A Case of Melioidosis: Still Unresolved and Undetected in Unexplored Regions

Saika Farook1; Farhan Muhib2; Mir Sajedul Karim3; Md. Shariful Alam Jilani4

¹Department of Microbiology, Ibrahim Medical College, Dhaka, Bangladesh.
²Department of Microbiology, Ibrahim Medical College, Dhaka, Bangladesh.
³Department of Microbiology, Ibrahim Medical College, Dhaka, Bangladesh; and Department of Microbiology, Popular Diagnostic Center Ltd, Dhaka, Bangladesh.
⁴Department of Microbiology, Ibrahim Medical College, Dhaka, Bangladesh.

*Corresponding author

Saika Farook MBBS, MD (Microbiology) Assistant Professor Department of Microbiology, Ibrahim Medical College, Dhaka, Bangladesh.

Abstract

Melioidosis, a fatal infectious disease, prevalent in southeast Asia and Northern Australia, is caused by the soil dwelling gram negative bacilli, Burkholderia pseudomallei. The disease may present with varied clinical manifestations and without prior knowledge regarding the clinical signs of the infection as well as detection methods of the causative agent, cases may be missed. Here, we report a case of melioidosis presenting as urinary tract infection in a diabetic patient, residing in a remote district of Bangladesh where melioidosis was not diagnosed before. The case study illustrates how a microbiology diagnostic laboratory not previously acquainted with the organism and the disease, may miss the case resulting in mismanagement, faulty treatment and missed diagnoses. Clinical and microbiological awareness regarding melioidosis and B. pseudomallei is of utmost importance in endemic countries, for early diagnosis and appropriate management in order to save lives.

Keywords: melioidosis, Burkholderia pseudomallei, laboratory diagnosis, Bangladesh, urinary tract infection, infectious disease

Introduction

Melioidosis, a disease of the tropics is caused by the fatal gram negative bacilli Burkholderia pseudomallei. The first case of melioidosis was diagnosed by Whitmore and Krishnaswami in 1912 in Rangoon, Myanmar [1]. Around 50 years later the organism was firstdetected from Bangladesh in a pus sample of a British sailor whose ship was deposited amidst paddy fields owing to a cyclone in Chittagong district of the country [2]. In the past 60 years, till October 2023, around 100 cases of melioidosis have been reported in Bangladesh. However, 90% of these cases have been detected in BIRDEM General Hospital, which is situated in the capital cityof Bangladesh, Dhaka [3]. Detailed history of these patients revealed that in spite of residing in different districts of the country, the disease is often misdiagnosed, treated with incorrect antibiotic regimen and finally with unresolved symptoms the cases land in BIRDEM, where the diagnoses are made. In doing so, the physicians of the said hospital belief many patients of melioidosis in various parts of the country may remain undiagnosed or even expire, due to a lack of diagnosis followed by incorrect management. Many awareness programs have been conducted in the country, to enrich the knowledge of this infection among clinicians, microbiologists as well as technologists such as workshops, seminars, and finally the 3rd South Asian Melioidosis Congress-2023, held in Dhaka. However, this particular case described below, gives a picture of how cases of melioidosis are missed in regions where laboratory personnel and doctors are not aware of the disease, leading to missed diagnosis, erroneous antimicrobial regimen, extensive expenses of a patient and the obvious hassle, an unwell patient has to go through owing to lack of knowledge on melioidosis.

Case summary

A 50 year old male, diabetic patient reported to a certain private clinic in Naogaon district of northern region of the country, with chief complaints of fever for 2 months and burningsensation during micturition for a week. Fever was intermittent to high grade in nature with highest recorded temperature being 104°F. General examination revealed the patient was mildly anemic with temperature, 104°F. His blood analysis revealed haemoglobin 11.4 g/dl, ESR 18 mm at first hour, total white cell count 11,200/ cumm, platelets 2,31,000/cumm.Widal test and chest radiography were advised which revealed normal findings. Routine and microscopic examination of urine showed it to be clear without sediments. Pus cell was found to be 6-8/ HPF, epithelial cells 10-12/ HPF, while no red blood cells were detected. At this point, unfortunately, culture and sensitivity of urine was not advised. Initially, in September, 2024 he was diagnosed as a case of urinary tract infection and was treated empirically with Ciprofloxacin for 7 days.

Figure 1: Colony of B. pseudomallei in MacConkey agar media following 24 hours of incubation at 37OC.

However, his symptoms did not improve and about a month later once again he reported to the clinic with similar clinical features. This time his random blood sugar (RBS) was found 8.07 mmol/L, C-reactive protein (CRP) 129.01 mg/L, and Widal test once again revealed antibodies within normal range. The second urine report revealed clear urine with pus cells reduced to 0-1/ HPF and epithelial cells also reduced to 1-2/ HPF. Culture of the urine yielded growth of mauve colored gram negative bacilli in MacConkey agar media (Figure-1), that were motile, oxidase positive, citrate negative and non-fermenter of lactose, glucose and sucrose. The isolate was sensitive to ceftazidime, meropenem, amoxicillin+clavulanic acid, piperacillin+tazobactum and doxycycline, while resistant to ciprofloxacin, aminoglycosides, trimethoprim- sulphamethoxazole (TMP-SMX) and colistin. What makes this case reportable is that the culture plate was almost discarded, considering the organism to be laboratory contaminant because of inexperience and lack of knowledge regarding this particular deadly bacteria. Very fortunately, a microbiologist trained and experienced on the laboratory detection of B. pseudomallei, from Dhaka city was present during that time in the said clinic on Naogaon district to conduct a training, who suspected the organism to be B. pseudomallei owing to the colony morphology, biochemical findings and antimicrobial sensitivity pattern. The culture plate was immediately sent to K A Monsur Research Laboratory in the Department of Microbiology of Ibrahim Medical college, Dhaka, maintaining adequate safety precautions.

