Chronic Melioidosis Research Articles

Melioidosis and Activation from Latency: The "Time Bomb" Has Not Occurred.

Burkholderia pseudomallei, the causative agent of melioidosis has long been considered able to exist in a latent form. Seropositivity among U.S. soldiers returning from the Vietnam conflict led to melioidosis being dubbed "the Vietnamese time bomb." Cases assigned to "(re)activation from latency" over 30 years of the Darwin Prospective Melioidosis Study (DPMS) were reviewed and reassessed and additional cases from DPMS years 31-34 were added. Historical reports of melioidosis attributed to activation from latency were reviewed. Some earlier DPMS cases and most historical cases described as activation from latency more accurately reflect undiagnosed chronic melioidosis, often with relapsing-remitting courses, rather than truly latent, asymptomatic infection. Such protracted disease should now be diagnosable much earlier, provided melioidosis is considered and laboratory facilities are available. The longest plausible duration of asymptomatic latency remains 29 years. In conclusion, activation from latency is a rare event in melioidosis, accounting in our analysis for under 3% of DPMS cases, consistent with why the Vietnamese time bomb never eventuated.

Acute, Chronic, and Latent Infection with (Re)Activation Melioidosis

Melioidosis can present as an acute as well as chronic disease and can be fatal. Type 2 diabetes mellitus is one of the most common risk factors for acquiring this infectious disease.We present a case of a 36-year-old diabetic male patient who presented in March 2022 with acute severe melioidosis and later developed chronic melioidosis. He did not take complete treatment and presented again in January 2023 with features of Latent infection with reactivation. The blood and pus culture showed positive results for Burkholderia pseudomallei (B. pseudomallei). The use of granulocyte colony-stimulating Factor (G-CSF) in addition to antimicrobial treatment with meropenem and later ceftazidime therapy played an effective role in the recovery of the patient. In this case report we present the acute and chronic manifestations with which he reported along with management of the case, review the literature on the impaired immunity in type 2 diabetic patient in melioidosis, latent infection with (re)activation, the suggested role of G-CSF and antimicrobial therapy.

Imaging manifestations of pulmonary melioidosis: A case series

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions.

Manifestaciones radiológicas de la melioidosis pulmonar. Serie de casos

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions.

Dysregulation of TNF-\u03b1 and IFN-\u03b3 expression is a common host immune response in a chronically infected mouse model of melioidosis when comparing multiple human strains of Burkholderia pseudomallei

BackgroundMelioidosis is endemic in Southeast Asia and Northern Australia and is caused by the Gram-negative, facultative intracellular pathogen Burkholderia pseudomallei. Diagnosis of melioidosis is often difficult because of the protean clinical presentation of the disease, and it may mimic other diseases, such as tuberculosis. There are many different strains of B. pseudomallei that have been isolated from patients with melioidosis, but it was not clear if they could cause a similar disease in a chronic BALB/c murine model of melioidosis. Hence, we wanted to examine chronically infected mice exposed to different strains of B. pseudomallei to determine if there were differences in the host immune response to the pathogen.ResultsWe identified common host immune responses exhibited in chronically infected BALB/c mice, although there was some heterogeneity in the host response in chronically infected mice after exposure to different strains of B. pseudomallei. They all displayed pyogranulomatous lesions in their spleens with a large influx of monocytes/macrophages, NK cells, and neutrophils identified by flow cytometry. Sera from chronically infected mice by ELISA exhibited elevated IgG titers to the pathogen, and we detected by Luminex micro-bead array technology a significant increase in the expression of inflammatory cytokines/chemokines, such as IFN-γ, IL-1α, IL-1β, KC, and MIG. By immunohistochemical and in situ RNA hybridization analysis we found that the increased expression of proinflammatory cytokines (IL-1α, IL-1β, TNF-α, IFN-γ) was confined primarily to the area with the pathogen within pyogranulomatous lesions. We also found that cultured splenocytes from chronically infected mice could express IFN-γ, TNF-α, and MIP-1α ex vivo without the need for additional exogenous stimulation. In addition by flow cytometry, we detected significant amounts of intracellular expression of TNF-α and IFN-γ without a protein transport blocker in monocytes/macrophages, NK cells, and neutrophils but not in CD4+ or CD8+ T cells in splenocytes from chronically infected mice.ConclusionTaken together the common features we have identified in chronically infected mice when 10 different human clinical strains of B. pseudomallei were examined could serve as biomarkers when evaluating potential therapeutic agents in mice for the treatment of chronic melioidosis in humans.

