The Beaufort Cases - Leptospirosis and Melioidosis

The Beaufort Cases - Leptospirosis and Melioidosis


The first news appeared in The Star on 21st October and was posted on ProMed the same day. An edited version is appended below.

UNDIAGNOSED ILLNESS, SWIMMERS - MALAYSIA (BEAUFORT) 

Source: The Star, 21 Oct 1999 [edited] 

A 15-year-old boy died and 37 others from a village in Beaufort district have been admitted to hospital after swimming in a stream near an oil palm plantation over the weekend. This has sparked off alarm in Kampung Kebatu, about 115km from here, as villagers now are afraid to use the stream where they have been bathing for many years. The health and environment departments sent teams to the village yesterday following the tragedy. The victims were all males although females were also in the group. The dead boy was a Form Three student of SMK Beaufort. His father said yesterday that his son died on the way to the Queen Elizabeth Hospital on Monday morning. He said The boy and his friends had gone for a dip in the stream. "He was fine on Saturday evening when he came home," the father said, adding that his son began suffering from high fever, dizziness and vomiting on Sunday morning. The father said when the boy became very weak after vomiting blood, they rushed him to Beaufort Hospital where doctors said that he was suffering from ruptured lungs and kidney. He said the following day the doctors sent him to the Queen Elizabeth Hospital but the boy died on the way there. "My son was an active and healthy boy," said the father, adding that others who swam in the stream that Saturday had complained of similar symptoms as the boy. Since Sunday, Beaufort Hospital treated a stream of people from Kampung Kebatu. As of yesterday, 37 people aged between 11 and 20 had been hospitalized, with some subsequently transferred to the Queen Elizabeth Hospital. 

A recent posting by Prof. Lam Sai Kit shades some light on the probable etiology.

UNDIAGNOSED ILLNESS, SWIMMERS - MALAYSIA (BEAUFORT) (05) 

 Date: Sat, 20 Nov 1999 09:36:43 +0800 From: Lam Sai Kit, Kenneth 

We have completed the serological investigation of the above outbreak and the findings are as follows. Forty-five paired samples were provided from patients ranging in age from 8 to 19 years, with 57.8% in the 14-16 years age group, 24.4% in 13 years and below age group and 17.8% in the 17 years and above age group. Fever was the most common feature, followed by vomiting and bodyache. Some of the patients reported headache, giddiness, cough, chest pain and conjunctivitis. In the fatal case, the 15-year-old boy had a one-week history of fever, malaise and lethargy and was referred to the Queen Elizabeth Hospital from Beaufort Hospital when he developed a fresh bout of haemoptysis and poor oxygen saturation. He died several hours after admission. No post mortem was performed and no samples were available for investigation. All the patients were from the same area and had bathed regularly in a river near an oil palm estate and a rubber-processing factory. The river was swollen by rainfall and flooding during the current monsoon season. Routine blood and liver function tests were normal and tests for malaria, typhoid, scrub typhus, dengue, and hantavirus were not significant. Blood and urine cultures yielded no growth. Serological tests revealed that the patients had recent exposures to melioidosis and leptospirosis. Of the 45 paired samples, 20 showed 4-fold increase in titres only to _Burkholderia pseudomallei_ in an IgG ELISA using purified antigen and 5 showed 4-fold increase only to _Leptospira biflexa_ in a micro-agglutination test. Two paired samples showed 4-fold increase in titres to both antigens and a number of samples had significant high titres to either or both antigen. Interpretation of serological results to these endemic diseases must be done with due consideration to full clinical signs and symptoms and epidemiological information in each case. 

Footnote: _Burkholderia pseudomallei_ is a saprophyte of certain soils and waters and is the causative agent of melioidosis in humans and animals in Southeast Asian countries, including Malaysia. Clinical manifestations in man are varied, ranging from latent, chronic, subacute to the acute septicemic variety, mimicking almost every known infectious disease. In endemic countries, serological diagnosis is often hampered by raised antibody levels in healthy population where subclinical and asymptomatic infections are common. Severe infection requires early and aggressive antimicrobial therapy since the mortality rate can exceed 60%. Latency and chronic infections are a major feature of melioidosis and relapses while on therapy have been recorded. Recrudescence of infection after an interval of 2-6 years after recovery following prolonged maintenance therapy has been reported. Leptospirosis is a zoonotic disease of worldwide prevalence caused by a spirochaete of the genus Leptospira. The natural reservoir is wild rodents but domestic animals such as dogs, cattle, swine, goats and horses serve as the major source of human infection. The transmission is often via indirect contact with soil, water and food contaminated by urine of infected animals. Leptospires can survive for long periods in stagnant water and wet soil. The clinical presentation in man includes fever, chill, headache, conjunctivitis, myalgia and gastrointestinal symptoms. The University Hospital Kuala Lumpur processes about 100 blood samples annually and about 10-20% are positive using the leptospiral microagglutination test.

