Imported melioidosis--South Florida, 2005

In 2005, two cases of melioidosis (one in August, one in October) were reported to the Florida Department of Health, the first cases since reporting the disease became mandatory in Florida in 2003. In one case, Burkholderia pseudomallei was not recognized as the bacterium that causes the disease melioidosis, which led to a delay in reporting the case to the local health department. In both cases, delayed recognition and unsafe laboratory practices resulted in laboratory workers being exposed to B. pseudomallei. This report summarizes the clinical and laboratory aspects of the cases and the epidemiologic study conducted by the Florida Department of Health. The findings emphasize the need for improved laboratory recognition and reporting of B. pseudomallei, safe laboratory handling of B. pseudomallei, and close adherence to antibiotic regimens for treating and preventing recurrence of melioidosis.     

The use of bone marrow culture for the diagnosis of melioidosis

We have evaluated prospectively the contribution of bone marrow culture to the diagnosis of melioidosis. Bone marrow (BMC) and blood cultures (BC) were collected concurrently from 105 patients with suspected acute, severe melioidosis. 67 patients were subsequently proved to have the disease whilst other significant organisms were isolated from these specimens in 5 cases. Overall, 67.2% of BC and 64.2% of BMC from melioidosis patients grew Pseudomonas pseudomallei. Time to positivity did not differ significantly in paired BC and BMC specimens. These results do not support the routine use of BMC in the diagnosis of acute, severe melioidosis. In one patient with pulmonary melioidosis, however, blood cultures were repeatedly negative, whilst bone marrow grew P. pseudomallei, and this preceded the development of a distant focus of infection. This suggests that culture of bone-marrow may be of value in certain blood culture-negative patients with melioidosis.     

Management of accidental laboratory exposure to Burkholderia pseudomallei and B. mallei

The gram-negative bacillus Burkholderia pseudomallei is a saprophyte and the cause of melioidosis. Natural infection is most commonly reported in northeast Thailand and northern Australia but also occurs in other parts of Asia, South America, and the Caribbean. Melioidosis develops after bacterial inoculation or inhalation, often in relation to occupational exposure in areas where the disease is endemic. Clinical infection has a peak incidence between the fourth and fifth decades; with diabetes mellitus, excess alcohol consumption, chronic renal failure, and chronic lung disease acting as independent risk factors. Most affected adults ( approximately 80%) in northeast Thailand, northern Australia, and Malaysia have >/=1 underlying diseases. Symptoms of melioidosis may be exhibited many years after exposure, commonly in association with an alteration in immune status. Manifestations of disease are extremely broad ranging and form a spectrum from rapidly life-threatening sepsis to chronic low-grade infection. A common clinical picture is that of sepsis associated with bacterial dissemination to distant sites, frequently causing concomitant pneumonia and liver and splenic abscesses. Infection may also occur in bone, joints, skin, soft tissue, or the prostate. The clinical symptoms of melioidosis mimic those of many other diseases; thus, differentiating between melioidosis and other acute and chronic bacterial infections, including tuberculosis, is often impossible. Confirmation of the diagnosis relies on good practices for specimen collection, laboratory culture, and isolation of B. pseudomallei. The overall mortality rate of infected persons is 50% in northeast Thailand (35% in children) and 19% in Australia.     

35例类鼻疽病例临床特点分析

目的分析类鼻疽的临床特点,并探讨其诊断及治疗的方法。方法回顾性分析某院2012年3月—2017年2月收治的有明确病原学依据的35例类鼻疽患者。结果 35例类鼻疽患者在入院时2例(5.7%)因有外院培养结果而确诊,3例(8.6%)高度疑似患者主要有相对典型的临床特点,误诊30例(85.7%),疑似患者入院后均经各种标本培养检出类鼻疽伯克霍尔德菌确诊;采用抗感染、外科穿刺引流(11.4%)及手术(20.0%)治疗,病情好转或痊愈26例(74.3%),放弃治疗2例(5.7%),死亡7例(20.0%)。临床首发症状以发热(88.6%)最常见,其次为咳嗽(34.3%)、气促(28.6%)、腹痛(14.6%)、上下肢痛(11.4%)、关节痛(5.7%);感染部位居前五位的分别为血液(85.7%)、肺(54.3%)、脾(20.0%)、皮肤软组织(20.0%)、肝(14.3%);以血培养出类鼻疽伯克霍尔德菌最为常见,占85.7%,其次为各种穿刺液(37.1%)、痰(20.0%)。结论类鼻疽的临床特点复杂多样,误诊率高,早期确诊和及时、合理、足疗程的治疗可降低病死率和复发率。     

Neurotropic Threat Characterization of Burkholderia pseudomallei Strains

The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989–October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.     

