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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 10-14

Clinical and laboratory profile of people afflicted with melioidosis: A retrospective study


1 Department of General Medicine, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
2 Department of Microbiology, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
3 Department of MBBS Student, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
4 Department of General Medicine, KS Hegde Medical College, Mangalore, Karnataka, India
5 Senior Scientist, Mangalore Institute of Oncology, Pumpwell Circle, Mangalore, Karnataka, India

Date of Submission26-Apr-2019
Date of Decision27-Sep-2019
Date of Acceptance10-Oct-2019
Date of Web Publication12-Feb-2020

Correspondence Address:
Dr. Ramakrishna Pai Jakribettu
Department of Microbiology, Father Muller Medical College, Kankanady, Mangalore - 575 002, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_45_19

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  Abstract 


Aim: Melioidosis, caused by Burkholderia pseudomallei, is an important disease in some parts of the developing countries and is now categorized as an emerging infection and a global threat. The present study was carried out to ascertain the alterations on the hematological, hepatic, and renal parameters in the infected people. Materials and Methods: This was a retrospective study and was conducted in a tertiary care hospital in India. Data were analyzed in people who were diagnosed to be infected by B. pseudomallei during January 2010–December 2016. A total of 28 people were included in the study and compared with healthy individuals who were tested negative for any infectious and chronic diseases. Results: The results indicated that the infection caused diverse clinical manifestations such as fever, cough, dyspnea, joint pain, headache, bodyache, weight loss, swelling, and decrease in appetite. There was significant difference in the various hematological and hepatic endpoints, while there was no such difference in the renal function test parameters. Conclusions: For the first time, this study indicates that acute infection with melioidosis causes alterations in hematological and hepatic parameters in people with melioidosis.

Keywords: Burkholderia pseudomallei, clinical, hematological, hepatic, melioidosis, renal


How to cite this article:
Swapna PK, Jakribettu RP, George T, Manoj Kumar PK, Baliga MS. Clinical and laboratory profile of people afflicted with melioidosis: A retrospective study. Indian J Med Spec 2020;11:10-4

How to cite this URL:
Swapna PK, Jakribettu RP, George T, Manoj Kumar PK, Baliga MS. Clinical and laboratory profile of people afflicted with melioidosis: A retrospective study. Indian J Med Spec [serial online] 2020 [cited 2020 Jul 6];11:10-4. Available from: http://www.ijms.in/text.asp?2020/11/1/10/278094




  Introduction Top


Melioidosis, caused by the Gram-negative bacteria Burkholderia pseudomallei, is an important infectious disease in the tropical regions of the world.[1] From historical perspective, the disease was first described as “Glanders-like disease” among morphia addicts by Alfred Whitmore and Krishnaswami in Burma in 1911.[2] Records indicate that the term 'Melioidosis' was derived from the Greek meaning, a condition similar to glanders in animals, especially in sheep, goats, and horses.[2] In the previous century, the disease was endemic to the areas of Southeast Asian and Northern Australia and was reported frequently from areas of today's Burma, Malaysia, and Singapore.[1] However, in the recent past, melioidosis is being reported from other countries in Asia, America, Caribbean Islands, Africa, and the Middle East, predominantly in the travelers returning from tropical countries.[1],[2],[3],[4],[5],[6],[7],[8] In lieu of all these reports, melioidosis is now categorized as an emerging infection and a global threat.[2]

From an etiological perspective, the pathogen B. pseudomallei are principally found in contaminated soil and water.[1],[2],[3],[4],[5],[6],[7],[8] It infects humans mostly through the percutaneous or respiratory routes.[1],[2],[3],[4],[5],[6],[7],[8] The bacterial load and the virulence factor of the strain of B. pseudomallei are known to impact the severity of the disease.[1],[2],[3],[4],[5],[6],[7],[8] Melioidosis is known to affect people of all age groups, but people with comorbidities such as impaired immunological response, diabetes, thalassemia, renal disease, alcoholism, chronic obstructive pulmonary disease, malignancies, and on steroid or antineoplastic therapy are at increased risk to develop septicemia.[1],[2],[3],[4],[5],[6],[7],[8] The disease spectrum can vary from asymptomatic infection or localized abscess without systemic manifestation to multifocal infection with septicemia.[7] If neglected or treated inappropriately, it can even cause death in infected individuals.[1],[2],[3],[4],[5],[6],[7],[8]

