|Specialty|| Infectious disease |
Melioidosis is an infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei , found in soil and water. It is of public health importance in endemic areas, particularly in northeast Thailand, Vietnam, and northern Australia. It exists in acute and chronic forms. Signs and symptoms may include pain in chest, bones, or joints; cough; skin infections, lung nodules, and pneumonia.
Burkholderia pseudomallei is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in Thailand and northern Australia. It infects humans and animals and causes the disease melioidosis. It is also capable of infecting plants.
Soil is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Earth's body of soil, called the pedosphere, has four important functions:
Water is a transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's streams, lakes, and oceans, and the fluids of most living organisms. It is vital for all known forms of life, even though it provides no calories or organic nutrients. Its chemical formula is H2O, meaning that each of its molecules contains one oxygen and two hydrogen atoms, connected by covalent bonds. Water is the name of the liquid state of H2O at standard ambient temperature and pressure. It forms precipitation in the form of rain and aerosols in the form of fog. Clouds are formed from suspended droplets of water and ice, its solid state. When finely divided, crystalline ice may precipitate in the form of snow. The gaseous state of water is steam or water vapor. Water moves continually through the water cycle of evaporation, transpiration (evapotranspiration), condensation, precipitation, and runoff, usually reaching the sea.
B. pseudomallei was previously classed as part of the genus Pseudomonas ; until 1992, it was known as Pseudomonas pseudomallei. It is phylogenetically related closely to Burkholderia mallei which causes glanders, an infection primarily of horses, donkeys, and mules. The name melioidosis is derived from the Greek melis (μηλις) meaning "a distemper of asses" with the suffixes -oid meaning "similar to" and -osis meaning "a condition", that is, a condition similar to glanders.
Pseudomonas is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 validly described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens.
Burkholderia mallei is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus Burkholderia causing glanders; the Latin name of this disease (malleus) gave its name to the species causing it. It is closely related to B. pseudomallei, and by multilocus sequence typing it is a subspecies of B. pseudomallei.B. mallei evolved from B. pseudomallei by selective reduction and deletions from the B. pseudomallei genome. Unlike B. pseudomallei and other genus members, B. mallei is nonmotile; its shape is coccobacillary measuring some 1.5–3.0 μm in length and 0.5–1.0 μm in diameter with rounded ends.
Glanders is an infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, goats and humans. It is caused by infection with the bacterium Burkholderia mallei, usually by ingestion of contaminated feed or water. Signs of glanders include the formation of nodular lesions in the lungs and ulceration of the mucous membranes in the upper respiratory tract. The acute form results in coughing, fever, and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating. Death can occur within months, while survivors act as carriers.
Most of the people who exposed to the bacteria experienced no symptoms. For those children staying in endemic areas, 25% of them experienced seroconversion (the time period needed for antibodies started to form against antigens) in between 6 months to 4 years. This means that high number of asymptomatic people will be tested positive in serology in endemic areas.
In epidemiology, an infection is said to be endemic in a population when that infection is constantly maintained at a baseline level in a geographic area without external inputs. For example, chickenpox is endemic in the UK, but malaria is not. Every year, there are a few cases of malaria reported in the UK, but these do not lead to sustained transmission in the population due to the lack of a suitable vector. While it might be common to say that AIDS is "endemic" in Africa, meaning found in an area, this is a use of the word in its etymological, rather than epidemiological, form. AIDS cases in Africa are increasing, so the disease is not in an endemic steady state. It is correct to call the spread of AIDS in Africa an epidemic.
In immunology, seroconversion is the time period during which a specific antibody develops and becomes detectable in the blood. After seroconversion has occurred, the disease can be detected in blood tests for the antibody. During an infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is, by definition, absent. During seroconversion, the antibody is present but not yet detectable.
In immunology, antigens (Ag) are structures specifically bound by antibodies (Ab) or a cell surface version of Ab ~ B cell antigen receptor (BCR). The terms antigen originally described a structural molecule that binds specifically to an antibody only in the form of native antigen. It was expanded later to refer to any molecule or a linear molecular fragment after processing the native antigen that can be recognized by T-cell receptor (TCR). BCR and TCR are both highly variable antigen receptors diversified by somatic V(D)J recombination. Both T cells and B cells are cellular components of adaptive immunity. The Ag abbreviation stands for an antibody generator.
The mean incubation period of acute melioidosis was 9 days (range 1–21 days). Symptoms usually appear 2 to 4 weeks after exposure. Those affected are presented with symptoms of sepsis (predominantly fever) with or without pneumonia, or localised abscess or other focus of infection. The presence of non-specific signs and symptoms has caused meliodosis to be nicknamed as "the great mimicker".
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, incubation period signifies the period taken by the multiplying organism to reach a threshold necessary to produce symptoms in the host.
Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. In the very young, old, and people with a weakened immune system, there may be no symptoms of a specific infection and the body temperature may be low or normal, rather than high. Severe sepsis is sepsis causing poor organ function or insufficient blood flow. Insufficient blood flow may be evident by low blood pressure, high blood lactate, or low urine output. Septic shock is low blood pressure due to sepsis that does not improve after fluid replacement.
Pneumonia is an inflammatory condition of the lung affecting primarily the small air sacs known as alveoli. Typically symptoms include some combination of productive or dry cough, chest pain, fever, and trouble breathing. Severity is variable.
Those people with diabetes mellitus or occupation or seasonal exposure to the bacteria are at increased risk of developing meliodosis. The disease should be considered in anyone who has fever and staying in endemic areas and those who has abscesses in liver, spleen, prostate, or parotid gland with pneumonia.The clinical manifestation of the disease can range from simple skin changes to severe organ involvement. Among the commonest organs affected are: liver, spleen, lungs, prostate, and kidneys. Bacteremia can occur in 40 to 60% of the people while septic shock occurs in 20% of the cases. Pneumonia is present in 50% of the cases. For those presented with septic shock together with pneumonia, there could be minimal cough. However, for those presented with pneumonia only, prominent cough with sputum and shortness of breath could be observed. On chest X-ray, the appearance could range from diffuse nodular infiltrates in those with septic shock to progressive pulmonary consolidation in the upper lobes for those presented with pneumonia only. Pleural effusion and empyema are more common for meliodosis affecting lower lobes of the lungs. Therefore, meliodosis should be differentiated from tuberculosis for those coming from endemic areas because both conditions show radiogical changes on the upper lobes of the lungs. 1% to 5% of those infected could develop encephalomyelitis or brain abscess, 40 to 60% of them could develop myocarditis or mycotic aneurysm, 14 to 28% of the cases could develop acute pyelonephritis, kidney abscess or prostatic abscesses, 0 to 30% would develop neck or parotid gland abscess, 10 to 33% would develop liver, spleen, or paraintestinal abscesses and 4 to 14% of the cases could develop septic arthritis and osteomyelitis. Specifically in Australia, up to 20% of the males can get prostatic abscess. In Thailand, 30% of the infected children can get parotid abscess.
Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic disorders characterized by high blood sugar levels over a prolonged period. Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes.
Bacteremia is the presence of bacteria in the blood. Blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal. It is distinct from sepsis, which is the host response to the bacteria.
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%.
Chronic melioidosis is usually defined by a duration of symptoms greater than two months and occurs in about 10% of patients.The clinical presentation of chronic melioidosis is protean and includes such presentations as chronic skin infections, chronic lung nodule, and pneumonia. In particular, chronic melioidosis closely mimics tuberculosis, and has sometimes been called "Vietnamese tuberculosis". Other clinical presentations include: fever, weight loss, productive cough with or without bloody sputum with long standing abscesses at multiple body sites.
Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. The classic symptoms of active TB are a chronic cough with blood-containing sputum, fever, night sweats, and weight loss. It was historically called "consumption" due to the weight loss. Infection of other organs can cause a wide range of symptoms.
Vietnamese tuberculosis refers to certain forms of chronic melioidosis that look clinically very similar to tuberculosis. It is derived from the clinical appearance of the disease in American soldiers returning from the Vietnam War.
In latent infection, immunocompetent people have the ability to clear out the infection without showing any symptoms. However, less than 5% of all meliodosis cases has activation after a period of latency.Patients with latent melioidosis may be symptom-free for decades; the longest period between presumed exposure and clinical presentation is 62 years. The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". Various cormorbidities such as diabetes, renal failure, and alcoholism can predispose to reactivation of meliodosis.
Meliodosis is caused by gram negative, opportunistic, facultative, intracellular, motile saprophyte bacteria named Burkholderia pseudomallei.The bacteria is also aerobic and oxidase test positive. A vacuole located at the centre of the bacteria makes it resembles “safety pin” appearance on gram stain. The bacteria produces glycocalyx polysaccharide capsule which makes it resistant to many types of antibiotics. The bacteria emits a strong soil smell after 24 to 48 hours of incubation. It is generally resistant to gentamicin and colistin antibiotics but is sensitive to Amoxicillin/clavulanic acid (co-amoxiclav). B. pseudomallei is a biosafety level 3 pathogen which requires specialized laboratory handling. In animals, another similar organism named Burkholderia mallei is the causing agent which results in a disease named glanders. B. pseudomallei can be differentiated from another closely related, but less pathogenic species B. thailandensis by its ability to assimilate arabinose. B. pseudomallei is highly adaptable to various host environments. The bacteria has been shown to survive inside Mycorrhiza fungi and amoeba. Thus it has a survival advantage in the human body.