Dose-dependant acute or subacute disease caused by Burkholderia pseudomallei strain NCTC 13392 in a BALB/c aerosol model of infection.

AimsThe goal of this study was to examine, for the first time, the virulence and pathogenicity of aerosolized Burkholderia pseudomallei, strain NCTC 13392, in BALB/c mice in order to develop an animal model for testing novel medical countermeasures (MCMs) for the treatment of human acute and subacute (a disease state between acute and chronic) melioidosis.Methods and ResultsBALB/c mice were exposed to varying doses of aerosolized bacteria. Acute disease was seen in animals exposed to a very‐high dose (≥103 CFU per animal) and death occurred 3–4 days postchallenge (pc). Bacteria were detected in the lungs, liver, kidney and spleen. In contrast, animals exposed to a low dose (<10 CFU per animal) survived to the end of the study (day 30 pc) but developed weight loss, a bacterial tissue burden and increasing clinical signs of infection from day 20 pc onwards, mimicking a subacute form of the disease. Pathological changes in the tissues mirrored these findings.ConclusionsThis proof of concept study has shown that B. pseudomallei strain NCTC 13392 is virulent and pathogenic in BALB/c mice, when delivered by aerosol. By varying the doses of aerosolized bacteria it was possible to mimic characteristics of both human acute and subacute melioidosis, at the same time, within the same study.Significance and Impact of the Study Burkholderia pseudomallei, the aetiological agent of melioidosis, causes a serious and often fatal disease in humans and animals. Novel MCMs are urgently needed for both public health and biodefense purposes. The present model provides a useful tool for the assessment and evaluation of new MCMs (e.g. therapeutics and vaccines) and offers the potential for testing new treatments for both subacute to chronic and acute melioidosis prior to human clinical trials.

Clinical Manifestations, Antimicrobial Drug Susceptibility Patterns, and Outcomes in Melioidosis Cases, India.

We studied the clinical manifestations and outcomes of 114 patients with culture-confirmed melioidosis treated at a tertiary hospital in southern India. Diabetes mellitus is the main risk factor, and chronic melioidosis mimicking tuberculosis was more common than acute disease. Septicemia and respiratory involvement were associated with poor outcomes.

Genitourinary melioidosis: a descriptive study.

Melioidosis is the disease caused by the soil and water bacterium, Burkholderia pseudomallei. Our study aimed to delineate its genitourinary manifestations. Over a 10-year period (2006-2016), 20 adults with culture-confirmed genitourinary melioidosis were identified. The patients were all men with a mean age of 45.3 ± 12.3 years. The common risk factors were diabetes mellitus (65%) and alcoholism (25%); a majority of patients (90%) had chronic melioidosis. Most had disseminated disease (n = 17) and 55% were bacteraemic. The prostate was the organ most frequently involved (60%, n = 12), followed by the kidney, bladder and seminal vesicles. Diagnosis was established by blood and urine cultures and imaging. Patients were successfully treated with ceftazidime intensive therapy followed by eradicative therapy, with surgical debridement and guided aspiration, when deemed necessary. There was one case fatality and no relapses. Melioidosis is an important differential to be considered in chronic genitourinary infections in the appropriate setting.

Relapse of chronic melioidosis in a paediatric cystic fibrosis patient: first case report from Malaysia

BackgroundBurkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia.Case presentationA 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse.ConclusionsCF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.

Complete Genome Sequence of the Environmental Burkholderia pseudomallei Sequence Type 131 Isolate MSHR1435, Associated with a Chronic Melioidosis Infection.

ABSTRACTThe Burkholderia pseudomallei isolate MSHR1435 is a fully virulent environmental sequence type 131 (ST131) isolate that is epidemiologically associated with a 17.5-year chronic melioidosis infection. The completed genome will serve as a reference for studies of environmental ecology, virulence, and chronic B. pseudomallei infections.

