Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Molecular characterization of rickettsial agents in ticks (Acari: Ixodidae) from Sri Lanka
    (Baltimore., 2022) Dasch, G.A.; Eremeeva, M.E.; Zambrano, M.L.; Premaratna, R.; Kularatne, S.A.M.; Rajapakse, R.P.V.J.
    Because the majority of spotted fever group rickettsiae are transmitted to humans by tick bites, it is important to understand which ticks might play a role in transmission of rickettsial pathogens in Sri Lanka. The purpose of our study was to conduct molecular surveillance of 847 ticks collected in different locations in central Sri Lanka to determine which were infected with Rickettsia and Anaplasmataceae. Molecular methods were used to identify the ticks and the agents detected. Most ticks (Amblyomma, Haemaphysalis, and Rhipicephalus) were collected by flagging, and lower number was collected from dogs, cattle, pigs, a pangolin, and tortoises. Five spotted fever genotypes were identified: a Rickettsia africae-like agent in Amblyomma larvae, Rhipicephalus massiliae and a related genotype identified in association with the tropical type of Rhipicephalus sanguineus from dogs and Rhipicephalus haemaphysaloides from dogs and cattle, and Candidatus R. kellyi and another novel genotype (SL94) in R. haemaphysaloides. Twenty-three ticks were positive for Anaplasmataceae, including one Anaplasma and two Ehrlichia genotypes. Because the sequence database for both ticks and rickettsial agents from Sri Lanka and southern India is not extensive, additional molecular characterization of the tick species of Sri Lanka and their rickettsial agents is required to understand their pathogenic potential more completely. However, several of the agents we identified in this survey may well be pathogenic for humans and domestic animals, and should be considered as a part of epidemiological surveillance and patient management.
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    Rickettsial infections and their clinical presentations in the Western Province of Sri Lanka: A hospital based study
    (American Society of Rickettsiology, 2007) Premaratna, R.; Loftis, A.D.; Chandrasena, T.G.A.N.; Dasch, G.A.; de Silva, H.J.
    Abstract Available
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    Etiology of fever of unknown origin in a selected group of Sri Lankan patients with prompt responses to Doxycycline
    (Centers for disease control and Prevention, 2008) Dasch, G.A.; Premaratna, R.; Rajapakse, R.P.; Chandrasena, T.G.A.N.; Eremeeva, M.E.; de Silva, H.J.
    BACKGROUND: Most patients with long duration of fever go undiagnosed in settings where diagnostic facilities are inadequate. Untreated rickettsial infections cause extended fevers; while both scrub typhus and tick typhus are re-emerging diseases in Sri Lanka, laboratory facilities to specifically diagnose rickettsial infections in Sri Lanka are not available. METHODS: We collected 2 ml venous blood from febrile patients who had no etiological diagnosis after 7 days of hospital admission, but who showed rapid clinical response to doxycycline, to verify whether they had experienced a rickettsial infection. Acute serum samples were analysed using IFA for rickettsial infections caused by Orientia tsutsugamushi, Rickettsia conorii and Rickettsia typhi. A positive IgG IFA titer >1:128 was used to define a probable case of rickettsial infection. RESULTS: 28 patients [15 males, mean age 32.5 (SD 9.2 yrs)] were studied. Mean duration of fever at admission was 6.1 days (SD 3.1). Two patients had features suggestive of encephalitis and two had erythema nodosum. Others had no specific clinical features. Routine investigations were inconclusive and blood cultures were negative. IgG-IFA titer of >128 was found in 10 for R. conorii, 6 for O. tsutsugamushi and 6 for both R. conorii and O. tsutsugamushi. None were positive for R. typhi. Six were negative for all tests. One patient with encephalitis and one with erythema nodosum had high titers for R. conorii. CONCLUSIONS: The majority of Sri Lankan patients with undiagnosed fever responding promptly to doxycycline had a rickettsial etiology. Patients with rickettsioses exhibit varied clinical presentations so greater use of doxycycline for patients with extended fevers in rickettsial-endemic settings with inadequate diagnostic facilities appears warranted. The high proportion of patients with tick typhus and antibodies against both spotted fever and scrub typhus rickettsiae was unexpected based on previous studies of patients from the same region who were confirmed to have scrub typhus by serology and by the presence of the classic eschar. It is unknown whether the etiology of tick typhus and vector(s) transmitting this agent on the Western lowland region of Sri Lanka are the same as those responsible for spotted fevers in the central hill country of Sri Lanka.
