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.
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.
Using an indirect immunofluorescence technique, sera from 113 cynomolgus monkeys (Macaca fascicularis), trapped in Peninsular Malaysia, were screened for the presence of antibody to six prototype strains of Rickettsia tsutsugamushi combined into three polyvalent groupings: I--Karp, TA716, and TA763; II--Gilliam; and III--TA678 and TH1817. Fifteen percent (17/113) of the monkeys had antibody titers greater than or equal to 1:50 to one or more of the antigenic groups. Although a titer greater than or equal to 1:150 is generally considered indicative or prior Rickettsia tsutsugamushi infection, we selected a less than 1:25 titer as a conservative standard to insure non-infected animals. Using this criterion, 62 (55%) of the 113 monkeys were accepted for use in scrub typhus studies. The high prevalence of antibody to scrub typhus in the semi-arboreal cynomolgus monkey is in marked contrast to the low prevalence reported in the strictly arboreal silvered leaf monkeys (Presbytis cristatus). The results of this study indicate that cynomolgus monkeys should be rigorously screened for evidence of prior infection before they are included in experimental scrub typhus studies.
Fifty-one Rickettsia tsutsugamushi isolates from small mammals collected in central Peninsular Malaysia serologically characterized by direct immunofluorescence using eight prototype strains. Karp-related (TA763, TA686, TA716) antigens were found in 90.2% of the isolates.
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.
One hundred and fourteen Rickettsia tsutsugamushi isolates, recovered from febrile patients in central Peninsular Malaysia, were antigenically analyzed by direct immunofluorescence using eight prototype strains. Twenty-nine antigenic types were detected. The TA763, TA716, Karp and TA686 strains were the most common and occurred singly or in combination with each other or other strains in 86% of the isolates.
Dog sera, collected from different communities throughout Selangor, Peninsular Malaysia, were investigated for the presence of antibodies to R. tsutsugamushi and R. typhi. Scrub typhus antibodies were present in animals from the rural areas only, whereas murine typhus antibodies were observed in equal numbers of dogs from both rural and metropolitan areas. Greater percentage of dogs from suburban areas had demonstrable antibody titers to murine typhus than from the urban area.
Serological surveillance for up to two years of 114 patients with laboratory confirmed scrub typhus showed that antibody to Rickettsia tsutsugamushi as demonstrated by the indirect fluorescent antibody test is short-lived. The mean reversion time from mean peak titre (1:499) was 48.9 weeks and the calculated annual reversion rate to a titre less than 1:50 was 61%. This can be used to estimate attack rates based on point prevalence of antibody. The relationship between antibody prevalence and attack rates observed by other workers was confirmed using this model. The possible uses of the finding and its implications in Malaysia are briefly discussed.
An epidemiological study in a mature oil palm estate in Peninsular Malaysia has demonstrated a low prevalence of R. tsutsugamushi infection in small mammals. The direct fluorescent antibody technique for assaying infections in chiggers proved more sensitive than mouse inoculation. Most infections in both chiggers and rodents were caused by the Karp strain.
A high prevalence of murine typhus was found in the human and rodent populations of Senaling, West Malaysia. In addition to 2 index cases which prompted the investigation, 45% of the humans and 35% of the rodents had IFA titers of 1/50 or greater. Serological studies provided evidence of recent infections in 3 human subjects. In a control group of Malaysian soldiers IFA titers of 1/50 or greater were found in only 13 (5%) of 265 sera tested.
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.