 406 Epidemiology: past, present and future; Kesteloot H; Epidemiology in the past was concerned essentially by the study of infectious diseases which were the cause of huge mortalities especially since urbanisation was initiated . Epidemics of pest, typhus, cholera, influenza a.o . were common . The epidemics were halted by better hygiene, vaccination and antibiotics . Since the second world war epidemiology was dominated by an "epidemic" of new chronic diseases, especially heart disease and cancer . This was due to an increase in life span and to an increase in smoking habits and in the intake of saturated fat and a too small intake of fruit and vegetables combined with a too high intake of salt (NaCl) . Gradually epidemiology evolved as the study of the causes, the distribution, the risk factors and the prevention of chronic diseases, but also including accidents, suicide, depression a.o., diseases with a mass occurrence at the population level . The importance of nutrition as a determinant of health gradually became recognized, but remains undervalued by the medical profession . Mortality at the population level follows some simple mathematical laws and can be represented accurately (r2>0.99) between the ages of 35 and 84 year by either Gompertz equations (ln mortality versus age) or by a polynomial equation (ln mortality versus age, age2) . This is valid for all populations and both sexes and remains valid at times of great and rapid changes in mortality . This shows that measures for prevention should be directed towards the total population . The future of epidemiology should be directed towards the slowing of the ageing process at the population level by a healthy life style consisting of: not smoking, avoiding obesity, a fair amount of physical activity and a healthy nutrition i.e little salt, little saturated fat, an adequate amount of omega-3 fatty acids and a large amount of fruit and vegetables, with an occasional glass of red wine . This contains the secret of a long and healthy life . Conceptually it will be important to determine whether a maximum human life span, genetically determined, exists . A maximal rectangularization of the mortality curve should then be the ultimate goal . At the same time the possible re-emergence of old and new infectious diseases (SARS, Ebola, BSE, AIDS) should be kept in mind. Wurzbg Medizinhist Mitt, 2004, 23, 217 - 32 {The epidemic typhus of 1813/14 in the area of lower Franconia}; Vasold M; When Napoleon left for Moscow, in June 1812, he marched at the head of a huge army, perhaps more than half a million men strong . Roughly one fifth of them survived and came back to Germany at the turn of 1812/13 . The "Grande Armee" had been subject to open battles and guerilla warfare, but even more to the ravages of hunger and infectious disease - it was epidemic typhus that killed off the soldiers.On their way back to France, the soldiers carried that disease to some areas of Germany, esp . those along the Main river . In late winter of 1813 some parts of Franconia suffered terribly . The epidemic subsided in summer 1813 when the lice - typhus is a louse-born disease - were less and better under control . But again in the winter of 1813/14, after the battle of Leipzig (Oct . 1813), a murderous epidemic of typhus broke out and killed very many people in cities like Wurzburg, Aschaffenburg, and Mainz . Mortality rose to a high percentage . Some contemporary German doctors had a rough idea that the carrier of the disease must be in the clothes . According to very conservative estimates one out of ten Germans fell sick, and ten percent of the sick died of typhus, a quarter of a million out of 23 million people.German historiography normally does not mention this epidemic in history text-books, so this epidemic is rather unknown. Acta Med Port, 2003 Nov-Dec, 16(6), 429 - 36 Epub 2003 Dec 01. {Epidemilogic features of Mediterranean spotted fever in Portugal.}; De Sousa R et al.; Mediterranean spotted fever (MSF) is a tick-borne rickettsial disease . It is endemic in Portugal and Ricardo Jorge recognized it in 1930 . Rhipicephalus sanguineus is the main vector and reservoir of the disease . In Portugal the etiologic agents are two strains of Rickettsia conorii complex: R . conorii Malish and "Israeli tick typhus" . MSF is clinically characterized by a vasculitis process with the classical clinical triad of fever, rash, and lesion at the site of tick bite . Although the majory MSF cases are considered benign, last years some districts presented more severe cases than expected . The reported incidence of MSF in Portugal for 1989 to 2000 was 9.8/10(5) inhabitants, the highest incidence compared to other mediterranean countries . Alentejo was the region who presents the highested incidence with 31/10(5) inhabitants . Nevertheless, Braganca was the district which appears with greater number of cases, 62/10(5) inhabitants . The highest annual incidence rate reported was among children, peaking in those 1-4 years of age with 60.2/10(5) inhabitants . Observation of mortality rates have shown that Beja district have the highest mortality rates for MSF in Portugal, but in 1997 in this district, mortality have unexpected values with 7.6 deaths per 100,000 inhabitants have occurred . Although is an obligatory notifiable disease, high number of underreported cases are detected. Pediatr Infect Dis J, 2004 Dec, 23(12), 1171 - 2 Spontaneous splenic rupture in a child with murine typhus; Fergie J et al.; A 10-year-old boy hospitalized with murine typhus infection had splenic rupture as a complication . Surgical intervention was not required . He recovered and was discharged a week after admission . This is the first reported case of spontaneous splenic rupture in a child with murine typhus. Indian Pediatr, 2004 Dec 7, 41(12), 1254 - 1257 Scrub Typhus; Pavithran S et al.; Scrub typhus is being increasingly reported in adults in India.It should be considered a strong possibility in all undifferentiated fevers . Two children with this infection are being reported highlighting the wide variation in clinical presentation . Specific tests should be preferred over Weil Felix test wherever possible especially in areas reporting a high incidence of the infection. Arch Hist Filoz Med, 2004, 67(1), 49 - 60 {Epidemic diseases in the Polish Kingdom in the thirties of the 19th century.}; Rutkowski M; We can observe that after downfall of the November Insurrection the authorities of the Polish Kingdom were effectively engaged in the fight against numerous epidemic diseases plaguing the local society . Among "contagions" of the time there were varicella, "gastric-nervous fever", "gastric-rhinitis fever" and typhus (especially in 1836) . As usual, cholera was the most dangerous one . All medical and epidemiological services in the Polish Kingdom were making effective remedial measures in order to neutralize results of the epidemics . The implemented methods were effective enough to limit considerably the incidence and number of deceased during the epidemic, which started in October 1836 and lasted till the next year . An obligation of effective cooperation between the Polish authorities and the Russian army was introduced then . The sanitary action against cholera in 1836-1837 should be very highly assessed from the logistic point of view . The wide action of protective vaccination against varicella and numerous sanitary rules completed the favorable image of the Polish Kingdom sanitary services . All the factors mentioned above lead to a conclusion that in the thirtieth of the 19th century both civil and military authorities of the Polish Kingdom did practically utmost in order to limit negative results of cyclical recurrences of epidemic diseases . It should be also stressed that the protective actions undertaken in that time were both direct and long lasting enterprises. NTM, 2004, 12(4), 213 - 32 {Paul Konitzer (1894-1947): hygienist, physician, social medicine and health politician}; Schneck P; Paul Konitzer was one of the outstanding and well-known physicians in the years after the World War II in East-Germany . THe paper describes his professional way as hygienist, social medical, municipal physician and last but not least as health politician in the times of four different political regimes: the imperial era in Germany till 1918, the time of "Weimarer Republic" till 1933, the Nazi dictatorship till 1945 and the early years in the Soviet occupation zone of Germany . The life of Konitzer is a typical example of the fate of a German doctor in the first half of the 20th century . Konitzer was arrested in February 1947 by the Soviet Military Government in Berlin in connection with some political troubles and reproach with a typhus epidemic in a German camp for Russian Prisoners of War in the Nazi era . On April 22nd 1947 he died in prison of Dresden by suicide without condemnation. Zhonghua Liu Xing Bing Xue Za Zhi, 2004 Aug, 25(8), 698 - 701 {Amplification and typing of Sta56 gene of Orientia tsutsugamushi from Shandong province}; Liu YX et al.; OBJECTIVE: To clarify the gene type of Orientia tsutsugamushi (Ot) from Shandong province . METHODS: Nested-polymerase chain reaction (nPCR) was used to identify the gene type of 23 isolated Ot strains, 2 pools of homogenized leptotrombidium (L.) scutellare, 10 blood specimens of scrub typhus patients, and at the same time to compare with the international reference strains Gilliam, Karp, Kato . Sequencing analysis of the Sta56 gene was also used to further identify the precise gene types . RESULTS: Of the 35 samples, 33 had the same products in the amplification of template Ot-DNA . They all belonged to Kawasaki strains endemic in Japan while 2 (FXS4 and LHGM2 strain) belonged to Karp strains . The Sta56 gene sequence homologies to Japan Kawasaki strain of the 2 representative strains (B-16 and FXS2 strain) of the 33 samples were 94.22%, 95.21% respectively, but they were less than 75.87% to other prototype strains; The homologies to Karp strain of FXS4 and LHGM2 strain were 83.03%, 96.45% respectively . B-16 and FXS2 strain were designated as of types strain Japan Kawasaki, FXS4 and LHGM2 as Karp strain . CONCLUSION: The results indicated that the dominant Ot strains in Shandong Province were similar to Kawasaki strains, but Karp strains also existed. Rev Inst Med Trop Sao Paulo, 2004 Sep-Oct, 46(5), 283 - 5 Epub 2004 Oct 22. Murine (endemic) typhus in Brazil: case report and review; Silva LJ et al.; Murine typhus has been increasingly recognized worldwide and is becoming a relevant differential diagnosis in febrile conditions . In Brazil, murine typhus has never received much attention . We present a recently diagnosed case and a literature review that suggests that the disease could be more prevalent in Southeastern Brazil than acknowledged until now. Scand J Infect Dis, 2004, 36(10), 743 - 51 Clinical deterioration in community acquired infections associated with lymphocyte upsurge in immunocompetent hosts; Cheng VC et al.; Clinical deterioration during the course of community-acquired infections can occur as a result of an exaggerated immune response of the host towards the inciting pathogens, leading to immune-mediated tissue damage . Whether a surge in the peripheral lymphocyte count can be used as a surrogate marker indicating the onset of immunopathological tissue damage is not known . In this study, we report the clinical presentations and outcomes of a cohort of immunocompetent patients with non-tuberculous community acquired infections who experienced clinical deterioration during hospital stay (n=85) . 12 (14.1%) patients had a surge in lymphocyte count preceding their clinical deteriorations, and their diagnoses included viral pneumonitis , viral encephalitis , scrub typhus , leptospirosis , brucellosis , and dengue haemorrhagic fever . The clinical manifestations during deterioration ranged from interstitial pneumonitis , airway obstruction , CNS disturbances , and systemic capillary leak syndrome , all of which were thought to represent immunopathological tissue damages . When compared with patients without lymphocyte surge, these patients were more likely to be infected with fastidious/viral pathogens (0 vs 12; p<0.05), in addition to having lower mean baseline lymphocyte counts (403+/-181 vs 1143+/-686 cells/microl; p<0.05) . We postulate that the peripheral lymphocyte count may be a useful surrogate marker indicating the presence of immunopathological damage during clinical deterioration in certain infectious diseases. Emerg Infect Dis, 2004 Oct, 10(10), 1838 - 40 Scrub typhus in the Republic of Palau, Micronesia; Durand AM et al.; In October 2001, an outbreak of febrile illness began in the southwest islands group of the Republic of Palau . Through October 2003, a total of 15 southwest islanders experienced fever >39.5 degrees C and abdominal distress, both lasting >7 days . Orientia tsutsugamushi, the agent of scrub typhus, was subsequently identified as the cause. Clin Infect Dis, 2004 Nov 1, 39(9), 1329 - 35 Epub 2004 Oct 11. A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus; Kim YS et al.; BACKGROUND: Scrub typhus is one of the most important endemic infections in the Asia-Pacific region . Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments . METHODS: We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus . The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens . RESULTS: A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline . Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117) . The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097) . There were no serious adverse events during the study . No relapses occurred in either group during a 1-month follow-up period . CONCLUSION: The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea. Biochim Biophys Acta, 2004 Nov 1, 1702(2), 145 - 52 Using LC-MS with de novo software to fully characterize the multiple methylations of lysine residues in a recombinant fragment of an outer membrane protein from a virulent strain of Rickettsia prowazekii; Chao CC et al.; The outer membrane protein B (OmpB) of the typhus group rickettsiae is an immunodominant antigen and has been shown to provide protection against typhus in animal models . Consequently, OmpB is currently being considered as a potential rickettsiae vaccine candidate to be used in humans . The OmpB from virulent strains are heavily methylated while the attenuated strains are hypomethylated . Western blot analysis of partially digested OmpB revealed that one of the reactive fragments was located at the N-terminus (fragment A, aa 33-272) . Recently, we have over expressed, purified, and chemically methylated the recombinant fragment A from Rickettsia prowazekii (Ap) . The methylated Ap was thoroughly characterized by LC/MS/MS on the ProteomeX workstation . The protein sequence of Ap with and without methylation was 87.7% and 100% identified, respectively . This high sequence coverage enabled us to determine the sites and extent of methylation on the lysine residues in Ap . All the lysine residues except the C-terminus lysine were either mono-, di- or tri-methylated . In addition, carbamylation on the N-terminus glycine was identified using a combination of denovo sequencing (DeNovoX) and the pattern recognition (SALSA) program with accurate mass measurement . We demonstrated that the use of peptide identification (SEQUEST) in combination with SALSA and denovo sequencing provided a useful means to characterize the sequence and posttranslational modifications of given proteins. J Korean Med Sci, 2004 Oct, 19(5), 668 - 73 Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity; Song SW et al.; Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known . This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus . We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus . We then compared these clinical factors between patients with and without IP . We also studied the relationship between IP and other chest radiographic findings . The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively . The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49) . The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP . Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus. Voen Med Zh, 2004 Aug, 325(8), 40 - 4, 79 {Diagnosis of Rickettsia prowazekii forms at the final stage of its elimination}; Flying squirrels and their ectoparasites: Disseminators of epidemic typhus; Joseph McDade is at the Division of Viral Diseases, Centers for Disease Control, 1600 Clifton Road NE, Atlanta, Georgia 30333, USAInformation gathered during the past decade indicates that the eastern flying squirrel, Glaucomys volans, is a zoonotic reservoir of Rickettsia prowazekii - causative agent of louse-borne (epidemic) typhus . The sporadic cases o f typhus that have occurred in the USA in association with flying squirrels provide evidence that flying squirrels can transmit R . prowazekii infection to humons . Strains of R . prowazekii, isolated from flying squirrels multiply readily in human body lice, but flying squirrel lice, although readily infected, are very host specific and tend not to bite humans . It may be that the infection is spread to humans in in fective ectoporasite faeces aerosolized when the flying squirrels groom themselves . As Joseph McDade emphasizes in this article, current concepts of typhus epidemiology and control must be re-evaluated to take into account this zoonotic aspect. Commun Dis Intell, 2004, 28(2), 267 - 9 Scrub typhus in the Northern Territory: exceeding the boundaries of Litchfield National Park; Ralph A et al.; Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in patients with a history of travel to Litchfield National Park in the Top End of the Northern Territory . All confirmed scrub typhus cases to date from the Northern Territory have visited the Park, but the presence of similar rainforest pockets elsewhere in the Top End suggested further infectious locations might be identified with increased tourism . We report a case of serologically confirmed Orientia tsutsugamushi infection in a man who had not been within Litchfield Park, but had visited another discrete Top End rainforest area. Curr Opin Infect Dis, 2004 Oct, 17(5), 433 - 7 Rickettsial infections--a threat to travellers? Rolain JM, Jensenius M, Raoult D. PURPOSE OF REVIEW: Recent developments in cell-culture techniques and molecular methods have led to the description of several new rickettsial diseases . An update on these new infections should be of interest to health workers with patients who are international travellers . RECENT FINDINGS: Epidemic typhus was reported last year in the United States when an outbreak of murine typhus was recorded in Hawaii . Among spotted fever group rickettsioses, African tick bite fever is now probably the most common rickettsial infection in Africa with numerous cases also reported in international travellers . For the first time the Astrakhan fever rickettsia has been described outside Europe, in a French patient returning from Chad . Similarly, the first case of Rickettsia sibirica mongolotimonae infection in Africa was reported in 2004 . Finally, a newly recognized agent of a spotted fever rickettsiosis, Rickettsia parkeri, has been reported in the United States during 2004 . SUMMARY: Because results of serological testing are only presumptive, sophisticated methods are crucial for the diagnosis and description of new rickettsial diseases, especially in atypical cases . Modern diagnostic tools include cross-adsorption assays, Western blot testing, and cell-culture and molecular-biological methods. J Infect Dis, 2004 Oct 1, 190(7), 1221 - 7 Epub 2004 Aug 18. T cells mediate cross-protective immunity between spotted fever group rickettsiae and typhus group rickettsiae; Valbuena G et al.; Rickettsioses are severe infections caused by obligately intracellular bacteria that preferentially infect the endothelium lining the vasculature . The causative agents, rickettsiae, have been divided according to biological, genetic, and antigenic parameters into 2 main groups: spotted fever and typhus . They have not been thought to stimulate cross-reactive protective immune responses; however, in this study, we show that, in relevant animal models that mimic human rickettsial infections, there is reciprocal immunological cross-protection between spotted fever group and typhus group rickettsiae . Furthermore, we present evidence that T cells are responsible for this cross-immunity and that cross-stimulation of T cells also occurs in humans. Trans R Soc Trop Med Hyg, 2003 Sep-Oct, 97(5), 570 - 2 Case reports: scrub typhus during pregnancy in India; Mathai E et al.; Scrub typhus, caused by Orientia tsutsugamushi, is a rural zoonosis endemic in the Asian Pacific region . Doxycycline and chloramphenicol, the recommended drugs for treating this infection, may not be safe during pregnancy . We report on 5 patients with scrub typhus during pregnancy who were seen in India between October 2001 and February 2002 . Four of the 5 women were treated initially with ciprofloxacin . Three women had stillbirths, 1 an abortion and 1 a low birthweight baby, which suggests that ciprofloxacin should not be used for treating pregnant women and that scrub typhus leads to severe adverse effects during pregnancy . Randomized controlled trials are urgently needed to ascertain the optimal drug choice, given that currently recommended drugs are contraindicated in pregnant women. J Clin Microbiol, 2004 Aug, 42(8), 3898 - 900 Reemerging threat of epidemic typhus in Algeria; Mokrani K et al.; We report a case of epidemic typhus in a patient from the Batna region of Algeria, who presented with generalized febrile exanthema . The clinical diagnosis was confirmed by serological cross-adsorption followed by Western blotting . Our report emphasizes the threat of epidemic typhus in the highlands of Algeria. J Clin Microbiol, 2004 Aug, 42(8), 3435 - 7 Evaluation of immunoglobulin M (IgM) and IgG rapid cassette test kits for diagnosis of melioidosis in an area of endemicity; Wuthiekanun V et al.; An enzyme-linked immunosorbent assay-based rapid cassette immunoglobulin G (IgG) and IgM immunochromogenic test kit was compared to the indirect hemagglutination test (IHA) for the diagnosis of acute melioidosis in northeastern Thailand . Admission sera from 70 culture-confirmed septicemic melioidosis patients and 30 patients with localized infections were tested . As a control group, 80 patients with other acute febrile illnesses (other bacterial infections, leptospirosis, or scrub typhus) and 119 healthy individuals were tested . The diagnostic sensitivity of the IgG and IgM tests and the IHA test were 79, 67, and 72%, respectively, with corresponding specificities of 90, 80, and 68% . This kit represents an improvement over IHA for the diagnosis of melioidosis an area of endemicity although, as with other serological tests, it has reduced diagnostic utility in a population with high background seropositivity. J Med Biogr, 2004 Aug, 12(3), 161 - 3 Sir William Jenner (1815-1898) and Queen Victoria; Seddon D et al.; This biographical note outlines the work of Sir William Jenner (1815-1898), court physician 1861-93 and President of the Royal College of Physicians 1881-8 . He was the first to distinguish between typhoid and typhus both clinically and pathologically. Z Arztl Fortbild Qualitatssich, 2004 May, 98 Suppl 5, 7 - 12 {Carl Adolph von Basedow--150th anniversary of his death}; Meng W; Carl Adolph von Basedow was the son of an aristocratic family and was born 1799 in Dessau . He was the grandson of the famous pedagogue Johann Bernhard Basedow . He studied medicine at the university of Halle and spent two years in the surgical service of Paris hospitals--the Charite and the Hotel Dieu . In 1822, he settled in Merseburg as a physician . He was soon acclaimed as a genial and skilled helper in all branches of medical practice . He performed his own post-mortem examinations and published findings on a number of different diseases . His famous contribution in the thyroid field appeared in 1840 entitled "Exophthalmos due to hypertrophy of the cellular tissue in the orbit" . Exophthalmos, goiter and palpitation of the heart have become known as the Merseburg Triad . In 1848, he published the autopsy findings on a patient who died from "exophthalmic cachexia" . In Germany and some other countries, the disease was named as Morbus Basedow since 1858 . In 1854 he pricked in his finger in the postmortem room when examining a patient who had died of typhus and he succumbed to septicemia at the early age of fifty-five . The date of his death was April 11, 1854 . On April 14, he was laid in the Sixtus Cemetery in Merseburg . Basedow postulated that a wrong mixing of the blood manifested in cell tissue congestion and glandular vegetation cause the manifestations of disease . If we abstract our modern knowledge and accept circulating antibodies and disturbance of the immune balance as a dyscrasia as well as the proliferation of lymphocytic clones and local cellulary infiltration in terms of immune thyroiditis and autoimmune orbitopathy as cell tissue congestion and glandular vegetations, then doubt arise whether we have indeed made much progress in the last 150 years . At least, respect for the genius of the general physician Carl Adolph von Basedow is becoming greater . We may all hope that in the contributions and the discussions, we shall learn where we stand at the end of the century and what new avenues of research are appearing on the horizon. Emerg Infect Dis, 2004 Apr, 10(4), 740 - 3 Murine typhus with renal involvement in Canary Islands, Spain; Hernandez Cabrera M et al.; Murine typhus and "murine-typhus-like" disease are reemerging infectious diseases . In Canary Islands (Spain), a rather distinct clinical pattern characterized by higher incidence of complications, especially renal damage (including acute failure and urinalysis