ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Epidemiology and clinical manifestations of Talaromyces (Penicillium) marneffei infection

Epidemiology and clinical manifestations of Talaromyces (Penicillium) marneffei infection
Literature review current through: Jan 2024.
This topic last updated: Apr 11, 2022.

INTRODUCTION — Talaromyces marneffei (formerly Penicillium marneffei) causes a systemic fungal infection referred to as talaromycosis. Talaromycosis (previously referred to as penicilliosis) was commonly diagnosed in individuals with human immunodeficiency virus (HIV) from endemic areas prior to the era of potent antiretroviral therapy (ART), and was an important cause of morbidity and mortality. The widespread use of ART has led to a significant decline in T. marneffei infections among patients with HIV in these areas [1]. However, talaromycosis continues to be seen in patients with acquired immunodeficiency syndrome (AIDS) (eg, those who are unaware of their HIV infection, who do not have access to ART, or who have suboptimal treatment responses to ART), as well as other immunocompromised individuals.

The mycology, epidemiology, and clinical manifestations of T. marneffei will be reviewed here. The diagnosis and treatment of this infection are discussed elsewhere. (See "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection".)

HISTORY — T. marneffei (formerly P. marneffei) was first isolated from the bamboo rat (Rhizomys sinensis) in Vietnam in 1956 [2]. P. marneffei was renamed T. marneffei in 2015, and the disease, which had been referred to as penicilliosis, is now called talaromycosis.

The first human case was reported in an American missionary with Hodgkin disease who had been living in Southeast Asia [3]. Thereafter, rare cases of T. marneffei infection were reported, mostly from Southeast Asia and Southern China [4,5]. The first case of talaromycosis in a patient with HIV was reported in 1989 from Bangkok, coinciding with the beginning of the AIDS epidemic in the region [6].

MYCOLOGY — T. marneffei is a dimorphic fungus [7]. The organism typically takes about four to seven days to grow in culture [8]. The growth characteristics include:

T. marneffei grows as a mold at 25ºC on Sabouraud dextrose agar; over time, colonies produce a soluble red pigment that diffuses into the agar [8]. Microscopically, the mycelia show septate hyphae with lateral and terminal conidiophores (picture 1).

When transferred to brain-heart infusion agar and incubated at 37ºC, white to tan-colored colonies of the yeast develop within a few days (picture 2). The yeast cells are round to oval with a central septum [3,4,9]  (picture 3).

A detailed discussion of how to diagnose T. marneffei infection is found elsewhere. (See "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection", section on 'Diagnosis'.)

EPIDEMIOLOGY — T. marneffei is an important cause of morbidity and mortality, particularly in immunocompromised patients, such as those with HIV infection and low CD4 cells counts from endemic areas (eg, Southeast Asia). Less commonly, infection has also been reported in patients who have had travel-related exposure to this organism.

Risk factors — Talaromycosis typically develops in immunocompromised individuals, especially those with HIV infection and other acquired cellular immune deficits (eg, transplant recipients, individuals with hematologic malignancies, those treated with steroids or cytotoxic agents) [10,11]. Among patients with HIV, the majority of cases are observed in those who have a CD4 count <100 cells/microL [12-14].

Disseminated infections have also been reported in patients from endemic areas in Asia who did not have HIV and had CD4 cell counts within normal limits [15,16]. Some of these patients had other underlying diseases (eg, autoimmune disorders, cancer, diabetes) [15,16]. However, those without underlying diseases were found to have auto-antibodies to interferon gamma as a reason for their increased susceptibility to disseminated [16].

Most patients who develop infection are from an endemic area. However, travel-related infections have been reported [17,18]. In one small series, some patients did not appear to immunocompromised, and travel to the area had occurred in the distant past [18].

Endemicity — T. marneffei is endemic in most countries in Southeast Asia, Northeastern India, Southern China, Hong Kong, and Taiwan [1,9,12,19-23] (figure 1). Cases of disseminated P. marneffei infection have also been reported in patients with HIV from the United States, Europe, Japan, and Australia following visits to endemic areas [24].