Table 1: Laboratory investigations of the patient.

*Note: ESR (Erythrocyte sedimentation rate); WBC (white blood cell); RBS (Random blood sugar); CRP (Creactive protein); RBC (Red blood cell)
*The antibiotic amoxicillin+clavulinic acid sensitivity is not provided by VITEK system. It was found sensitive by disc diffusion method.

The isolate was confirmed to be B. pseudomallei by monoclonal antibody based latex agglutination test for B. pseudomallei (Melioidosis Research Center, Khon Kaen, Thailand), VITEK 2 system and Polymerase Chain Reaction (PCR). As the patient resided in a remote area of the country other supportive investigations such as computed tomography of the chest, or radiological imaging of the lower abdomen were not conducted for exclusion of any deep seated abscess. The patient’s physician in Rajshahi Medical College was consulted about the appropriate management of melioidosis. However, perhaps due to miscommunication or a lack of understanding, he was prescribed with oral tetracycline just for a week. Initially, his symptoms subsided but about a month later in the early weeks of November, the patient reported to Ibrahim Medical College in Dhaka with high grade feveronce again. Finally, his antimicrobial regimen began in intensive phase.

Discussion

Melioidosis, a tropical disease, is considered endemic in southeast Asia and Australia [4]. The causative agent, B. pseudomallei is a gram negative soil-dwelling bacilli, often acquired through contaminated or abraded skin or inhalation of dust contaminated with the organism [5]. The concerned patient own agricultural lands and poultry farms although he denied being involved in farming himself. Nonetheless, he supervised cultivation on paddy fields which may lead to inoculation of the bacteria.

Melioidosis can present with a myriad of clinical symptoms, for which definite diagnosis depends on the isolation and identification of B. pseudomallei from clinical specimens [6]. Although, it has been mentioned earlier that urinary tract melioidosis is uncommon, in Bangladesh, previously 13.2% melioidosis patients presented with burning sensation in micturition [7,8]. Bangladesh is considered a definite country for melioidosis, owing to the presence of the organism in both clinical and soil specimen [9]. Culture remains the gold standard for the isolation of B. pseudomallei from clinical specimens, followed by identification of the bacteria by colony morphology, biochemical analysis and antimicrobial resistance pattern as the isolate is intrinsically resistant to aminoglycosides and colistin [10]. However, in Bangladesh, when laboratories are suddenly faced with a melioidosis case outside the capital city of Dhaka, identification becomes difficult because of the lack of specific signs of the disease along with minimal clinical and laboratory experience regarding the disease. The case study illustrates how this diagnosis could come as a bit of a surprise to a standard diagnostic laboratory outside Dhaka city. Moreover, previously no patient was identified from the Northern region of the country which provides reason for the unfamiliarity of the microbiologists of the said laboratory to suspect and identify the organism [11].

Since B. pseudomallei is categorized as a Biosafety Level 3 agent, the microbiology laboratory must be well equipped to handle the organism [6]. If the organism is not accurately identified, laboratory personnel may be accidentally and unintentionally exposed. A laboratory staff involved in cleaning culture plates, was diagnosed with melioidosis in 2020 in the Department of Microbiology, BIRDEM General Hospital which has also raised concern regarding maintenance of biosafety while handling the organism [7]. However, as there have only been a few documented laboratory-acquired cases, it is reasonable to conclude that the real risk is minimal if safe work procedures are followed [12,13].

Diabetes mellitus, chronic kidney disease, thalassaemia, alcoholic usage, chronic lung disease, male gender, age > 45 years, and immunosuppression are among the risk factors for developing melioidosis [14,15]. Our patient exhibiteddiabetes mellitus, old age and male gender as risk factors. Previously, in Bangladesh, 83.82% melioidosis patients were male, with 88.23% of patients having diabetes as a comorbidity [7].

pseudomallei is resistant to penicillin, first-/second-generation cephalosporins, colistin and aminoglycosides [5,16].It also shows some degree of resistance to quinolones[6]. The intensive therapy should include ceftazidime, imipenem or meropenem followed by a longer eradication period with co-trimoxazole, amoxicillin-clavulanate or doxycycline depending on susceptibility testing [5,16]. In our patient, initially the patient was treated with ciprofloxacin to which the isolate later demonstrated resistance. Even after a diagnosis of melioidosis was made, the patient’s antibiotic regimen included oral tetracycline instead of injectable antibiotics mentioned above. Finally, one month after diagnosis, intensive therapy began with meropenem following which the patient reported improved physical condition. Till the case report has been written, the patient has received the antibiotic for 3 weeks following which he reported improved physical condition.

Conclusions

The negligence about the knowledge regarding melioidosis will continue to heighten the rate of death tolls, if not acknowledged globally. Melioidosis must be included in the differential diagnosis of pyrexia of unknown origin in case of patients belonging to endemic countries, even in regions from where no previous case have been reported. Until physicians and microbiologists have a better understanding of the disease' varied symptoms, detection methods and isolation techniques, melioidosis will remain a rare diagnosis.

Funding: No fund was available for this study.

Author contributions: SF wrote the manuscript and supervised the work; FM and MSK were involved in diagnosis of the disease, analysis of the case and maintaining routine follow up; MSAJ contributed in editing the manuscript and was involved in providing critical insights regarding the management of the patient.

Statement and Declarations: Not applicable

Ethics statement: The Ethical Review Committee (ERC) of Ibrahim Medical College (IMC) has approved a research project on melioidosis, under which the case report has been conducted.

Conflicts of Interest: The authors declare no conflict of interest.

Declaration of patient consent: The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his clinical information to be reported in the journal. The patient understand that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

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