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Protothecosis

Protothecosis is a rare opportunistic infectious disease caused by achlorophyllous microalgae of the genus Prototheca, which are ubiquitous in the environment, particularly in aquatic habitats such as sewage, wastewater, and slime fluxes from trees.^[1] These infections primarily affect immunocompromised humans and various animals, including cattle, dogs, and cats.^[2] The disease is acquired exogenously through traumatic inoculation or inhalation/ingestion of contaminated materials, with no evidence of person-to-person transmission.^[1] The causative agents belong to the class Trebouxiophyceae and include several species, with Prototheca wickerhamii being the most common in human cases (approximately 68%), followed by P. zopfii (now often classified as P. bovis in veterinary contexts, about 22%).^[3] These organisms are non-pigmented relatives of green algae, lacking chlorophyll but capable of fermentation and growth on fungal media, which can lead to initial misidentification as yeasts.^[1] In humans, approximately 335 cases have been documented worldwide as of 2023 since the first report in 1952, with cases increasing in recent decades, predominantly in immunocompromised individuals such as those with AIDS, organ transplants, malignancies, or on corticosteroid therapy; however, infections can occur in immunocompetent hosts following trauma.^[3]^[4] Epidemiologically, cutaneous forms account for about 58-66% of human cases, systemic/disseminated infections for 9-19%, and olecranon bursitis for 15%, with a notable male predominance (70%) and higher incidence in regions like the United States.^[1]^[3] In animals, protothecosis is more prevalent, especially as bovine mastitis caused by P. bovis, affecting dairy herds globally with herd prevalence up to 10%, leading to economic losses through reduced milk quality and animal culling.^[2] Canine cases, often disseminated and involving the eyes and central nervous system, have a poor prognosis with a cure rate of only about 10%, while feline and equine infections are rarer.^[5] The zoonotic potential is low but exists, particularly through contaminated milk or water, emphasizing a One Health approach to prevention via improved farm hygiene, pasteurization, and environmental monitoring.^[2]

Introduction

Definition and Classification

Protothecosis is a rare opportunistic infection caused by achlorophyllous algae of the genus Prototheca, primarily affecting the skin, mucous membranes, eyes, gastrointestinal tract, and disseminated sites in both humans and animals.^[6] These infections are typically localized but can become systemic in immunocompromised hosts, manifesting as cutaneous lesions, olecranon bursitis, or widespread dissemination.^[7] The genus Prototheca belongs to the phylum Chlorophyta, class Trebouxiophyceae, order Chlorellales, and family Chlorellaceae, comprising unicellular microalgae that have lost chlorophyll production and thus appear non-pigmented.^[8] Key pathogenic species include P. wickerhamii, the most common isolate in human infections; P. bovis (formerly P. zopfii genotype 2), frequently associated with bovine mastitis; and less common species such as P. cutis and P. blaschkeae.^[9] Additional species like P. ciferrii (formerly P. zopfii genotype 1) and P. miyajii have been identified, though their roles in disease are rarer.^[10] Morphologically, Prototheca cells are spherical to oval, measuring 3–30 μm in diameter, and reproduce asexually via endosporulation within sporangia.^[11] Under light microscopy, mature sporangia exhibit a characteristic morula-like appearance due to internal septations dividing the cell into multiple endospores, which aids in distinguishing the organism from similar pathogens.^[6] Although Prototheca species are algae by taxonomy, they mimic yeast-like fungi in their infectious behavior, growing as saprophytes in the environment and lacking pigmentation or photosynthetic capability.^[12] This algal-fungal mimicry complicates initial identification, as they do not produce hyphae or demonstrate dimorphism typical of true fungi.^[13]