In northern Thailand, talaromycosis is the fourth most common opportunistic infection, following tuberculosis, extrapulmonary cryptococcal infection, and Pneumocystis pneumonia [25]. Between 1991 and 2004, more than 6000 cases of P. marneffei infection in patients with HIV were reported to the Thai Ministry of Public Health.

As the HIV/AIDS epidemic spread, the prevalence of T. marneffei infection also increased in other countries in the region (Vietnam, India, Taiwan, Malaysia, Cambodia, and the provinces of Guangxi and Guangdong of China) [22,26]. The epidemic in Vietnam, which peaked in 2007, followed the same pattern as the one previously observed in Thailand [1].

Potential reservoirs — Many aspects of the ecology of T. marneffei and its relationship to human infection remain unknown. Humans and bamboo rats are the only known hosts [27]. The geographic habitats of these bamboo rats correspond with the regional areas where human cases of T. marneffei infection have been found.

However, definitive proof of an environmental reservoir for T. marneffei is still lacking [28]. Some studies of patients with HIV and advanced immunosuppression in Thailand suggest an association between T. marneffei infection and soil exposure, especially during the rainy season [1,29]. As examples:

In two epidemiologic studies from Chiang Mai, identification of patients with disseminated T. marneffei infection significantly increased during the rainy season, whereas cases of cryptococcal infection were steady throughout the year [29].

In a case-control study of 240 AIDS patients, 80 of whom had T. marneffei infection, cases were more likely than controls to have a recent history of an exposure (eg, occupational) to soil, particularly during the rainy season [30].

Although these observations suggest there may be seasonal expansion of the environmental reservoir, attempts to isolate the fungus from soil, bamboo, or vegetation have yielded negative results [31].

Transmission — The mode of transmission of T. marneffei is still unknown. Similar to other endemic fungi (eg, Coccidioides and Histoplasma), an airborne route is suspected via inhalation of conidia from an environmental reservoir [4]. In one case report, a physician with HIV who had never visited an endemic area developed T. marneffei infection shortly after entering a mycology class on the morphologic identification of T. marneffei [32]. However, air samples taken in the building did not yield any organisms.

In addition to airborne transmission, direct inoculation can cause localized disease. This type of transmission was described when infection resulted from a T. marneffei-contaminated needle stick injury in the mycology lab [33].

Subclinical infection — It is likely that subclinical infection may occur in persons living in endemic areas who are exposed to T. marneffei in the environment. As an example, in one study in northern Thailand, about 10 percent of the population had latent T. marneffei infection detected by Western immunoblot testing [34]. The presence of latent infection in humans is also supported by a case report from Australia of a patient with HIV who had a 10-year period between probable exposure and onset of clinical infection [35].

CLINICAL MANIFESTATIONS

Overview — Talaromycosis should be suspected in immunocompromised individuals from endemic areas, especially those with HIV infection and other acquired cellular immune deficits. T. marneffei infections have also been reported in patients who did not have HIV and had CD4 counts within the normal range, but were possibly immunocompromised from having auto-antibodies to interferon gamma [15,16]. (See 'Risk factors' above and "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection", section on 'Diagnosis'.)

The clinical manifestations of talaromycosis are secondary to hematogenous dissemination. The signs and symptoms can vary from isolated skin lesions to respiratory failure and circulatory collapse, and are similar in both children and adults [36]. However, the clinical manifestations appear to differ somewhat in patients with and without HIV. As an example, in a study from Northern Thailand that compared 116 patients with HIV with 34 patients without HIV, patients without HIV were more likely to have bone and joint infections but were less likely to have fever, splenomegaly, umbilicated skin lesions, elevated alanine transaminase levels, or positive fungal blood cultures [15].

All patients with talaromycosis require prompt treatment to prevent life threatening complications. However, the approach to treatment depends upon the severity of disease:

Severe disease – Severe disease is characterized by multiple organ involvement with respiratory failure or circulatory collapse

Moderate disease – Moderate disease is characterized by multiple organ involvement without respiratory failure or cardiovascular collapse

Mild disease – Mild disease refers to patients who only have skin lesions

A detailed discussion of the diagnosis and treatment of talaromycosis is found elsewhere. (See "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection".)