Amoxycillin-clavulanic acid treatment of melioidosis.

Melioidosis is a serious infection with high acute mortality, and a high rate of relapse despite protracted antimicrobial treatment. The current recommended conventional oral treatment regimen is a 4-drug combination of high-dose chloramphenicol, doxycycline and trimethoprim-sulphamethoxazole given for between 6 weeks and 6 months. We have evaluated prospectively the use of amoxycillin-clavulanic acid, to which Pseudomonas pseudomallei is consistently sensitive in vitro, for the oral maintenance treatment of melioidosis. Amoxycillin-clavulanic acid was used either as sole treatment of localized disease, or as maintenance therapy following either parenteral ceftazidime or the conventional 4-drug regime; 20 patients with localized infections and 26 with septicaemic melioidosis received a median of 7.5 (2-12) weeks treatment. After a mean follow-up period of 6 months (range 1-19), 31 patients (67%) remain free of disease. The drug was well tolerated. Three patients had fatal relapses, one other died suddenly at home, and another died from underlying promyelocytic leukaemia. The remaining 10 relapses were treated successfully. Resistance developed in one case. Amoxycillin-clavulanic acid is a safe alternative to the conventional 4-drug antimicrobial combination for the oral treatment of melioidosis. It may be of particular value in children, pregnant women, and in infections with Ps. pseudomallei resistant to the potentially toxic conventional regimen, but the optimum dose and duration of therapy need to be established.     

Preliminary report on the northern Australian melioidosis environmental surveillance project

An environmental surveillance programme was developed to determine whether water supplies could be a source of Burkholderia pseudomallei as noted during previous melioidosis outbreak investigations. Water supplies to communities in the three northern Australian jurisdictions (Western Australia, Northern Territory and Queensland) were sampled periodically during 2001 and 2002. Water and soil samples were collected from communities known to have had recent culture-positive melioidosis cases and nearby communities where no cases had been diagnosed. Clinical isolates of B. pseudomallei obtained from northern Australian patients during 2001 and 2002 were compared with the environmental B. pseudomallei isolates by ribotyping and pulsed-field gel electrophoresis. B. pseudomallei was isolated from 11 distinct locations, all in the Northern Territory, seven of which were associated with culture-positive melioidosis cases (>1 case at three locations). Water was implicated as a possible environmental source of melioidosis in six locations. A variety of free-living amoebae including Acanthamoeba and Hartmannella spp. that are potential hosts to B. pseudomallei were recovered from environmental specimens. Culturable B. pseudomallei was not found to be widely dispersed in the environments sampled.     

Melioidosis outbreak after typhoon, southern Taiwan

From July through September 2005, shortly after a typhoon, 40 cases of Burkholderia pseudomallei infection (melioidosis) were identified in southern Taiwan. Two genotypes that had been present in 2000 were identified by pulsed-field gel electrophoresis. Such a case cluster confirms that melioidosis is endemic to Taiwan.     

Cerebral melioidosis in Singapore: a review of five cases

A variety of neurological manifestations of infection with Burkholderia pseudomallei have been described including cerebral abscesses, which are a well-recognized form of neurological melioidosis. The optimal antibiotic therapy for this condition has not been defined; however, combinations of intravenous antibiotics are frequently used in the early stages. Five cases of melioidosis involving brain abscesses are described which presented in Singapore over the past 3 years (1997-2000), 4 of which cases had evidence of disseminated infection. Despite profound neurological deficits and low Glasgow Coma Scale scores at presentation in 3 of these cases, all survived after surgical drainage and prolonged courses of intravenous ceftazidime or imipenem, and only 2 of whom had residual neurological impairment. One incidental finding on computed tomography (CT) or magnetic resonance imaging (MRI) scans not described before as an association with cerebral melioidosis was sinusitis in 4 out of the 5 cases.     

Acute melioidosis outbreak in Western Australia

A cluster of acute melioidosis cases occurred in a remote, coastal community in tropical Western Australia. Molecular typing of Burkholderia pseudomallei isolates from culture-confirmed cases and suspected environmental sources by pulsed-field gel electrophoresis (PFGE) of XbaI chromosomal DNA digests showed that a single PFGE type was responsible for five cases of acute infection in a community of around 300 during a 5 week period. This temporal and geographical clustering of acute melioidosis cases provided a unique opportunity to investigate the environmental factors contributing to this disease. B. pseudomallei isolated from a domestic tap at the home of an asymptomatic seroconverter was indistinguishable by PFGE. Possible contributing environmental factors included an unusually acid communal water supply, unrecordable chlorine levels during the probable exposure period, a nearby earth tremor, and gusting winds during the installation of new water and electricity supplies. The possible role of the potable water supply as a source of B. pseudomallei was investigated further.     

Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong

A serological survey of 275 Chinese patients with underlying pulmonary diseases in a tuberculosis sanatorium in Hong Kong showed that 39 (14%) had haemagglutinating antibody (HA) against Pseudomonas pseudomallei in a titre of 1: 80 or above. Only 9 of these 39 patients had travelled to endemic areas, suggesting that at least 30 patients (11%) had been exposed to Ps. pseudomallei locally. Females are affected as often as males, and the seropositive rate is the same whether patients are immunosuppressed or not. Because subclinical melioidosis is prevalent and HA may persist for a long time, even at a high titre, after infection, determination of HA alone cannot differentiate between active melioidosis and its masquerade--active tuberculosis.     

基于人为因素实验室获得性感染风险与生物安全应对策略

病原微生物实验室生物安全通常强调使用保护设备、程序和操作规范来保护人员和环境免受潜在危险生物材料的影响。实验室获得性感染是实验室人员安全的主要威胁,会导致疾病、残疾甚至死亡;病原微生物还可能被携带到周围环境,造成社区感染,应当受到重视。研究分析实验室获得性感染案例有助于了解暴露发生的原因,明确暴露后预防和应对措施的潜在风险,进而维护生物安全。随着设备和基础设施的优化,人为因素所导致的实验室获得性感染趋于增加。与气溶胶化和液滴飞溅、锐器材料有关的实验室活动、执行工作人员的生物安全素质能力、实验室设施和管理4种主要因素密切相关。本研究从导致实验室获得性感染的人为因素出发,探讨病原微生物实验室的生物安全风险,回顾实验室生物安全的发展演变,以及目前对实验人员的保护措施,并据此提出应对策略和建议。     

Pseudomonas pseudomallei isolates collected over 25 years from a non-tropical endemic focus show clonality on the basis of ribotyping.

Between 1966 and 1991, melioidosis, a disease caused by Pseudomonas pseudomallei that is mostly confined to tropical regions, occurred in farm animals and a farmer in temperate south-west Western Australia. Using an Escherichia coli probe containing a ribosomal RNA operon, P. pseudomallei DNA from isolates from 8 animals, a soil sample and the human case showed an identical ribotype on Southern blotting. The ribotype was different from the 3 commonest ribotypes seen in tropical Australia. This molecular typing supports the theory of clonal introduction of P. pseudomallei into a non-endemic region, with environmental contamination, local dissemination and persistence over 25 years. As melioidosis is often fatal in humans, such persistence in a temperate region is cause for concern.     

Advances and remaining uncertainties in the epidemiology of Burkholderia pseudomallei and melioidosis

Major advances have been made in molecular studies of Burkholderia pseudomallei and the immunology of melioidosis. However, there remain large gaps in understanding of the epidemiology of this enigmatic disease. Identified global distribution boundaries of melioidosis continue to expand. Recent data suggest Australian strains of B. pseudomallei may be ancestral to those from Southeast Asia, but the ecology of this environmental bacterium remains elusive. Despite the potential for rapidly progressive septicaemia, the critical virulence factors in B. pseudomallei remain to be clarified. Inhalation following aerosolization of B. pseudomallei may account for the high mortality when melioidosis occurs after severe weather events.     

A proposed scoring system for predicting mortality in melioidosis

Melioidosis, due to infection with the environmental organism Burkholderia pseudomallei, continues to be associated with high mortality despite improvements in antibiotic therapy. Using simple clinical findings and baseline laboratory tests available at the time of admission, we attempted to define those patients with acute melioidosis who were at higher risk of death. Using data, collected prospectively from the period October 1989 to June 2002, from patients with acute culture-confirmed melioidosis presenting at the Royal Darwin Hospital, Darwin, Australia, a number of variables were selected that were easily available at the time of admission and reflected organ dysfunction. Mortality was predicted in univariate logistic and multivariate models by the presence of pneumonia, age at diagnosis, serum urea, serum bilirubin, lymphocyte count, and serum bicarbonate. A score was assigned from 0 to 2, based on the degree of abnormality. A melioidosis score was formed from the sum of these scores, with a maximum score of 11. A score of < or = 3 (n = 140) was associated with a mortality of 8.6%, whereas a score of > or = 4 (n = 112) was associated with a mortality of 44.6%. Although this scoring system requires external validation, it may help identify a suitable target group of patients for intensive intervention such as early admission to an intensive care unit, the early use of meropenem, and goal-directed resuscitation therapies.     

