Protothecosis
| Classification according to ICD-10 | |
|---|---|
| B88.8 | Other specified parasite infestation on the skin |
| ICD-10 online (WHO version 2019) | |
The protothecosis is an infectious disease , which in humans, cattle , dogs and other species may occur and green algae of the genus Prototheca is triggered. These algae and their relatives from the genus Helicosporidium are special within the algae in that they can also trigger infections in organisms that do not show any disturbance of the immune system. The two most common species are Prototheca wickerhamii and Prototheca zopfii . In humans, the disease, first described in 1964, is mostly caused by P. wickerhamii . Both types are pathogenic to dogs . The algae occur worldwide in wastewater and in soils; However, despite the relatively high infection pressure, infections are rare and can be related to defects in the immune system . Therapy is not standardized, various procedures with antifungal agents , surgical excision and disinfection are described in the literature .
Prototheques
When prototheques were first isolated in 1894, they were still considered mushrooms . After their taxonomic status had long been controversial, prototheques are now considered to have evolved through mutations from the unicellular green algae of the genus Chlorella . However, the cell wall of Chlorella contains galactose and galactosamine , while Prototheca does not contain these substances . Chlorelles contain chlorophyll and thus carry out photosynthesis , while prototheques contain no chlorophyll and feed saprotrophically , i.e. on rotting organic material.
Protothecosis in humans
Pathogenesis
About the pathogenesis of protothecosis little is known. Prototheques are generally of low virulence and infections are usually localized. The infection occurs on the one hand through superficial contact with contaminated substances; however, contamination of skin injuries with prototypes appears to be more common.
More severe forms of protothecosis usually only occur when the immune system is disrupted . Cellular immunity in particular seems to play an important role: Prototheken are phagocytosed in the healthy organism by neutrophil granulocytes (PMNs) and thus rendered harmless, whereby the presence of IgG and heat-stable opsonin is important for optimal control. However, neither a cause neutropenia due to cancer yet most cases of AIDS usually to an increased risk of protothecosis. It is assumed that more severe forms of protothecosis are associated with qualitative and quantitative deficiencies in the function of the PMNs.
Epidemiology
Protothecosis is a rare infection in humans and is usually not transmitted from person to person; rather, infection occurs through prototheques in the environment. Prototheques living commensally on the body surface can trigger an opportunistic infection in the presence of predisposing factors : Prototheques on the skin and fingernails as well as in the respiratory and digestive tracts could also be detected in healthy people. In more than half of all clinical cases of protothecosis, local or systemic immunodeficiency can be demonstrated as a favorable factor.
Risk factors for protothecosis include a weakened immune system associated with the use of corticosteroids or cancers of the hematopoietic system , organ transplants and surgery in general, diabetes mellitus, and alcohol addiction . Illnesses treated with immunosuppressive drugs also increase the risk of protothecosis. The majority of patients are older than 30 years; Cases in newborns and children also occur.
Geographically, protothecosis occurs on all continents except Antarctica . It is above average in the southwestern United States and in rural areas of Taiwan . Rice field workers, fishermen, farmers, aquarium workers and people who handle raw seafood are particularly exposed .
clinic
Protothecosis is divided into three clinical forms: cutaneous lesions ( Cutaneous protothecosis ), bursitis olecranon (elbow bursitis) and body widespread or systemic infections. Unusual forms are also described, such as urinary tract infection , colpitis (inflammation of the female genital organs), pneumonia and meningitis . Skin infections and olecranon bursitis are usually chronic; acute systemic forms are rare and only occur in patients with a severely weakened immune system.
Cutaneous protothecosis
Cutaneous protothecosis (skin form) is the most common form of the disease that occurs in humans and accounts for a little more than half of all cases. It can occur in connection with injuries to the skin and / or mucous membrane, but also occurs independently of injuries. Symptoms develop slowly and do not usually heal spontaneously. The lesions are usually ulcerated (ulcerated), purulent, and crusty, but they can take other forms. If protothecosis occurs as a complication after a surgical procedure, it can lead to nodule formation, synovitis (joint inflammation) and chronic weeping wounds.