Signs and symptoms — Most patients with talaromycosis present with signs and symptoms related to infection of the reticuloendothelial system, including generalized lymphadenopathy, hepatomegaly, and splenomegaly (table 1) [9,20,22]. As examples:

T. marneffei was demonstrated in the liver and cultured from the blood of six patients who presented with fever, hepatomegaly, and markedly elevated serum alkaline phosphatase levels [37].

In another series, three children presented with peritonitis and appendicitis; they were later diagnosed with mesenteric adenitis, and all had positive blood and bone marrow cultures [38].

In addition to these more generalized symptoms (table 1), patients may also present with:

Respiratory symptoms – The respiratory system is commonly involved and cough, fever, dyspnea, and chest pain may be present. For patients presenting with pulmonary symptoms, chest radiography can show diffuse reticulonodular, localized alveolar, or diffuse alveolar infiltrates [20]. Atypical pulmonary presentations have also been reported, including single or multiple cavitary lesions and a lung mass [39,40].

Gastrointestinal symptoms – Approximately one-third of patients exhibit gastrointestinal symptoms, such as diarrhea. In addition, some individuals present with abdominal pain [37,38].

Skin lesions – Skin lesions are seen in approximately 70 percent of patients, and when present, they are the best clue to diagnosis. Skin lesions typically present as papules on the face, chest, and extremities. The center of the papule subsequently becomes necrotic, giving the appearance of an umbilicated papule, which can resemble molluscum contagiosum [41] (picture 4 and picture 5 and picture 6). (See "Molluscum contagiosum".)

Mucosal lesions – Mucosal lesions (which appear similar to the skin lesions) have been described in the oral cavity, oropharynx, hypopharynx, stomach, colon, and genitalia [9,42-44].

Neurologic manifestations – Patients can present with an acute onset of altered mental status, fever, and nonspecific constitutional symptoms. A case series described this type of syndrome in 21 patients from Vietnam, and all had T. marneffei isolated from their cerebrospinal fluid [45].

Other manifestations – Patients with talaromycosis can also present with arthritis and osteomyelitis [22].

In the majority of patients with HIV, the clinical manifestations associated with late HIV infection (eg, anorexia, asthenia, anemia, weight loss, and cachexia) are also seen. (See "The natural history and clinical features of HIV infection in adults and adolescents", section on 'AIDS and advanced HIV infection'.)

In those with autoantibodies to interferon gamma, in addition to symptoms and signs of disseminated talaromycosis above, a significant number of patients also presented with skin lesions typical of acute febrile neutrophilic dermatosis, also known as Sweet syndrome [16].

Laboratory abnormalities — Anemia is seen in about 75 percent of patients (table 1). Mild elevations of aminotransferases and bilirubin, leukocytosis, and/or leukopenia can be found in about 30 to 50 percent of patients.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opportunistic infections in adults with HIV".)

SUMMARY AND RECOMMENDATIONS

MycologyTalaromyces marneffei (formerly Penicillium marneffei) is a dimorphic fungus that causes a systemic fungal infection referred to as talaromycosis. (See 'Introduction' above and 'Mycology' above.)

Risk factors – Talaromycosis typically develops in severely immunocompromised individuals, such as those with HIV infection and low CD4 cell counts. However, cases have also been reported in those with other underlying conditions (eg, autoimmune disorders, cancer, diabetes). (See 'Risk factors' above.)

Transmission – Although the mode of transmission of T. marneffei is unknown, an airborne route via inhalation of conidia from an environmental reservoir is suspected. Direct inoculation can also occur. (See 'Transmission' above.)

Clinical manifestations

The clinical manifestations are secondary to hematogenous dissemination and can vary from isolated skin lesions to respiratory failure and circulatory collapse. (See 'Overview' above.)

Most patients with talaromycosis present with signs and symptoms related to infection of the reticuloendothelial system, including generalized lymphadenopathy, hepatomegaly, and splenomegaly. Skin lesions are seen in approximately 70 percent of patients, and when present, they are the best clue to diagnosis. Patients may also present with respiratory, gastrointestinal, and neurologic findings. (See 'Signs and symptoms' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thira Sirisanthana, MD, who contributed to an earlier version of this topic review.

