This case come from Dr Sally Singleton, Broome ED JMO, who is currently studying her diploma in Tropical Med.
A 43 year old Burmese male was transferred to our hospital from an Australian customs ship. Three days earlier, he and his fellow asylum seekers had been found off the North-West Australian coast. They were in an overcrowded boat that they had boarded following the wreckage of their first ship from Malaysia, one to two weeks previously, on an unknown Island. In total he estimated he had been at sea for one month, with minimal oral intake in this time due to a combination of limited supplies and severe sea sickness.
He was initially seen by the doctor of the customs ship for a general check up and reported symptoms including a dry cough, night sweats associated with fever, headaches and loss of weight. On examination he was febrile (>38oC), tachycardic and had five lesions, which were described as ulcers, on his lower back and buttocks.
He was treated with an empiric dose of doxycycline 200 mg and commenced on oral combination amoxicillin and clavulanic acid. A BinaxNOW malaria test was negative. On review the next day, he experienced ongoing fevers (>38oC) and was commenced on intravenous dicloxacillin and gentamicin in addition to continuing daily oral doxycycline 100 mg. This regimen was continued for 24 hours until he was transferred to our care.
He arrived to us on day three of his treatment with doxycycline and reported via an interpreter to feel generally better in himself, compared with three days earlier. He reported no known past medical problems. On arrival he was afebrile and haemodynamically stable. He had five sloughy sores with surrounding erythema on his lower back and buttocks and palpable axillary lymph nodes. He was admitted for ongoing management, including nutritional support, and all antibiotics were ceased awaiting further results. Investigations were ordered in consultation with the infectious diseases unit at a tertiary hospital.
What investigations would you do?
Investigation Results :
Full Blood Examination Hb 128 (135-180), MCV 71 (80-100), MCH 22.1 (27-32) WCC, neutrophils, eosinophils and lymphocytes within normal limits
Urea and electrolytes Within normal limits
Calcium, magnesium, phosphate Within normal limits
Liver function tests Albumin 27 (35-50) ALP 174 (35-135) ALT 71 (<40) GGT 157 (<60)
C reactive protein 46 (<5)
Iron, Folate and B12 studies Fe 16 (9-30), transferrin 13 (23-43), ferritin 1230 (30-620)
Peripheral blood smear Malaria thick and thin films and P.falciparum antigen screening negative
Hepatitis A, B, C serology Hepatitis A IgG positive All else negative HIV and syphilis serology
Negative Urine for microscopy and culture and Chlamydia and Gonorrhoea PCR
No abnormality detected Stool for microscopy and culture No abnormality detected
Rickettsia serology* R.typhi IFA 256 R.conorii IFA <128 O.tsutsugamushi IFA >1024 Arbovirus serology
Sputum for microscopy, culture and acid fast bacilli = Klebsiella pneumoniae, resistant to amoxicillin and sensitive to ciprofloxacin, cotrimoxazole and gentamicin Acid fast bacilli not seen
Chest X-Ray Reported as normal
Wound swab (of lesions on back) for microscopy and culture Staphylococcus aureus sensitive to flucloxacillin
Diagnosis / discussion
Diagnosis of scrub typhus Clinical and laboratory features of scrub typhus are non-specific (1, 4). An eschar is a useful diagnostic clue, however this is less useful in areas where medical practitioners have limited experience or exposure to seeing them. The confirmatory test of choice is IFA, which detects scrub typhus-specific antibodies bound to smears of scrub typhus antigen (13). Other less accurate methodologies in use include indirect immunoperoxidase and Weil-Felix assays. An accurate dot blot immunoassay is available, but cost factors are limiting its use in resource-poor settings. Choice of positive titre cut off points varies between countries, limiting comparison of seroprevalence rates between studies. A review of 123 studies found that the diagnosis of scrub typhus should be based on a greater than four-fold increase in the IFA titre in paired serum samples. The review recommended that the diagnosis should only be based on a single sample titre when there is adequate local evidence base (13). It further acknowledged the difficulties in determining relevant seroprevalence levels based on potential past exposures of an individual compared with the levels in the general population of a locality. The authors also noted that in practice, diagnosis is usually made on the basis of a single serological sample. In our case, it is presumed that the patient had exposure to the chigger in Malaysia, or possibly on the island where he was temporarily stranded (details around location and circumstances of the time spent on this island are unfortunately limited). We also only have limited details of where the patient has previously lived – possibly a combination of time in areas of Myanmar (Burma) and most recently Malaysia. Therefore, it would be ideal to repeat serum specimens for IFA two weeks later to confirm diagnosis. However, it could be argued that this is an academic exercise, given a reasonable response to presumptive treatment and no anticipated change in management based on repeat serology. A study between 1995 and 1997 in rural Malaysia using indirect immunoperoxidase assay found antibodies to O.tsutsugamushi in 24.9% of 1596 febrile patients. However, the amount of serological cross-reactivity was unclear, with only 4.3% of the patients showing positive antibodies to O.tsutsugamushi alone. Prevalence also varied according to occupation; scrub typhus was more likely in those working in agriculture (5).
Treatment
Trials on treatment of scrub typhus have mainly focussed on mild to moderate disease. A Cochrane review in 2010 reported limited data, which was based on small trials only. However, in the data available, there were no obvious differences in efficacy between tetracycline, doxycycline or azithromycin (15). They concluded that rifampicin may be superior to doxycycline in areas where scrub typhus responds poorly to standard anti-rickettsial drugs. Drug resistance is of particular concern in Northern Thailand (16). Although doxycycline is associated with more side effects, it is one third the price of a course of azithromycin on a global scale (16, 17). There are data to support the role of weekly doses of 200 mg doxycycline for chemoprophylaxis. Interestingly, the efficacy of daily malarial doxycycline chemoprophylaxis against scrub typhus is unknown, with case reports of other rickettsial diseases in travellers using daily tetracycline malaria prophylaxis (1, 3). There is currently no vaccine available. Therefore, the best prevention is to avoid high-risk environments, and to use protective clothing and topical repellents if travel or work in these environments is required.
If you want to see Dr Sally Singleton’s whole discussion and references Click here
