Killer disease remains an open secret in Southeast Asia

‘. . . most of the time, the patient has already passed away.’

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The bacterium that causes Melioidosis.  Source: Eye of Science

There may be some folks who call a disease that still kills the “Vietnam Time-Bomb.”  More than 300 U.S. servicemen who fought in Vietnam were infected with it.

Melioidosis, as it is known medically, caused their deaths.  It may be Southeast Asia’s most quiet killer, a stealthy predator.

The deadly disease occurs throughout the world’s warm climes; in Southeast Asia, it is especially present in northeastern Thailand and perhaps less so in Cambodia as far as can be known.  Because it lurks with so little public awareness, physicians here don’t tend to look for it in ailing individuals, and those patients just perish, often within days.

“In Cambodia, we think 70 per cent at the very least die with treatment,” says Dr. Patrick Galmiche, a 68-year-old respected specialist in parasitic and infectious diseases who has lived and worked in Phnom Penh for the last 11 years.  The physician should know: He has no doubt that he came quite recently within days of dying of melioidosis.  Galmiche is still recovering.

“Every day I feel better,” he allows, convinced that he contracted the disease on Jan. 17 during a family swim in a sluggish Mekong River off Diamond Island across from Phnom Penh’s Riverside neighborhood.

Born and educated primarily in France, he has treated patients with tropical diseases most of his professional life in Africa —  including lengthy stints with Doctors Without Borders and what was then the French Cooperation Ministry — prior to moving here with his Cambodian wife.

After a subsequent divorce, Galmiche married another Cambodian woman, and they live with their four-year-old son in an expansive apartment overlooking the Tonle Sap River from the Riverside neighborhood on the other side of Diamond Island.  (The Mekong and Tonle Sap diverge at the island’s tip.)  The doctor has established a medical office for his independent practice on the unit’s second floor.

The Centers for Disease Control in the U.S.describes the affliction that battered Galmiche this way:

Melioidosis, also called Whitmore’s disease, is an infectious disease that can infect humans or animals. The disease is caused by the bacterium Burkholderia pseudomallei. . .

The bacteria causing melioidosis are found in contaminated water and soil. It is spread to humans and animals through direct contact with the contaminated source.

Along with HIV and tuberculosis, melioidosis is one of the top three causes of death — after tuberculosis and HIV — by infectious disease in parts of Southeast Asia.  It can enter the body through the lungs or through open wounds.

It causes either an acute form of the disease, emerging almost immediately upon infection, or it can lay dormant in the body until it strikes many years, often decades, later. In the acute form of the disease, even with a long course of treatment, mortality rates in some endemic areas can be extraordinarily high.  (Sources vary on mortality rates.)  With a wide range of symptoms, melioidosis can be extremely difficult to diagnose if it is unsuspected, hampering medical intervention.

Consider these alarming facts:

  • Not only did more than 300 American servicemen die of melioidosis during the Vietnam war, but Dr. Galmiche believes the number in contact with B. pseudomallei must be in the hundreds of thousands.
  • “Doctors in Southeast Asia and Northern Australia know it as a stubborn, potentially deadly infection that causes pneumonia, abscesses and, in the most severe cases, organ failure,” National Public Radio (NPR) reported in January.
  • Without treatment, the NPR added, it can kill within 48 hours and military officials worry it could be converted into an agent of terror.
  • There is no vaccine against melioidosis, though one is reported to be under development despite an eventual cost for large and poor populations that undoubtedly would inhibit its use.

An article in Nature Microbiology this year also is alarming.  It estimates the number of cases worldwide at 165,000 with a death rate of 70 per cent, or 89,000 annually.

“Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is probably endemic in a further 34 countries that have never reported the disease,” the authors of the Nature Microbiology article write, adding that insufficient attention has been paid to its prevalence.

Observes David Dance in the journal Clinical Microbiology Reviews:

There is remarkably little known about the incidence of melioidosis outside a few countries (Thailand, Australia, Singapore and Malaysia). Presumably it is widespread in tropical south east Asia. Elsewhere there are tantalising glimpses of the tip of what may be a large iceberg. Since a specific diagnosis of melioidosis requires awareness on the part of clinicians, and the existence of a laboratory capable of isolating and identifying Burkholderia pseudomallei, a luxury not available in most rural tropical areas, the size of this iceberg is likely to remain unknown for the foreseeable future.