History and Discovery

The genus Prototheca was first established in 1894 by Wilhelm Krüger, who isolated achlorophyllous algae from the mucous flux of trees such as Tilia and Ulmus species in Germany, initially misclassifying them as fungus-like organisms due to their yeast-like morphology and sporulation.^[6] Krüger described two species, P. zopfii and P. moriformis, marking the initial recognition of these environmental microalgae, though their algal nature was not immediately apparent. In 1913, R. Chodat reclassified Prototheca species as achlorophyllous green algae closely related to Chlorella, based on their internal sporangiospore production, distinguishing them from true fungi and solidifying their taxonomic position within the Chlorophyta phylum.^[1] The pathogenic potential of Prototheca emerged in the mid-20th century, with the first documented animal case reported in 1952 by W. Lerche in Germany, involving P. zopfii causing bovine mastitis in dairy cattle.^[6] By the 1960s, protothecosis gained recognition as an opportunistic infection in veterinary medicine, particularly for chronic mastitis in cattle, where P. zopfii was frequently implicated, leading to economic losses in dairy herds worldwide. The first human case was reported in 1964 by Davies et al., describing a cutaneous lesion on the foot of a barefoot rice farmer in Sierra Leone, infected by P. wickerhamii, which had been newly described as a species in 1959.^[1] Systemic human infections were first clearly documented in the 1970s, with Cox et al. reporting a multiorgan case in 1974 involving a patient with impaired cellular immunity.^[1] In the 1990s, P. wickerhamii was established as the primary human pathogen, responsible for the majority of over 100 reported cases, often presenting as localized cutaneous infections or olecranon bursitis in immunocompetent individuals, while P. zopfii predominated in animal cases.^[1] Post-2000, increased surveillance revealed outbreaks in dogs, with systemic protothecosis causing gastrointestinal and ocular disease, and emerging cases in immunocompromised humans, including those with HIV/AIDS, highlighting Prototheca as an opportunistic pathogen in the context of rising immunosuppression.^[14] Recent developments in the 2020s have focused on molecular epidemiology, with studies identifying P. bovis (formerly P. zopfii genotype 2) as the dominant strain in bovine mastitis outbreaks across Europe and Asia, utilizing genotyping techniques like PCR-RFLP for enhanced surveillance and source tracking.^[2]

Etiology and Pathogenesis

Causative Agents

Prototheca species are achlorophyllous, unicellular microalgae classified within the Chlorophyta phylum, functioning as ubiquitous environmental saprophytes commonly isolated from sewage, wastewater, soil, and decaying vegetation such as tree slime flux.^[2] These organisms exhibit optimal growth at temperatures ranging from 25°C to 37°C, with many strains thriving on glucose-based media like Sabouraud dextrose agar, where they ferment glucose into lactic acid but do not ferment other common sugars.^[15]^[16] They reproduce asexually through endosporulation, producing 2 to 20 endospores within a sporangium every 5 to 6 hours, which facilitates their persistence and dissemination in moist, organic-rich environments.^[2] Key virulence factors of Prototheca species include structural components of their two-layered cell wall, which contains β-(1,4)-glucans that contribute to resistance against phagocytosis by host immune cells, particularly in species like P. wickerhamii where uptake by macrophages remains below 1% even after prolonged exposure.^[17] Additionally, these algae can form biofilms composed of surface-attached cells linked by extracellular DNA and polysaccharides, which enhance resistance to sanitizers and reduce activation of immune responses such as IL-6 production.^[6] Endospore production further aids in dissemination within the host, allowing replication inside phagolysosomes and survival against macrophage digestion.^[18] Species differentiation within the genus Prototheca is critical for understanding their pathogenic roles, with identification often achieved through molecular methods like PCR targeting the cytb gene.^[19] Prototheca wickerhamii is the predominant cause of human protothecosis, particularly cutaneous and ocular infections, and is distinguished by smaller sporangia (3–10 μm) with radially arranged, wedge-shaped sporangiospores.^[20] In contrast, Prototheca zopfii (now reclassified with genotype 1 as P. ciferrii and genotype 2 as P. bovis) is primarily associated with bovine mastitis, where genotype 2 (P. bovis) demonstrates higher virulence due to greater biofilm formation and inflammatory potential in mammary tissue.^[21]^[22] Prototheca cutis, a rarer species described in the 2010s, has been implicated in isolated cases of human skin infections, often in immunocompromised individuals.^[23] Prototheca species exhibit opportunistic pathogenic potential, causing infections primarily in immunocompromised hosts or those with disrupted barriers, but they are not contagious between individuals as transmission occurs solely from environmental sources.^[12] Their ability to evade immune responses stems from the absence of photosynthetic pigments, which reduces recognition by host defenses, and their yeast-like morphology that mimics fungal cells, allowing intracellular survival and chronic persistence without eliciting strong innate immunity.^[18]^[24]

