Two fatal cases of melioidosis on the Thai-Myanmar border

Presentation

Melioidosis, caused by Burkholderia pseudomallei, is endemic in areas of Southeast Asia. Published case reports from the Thai-Myanmar border are absent and the general belief is that meliodosis does not occur in this region. Presented below are two fatal case reports suggesting that meliodosis does in fact occur and may be under-recognized and not reported.

The first case of this series was a 17-year old female who presented with an intermittent fever for two months, more than 10% weight loss and confusion. She had been previously healthy. Her parents were farmers and the family lived in close proximity to the farm in eastern Myanmar along the Thailand border. On physical examination, her temperature was 40.1°C, pulse 130 bpm, respiration 28/min, and blood pressure 80/50 mmHg. In general, she was prostrate with conjunctival pallor. Her Glasgow Coma Score was 10/15. The cardiovascular and pulmonary exams were normal aside from tachycardia and tachypnea. Abdominal examination revealed a 1 cm liver and spleen. There were no other significant findings on clinical exam. Evidence from a random dextrose level test (432 mg/dL) and a urine dipstick was consistent with anorexia. A malaria smear showed Plasmodium vivax at a low parasitemia. Because of decreased consciousness, a lumbar puncture was performed and clear cerebrospinal fluid (CSF) was obtained. The CSF cell counts were normal and no organisms were grown after 48 hours of culture. Blood cultures were also sent. The patient was resuscitated with normal saline, given ceftriaxone 1 g intravenous BID and stabilized. Over the following two days, further laboratory results were obtained. A complete blood count (CBC) showed an elevated white blood count (WBC) at 13.5 10³/µL with a neutrophilia, hemoglobin (Hgb) 14.1 g/dL and a normal platelet count. Chest X-ray was abnormal with a left sided consolidation, cavitation on the right side and bilateral hilar lymphadenopathy. Sputum tested for acid fast bacilli was negative. Despite the addition of gentamicin 280 mg intravenous daily and oxygen, the patient deteriorated and died more than 8 weeks after the onset of symptoms. Admission blood cultures grew Burkholderia pseudomallei after one day of incubation.

The second case was a 45-year-old male who presented with fever and weakness for two days. He also complained of chills, rigors, cough and generalized body aches. He had a history of gastric ulcer and hypertension, neither of which were currently being treated. He was a rice farmer on the eastern border of Myanmar and Thailand and had continued to work until he fell ill. He was treated with ceftriaxone 1 g intravenous daily and metronidazole 500 mg oral TID by a village health worker. At this time a malaria smear was negative and other diagnostic testing was not performed. On the sixth day of illness he had still not improved and was sent to our clinic. At initial consultation, tympanic temperature was 36°C, pulse 76 bpm, respiration 20/min, and blood pressure 100/70 mmHg. His general appearance was weak but he was ambulatory with a Glasgow Coma Score of 15/15. He had icteric sclera and pale conjunctivae. The cardiovascular, pulmonary and abdominal exams were normal. On skin examination, a 3 cm lesion that appeared like a superficial abscess was noted on the right leg. Additional history revealed that this lesion had intermittently appeared and resolved over more than two years.

During his hospitalization, the patient developed congestive heart failure and pulmonary edema that improved with initial management. A random venous dextrose level was 110 mg/dL and field hematocrit 27%. A Urine dipstick result was abnormal with protein 2+ and blood 4+. Urine sediment was normal. Dengue rapid test was NS-1 negative, IgM and IgG positive (Standard Diagnostics, Inc, Kyonggi province, Korea). A scrub typhus rapid test for total antibody was positive (Standard Diagnostics, Inc). Stool test microscopy was negative and the stool sample was noted to be of black color. His CBC showed a Hgb 8.1 g/dL, WBC 26.2 10³/µL with a neutrophilia and normal platelets. Blood culture was negative. Biochemistry was sent to the district hospital, however, the results were not available immediately. His treatment regimen included cloxacillin 1 g intravenous QID, ceftriaxone 1 g intravenous daily, doxycycline 100 mg oral BID and furosemide 40 mg oral BID. Six days after admission the biochemistry results were returned and showed markedly abnormal renal function; blood urea nitrogen (BUN) 112.5 mg% and creatinine 15.4 mg%. He was diagnosed with chronic renal failure exacerbated by dengue and scrub typhus infections. After two weeks of hospitalization, the patient’s clinical condition deteriorated and he died despite prolonged broad antibiotic coverage. A second blood culture obtained one day prior to his death grew Burkholderia pseudomallei after one day of incubation.