abnormalities), is apparent and highly suggestive . It could be related to different strains of Rickettsia typhi or other cross-reactive species. Am J Trop Med Hyg, 2004 May, 70(5), 576 - 9 Comparison of the effectiveness of five different antibiotic regimens on infection with Rickettsia typhi: therapeutic data from 87 cases; Gikas A et al.; This study estimated the clinical effectiveness of five different antibiotic regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection with Rickettsia typhi in terms of the duration of the fever . Eighty-seven patients with endemic typhus were hospitalized between 1993 and 1998 at the General Hospital of Chania in Chania, Crete, Greece . The mean time to defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2 days for ciprofloxacin . In patients receiving combinations of doxycycline plus chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0 days, respectively . The outcome was favorable in all patients, and no deaths or relapses were observed within two months. J Nephrol, 2004 Jan-Feb, 17(1), 175 - 9 Jakub Penson and his studies on acute renal failure during typhus epidemics in Warsaw Ghetto; Rutkowski B; In the Warsaw Ghetto established by the German Nazis as a special district for Polish Jews in 1940 there were two typhus epidemics . Many patients affected by this disease (1500 during the first and 6500 during second epidemic) were treated at The Department of Infectious Disease of Czyste Hospital headed by Dr Jakub Penson--a Polish physician of Jewish origin . A heroic group of 20 physicians not only treated patients in these tragic circumstances, but also performed in defiance of Nazi prohibition, scientific studies on the clinical course of typhus with special attention on hyperazotemia and renal complication . The results of their observations were presented in 1941-42 during clinical meetings in Czyste Hospital and later published by Penson in 1946 in the Polish Physicians Weekly . Among other clinical statements a description of acute renal failure of extrarenal origin, caused by dehydration and toxic influence of primary disease seems the most important one . It has to be taken into account that acute renal failure appearing during Crush Syndrome was described by Bywaters in 1941 . Jakub Penson survived the German Nazi occupation and later become a head of the Internal Medicine Department in Gdansk Medical University and one of the precursors of clinical nephrology in Poland. Int J Med Microbiol, 2004 Apr, 293(7-8), 463 - 70 Host cell modulation by human, animal and plant pathogens; Andersson SG et al.; Members of the alpha-proteobacteria display a broad range of interactions with higher eukaryotes . Some are pathogens of humans, such as Rickettsia and Bartonella that are associated with diseases like epidemic typhus, trench fever, cat scratch disease and bacillary angiomatosis . Others like the Brucella cause abortions in pregnant animals . Yet other species have evolved elaborate interactions with plants; in this group we find both plant symbionts and parasites . Despite radically different host preferences, extreme genome size variations and the absence of toxin genes, similarities in survival strategies and host cell interactions can be recognized among members of the alpha-proteobacteria . Here, we review some of these similarities, with a focus on strategies for modulation of the host target cell. Harefuah, 2004 Apr, 143(4), 272 - 6, 318 {Morbidity in the concentration camps of the Third Reich}; Shasha SM; Life in the concentration camps of the Third Reich was like living on another planet . The prisoners, stripped of all rights, experienced constant humiliation, uncertain survival and endless terror . Living conditions were harsh, characterized by crowding, poor sanitation and personal hygiene, lack of proper clothing and heating . The days began early with long marches and slave labor . Sleep was short and interrupted, and fatigue was constant and severe . Above all hoovered the dark cloud of ever-present famine . The prisoners were given about a fourth of the daily calorie requirements, and the food lacked vital components such as vitamins and other essential ingredients . The psychological stress was extreme, yet morbidity and mortality were mainly due to infections, injuries and hunger . Lice, scabies and other skin diseases were common . Typhus fever was ever-present, both endemic and epidemic, with a fatal outcome . Many suffered from tuberculosis, typhoid, dysentery, pneumonia and other infections diseases . Injuries were common, caused by beating, punitive whiplashing and other forms of physical abuse, gunshot wounds and dog-bites . Skull injuries with brain contusions and hemorrhages were prevalent, as well as fractured limbs, ribs and pelvic bones . Blunt injuries to chest and abdomen often had fatal outcomes due to the perforation of viscera and peritonitis or as a result of massive hemorrhage from ruptured blood vessels . The harsh winters were marked by frozen gangrenous limbs and hypothermia . Yet, the most ominous condition was the "hunger disease" with its multiple clinical expressions which, in their extreme form, led to the emaciated "musleman" and eventual death. Southeast Asian J Trop Med Public Health, 2003 Dec, 34(4), 831 - 8 Early diagnosis of scrub typhus in Thailand from clinical specimens by nested polymerase chain reaction; Manosroi J et al.; The early detection of scrub typhus in Thailand by nested polymerase chain reaction (PCR) is presented . The diagnosis of scrub typhus, from clinical samples obtained from hospitals in the northern part of Thailand, by nested PCR was compared to immunofluorescence (IF) and Weil-Felix (WF) tests . The primer pairs used for the nested PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen, and RFLP analysis was used for identification . Clotted blood from 80 patients suspected of scrub typhus infection were tested . With the IF test, antibodies for Orientia tsutsugamushi were observed in 38 patients checking IgM and IgG titers . Only 21 patients showed positive seroconversion while 17 patients were negative . For the WF test, only 13 patients gave a positive seroconversion . In the early stage of infection, 19, 13 and 3 patients were detected with a sensitivity of 90.47% (19/21), 61.90% (13/21) and 14.28% (3/21) by the nested PCR, IF and WF test respectively . Two patients who were negative for seroconvesion by IF and WF were positive by nested PCR . Therefore, this suggests that nested PCR is applicable for specific rapid diagnosis at an early stage of scrub typhus in endemic regions. Southeast Asian J Trop Med Public Health, 2003 Dec, 34(4), 826 - 30 Epidemiological studies on host animals of scrub typhus of the autumn-winter type in Shandong Province, China; Liu Y et al.; In order to elucidate the host animals of scrub typhus in Shandong Province, epidemiological studies on host rodents of the autumn-winter type scrub typhus were carried out from 1995 to 2002 at four localities in the Shandong Province . Based upon ecological observations of the composition, seasonal fluctuation of animal hosts, isolation of Orientia tsutsugamushi, detection and identification of serotypes of antibodies to O . tsutsugamushi were conducted . Two thousand eight hundred and eighty-four rodents and insectivores were captured, including 2,055 Apodemus agrarius (71.26%), 408 Cricetulus triton (14.15%), 64 C . barabensis (2.22%), 12 Crocidura suaveolens (0.42%), 313 Rattus (R.) norvegicus (10.85%), 32 Mus (M.) musculus (1.11%) . A . agrarius was predominant in the field and the seasonal fluctuation was correlated significantly to that of scrub typhus (r=0.810, p<0.005) . R . norvegicus was predominant indoors . The average capture rate per year in the field was 12.76% from 1995 to 1997 . Of the total 2,884 rodents and insectivores captured out- and in-doors, 527 were living rodents (including 335 A . agrarius, 119 C . triton, 6 C . barabensis, 2 C . suaveolens, 63 R . norvegicus and 2 M . musculus, and 15,467 chigger mites were collected from them . Two hundred and fifty-three of 335 A . agrarius were parasitized by chiggers, showing 75.52% (253/335) of the infestation rate and 17.53 of the chigger index; 106 C . triton were parasitized by chiggers, showing 89.08% (106/119) infestation rate and 75.93 of the chigger index . The average antibody positive rate of rodents was 14.78% . The seasonal change of the antibody positive rate was higher during December-February (the second year), and varied from 20% to 28%, but the level of antibodies remained relatively low (5.26-16.67%) during March-November . The results of serotyping with 47 antibody-positive sera were as followings: 39 sera were Gilliam types, 7 sera were Karp types, 1 serum was Kato type . Twelve strains of O . tsutsugamushi were isolated from A . agrarius (8 strains), C . triton (3 strains) and R . norvegicus (1 strain), out of the isolated 12 strains, 10 were Gilliam strains, 2 were Karp strains . A . agrarius and R . norvegicus were the main host animals in out- and indoors respectively. Am J Trop Med Hyg, 2004 Apr, 70(4), 351 - 6 Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi; Jiang J et al.; Two specific and sensitive polymerase chain reaction (PCR) assays were developed to detect and quantitate Orientia tsutsugamushi, the agent of scrub typhus, using a portion of the 47-kD outer membrane protein antigen/ high temperature requirement A gene as the target . A selected 47-kD protein gene primer pair amplified a 118-basepair fragment from all 26 strains of O . tsutsugamushi evaluated, but it did not produce amplicons when 17 Rickettsia and 18 less-related bacterial nucleic acid extracts were tested . Similar agent specificity for the real-time PCR assay, which used the same primers and a 31-basepair fluorescent probe, was demonstrated . This sensitive and quantitative assay determination of the content of O . tsutsugamushi nucleic acid used a plasmid containing the entire 47-kD gene from the Kato strain as a standard . Enumeration of the copies of O . tsutsugamushi DNA extracted from infected tissues from mice and monkeys following experimental infection with Orientia showed 27-5552 copies/microL of mouse blood, 14448-86012 copies/microL of mouse liver/spleen homogenate, and 3-21 copies/microL of monkey blood. Trans R Soc Trop Med Hyg, 2004 Jun, 98(6), 360 - 6 Evaluation of nested PCR for the diagnosis of scrub typhus among patients with acute pyrexia of unknown origin; Saisongkorh W et al.; A nested PCR technique was performed to detect a specific 483 bp DNA fragment of Orientia tsutsugamushi, the aetiological agent of scrub typhus, in 53 blood samples from 36 patients with acute pyrexia of unknown origin in southern Thailand . The specific primers could amplify the specific DNA from all 10 prototype strains of O . tsutsugamushi and all nine seropositive patients and three seronegative patients, while no DNA amplification was obtained with DNAs from other rickettsiae or from healthy persons or from patients with murine typhus . The specific PCR product was detectable in the blood for as long as 22 days after the onset of disease in patients without specific treatment and 27 days after receiving a single dose of doxycycline . Thus, nested PCR may be more sensitive than the serological test for diagnosis of scrub typhus and prolonged persistence of O . tsutsugamushi DNA in patients' blood was demonstrated despite clinical recovery of the patients. Trans R Soc Trop Med Hyg, 2004 Jun, 98(6), 354 - 9 Paediatric scrub typhus in Thailand: a study of 73 confirmed cases; Silpapojakul K et al.; We studied 73 Thai children with scrub typhus (median age 9 years, range 3-14 years, male:female ratio 1.8:1) . Most patients (86%) lived in rural areas . They presented with subacute fever (median, 9 d) with vomiting (35%), hepatomegaly (59%), splenomegaly (18%), and tachypnea (26%) . Skin rash (7%), eschar (7%), and history of mite bite were rare . Blood leucocyte counts were usually normal but 19% of patients were thrombocytopenic . Twenty (22%) patients had pneumonia and six (8%) had neurological involvement . Defervescence occurred a median of 1 d and 3 d after initiation of doxycycline and chloramphenicol, respectively, and these responses were more rapid than in those who received other antibiotics or no treatment (P < 0.001) . There was one death . Only 55% of the patients were initially diagnosed as having scrub typhus. Infect Dis Clin North Am, 2004 Mar, 18(1), 127 - 40 The history of epidemic typhus; Raoult D et al.; Few infectious diseases have influenced human civilization to the same degree as louse-transmitted typhus . Rickettsia prowazekii continues to strikes tens to hundreds of thousands of persons who live with war, famine, crowding, and in squalid conditions associated with social unrest, with mortality rates in excess of 10% to 15% . Historical documents confirm that such devastation has been a continuous feature of human existence to the extent that typhus