Transmission and Risk Factors

Protothecosis is acquired primarily through environmental exposure to Prototheca species, which serve as opportunistic pathogens entering hosts via disrupted barriers rather than direct interpersonal or interspecies transmission. The main routes include percutaneous inoculation, such as through skin wounds, surgical sites, or indwelling catheters in contact with contaminated sources, and oral ingestion of polluted water or feed. Inhalation is considered rare and poorly documented. No evidence supports direct host-to-host transmission, underscoring the infection's non-zoonotic character, with an incubation period typically spanning weeks to months, though cases have reported onset from 10 days to 4 months post-exposure. Environmental reservoirs of Prototheca abound in aqueous and organic-rich settings, including sewage sludge, wastewater treatment plants, natural freshwater and saltwater bodies, soil, and agricultural waste like animal manure. These algae persist in such niches due to their resilience to chlorination, pasteurization, and pH variations, with isolation rates reaching up to 14.1% in urban river waters and similar aquatic ecosystems. Contamination often traces to high-humidity areas with decaying vegetation, such as tree slime flux or farm bedding. In humans, key risk factors center on compromised immunity and physical breaches, including immunosuppression from HIV/AIDS, diabetes mellitus, solid organ transplantation, chemotherapy, or corticosteroid use, which impair cellular defenses and neutrophil function. Trauma, surgical procedures, or occupational exposures—such as farming, fishing, or aquaculture in tropical and subtropical regions—further elevate susceptibility by facilitating algal entry through skin or mucosal defects. Endogenous dissemination may occur from gastrointestinal colonization in vulnerable patients, leading to systemic spread. For animals, transmission and risks align closely with environmental and management practices. In cattle, poor dairy farm hygiene promotes bovine mastitis via contaminated milking equipment, water troughs, or bedding, particularly in warm, humid climates with heavy rainfall or recycled manure effluent. Outdoor dogs face heightened risk from accessing sewage or polluted waters, often via fecal-oral routes, while cats are predisposed through open wounds in contaminated settings. Breeds like Boxers and Labrador Retrievers appear overrepresented in canine cases, though underlying immune deficits remain unproven in most animal infections.

Epidemiology

Global Distribution

Protothecosis is a rare infection caused by achlorophyllous algae of the genus Prototheca, with sporadic cases reported globally on every continent except Antarctica. The disease exhibits a higher prevalence in temperate and tropical regions, where environmental conditions favor the proliferation of Prototheca species in organic-rich habitats such as sewage and wastewater. Notable examples include occurrences in the United States, Europe, Asia, and Africa, reflecting the ubiquitous nature of these organisms in moist environments worldwide.^[3]^[25]^[1] Endemic hotspots for protothecosis are particularly evident in agricultural settings for bovine cases and in specific locales for human infections. In dairy farms, outbreaks of bovine protothecosis caused by P. zopfii (particularly genotype 2) have been documented in Germany, Japan, and the United States, often linked to large-scale industrial operations in temperate zones. Human cases show clustering in the United States, accounting for approximately 40% of reported disseminated infections, with notable instances in states like Florida and California, as well as in Australia, where cutaneous forms predominate in subtropical areas.^[22]^[24]^[26] Temporal trends indicate an increase in reported protothecosis cases since 2000, attributed to advancements in diagnostic techniques such as molecular identification and improved surveillance. Animal outbreaks, especially in cattle, have been associated with seasonal contamination from wastewater sources, peaking during warmer months when algal growth in sludge and effluents intensifies. This rise underscores the growing recognition of Prototheca as an emerging pathogen in veterinary and human medicine.^[2]^[6]^[22] Geographic variations in causative species highlight distinct patterns: P. wickerhamii is the predominant species in human protothecosis cases worldwide, with reports from developing countries including China and other Asian regions, often involving cutaneous or disseminated forms in immunocompromised individuals. In contrast, P. zopfii is more prevalent in bovine cases within industrial dairy regions of Europe and North America, reflecting environmental reservoirs tied to agricultural wastewater.^[27]^[28]^[22] Surveillance data from veterinary reports and health authorities, including the European Food Safety Authority (EFSA) for animal cases and Centers for Disease Control and Prevention (CDC) compilations for human infections, estimate an extremely low global incidence of fewer than 10 human cases annually, emphasizing the disease's rarity despite its global footprint. These sources track patterns through case registries and environmental monitoring, aiding in identifying at-risk areas like contaminated water systems.^[29]^[2]^[4]

