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Studies on tropical typhus in British Malaya (preliminary note)

Anigstein L

Malayan Medical Journal, 1930;5:62-4.

Matched MeSH terms: Scrub Typhus
A summary topographical account of scrub typhus, 1908-1946

Audy JR

Bull Inst Med Res Kuala Lumpur, 1949.

Matched MeSH terms: Scrub Typhus
The prophylaxis of typhus fever and vaccination against that disease

Biraud Y

Malayan Medical Journal, 1937;12:155-6.

Matched MeSH terms: Scrub Typhus
Fulltext Febrile illness in Malaysia--an analysis of 1,629 hospitalized patients

Brown GW, Shirai A, Jegathesan M, Burke DS, Twartz JC, Saunders JP, et al.

Am J Trop Med Hyg, 1984 Mar;33(2):311-5.
PMID: 6324601

We studied 1,629 febrile patients from a rural area of Malaysia, and made a laboratory diagnosis in 1,025 (62.9%) cases. Scrub typhus was the most frequent diagnosis (19.3% of all illnesses) followed by typhoid and paratyphoid (7.4%); flavivirus infection (7.0%); leptospirosis (6.8%); and malaria (6.2%). The hospital mortality was very low (0.5% of all febrile patients). The high prevalence of scrub typhus in oil palm laborers (46.8% of all febrile illnesses in that group) was confirmed. In rural Malaysia, therapy with chloramphenicol or a tetracycline would be appropriate for undiagnosed patients in whom malaria has been excluded. Failure to respond to tetracycline within 48 hours would usually suggest a diagnosis of typhoid, and indicate the need for a change in therapy.

Matched MeSH terms: Scrub Typhus/diagnosis
Development of antibody to Rickettsia tsutsugamushi in soldiers in Malaysia

Brown GW, Shirai A, Groves MG

Trans R Soc Trop Med Hyg, 1983;77(2):225-7.
PMID: 6408770

Malaysian, British and New Zealand soldiers were tested for evidence of infection with Rickettsia tsutsugamushi after several weeks' exposure to the infection during field exercises in Malaysia. 39 (5.0%) of 787 British and New Zealand soldiers developed immunofluorescent antibody (IFA) to R. tsutsugamushi to a titre of 1:50 and two (0.3%) to a titre of 1:100. 11 (1.5%) of 751 Malaysian soldiers also developed low titres less than or equal to 1:100. These low antibody levels were not correlated with clinical disease, and their significance is unknown. Seven (0.9%) of the Malaysians showed an IFA rise to greater than or equal to 1:200, and three of these experienced febrile illnesses, one lasting two weeks. An additional eight Malaysian soldiers had an IFA titre of greater than or equal to 1:400 when first tested and six of these also had a Proteus OXK agglutinin titre of greater than or equal to 1:160, indicating infection shortly before the study.

Matched MeSH terms: Scrub Typhus/diagnosis
Diagnostic criteria for scrub typhus: probability values for immunofluorescent antibody and Proteus OXK agglutinin titers

Brown GW, Shirai A, Rogers C, Groves MG

Am J Trop Med Hyg, 1983 Sep;32(5):1101-7.
PMID: 6414321

The sensitivities and specificities of the indirect microimmunofluorescent antibody (IFA) and Weil-Felix (OXK) tests for scrub typhus were established for a range of titers using groups of diseased and control (other febrile illnesses) patients diagnosed by other methods. At a cut-off point of greater than or equal to 1:400, the IFA test was 0.96 specific, and at greater than or equal to 1:320, the OXK was 0.97 specific. Using either these highly specific levels of antibody or other rigorous diagnostic criteria (isolation or 4-fold rising titers), the prevalence of scrub typhus infection was determined to be 0.22 in an unselected population of febrile patients in a rural Malaysian hospital. Probability values (Pr) for the correct diagnosis of scrub typhus were then calculated from the specificity, sensitivity and prevalence determination for a range of titers. The Pr for an OXK titer of greater than or equal to 1:320 was 0.79, and the Pr for an IFA titer of greater than or equal to 1:400 was 0.78. When both these titers were present in a single specimen, the Pr increased to 0.96.

Matched MeSH terms: Scrub Typhus/diagnosis*; Scrub Typhus/immunology; Scrub Typhus/epidemiology
Recent studies in scrub typhus: a review

Brown GW

J R Soc Med, 1978 Jul;71(7):507-10.
PMID: 359809
Matched MeSH terms: Scrub Typhus/diagnosis*; Scrub Typhus/epidemiology; Scrub Typhus/therapy
Serological evidence for a high incidence of transmission of Rickettsia tsutsugamushi in two Orang Asli settlements in Peninsular Malaysia

Brown GW, Robinson DM, Huxsoll DL

Am J Trop Med Hyg, 1978 Jan;27(1 Pt 1):121-3.
PMID: 415625

Two communities of Orang Asli (aborigines) in Peninsular Malaysia were observed for evidence of Rickettsia tsutsugamushi infection over periods of 1-8 mo. Sequential sera were examined for antibody by the indirect immunofluorescence test. The incidence of infection in the two self-selected populations in the two communities was calculated to be 3.9% per month and 3.2% per month.