NPR quotes Dr. Eric Bertherat of the World Health Organization as saying that research “demonstrates the potential burden of this disease is much bigger than what everybody expected. . . It’s a big burden, equivalent to rabies, and that’s a severe disease.”

Patrick Galmiche

Dr. Patrick Galmiche in the medical office that he has installed on the second floor of his home overlooking the Tonle Sap in Phnom Penh’s Riverside neighborhood.

In contrast to cases numbering 2,000 per year in northeast Thailand, the first documentation of melioidosis in Cambodia was published no earlier than in 2008.  It detailed the cases of two patients who presented with respiratory illnesses featuring multiple lung abscesses and ultimately survived.

High-risk groups include patients with diabetes, chronic kidney disease, chronic lung disease and excessive alcohol intake, each of them common in Cambodia.  That melioidosis is more prevalent by whole magnitudes in low-income than in high-income countries makes the disease much more of a public-health issue here than in cooler latitudes.

Melioidosis is all too easy to catch.  A study published by National Center for Biotechnology Information found that more than a third of the Marines who visited Thailand in 2006 were infected with the bacterium that causes the disease.  Specifically, the blood tests produced the following results:

Thirteen (38%) of 34 previously unexposed U.S. Marines had positive serology after two weeks in Thailand, and one developed acute disseminated disease. Asymptomatic infection with Burkholderia pseudomallei may be common, even from brief exposures.

Fortunately, only one of the Marines developed acute melioidosis by the time that the study was conducted.

The “Vietnamese time bomb,” received wide attention largely after the Vietnam (or American, as it is called in Vietnam) War, according to a report in Science.  As helicopters deposited troops throughout the tropical nation, their blades kicked up dirt, exposing soldiers and pilots to hidden pathogens in the soil.”  The journal continued:

Melioidosis tends to cause a wide range of symptoms similar to other conditions, leading some scientists to give it the second nickname “the Great Mimicker.” “You might look like you have some skin irritation, … or you might have an abscess on your liver,” says study co-author Stuart Wilson, a molecular biologist at the University of Sheffield in the United Kingdom. “And it’s the same disease.”

Especially concerning about the disease, which can survive in distilled water for decades, is not only how difficult it is to diagnose and but how damaging is treatment with the wrong antibiotics.

An incorrect diagnosis  — for example, dengue fever or tuberculosis — can be fatal.  Dr. Direk Limmathurotsakul, a microbiologist with the University of Oxford and Mahidol University in Bangkok and lead author of the study cited by NPR, said that it is “worrying for areas outside of our research center” in northeastern Thailand.  “And we know that’s happening in many emerging areas — like India, Brazil, Indonesia,” he added.

NPR noted that B. pseudomallei is naturally resistant to many commonly prescribed antibiotics. It continued:

With good supporting care and access to proper medications, fatalities drop to around 1 in 10, and most healthy adults are able to survive an infection with good care. Otherwise, death sets in quickly. “There are many who have been treated with ineffective antibiotics for a period,” says Limmathurotsakul. But by the time the disease is confirmed as melioidosis, he notes, “most of the time, the patient has already passed away.”

In fact, the patients who consisted of the first documented cases in Cambodia were misdiagnosed and mistreated.  “The two study cases illustrate issues relating to the misdiagnosis of melioidosis in Cambodia; an unfamiliarity of clinicians with the disease, which is associated with a high prevalence of TB,” the researchers reported.

“Under the ‘classical’ trimethoprim-sulphamethoxazole, chloramphenicol and doxycycline treatment, their clinical status improved considerably within 2 weeks.”

Unsurprisingly, a leading infectious disease specialist at a major hospital in Phnom Penh is rumored recently to have denied the existence of melioidosis.  The rumor strains credulity, but a mindset that overlooks melioidosis is certainly worrisome: If the disease is not even suspected in a patient, of course there can be only one result in most instances.

Without access to appropriate antibiotics, with ceftazidime now preferred to chloramphenicol, the mortality rate approaches 80 per cent, according to a 1989 study published in the Lancet by researchers at Bangkok Hospital for Tropical Diseases.