Incidence in Humans and Animals

Protothecosis remains an exceedingly rare infection in humans, with fewer than 400 cases documented worldwide since the first report in 1964. Approximately 335 cases had been reported as of 2023, predominantly involving cutaneous or localized manifestations, though disseminated forms occur in severe instances. The disease is far more prevalent in animals, particularly cattle, where outbreaks of mastitis can affect thousands of individuals annually in endemic regions, though global surveillance is limited and cases are likely underreported due to diagnostic challenges.^[30]^[4] In humans, protothecosis primarily affects immunocompromised individuals, accounting for about 80% of cases, including those with AIDS, organ transplants, malignancies, or prolonged corticosteroid use. Incidence is increasing alongside the rise in immunosuppressive conditions, but the overall rate remains low, with most reports from North America and Europe. Demographically, cases skew toward adults over 50 years of age, with a slight male predominance (around 65-70% male), though infections span all ages from neonates to the elderly. Geographic hotspots include the USA and Europe, where environmental exposure via contaminated water or soil facilitates sporadic occurrences.^[1]^[31]^[20] Among animals, bovine protothecosis manifests mainly as mastitis, impacting 0.1-5% of herds in endemic areas such as parts of Europe and Asia; for instance, cow-level prevalence reaches 4-8% within affected herds, with subclinical cases comprising the majority. In dogs, over 120 cases have been reported globally up to 2023, often presenting as disseminated and fatal infections, with an underestimation due to limited veterinary screening. Certain breeds like Collies and Boxers show predisposition. Infections in cats, sheep, and goats are exceptionally rare, with fewer than 10-20 documented cases per species over decades, typically involving localized skin or nasal lesions. Underreporting across species stems from frequent misdiagnosis as yeast or fungal infections and the absence of routine Prototheca-specific testing in clinical practice.^[32]^[33]^[34]

Clinical Features

In Humans

Protothecosis in humans is typically classified into three main clinical forms: cutaneous lesions (accounting for approximately 66% of cases), olecranon bursitis (about 15%), and disseminated or systemic infections (around 19%).^[7]^[35] Cutaneous protothecosis often presents as erythematous plaques, nodules, ulcers, or eczematous lesions, primarily on exposed areas such as the face, arms, and legs, frequently following traumatic inoculation. These lesions progress slowly if untreated and are more common in immunocompetent individuals.^[36]^[37] Olecranon bursitis manifests as localized swelling, erythema, and pain in the elbow bursa, often associated with trauma or repeated pressure, and is usually seen in otherwise healthy individuals.^[20]^[24] Disseminated protothecosis, more prevalent in immunocompromised patients (e.g., those with AIDS, transplants, or malignancies), involves multiple organs and presents with nonspecific symptoms such as fever, weight loss, fatigue, and skin lesions, alongside involvement of the bloodstream, peritoneum, or other sites; mortality exceeds 45% in these cases.^[38]^[39]