An incubation period of several weeks is assumed . The lesions usually remain local and only spread in immunocompromised patients. They are mainly found in exposed places, i.e. on the extremities and face .
Olecranon bursitis
Caused by Proto counters bursitis olecranon is an inflammation of the back of the elbow joint located bursa , the bursa subcutanea olecranon . The infection is usually a result of perforating (skin-penetrating) injuries that allow the prototheca to enter the bursa. Symptoms appear several weeks after the injury and are manifested by a swollen, slightly hardened, and painful bursa. Infections caused by contamination of an existing wound and infections without previous perforating injuries have also been described.
Systemic protothecosis
The systemic or disseminated protothecosis occurs primarily in immunocompromised patients. 23 cases have been described worldwide; in 21 of them the pathogen was P. wickerhamii . The most commonly affected structures are the skin and subcutaneous tissue , intestines , peritoneum , blood and spleen . Systemic protothecosis is most common as a complication of cancer, organ transplants, or AIDS. In three of the cases described, the protothecal peritonitis was the result of catheterization . Protothecal sepsis as a complication of a central venous catheter has also been described. Often, in addition to protothecosis, other infections with opportunistic pathogens are found in affected patients due to their immune deficiency .
diagnosis
Protothecosis is usually detected late because it is not a high priority as a differential diagnosis of infection. Typically, a suspicion of protothecosis only arises when patients have been treated unsuccessfully against other pathogens over a long period of time. The diagnosis is mostly based on the morphological identification of the prototypes under the microscope , whereby different colors can be used. The examination can be carried out directly with wound exudate and / or tissue samples; In addition, a microbiological culture is recommended. In addition, molecular biological methods for diagnosis have been described. Serological tests , however, do not seem to be suitable for diagnosis in humans.
microscopy
Prototheken are spherical to ellipsoid , have a very pronounced cell wall and contain several thick-walled car pores . The diameter varies between 8.1 × 24 μm and 10.8 × 26.9 μm; the spherical car pores have a diameter of 9 to 11 μm. In contrast to yeast , prototheke do not form buds . They are difficult to stain with HE staining , but they can easily be stained with Gridley staining , Grocott-Gömöri staining or PAS reaction . The prototheca can be confused morphologically with several fungi , including Blastomyces dermatitidis , Cryptococcus neoformans and Pneumocystis jirovecii .
HE staining ( eosinophilic infiltrate clearly visible)
Grocott-Gömöri staining
PAS staining
In addition to large quantities of prototypes, a number of pathological reactions can also be observed in tissue sections . Possible reactions range from a granulomatous inflammation with pronounced tissue necrosis to the complete absence of inflammatory reactions despite evidence of prototypes. In cutaneous protothecosis, the organisms are usually located in the middle and papillary dermis . Disseminated protothecoses lead to pronounced eosinophilic infiltrates and fibrosis of the affected organs.
microbiology
The microbiological identification of prototypes is based on the appearance of the colonies , microscopic identification and several characteristic metabolic properties in the culture. Prototheks are relatively undemanding and can be easily grown on various routinely available nutrient media . However, many of the selective nutrient media common in fungal culture are unsuitable for cultivation because the cycloheximide they contain also inhibits the proliferation of prototheca. Media suitable for growing prototheques are Sabouraud dextrose agar , blood agar , beef broth and brain-heart agar . Since samples often contain other microorganisms in addition to prototypes , 5-fluorocytosine and potassium hydrogen phthalate , which inhibit the growth of most bacteria and fungi , are added for selection . Protothecae can be distinguished from yeast by the addition of ribostamycin , which inhibits the growth of the prototheca, but not of yeast.