The genome of B. pseudomallei consists of two replicons: chromosome 1 which encodes for housekeeping function of the bacteria such as cell wall synthesis, mobility, and metabolism, and chromosome 2 which encodes for functions that allow the bacteria to adapt to various environments. Horizontal gene transfer between two bacteria causes highly variable genome in B. pseudomallei. Australia has been suggested as the early reservoir for B. psudomallei because of high genetic variability of the bacteria found in this region. The bacteria isolates from Africa, Central and South America seems to have a common ancestor originated from 17th to 19th century.
Infection can enter through wounds, inhalation, and ingestion of polluted water.Person-to-person transmission have been reported, but is extremely rare. Melioidosis is a recognised disease in animals, including cats, goats, sheep, and horses. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. Birds are also considered as relatively resistant to meliodosis. An outbreak at the Paris Zoo in the 1970s ("L’affaire du jardin des plantes") was thought to have originated from an imported panda or horses from Iran. Transmission from animals to humans (zoonosis) is also rare.
B. pseudomallei is normally found in soil and surface water, and is more abundant at greater than 10 cm from the soil surface °C (75.2 °F) to 32 °C (89.6 °F). However, the bacteria does not survive in the presence of ultraviolet light. A history of contact with soil or surface water is, therefore, almost invariable in patients with melioidosis; that said, the majority of patients who do have contact with infected soil suffer no ill effects. Even within an area, the distribution of B. pseudomallei within the soil can be extremely patchy, and competition with other Burkholderia species has been suggested as a possible reason. Contaminated ground water was implicated in one outbreak in northern Australia. Also implicated are severe weather events such as flooding tsunamis and typhoons. Inadequate chlorination of water supply had been associated with B. pseudomallei outbreak in Northern and Western Australia. The bacteria is also found in unchlorinated water supply in rural Thailand. Irrigation fluid contaminated with B pseudomallei is associated with nosocomial wound infection in hospitals. Based on whole genome sequencing, humans may play a role in moving B. pseudomallei from place to place.up to 80cm to 90 cm. It has been found in soils, ponds, streams, pools, stagnant water, and paddy rice fields. B. pseudomallei can survive in nutrient poor condition such as distilled water, desert, and nutrient depleted soil for more than 16 years. It can also survive in antiseptic and detergent solutions, acidic environments with pH up to 4.5 for 70 days within temperature range from 24
Meliodosis is found in all age groups.For Australia and Thailand, the median age of infection is 50 years; 5 to 10% of the patients are less than 15 years. The single most important risk factor for developing melioidosis is diabetes mellitus, followed by hazardous alcohol use, chronic kidney disease, and chronic lung disease. In all people with meliodosis, greater than 50% of them have diabetes. Diabetes has 12 folds increased risk of meliodosis. Diabetes decreases the ability of macrophages to fight the bacteria and reduced the ability of T helper cell production. Excessive release of Tumor necrosis factor alpha (TNF) and Interleukin 12 by mononuclear cells causes greater risk of septic shock. The Glibenclamide drug taken by diabetes patients can also cause blunting of monocyte’s inflammatory responses. Other risk factors include thalassaemia, occupation (rice paddy farmers), cystic fibrosis, , recreational exposure to soil, water, male, age > 45 years, and prolonged steroids/immunosuppresion. However, 8% of the peadiatrics and 20% of the adult with meliodosis have no risk factors. HIV infection does not predispose to melioidosis. Neonatal cases have been reported possibly due to mother-to-child transmission, community acquired infection, or healthcare-associated infection.
The bacteria has the ability to infect various types of cells and to evade human immune response.When skin is broken, B pseudomallei first enters and replicates in the epithelial cells of the broken skin. The bacteria then can infect both phagocytes and non-phagocytes in the blood stream. The bacteria enters these cells through endocytosis inside an endocytic vesicle. B pseudomallei has multiple secretory systems and can be transported across cellular membranes, aiding invasion into a host cell. B. pseudomallei uses Type III secretion system (T3SS) system effector proteins for invasion into a cell. T3SS is a molecular syringe that injects effector proteins into host cells. The effector proteins rearrange the host cytoskeleton to facilitate invasion.The cell entry is aided by flagella, LPS, type IV pilin, and adhesion proteins BoaA and BoaB. The T3SS effector protein bopA helps to disrupt endocytic vesicle and thus avoid the bacteria from being digested by lysosomes inside the cell. The bacteria then replicates inside the cytoplasm of the cell. The bacteria are also able to withstand high oxidative stress in an endocytic vesicle by creating an acidic environment. Once inside cytoplasm, BimA autotransporter proteins protein helps escape the bacteria from phagosome. Premature killing of macrophage can also cause the evasion of B. pseudomallei from being digested. Besides, the delayed degradation of infected neutrophils ingested by macrophages also causes the bacteria to proliferate inside the host cells. CD4 T cells and cytotoxic CD8 T cells are important to keep meliodosis at bay. Reduction of these cells is associated with higher risk of death. Although activation of coagulation cascade is helpful in containing meliodosis infection, overactivation coagulation cascade can cause disseminated intravascular coagulation (DIC).