In Animals

Protothecosis in animals manifests primarily as a chronic infectious disease caused by algae of the genus Prototheca, with bovine mastitis representing the most common veterinary presentation, accounting for the majority of reported cases worldwide. In cattle, infections typically involve the mammary gland, leading to subclinical or clinical mastitis characterized by udder swelling, reduced milk yield, and production of watery milk containing white flakes or clots. Outbreaks, often linked to P. zopfii genotype 2, have been documented in dairy herds, exacerbated by poor hygiene and environmental contamination, resulting in significant economic losses through decreased productivity and the need for premature culling of affected animals. Pathologically, lesions exhibit granulomatous inflammation with clusters of algal cells forming characteristic morula-like structures in mammary tissue and regional lymph nodes.^[6]^[40] In dogs, protothecosis frequently presents as a disseminated infection with multisystem involvement, particularly affecting the gastrointestinal, ocular, and central nervous systems, and carries a grave prognosis with mortality exceeding 80% in systemic cases. Gastrointestinal signs are the most prevalent, including chronic bloody diarrhea, weight loss, tenesmus, and mucus-laden feces due to colitis, often progressing to systemic spread involving the colon and rectum. Ocular manifestations, observed in approximately 9% of cases, include uveitis, retinal detachment, and blindness, while central nervous system involvement, seen in about 5% of dogs, leads to ataxia, seizures, and paresis from lesions in the brain or spinal cord. Pathological examination reveals granulomatous inflammation with algal sporangia in affected organs such as the intestines, eyes, kidneys, and brain, confirming the disseminated nature in over 67% of canine infections.^[14] Protothecosis is less common in other species but can cause varied clinical syndromes. In cats, infections are rare and typically limited to cutaneous lesions, presenting as nodular, ulcerative wounds on the face, limbs, or at trauma sites, with P. wickerhamii as the predominant isolate and granulomatous dermatitis on histopathology. Sheep and goats experience sporadic cases, primarily cutaneous in goats with pyogranulomatous lesions on the nasal vestibule, face, and mucocutaneous junctions, accompanied by mucopurulent discharge, dyspnea, and sneezing, though systemic dissemination is uncommon and no abortions have been directly linked. In fish, particularly in aquaculture settings like carp, infections lead to gill and skin involvement with ulcerative nodules, erosions, underweight appearance, and ataxia, featuring algal clusters in liver and intestinal lesions. Horses rarely develop protothecosis, with reports limited to upper respiratory tract disease such as rhinitis and sinusitis, or ocular keratitis, resulting in localized granulomatous inflammation. Overall, while bovine cases drive economic impacts through herd management, canine infections highlight high fatality rates, underscoring the need for early veterinary intervention across species.^[6]^[41]