has been a major determinant in the outcome of many wars, altering human history in its wake-despite incomplete knowledge of its precise origin . In the twenty-first century, circumstances are still conductive for outbreak; the emerging threat of bioterrorism raises justifiable concerns that typhus could affect civilization just as greatly in the future as it has in the past. Infect Dis Clin North Am, 2004 Mar, 18(1), 111 - 25 Osler on typhoid fever: differentiating typhoid from typhus and malaria; Cunha BA; Early in the history of medicine, physician had a difficult time differentiating acute febrile illnesses without localizing signs . Typhoid fever and malaria share common features, which caused diagnostic problems during the 1800s . Physician even introduced a new term, typho-malaria, a testimony to their diagnostic confusion . Osler, consummate clinician and careful observer, had vast experience with typhoid fever and malaria . He was able to easily discern between the key features of both of these infections . He also relied on fever patterns to clearly differentiate typhoid fever from malaria . Osler is credited for debunking the term typho-malaria . His clinical description of typhoid fever remains unsurpassed . Clinicians still can benefit greatly from reading Osler's clinical description of typhoid fever. Infect Dis Clin North Am, 2004 Mar, 18(1), 29 - 43 The cause of the plague of Athens: plague, typhoid, typhus, smallpox, or measles? Cunha BA. The plague of Athens raged for 4 years and resulted in the defeat of Athens . The cause of the plague of Athens continues to be debated . Infectious diseases most often cited as causes of the plague include influenza, epidemic typhus, typhoid fever, bubonic plague, smallpox, and measles . Thucydides provides the only available description of the plague of Athens . Given the nuances of the translation, bubonic plague, smallpox, and measles are the most likely causes of the plague . In my view, measles is the most likely cause of the plague of Athens. Med Vet Entomol, 2004 Mar, 18(1), 61 - 3 Ectoparasites of the Pallas squirrel, Callosciurus erythraeus, introduced to Japan; Shinozaki Y et al.; The squirrel Callosciurus erythraeus (Pallas) (Rodentia: Sciuridae) was intentionally introduced to Japan in 1935 and has become established throughout much of the country . Although they live mainly in forests, Pallas squirrels come into gardens and are frequently fed by people or kept as pets, so their ectoparasites could be of potential medical as well as veterinary importance . During 2001-2003 we conducted the first ectoparasite survey of Pallas squirrels in Japan . From 105 C . erythraeus captured in Kamakura District of Kanagawa Prefecture on Honshu Island, three types of ectoparasite were found: 52 specimens of the sucking louse Neohaematopinus callosciuri Johnson (Anoplura: Haematopinidae), 26 fleas Ceratophyllus (Monopsyllus) anisus Rothschild (Siphonaptera: Ceratophyllidae) and four nymphs of the tick Haemaphysalis flava Neumann (Acari: Ixodidae) on 22, 13 and one squirrels, respectively . Evidently in Japan C . erythraeus carries relatively few ectoparasite species; this may be a contributory factor to their invasive success . Further investigations are needed to assess risks of zoonotic transmission of plague or murine typhus by C . anisus, of louse-borne typhus by N . callosciuri and of tularaemia and especially Japanese spotted fever (Rickettsia japonica) by H . flava. J Med Entomol, 2004 Jan, 41(1), 107 - 14 Mite vectors (Acari: Trombiculidae) of scrub typhus in a new endemic area in northern Kyoto, Japan; Takahashi M et al.; Between 1983 and 1999, 27 human cases of scrub typhus (two fatal) occurred in the Nodagawa River basin of northern Kyoto, Japan, an area where no cases had been previously reported . Antibody screening of infected patients' sera showed that nine of 15 patients had high titers against the Gilliam type of Orientia tsutsugamushi (Hayashi) . To determine the vector mite transmitting the disease, we studied rodent and chigger populations in and near a rice field alongside the Nodagawa River between 1996 and 1999 . The most common rodent species was Microtus montebelli (Milne-Edwards), representing 73.3% (33/45) of the population . The mite index (average number of mites per infested host) was highest (190.8) in Leptotrombidium pallidum Nagayo, Mitamura & Tamiya parasitizing on M . montebelli, followed by Leptotrombidium intermedium (Nagayo, Mitamura & Tamiya) (174.9) on the same host species . Orientia tsutsugamushi was isolated from 60.5% (23/38) of rodents and from 71.2% (37/52) of pools of engorged L . pallidum . The Gilliam type of O . tsutsugamushi was most prevalent in rodents, and in engorged L . pallidum and it was the only type recovered from 10 isolates inoculated into L 929 cells for indirect immunofluorescence examination . Orientia tsutsugamushi infected 14.3% (181/1263) and 14.8% (306/2066) of engorged and unfed L . pallidum larvae, respectively, and was also detected in 0.055% (2/3634) of unfed L . intermedium, although previous studies suggest that this mite rarely bites humans . These results show that L . pallidum is the primary vector species of scrub typhus in this new endemic area in Japan. J Microbiol Immunol Infect, 2003 Dec, 36(4), 285 - 7 Acute acalculous cholecystitis and pancreatitis in a patient with concomitant leptospirosis and scrub typhus; Wang NC et al.; Concomitant leptospirosis and scrub typhus is rare . The spectrum of clinical severity for both scrub typhus and leptospirosis ranges from mild to fatal . Acute pancreatitis and cholecystitis are infrequent complications in adult patients with either leptospirosis or scrub typhus . We report a case of leptospirosis and scrub typhus coinfection in a 41-year-old man presenting with acute acalculous cholecystitis, pancreatitis and acute renal failure . Abdominal computed tomography revealed edematous change of the gallbladder without intrahepatic or pancreatic lesions . The patient was successfully treated with doxycycline and ceftriaxone, and supportive management. Emerg Infect Dis, 2003 Dec, 9(12), 1638 - 41 Scrub typhus reemergence in the Maldives; Lewis MD et al.; In summer 2002, an outbreak of febrile illness began in the Maldives in the Indian Ocean . Through April 2003, officials recorded 168 cases with 10 deaths . The Armed Forces Research Institute of Medical Sciences in Bangkok confirmed Orientia tsutsugamushi and conducted a joint investigation with the Ministry of Health, Maldives . These cases of scrub typhus were the first in the Maldives since World War II. J Bacteriol, 2004 Jan, 186(2), 556 - 65 Comparative genomics of Rickettsia prowazekii Madrid E and Breinl strains; Ge H et al.; Rickettsia prowazekii, the causative agent of epidemic typhus, has been responsible for millions of human deaths . Madrid E is an attenuated strain of R . prowazekii, while Breinl is a virulent strain . The genomic DNA sequence of Madrid E has recently been published . To study the genomic variations between Madrid E (reference) and Breinl (test) DNAs, cohybridization experiments were performed on a DNA microarray containing all 834 protein-coding genes of Madrid E . Of the 834 genes assessed, 24 genes showed 1.5- to 2.0-fold increases in hybridization signals in Breinl DNA compared to Madrid E DNA, indicating the presence of genomic variations in approximately 3% of the total genes . Eighteen of these 24 genes are predicted to be involved in different functions . Southern blot analysis of five genes, virB4, ftsK, rfbE, lpxA, and rpoH, suggested the presence of an additional paralog(s) in Breinl, which might be related to the observed increase in hybridization signals . Studies by real-time reverse transcription-PCR revealed an increase in expression of the above-mentioned five genes and five other genes . In addition to the elevated hybridization signals of 24 genes observed in the Breinl strain, one gene (rp084) showed only 1/10 the hybridization signal of Madrid E . Further analysis of this gene by PCR and sequencing revealed a large deletion flanking the whole rp084 gene and part of the rp083 gene in the virulent Breinl strain . The results of this first rickettsial DNA microarray may provide some important information for the elucidation of pathogenic mechanisms of R . prowazekii. J Am Acad Dermatol, 2004 Jan, 50(1), 1 - 12; quiz 13-4 Pediculosis; Ko CJ et al.; The 3 major lice that infest humans are Pediculus humanus capitis (head louse), Pthirus pubis (crab louse), and Pediculus humanus humanus (body louse) . Patients with louse infestation present with scalp pruritus, excoriations, cervical lymphadenopathy, and conjunctivitis . A hypersensitivity rash, or pediculid, may mimic a viral exanthem . Head lice infestation crosses all economic and social boundaries, whereas body lice infestation preferentially affects the homeless and displaced . Body lice are major vectors of diseases such as typhus, trench fever, and relapsing fever . Pubic lice infestation often is acquired as a sexually transmitted disease and may be a marker to screen for other sexually transmitted diseases . Treatment of louse infestation can be challenging . Mechanical measures, such as combing, are helpful as adjunctive measures, but most studies suggest they are not as effective as chemical agents . Resistance to chemical agents is a growing problem . Major types of resistance include knock-down resistance, glutathione-S-transferase-based resistance, and monooxygenase-based resistance . Research is needed to identify new effective treatments. Am J Trop Med Hyg, 2003 Nov, 69(5), 519 - 24 Occurrence of Orientia tsutsugamushi in small mammals from Thailand; Coleman RE et al.; Extensive sampling of small mammals was conducted in eight provinces of Thailand between September 9, 1992 and April 29, 2001 . A total of 3,498 specimens representing 22 species were collected . Eighty-eight percent (3,089 of 3,498) of the animals were collected from a region in Chiangrai Province, which is commonly recognized as endemic for human scrub typhus . Blood and tissue samples from each animal were tested for the presence of Orientia tsutsugamushi, the etiologic agent of scrub typhus . The predominant species collected were Rattus rattus (53%, n = 1,863), R . losea (18%, n = 638), Bandicota indica (16%, n = 564), and R . exulans (4%, n = 146) . Orientia tsutsugamushi was detected in 10 of the 22 species of mammals that included R . bukit (25% infected, 1 of 4), R . rattus (23%, 419 of 1,855), R . argentiventer (22%, 5 of 23), R . berdmorei (22%, 2 of 9), R . losea (13%, 82 of 638), B . indica (9%, 52 of 564), R . koratensis (8%, 1 of 12), B . savilei (3%, 1 of 30), R . exulans (1%, 2 of 146), and Tupaia glis (2%, 1 of 49) . Infected animals were found in Chiangrai (18% infected, 563 of 3,084), Bangkok (11%, 1 of 9), Sukothai (3%, 1 of 30), and Nonthaburi (1%, 1 of 69) Provinces . The implications towards scrub typhus maintenance and transmission are discussed. MMWR Morb Mortal Wkly Rep, 2003 Dec 19, 52(50), 1224 - 6 Murine typhus--Hawaii, 2002; Centers for Disease Control and Prevention (CDC); Murine typhus, a zoonotic disease caused by Rickettsia typhi, is uncommon in the United States . Hawaii typically reports five or six cases annually; however, 47 cases were reported in 2002 . This report summarizes clinical data for three of these cases and describes murine typhus activity in Hawaii during 2002 and control efforts of the Hawaii Department of Health (HDH) . The high number of reported cases in 2002 underscores the need for community education to prevent murine typhus and an assessment of environmental factors that might contribute to local disease transmission. J Clin Microbiol, 2003 Dec, 41(12), 5466 - 72 Evaluation of a PCR assay for quantitation of Rickettsia rickettsii and closely related spotted fever group rickettsiae; Eremeeva ME et al.; A spotted fever rickettsia quantitative PCR assay (SQ-PCR) was developed for the detection and enumeration of Rickettsia rickettsii and other closely related spotted fever group rickettsiae . The assay is based on fluorescence detection of SYBR Green dye intercalation in a 154-bp fragment of the rOmpA gene during amplification by PCR . As few as 5 copies of the rOmpA gene of R . rickettsii can be detected . SQ-PCR is suitable for quantitation of R . rickettsii and 10 other genotypes of spotted fever group rickettsiae but not for R . akari, R . australis, R . bellii, or typhus group rickettsiae . The sensitivity of SQ-PCR was comparable to that of a plaque assay using centrifugation for inoculation . The SQ-PCR assay was applied successfully to the characterization of rickettsial stock cultures, the replication of rickettsiae in cell culture, the recovery of rickettsial DNA following different methods of extraction, and the quantitation of rickettsial loads in infected animal tissues, clinical samples, and ticks. J Clin Microbiol, 2003 Dec, 41(12), 5456 - 65 Gene sequence-based criteria for