Genavense Infection Research Articles

Disseminated mycobacterium genavense infection with central nervous system involvement in an HIV patient: a case report and literature review

BackgroundImmunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients.Case PresentationWe describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses.ConclusionThe diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system.

Central nervous system mycobacteriosis caused by Mycobacterium genavense in degus (Octodon degus).

Degus (Octodon degus) that were kept at a breeding facility presented with neurological or respiratory symptoms and died. Necropsies were performed on 9 individuals, and no significant gross lesions were found. Histologically, spinal cord necrosis was observed in all 9 cases and granulomatous myelitis in 5 of the 9 cases. Locally extensive necrosis of the brain and encephalitis were observed in 7 of the 9 cases. Acid-fast bacteria were found in the spinal cords, brains, and lungs from all 9 cases. Immunohistochemically, Mycobacterium tuberculosis antigen was observed in the spinal cords, brains, and lungs from all 9 cases. Double-labeling immunofluorescence revealed M. tuberculosis antigen in IBA1- and myeloperoxidase-immunopositive cells. Extracted genomic DNA from 8 of the 9 cases was successfully amplified with the primers for Mycobacterium genavense ITS1 and hypothetical 21 kDa protein genes, and the polymerase chain reaction products were identified as M. genavense by DNA sequencing. This report highlights the susceptibility of degus to M. genavense infection in the central nervous system.

Concurrent Mycobacterium genavense infection and intestinal B-cell lymphoma in a pet rabbit (Oryctolaguscuniculus)

A 6-year-old male intact pet rabbit was evaluated for chronic weight loss. A large mass was detected by palpation in the mid-abdomen and ultrasound examination suggested a jejunal location. Explorative laparotomy revealed a nodular mass within the jejunal wall. Histological examination of a biopsy revealed mycobacterial granulomatous enteritis with an atypical lymphoblastic proliferation suggestive of lymphoma. Neoplastic lymphocytes were immunopositive for Pax-5 but negative for CD3, which is diagnostic of a B-cell neoplasm. Numerous acid-fast bacteria were seen within histiocytes and identified by polymerase chain reaction as Mycobacterium genavense, which is a non-tuberculous and opportunistic mycobacterium with zoonotic potential. To the best of our knowledge, this is the first documented case of a concurrent B-cell lymphoma and M. genavense infection in a rabbit. Concomitant mycobacteriosis and lymphoma have been rarely described in animals and the coexistence of neoplasia and mycobacterial infection within the jejunum suggests a potential pathogenetic association. Interestingly, the rabbit owner worked in an anti-tuberculosis clinic, and an anthropic origin of the mycobacterial infection could not be excluded.

Mycobacterium genavense splenitis in a pet rabbit (Oryctolagus cuniculus) presented for fracture

Mycobacteriosis is an uncommon infection that has been sporadically described among wild, farmed and pet rabbits. To date, only one case of Mycobacterium genavense infection has been reported in a dwarf rabbit presenting with granulomatous pneumonia. This new case report describes granulomatous splenitis caused by M. genavense in a pet rabbit brought in for lameness caused by a femoral fracture. The initial blood test, X-ray, abdominal ultrasound, and bone marrow and spleen cytology results were consistent with a diagnosis of a metastatic giant-cell tumour. The rabbit underwent successful femoral osteosynthesis, and six months later, following the occurrence of a second spontaneous fracture and a worsening of overall health, the patient was euthanised. The postmortem histological examination showed severe granulomatous splenitis caused by acid-fast bacilli identified as M. genavense by real-time PCR analysis. The route of infection remains unknown, yet the lack of pulmonary involvement likely rules out airborne transmission. M. genavense infection, although rarely described in pet rabbits, appears to be an emerging pathogen and should be included among the differential diagnoses for pneumonia and splenomegaly.

Disseminated Mycobacterium genavense infection in an otherwise healthy child: a clinical case and literature review

This paper presents the first clinical case of combined pulmonary and abdominal M. genavense infection in an otherwise healthy, immunocompetent child with an early treatment response and full recovery. The favorable outcome was determined by rapid microbiological diagnosis using up-to-date diagnostic methods followed by targeted antimicrobial therapy.