The incubation is carried out at 30 ° C for 72 hours. For slow-growing prototypes, incubation for seven days at 25 ° C may be necessary. The temperature optimum is between 25 and 37 ° C and colonies are usually visible after 48 hours. Macroscopically, they appear soft, moist, yeast-like, white or slightly yellowish. The organisms grow either aerobically or microaerophilically .
P. wickerhamii and P. zopfii , the two most important pathogens of protothecosis, can be distinguished on the basis of several properties, which are described in the following table:
| property | Prototheca wickerhamii | Prototheca zopfii |
|---|---|---|
| Appearance of the colonies | Hemispherical, smooth edge |
Flat, rough, button in the middle, wavy edge |
| Glycerol intake | + | + |
| Growth on sucrose | - | - |
| Growth on trehalose | + | - |
| Growth on n-propanol | - | + |
| Growth on arginine | + | + |
| Growth on glucose | + | + |
| Growth on galactose | ± | ± |
| Growth on clotrimazole | - | + |
| Growth at 37 ° C | + | + |
Molecular biology
Microscopic and microbiological examinations are usually sufficient to diagnose protothecosis. In addition, but also molecular biological methods can be used: The identification of P. wickerhamii is by fluorescence in situ hybridization (FISH) using rRNA by corresponding DNA - probes possible because the cell walls of the Proto counters by pretreatment with CTAB for these probes can be made permeable . Identification of P. zopfii by means of PCR of the rDNA is also possible.
therapy
Resistance situation in vitro
Prototheks show some natural resistance to antibiotics and antimycotics in vitro and can also acquire new resistances in the course of therapy. The natural resistance situation is shown in the following table. In addition, the presence of a β-lactamase was detected for P. zopfii .
| substance | Minimum inhibitory concentration (MIC) in μg / ml |
|---|---|
| Gentamicin | 0.2 to 0.9 |
| Tetracycline * | > 100 |
| Fluconazole | 8 to> 200 |
| Itraconazole | 0.39 to> 100 |
| Ketoconazole | 1 to 60 |
| Miconazole | 0.1 to> 100 |
| Clotrimazole | 5 to 6 |
| Polymyxin B | 0.39 to 100 |
| 5-fluorocytosine | > 100 |
| Amphotericin B * | 0.15 to 12.5 |
| Voriconazole | 0.15 to> 16 |
| Nystatin | 1 to> 100 |
| Pentamidine | 4th |
| Griseofulvin | > 200 |
* Tetracycline and Amphotericin B show a synergistic effect against Prototheken.
The sensitivity of the Prototheken to polyenes and azoles is explained by the fact that their cell membranes contain ergosterol . An MIC test of the prototypes for resistance is usually not necessary in practice, because the results obtained thereby correlate only to a limited extent with the clinical success of the therapy . Resistance tests are therefore only recommended if therapy attempts are unsuccessful.
Therapy protocols
There are neither standardized treatment recommendations nor consistent clinical treatment results for protothecosis. There are also no clinical studies that compare different therapies with one another. In practice, surgical and drug therapy forms are combined. Protothecosis does not heal spontaneously, and treatment failure is not uncommon.
In cutaneous protothecosis, the successful therapies described include complete surgical excision of the affected skin area, topical application of amphotericin B and various azoles, topical application of amphotericin B in combination with systemic administration of tetracyclines, systemic administration of amphotericin B with and without excision and the systemic administration of tetracyclines. Treatment failures have been described for tetracycline, itroconazole, fluconazole, fluorocytosine and ketoconazole; inconsistent therapeutic success for the systemic administration of penicillin , griseofulvin and emetine as well as for local applications of disinfectants such as hydrogen peroxide , chlorhexidine , potassium permanganate , copper sulfate , picric acid , ammonium compounds and potassium iodide . The duration of therapy varies between a few days and several weeks.