Meliodosis infection induces humoral immunity through the release of interferon gamma (IFN) and cell-mediated immunity.In the host, Protease-activated receptor-1 (PAR-1) expressed on the surface of endothelial cells, platelets, and monocytes helps B. pseudomallei invasion. However, macrophages activated by IFN has improved killing of B. pseudomallei via the production of inducible nitric oxide synthase (NOS). Human Toll-like receptor (TLRs) such as TLR2, TLR4, TLR 5 recognizes the pathogen-associated molecular pattern (PAMPs) of the bacteria such as LPS and flagella, thus initiating immune response against the bacteria. As a result, Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18) are produced. Neutrophils, dendritic cells, B cell and T cells activate the human complement membrane attack complex (MAC) but the complement activity is hampered by external capsule and lipopolysaccharide (LPS) of the bacteria. These two features of the bacteria are also resistant to lysosomal degradation, thus enabling the survival of the bacteria in human phagocytes. Once B. pseudomallei escaped from the lysosomal destruction, it enters the cytosol of the cell. Meanwhile, inside the human cell, Pattern recognition receptors of the cytosol namely NOD-like receptors detects the Damage-associated molecular pattern (DAMP)s of the bacteria. As a result, inflammasomes which contains Caspase 1 are released to digest the bacteria. Activation of Caspase 1 enables the pyroptosis of the bacteria and increases the production of Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18). IL-18 increases IFN production through natural killer cells while IL-1beta reduces the IFN production. Thus, reduction in IFN gamma contributes to the persistence of the bacteria intra-cellularly. However, HIV infection is not a risk factor for meliodosis. Although macrophages show deregulated cytokine response in individuals with HIV infection, bacterial internalization and intracellular killing are still effective.
The bacteria then proceeds to spread from cell to cell. The bacteria rearrange the host cell cytoskeleton using Bim A to allow the latter to form a membranous protusions that extends into neighbouring cells. The bacteria then travel into another cell using actin. The action of these bacteria causes the fusion of the adjacent cells which leads to the formation of multinucleated giant cells (MNGCs). When MNGCs lyse, they form plaques (a central clear area with a ring of fused cells). These plaques then provide shelter for the bacteria for further replication or latent infection. With the help of Bim A autotrasporter protein, the bacteria are able to travel through nerve roots in the spinal cord and brain, thus leading to encephalomyelitis (inflammation of the brain and spinal cord).
Besides spreading from cell to cell, the bacteria can also spread through blood stream, causing sepsis. The bacteria can survive in antigen presenting cells and dendritic cells. Thus, these cells acts as vehicles that transport the bacteria into the lymphatic system, causing widespread dissemination of the bacteria in the human body.
B. pseudomallei can remain latent in the human body from 19 to 29 years until it is reactivated duringhuman immunosuppression or stress response. The mechanism of latent infection remains unclear as of 2018. Amongst mechanisms suggested are: residing in the nucleus of the cell to prevent being digested, entering a stage of slower growth rate, antibiotic resistance, and genetic adaption to the host environment.Granulomas (containing neutrophils, macrophages, lymphocytes, and multinucleated giant cells) formed at the infection site in meliodosis has been associated with latent infection in human body.
A gold standard of meliodosis diagnosis have not been identified. °C (98.6 °F) in air and inspected daily for four days. B. pseudomallei can be grown on sheep blood agar, MacConkey agar, and Ashdown's medium (containing gentamicin). On agar plates, B. pseudomallei will be seen as creamy, non-haemolytic, with shape similar to a rod on Day 2 of incubation. On Day 4 of incubation, the colonies will appear dry and wrinkled. Francis medium, which is a modification of Ashdown medium, where the concentration of gentamicin increased from 4mg/L to 8 mg/L. Yellow colonies of B. pseudomallei are grown on Francis medium. For laboratories located outside endemic areas, Burkholderia cepacia selective agar or Pseudomonas selective agar can be used alternative if Ashdown's medium is not available.Bacterial culture is the definitive diagnosis of melidosis. It is important not misinterpret the bacterial growth as Pseudomonas or Bacillus spp. B. pseudomallei is never part of human flora. Therefore, any growth of the bacteria should be regarded as diagnostic of meliodosis. Blood culture is the most important sample for culture because the bacteria are usually found in blood. Other samples such as throat, rectal swabs, pus from abscesses, and sputum can also be used for culture. Blood cultures can be positive in 50 to 60% of the cases. For those strongly suspected of meliodosis but with initial negative culture, repeated cultures can be taken because the culture can become positive subsequently. The agar plates should be incubated at 37
Latex agglutination is useful in screening for suspected B. pseudomallei colonies.Molecular methods such as 16srDNA and polymerase chain reaction (PCR) can be used to detect B. pseudomallei bacteria.