Matched MeSH terms: Scrub Typhus/epidemiology*
Scrub typhus: a common cause of illness in indigenous populations

Brown GW, Robinson DM, Huxsoll DL, Ng TS, Lim KJ

Trans R Soc Trop Med Hyg, 1976;70(5-6):444-8.
PMID: 402722

An explanation was sought for the disparity between the low reported incidence of scrub typhus and the high prevalence of antibody to Rickettsia tsutsugamushi in the rural population of Malaysia. A combination of isolation of the organism, titration of antibody by indirect immunofluorescence, and the Weil-Felix test was used to confirm infections. Scrub typhus was found to be very common, causing 23% of all febrile illnesses at one hospital. The infection was particularly prevalent in oil-palm workers, causing an estimated 400 cases annually in a population of 10,000 people living on one plantation. The clinical syndrome, whether mild or severe, was difficult to distinguish from that due to other infections. Eschars, rashes and adenopathy were uncommon. When used to examine early sera, the Weil-Felix test failed to confirm the diagnosis in most infections.20

Matched MeSH terms: Scrub Typhus/immunology; Scrub Typhus/epidemiology*
The effect of habitat on the prevalence of human scrub typhus in Malaysia

Cadigan FC, Andre RG, Bolton M, Gan E, Walker JS

Trans R Soc Trop Med Hyg, 1972;66(4):582-7.
PMID: 4561007
Matched MeSH terms: Scrub Typhus/diagnosis; Scrub Typhus/epidemiology*
Variation in populations of chigger vectors of scrub typhus in developing oil palm areas of different ages

Dohany AL, Shirai A, Lim BL, Huxsoll DL

Jpn. J. Med. Sci. Biol., 1980 Oct;33(5):263-70.
PMID: 7300038

The populations of scrub typhus vector chiggers were compared in two developing oil palm areas, one 5 years old and the other 7 years old at the inception of the study. Both areas were located within the same oil palm scheme in central Peninsular Malaysia. Leptotrombidium (L.) deliense, a principal vector of scrub typhus in Malaysia, was found in reduced numbers in the older oil palm habitat. This reduction is attributed to changes in the microhabitat, specifically the elimination of grasses between the oil palm trees due to canopy shading and to cultural practices.

Matched MeSH terms: Scrub Typhus*
An approach to treatment and illustrative cases including a case of Japanese river fever treated with stabilarsan (Boots) and lumbar puncture

Dunlop GA

Malayan Medical Journal, 1928;3:107-12.

Matched MeSH terms: Scrub Typhus
THE INDIRECT FLUORESCENT ANTIBODY TECHNIQUE IN SCRUB TYPHUS STUDIES

ELLISON DW, BAKER HJ

Med J Malaysia, 1964 Sep;19:65-6.
PMID: 14244224
Matched MeSH terms: Scrub Typhus*
Fulltext Antibiotics for treating scrub typhus

El Sayed I, Liu Q, Wee I, Hine P

Cochrane Database Syst Rev, 2018 09 24;9:CD002150.
PMID: 30246875 DOI: 10.1002/14651858.CD002150.pub2

BACKGROUND: Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.
OBJECTIVES: To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.
SEARCH METHODS: We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.
SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).
DATA COLLECTION AND ANALYSIS: For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.
MAIN RESULTS: We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.
AUTHORS' CONCLUSIONS: Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

Matched MeSH terms: Scrub Typhus/drug therapy*
Screening and genotyping of Orientia tsutsugamushi from field-collected on-host chiggers (Acari: Prostigmata) recovered from a positive scrub typhus locality in Kelantan, Malaysia

Ernieenor FCL, NorJaiza MJ, Fadillah A, Canedy J, Mariana A

Exp Appl Acarol, 2021 May;84(1):171-182.
PMID: 33826009 DOI: 10.1007/s10493-021-00609-3

Orientia tsutsugamushi is the causative agent of scrub typhus vectored by larval stages of trombiculid mites (chiggers) that occur in most tropical regions of Southeast Asia. A total of 242 chiggers extracted from eight small mammals captured from a positive scrub typhus locality in Kelantan, Malaysia, were screened for the presence of O. tsutsugamushi. The chiggers were grouped in 16 pools for extraction of DNA prior to screening of O. tsutsugamushi based on the nucleotide sequence of 56-kDa type specific antigen (TSA) gene using nested polymerase chain reaction. Two species of on-host chiggers were identified, the one, Leptotrombidium deliense, much more dominant (94.8%) than the other, Ascoshoengastia sp. (5.2%). The pathogen was detected in two pools (12.5%) of L. deliense recovered from Rattus rattus and Tupaia sp. The 56-kDa TSA gene sequence analysis revealed the O. tsutsugamushi harboured in those chiggers were Karp prototype strain with high similarity (99.3%). Findings of this study strongly supported the existence of scrub typhus infections in certain parts of Malaysia which agrees with previous local reports. Moreover, this study highlighted the pressing need of a large-scale close observation of O. tsutsugamushi DNA sequences from chiggers that can probably be collected from other positive scrub typhus localities to precisely provide the distribution and prevalence of this zoonotic pathogen.