identification of new rickettsia isolates and description of Rickettsia heilongjiangensis sp . nov; Fournier PE et al.; We propose genetic guidelines for the classification of rickettsial isolates at the genus, group, and species levels by using sequences of the 16S rRNA (rrs) gene and four protein-coding genes, the gltA, ompA, and ompB genes and gene D . To be classified as a member of the genus Rickettsia, an isolate should exhibit degrees of rrs and gltA homology with any of the 20 Rickettsia species studied of >/=98.1 and >/=86.5%, respectively . A member of the typhus group should fulfill at least two of the following four criteria: pairwise nucleotide sequence homologies with rrs, gltA, ompB, and gene D of either Rickettsia typhi or Rickettsia prowazekii of >/=99.4, >/=96.6, >/=92.4, and >/=91.6%, respectively . A member of the spotted fever group should either possess the ompA gene or fulfill at least two of the following four criteria: pairwise nucleotide sequence homologies with rrs, gltA, ompB, and gene D of any member of this group of >/=98.8, >/=92.7, >/=85.8, and >/=82.2%, respectively . The existence of a distinct "ancestral" group should be questioned . To be classified as a new Rickettsia species, an isolate should not exhibit more than one of the following degrees of nucleotide similarity with the most homologous validated species: >/=99.8 and >/=99.9% for the rrs and gltA genes, respectively, and, when amplifiable, >/=98.8, >/=99.2, and >/=99.3% for the ompA and ompB genes and gene D, respectively . By use of our classification scheme, "Rickettsia heilongjiangii" belongs to a new species for which we officially propose the name Rickettsia heilongjiangensis sp . nov. Medicina (Kaunas), 2003, 39(11), 1121 - 6 {Kedainiai Hospital - one of the oldest hospitals in the region}; Kasperaviciene A; The review presents the facts of the origination of hospitals in Lithuanian villages based on historical documents . This process took place within the occupation period of czarist Russia . The recurrence of epidemics of grave infections diseases, such as cholera, typhus and diphtheria was one of the most important reasons leading to the establishment of network of rural health care institutions . Free outpatient and inpatient treatment of rural population was introduced for the first time, however this was accomplished not in all small towns . Kedainiai is a very old town with interesting and unique history . The article reviews development of health care in Kedainiai within the period of Kaunas Province. Med Clin (Barc), 2003 Nov 8, 121(16), 613 - 5 {Murine typhus in Tenerife . Clinicoepidemiological study and differential clinical features with Q fever}; Miguelez M et al.; BACKGROUND AND OBJECTIVE: Our aim was to conduct a study to define the clinical and epidemiological characteristics of patients with murine typhus in Tenerife island (Canary islands, Spain) . Moreover, we investigated the differential clinical features of this disease with regard to Q fever . PATIENTS AND METHOD: 5-year prospective study of patients with murine typhus (1998-2002) admited in a reference hospital in Tenerife, Spain . RESULTS: Thirty two patients were included . Flea bite and rat exposure were iuncommon (6.25%) . The monthly distribution showed a peak of incidence in January, August and September, without a clear seasonal prevalence . Fever and headache were the most common clinical features . Rash was present in 28% of the cases . Both an increase in liver enzyme levels (88%) and thrombocytopenia (37.5%) were the most relevant laboratory findings . Organ complications were uncommon (18.75%) . Antibiotics were administered to 90% of patients and cure was achieved in all them . Compared with Q fever, patients with murine typhus more commonly had rash (p = 0.006) and thrombocytopenia (p < 0.001) . CONCLUSION: Murine typhus is an emerging rickettsiosis in Tenerife and must be considered in the differential diagnosis with Q fever. Vaccine, 2003 Nov 7, 21(31), 4550 - 4 Development of a rapid method for determining the infectious dose (ID)50 of Orientia tsutsugamushi in a scrub typhus mouse model for the evaluation of vaccine candidates; Chan TC et al.; The infectious dose (ID) of an inoculum for which 50% of susceptible mice will become infected (ID(50)) with Orientia tsutsugamushi is usually determined by rechallenging mice that have already been challenged with O . tsutsugamushi to determine the lethal dose (LD)(50) titer of the inoculum . Those mice not killed by the initial challenge and which survived a rechallenge with 1000 LD(50) were considered immune and to have been initially infected with O . tsutsugamushi . Mice that succumbed to the rechallenge were considered not to have been initially infected . We have developed a more rapid method of determining the ID(50) of inocula for use in our vaccine studies based upon the observation that mice surviving initial challenge and that go on to survive rechallenge produced detectable IgG to O . tsutsugamushi antigens by enzyme-linked immunosorbent assay (ELISA) . Mice that did not survive rechallenge, and therefore did not receive an initial infectious inoculum did not produce detectable IgG to O . tsutsugamushi antigens . Both original LD(50) and ID(50) titers determinations require observation of mice for 21 days post-challenge . Our new ID(50) determination does not require mice or the additional 21-day observation period for rechallenge and therefore is more rapid and cost-effective than the previous standard method of determining ID(50) titer necessary for the evaluation of vaccine candidates. Lancet, 2003 Oct 11, 362(9391), 1201 - 2 Rickettsia sibirica infection in members of scientific expeditions to northern Asia; Lewin MR et al.; The risk of acquiring North Asian tick typhus (infection by Rickettsia sibirica) during travel to regions of Asia where this disease is endemic is unknown . We investigated prospectively 13 paleontologists on expedition to Mongolia . Four paleontologists had acute illness characterised by fever, rash, headache, and lymphadenopathy . All had IgM and IgG antibodies to R sibirica . Paleontologists with no illness and people who went on expeditions in other parts of the world did not have antibodies to R sibirica . Only two of the four infected persons were aware of tick bites . Travellers to regions endemic for R sibirica are at risk of contracting North Asian tick typhus even in the absence of recognised tick-bites. Can Bull Med Hist, 1999, 16(2), 271 - 91 {Epidemic disease and regulation of migration in Canada}; Paquet M; Beginning with the French Revolution and the Napoleonic Wars, the Parliament of Lower Canada adopted a rational and scientific mechanism for regulating migratory movements within its territory . Other than internal imperatives pertaining to security, this mechanism revolved around a prophylactic control of these movements of population . With the great migrations of 1830-1834 and 1847, the politicians of Lower Canada and the United Canada subsequently needed to revisit their regulatory mechanism in order to render it more efficient . In truth, new arrivals were frequently the spreaders of infectious diseases . Yet more importantly, the great epidemics, such as that of cholera in 1832, or of typhus in 1847, were not merely physically lethal, but were potentially disastrous to the social order . How then to resolve the potential pathological threats to the physical body with those to the political body? The political powers of the day adopted an entire method of thinking and a vocabulary which was more scientific, replete with medical references . Adopted under the seal of an emergency, these new measures of state control of prophylaxis were greatly inspired by those medical theories concerning infection and contagion which were prevalent prior to the arrival of the Pasteurian model of medicine . Those in power then used this new framework to analyze the question as a rational political problem . In the end, they would establish a tighter mechanism of state-controlled prophylaxis through the law, through regulations, and through devices for surveillance and control such as quarantine . The guarantor of social discipline through the erosion of individual freedom, this mechanism of state-run prophylaxis of migratory movements would, from that point forward, be justified by the health demands of the Cite organique, of the public health. J Am Mosq Control Assoc, 2001 Sep, 17(3), 166 - 80 Mosquito vector control and biology in Latin America--an eleventh symposium; Clark GG et al.; The 11th annual Latin American symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 67th Annual Meeting in Dallas, TX, in February 2001 . The principal objective, as for the previous 10 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America . This publication includes summaries of 45 presentations that were given orally in Spanish or presented as posters by participants from 8 countries in Latin America . Topics addressed in the symposium included results from chemical and biological control programs and studies; studies of insecticide resistance; and population genetics, molecular, ecological, and behavioral studies of vectors of dengue (Aedes aegypti), malaria (Anopheles albimanus and Anopheles aquasalis), leishmaniasis (Lutzomyia), murine typhus, and Chagas' disease (Triatoma) . Related topics included biology and control of Rhodnius, scorpions, Loxosceles spp., Chironomus plumosus, and Musca domestica. Taehan Kan Hakhoe Chi, 2003 Sep, 9(3), 198 - 204 {Outbreak of hepatitis by Orientia tsutsugamushi in the early years of the new millenium}; Park JI et al.; BACKGROUND/AIMS: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva . The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis . METHODS: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed . RESULTS: Female gender was dominant in the ratio of 3.4:1 . Mean age was 56.4 +/- 2.6 . Admission was between 23rd September and 15th November with the peak between mid October and early November . Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6 . An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2) . Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal . All the patients improved with doxycycline therapy . CONCLUSIONS: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease. Curr Opin Infect Dis, 2003 Oct, 16(5), 429 - 36 Scrub typhus and tropical rickettsioses; Watt G et al.; PURPOSE OF REVIEW: Recent developments in molecular taxonomic methods have led to a reclassification of rickettsial diseases . The agent responsible for scrub typhus (Orientia tsutsugamushi ) has been removed from the genus Rickettsia and a bewildering array of new rickettsial pathogens have been described . An update of recent research findings is therefore particularly timely for the nonspecialist physician . RECENT FINDINGS: An estimated one billion people are at risk for scrub typhus and an estimated one million cases occur annually . The disease appears to be re-emerging in Japan, with seasonal transmission . O . tsutsugamushi has evolved a variety of mechanisms to remain viable in its intracellular habitat . Slowing the release of intracellular calcium inhibits apoptosis of macrophages . Subsets of chemokine genes are induced in infected cells, some in response to transcription factor activator protein 1 . Cardiac involvement is uncommon and clinical complications are predominantly pulmonary . Serious pneumonitis occurred in 22% of Chinese patients . Dual infections with leptospirosis have been reported . Standardized diagnostic tests are being developed and attempts to improve treatment of women and children are being made . Of the numerous tick-borne rickettsioses identified in recent years, African tick-bite fever appears to be of particular importance to travellers . The newly described flea-borne spotted fever caused by Rickettsia felis may be global in distribution . SUMMARY: Rash and fever in a returning traveler could be rickettsial and presumptive doxycycline treatment can be curative . Recent research findings raise more questions than answers and should stimulate much needed research. Southeast Asian J Trop Med Public Health, 2003 Mar, 34(1), 175 - 8 The etiology of acute pyrexia of unknown origin in children after a flood; Pradutkanchana J et al.; Acute pyrexia of unknown origin (PUO) is a major public health problem in Thailand . We studied the etiology of 180 cases of acute PUO in children after a sudden severe flood in Hat Yai city in 2000 . Dengue infection and leptospirosis accounted for more than half of the total cases . Dengue hemorrhagic fever was the most common (29.4%) followed by leptospirosis (27.2%) and scrub typhus infection (1.1%) . Five serovars of leptospires were involved in this study . Leptospira interrogans bataviae was the most common (86.5%) . Acute serum antibody testing could detect only 52.8% and 40.8% of dengue and leptospirosis cases, respectively . This study showed both should be