A second posting on 22 October 1999 by a ?doctor Fazlon Dennis from Malta MOH hit the diagnosis spot-on. His posting to ProMed is appended below.

UNDIAGNOSED ILLNESS, SWIMMERS - MALAYSIA (BEAUFORT) (02)

Date: Fri, 22 Oct 1999 08:47:00 +0200 From: Falzon Dennis at MOH 

While more information about common symptomatology and mortality in fellow swimmers would be helpful, a distinct possibility would be leptospirosis, more so considering the location (stream, SE Asia, oil palms). Another less likely one would be melioidosis. Other common exposures over the previous days would be useful, such as environmental exposure (malaria) and common meals (intoxication). Look forward to more clues. 

I think this is yet another example on how the Internet has crossed boundaries, religion and culture in dissemination, sharing and exchange of information. So what do we know of these two diseases?

Leptospirosis

From CDC site on FAQ on Leptospirosis as well as from Health Canada - Laboratory Centre for Disease Control, and Medical Microbiology (Russell C. Johnson) we have the following.

What is leptospirosis

Leptospirosis (Leptospirosis, Weil's disease, Canicola fever, Hemorrhagic jaundice, Mud fever, Swineherd's disease) is a bacterial disease that affects humans and animals. It is caused by bacteria of the genus Leptospira. In humans it causes a wide range of symptoms, and some infected persons may have no symptoms at all. Symptoms of leptospirosis include high fever, severe headache, chills, muscle aches, and vomiting, and may include jaundice (yellow skin and eyes), red eyes, abdominal pain, diarrhea, or a rash. If the disease is not treated, the patient could develop kidney damage, meningitis (inflammation of the membrane around the brain and spinal cord), liver failure, and respiratory distress. In rare cases death occurs.
Leptospira is a flexible, spiral-shaped, Gram-negative spirochete with internal flagella. Leptospira interrogans has many serovars based on cell surface antigens. Many of these symptoms can be mistaken for other diseases. Culture for leptospirosis from blood, urine and other body fluids or tissues is the gold standard. It requires special techniques and mass media but is otherwise not difficult. Organisms can only be isolated from blood and CSF during the first 10 days of the illness and appear in the urine during the second week. Cultures have to be incubated for 5-6 weeks, however laboratry diagnosis is usually made by serology using agglutination testing.

How do people get leptospirosis?

Outbreaks of leptospirosis are usually caused by exposure to water contaminated with the urine of infected animals. Many different kinds of animals carry the bacterium; they may become sick but sometimes have no symptoms. Leptospira organisms have been found in cattle, pigs, horses, dogs, rodents, and wild animals. Humans become infected through contact with water, food, or soil containing urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact, especially with mucosal surfaces, such as the eyes or nose, or with broken skin. The disease is not known to be spread from person to person.

How long is it between the time of exposure and when people become sick?

The time between a person's exposure to a contaminated source and becoming sick is 2 days to 4 weeks. Illness usually begins abruptly with fever and other symptoms. Leptospirosis may occur in two phases; after the first phase, with fever, chills, headache, muscle aches, vomiting, or diarrhea, the patient may recover for a time but become ill again. If a second phase occurs, it is more severe; the person may have kidney or liver failure or meningitis. This phase is also called Weil's disease.

The illness lasts from a few days to 3 weeks or longer. Without treatment, recovery may take several months.

Where is leptospirosis found?

Leptospirosis occurs worldwide but is most common in temperate or tropical climates. It is an occupational hazard for many people who work outdoors or with animals, for example, farmers, sewer workers, veterinarians, fish workers, dairy farmers, or military personnel. It is a recreational hazard for campers or those who participate in outdoor sports in contaminated areas and has been associated with swimming, wading, and whitewater rafting in contaminated lakes and rivers. The incidence is also increasing among urban children.

How is leptospirosis treated?

Leptospirosis is treated with antibiotics, such as doxycycline or penicillin, which should be given early in the course of the disease. Intravenous antibiotics may be required for persons with more severe symptoms. Persons with symptoms suggestive of leptospirosis should contact a
health care provider.

Can leptospirosis be prevented?

The risk of acquiring leptospirosis can be greatly reduced by not swimming or wading in water that might be contaminated with animal urine.
Protective clothing or footwear should be worn by those exposed to contaminated water or soil because of their job or recreational activities.

Melioidosis

The following information were obtained from Melioidosis (Down), Medicinenet, DBMB, eMedicine, Wrong Diagnosis, UMMC* and Medical Microbiology (Barbara H. Iglewski) .