Relationships Between Resistance and Virulence in Burkholderia pseudomallei

Aroused by the capacity of bacteria to develop antimicrobial resistance which allows them to persist in patient under antibiotic treatment, and their adaptation to host defenses by modifying their virulence, we review the relationship between antibiotic resistance and virulence in Burkholderia pseudomallei. Few studies focused on both antibiotic resistance and virulence. The relationship between these two mechanisms is very complex. Main resistance mechanisms such as efflux, biofilm, morphological changes or persistence are linked to virulence but results are still controversial. Recent clinical reports seem to indicate that reductive evolution is involved for balancing antibiotic resistance and virulence in chronic melioidosis cases. The relation of virulence and resistance should be more considered to better understand the resistance, persistence, and pathogenicity of B. pseudomallei. Focusing on these two mechanisms, it will be possible to improve therapeutic options against this important emerging disease and avoid therapy failures or relapses for B. pseudomallei.

Melioidosis: A Diagnostic Dilemma

Purpose: Melioidosis is a disease caused by the gram negative bacteria Burkholderia pseudomallei, which is distributed in soil and surface water in tropical regions of Southest Asia and Northern Australia. Findings in chronic melioidosis include cavitating, nodular or streaky infiltrates mimicking tuberculosis. The clinical features (chronic night sweats, weight loss, fatigue) and radiological findings in melioidosis (mediastinal lymphadenopathy) may mimic underlying malignancy. The gold standard for diagnosis of melioidosis is microscopy and culture. The role of cardiothoracic surgery is to provide tissue diagnosis through mediastinal biopsy, to rule out malignancy, and to therapeutically drain abscesses. Methodology: A retrospective study was performed at the Townsville Hospital of patients treated within the last 5 years who underwent drainage of abscess and/or mediastinal biopsy and subsequent diagnosis of melioidosis by culture. Results: Five patients were diagnosed with melioidosis following thoracic surgery and mediastinal biopsy. Four of these patients were to rule out malignancy and the fifth to rule out tuberculosis. All five patients had diabetes. Four out of five were male and three out of 5 patients were Indigenous. Three patients had thoracotomies, one had VATS and one mediastinoscopy. All five patients have subsequently undergone full treatment for melioidosis with 3 to 6 months of ceftazidime, meropenum or bactrim. Conclusion: Melioidosis often presents with lymphadenopathy, and may mimic both tuberculosis and malignancy. Mortality in the setting of systemic disease is very high. Prompt diagnosis via surgical biopsy and treatment through drainage of abscess is crucial for successful management.

Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease

There is an urgent need for an effective vaccine against human disease caused by Burkholderia pseudomallei, and although a wide range of candidates have been tested in mice none provide high level protection. We considered this might reflect the inability of these vaccine candidates to protect against chronic disease. Using Q-RT PCR we have identified 6 genes which are expressed in bacteria colonising spleens and lungs of chronically infected mice. Three of the genes (BPSL1897, BPSL3369 and BPSL2287) have been expressed in Escherichia coli and the encoded proteins purified. We have also included BPSL2765, a protein known to induce immune responses associated with a reduced incidence of chronic/recurrent disease in humans. Immunisation of mice with a combination of these antigens resulted in the induction of antibody responses against all of the proteins. Compared with mice immunised with capsular polysaccharide or LolC protein, mice immunised with the combination of chronic stage antigens showed enhanced protection against experimental disease in mice.

The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease.

Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. In this study, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic, or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodeling, including matrix metalloproteases and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response occurring in both mice and humans.

Whole-genome sequencing of Burkholderia pseudomallei isolates from an unusual melioidosis case identifies a polyclonal infection with the same multilocus sequence type.

Twelve Burkholderia pseudomallei isolates collected over a 32-month period from a patient with chronic melioidosis demonstrated identical multilocus sequence types (STs). However, whole-genome sequencing suggests a polyclonal infection. This study is the first to report a mixed infection with the same ST.