From a clinical perspective, the diagnosis of melioidosis and the organism B. pseudomallei has been under-reported principally due to lack of awareness, low index of suspicion, and morphological resemblance to Pseudomonas species.[9],[10] However, the development of B. pseudomallei selective agar and B. cepacia medium by Howard and Inglis[11] has revolutionized the microbiological identification and reduced the chances of misdiagnosis of melioidosis.[10]

In the recent past, a plethora of case reports, case series, and clinical papers addressing the etiological, epidemiological, pathological, microbiological aspects, and treatment have been published.[8],[12],[13],[14],[15],[16],[17],[18] However, reports on the changes in the clinicohematological, biochemical (liver function test [LFT], and renal function test) parameters are lacking. In this study, attempts are made to understand clinicohematological changes, symptoms, and the treatment profile of the people inflicted by melioidosis.


  Materials and Methods Top


The present study was a noninterventional observational retrospective study and was conducted by the Departments of Clinical Microbiology and General Medicine, at Father Muller Medical College Hospital, Mangalore. The study was undertaken after approval by the Institutional Ethics Committee. The inpatient records of patients who were confirmed to have been infected by B. pseudomallei by microbiological methods were collected from the medical records department. Care was taken to see that people with coinfections to malaria, dengue, leptospirosis,  Brucellosis More Details, filariasis, tuberculosis, hepatitis, H1N1, and HIV were excluded from the study. The investigators restricted their study period to January 2010–December 2016. All the files were thoroughly reviewed by a senior student and an experienced physician. As a baseline control, the investigators also collected the biochemical and hematological details from healthy volunteers who had visited the hospital for a general health-care checkup. The pertinent details such as demographic, diagnostic, and treatment details were subjected to Chi-square test, while the biochemical and hematological data were analyzed using the unpaired “t”-test using the SPSS statistical program 32 (IBM version 22, Chicago Inc, USA). P = 0.05 was considered statistically significant.


  Results Top


In the present study, a total of 28 patients (male [20; 71.4%] and female [8; 28.6%]) confirmed to be infected only with B. pseudomallei could be retrieved in the study during the period of January 2010-December 2016. It was observed that 60.71% (17/28) were from the rural areas, 50% (14/28) had bacteremic conditions, and that 67.86% (19/28) had unifocal infections. The demographic, symptoms, and treatment details were categorized into frequency and are represented in [Table 1] and [Table 2], while the hematological and biochemical data are represented as mean, standard deviation, and lower and upper bound in [Table 2].
Table 1: Incidence of various clinical symptoms observed in adults diagnosed with melioidosis

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Table 2: Alterations in the hematological and biochemical parameters in people afflicted with melioidosis

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The results from the present study indicate that infection with B. pseudomallei causes myriad and diverse clinical manifestations. In this study, it was observed that joint pain (85.72%) and fever (67.85%) were the two most commonly observed presentations in the patients [Table 1]. Other symptoms were cough, dyspnea, headache, bodyache, weight loss, swelling, abscess, and decrease in appetite [Table 1]. The details on the duration (in weeks) of fever in the patients and details on joint pains are represented in [Figure 1] and [Figure 2], respectively. There was no death reported during the study period.
Figure 1: Percentage representation of the duration of fever in patients confirmed to be infected by Burkholderia pseudomallei

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Figure 2: Percentage representation of the pain in joints in patients confirmed to be infected by Burkholderia pseudomallei

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With respect to the hematological parameters, a significant difference in the Hb (P < 0.04), total leucocyte count (P < 0.0001), neutrophils (P < 0.0001), lymphocytes (P < 0.0001), eosinophils (P < 0.0004), monocytes (P < 0.001), and erythrocyte sedimentation rate (ESR) (P < 0.0001) was observed. The liver function parameters indicated a significant difference in bilirubin (P < 0.015), conjugated bilirubin (P < 0.003), aspartate aminotransferase (AST) (P < 0.002), alanine aminotransferase (ALT) (P < 0.005), and alkaline phosphatase (ALP) (P < 0.005). However, statistically significant difference was not seen with creatinine, unconjugated bilirubin, and in platelets [Table 2].