Sudden unexplained death syndrome--a new manifestation in melioidosis?

The indirect haemagglutination (IHA) test using sensitized turkey erythrocytes and the indirect immunofluorescence assay (IgM-IFA) was confirmed to be sensitive in the detection of a recent or current Pseudomonas pseudomallei infection in 19 culture-confirmed Singapore melioidosis patients. All were found to have antibody titres from 4 to 32768 in the IHA test and 10 to 320 in the IgM-IFA test. When these tests were employed on sera from 16 immigrant Thai construction workers who died of sudden unexplained death syndrome (SUDS) and 73 healthy Thai fellow workers, 93.8% and 68.8% of SUDS cases had IHA titre of greater than or equal to 4 and IgM-IFA titre of greater than or equal to 10 respectively, in contrast to 39.7% and 12.3% found among healthy Thai workers. These data indicate that at the time of death, most of the SUDS patients had an active infection with P. pseudomallei, possibly resulting from reactivation of a latent infection. The aetiological role of P. pseudomallei as the major cause of SUDS is discussed.     

The epidemiology of melioidosis in the Balimo region of Papua New Guinea

The distribution of Burkholderia pseudomallei was determined in soil collected from a rural district in Papua New Guinea (PNG) where melioidosis had recently been described, predominately affecting children. In 274 samples, 2.6% tested culture-positive for B. pseudomallei. Pulsed-field gel electrophoresis using SpeI digests and rapid polymorphic DNA PCR with five primers demonstrated a single clone amongst clinical isolates and isolates cultured from the environment that was commonly used by children from whom the clinical isolates were derived. We concluded that individuals in this region most probably acquired the organism through close contact with the environment at these sites. Burkholderia thailandensis, a closely related Burkholderia sp. was isolated from 5.5% of samples tested, an observation similar to that of melioidosis-endemic areas in Thailand. This is the first report of an environmental reservoir for melioidosis in PNG and confirms the Balimo district in PNG as melioidosis endemic.     

Melioidosis, northeastern Brazil

Melioidosis was first recognized in northeastern Brazil in 2003. Confirmation of additional cases from the 2003 cluster in Ceará, more recent cases in other districts, environmental isolation of Burkholderia pseudomallei, molecular confirmation and typing results, and positive serosurveillance specimens indicate that melioidosis is more widespread in northeastern Brazil than previously thought.     

Laboratory exposure to Burkholderia pseudomallei--Los Angeles, California, 2003

On July 26, 2003, the Los Angeles County Department of Health Services (LACDHS) received a report that a local clinical laboratory had isolated from specimens Burkholderia pseudomallei, a category B biologic terrorism agent and the causative organism for melioidosis, which is endemic to certain tropical areas. Because laboratory workers had manipulated cultures of the organism, CDC was asked to assist in the subsequent investigation. This report summarizes the results of that investigation, which included assessment of laboratory exposures, postexposure chemoprophylaxis, and serologic testing of exposed laboratory workers. The findings underscore the need to reinforce proper laboratory practices and the potential benefits of chemoprophylaxis after laboratory exposures.     

Analysis of peptide mimotopes of Burkholderia pseudomallei exopolysaccharide

Previously two capsule-specific monoclonal antibodies (4VA5 and 3VIE5) were identified as protective against Burkholderia pseudomallei in passive transfer experiments. Panning these antibodies against evolutionary phage libraries identified reactive peptides capable of inhibiting its parent monoclonal from binding to B. pseudomallei. Mice immunized with peptide conjugated to thyroglobulin developed serum antibodies capable of recognizing the immunizing peptide of which a subset recognized exopolysaccharide in the context of whole B. pseudomallei cells. These serum antibodies recognized protease treated B. pseudomallei but not B. thailandensis suggesting that these peptides are mimotopes of the B. pseudomallei capsular exopolysaccharide. In a murine model of acute melioidosis, immunization with the mimotope of the 4VA5 binding site extended the mean time to death to 8.00 days over the 2.18 days afforded by immunization with thyroglobulin alone. This mimotope may be of use in developing an antibody response against B. pseudomallei exopolysaccharide.