Melioidosis: acute and chronic disease, relapse and re-activation

Abstract

In melioidosis-endemic regions the importance of re-activation of Burkholderia pseudomallei from latent foci remains unclear. This topic was assessed in a 10-year prospective study (1989-99) of melioidosis in the tropical north of the Northern Territory of Australia, together with other aspects of the nature of melioidosis. Incubation period from defined inoculating events was previously ascertained as 1-21 (mean 9) days. Of 252 total cases 244 (97%) were considered to be from recent acquisition of B. pseudomallei infection and 8 (3%) were considered to be re-activation from a latent focus. Acute illness occurred in 222 (88%) cases; 30 (12%) cases had chronic illness (symptomatic for > 2 months). Of the 207 patients surviving the initial illness, 27 (13%) had a confirmed relapse (mean time from initial diagnosis of 8 months), with 5 relapsing twice. Of these 32 relapses, 15 (3 fatal) were associated with poor adherence to the eradication therapy antibiotics and 10 (none fatal) were failures of eradication with doxycycline monotherapy. Following initial intensive therapy with ceftazidime or meropenem for at least 14 days, eradication therapy with trimethoprim-sulphamethoxazole monotherapy for at least 3 months had been more successful.

Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B. thailandensis and B. mallei

“…The chronic form of the disease is evident from discovery at autopsy or by subsequent activation causing other forms of the disease. It is known that B. pseudomallei can enter a dormant state following initial infection or recovery from clinical disease [3], and that dormant cells can be triggered, leading to relapse or the onset of acute melioidosis [4]. The mechanisms underlying these different clinical manifestations and the triggers causing the more serious forms of the disease are poorly understood.…”

Outcomes of Patients with Melioidosis Treated with Cotrimoxazole Alone for Eradication Therapy

“…3,4 Earlier studies indicated that 13-23% of patients with melioidosis had such a recurrence and as high as onefifth of these recurrences could be fatal. 4,5 However, the choice and duration of antibiotic treatment to prevent these recurrences remains unsettled, as evidenced by several different regimen reported in the literatures during the last two decades. 5,8,[10][11][12]14 The currently recommended eradication therapy with the combination of cotrimoxazole and doxycycline, given for 12-20 weeks, has decreased the 1-year recurrence rate of culture-proven melioidosis to~6%.…”

“…4,5 However, the choice and duration of antibiotic treatment to prevent these recurrences remains unsettled, as evidenced by several different regimen reported in the literatures during the last two decades. 5,8,[10][11][12]14 The currently recommended eradication therapy with the combination of cotrimoxazole and doxycycline, given for 12-20 weeks, has decreased the 1-year recurrence rate of culture-proven melioidosis to~6%. 8 In our study, the 5% recurrence rates in patients who had received this combination regimen drugs is comparable to that of the original clinical trial and the 3.2% culture-proven recurrence rate in recipients of cotrimoxazole alone is quite low.…”

“…9 Furthermore, 19% of the patients had to switch treatment because of adverse drug events from the three drugs. 8 Because poor adherence to treatment are associated with recurrence of the disease, 5 other less toxic, alternative eradication regimens including amoxicillin-clavulanate with supplemental amoxicillin, quinolone monotherapy, and a combination of azithromycin and ciprofloxacin, have been tried. [10][11][12] However, all these regimens were associated with recurrence rates exceeding 15% and another simple but more effective regimen is needed.…”

“…[10][11][12] Cotrimoxazole alone had been successfully used to treat an acute form of melioidosis in the Philippines and is used for eradication therapy in Australia. 5,13 However, there are no published studies that have compared the effectiveness and side-effect profile of cotrimoxazole monotherapy with that of the co-trimoxazole plus doxycycline for the eradication treatment of this condition. In this report, we present such a study.…”