In the case of olecranon bursitis caused by Prototheken, therapy consists of surgical removal of the infected bursa. Alternatively, drainage combined with instillation of amphotericin B into the bursa can be considered. Systemic treatment with itraconazole for two months is also recommended.
Systemic treatments with amphotericin B, a combination of amphotericin B and doxycycline, and fluconazole have been described for disseminated protothecosis . Peritonitis caused by Prototheken was treated by administering amphotericin B directly intraperitoneally . Cutting out the original infection site or removing foreign bodies in combination with systemic drug administration is recommended as the most careful therapy method. Therapy with azoles is viewed critically, since most therapy failures occurred with this group of drugs; the use of amphotericin B therefore seems to make more sense. The duration of therapy described varies greatly and ranges from five days to eight months; as an extreme case, a therapy of meningitis caused by Prototheken with amphotericin B and azoles over six years has been described, which however could not eliminate the pathogens.
Protothecosis in veterinary medicine
Domestic cattle
In domestic cattle, infections with Prototheken lead to intestinal and udder infections (mastitis). Prototheque mastitis occurs worldwide; most cases of infected herds are reported from Germany , the USA and Brazil . Prototheque mastitis is a severe inflammation of the udder that cannot be treated with medication. The infection is apparently sustained in a herd by subclinically diseased excretors. A population restoration can be done by identifying and culling infected animals. For diagnosis are serological tests for antibodies against Proto counters helpful; the detection of P. zopfii can also be effected by PCR. Prototheks are not safely killed by pasteurizing the milk and therefore represent a potential zoonotic risk.
Domestic dog
In domestic dogs , some single cases have been reported with cutaneous, systemic and disseminated protothecosis. It was first described in 1969. There is a predisposition to collies and females. Infections with protothecae lead either to a skin infection or, more often, to disseminated protothecosis. In this case, the algae penetrate the body through the mouth or nose and lead to an intestinal infection. From there they spread into the eyes , brain and kidneys . The symptoms of the disease are diarrhea , weight loss, weakness, eye inflammation , retinal detachment , incoordination, and seizures .
Dogs with acute blindness and diarrhea that develop exudative retinal detachment should be evaluated for protothecosis. The diagnosis is made through culture or directly through microscopic detection of the algae in a biopsy or in the cerebrospinal fluid , vitreous humor or urine . Disseminated protothecosis is difficult to treat, but antifungal drugs have been shown to be effective in some cases. The prognosis for cutaneous protothecosis is moderate and depends on the ability to surgically remove the affected skin. The prognosis of the disseminated form is poor, which may also be related to the fact that the disease is usually recognized and treated late.
Other animal species
Protothecosis is very rare in domestic cats . The first case was described in 1976; the affected cat had a fluctuating mass on the hind leg. The few other cases described were skin infections.
In the case of Atlantic salmon , an infection of juveniles by Prototheca salmonis in a fish farm has been described, which is clinically expressed as a kidney infection and in which a systemic infection has been demonstrated histologically.
Web links
Individual evidence
- ↑ Tartar A, Boucias DG, Adams BJ, Becnel JJ: Phylogenetic analysis identifies the invertebrate pathogen Helicosporidium sp as a green alga (Chlorophyta) . In: Int J Syst Evol Microbiol . 52, 2002, pp. 273-9. PMID 11837312 .
- ↑ Davies RR. et al .: A Case of Human Protothecosis . In: Trans R Soc Trop Med Hyg . 58, 1964, pp. 448-51. PMID 14206703 .
- ↑ Leimann B, Monteiro P, Lazéra M, Candanoza E, Wanke B: Protothecosis . In: Med Mycol . 42, No. 2, 2004, pp. 95-106. doi : 10.1080 / 13693780310001653653 . PMID 15124862 .
- ↑ a b Hosaka S, Hosaka M: A case report of canine protothecosis . In: J Vet Med Sci . 66, No. 5, 2004, pp. 593-7. doi : 10.1292 / jvms.66.593 . PMID 15187378 .