Ashdown's medium, a selective medium containing gentamicin, may be required for cultures taken from nonsterile sites. Burkholderia cepacia medium may be a useful alternative selective medium in nonendemic areas, where Ashdown's is not available.A new medium derived from Ashdown, known as Francis medium, may help differentiate B. pseudomallei from B. cepacia and may help in the early diagnosis of melioidosis, but has not yet been extensively clinically validated.
B. pseudomallei can be observed under microscopy. The organism is described as gram negative rod shaped bacterium with bipolar staining similar to safety pin appearance. However, light microscopy is both not specific and not sensitive. Immunofluorescent microscopy approaches 100% in specificity and while achieved less than 50% sensitivity. A lateral flow immunoassay has been developed but not extensively evaluated.
Serological tests such as indirect haemagglutination test has been used to detect the presence of antibodies against B. pseudomallei. However, the test suffered from poor sensitivity and specificity because those staying in meliodosis endemic areas usually shows high background antibody titres.For Autralia, the cut-off point of antibody titer is 1:40. In Thailand, the cut-off antibody titre is 1:160. Thailand also uses direct immunofluorescent antibody test (IFAT) and latex agglutination. In IFAT, both B. pseudomallei antigen and B. thailandensis can be used to quantity the amount of antibodies produced against the bacteria. Therefore, the results have to be interpreted with caution as there could be false positive reaction when the human body is exposed to non-pathogenic B. thailandensis infection.
A commercial ELISA kit for melioidosis appears to perform well.but no ELISA test has yet been clinically validated as a diagnostic tool.
It is not possible to make the diagnosis on imaging studies alone(such as X-rays, ultrasound, and CT scans), but imaging is routinely performed to assess the extent of disease spread. Imaging of the abdomen using CT scans or ultrasound is recommended routinely, as abscesses may not be clinically apparent and may coexist with disease elsewhere. Australian authorities suggest imaging of the prostate specifically due to the high incidence of prostatic abscesses in northern Australian patients. A chest X-ray is also considered routine, with other investigations as clinically indicated. The presence of honeycomb abscesses in the liver is considered characteristic, but is not diagnostic.
The differential diagnosis is extensive; melioidosis may mimic many other infections, including tuberculosis.
Person-to-person transmission is exceedingly unusual;and patients with melioidosis should not be considered contagious. Lab workers should handle B. pseudomallei under BSL-3 isolation conditions, as laboratory-acquired melioidosis has been described. There are also several cases of hospital-acquired infection of meliodosis. Therefore, healthcare providers are still recommended to practice hand hygiene and universal precautions.
Large scale water chlorination has been successful in Australia. In middle to low income countries, water should be boiled before consumption. In high income countries, water could be treated with ultraviolet light for those at risk of contracting melidosis. Those who are high risk of contact with the bacteria should wear protective gear (such as boots and gloves) during work. Those who are staying in endemic areas should avoid direct contact with soil, and outdoor exposure to heavy rain, or dust clouds. Bottled water or boiled water are preferred as drinking water.
After exposure to B. pseudomallei (particularly following a laboratory accident), treatment with co-trimoxazole is recommended. Alternatively, co-amoxiclav and doxycycline can be used for those who is intolerant co-trimoxazole. In view of possibility of severe side effects caused by co-trimoxazole, only high risk individuals will receive such treatments. Low risk individuals would receive frequent monitoring instead.
Several vaccine candidates are being researched; but as of 2018, there is no vaccine approved for public use.There is a fear that when a vaccine is licensed, financial constraints will make the vaccination an unrealistic factor for many countries that are suffering from high rates of melioidosis.
The treatment of melioidosis is divided into two stages, an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various types of antibiotics. B. pesudomallei are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs are designed to kill the bacteria. B. pseudomallei is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs are designed to inhibit the growth of the bacteria. However, the bacteria is resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins.On the other hand, B. pseudomallei isolates from the region of Sarawak, Malaysia are susceptible to gentamicin. Optimal therapy for meliodosis have been determined as a result from clinical trials in Thailand.
Intravenous ceftazidime is the current drug of choice for treatment of acute melioidosis and should be administered 10 to 14 days after getting the infection.Meropenem, imipenem and the cefoperazone-sulbactam combination (Sulperazone) are also effective. Intravenous amoxicillin-clavulanate (co-amoxiclav) may be used if none of the above four drugs is available, but it produces inferior outcomes. Intravenous antibiotics are given for a minimum of 10 to 14 days, and are not usually stopped until the patient's temperature has returned to normal for more than 48 hours. Even with appropriate antibiotic therapy, fevers often persist for weeks or months, and patients may continue to develop new lesions even while on appropriate treatment. The median fever clearance time in melioidosis is 10 days: and failure of the fever to clear is not a reason to alter treatment.