Dr. Glamiche has a vivid recollection of the onset of his illness and a sheaf of medical records to demonstrate how it progressed.

He became ill exactly 10 days after his presumed exposure while swimming, actually plodding like a hippopotamus, he says, in water that was waist high because of Cambodia’s drought. Galmiche recalls having remained in Phnom Penh for the previous three or four months, well outside that parameter of the average of nine or 10 days before acute melioidosis strikes.

On Jan. 28, as he left his home office, Galmiche felt woozy and collapsed into something like a coma for perhaps half an hour.  He was shivering and registered a fever of 41.5° C. or 106.7 F after dragging himself up.  “I never was sick like this,” the doctor says.

In his telling, he first thought that dengue fever — which, like malaria, is pervasive in Southeast Asia — was the cause.  Because of the fever, he dosed himself with paracetamol (also known as acetaminophen and Tylenol) with low expectations that it would help.

By Feb. 3 or 4, he also was in unbearable pain that no medication would minimize, and his fever continued to soar.  Across the desk from me in his office, he said, “I felt I was going to die, I swear.”  He was having bad dreams, had lost his strength and was too nauseated to tolerate food.  Within a week, his weight had plunged by 18 kilograms, nearly 40 pounds.

He was admitted to a Phnom Penh hospital on Saturday, Feb. 6.  Some of the early lab test results were strange to Galmiche and his four physicians, but they wouldn’t be able to obtain more comprehensive results for a week in part because his blood was drawn on a weekend.

Lacking a confirmed diagnosis, the group made a presumptive diagnosis.  The consensus was to take the risky step of administering four antibiotics four times a day intravenously at a cost of $50 for each plastic bag of solution, massive doses.

Although everyone involved was aware that the wrong medications could postpone the correct ones long enough to prove fatal, Galmiche decided that the possibility of dying because of their use was an acceptable course of action.  “Me, I know because I am a doctor.  If I am not a doctor, I would die on Monday or Tuesday,” he had concluded.  “It was antibiotics or die.”

When the first lab tests came back, the one for C-reactive protein, was off the charts — approximately 23 times normal.  I’ve never seen so much in my life,” he relates, saying that a patient with such a number normally succumbs within two or three days.  In addition, the white cell count was too high and the red cell count was too low.  Testing also ruled out other diseases such as tuberculosis.

Additional analysis showed no damage to his brain or lungs.  That was the good news in that death would come quickly had they appeared on those organs.  The bad news was presence of three 9-centimeter (3.5-inch) abscesses on his liver, such abcesses being characteristic of melioidosis.

There also was an infected thigh bone on which clung a stubborn stretch of pus along its length.  The substance was so thick that it couldn’t be extracted without a deep incision. Galmiche was adamant about the need for immediate major surgery.

Galmiche 2

Galmiche has surgical wound dressed. Note IV lines on his right wrist.

After the surgery, he was in expected pain.  Morphine caused him problems, so he depended again on paracetamol.  In a matter of 12 hours, all the post-operative pain and the agony he had endured from the beginning subsided measurably.  His fever also began to abate.

The combination therapy continued for three weeks, and the liver abscesses are shrinking. Galmiche now downs one of the antibiotics daily.  He will do so until six months have elapsed.

He is certain that he would have died if hadn’t drawn on his experience and knowledge to insist on the treatment that made possible his survival.  “I saved myself,” Galmiche declares with evident wonder.  “I am a miracle.”

The doctor recounts his ordeal because of his concern about the prevalence of the disease in Cambodia, where it sometimes is recognized and often is not.

When someone dies in the provinces, according Glamiche, they’ll just report, “Oh, he had a fever.”  Post-mortem work is exceedingly rare in Cambodia, so few questions are asked and there is no further examination.  Arguably worse, he relates, when someone has a bone infection, surgery like Glamiche’s is achieved with a razor and no anesthesia.

In instances when melioidosis is correctly diagnosed, death may well follow anyway.  That is because of the cost of treatment in this impoverished nation, the physician theorizes, as well as, perhaps, its availability.

Although Galmiche has health insurance in France, he has none here.  As a result, he is out of pocket approximately $20,000 so far, some of it borrowed.  It is safe to say Galmiche believes that it has been a worthwhile expense.

E-mail: malcolmncarter@gmail.com

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