- ^ A b Hollingsworth S: Canine protothecosis . In: Vet Clin North Am Small Anim Pract . 30, No. 5, 2000, pp. 1091-101. PMID 11033876 .
- ↑ a b c d e f g h i j k l m n o p q r s t u v w Lass-Flörl C, Mayr A. Human protothecosis. Clin Microbiol Rev. 2007 Apr; 20 (2): 230-42. Review. PMID 17428884
- ↑ a b c Onozaki M. et al .: Rapid identification of Prototheca zopfii by nested polymerase chain reaction based on the nuclear small subunit ribosomal DNA . In: Journal of Dermatological Science . 54, No. 1, 2009, pp. 56-9. doi : 10.1016 / j.jdermsci.2008.10.009 . PMID 19203861 .
- ↑ a b Ueno R .: Visualization of sporopollenin-containing pathogenic green micro-alga Prototheca wickerhamii by fluorescent in situ hybridization (FISH) . In: Can J Microbiol . 55, No. 4, 2009, pp. 465-72. doi : 10.1139 / W08-155 . PMID 19396247 .
- ↑ Takaki K. et al .: Chronic Prototheca meningitis . In: Scand J Infect Dis . 28, No. 3, 1996, pp. 321-3. PMID 8863372 .
- ↑ Osterstock J, Mansell J, Roussel A: Protothecal enteritis as a cause of protein-losing enteropathy in a bull . In: J Am Vet Med Assoc . 227, No. 9, 2005, pp. 1476-9, 1418. doi : 10.2460 / javma.2005.227.1476 . PMID 16279394 .
- ↑ Roesler U, Hensel A: Longitudinal analysis of Prototheca zopfii-specific immune responses: correlation with disease progression and carriage in dairy cows . In: J Clin Microbiol . 41, No. 3, 2003, pp. 1181-6. doi : 10.1128 / JCM.41.3.1181-1186.2003 . PMID 12624049 .
- ↑ Uwe Rösler and Andreas Hensel: Restoration of Prototheca zopfii mastitis in a dairy herd. In: Dtsch. Veterinarian Wschr. 110 (2003), pp. 374-7. PMID 14560445
- ^ Melville PA. et al .: Evaluation of the susceptibility of Prototheca zopfii to milk pasteurization . In: Mycopathologia . 146, No. 2, 1999, pp. 79-82. doi : 10.1023 / A: 1007005729711 . PMID 10822507 .
- ↑ Sonja Gorissen: Protothecosis in a giant schnauzer . In: Kleintierpraxis 56 (2011), pp. 16–20.
- ↑ a b Ettinger, Stephen J.; Feldman, Edward C .: Textbook of Veterinary Internal Medicine , 4th. Edition, WB Saunders Company, 1995, ISBN 0-7216-6795-3 .
- ↑ Juliet R. Gionfriddo: An unusual cause of blindness in a Siberian husky . In: Advanstar Communications (Ed.): Veterinary Medicine . 102, No. 3, March 2007, pp. 172-8.
- ^ Kaplan W. et al .: Protothecosis in a cat: first recorded case . In: Sabouraudia . 14, No. 3, 1976, pp. 281-6. doi : 10.1080 / 00362177685190421 . PMID 996693 .
- ↑ Finnie JW. et al .: Cutaneous protothecosis in a cat . In: Aust Vet J . 57, No. 6, 1981, pp. 307-308. PMID 7316900 .
- ^ Dillberger JE. et al .: Protothecosis in two cats . In: JAVMA . 192, No. 11, 1988, pp. 1557-9. PMID 3410772 .
- ^ Gentles JC. et al .: Protothecosis of Atlantic Salmon . In: Sabouraudia . 15, No. 2, 1977, pp. 133-9. doi : 10.1080 / 00362177785190211 . PMID 905919 .