Sarcoid-like lesions obfuscating the diagnosis of disseminated Mycobacterium genavense infection in a patient with IL-12Rβ1-associated immunodeficiency

BackgroundSarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis.Case presentationA 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months.ConclusionsDifferentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

Mycobacterium genavense Infections in Immunocompromised Patients Without HIV: Case Series of Solid Organ Transplant Patients and Literature Review.

Background Mycobacterium genavense infection is rare and can occur in immunocompromised patients without human immunodeficiency virus (HIV).MethodsWe describe 2 cases of M genavense infection in solid organ transplant (SOT) recipients, and we performed a literature review of immunocompromised patients without HIV.ResultsFifty-two cases are reported. Predisposing factors were receipt of SOT (40.4%) and autoimmune disease (36.5%). Infection was disseminated in 86.5% of cases. Organs involved were lymph nodes (72.3%), gastrointestinal tract (56.5%), lung (35.5%), and bone marrow (28.8%). Most patients were treated with at least 3 antimycobacterial agents (98%), with a clinical cure achieved in 54.9%. In multivariate analysis, lack for cure was associated with age of the time infection (odds ratio [OR], 15.81 [95% confidence interval {CI}, 2.92–152.93]; P = .011) and positive bone marrow culture (OR, 1.05 [95% CI, 1.01–1.12]; P = .042).Conclusions Mycobacterium genavense infection is a rare and generally disseminated disease with a poor prognosis. Optimal treatment regimen and its duration remain to be defined.

Disseminated Mycobacterium genavense infection in a guinea pig (Cavia porcellus): a case report

BackgroundMycobacteria are found in many environmental conditions and infect a variety of species, including rodents and rabbits. Guinea pigs are used experimentally as a model for Mycobacterium tuberculosis, but natural mycobacteriosis in guinea pigs has not been reported.Case presentationA 1.5-year-old female guinea pig was found acutely deceased with no premonitory illness. On gross post-mortem examination, multifocal to coalescing, raised, firm, pale tan nodules with discrete, irregular margins were noted over the surfaces of all lung lobes. Histopathology revealed nodules composed of clustered foamy macrophages and multinucleated giant cells containing numerous bacterial rods. Similar bacteria-laden macrophages were noted within sections of the liver, heart, palpebral conjunctiva, duodenum, and cecum. Polymerase chain reaction was performed on tissues collected during post-mortem examination. The 16S rRNA gene product was sequenced and was identical to the Mycobacterium genavense type strain.ConclusionsTo the best of the author’s knowledge, this report details the first documented case of Mycobacterium genvaense infection in a guinea pig and a follow up investigation of close-contact animals. Given their experimental susceptibility and this clinical case report, mycobacteriosis should be considered as a differential in guinea pigs exhibiting weight loss in the absence of other clinical signs. With the potential for zoonotic transmission in immunosuppressed individuals, precautions should be taken to safeguard human health in cases of guinea pigs with suspected M. genavense infection.

Monitored Therapy of Sporadic Mycobacteriosis Caused By Mycobacterium Genavense in Atlantic Canaries (Serinus Canaria) and Bengalese Finch (Lonchura Striata).

IntroductionMycobacteriosis is a significant disease of companion and wild birds which causes emaciation and widely distributed lesions, as well as being a potential zoonosis. Its primary aetiological agents in birds are Mycobacterium avium subsp. avium and the fastidious Mycobacterium genavense. This study monitored the therapy of birds naturally infected with Mycobacterium genavense to gain understanding of its effectiveness and the interrelation of co-infections with the disease course and pharmacotherapy.Material and MethodsFive Atlantic canaries (Serinus canaria) and one Bengalese finch (Lonchura striata) with tentative diagnoses of mycobacteriosis resulting from M. genavense infection were treated twice daily with clarithromycin at 40 mg/kg, ethambutol at 30 mg/kg, and moxifloxacin at 10 mg/kg for 6 months. Two canaries were also found to be carriers of Cryptosporidium galli. Mycobacteria in faecal samples of all birds were investigated by bacterioscopy and quantitative PCR.ResultsMolecular tests yielded positive results for up to four months after treatment initiation for M. genavense and Cryptosporidium, but microscopy failed to detect the latter after four weeks in specimens from one canary. Co-infections with polyomavirus (in all birds) and circovirus and bornavirus (in canaries) were diagnosed. Two birds died during treatment and one was euthanised because of other disease, 1 month after treatment completion. Three canaries were in relatively good health a year after treatment.ConclusionCanary circovirus and polyomavirus co-infection may suppress the immune system and this may facilitate the development of mycobacteriosis. The set of drugs used led to the complete cure of mycobacteriosis in three canaries. In one bird the disease returned. Clarithromycin was the active drug against C. galli. Molecular methods serve well to monitor mycobacteriosis therapy and identify M. genavense and C. galli carriage.

