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MELIOIDOSIS : THE ENEMY WITHIN

                   Since last year, I have written articles by wearing the SCHOMOS and sometimes the MMA hat. In this issue of Berita, I thought of writing an article by putting on something that I do daily, a physician’s hat. As a person with special interest in Melioidosis, I have recently published an article in The Medical Journal of Malaysia (MMJ) December 2005 issue titled “Melioidosis: The Johor Bahru Experience” ( Pagalavan L. Melioidosis: The Johor Bahru Experience. Med J Malaysia;2005;60:599-605). In that article, a 5 year retrospective review of confirmed Melioidosis cases in Hospital Sultanah Aminah, Johor Bahru was published. The mortality was almost 50% and 75% of the cases were diabetics.

                   Melioidosis is an infection caused by Burkholderia pseudomallei, a gram negative soil saprophyte that is endemic in South East Asia but grossly underreported in Malaysia. I have suggested in my journal article that Melioidosis should be made as a notifiable disease in Malaysia to identify the exact number of cases in Malaysia as it is in Singapore. Dr. Jayaram in his editorial in the same issue of MMJ has agreed with me and have interesting said that Melioidosis is not dissimilar to avian flu. With increasing number of diabetics in Malaysia, Melioidosis is going to become a major public health issue in the near future.

                   The number of cases reported in my article and the article from How et al (Melioidosis in Pahang) may look small but the actual fact is that many are not being diagnosed. Many patients might have died in the hospitals and district hospitals with full blown sepsis without any proper cultures taken. Since Melioidosis can affect any organs in the body except hair and nail, the patients could be admitted into any disciplines in the hospital. Frankly speaking, do all doctors in various disciplines do proper cultures? I remember cases from surgical ward that develop sepsis but no blood cultures taken. I understand that not all surgeons take blood cultures routinely in their patients who are admitted for surgical sepsis. Many at times cultures were only taken by anesthetists when the patient is admitted into ICU. I had atleast 2 experience in which the above event took place where the cultures were only taken in the ICU and grew Burkholderia pseudomallei. So, we do not know how many patients who had developed intra-abdominal sepsis and died of Melioidosis in surgical wards as well as other surgical or medical fields.

          It is rather surprising for me to notice that 20% and 7% of pneumonias in Thailand and Singapore respectively were due to Melioidosis. So it is unlikely that Malaysia which sits between both the above two countries only sees less than 2% of its pneumonia cases being attributed to Melioidosis. Something is definitely wrong somewhere. This could be probably because we do not have proper microbiology laboratories in smaller district hospitals. At the same time we also do not have trained microbiologist in every hospital in this country except in bigger general hospitals. If the lab technician is not familiar with this bug, it could be misinterpreted as Pseudomonas spp. or even Burkholderia cepacia. I am sure many doctors or physicians would have come across this form of reports. Burkholderia cepacia could easily be confused with Burkholderia pseudomallei. In Hospital Sultanah Aminah, Johor Bahru everytime when the lab reports the culture as B.cepacia, I would contact the Microbiologist (Datin Dr. Ganeshwarie) and many at times it would turn out to be B.pseudomallei instead.

            Cultures are important as it is the only way Melioidosis can be diagnosed at this point of time. I had a patient who grew the organism in almost every fluid from his body which includes blood, urine, tracheal secretion and pus aspirate from septic arthritis of the knee. I even have had a patient with corneal scrapping growing the organism. Every patient with a confirmed blood culture should have an Ultrasound or even better, a CT scan of Abdomen to look for splenic and liver micro-abscesses. It is utmost important that doctors in every discipline should know about this deadly disease which has a mortality rate of 50-70%.

          Making a diagnosis is only the first step in Melioidosis as how many doctors out there knows how to treat Melioidosis. I remember a Houseofficer who wrote it down as Amyloidosis when I actually said Melioidosis. I have had many medical officers in my very own medical department who do not know anything about melioidosis and the treatment for it. I even had a specialist who was unaware that melioidosis can cause pneumonia! Burkholderia pseudomallei is an intracellular organism which can remain dormant in our body for many years, even up to 20-30 years. It is not dissimilar to Tuberculosis and so is its treatment. It needs long duration of therapy and drugs that has good intracellular penetration. Antibiotics that the bug is sensitive in-vitro may not be effective in-vivo.

          Since the publication of “Halving of mortality of severe melioidosis by Ceftazidime” in the Lancet 1982, the gold standard of treatment of melioidosis has been with intravenous (I/V) high dose Ceftazidime. I/V Ceftazidime should be given at a dose of 40mg/kg every 8 hours, total 120mg/day. This roughly comes to 2g tds for an adult. It should be given for atleast 10-14 days but may need to prolong up to 4-6 weeks if the patient has intraabdominal abscess. I had a patient who still grew Burkholderia pseudomallei in his blood even after 18 days of Ceftazidime! A single monotherapy is adequate but the addition of Ciprofloxacin (for 2 weeks in cases of pneumonia and septic arthritis), Bactrim or Doxycycline may be useful. Intravenous Augmentin can be used as an alternative but has higher treatment failure rate. It is also important to understand that the dosage is 27mg/kg every 4 hourly (max 162mg/kg per day) and not 8 hourly! This comes to roughly 1.2g 4hourly. Imipenem at 20mg/kg every 8hourly (about 1g tds) in another alternative.

          The treatment of Melioidosis does not end there. The patients should be on a maintenance therapy for atleast 5-6 months and sometimes even up to a year. The usual maintainance therapy includes a combination of Bactrim (2 tabs bd) and Doxycycline (100mg bd). Clinical resolution of any abscess should be monitored radiologically. Children below 8 years and pregnant women can be treated with oral Augmentin.

         “Once a Melioidosis Always a Melioidosis”, this is a tag that any patient with confirmed diagnosis of Melioidosis should carry with him/her lifelong. Despite adequate treatment, the relapse rate still remains at around 10% in Thailand. If a patient, who had been treated as Melioidosis before, comes with a fever without any clinically known cause, he should be treated as a relapse case with I/V Ceftazidime until proven otherwise. I always give my patients a small book with the instruction clearly written in it as to what to do if this patient goes to any hospital with fever.

          Clearly Melioidosis is a growing but under diagnosed and underreported disease. It is an enemy that is sitting within our very own soil and awaiting the right time to concur. It has also been thought of being a biological agent for war. I do agree with Dr. Jayaram that it is time now for us to act and make it a notifiable disease. The growing number of diabetics in our population is also going to increase the number of Melioidosis cases. It is an enemy within us……….