Since the discovery of a glanders-like organism as the cause of a lethal metastatic abscess-forming infection by Whitmore and Krishnaswamy over eighty years ago, Burkholderia pseudomallei has come to be recognised as a major pathogen in East Asia and Northern Australia. 

Definition

Melioidosis (Whitmore's bacillus, Melioidosis; (formerly Pseudomonas)) is an infectious disease of humans and animals caused by a gram-negative bacillus found in soil and water. It has both acute and chronic forms. Most infection is thought to be acquired through percutaneous inoculation.

Description

Melioidosis, which is sometimes called B. pseudomallei  infection, is endemic (occurring naturally and consistently) in Southeast Asia, Australia, and parts of Africa. It was rare in the United States prior to recent immigration from Southeast Asia.

Causes & symptoms

The bacillus can cause disease in sheep, goats, pigs, horses, and other animals, as well as in humans. The organism enters the body through skin abrasions, burns, or wounds infected by contaminated soil; inhalation of dust.

Pneumonia is the commonest presentation of melioidosis. As well as severe septicaemic pneumonia with a mortality of over 50%, many patients present with milder forms of pneumonia which respond well to appropriate antibiotics. Other presentations of melioidosis include skin abscesses or ulcers, abscesses in the internal organs such as the prostate, spleen, kidney and liver, fulminant septicemia with multi-organ abscesses and unusual neurological illnesses such as brainstem encephalitis and acute paraplegia. Persons without symptoms or a known history of disease can also be found to be positive on serological testing.

Diabetes is the most important risk factor for melioidosis, with around 40% of cases being diabetic. In addition, excessive alcohol consumption, chronic renal disease, chronic lung disease and excessive kava drinking are risk factors for melioidosis. While the majority of patients with melioidosis have one or more of these risk factors, melioidosis can also occur occasionally in children and healthy adults.

Chronic melioidosis is characterized by osteomyelitis (inflammation of the bone) and pus-filled abscesses in the skin, lungs, or other organs. Acute melioidosis takes one of three forms: a localized skin infection that may spread to nearby lymph nodes; an infection of the lungs associated with high fever (102[deg]F/38.9[deg]C), headache, chest pain, and coughing; and septicemia (blood poisoning) characterized by disorientation, difficulty breathing, severe headache, and an eruption of pustules on the head or trunk.

Diagnosis

Melioidosis is usually suspected based on the patient's history, especially travel, occupational exposure to contaminated soil, water and infected animals. Diagnosis must then be confirmed through laboratory tests. B. pseudomallei can be cultured from samples of the patient's sputum, blood, or tissue fluid from abscesses. Blood tests, including complement fixation (CF) tests and hemagglutination tests, also help to confirm the diagnosis. These serological tests are now replaced by Immunoflourescent and ELISA. In acute infections, chest x rays and liver function tests are usually abnormal.

How is melioidosis treated?

For the last 9 years high-dose intravenous ceftazidime has been the drug of choice for the treatment of severe melioidosis, after ceftazidirne was shown to be superior to the "conventional" four drug regimen (chloramphenicol, doxycycline and trimethoprim-sulphamethoxazole) in a randomised trial. Combination ceftazidime-trimethoprim-sulphamethoxazole was compared with the conventional regimen in a separate trial with similar results, but we still do not know whether such combination therapy is needed in melioidosis. Co-amoxiclav (amoxycillin-clavulanate) has been shown to be effective but was associated with a higher rate of treatment failure than ceftazidime. Two further treatment trials in acute melioidosis have recently been conducted in Thailand. In the first of these, high-dose intravenous imipenem was compared with ceftazidime and the results suggest that the two regimens possess similar efficacy. Cefoperazone-sulbactam has been compared with ceftazidime-trimethoprim-sulphamethoxazole in a small number of patients, further results are awaited. Relapses of melioidosis should be treated in a similar manner to primary infections.

A maintenance phase of treatment with either Bactrim or Doxycycline (depending on sensitivity) is required following intravenous therapy. This maintenance therapy is required for a prolonged period of approximately 3-6 months.

Prognosis

The mortality rate in acute cases of pulmonary melioidosis is about 10%; the mortality rate for the septicemic form is higher (70% - 80%), with or without pulmonary involvement. The prognosis for recovery from mild infections is excellent.

Prevention

There is no form of immunization for melioidosis. Prevention requires prompt cleansing of scrapes, burns, or other open wounds in areas where the disease is common. Public education remains very important so that wherever possible people avoid contact with wet season soils or muddy water. Wearing footwear and the use of gloves whilst gardening or working outdoors are very important measures to avoid possible exposure. These are especially important to emphasize for all diabetics.

 

*Thanks to  Prof. Adeeba bte Kamarulzaman,  Prof. Puthucheary and Prof. Jamunarani Vadivelu from University Malaya Medical Centre for their input.

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