Meropenem is the preferred antibiotic therapy for neurological meliodosis. Co-trimoxazole is recommended for neurological melidosis, osteomyelitis, septic arthritis, skin and gastrointestinal infection, and deeply seated abscess.For deep seated infections such as abscesses of internal organs, osteomyelitis, septic arthritis, and neurological meliodosis, the duration of antibiotics given should be longer (up to 4 to 8 weeks). The time taken for fever to be resolved can be more than 10 days in those with deep seated infection. The dosage for intravenous ceftazidime is 2g 6 hourly in adults (50 mg/kg up to 2g in children less than 15 years old). The dosage for meropenem is 1g 8 hourly in adults (25 mg/kg up to 1g in children). Resistance to ceftazidime, carbapenems, and co-amoxiclave are rare. There is no differences when using cefoperazone/sulbactam or ceftazidime to treat meliodosis as both of them shows similar death rates and disease progression following treatment.
Theoretical reasons are given for believing mortality might be lower in patients treated with imipenem: first, less endotoxin is released by dying bacteria during imipenem treatment, pseudomallei than for many other organisms, and patients being haemofiltered will need more frequent or higher doses. Intravenous meropenem is routinely used in Australia. Meropenem is the drug of choice for severe meliodosis with septic shock in Australia. Once the clinical condition improved, meropenem can be switched back to ceftazidime.and the minimum inhibitory concentration (MIC) for imipenem is lower than for ceftazidime. However, no clinically relevant difference was found in mortality between imipenem and ceftazidime treatments. The MIC of meropenem is higher for B.
Moxifloxacin, cefepime, tigecycline, and ertapenem do not appear to be effective in vitro.Piperacillin-sulbactam, doripenem and biapenem appear to be effective in vitro, but no clinical experience exists on which to recommend their use.
Adjunctive treatment with granulocyte colony-stimulating factoror co-trimoxazole were not associated with decreased fatality rates in trials in Thailand.
Following the treatment of the acute disease, eradication (or maintenance) treatment with co-trimoxazole is the drug of choice which should be used for at least 3 months. For those with neurological meliodosis and osteomyelitis, duration more than 6 months. Co-amoxiclav and doxycycline are drugs of second choice. Co-trimoxazole should not be used in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it can cause haemolytic anemia. Other side effects such as rash, hyperkalemia, renal dysfunction, and gastrointestinal symptoms should prompt the reduction of co-trimoxazole doses.Chloramphenicol is no longer routinely recommended for this purpose. Co-amoxiclav is an alternative for those patients who are unable to take co-trimoxazole and doxycycline (e.g., pregnant women and children under the age of 12), but is not as effective. Single agent treatment with a fluoroquinolone (e.g., ciprofloxacin) or doxycycline for the oral maintenance phase is ineffective.
In Australia, co-trimoxazole is used in children and could also be used in pregnant mothers after the first 12 weeks of pregnancy. Meanwhile, in Thailand, co-amoxiclav is the drug of choice for children and pregnancy women. However, the co-amoxiclav dosing is problematic and B. pseudomallei can easily acquire resistance when this drug is used.The dosing regimen for co-trimoxazole (trimethoprim/sulfamethoxazole) in eradication phase is 6/30 mg/kg, up to maximum 240/1200 mg in children, 240/1200 mg in adults weighing 40 to 60 kg, and 320/1600 mg in adults weighing more than 60 kg, taken orally every 12 hours. In children, co-trimoxazole is taken together with folic acid (0.1 mg/kg up to 5mg in children). There are also cases where melidosis is successfully treated with co-trimoxazole for 3 months without going through intensive therapy provided that there is only skin manifestations without involvement of internal organs or sepsis. Resistance to cotrimoxazole is quite rare in Australia.
Surgical drainage is indicated for single, large abscess in the liver, muscle, and prostate. However, for multiple abscesses in the liver, spleen, and kidney, surgical drainage may not be possible or necessary. For septic arthritis, arthrotomy washout and drainage is required. Surgical debridement may be necessary for surgical debridement. For those with mycotic aneurysm, urgent surgery is required for prosthetic vascular grafts. Life-long therapy with co-trimoxazole may be needed for those with prosthetic vascular grafts. Other abscesses rarely need to be drained because majority of them can resolve with antibiotic treatment.
Immunomodulating therapies such as granulocyte colony-stimulating factor (G-CSF), Interleukin 7 (IL-7), and anti-PDI (programmed cell death) could be useful in meliodosis treatment. This is because immune function is strongly associated with the pathogenesis of meliodosis.
In resourceful settings, where the disease can be detected and treated early, the risk of death is 10%. Meanwhile, in resource poor settings, the risk of death from the disease is more than 40%.
