Journal of The Association of Physicians of India ■ Vol. 67 ■ December 201940

Melioidosis - A Case Series from Kerala

Elsa George1*, A Rajalakshmi2

1Resident, Dept. of Internal Medicine, 2Consultant in Infectious diseases and Hospital Infection Control, Kerala Institute of Medical Sciences (KIMS), Trivandrum, Kerala; *Corresponding AuthorReceived: 03.04.2019; Accepted: 29.08.2019

AbstractMelioidosis is an infectious disease caused by gram negative bacterium Burkholderia pseudomallei. It is a soil and water pathogen and transmitted to humans through inoculation or inhalation. This disease is considered endemic in India and largely remains under reported. The most common presentation is pneumonia and bacteraemia, which can present acutely and as septic shock. Chronic presentation include-abscess, septic arthritis, osteomyelitis. The major risk factors are diabetes, liver disease, renal disease, chronic lung disease.

In this article 18 cases have been reviewed; their clinical features, treatment and outcome are discussed. This is to highlight the varied presentations, high degree of clinical suspicion needed to suspect and start empiric therapy, good microbiological support to arrive at right diagnosis and timely treatment of this infection as it carries high mortality, if left untreated. Also, this is the largest reported case series from Kerala till date.

Introduction

Me l i o i d o s i s i s c a u s e d b y B . pseudomallei , a gram-negative

bacterium that resides in soil and surface water in endemic regions. Outbreaks of melioidosis have been described following heavy rainfall and floods from Australia and Thailand.1,2 The disease has a var ied c l in ica l presenta t ion f rom asymptomat ic d i s e a s e t o c h r o n i c a b s c e s s e s o r pneumonia, to fulminant bacteremic disease. It is an important cause of sepsis in several tropical areas. In India it has been reported sporadically, of

Methods

The data of 18 proven cases of melioidosis (blood or any other site specimen growing B. pseudomallei) diagnosed at our tertiary care hospital, in the past 7 years from 2012 - 18 were analysed from the medical records.

which largest number of case series are from the south3. But with better diagnostic facilities and improved awareness, more cases of melioidosis are being reported. Melioidosis is not generally considered in the differential diagnosis of a community acquired sepsis syndrome because of low degree of suspicion and it being a mimicker of several other community onset infections.

Journal of The Association of Physicians of India ■ Vol. 67 ■ December 2019 41

Blood cultures were performed with the BacT-Alert automated blood culture system using brain heart infusion broth and incubated at 37°C. Positive cultures were sub-cultured in appropriate medium; ident i f icat ion and drug susceptibility was done on Vitek 2 system. All other specimens were cultured on the following media: sheep blood agar, chocolate agar, MacConkey agar, with isolate identification through standard microbiological techniques. C l i n i c a l f e a t u r e s , t r e a t m e n t a n d outcome were looked into.

Results

T a b l e 1 s u m m a r i s e s t h e characteristics, epidemiology and site of infection of patients included in the study. Ten out of 18 were from Kerala and the rest 8 from neighbouring state of Tamil Nadu. Most of these patients were from the coastal belt area. 11 out of 18 patients had presented with sepsis syndrome and 7 of them had visceral abscess or skin and soft tissue infection. Samples that grew B. pseudomallei were either blood, abscess fluid, ET secretion or representative tissue sample.

83% of the patients were males. Diabetes mell i tus, chronic kidney disease and alcoholism are known risk factors for melioidosis and our findings are consistent with this, as 78% of patients in this series were diabetic (Figure 1).

History of exposure to soil, rain water and storm are considered important risk factors and a definite history of exposure to one of these was obtained in 9 of our patients. Case 8 depicted in the table developed disseminated melioidosis following Vardah storm (Figure 3). Case 16 depicted in the table was following exposure to cyclone Ochki. Figure 2 shows the monthly cases that occurred over the year and correlation with average rainfall.

The duration of illness to the time of diagnosis ranged from 1 week to 2 years with an average of 2 months. Blood stream infection was the commonest finding. Lungs were the most common organ affected followed by skin and soft tissue. Eight of them had single site of infection and the rest had infection at multiple sites (Table 2).

The suscept ib i l i ty to d i f ferent antibiotics were looked into. Fifteen out of eighteen isolates were susceptible to meropenem, one showed intermediate susceptibility and two were resistant. Seventeen isolates were susceptible to Ceftazidime and one was resistant. Cotrimoxazole was found susceptible in 17 isolates and one showed intermediate s u s c e p t i b i l i t y . D o x y c y c l i n e susceptibility was noted in 11 patients out of which 10 were susceptible and 1 showed intermediate susceptibility. Nine patients were empirically treated with meropenem or imipenem and later de-escalated after antibiot ic

susceptibility report, to ceftazidime and continued in the intensive phase. In the eradication phase, 11 patients were treated with cotrimoxazole alone and 6 in combination with doxycycline. Only one patient succumbed to his illness and the rest improved with treatment.