26: Murine melioidosis with CNS syndrome induced by CD11bCD62L cells harboring Burkholderia pseudomallei

Backgrounds As an infectious agent, Burkholderia pseudomallei is capable of persisting in CD11b phagocytes and escapes from innate immunity during subacute or chronic melioidosis. We hypothesized that those infected cells were used as a vehicle that facilitate the bacterial invading to CNS (central nerve system). Materials and methods The BALB/c and C57BL/6 respectively as subacute and chronic infectious models were used to evaluate the murine melioidosis with CNS syndromes via an intravenous injection of B. pseudomallei GFP or through an adoptively transferred by CD11b cells harboring B. pseudomallei GFP. Observation on occurrence of CNS melioidosis was performed by histological examination, cytokine analysis and bacterial loads in brain. Results We found that, during an initial 14 d-infection, by injecting B. pseudomallei GFP, the sL-selectin, sP-selectin, sICAM-1, MCP-1 and IFN-gamma were increased in blood and CSF specimens for the mice with melioidosis. After a 14 d-infection, the CD11b + CD45 + subpopulation of brain infiltrating leukocytes (BILs) were significantly increased. Approximately 6.5% of BILs were harbored with B. pseudomallei GFP. After adoptive transfer of infected CD11b cells that collected from C57BL/6 WT (wild-type) with melioidosis, the bacterial colonization in the brain and neutrophil infiltration in meninges were obviously occurred while they did not occur in recipients after adoptively transferred if the donor cells were isolated from C57BL sel −/− (selectin knock-out mice). Conclusions/Significance We suggest that B. pseudomallei -infected CD11b + CD62L + cells play an important role in inducing melioidosis with meningitis that could be due to the migration of infected leukocyte involving in a selectin-dependent manner.

Pathogenesis of percutaneous infection of goats with Burkholderia pseudomallei: clinical, pathologic, and immunological responses in chronic melioidosis

Melioidosis is a severe suppurative to granulomatous infection caused by Burkholderia pseudomallei. The disease is endemic to South-East Asia and Northern Australasia and is also of interest as a potential biological weapon. Natural infection can occur by percutaneous inoculation, inhalation or ingestion, but the relative importance of each route is unknown. Experimental infection models using mice have shown inhalation to be the most lethal route of exposure, but few studies have examined the pathogenesis of percutaneous infection despite its presumptive importance in natural disease. Caprine models are useful in the study of melioidosis because goats are susceptible to natural infection by B.pseudomallei, display similar epizootiology/epidemiology to that of humans within the endemic range and develop similar pathologic lesions. Percutaneous inoculation with 10(4) CFU of B.pseudomallei produced disease in all experimental animals with rapid dissemination to the lungs, spleen and kidneys. Initial fever was brief, but temperatures did not return to pre-infection levels until day 18, concurrent with a dramatic lymphocytosis and the transition to chronic disease. Distribution and appearance of gross pathologic and radiographic lesions in goats were similar to caprine aerosol infection and to reported human disease. The similarities seen despite different routes of infection suggest that host or bacterial factors may be more important than the route of infection in disease pathogenesis. The nature of melioidosis in goats makes it amenable for modelling additional risk factors to produce acute clinical disease, which is important to the study of human melioidosis.

Melioidosis Requires Better Data Sharing for Improved Diagnosis and Management in the Mekong Region