included in the presumptive diagnosis of acute PUO in patients after flooding. Southeast Asian J Trop Med Public Health, 2003 Mar, 34(1), 165 - 70 Antibody prevalence of Orientia tsutsugamushi, Rickettsia typhi and TT118 spotted fever group rickettsiae among Malaysian blood donors and febrile patients in the urban areas; Tay ST et al.; The seroprevalence of Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) among blood donors and febrile Malaysian patients in the urban areas was determined . Of the 240 blood donors, 5.4%, 9.2% and 1.7% had either present or previous exposure to OT, RT and SFG rickettsiae, respectively . Patients admitted to an urban hospital had high seroprevalences of OT (43.5%) and RT (22.9%), as compared to SFGR (11.6%) . Antibody levels suggestive of recent infections of scrub typhus, murine typhus and tick typhus were detected in 16.8%, 12.7% and 8.2% of patients respectively . No significant difference was noted in the distribution of rickettsial antibodies among urban patients from 2 geographical locations . However, the serologic patterns of rickettsial infection in the urban areas were different form those of rural areas. Trop Med Int Health, 2003 Sep, 8(9), 803 - 11 Emerging rickettsial infections in Sri Lanka: the pattern in the hilly Central Province; Kularatne SA et al.; OBJECTIVES: To identify different rickettsial infections using a specific immunofluorescent technique in patients clinically diagnosed as 'typhus fever' in the Central Province of Sri Lanka, and to define the clinical picture, assess the severity of infection and to determine the pattern of geographical distribution of the infections of the hospital-based patients . METHODS: A specific indirect immunofluorescent antibody technique was used on the sera of two groups of patients in laboratories in Japan and Thailand . RESULTS: We serodiagnosed infections with Orientia tsutsugamushi, Rickettsia typhi and spotted fever group in 56 of 118 clinically investigated patients . There were eight infections with O . tsutsugamushi, two with R . typhi and 10 spotted fever group patients with IgM antibodies suggestive of acute infection . Nineteen patients had antibodies against these three rickettsial species, suggestive of past exposure, co-infection or cross-reactivity of antigens . Discrete, erythematous maculopapular rash was common to all three types of infection except for five patients who had no rash . Five patients positive for spotted fever antibodies developed fern-leaf type skin necrosis with severe illness . Duration of the febrile period ranged from 4 to 23 days with defervescence occurring after specific antibiotic treatment . CONCLUSIONS: The study has shown the presence of different types of rickettsial infections in the Central Province of Sri Lanka . The characterization of the clinical picture and the severity of infection provide useful information for the proper management of the patients in the future. Am J Trop Med Hyg, 2003 Jul, 69(1), 60 - 6 Laboratory diagnosis of two scrub typhus outbreaks at Camp Fuji, Japan in 2000 and 2001 by enzyme-linked immunosorbent assay, rapid flow assay, and Western blot assay using outer membrane 56-kD recombinant proteins; Jiang J et al.; Two scrub typhus outbreaks occurred among U.S . Marines training at Camp Fuji, Japan, between October 25 and November 3, 2000 and October 17 and November 30, 2001 . Nine cases in approximately 800 Marines in 2000 and eight cases in approximately 900 Marines in 2001 (approximate attack rates = 1.1% and 0.9%, respectively) reported with signs and symptoms of fever, rash, headache, lymphadenopathy, myalgia, and eschar . Serologies and rapid response to doxycycline treatment indicated they had scrub typhus . Sixty-four convalescent serum samples (18 suspected cases and 46 negative controls) from U.S . Marines training at Camp Fuji during the outbreaks were assessed by enzyme-linked immunosorbent assay (ELISA), rapid flow assay (RFA), and Western blot assay for evidence of infection with Orientia tsutsugamushi, the causative agent of scrub typhus . All but one suspected case had serologic evidence of scrub typhus and all 46 control sera were non-reactive to O . tsutsugamushi antigens . The recombinant 56-kD antigen (r56) from the Karp, Kato and Gilliam strains of O . tsutsugamushi in an ELISA format provided better results than Karp r56 alone (ELISA and RFA) or whole cell antigen preparation from Karp, Kato and Gilliam (ELISA). Przegl Epidemiol, 2003, 57(1), 225 - 30 {Rudolf Stefan Weigl--scientist and human being}; Tylewska-Wierzbanowska S et al.; Rudolf Stefan Weigl died in 1957, 45 years ago . This year we are celebrating 120 anniversary of his birthday . He was a great Polish scientist who led research on Rickettsia prowazeki and epidemic typhus . R . Weigl developed a method of R . prowazeki culture in louse gut and elaborated the technology of epidemic typhus vaccine production . He and his co-workers introduced first vaccination of medical staff, people from endemic area in Poland and missionaries working in Asia . He was an international authority on prophylactics and control of rickettsial epidemic typhus. J Med Assoc Thai, 2003 Jun, 86(6), 516 - 21 Seroprevalence of rickettsial infection in commensal rodents and shrews trapped in the Bangkok Metropolitan Area; Siritantikorn S et al.; Murine typhus and scrub typhus are important human rickettsial diseases in Thailand . Small mammals, including many species of rodents and shrews, serve as the reservoir host of rickettsial diseases . Rickettsia typhi can be transmitted to humans by fleas causing murine typhus, while infection with Orientia tsutsugamushi causing scrub typhus in humans is transmitted by chiggers . The prevalence of rickettsial infection depends on the geographic area . The seroprevalence of antibody to R . typhi and O . tsutsugamushi was studied in commensal rodents and shrews trapped in markets in the Bangkok Metropolitan Area (BMA) . R . typhi and O . tsutsugamushi antigen prepared in the yolk sac of embryonated eggs were used to determine the specific antibody in trapped animals' sera by using fluorescein isothiocyanate (FITC)-anti rat immunoglobulins as a second antibody . Antibody to R . typhi was found in 25 (5%) of 500 sera tested and no antibody to O . tsutsugamushi was detected . R . typhi antibody titer ranged from 40-1280 and was found in Rattus norvegicus (4.2%), Rattus rattus (0.4%), Rattus exulans (0.2%), and Mus musculus (0.2%) trapped in 8 of 47 markets in the BMA . R . typhi antibody was commonly found in R . norvegicus . The authors concluded that murine typhus is an important rickettsial disease and R . norvegicus is an important reservoir species of rodents found in markets of the BMA. Am J Trop Med Hyg, 2003 Apr, 68(4), 480 - 4 Serologic evidence of infection with ehrlichiae and spotted fever group rickettsiae among residents of Gag Island, Indonesia; Richards AL et al.; The causative agents of scrub and murine typhus are considered endemic to Indonesia . However, the presence of spotted fever group rickettsiae and ehrlichiae have not been previously described in this country . During an investigation of arthropod-borne diseases on Gag Island, located northwest of the island of New Guinea in eastern Indonesia, the prevalence of antibody to the etiologic agents of monocytic ehrlichiosis, spotted fever rickettsiosis, and scrub and murine typhus were determined . Analysis of 55 blood samples from residents of Gag Island showed seroreactivity to antigen preparations of Ehrlichia chaffeensis (7 of 48, 14.6%), two spotted fever group rickettsiae: Rickettsia rickettsii (5 of 48, 10.4%) and R . conorii (10 of 49, 20.4%), Orientia tsutsugamushi (5 of 53, 9.4%), and R . typhi (1 of 48, 2.1% {by an indirect immunofluorescence assay} and 1 of 50, 2.0% {by an enzyme-linked immunosorbent assay}) . These results show serologic evidence of infection with ehrlichiae and spotted fever group rickettsiae for the first time in Indonesia in a location where the prevalence of antibody to O . tsutsugamushi and R . typhi was lower. Am J Trop Med Hyg, 2003 Apr, 68(4), 477 - 9 Prevalence of relative bradycardia in Orientia tsutsugamushi infection; Aronoff DM et al.; We investigated 100 febrile patients infected with Orientia tsutsugamushi (the etiologic agent of scrub typhus) for the presence of relative bradycardia, defined as in increase in heart rate of < 10 beats/minutes/1 degree C increase in temperature . The median heart rate response for the entire febrile scrub typhus population was 9.3 beats/minute/degrees C and the prevalence of relative bradycardia was 53% . The occurrence of relative bradycardia was independent of patient age or gender . There were no differences in median basal temperature or febrile temperature between those patients exhibiting relative bradycardia and those with a normal febrile pulse increase . However, febrile patients with relative bradycardia had a significantly higher resting pulse rate following recovery from infection than did patients who had a normal pulse increase during their illness . These data demonstrate that relative bradycardia frequently accompanies mild infection with O . tsutsugamushi and that baseline cardiovascular parameters may affect the febrile heart rate response to scrub typhus. J Bacteriol, 2003 Aug, 185(15), 4578 - 84 Molecular and functional analysis of the lepB gene, encoding a type I signal peptidase from Rickettsia rickettsii and Rickettsia typhi; Rahman MS et al.; The type I signal peptidase lepB genes from Rickettsia rickettsii and Rickettsia typhi, the etiologic agents of Rocky Mountain spotted fever and murine typhus, respectively, were cloned and characterized . Sequence analysis of the cloned lepB genes from R . rickettsii and R . typhi shows open reading frames of 801 and 795 nucleotides, respectively . Alignment analysis of the deduced amino acid sequences reveals the presence of highly conserved motifs that are important for the catalytic activity of bacterial type I signal peptidase . Reverse transcription-PCR and Northern blot analysis demonstrated that the lepB gene of R . rickettsii is cotranscribed in a polycistronic message with the putative nuoF (encoding NADH dehydrogenase I chain F), secF (encoding protein export membrane protein), and rnc (encoding RNase III) genes in a secF-nuoF-lepB-rnc cluster . The cloned lepB genes from R . rickettsii and R . typhi have been demonstrated to possess signal peptidase I activity in Escherichia coli preprotein processing in vivo by complementation assay. Ann N Y Acad Sci, 2003 Jun, 990, 757 - 64 Development of Rickettsia prowazekii DNA vaccine: cloning strategies; Coker C et al.; Rickettsia prowazekii, the etiologic agent of louse-borne typhus, is listed as a category B agent under the select agent list of the United States Centers for Disease Control and Prevention . R . prowazekii was placed on the select agent list due to its potential to cause epidemic, high mortality in untreated and/or misdiagnosed cases, and ease of spread in vulnerable populations . Historically, R . prowazekii vaccines using crude antigen and/or inactivated rickettsia were partially protective but have been accompanied with undesirable toxic reactions and difficulties in standardization . The availability of the genome sequence of R . prowazekii allowed us to select genes that encode proteins with potential in immuno-protection against this human pathogen . We successfully PCR-amplified a group of genes involved in invasion (invA), cell division (fts), protein secretion (sec gene family), and virulence (ompA and ompB, virB gene family, cap and tlyA and tlyC) . The generated PCR products were cloned into the Gateway cloning system and the cloned products will be introduced into Vical VR 1020-DV and VR 1012-DV DNA vaccine plasmids . Twenty-four target genes from R . prowazekii have been PCR amplified, of which fifteen have been introduced into the pENTR/SD/D-TOPO entry cloning vector. Ann N Y Acad Sci, 2003 Jun, 990, 726 - 33 rRNA intergenic spacer regions for phylogenetic analysis of Rickettsia species; Vitorino L et al.; Species of the genus Rickettsia are responsible for several human diseases, namely epidemic typhus, Rocky Mountain spotted fever, and tick-borne typhus transmitted by arthropod vectors . The rrl-rrf intergenic spacer region (rrl-rrf ITS) was sequenced for 12 Rickettsia strains, including R . typhi, 6 untested species, R . aeschlimannii, Bar29, R . helvetica, R . honei, R . massilae, and R . slovaca as well as 5 Portuguese isolates . Phylogenetic trees inferred from rrl-rrf spacer sequences using maximum-parsimony and distance methods provided largely congruent tree topologies, supported by significant bootstrap values, enabling the identification of five distinct rickettsiae clusters. Ann N Y Acad Sci, 2003 Jun, 990, 617 - 27 An experimental model of human body louse infection with Rickettsia typhi; Houhamdi L et al.; Murine (endemic) typhus caused by Rickettsia typhi, one of the most widely