With regard to the treatment, of the 28 patients, four patients left against medical advice, and the remaining 24 completed the initial intensive therapy and then got discharged with prescription for the eradication therapy. The empirical treatment prescribed on arrival till the availability of the microbiology reports confirming B. pseudomallei is enlisted in [Table 3].
Table 3: Empirical treatment used in the people afflicted with melioidosis (n=28)

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  Discussion Top


The patients with melioidosis can present with a spectrum of clinical manifestations from localized abscess to sepsis. In our study, patients have presented in the form of suppurative parotitis, lymphadenitis, subcutaneous and deep-seated abscess formation, liver and splenic abscesses, and is in agreement to earlier reports.[19]

Melioidosis is known to affect the bone and joints also, and the clinical features resemble arthritis,[13] and in our study we observed that one patient had osteomyelitis of the femur. Another important aspect that needs to be recognized is that melioidosis may manifest with fever and cervical lymphadenopathy. These features mimic tuberculous lymphadenitis and may lead to wrong diagnosis and treatment. A confirmed differential diagnosis needs to be performed to ascertain the bacterial infection before initiating treatment.

With respect to the hematological parameters, the results indicated that leukocytosis with neutrophilia, monocytosis, and relative lymphopenia was observed in our study, which is conclusively suggestive of chronic bacterial infection.[20] In addition, it was also observed that the ESR was elevated up to 130 mm/h (mean of 81.52 ± 28.90) and was 7.4 folds more than the age-matched healthy controls (11.16 ± 9.81). ESR is usually elevated in bacterial infections, and these results suggest that there has been an increase in the acute-phase reactant protein levels in the plasma.[20] The biochemical results indicated that there were alterations in LFTs and that the levels of total bilirubin, conjugated bilirubin, AST, ALT, and ALP were increased, suggesting hepatocellular damage and that the sepsis was the possible causative factor for the change.[21],[22],[23] However, no such changes in the renal function marker creatinine were observed, indicating that in the patients we studied, melioidosis did not affect the kidneys except in disseminated infection with sepsis.

With regard to the treatment adopted, the records indicate that the patients were initiated with variety of empirical antibiotic therapy, but on establishing the diagnosis, the treatment was switched to injection ceftazidime 2 g intravenously thrice a day for 2 weeks, followed by eradication therapy with sulfamethoxazole-trimethoprim for 3 months and discharged. Previous studies have shown that B. pseudomallei is susceptible to newer β-lactam antibiotics, especially ceftazidime, imipenem, meropenem, piperacillin, amoxicillin-clavulanate, ceftriaxone, and cefotaxime, with various degrees of bactericidal activity.[5],[7],[17],[22],[23],[24] However, reports indicate that ceftazidime is the drug of choice for initial intensive therapy for melioidosis and is effective.[7],[16],[17]

An open-label randomized trial in Thailand showed that use of ceftazidime was associated with a 50% lower overall mortality in severe melioidosis.[24] Randomized controlled trials have shown that the combination therapy with ceftazidime and sulfamethoxazole-trimethoprim was superior to ceftazidime alone and was effective for cutaneous, bone and joint, neurologic, and prostatic melioidosis.[24] Studies do also suggest that amoxicillin-clavulanate and carbapenems were equally effective as ceftazidime in the treatment of melioidosis.[17]

The treatment profile for B. pseudomallei comprised two stages: the initial intensive therapy followed by the prolonged eradication therapy for preventing recrudescence or later relapse of melioidosis.[5],[25] The drugs recommended by consensus are ceftazidime or meropenem for initial intensive therapy and trimethoprim/sulfamethoxazole or amoxicillin/clavulanic acid for eradication therapy.[5] The most important factor responsible for most recrudescence or relapse of melioidosis is poor compliance with eradication therapy. Period of eradication therapy is also critical, with relapses being more if oral therapy is advised for 8 weeks or less, than if eradication therapy is given for >12 weeks.[17],[18]

Since melioidosis is an emerging infectious disease, we have tried to collect all the clinicolaboratory parameters and the therapeutic details in this retrospective study. We are able to collect all the presenting complaints of the patients. However, the disadvantage of this study is that we are not able to follow-up cases posttreatment.