Diagnosis

B. pseudomallei isolates from both cases were obtained using the BacT/Alert^® 3D automatic blood culture system (bioMérieux, Marcy L’Etoile, France). The isolate from case one was identified using the API 20NE test kit (bioMérieux) and confirmed with a B. pseudomallei latex agglutination test. The B. pseudomallei latex test, produced and provided by Mahidol Oxford Tropical Medicine Research Unit (MORU), is based on an anti-exopolysaccharide monoclonal antibody¹. The B. pseudomallei isolate from case two was identified using the B. pseudomallei latex test and then sent to MORU for confirmation. Susceptibility testing by disc diffusion was performed at SMRU for the first isolate and at MORU for the second (Table 1). Two colony morphologies were found for case 2; one, which was susceptible to meropenem, and one with intermediate susceptibility to meropenem (bioMérieux Etest minimum inhibitory concentration of 8 μg/mL).

Discussion

At the beginning of the 20^th century in Rangoon, Burma, Dr. Alfred Whitmore and his assistant Krishnaswami identified a new bacteria causing a “glanders-like illness” in humans. It was originally named Bacillus pseudomallei^2,3 and renamed as Burkholderia pseudomallei in 1992⁴. They proceeded to document over a hundred cases and the bacterium was isolated in over 5% of Rangoon’s autopsies at that time⁵. The disease, now termed melioidosis, was named by Stanton and Fletcher in 1932⁶ and is characterised by severe sepsis, pneumonia, abscess formation and is associated with a high mortality⁷. It has become an important public health concern across Southeast Asia and northern Australia. In this region, incidence rates vary between 1.1/100000 and 412.7/100000⁸, and Lao PDR has recorded 400 cases between 1999 and 2010^9,10. This variability may be explained by the geographical preference of B. pseudomallei for specific soils^11,12, the locations of the necessary containment level three laboratories for culture diagnosis⁷ and population risk factors that include occupation⁸ or medical conditions such as diabetes, renal failure and immunosuppressed states⁷. Little is known about the current disease burden in Myanmar and along its borders. Indeed the last published case report from within Myanmar was in 1945⁷. A recent serological survey of new Burmese migrants to Thailand revealed that 78% were seropositive for antibodies to B. pseudomallei¹³. This high seropositivity rate is supported by Aung et al who found that 2% of pus specimens obtained from abscesses from patients examined in Yangon, also known as Rangoon, Myanmar, contained organisms consistent with B. pseudomallei¹⁴.

The first case described here was a healthy young female and her only risk factor was environmental exposure. The elevated dextrose on admission was attributed to glycemic dysregulation rather than from new onset diabetes. Concurrent vivax malaria infection may have caused immunosuppression enabling sepsis with B. pseudomallei. The second case was a male with environmental exposure as well as undiagnosed chronic renal disease. The first blood culture was negative, however, concurrent infection with dengue and possibly scrub typhus (the rapid test used detects IgG, IgM and IgA as total Ab and cannot differentiate acute or resolved infection) may have caused worsening immunosuppression resulting in B. pseudomallei sepsis. Both cases had risk factors and concomitant infections.

Management

Antimicrobial therapeutic options for melioidosis are limited due to the intrinsic resistance of the organism. Current guidelines recommend parenteral ceftazidime 50 mg/kg up to 2 g every 6 hours or meropenem 25 mg/kg up to 1 g every 8 hours for at least 10–14 days (longer in severe or complicated cases) followed by oral co-trimoxazole plus doxycycline (first-line) or co-amoxiclavulanate alone (second-line) for 20 weeks. In these cases, ceftazidime or meropenem was not given due to the low suspicion for B. pseudomallei sepsis. New data supports the use of monotherapy with oral trimethoprim-sulfamethoxazole for the oral phase of treatment¹⁵. This simplifies the treatment regimen and should have a positive impact on prescribing patterns in suspected cases. Melioidosis has not been reported to be endemic in eastern Myanmar along the Thailand border, therefore, health providers may not consider it as a diagnosis in persons with sepsis. The detection of B. pseudomallei in this case series highlights the need for further epidemiologic study and case diagnosis in this region.

Consent

Written informed consent to report these cases was obtained from the families of the patients.