  1. Le T, Wolbers M, Chi NH, et al. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis 2011; 52:945.
  2. CAPPONI M, SEGRETAIN G, SUREAU P. [Penicillosis from Rhizomys sinensis]. Bull Soc Pathol Exot Filiales 1956; 49:418.
  3. DiSalvo AF, Fickling AM, Ajello L. Infection caused by Penicillium marneffei: description of first natural infection in man. Am J Clin Pathol 1973; 60:259.
  4. Jayanetra P, Nitiyanant P, Ajello L, et al. Penicilliosis marneffei in Thailand: report of five human cases. Am J Trop Med Hyg 1984; 33:637.
  5. Deng ZL, Yun M, Ajello L. Human penicilliosis marneffei and its relation to the bamboo rat (Rhizomys pruinosus). J Med Vet Mycol 1986; 24:383.
  6. Sathapatayavongs B, Damrongkitchaiporn S, Saengditha P, et al. Disseminated penicilliosis associated with HIV infection. J Infect 1989; 19:84.
  7. Woo PC, Zhen H, Cai JJ, et al. The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts. FEBS Lett 2003; 555:469.
  8. Vanittanakom N, Vanittanakom P, Hay RJ. Rapid identification of Penicillium marneffei by PCR-based detection of specific sequences on the rRNA gene. J Clin Microbiol 2002; 40:1739.
  9. Supparatpinyo K, Khamwan C, Baosoung V, et al. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 1994; 344:110.
  10. Chan YH, Wong KM, Lee KC, et al. Pneumonia and mesenteric lymphadenopathy caused by disseminated Penicillium marneffei infection in a cadaveric renal transplant recipient. Transpl Infect Dis 2004; 6:28.
  11. Wong SS, Wong KH, Hui WT, et al. Differences in clinical and laboratory diagnostic characteristics of penicilliosis marneffei in human immunodeficiency virus (HIV)- and non-HIV-infected patients. J Clin Microbiol 2001; 39:4535.
  12. Clezy K, Sirisanthana T, Sirisanthana V, et al. Late manifestations of HIV in Asia and the Pacific. AIDS 1994; 8 Suppl 2:S35.
  13. Tsang DN, Chan JK, Lau YT, et al. Penicillium marneffei infection: an underdiagnosed disease? Histopathology 1988; 13:311.
  14. Chariyalertsak S, Supparatpinyo K, Sirisanthana T, Nelson KE. A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand. Clin Infect Dis 2002; 34:277.
  15. Kawila R, Chaiwarith R, Supparatpinyo K. Clinical and laboratory characteristics of penicilliosis marneffei among patients with and without HIV infection in Northern Thailand: a retrospective study. BMC Infect Dis 2013; 13:464.
  16. Browne SK, Burbelo PD, Chetchotisakd P, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med 2012; 367:725.
  17. Walsh TJ, Groll A, Hiemenz J, et al. Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 2004; 10 Suppl 1:48.
  18. Castro-Lainez MT, Sierra-Hoffman M, LLompart-Zeno J, et al. Talaromyces marneffei infection in a non-HIV non-endemic population. IDCases 2018; 12:21.
  19. Deng Z, Ribas JL, Gibson DW, Connor DH. Infections caused by Penicillium marneffei in China and Southeast Asia: review of eighteen published cases and report of four more Chinese cases. Rev Infect Dis 1988; 10:640.
  20. Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clin Infect Dis 1996; 23:125.
  21. Singh PN, Ranjana K, Singh YI, et al. Indigenous disseminated Penicillium marneffei infection in the state of Manipur, India: report of four autochthonous cases. J Clin Microbiol 1999; 37:2699.
  22. Louthrenoo W, Thamprasert K, Sirisanthana T. Osteoarticular penicilliosis marneffei. A report of eight cases and review of the literature. Br J Rheumatol 1994; 33:1145.
  23. Ranjana KH, Priyokumar K, Singh TJ, et al. Disseminated Penicillium marneffei infection among HIV-infected patients in Manipur state, India. J Infect 2002; 45:268.
  24. Vanittanakom N, Sirisanthana T. Penicillium marneffei infection in patients infected with human immunodeficiency virus. Curr Top Med Mycol 1997; 8:35.