Matched MeSH terms: Scrub Typhus*
Tropical typhus in the Federated Malay States [duplicate2]

Fletcher W, Lesslar JE

Malayan Medical Journal, 1926;1:17-22.

Matched MeSH terms: Scrub Typhus
The tsutsugamushi disease in the Federated Malay States

Fletcher W, Field JW

Bull Inst Med Res Kuala Lumpur, 1927.

Matched MeSH terms: Scrub Typhus
Tropical typhus in the Federated Malay States [duplicate1]

Fletcher W

Bull Inst Med Res Kuala Lumpur, 1925.

Matched MeSH terms: Scrub Typhus
The Weil-Felix reaction in sporadic tropical typhus

Fletcher W, Lesslar JE

Bull Inst Med Res Kuala Lumpur, 1926.

Matched MeSH terms: Scrub Typhus
The aetiology of the tsutsugamushi disease and tropical typhus in the Federated Malay States. Part II

Fletcher W, Lesslar JE, Lewthwaite R

Trans R Soc Trop Med Hyg, 1929;23:57-70.
DOI: 10.1016/S0035-9203(29)90849-X

Tropical typhus bears a close clinical resemblance to mild typhus fever, but it does not spread from man to man, nor does it give rise to epidemics. Lice are not the vectors of the virus. There are two kinds of tropical typhus, the W. form and the K. form. In the W. form, the serum agglutinates the ordinary strains of B. proteus X. 19, and Wilson's B. agglutinabilis, but it does not agglutinate the non-indologenic strain, Kingsbury. In the K. form the serum agglutinates the non-indologenic strain, Kingsbury, but it does not agglutinate the ordinary strains of B. proteus X. 19, or B. agglutinabilis.
The W. form of tropical typhus is a disease of the house and the town; the majority of those affected are indoor workers, such as clerks and shopkeepers, particularly those who deal with foodstuffs. MAXCY has found that the " endemic typhus " or Brill's disease of the United States, which is clinically identical with tropical typhus, has a similar distribution. The like is true of the typhus-like fever described by HONE in Australia which is probably the same disease as the W. form of tropical typhus.
The distribution of the K. form is very different, it is essentially a disease of the open country and affects outdoor workers. It has a patchy distribution and outbreaks occur particularly in areas which, after being cleared of jungle, are allowed to grow up in weeds and scrub. For this reason, we propose the name scrub-typhus for the K. form of tropical typhus. Some of the cases of typhus-like diseases described in India are probably the same as scrub-typhus.
An account is given of an outbreak of sixty-one cases of scrub-typhus on an oil-palm estate where cases of the tsutsugamushi disease had occurred among the European staff. This outbreak illustrates the limited distribution of the disease. Five adjacent estates, served by the same hospital, were unaffected, and the outbreak was confined almost entirely to one of the three Divisions of the oil-palm estate. This Division differed from the other two in being overrun with weeds and undergrowth, with which scrub-typhus is always associated. An attack appears to confer immunity. The cases occurred among the newly recruited labourers, those who had been on the estate for a long time escaped infection. Coolies recruited in the Federated Malay States were as susceptible as those from India, from which it appears that the Indian population of Malaya has not been generally exposed to infection. The outbreak consisted entirely of the K. form of tropical typhus (scrub-typhus); there were no cases of the W. form (? endemic typhus).
Attention is drawn to the relationship of scrub-typhus and the tsutsugamushi disease by the occurrence of the latter on the same estate. The tsutsugamushi disease of the East Indies and scrub-typhus both occur in circumscribed areas which are covered with undergrowth, and their symptoms are much alike There are, however, the following points of distinction : (a) The fever of tsutsugamushi does not end abruptly at the end of the second week as it does in scrub-typhus, nor is convalescence so rapid. (b) A primary sore and bubo are present in tsutsugamushi, but absent in scrub-typhus. (c) The titre of agglutination with B. proteus, Kingsbury, is low in the tsutsugamushi disease but very high in scrub-typhus. In some cases of the tsutsugamushi disease, the serum agglutinates B. proteus, Kingsbury, in higher dilutions than that of normal persons, but not to titres nearly so high as in scrub-typhus.
It is suggested that the two diseases have a similar ~etiology and that scrubtyphus, like the tsutsugamushi disease, is carried by trombiculae.

Matched MeSH terms: Scrub Typhus