For those with incomplete treatment, recrudescence can occur. Then, hospital admission is needed for intravenous antibiotics. For those completed treatment successfully, recurrence can also occur due to recrudescence or new meliodosis infection. With better therapies, the recrudescence rate has reduced from 10% to 5%. New infection is now more common than recrudescence.Recurrence occurs in 10 to 20% of patients, but with co-trimoxazole eradication therapy, this can be reduced to 4%. While molecular studies have established the majority of recurrences are due to the original infecting strain, a significant proportion of recurrences (perhaps up to a quarter) in endemic areas may be due to reinfection, particularly after two years. Risk factors include severity of disease (patients with positive blood cultures or multifocal disease have a higher risk of relapse), choice of antibiotic for eradication therapy (doxycycline monotherapy and fluoroquinolone therapy are not as effective), poor compliance with eradication therapy and duration of eradication therapy less than 8 weeks.
Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and malignancy can worsens the long term survival and disability of those recovered from infection. The most severe complication of meliodosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs) or partial, flaccid paraparesis (muscle weakness of both legs) or foot drop. For those with previous meliodosis associated bone and joint infection, complications such as sinus tract infection, bones and joint deformities with limited range of motion can occur.
Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. It is classified by the US Centers for Disease Control (CDC) as a category B,Tier 1 select agent. Another similar bacteria, Burkholderia mallei was used by the Germans in World War I to infect livestocks shipped to Allied countries. Soviet Union reportedly used B. mallei during Soviet–Afghan War in 1982 and 1984. B. pseudomallei, like B. mallei, was studied by both US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may potentially have investigated the properties of the bacteria for biological weapons. The bacteria is readily available in the environment and is cost effective to produce. It can also be aerosolized and transmitted via inhalation. However, the bacteria has never been used in biological warfare.
Meliodosis is an understudied disease which remained endemic in developing countries. As of 2018, meliodosis is not included in the WHO list of neglected tropical diseases. In 2015, International Meliodosis Society (IMS) was formed to raise awareness regarding the disease.Melioidosis is endemic in parts of southeast Asia (including Thailand, Laos, Singapore, Brunei, Malaysia, Burma and Vietnam), China, Taiwan and northern Australia. Flooding can increase its extent, including flooding in central Australia. Multiple cases have also been described in Hong Kong and Brunei India, and sporadic cases in Central and South America, the Middle East, the Pacific and several African countries.
Although only one case of melioidosis has ever been reported in Bangladesh, pseudomallei has been isolated from soil in Bangladesh, but this remains to be verified scientifically. This suggests that melioidosis is endemic to Bangladesh and that a problem of underdiagnosis or under-reporting exists there. most likely due to a lack of adequate laboratory facilities in affected rural areas. A high isolation frequency (percentage of positive soil samples) was found in east Saravan in rural Lao PDR distant from the Mekong River, thought by the investigators to be the highest geometric mean concentration in the world (about 464 (25-10,850 CFU/g soil).at least five cases have been imported to the UK from that country. Recent news reports indicate B.
A statistical model indicated that the incidence will be 165,000 cases per year in 2016 (95% confidence interval, 68,000 to 412,000), with 138,000 of those occurring in East and South Asia and the Pacific.In about half of those cases (54% or 89,000), people will die. Northeast Thailand has the highest incidence of melioidosis recorded in the world (an average incidence of 12.7 cases per 100,000 people per year). In Northeast Thailand, 80% of children are positive for antibodies against B. pseudomallei by the age of 4; the figures are lower in other parts of the world. Under-reporting is a prevalent problem because only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on modeling. Besides, lack of laboratory diagnositic capabilities and the lack of disease awareness amongst health care providers also causes underdiagnosis. Even if the culture turns positive for ‘’B. pesudomallei’’, it could discarded as contaminant especially in laboratories in non-endemic areas.
The disease is clearly associated with increased rainfall, with the number (and severity) of cases rising following increased precipitation.
Pathologist Alfred Whitmore and assistant Krishnaswami first reported the disease among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. pseudomallei, also known as the Whitmore bacillus, was identified in 1917 in Kuala Lumpur. First human case of meliodosis was reported in Sri Lanka in 1927. In 1932, 83 cases were reported in South and Southeast Asia with 98% mortality. In 1936, first animal (sheep) case of meliodosis was reported in Madagascar, South Africa. In 1937, soil and water are identified as habitat of B pseudomallei. During Vietnam War from 1967 to 1973, 343 American soldiers were reported with meliodosis, with about 50 cases reported to have transmitted through inhalation. First evidence of B. pseudomallei (in soil) in Brazil was reported in 1983.Arthur Conan Doyle may have read the 1912 report before writing a short story that involved the fictitious tropical disease "tapanuli fever" in a Sherlock Holmes adventure. The term “meliodosis” was first coined in 1921. They distinguished it from glanders, a disease of humans and animals that is similar in presentation, but caused by a different micro-organism. B.
Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer be used unless no other alternatives are available.All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline. Aerosolised B pseudomallei was first isolated in 1989. In the same year, Ceftazidime had been shown to reduce the risk of death of meliodosis from 74% to 37%. In 1992, the pathogen was formally named B. pseudomallei. In 2002, B. pseudomallei was classified as "Category B agent". Attenuated vaccine was developed on the same year. In 2003, multilocus sequence typing for B. pseudomallei was developed. In 2012, B pseudomallei was classified as "Tier 1 select agent" by CDC. In 2014, co-trimoxazole was established as the oral eradication therapy. In 2015, B pseudomallei DNA was detected in filtered air using quantitative PCR. In 2016, a statistical model was developed to predict the occurrence of global meliodosis per year. In 2017, whole genome sequencing points to Australia as the early reservoir for meliodosis.
Septic arthritis, also known as joint infection or infectious arthritis, is the invasion of a joint by an infectious agent resulting in joint inflammation. Symptoms typically include redness, heat, and pain in a single joint associated with a decreased ability to move the joint. Onset is usually rapid. Other symptoms may include fever, weakness, and headache. Occasionally, more than one joint may be involved.
Trimethoprim/sulfamethoxazole (TMP/SMX), also known as co-trimoxazole among other names, is an antibiotic used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole. It is used for urinary tract infections, MRSA skin infections, travelers' diarrhea, respiratory tract infections, and cholera, among others. It may be used both to treat and prevent pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS. It can be given by mouth or intravenously.
Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure.
Actinomycosis is a rare infectious bacterial disease caused by Actinomyces species. About 70% of infections are due to either Actinomyces israelii or A. gerencseriae. Infection can also be caused by other Actinomyces species, as well as Propionibacterium propionicus, which presents similar symptoms. The condition is likely to be polymicrobial aerobic anaerobic infection.
Ceftazidime, sold under the brand names Fortaz among others, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein or muscle.
Carbapenems are a class of highly effective antibiotic agents commonly used for the treatment of severe or high-risk bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.
Burkholderia cepacia complex (BCC), or simply Burkholderia cepacia, is a group of catalase-producing, lactose-nonfermenting, Gram-negative bacteria composed of at least 20 different species, including B. cepacia, B. multivorans, B. cenocepacia, B. vietnamiensis, B. stabilis, B. ambifaria, B. dolosa, B. anthina, B. pyrrocinia and B. ubonensis. B. cepacia is an opportunistic human pathogen that most often causes pneumonia in immunocompromised individuals with underlying lung disease. Patients with sickle-cell haemoglobinopathies are also at risk. The species also attacks young onion and tobacco plants, as well as displaying a remarkable ability to digest oil.
Yersiniosis is an infectious disease caused by a bacterium of the genus Yersinia. In the United States, most yersiniosis infections among humans are caused by Yersinia enterocolitica.
Bacteroides fragilis is an obligately anaerobic, Gram-negative, rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.
Chromobacterium violaceum is a Gram-negative, facultative anaerobic, non-sporing coccobacillus. It is motile with the help of a single flagellum which is located at the pole of the coccobacillus. Usually, there are one or two more lateral flagella as well. It is part of the normal flora of water and soil of tropical and sub-tropical regions of the world. It produces a natural antibiotic called violacein, which may be useful for the treatment of colon and other cancers. It grows readily on nutrient agar, producing distinctive smooth low convex colonies with a dark violet metallic sheen. Some strains of the bacteria which do not produce this pigment have also been reported. It has the ability to break down tarballs.
Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.
Medical microbiology , the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases. In addition, this field of science studies various clinical applications of microbes for the improvement of health. There are four kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.
Burkholderia thailandensis is a nonfermenting motile, Gram-negative bacillus that occurs naturally in soil. It is closely related to Burkholderia pseudomallei, but unlike B. pseudomallei, it only rarely causes disease in humans or animals. The lethal inoculum is approximately 1000 times higher than for B. pseudomallei. It is usually distinguished from B. pseudomallei by its ability to assimilate arabinose. Other differences between these species include lipopolysaccharide composition, colony morphology, and differences in metabolism.
Ashdown's medium is a selective culture medium for the isolation and characterisation of Burkholderia pseudomallei.
Pathogenic bacteria are bacteria that can cause disease. This article deals with human pathogenic bacteria. Although most bacteria are harmless or often beneficial, some are pathogenic, with the number of species estimated as fewer than a hundred that are seen to cause infectious diseases in humans. By contrast, several thousand species exist in the human digestive system.
Amoebiasis, also known amoebic dysentery, is an infection caused by any of the amobae of the Entamoeba group. Symptoms are most common during infection by Entamoeba histolytica. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. People affected may develop anemia due to loss of blood.
Ceftazidime/avibactam is a combination drug composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used for the treatment of serious bacterial infections.
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