Discussion

Melioidosis is an emerging infection in India especially in rural areas.5-7 It is largely a tropical disease. Studies done on soil in Southern India have shown that B. pseudomallei is found in many samples.8 There are not many reports of B. pseudomallei infection from Kerala, one case series is from south Kerala, Thiruvananthapuram distr ict that cites 4 case reports and another from the district of Thrissur detailing on 8 case series.9,10 The study done by Nayar S in Thiruvananthapuram Medical College isolated 4 samples with B. pseudomallei in a 6 month period, among which 2 were pneumonia, one was a breast abscess and another one was septicemia. The risk factors identified in these patients were diabetes mellitus, chronic l iver disease and chronic kidney disease. One of the patient was a farmer with a possible exposure to agriculture soil.9 All the isolates were sensitive strains and out of 4, three survived and the bacteremic case succumbed to death. The study in Thrissur district by Shankara VB et al has described 8 case characteristics identified in a period of 1 year and 8 months. They observed that majority of their patients were males from rural area with an average duration of illness of 25 days and risk factors being diabetes mellitus, renal failure, chronic alcoholism. Majority of the patients had localised abscess and only two had pneumonia and septicaemia out of which an elderly male succumbed to death. 3 isolates showed antibiotic resistance to cotrimoxazole.10

Ten patients in the current study were from south Kerala and the rest 8 from Tamil Nadu. Nine patients from Kerala were residents of coastal area. All the patients from Tamil Nadu were from coastal area.

B. pseudomallei is a soil pathogen and is also present in surface water.11 The association between surface water and melioidosis is strengthened by occurrence of melioidosis following monsoon rains and with occupational

Table 1: Characteristics, epidemiology and site of infection of patients included in the study.

Case Age (yrs) Diagnosis Region Sample which grew B. pseudomallei

1 33 Sepsis Trivandrum Blood2 66 Sepsis, rt. hip osteomyelitis Pathanamthitta Blood

3 40 Hepatic abscess Kanyakumari Liver abscess4 49 Liver abscess Trivandrum Blood, liver abscess5 39 Lung abscess Kanyakumari Lung tissue6 55 Pneumonia, sepsis Kanyakumari Blood7 55 Disseminated melioidosis - bone and lung Quilon Bone tissue8 44 Bacteremic melioidosis with cavitary pneumonia

and multiple cutaneous septic emboliTirunelveli Blood, ET secretions,

soft tissue pus9 60 Pneumonia, sepsis Quilon Blood10 45 Skin and Soft Tissue Infection (SSTI), pneumonia,

sepsisKanyakumari Blood

11 63 Pneumonia, sepsis, cellulitis Trivandrum Blood12 54 Sepsis, osteomyelitis-right knee Trivandrum Blood13 49 Psoas abscess, Bell’s palsy Quilon Muscle abscess14 55 Recurrent soft tissue abscess Trivandrum Soft tissue abscess15 33 Sepsis with MODS, peripartum cardiomyopathy,

aortic valve vegetation / thrombus, brain multiple microinfarct

Kanyakumari Blood

16 34 Bacteremic melioidoisis, SSTI, sepsis, MODS Kanyakumari Blood17 34 Disseminated meloidosis-brain, spleen, lung Quilon Blood18 49 Liver abscess Kanyakumari Liver abscess

Journal of The Association of Physicians of India ■ Vol. 67 ■ December 201942

exposure to surface water and mud in rice paddies at the commencement of monsoon. 12 The incidence of pneumonia and sepsis is significantly higher with rainfall during monsoons, suggest that inhalation is an important mode of acquisition rather than inoculation in such cases.12 Two patients in this series were following exposure to cyclone or storm. One patient (Figure 3) following exposure to heavy winds dur ing cyclone ‘Vardah’ in December 2016, presented as septicaemic melioidosis wi th necrot iz ing pneumonia and cutaneous septic emboli . Another case, (Case No.16) reported with leg wound and cellulitis following injury to his leg and later waded in water following cyclone ‘Ochki’ during the year 2017. Previous studies have shown a clustering of cases in endemic areas following the exposure to flood water. In a study done by Arjun R et al during the post-flood period in Chennai in the year 2015, 11 out of 12 cases had defintie history of exposure to flood water.6 Another study done in Thailand by Chierakul W et al, in the post-tsunami period in 2005 identified 6 cases of melioidosis.13

The reasons postulated for an increase in incidence of melioidosis following rainfall and winds include aerosolization of bacteria from soil or surface water due to heavy winds and rainfall, leading to a larger bacterial inoculum.2 Another reason postulated is the transportation of B. pseudomallei from deeper layers of the soil to the surface due to rising water table.14