distributed arthropod-borne diseases, is transmitted to humans mainly by the oriental rat flea . The human body louse, Pediculus humanus corporis, has been suspected to have a role in the transmission of R . typhi to humans . To evaluate the potential role of Pediculus humanus corporis as a vector of murine typhus, we used R . typhi in an experimental model of human body louse infection previously used with R . prowazekii . A rabbit was made bacteremic by inoculating it with 2 x 10(6) plaque-forming units of R . typhi; it remained bacteremic for at least 59 hours . Two hundred body lice infected by feeding on the bacteremic rabbit were compared to 200 uninfected control lice . Each louse population was fed once a day on the abdomen of a seronegative rabbit . On day 8 post-infection, as a result of disruption of the gut cells and leakage of the blood meal into the hemolymph, four infected lice became bright red and died within four hours . The life span of infected lice was 20 days less than that of the controls . Infected lice did not transmit R . typhi to their progeny (eggs and larvae) as demonstrated by PCR amplification and cell culture . With an immunofluorescence assay, R . typhi was detected in feces from day 7 post-infection, and the organism remained viable in feces for up to 80 days as demonstrated by cell culture . From the 21st day post-infection, the rabbit used to feed the R . typhi-infected lice developed an immunoglobulin response with a titer of 1:50 increasing to 1:200 at the 42nd day post-infection . It showed no clinical signs of infection . The rabbit that was used to feed uninfected lice remained seronegative . Although body lice are not clearly identified vectors of R . typhi, it seems that under certain circumstances they could transmit R . typhi. Ann N Y Acad Sci, 2003 Jun, 990, 331 - 43 Report of eight cases of fatal and severe Mediterranean spotted fever in Portugal; Amaro M et al.; Mediterranean spotted fever (MSF), endemically present, is associated with a low mortality and morbidity in Portugal . Etiological agents are Malish and Israeli tick typhus strains of Rickettsia conorii . In the last few years severe forms of MSF have emerged, with patients presenting atypical symptoms, major neurological manifestations, and multiorgan involvement, who have required intensive care facilities . Advanced age, underlying chronic disease, and delay of appropriate treatment are bad prognostic factors . In the acute phase of diagnosis, serological studies are delayed, inconclusive, and often unhelpful . A definitive diagnosis can only be made using isolation or molecular biology which can establish and clearly identify agents . Using evidence-based case reports, clinical and laboratory data were evaluated from patients with severe or fatal MSF observed in Garcia da Orta Hospital-Almada . Of the eight reference cases, four died, three in an acute fulminant stage . Of the survivors, four presented atypical involvement: ocular inoculation, massive gastric hemorrhage, acute respiratory disease (ARDS), and necrotizing vasculitis . Diagnosis by isolation of the agent was made in two cases, by immunohistochemistry in three, and by the indirect fluorescent antibody test (IFA) in three others . Israeli tick typhus and Malish R . conorii strains were isolated once each in fatal cases . In early stages, diagnosis continues to be clinical and patients should start appropriate therapy without delay if clinical suspicion of rickettsiosis arises to prevent poor outcome . Patients ranged in age from 39 to 71 years (mean 60), APACHE II ranged from 15 to 38 points and TISS 28 was between 24 and 46 points . In reported cases severity of disease was not obviously related to the usual comorbidities . Accelerated clinical course may not suggest classical MSF . Another relevant factor was prior prescription of an inappropriate antibiotic that contributed to misleading clinical features . The reported complications and atypical manifestations illustrate well the diversity of this disease. Ann N Y Acad Sci, 2003 Jun, 990, 205 - 12 Characterization of Orientia tsutsugamushi isolated from wild-caught rodents and chiggers in northern Thailand; Khuntirat B et al.; We previously reported Orientia tsutsugamushi detection from tissue samples (kidney, liver, spleen, and whole blood) of 12 wild-caught rodents from Chiangrai Province, northern Thailand . Of the 30 chiggers individually removed from scrub typhus-infected rodents, 2 were found positive for O . tsutsugamushi . We further characterized the O . tsutsugamushi detected from these rodents and chiggers by RFLP using three different enzyme digestions . All 14 O . tsutsugamushi samples (12 from tissue samples and 2 from chiggers) showed different digestion patterns when compared to those of reference strains (Karp, Kato, and Gilliam) . Interestingly, nine RFLP profiles were observed from these 14 samples suggesting the presence of high genetic diversity of O . tsutsugamushi in this area . Furthermore, one sample displayed the same RFLP pattern as that of O . tsutsugamushi mild resistant strain previously isolated from scrub typhus patient in Chiangrai . Of the two samples from positive chiggers, only one was found to have a similar RFLP pattern to that of its host rodent . DNA sequencing of the entire 56 kDa genome of these O . tsutsugamushi samples is in progress. Ann N Y Acad Sci, 2003 Jun, 990, 62 - 6 Rickettsia honei: a spotted fever group Rickettsia on three continents; Graves S et al.; Rickettsia honei (also known as strain TT-118) has been detected on three continents . Originally isolated in Thailand in 1962 (and confirmed in 2001), it has also been detected on Flinders Island (Australia) in 1993 and in Texas (USA) in 1998 . On each continent it has been associated with a different species of tick . The original isolate (Thai Tick Typhus strain TT-118) was from a pool of larval Ixodes and Rhipicephalus ticks . Later it was detected in I . granulatus from Rattus rattus . Its pathogenicity for humans has not yet been confirmed in Thailand, but it is possibly responsible for the Spotted Fever Group human rickettsiosis in Thailand . The strain from Texas (USA) was isolated from Amblyomma cajennense ticks taken from cattle . Its pathogenicity for humans has not yet been confirmed in Texas . However, this tick is known to bite humans . The strain from Flinders Island (Australia) described as R . honei, has been isolated from patients with "Flinders Island Spotted Fever" and from Aponomma hydrosauri ticks taken from blue-tongue lizards (Tiliqua nigrolutea), tiger snakes (Notechis ater humphreysi), and copperhead snakes (Austrelaps superbus) on Flinders Island . The ecology of R . honei in this location is unusual in that reptiles, rather than mammals, are the vertebrate hosts. Ann N Y Acad Sci, 2003 Jun, 990, 1 - 11 Pathogenic mechanisms of diseases caused by Rickettsia; Walker DH et al.; The specter of bioterrorism employing genetically engineered Rickettsia resistant to all antibiotics should reawaken the world's desire to elucidate the pathogenesis of typhus and spotted fever rickettsioses in a search for mechanisms vulnerable to interdiction . The pathogenetic sequence includes rickettsial entry into the dermis, hematogenous dissemination to vascular endothelial cells (most critically in brain and lungs), increased vascular permeability, edema, and immunity mediated by NK cells, IFN-gamma, TNF-alpha, RANTES, antibodies, and cytotoxic T lymphocytes . Silverman has demonstrated the role of reactive oxygen species (ROS) produced by R . rickettsii-infected endothelial cells in peroxidative damage to cell membranes in vitro, and Heinzen has described actin-based rickettsial intracellular mobility and intercellular spread . At this point the availability of sequences of rickettsial genomes and excellent animal models of rickettsioses have yielded insufficient progress towards the identification of rickettsial virulence factors and knowledge of the importance of injury mediated by ROS, phospholipase A(2), protease(s) or other mechanisms in vivo . Attention to the rickettsiosis-associated procoagulant state led to determination that hemostatic mechanisms largely prevent major hemorrhage without disseminated intravascular coagulation or thrombosis-mediated ischemia . Particularly lacking is knowledge of early events in vivo at the portal of entry in skin (or lung), of the effects of the inoculum medium (arthropod saliva or feces), mediators produced by infected endothelium under conditions of flow and of the contributions in vivo of immune effectors to pathology, of the role of apoptosis in rickettsial infection, and of the endothelial cell alterations that account for increased vascular permeability . The host cell receptor for the Rickettsia ligand and the mechanism of rickettsial escape from the phagosome need to be elucidated. J Clin Microbiol, 2003 Jul, 41(7), 2952 - 60 Differentiation of rickettsiae by groEL gene analysis; Lee JH et al.; The nucleotide sequences (534 to 546 bp) of the groEL gene, which encodes the 60-kDa heat shock protein GroEL, from 15 rickettsial strains were determined and compared . In the phylogenetic tree created by the unweighted pair group method with arithmetic averages and the neighbor-joining method, rickettsial strains could be distinguished from Ehrlichia strains . Five spotted fever group strains, four typhus group strains, and six scrub typhus group (STG) strains were differentiated as distinct entities . Unlike gltA and ompA gene analyses, differentiation between members of the genus Rickettsia and the STG rickettsiae by groEL gene analysis was possible . In comparison with 16S rRNA gene analysis, the groEL gene has a higher degree of divergence among the rickettsiae . We therefore successfully developed rapid differentiation methods, PCR-restriction fragment length polymorphism analysis and a species-specific PCR, based on the groEL gene sequences . Four Korean isolates were identified by these methods and groEL gene analysis . The results suggest that the groEL gene is useful for the identification and characterization of rickettsiae. Scand J Infect Dis, 2003, 35(4), 247 - 50 Rickettsioses in Swedish travellers, 1997-2001; Rahman A et al.; From laboratory records, information was collected on all 77 cases of rickettsioses diagnosed in Sweden during 1997-2001, 14 of which were diagnosed as belonging to the typhus group and 63 to the spotted fever group . Signs of hepatic involvement occurred more frequently in the typhus group . Denominators for the number of journeys to different parts of the world were retrieved from a commercial Swedish tourist database . The estimated risk of rickettsioses in destinations outside Europe varied from 1 case in 140,000 travellers to south-east Asia to 1 in 1600 travellers to southern Africa . The risk of infection in southern Africa increased over the 5 y period and is now 4-5 times higher than the risk of acquiring malaria in the same region . Rickettsiosis is an important differential diagnosis to consider in the febrile traveller, especially from South Africa . It should be remembered that the serological response may be considerably delayed and in patients with a negative first serology, serological testing should be repeated . Where there is a strong suspicion of rickettsiosis treatment may have to be started without a confirmed diagnosis. Am J Trop Med Hyg, 2003 May, 68(5), 536 - 8 Differentiating dengue virus infection from scrub typhus in Thai adults with fever; Watt G et al.; Dengue fever and scrub typhus are common infections in Asia that often present as acute febrile illness of unclear etiology . We prospectively evaluated febrile adults presenting to the outpatient department of a hospital in northern Thailand to attempt to identify distinguishing characteristics between the two infections . Fifty-four patients were infected with scrub typhus and 35 were infected with dengue virus . Dengue virus infection was associated with hemorrhagic manifestations, particularly bleeding from the gums, which was reported by 27% of the dengue patients, but by none of the scrub typhus patients (P < 0.001, by Fisher's exact test) . A low platelet count (< 140,000/mm3) and low white blood cell count (< 5,000/mm3) were strongly associated with dengue infections: odds ratio = 26.3 (95% confidence interval {CI} = 7.4-93.2) for platelet count and 8.2 (95% CI = 2.6-25.5) for leukocyte count . Prospective evaluations of the usefulness of these simple criteria to differentiate scrub typhus from dengue infection are needed in other areas, particularly where rapid confirmatory diagnostic tests are not available. Ren Fail, 2003 May, 25(3), 397 - 410 Scrub typhus: a frequently overlooked cause of acute renal failure; Yen TH et al.; Acute renal failure associated with scrub typhus infection is not rare as previously thought . The possibility of scrub typhus should be borne in mind when patients present with fever and varying degrees of acute