High overall mortality of Mycobacterium genavense infections and impact of antimycobacterial therapy: Systematic review and individual patient data meta-analysis

IntroductionMycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in HIV-positive individuals and increasingly in patients without HIV. The infections are difficult to treat and the optimal antimycobacterial regimen is still unknown. MethodsAn individual patient data meta-analysis was conducted aiming at including all hitherto published cases of infection with M. genavense. Clinical manifestations, microbiological data, dispositions and immunosuppression were recorded. Antimycobacterial therapies and mortality were analyzed by logistic regression and time-to-event analysis. ResultsWe included 223 patients with infection due to M. genavense published from 1992 to 2021. While the majority was HIV positive (n = 171, 76.7%), 52 patients were non-HIV-patients (23.3%), 36 of whom received immunosuppressive therapy (69%). We could confirm the bacterium's tropism for the gastrointestinal tract with abdominal pain, hepato-/splenomegaly and abdominal lymphadenopathy being major clinical manifestations. More than 90% of patients received antimycobacterial therapy. The regimens consisted mainly of macrolides, rifamycins and ethambutol. Overall mortality was high, but in logistic regression and time-to-event analysis a macrolide containing regimen was associated with better outcomes. ConclusionIn this first individual patient data meta-analysis of infections with M. genavense we confirm its tropism for the gastrointestinal tract. The high overall mortality underlines the clinical relevance of infection with this bacterium for the individual patient. In addition, our data give a hint that a macrolide containing regimen is associated with better survival.

Morbidity in an adenosine deaminase-deficient patient during 27 years of enzyme replacement therapy

IntroductionAdenosine deaminase (ADA) deficiency causes severe immunodeficiency that is lethal in infancy. Enzyme replacement therapy (ERT) can improve the metabolic, immune and non-immune abnormalities in patients prior to transplantation, however, its benefits over extended periods are not well characterized.We describe a 28-year-old female who received ERT for 27 years. She suffered from EBV negative B cell lymphoma of the hip at 14 years of age and Guillian-Barre Syndrome 2 years later. At 22 years of age, she experienced a gastrointestinal infection with Mycobacterium genavense. At 26 years of age, lymphoma reoccurred with multiple liver lesions followed by Mycobacterium genavense infection with dissemination to the brain. Throughout this period, ADA activity in the plasma was within the therapeutic range. Repeated evaluations demonstrated very low lymphocyte counts and impaired T cell function. ConclusionsERT might be insufficient to maintain normal immunity over extended periods in some ADA-deficient patients.

An unusual case of abdominal mycobacterial infection: Case report and literature review.

This article presents a case of an HIV-infected paediatric patient with an unusual Mycobacterium genavense infection with predominantly abdominal organ involvement.

Sclerosing mesenteritis by Mycobacterium Genavense mimicking a lymphoproliferative syndrome: The value of 18F-FDG PET/CT

A 39-year-old man with HIV presented fever, hepatosplenomegaly and mesenteric and retroperitoneal enlarged lymph nodes in abdominal CT (Fig. 1a,b), so a lymphoproliferative syndrome was suspected. Therefore a 18F-FDG PET/CT (Fig. 1c) was requested to assess the initial staging and to locate the most accessible adenopathy for biopsy, revealing high uptake of FDG in mesenteric and retroperitoneal lymph nodes, spleen and bone marrow involvement, and normometabolic hepatomegaly. The biopsy of mesenteric adenopathies excluded lymphoma and confirmed the diagnosis of Mycobacterium Genavense (MG) infection.