B. pseudomallei is a gram-negative bacillus with bipolar staining and is vacuolated and slender and has rounded ends. Isolation of B. pseudomallei from body fluids of patients remains the gold standard in diagnosis and the use of selective media for specimen from a non sterile site will improve the diagnosis. On culture, the organism demonstrates wrinkled colonies15 (Figure 6) and has a safety pin appearance on gram stain.15

Inhalation, ingestion and inoculation a r e c o n s i d e r e d t h e t h r e e m o d e s of acquisit ion. 16 Six patients were suspected to have inoculat ion as the mode of transmission, who had agricultural or rain water exposure fo l lowed by sk in and sof t t i ssue infection. Apart from environmental exposure, presence of comorbidities are

considered an important risk factor for developing melioidosis, most common being diabetes mellitus; others include alcohol consumption, chronic lung disease, chronic renal disease.17 89% of the patients included in the study had underlying comorbidity with the most common association being diabetes mellitus noted in 78%. These risk factors are in similar lines with previous studies done by Vidyalakshmi K et al, Jesudason MV et al, and Currie BJ et al.6,8,17

Melioidosis can have varied clinical presentation, and most commonly affected organ is lung.17 In our study too, we found that lungs were the most common organ affected followed by soft tissue, liver and bone. The commonest mode of presentat ion was bacteremia with pneumonia . Eleven patients had mult iple s i te involvement, with or without blood stream infection. Ten out of 18 patients presented with sepsis like syndrome. Sixteen patients had presented within 2 months of symptom onset and the longest duration of i l lness before diagnosis was 2 years, a patient with recurrent soft tissue abscesses. In one patient with chronic pneumonia with osteomyeltis, the disease mimicked tuberculosis and patient was initiated on anti-tuberculous therapy before arriving at the diagnosis of melioidosis. An epidemiological study done by Currie et al noted that the incubation period ranged from 1-21 days and chronic presentations were also noted.17

Fig. 1: Comorbidities associated with melioidosis cases in this studyFig. 2: Incidence of cases and average rainfall

during a year in Kerala4

Fig. 3: Case No.8-Post cyclone (‘Vardah’ storm in December 2016) bacteremic melioidosis with cutaneous and pulmonary dissemination. The CT chest of the patient showing areas of consolidation

DIABETESMELLITUS

ALCOHOLABUSE

C/C LUNGDISEASE

CKD STEROID USE NONE0

2

4

6

8

10

12

1414

5

2

0

2 2

Chart Title

Table 2: Sites involved

Blood stream infection 12Lungs 8Skin and soft tissue 5Liver 3Bone 2Spleen 1Brain 1

Fig 3. Case No.8 -Post cyclone (‘vardah’ storm in December 2016) bacteremic

melioidosis with cutaneous and pulmonary dissemination. The CT chest of the

patient showing areas of consolidation.

Fig 4. 43 year old male presented with fever and cough. Chest radiograph

showing a cavitary lesion mimicking tuberculosis. Later developed knee pain ,

MRI showing features of osteomyelitis. A tissue biopsy from knee, proved

melioidosis.

0

100

200

300

400

500

600

700

0

1

2

3

4

5

6

JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC

incidence

Averagerainfall

Journal of The Association of Physicians of India ■ Vol. 67 ■ December 2019 43

The treatment of melioidosis include initial intensive therapy for a minimum of 10-14 days with either ceftazidime or carbapenem depending on the antibiotic susceptibility and may be combined with cotrimoxazole. This is followed by eradication phase with cotrimoxazole with or without doxycycline for atleast 3 months.18 Appropriate drug given for adequate duration in eradication and maintenance phase is important for good outcome. In the Northern territory series, the mortality rate was only 4% in non-septicaemic cases compared with 37% in bacteremic cases.17 There were no case fatalities in those with chronic melioidosis (symptoms of > 2 months duration before diagnosis).19 In our study we had only one death (6%) who had an acute presentation in the form of pneumonia.Acknowledgement

Kerala Institute of Medical Sciences for their support for the c l in ica l research.

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Fig. 5: 49 year old male presented with complaints of fever, vomiting and jaundice of 4 weeks duration. CT abdomen showed hepatic abscesses. Both blood and liver abscess samples grew B. pseudomallei

Fig. 6: B. pseudomallei showing wrinkled colony appearance on culture plate

Fig. 4: 43 year old male presented with fever and cough. Chest radiograph showing a cavitary lesion mimicking tuberculosis. Later developed knee pain , MRI showing features of osteomyelitis. Tissue biopsy from knee grew B. pseudomallei

Wuthiekanun V, Rugtaengan T, Rattanalertnavee J et al. Melioidosis in 6 tsunami survivors in southern Thailand. Clin Infect Dis 2005; 41:982-90.

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