  Conclusions Top


The important observations of this study are that melioidosis causes myriad clinical symptoms and alters the hematological and some biochemical results of the LFT. In cases who present with fever and localized abscess, culture and isolation of the organism are of importance to rule out Burkholderia infections as a longer duration of treatment is required in order to achieve complete cure and prevent recurrence. Since bone involvement is known in Burkholderia infections, it needs to be considered as a differential diagnosis in cases of bone and joint tuberculosis and bacterial osteomyelitis.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kingsley PV, Arunkumar G, Tipre M, Leader M, Sathiakumar N. Pitfalls and optimal approaches to diagnose melioidosis. Asian Pac J Trop Med 2016;9:515-24.  Back to cited text no. 9
    
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Howard K, Inglis TJ. Novel selective medium for isolation of Burkholderia pseudomallei. J Clin Microbiol 2003;41:3312-6.  Back to cited text no. 11
    
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Benoit TJ, Blaney DD, Doker TJ, Gee JE, Elrod MG, Rolim DB, et al. A review of melioidosis cases in the Americas. Am J Trop Med Hyg 2015;93:1134-9.  Back to cited text no. 12
    
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Zueter AM, Abumarzouq M, Yusof MI, Wan Ismail WF, Harun A. Osteoarticular and soft-tissue melioidosis in Malaysia: Clinical characteristics and molecular typing of the causative agent. J Infect Dev Ctries 2017;11:28-33.  Back to cited text no. 13
    
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Hemarajata P, Baghdadi JD, Hoffman R, Humphries RM. Burkholderia pseudomallei: Challenges for the clinical microbiology laboratory. J Clin Microbiol 2016;54:2866-73.  Back to cited text no. 14
    
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Kingsley PV, Leader M, Nagodawithana NS, Tipre M, Sathiakumar N. Melioidosis in Malaysia: A review of case reports. PLoS Negl Trop Dis 2016;10:e0005182.  Back to cited text no. 15
    
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Perumal Samy R, Stiles BG, Sethi G, Lim LHK. Melioidosis: Clinical impact and public health threat in the tropics. PLoS Negl Trop Dis 2017;11:e0004738.  Back to cited text no. 16
    
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Limmathurotsakul D, Chaowagul W, Chierakul W, Stepniewska K, Maharjan B, Wuthiekanun V, et al. Risk factors for recurrent melioidosis in Northeast Thailand. Clin Infect Dis 2006;43:979-86.  Back to cited text no. 17
    
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Chaowagul W, Suputtamongkol Y, Dance DA, Rajchanuvong A, Pattara-Arechachai J, White NJ, et al. Relapse in melioidosis: Incidence and risk factors. J Infect Dis 1993;168:1181-5.  Back to cited text no. 18
    
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Cook GC, Zumla AI. Manson's Tropical Diseases. 22nd ed., Ch. 66. Edinburgh: Saunders Elsevier; 2009. p. 1127-9.  Back to cited text no. 19
    
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Giannini EG, Testa R, Savarino V. Liver enzyme alteration: A guide for clinicians. CMAJ 2005;172:367-79.  Back to cited text no. 21
    
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Limmathurotsakul D, Peacock SJ. Melioidosis: A clinical overview. Br Med Bull 2011;99:125-39.  Back to cited text no. 23
    
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Chierakul W, Anunnatsiri S, Short JM, Maharjan B, Mootsikapun P, Simpson AJ, et al. Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis. Clin Infect Dis 2005;41:1105-13.  Back to cited text no. 24
    
25.
Lipsitz R, Garges S, Aurigemma R, Baccam P, Blaney DD, Cheng AC, et al. Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei infection, 2010. Emerg Infect Dis 2012;18:e2.  Back to cited text no. 25
    


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