High prevalence of Mycobacterium genavense within flocks of pet birds

Mycobacterium genavense is regarded as the primary cause of mycobacteriosis in psittaciform and passeriform birds, which are commonly kept as pets. In humans, Mycobacterium genavense is especially pathogenic for young, old, pregnant and immunocompromised people (YOPIs). In birds, only few studies, mainly case reports, exist and there is still little e information about occurrence and relevance of this zoonotic pathogen.In this first pilot study concerning the prevalence of Mycobacterium genavense within flocks of naturally infected pet birds, real-time PCR examinations of 170 individual passeriform and psittaciform birds, including commonly kept budgerigars, lovebirds and zebra finches as well as gold finches and weaver finches, were conducted to determine the infection rate in six different aviaries. Antemortem examinations of faeces and cloacal swabs were compared with postmortem examinations of tissue samples to evaluate the reliability of antemortem diagnostics. Additional ophthalmologic examinations were performed to evaluate their diagnostic potential. Molecular examinations for viral co-infections, including circovirus, polyomavirus and adenovirus, were conducted to identify potential risk factors.PCR results revealed a detection prevalence of Mycobacterium genavense in the flocks varying from 3% to 91% based on postmortem testing, while antemortem diagnostics of faecal samples and swabs showed 64% discrepant (false negative) results. Ophthalmologic examinations were not useful in identifying infected birds within the flocks. Viral co-infections, especially with polyomavirus, were common.It has to be assumed that Mycobacterium genavense infections are widespread and underdiagnosed in companion birds. Viral infections might be an important risk factor. There is urgent need to improve antemortem diagnostics.

Disseminated Mycobacterium genavense Infection in Patient with Adult-Onset Immunodeficiency

We report a case of disseminated Mycobacterium genavense infection resulting from neutralizing anti–interferon-γ autoantibodies in the patient. We identified M. genavense targeting the hsp65 gene in an aspiration specimen of the lymph node. Adult-onset immunodeficiency caused by neutralizing anti–interferon-γ autoantibodies, in addition to HIV infection, can lead to disseminated nontuberculous mycobacterial infection.

Disseminated Mycobacterium genavense in the immunocompromised: A Case Series at Mayo Clinic Rochester

Background Mycobacterium genavense can cause serious disease in the immunocompromised. We report our experience with this uncommon infection.MethodsRetrospective review of M. genavense infection at Mayo Clinic (2010–2017).ResultsThree patients were diagnosed with M. genavense from 2010 to 2017 (Table 1). Lymph node biopsy noted non-necrotizing granulomatous inflammation with AFB in 2 patients. Delayed growth in culture was noted after at least 6 weeks incubation. All patients were started on mycobacterial therapy; no isolate grew sufficiently for drug susceptibility testing.AgeGenderRisk factorPresentationMicrobiologyAntimicrobialsManagementOutcome51MRenal transplant Prednisone2 months right TKA painPositive right knee operative culture at 12 weekCiprofloxacin Ethambutol Rifampin ClarithromycinTKA resection + arthrodesis 24 mo antimicrobials9 y – no relapse66FAzathioprine Idiopathic CD4 lymphopeniaAbdominal pain, fever, weight lossIntra-abdominal lymphadenopathy (Figure 1 and 2)Positive mesenteric lymph node culture at 8 week, blood cultures at 6 weekClarithromycinMoxifloxacinRifabutinSymptoms resolvedExpired from stroke - 7 mo36FAIDSAbdominal painIntra-abdominal lymphadenopathyPositive mesenteric lymph node culture at 11 weekClarithromycin Rifabutin EthambutolSymptoms improved at 1 moLost to followupConclusion M. genavense is an environmental mycobacteria, it rarely causes infection in non-HIV hosts. Our cases involved advanced HIV, solid organ transplant and idiopathic CD4 lymphopenia. Presentation with GI and systemic symptoms is common, pulmonary and cutaneous less so. Growth in culture requires prolonged incubation (8–12 weeks) in broth media with Mycobactin J supplementation. Positive pathological examination for AFB organisms, negative probes for MTB or MAC combined with persistently negative cultures, should raise the suspicion for this organism in the right clinical setting. It is generally susceptible to rifamycins, fluoroquinolones and macrolides; resistant to isoniazid and sometimes pyrazinamide. Immunosuppression should be reduced if possible to speed recovery. Duration of therapy is usually at least 12 months for disseminated disease, depending on response and immunosuppression.Disclosures All authors: No reported disclosures.