Dear Sir: We commend Suntornsut and others for reminding us that pulmonary melioidosis should be considered in every patient with a tuberculosis (TB)–like chest radiographic result and negative acid-fast bacilli (AFB) smears in melioidosis-endemic countries, such as Thailand.1 This finding confirms the conclusion we drew from our analysis of a series of pulmonary melioidosis cases in neighboring Cambodia.2 Among 2,840 acute lower respiratory infections in all-age patients, we found 39 (1.4%) infected with Burkholderia pseudomallei. Six of these patients had a TB-like chest radiographic result. All but one were AFB smear negative. Chronic pulmonary melioidosis and tuberculosis share common clinical features, such as a latency stage for years after initial contact with the bacilli. Two experimental murine models of chronic pulmonary melioidosis showed that the main histopathologic feature was granuloma.3,4 In some cases, the pulmonary lesions were highly suggestive of tuberculosis with large granuloma characterized by a caseous necrotic center.3 This finding might be caused by similar virulence factors.5 Furthermore, in another study in Cambodia, we reported that melioidosis can be associated with pulmonary sequelae mimicking TB sequelae.6 Dysregulation of granuloma formation and of extracellular matrix turnover could lead to similar sequelae in B. pseudomallei and Mycobacterium tuberculosis infections.7 Radiologic and clinical outcomes therefore seem to be closely linked with granuloma formation in TB and melioidosis. We also agree that the burden of pulmonary melioidosis is a heavy one, with a high case-fatality rate (CFR) in low-income countries of the region. In Cambodia, the CFR was 61.5% in our 39-case cohort within two months post-discharge and 52% in another recent series of 58 cases in Cambodia.8 At the time of the study, we linked the high CFR in Cambodia not so much to the severity of the cases, but rather to under-recognition of the disease by clinicians and to the unavailability of appropriate treatment. Since that time, treatment has become available. Pulmonary melioidosis misdiagnosis leads to unnecessary TB treatment. Efforts should be placed on earlier diagnosis of melioidosis and TB. Suntornsut and others proposed that all residual sputum collected from smear-negative patients be cultured to search for B. pseudomallei in countries to which melioidosis is endemic.1 The use of Ashdown's selective agar, which is specific for B. pseudomallei culture, could be easily spread in resource-limited settings. The quality of sputum samples, however, could lead to missing cases. In children, sputum samples are difficult to obtain. In 2011, we suggested the use of throat swab specimens for detecting B. pseudomallei. We believe that this method with 100% specificity (but low sensitivity, 36%)9 could be more useful in children and more easily disseminated in low-income tropical countries in Asia. Tuberculosis diagnosis could also be improved in Cambodia. For 93 consecutive adult patients with at least three AFB smears, 11% discrepancy in AFB smear positivity for TB culture-confirmed samples were observed between two laboratories (Institut Pasteur, unpublished data). New molecular tools, such as GenExpert, could avoid useless TB treatments.10 Larger and smaller case series are documented in tropical countries, especially in the Mekong Basin. A network dynamic and careful aggregation of standardized melioidosis data across the region would help better document the epidemiology and fill knowledge gaps in melioidosis.

Less Is More: Burkholderia pseudomallei and Chronic Melioidosis

ABSTRACTThe Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. Once considered an esoteric tropical disease confined to Southeast Asia and northern Australia, research on B. pseudomallei has recently gained global prominence due to its classification as a potential bioterrorism agent by countries such as the United States and also by increasing numbers of case reports from regions where it is not endemic. An environmental bacterium typically found in soil and water, assessing the true global prevalence of melioidosis is challenged by the fact that clinical symptoms associated with B. pseudomallei infection are extremely varied and may be confused with diverse conditions such as lung cancer, tuberculosis, or Staphyloccocus aureus infection. These diagnostic challenges, coupled with lack of awareness among clinicians, have likely contributed to underdiagnosis and the high mortality rate of melioidosis, as initial treatment is often either inappropriate or delayed. Even after antibiotic treatment, relapses are frequent, and after resolution of acute symptoms, chronic melioidosis can also occur, and the symptoms can persist for months to years. In a recent article, Price et al. [mBio 4(4):e00388-13, 2013, doi:10.1128/mBio.00388-13] demonstrate how comparative genomic sequencing can reveal the repertoire of genetic changes incurred by B. pseudomallei during chronic human infection. Their results have significant clinical ramifications and highlight B. pseudomallei’s ability to survive in a wide range of potential niches within hosts, through the acquisition of genetic adaptations that optimize fitness and resource utilization.

Low-Dose Exposure of C57BL/6 Mice to Burkholderia pseudomallei Mimics Chronic Human Melioidosis

Burkholderia pseudomallei is the etiological agent of human melioidosis, a disease with a broad spectrum of clinical manifestations ranging from fatal septicemia to chronic localized infection or asymptomatic latent infection. Most clinical and immunological studies to date have focused on the acute disease process; however, little is known about pathology and immune response in chronic melioidosis. Here, we have developed a murine model of chronic disease by challenging C57BL/6 mice intranasally with a low dose of B. pseudomallei and monitoring them up to 100 days postinfection. Bacterial burdens were heterogeneous in different animals at all time points, consistent with the spectrum of clinical severity observed in humans. Proinflammatory cytokines such as gamma interferon (IFN-γ), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were induced during chronic infection, and histopathological analysis showed features in common with human melioidosis. Interestingly, many of these features were similar to those induced by Mycobacterium tuberculosis in humans, such as development of a collagen cord that encapsulates the lesions, the presence of multinucleated giant cells, and granulomas with a caseous necrotic center, which may explain why chronic melioidosis is often misdiagnosed as tuberculosis. Our model now provides a relevant and practical tool to define the immunological features of chronic melioidosis and aid in the development of more effective treatment of this disease in humans.