renal failure, particularly if an eschar exists, along with a history of environmental exposure in an area like Taiwan, where scrub typhus is endemic . Prompt diagnosis and the use of appropriate antibiotics can rapidly alter the clinical course of the disease and prevent the development of serious or fatal complications . To illustrate the above point, this study reports 3 cases of scrub typhus associated with acute renal failure . They were seen at Chang Gung Memorial Hospital in a 2-year interval . Case 1 was referred from district hospital with clinical features of multiple organ dysfunctions, including shock, fever, acute respiratory failure, acute renal failure, and acute hepatitis . Case 2 was admitted with the chief problems of shock, fever, acute renal failure, and DIC . Case 3 visited our outpatient clinic due to fever, maculopapular rash and acute renal failure . In all these patients, the diagnosis was confirmed using immunofluorescence techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or greater . Notably, despite having varying degrees of acute renal deterioration, the patients responded very well to doxycycline therapy and recovered completely . Additionally, a total of 4 similar cases of scrub typhus associated with acute renal failure were reviewed from the past literature. Hist Sci Med, 2003 Jan-Mar, 37(1), 43 - 6 {The laboratory breeding of lice}; Huet M; The breeding of lice started in Poland as R . Weigl used to prepare a typhus vaccine from the guts of infected lice . Helene Sparrow introduced this breeding technique in the Institut Pasteur of Tunis in 1927 . Lice will feed only on human blood . They were put in small wooden boxes with a thin cloth bottom through which they could bite and feed . Once a day the boxes were placed against the skin of human feeders whose role was essential in the process . The breeding of lice at the Institut Pasteur of Tunis lasted until 1980 and allowed significant advances in the study of typhus and relapsing fever. Parasitol Res, 2003 Jun, 90(3), 209 - 11 Epub 2003 Feb 27. Potential role of head lice, Pediculus humanus capitis, as vectors of Rickettsia prowazekii; Robinson D et al.; Since the pioneering work of Charles Nicolle in 1909 {see Gross (1996) Proc Natl Acad Sci USA 93:10539-10540} most medical officers and scientists have assumed that body lice are the sole vectors of Rickettsia prowazekii, the aetiological agent of louse-borne epidemic typhus (LBET) . Here we review the evidence for the axiom that head lice are not involved in epidemics of LBET . Laboratory experiments demonstrate the ability of head lice to transmit R . prowazekii, but evidence for this in the field has not been reported . However, the assumption that head lice do not transmit R . prowazekii has meant that head lice have not been examined for R . prowazekii during epidemics of LBET . The strong association between obvious (high) infestations of body lice and LBET has contributed to this perception, but this association does not preclude head lice as vectors of R . prowazekii . Indeed, where the prevalence and intensity of body louse infections may be high (e.g . during epidemics of LBET), the prevalence and intensity of head louse infestations is generally high as well . This review of the epidemiology of head louse and body louse infestations, and of LBET, indicates that head lice are potential vectors of R . prowazekii in the field . Simple observations in the field would reveal whether or not head lice are natural vectors of this major human pathogen. Southeast Asian J Trop Med Public Health, 2002 Dec, 33(4), 787 - 93 Borrelia burgdorferi (strain B . afzelii) antibodies among Malaysian blood donors and patients; Tay ST et al.; In this study, the presence of IgG and IgM antibodies against Borrelia burgdorferi (strain B . afzelii) among Malaysian blood donors and patients admitted to hospital with various infectious diseases was determined . Sera were screened using enzyme-linked immunosorbent assay (ELISA); positive sera were then subjected to Western blot testing . All but one of the blood donors were negative for borrelial antibodies . Of 121 patients' sera, IgM antibodies were detected in 24 (19.8%) and IgG antibodies were detected in 5 (4.1%) sera . Only one of two patients with skin manifestations suggestive of Lyme disease had IgM antibody against B . afzelii . Of 30 patients with exposure to tick typhus, 4 (13.3%) were IgM positive and 1 (3.3%) was IgG positive . Based on the detection of antigenic bands by Western blot, 6 patients' sera showed positive reactions . Antigenic bands of p39, p41 and p59/62 kDa were the commonest findings of Western blotting . This study provides serological evidence of B . afzelii infections in Malaysia; further investigation is needed to correlate serological and clinical findings. Southeast Asian J Trop Med Public Health, 2002 Dec, 33(4), 780 - 6 Septic shock secondary to scrub typhus: characteristics and complications; Thap LC et al.; Scrub typhus is an acute febrile illness caused by infection with Orientia tsutsugamushi transmitted by the bite of larval trombiculid mites (chiggers) . A prospective study was conducted in septic shock patients in Maharat Hospital, Nakhon Ratchasima Province, Thailand, from 12 November 2001 to 5 January 2002 . Of the 51 septic shock patients studied during the 7 week period, 18 (35.3%) were found to have evidence of scrub typhus infection; 3 patients (16.7%) died . In this study, septic shock caused by Orientia tsutsugamushi is the most prominent (35.3%) in endemic area of scrub typhus . Scrub typhus with septic shock patients results in organ failure: respiratory failure, DIC were predominant, followed by renal and hepatic involvement . Two deaths were due to respiratory failure and one death was as a result of combined respiratory and renal failure . Fever was the most common symptom, followed by headache, myalgia and dyspnea; lymphadenophathy and eschar are common signs . Laboratory findings revealed that almost all of the patients had a mild leukocytosis, reduced hematocrit and thrombocytopenia; SGOT, ALP, direct bilirubin (DB), total billirubin (TB), BUN, Cr were elevated; hypoalbuminemia was noted . Urinalysis showed that 88.9% of the patients had albuminuria . 77.8% of patients had abnormal chest X-rays. Southeast Asian J Trop Med Public Health, 2002 Dec, 33(4), 772 - 9 Isolation and PCR detection of rickettsiae from clinical and rodent samples in Malaysia; Tay ST et al.; Isolation of rickettsiae from patients' blood samples and organ samples of wild rodents from areas with high seroprevalence of rickettsial infections was attempted using cell culture assay and animal passages . L929 mouse fibroblast cells grown in 24 well tissue culture plate were inoculated with buffy coat of febrile patients and examined for the growth of rickettsiae by Giemsa, Gimenez staining and direct immunofluorescence assay . No rickettsiae were isolated from 48 patients' blood samples . No symptomatic infections were noted in mice or guinea pigs infected with 50 organ samples of wild rodents . There was no rickettsial DNA amplified from these samples using various PCR detection systems for Orientia tsutsugamushi, typhus and spotted fever group rickettsiae. Clin Diagn Lab Immunol, 2003 May, 10(3), 394 - 8 Evaluation of an immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of Orientia tsutsugamushi infection; Jang WJ et al.; To differentiate scrub typhus from other acute febrile diseases, a rapid and reliable serological diagnosis is important . We developed an immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) for diagnosis of recent Orientia tsutsugamushi infections in humans . The 56-kDa major outer membrane protein of O . tsutsugamushi is well known as the most immunodominant antigen in scrub typhus . The test is based on the use of the biotinylated recombinant 56-kDa protein of O . tsutsugamushi Boryong, Bor56, which was expressed as a fusion protein with a maltose-binding protein in Escherichia coli . In the test, the serum IgM antibodies were captured by anti-human IgM antibodies coated onto a microtiter plate . The captured IgM antibodies were revealed through sequential addition of biotinylated Bor56 antigen and peroxidase-conjugated streptavidin to the plate . The IgM capture ELISA was compared with the immunofluorescence antibody assay (IFA) by testing 176 serum samples from patients with diagnosed cases of rickettsial disease and patients with other acute febrile diseases . Of the 81 IgG IFA-positive samples, 78 tested positive (sensitivity, 96.3%) and all 31 IgM IFA-positive samples tested positive (sensitivity, 100%) by the IgM capture ELISA . The specificity of the IgM capture ELISA was 99%, and 1 of the 95 IFA-negative samples was positive in the assay . These results strongly suggest that IgM capture ELISA using the recombinant Bor56 antigen is a reliable and detailed method for the detection of early O . tsutsugamushi infection. Emerg Infect Dis, 2003 May, 9(5), 592 - 5 Emerging rickettsioses of the Thai-Myanmar border; Parola P et al.; To investigate the presence of rickettsioses in rural residents of the central Thai-Myanmar border, we tested the blood of 46 patients with fever . Four patients had murine typhus, three patients had scrub typhus, and eight patients had spotted fever group rickettsioses, including the first case of Rickettsia felis infection reported in Asia. Jpn J Infect Dis, 2003 Feb, 56(1), 26 - 8 Detection of antibodies against spotted fever group Rickettsia (SFGR), typhus group Rickettsia (TGR), and Coxiella burnetii in human febrile patients in the Philippines; Camer GA et al.; A total of 157 sera from febrile patients in the Philippine General Hospital in Manila, Luzon, and the Northern Samar Provincial Hospital, the Philippines, were used . Serum antibodies against spotted fever group Rickettsia (SFGR) and typhus group Rickettsia (TGR) were detected by indirect immunofluorescence test . Antibody positive rates were 1.3% for SFGR (Rickettsia japonica) and 2.5% for TGR (R . typhus), respectively . Rickettsial antibodies in humans in the Philippines were found for the first time . These results underscore the need for further epidemiological study of clinical rickettsioses in the Philippines. Emerg Infect Dis, 2003 Apr, 9(4), 480 - 2 Scrub typhus in the Torres Strait islands of north Queensland, Australia; Faa AG et al.; Scrub typhus, caused by Orientia tsutsugamushi, occurs throughout Southeast Asia . We descript ten cases that occurred in the Torres Strait islands of northern Australia during 2000 and 2001 . Preceding heavy rain may have contributed to the outbreak . The successful use of azithromycin in two pediatric patients is also reported. Southeast Asian J Trop Med Public Health, 2002 Sep, 33(3), 565 - 9 Virulence of Malaysian isolates of Orientia tsutsugamushi in mice; Tay ST et al.; The pathogenicity of Malaysian isolates of Orientia tsutsugamushi was investigated by a mouse virulence assay . The isolates could be differentiated as low (4 isolates), moderately (3 isolates) and highly virulent (2 isolates) based on the different responses in infected mice . No direct correlation between severity of human scrub typhus infections and virulence of the O . tsutsugamushi in mice was observed . Mice infected with virulent strains of O . tsutsugamushi showed splenomegaly, ascitis accumulation and enlargement of kidneys and livers whereas avirulent O . tsutsugamushi strains were asymptomatic and exhibited ruffled fur for a short period after infection . There was low antibody response in mice infected with isolates of low pathogenicity as compared with those of highly virulent isolates . Upon dissection of the infected mice, enlargement of mouse organs such as spleen, kidney and liver was noted . Presence of rickettsemia in mice was confirmed by the growth of O . tsutsugamushi in the L929 cells when inoculated with blood from infected mice . O . tsutsugamushi was also cultured from the peritoneal exudates of the infected mice . However, DNA of O . tsutsugamushi was only detected in the peritoneal exudates (by PCR) and blood (by cell culture) and not from other tissue samples. Southeast Asian J Trop Med Public Health, 2002 Sep, 33(3), 557 - 64 Antigenic types of Orientia tsutsugamushi in Malaysia; Tay ST et al.; The seroprevalence of various Orientia tsutsugamushi (OT) strains among Malaysian patients with suspected scrub typhus infections was determined using an indirect immunoperoxidase (IIP) assay . IgG against a single OT strain were detected in six sera (3 Karp, 1 Gilliam and 2 TC586), whereas IgM antibodies against a single OT strain (Gilliam) were noted in 3 sera (Gilliam) . IgG reactive to all OT strains were present in 33 (47.1%) of the 70 sera and IgM reactive to all OT strains were present in 22 (78.6%) of the 28 sera . The fact that most sera were reactive to multiple OT strains suggests that group-specific antigens are involved in scrub typhus infections, whereas very few were du