Mycobacterium genavense infection in two species of captive snakes.

Background Mycobacterium is an important zoonotic agent with companion, livestock and wildlife animals reportedly playing a role as reservoirs. Although its association with reptiles has been described, the disease cycle remains to be fully established, particularly in snakes. Accordingly, this study aimed to report the occurrence of mycobacteriosis with clinical pneumonia in one exotic python snake (Python molurus) and one native green snake (Philodryas olfersii) from the Sorocaba Zoo, São Paulo state, Brazil.MethodsDiagnosis was based on necropsy, histopathological examination, Ziehl-Neelsen stain and immunohistochemistry.ResultsUsing a nested PCR followed by DNA sequencing and bioinformatics analysis, the causative Mycobacterium species was identified as Mycobacterium genavense.Conclusion Mycobacterium genavense is an infectious zoonotic agent of animal and public health concerns.

Immune reconstitution inflammatory syndrome due to Mycobacterium genavense in an HIV-infected patient: Impact of rapid species identification by rpoB sequencing on clinical management

Introduction: Diagnosis of infections due to Mycobacterium tuberculosis has been recently facilitated with the worldwide implementation of rapid molecular tests. However, the diagnosis of non-TB mycobacteria (NTM) remains a major challenge for laboratories, as this group of bacteria contains over 150 different species with highly variable bacteriological properties. The development and implementation in clinical practice of techniques allowing rapid identification of NTM at the species level is, therefore, important for clinical laboratories. We report the case of an HIV-1 positive patient presenting with severe NTM infection who benefited from a novel rapid diagnostic technique, based on the direct sequencing of the rpoB gene from smear-positive clinical samples. Case Presentation: A 43-year-old HIV-1 positive woman was hospitalized for bicytopenia in the presence of an inflamed supraclavicular lymph node. The diagnosis of disseminated Mycobacterium genavense infection, which involved the bone marrow and several lymph nodes, was missed by conventional mycobacteriological techniques. Identification was obtained by performing direct sequencing of the rpoB gene. Conclusion: We describe a novel technique that allows the rapid diagnosis of NTM infections directly from biological samples. This technique is now implemented in our routine workflow for smear and culture-positive samples, after the exclusion of TB, by rapid molecular assays.

An outbreak of Mycobacterium genavense infection in a flock of captive diamond doves (Geopelia cuneata).

Two diamond doves (Geopelia cuneata) in a flock of 23 birds housed in an aviary in a zoo in central Japan were found dead as a result of mycobacteriosis. Fecal samples of the remaining doves were positive for mycobacterial infection, and thus they were euthanatized. Clinical signs and gross pathology, including weight loss and sudden death and slight enlargement of the liver and intestine, were observed in a small number of birds (3/23). Disseminated histiocytic infiltration of either aggregates or sheets of epithelioid cells containing acid-fast bacilli, in the absence of caseous necrosis, were observed in different organs of the infected doves, especially lungs (23/23), intestines (9/23), livers (7/23), and hearts (6/23). Mycobacterium sp. was isolated from the livers of three birds (3/23). DNA extracted from frozen liver and formalin-fixed, paraffin-embedded tissues (5/23) were used for amplification of the gene encoding mycobacterial 65-kDa heat shock protein (hsp65). The causative Mycobacterium species was identified by PCR-restriction fragment length polymorphism analysis. Mycobacterium genavense infection was confirmed in three of the diamond doves. Moreover, partial 16S rDNA gene sequencing revealed 100% identity across the three samples tested, and 99.77% nucleotide homology of the isolate sequence to M. genavense. The main route of M. genavense infection in the diamond doves was most likely airborne, suggesting a potential zoonotic risk of airborne transmission between humans and birds.

Disseminated Mycobacterium genavense infection in a patient with immunosuppressive therapy and lymphoproliferative malignancy

We present the case of a 51-year-old woman who presented a right supraclavicular mass corresponding to lymphadenitis with atypical mycobacterium (Mycobacterium genavense). Later, she developed subcutaneous purulent small nodules containing the same germ. The presence of this mycobacterium was in the context of recurrent peripheral T-cell lymphoma and immunosuppressive therapy for seronegative inflammatory polyarthritis.