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    A descriptive study of 63 patients with rickettsial infections: reasons for delay in the diagnosis
    (Sri Lanka Medical Association, 2008) Premaratna, R.; Chandrasena, T.G.A.N.; Bailey, M.S.; Loftis, A.D.; Dasch, G.A.; de Silva, H.J.
    BACKGROUND: Most patients with rickettsial infections present to hospital as cases of "febrile illness of unknown origin". The delay in diagnosis may result in severe complications. Objectives: To determine reasons for the delay in diagnosis of rickettsial infections. DESIGN, SETTING AND METHODS: Patients admitted to the University Medical Unit, Colombo North Teaching Hospital, Ragama from November 2004 and diagnosed as having rickettsial infections and junior medical staff (JMS) were interviewed retrospectively to find possible reasons for delay in diagnosis. RESULTS: 63 patients [31 males; mean age 36 years (SD:12.2)] were recruited. (39 and 24 were later confirmed for Orientia tsutsugamushi, R. conorii infection byiFA titre >1:128) The mean duration of illness on admission was 9 days (SD:2.2). Clinical features on admission were fever 63(100%), headache 56(89%), lymphadenopathy 42(67%), eschar 42(67%), rash 12(19%), hepatomegaly 22(34%), splenomegaly 17(26%), deafness 6(9%), and tinnitus 8(12%). All 49 patients who could recall pre¬admission medication said they had not been given anti-rickettsial antibiotics. Interview of JMS (after-admission) showed that rickettsial infections were not considered in the differential diagnosis of 38(60%) patients. The other 25 were examined for an eschar: missed in 10(40%), detected in 9(36%) but not interpreted correctly in 7 of the 9 (63%). Rash was detected in all 12 patients who had it, but diagnosis was not considered in 10(83%). CONCLUSION: The main reasons for the delay in diagnosis seem to be lack of awareness of the high prevalence of rickettsial infections and poor knowledge of clinical features among junior medical staff.
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    Acute hearing loss in febrile patients: a predictor of scrub typhus
    (Sri Lanka Medical Association, 2005) Premaratna, R.; Chandrasena, T.G.A.N.; Dassanayake, A.S.; Loftis, A.; Dasch, G.A.; de Silva, H.J.
    INTRODUCTION: Rickettsial infections are re-emerging in Sri Lanka. Complications such as pneumonitis, myocarditis and encephalitis can occur late in the disease, and result in a high mortality. Early diagnosis reduces morbidity and mortality, but as laboratory facilities for definitive diagnosis are lacking, early diagnosis depends on clinical suspicion. Acute hearing loss which occurs in about 30% of patients has been recognised as a predictor of scrub typhus. METHODS: Six patients admitted to hospital with high fever and hearing impairment were further investigated. RESULTS: All were females with a mean age of 65 years (SD 2). The mean duration of fever at presentation was 12 days (SD 1), Hearing impairment was observe
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    Clinically helpful rickettsial disease diagnostic IgG titers in relation to duration of illness in an endemic setting in Sri Lanka
    (Biomed Central, 2012) Premaratna, R.; Weerasinghe, S.; Ranaweera, A.; Chandrasena, T.G.A.N.; Bandara, N.W.; Dasch, G.A.; de Silva, H.J.
    BACKGROUND: Although an initial IFA-IgG titer greater or equal to 1/64 or 1/128 is considered positive in presumptive diagnosis, in clinical practice in an endemic setting for rickettsioses in Sri Lanka, some patients with IFA-IgG titer of 1/128 for either spotted fever group (SFG) or scrub typhus (ST) did not respond to treatment. FINDINGS: To determine a clinically helpful diagnostic algorithm, IFA-IgG results of serologically confirmed treatment responders were analyzed in relation to duration of illness at sampling. Of 146 suspected SFG, 3 responders of 25 patients had titers ≤1/128 with < 7 days of illness while all 9 with titers ≥1/256 responded (false negative with 1/256 cutoff was 12%, false positive was 0%). For illness > 7 days, the false negative and positive rates were 4.3% (3/59) and 11.3% (6/53). Of 115 suspected ST, false negative and positive rates with ≥1/256 cutoff at <7 days of illness were 14.2% (2/14) and 0% (0/8) respectively while > 7 days, false negative and positive rates were 2% (1/51) and 0% (0/42). CONCLUSIONS: For clinical decision making, duration of illness at sampling is important in interpreting serology results in an endemic setting. If sample is obtained ≤7 day of illness, an IgG titer of ≤1/128 requires a follow up sample in the diagnosis and > 7 days of illness, a single ≥1/256 titer is diagnostic for all ST and 90% of SFG.