  25. Chariyalertsak S, Sirisanthana T, Saengwonloey O, Nelson KE. Clinical presentation and risk behaviors of patients with acquired immunodeficiency syndrome in Thailand, 1994--1998: regional variation and temporal trends. Clin Infect Dis 2001; 32:955.
  26. Huynh TX, Nguyen HC, Dinh Nguyen HM, et al. [Penicillium marneffei infection and AIDS. A review of 12 cases reported in the Tropical Diseases Centre, Ho Chi Minh City (Vietnam)]. Sante 2003; 13:149.
  27. Gugnani H, Fisher MC, Paliwal-Johsi A, et al. Role of Cannomys badius as a natural animal host of Penicillium marneffei in India. J Clin Microbiol 2004; 42:5070.
  28. Corbet GB, Hill JE. Subfamily Rhizomyinae: bamboo rats. In: The Mammals of the Indo Malaya Region: A Systematic Review, Oxford University Press, Oxford, UK 1992. p.404.
  29. Chariyalertsak S, Sirisanthana T, Supparatpinyo K, Nelson KE. Seasonal variation of disseminated Penicillium marneffei infections in northern Thailand: a clue to the reservoir? J Infect Dis 1996; 173:1490.
  30. Chariyalertsak S, Sirisanthana T, Supparatpinyo K, et al. Case-control study of risk factors for Penicillium marneffei infection in human immunodeficiency virus-infected patients in northern Thailand. Clin Infect Dis 1997; 24:1080.
  31. Chariyalertsak S, Vanittanakom P, Nelson KE, et al. Rhizomys sumatrensis and Cannomys badius, new natural animal hosts of Penicillium marneffei. J Med Vet Mycol 1996; 34:105.
  32. Hilmarsdottir I, Coutellier A, Elbaz J, et al. A French case of laboratory-acquired disseminated Penicillium marneffei infection in a patient with AIDS. Clin Infect Dis 1994; 19:357.
  33. SEGRETAIN G. [Penicillium marneffei n.sp., agent of a mycosis of the reticuloendothelial system]. Mycopathol Mycol Appl 1959; 11:327.
  34. Vanittanakom N, Mekaprateep M, Sittisombut N, et al. Western immunoblot analysis of protein antigens of Penicillium marneffei. J Med Vet Mycol 1997; 35:123.
  35. Jones PD, See J. Penicillium marneffei infection in patients infected with human immunodeficiency virus: late presentation in an area of nonendemicity. Clin Infect Dis 1992; 15:744.
  36. Sirisanthana V, Sirisanthana T. Disseminated Penicillium marneffei infection in human immunodeficiency virus-infected children. Pediatr Infect Dis J 1995; 14:935.
  37. Kantipong P, Panich V, Pongsurachet V, Watt G. Hepatic penicilliosis in patients without skin lesions. Clin Infect Dis 1998; 26:1215.
  38. Ukarapol N, Sirisanthana V, Wongsawasdi L. Penicillium marneffei mesenteric lymphadenitis in human immunodeficiency virus-infected children. J Med Assoc Thai 1998; 81:637.
  39. McShane H, Tang CM, Conlon CP. Disseminated Penicillium marneffei infection presenting as a right upper lobe mass in an HIV positive patient. Thorax 1998; 53:905.
  40. Cheng NC, Wong WW, Fung CP, Liu CY. Unusual pulmonary manifestations of disseminated Penicillium marneffei infection in three AIDS patients. Med Mycol 1998; 36:429.
  41. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines (Accessed on July 25, 2023).
  42. Tong AC, Wong M, Smith NJ. Penicillium marneffei infection presenting as oral ulcerations in a patient infected with human immunodeficiency virus. J Oral Maxillofac Surg 2001; 59:953.
  43. Kronauer CM, Schär G, Barben M, Bühler H. [HIV-associated Penicillium marneffei infection]. Schweiz Med Wochenschr 1993; 123:385.
  44. Leung R, Sung JY, Chow J, Lai CK. Unusual cause of fever and diarrhea in a patient with AIDS. Penicillium marneffei infection. Dig Dis Sci 1996; 41:1212.
  45. Le T, Huu Chi N, Kim Cuc NT, et al. AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis 2010; 51:1458.
Topic 3033 Version 27.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