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    Contribution of rickettsioses in Sri Lankan patients with fever who responded to empirical doxycycline treatment
    (Oxford University Press, 2010) Premaratna, R.; Rajapakse, R.P.V.J.; Chandrasena, T.G.A.N.; Nanayakkara, D.M.; Bandara, N.K.B.K.R.G.W.; Kularatne, S.A.M.; Eremeeva, M.E.; Dasch, G.A.; de Silva, H.J.
    Twenty-eight febrile Sri Lankan patients with undiagnosed fever for 7 days after hospital admission, who responded to empirical treatment with doxycycline, were retrospectively investigated using microimmunofluorescence assay to verify whether they had rickettsial infection. Eleven (39%) patients were confirmed as having spotted fever group rickettsioses and 10 (36%) as having Orientia tsutsugamushi. Seven were negative for all tests. This suggests that greater use of doxycycline appears justified for patients with undiagnosed fever in settings where rickettsial diseases are endemic or re-emerging with inadequate diagnostic facilities.
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    Rickettsioses presenting as major joint arthritis and erythema nodosum: description of four patients
    (Springer International, 2009) Premaratna, R.; Chandrasena, T.G.A.N.; Rajapakse, R.P.V.J.; Eremeeva, M.E.; Dasch, G.A.; Bandara, N.K.B.K.R.G.W.; de Silva, H.J.
    Erythema nodosum and aseptic arthritis are recognized associations of rickettsial infections. However, they usually present with a febrile illness rather than with severe arthritis. We report three patients who presented with incapacitating major joint arthritis and one who presented with severe spondyloarthropathy in addition to major joint arthritis due to serologically confirmed Orientia tsutsugamushi and Rickettsia conorii infections. All of them had erythema nodosum and low-grade fever. They had rapid clinical response to doxycycline.
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    Rickettsial infections and their clinical presentations in the Western Province of Sri Lanka: a hospital-based study
    (Elsevier, 2008) Premaratna, R.; Loftis, A.D.; Chandrasena, T.G.A.N.; Dasch, G.A.; de Silva, H.J.
    BACKGROUND: Rickettsial infections are re-emerging. A study of the geographical distribution of rickettsial infections, their clinical manifestations, and their complications would facilitate early diagnosis.METHODS: Thirty-one selected patients from the Western Province of Sri Lanka were studied for rickettsial species, clinical manifestations, and complications. RESULTS: Of 31 patients with possible rickettsioses, 29 (94%) fell into the categories of confirmed, presumptive, or exposed cases of acute rickettsial infections (scrub typhus was diagnosed in 19 (66%), spotted fever group in eight (28%)). Early acute infection or past exposure was suggested in two (7%) cases; cross-reactivity of antigens or past exposure to one or more species was suggested in nine (31%). Seventeen out of 19 (89%) patients with scrub typhus had eschars. Nine out of 29 (32%) patients had a discrete erythematous papular rash: seven caused by spotted fever group, two by scrub typhus. Severe complications were pneumonitis in eight (28%), myocarditis in five (17%), deafness in four (14%), and tinnitus in two (7%). The mean duration of illness before onset of complications was 12.0 (SD 1.4) days. All patients except one made a good clinical recovery with doxycycline or a combination of doxycycline and chloramphenicol. CONCLUSIONS: In a region representing the low country wet zone of Sri Lanka, the main rickettsial agent seems to be Orientia tsutsugamushi. Delay in diagnosis may result in complications. All species responded well to current treatment
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    Acute hearing loss due to scrub typhus: a forgotten complication of a reemerging disease
    (Oxford University Press, 2006) Premaratna, R.; Chandrasena, T.G.A.N.; Dassanayake, A.S.; Loftis, A.D.; Dasch, G.A.; de Silva, H.J.
    We describe 6 patients with scrub typhus who presented with acute hearing loss, a forgotten complication of this reemerging disease. They were admitted with fever of 10-14 days' duration and had clinical evidence of deafness and pneumonitis. Five patients had eschars, which prompted the diagnosis of typhus fever and led to early institution of treatment. Deafness has been described as a clue to the diagnosis of scrub typhus; awareness of this symptom facilitated early diagnosis in 4 of 5 patients who recovered. Acute hearing loss or hearing impairment in a febrile patient should arouse strong suspicion of scrub typhus.
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