Diagnosis

Laboratory Methods

Laboratory diagnosis of protothecosis relies on direct detection of the causative Prototheca species through microbiological and molecular techniques, confirming the presence of these achlorophyllic algae in clinical specimens such as tissue biopsies, fluids, or exudates. Microscopy serves as a rapid initial tool, with wet mounts prepared using lactophenol cotton blue, calcofluor white, or methylene blue revealing the pathognomonic morula-like sporangia containing multiple endospores. These structures appear as spherical to ovoid cells, 3–30 μm in diameter, with symmetrical morula forms typical of P. wickerhamii and asymmetrical ones for P. bovis; Gram staining further highlights the gram-positive, non-budding sporangia in smears from infected material.^[42]^[13]^[6] Culture remains a cornerstone for isolation and preliminary identification, with specimens inoculated onto Sabouraud dextrose agar, blood agar, or Prototheca isolation medium and incubated at 25–37°C for 2–7 days. Colonies emerge as creamy white to light tan, yeast-like, and wrinkled, mimicking non-albicans Candida species but lacking aerial hyphae or pseudohyphae.^[42]^[13] Biochemical profiling, including urease negativity on Christensen urea agar and carbohydrate assimilation tests via API 20C AUX system, differentiates species—for instance, P. wickerhamii assimilates trehalose while P. bovis does not.^[42]^[43]^[6] Histopathology provides definitive evidence in tissue samples, where periodic acid-Schiff (PAS) or Gomori methenamine silver (GMS) stains accentuate the thick-walled algal cells and sporangia within granulomatous inflammation. Tissues often show suppurative or pyogranulomatous responses with multinucleated giant cells surrounding clusters of organisms, particularly in cutaneous, ocular, or disseminated lesions.^[42]^[13] Molecular identification enhances species differentiation and detection sensitivity, especially in culture-negative or low-burden cases. Polymerase chain reaction (PCR) assays target the 18S rRNA, internal transcribed spacer (ITS) regions, 28S rRNA D1/D2 domain, or mitochondrial cytochrome b (cytb) genes, with sequencing confirming identities such as P. wickerhamii at >99% homology to reference strains.^[42]^[44] Real-time PCR variants, including SYBR green or TaqMan probes, amplify Prototheca DNA from fresh, fixed, or fecal specimens, while matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers rapid proteomic profiling for genus and species-level identification.^[13]^[44] Culture confirms infection in the majority of suspected cases, though positivity rates vary across series (e.g., 27-49% in larger canine reviews as of 2025), with PCR improving yield in formalin-fixed tissues or low-organism loads where culture may fail.^[14]^[44]

Imaging and Other Tests

Imaging modalities play a supportive role in diagnosing protothecosis by identifying lesions and guiding biopsies, particularly in cutaneous, bursal, central nervous system (CNS), or disseminated cases. Ultrasound is useful for evaluating olecranon bursitis, a common presentation, where it reveals fluid collections in the bursa, synovial proliferation, and potential hyperemia, aiding in aspiration for further analysis.^[45] In cutaneous lesions, ultrasound can delineate superficial involvement or abscess formation.^[46] For systemic or CNS involvement, computed tomography (CT) and magnetic resonance imaging (MRI) are essential to detect abscesses, ring-enhancing lesions, and surrounding edema. In cerebral protothecosis, non-contrast CT may show high-density lesions suggestive of primary brain pathology, while MRI typically demonstrates multifocal abnormalities with patchy diffusion restriction, contrast enhancement, and vasogenic edema in areas such as the frontal lobe, thalamus, or cerebellum.^[47]^[48] These findings support clinical suspicion in disseminated human cases, though thoracic radiographs are often unremarkable.^[25] Ocular involvement, more commonly reported in animals but rare in humans, is assessed via ophthalmoscopy, which may reveal bilateral whitish-yellow lesions at the retinal pigment epithelium, vitritis, and choroiditis in disseminated disease.^[49] Serological tests, such as enzyme-linked immunosorbent assay (ELISA) for anti-Prototheca antibodies, have limited utility in routine diagnosis due to poor sensitivity, specificity, and cross-reactivity with other organisms; they are primarily employed in research settings, particularly for veterinary mastitis.^[50] Tissue biopsy is crucial for histopathologic confirmation in deep or disseminated infections, revealing granulomatous inflammation with characteristic morula-like algal structures.^[47] In disseminated cases, blood cultures can isolate Prototheca species, while cerebrospinal fluid (CSF) analysis, though rarely positive in protothecal meningitis, may show mild pleocytosis or negative microbiology, supporting the need for brain biopsy.^[48] Overall, these tests enhance localization and corroborate microbiologic findings but do not replace direct pathogen identification.^[1]

Treatment and Management

Pharmacological Therapy

The pharmacological therapy for protothecosis lacks a standardized regimen due to the infection's rarity and variable clinical presentations, necessitating individualized approaches guided by in vitro susceptibility testing.^[4] First-line treatment for disseminated disease typically involves systemic amphotericin B, administered intravenously at 0.5-1 mg/kg daily, which demonstrates broad efficacy against Prototheca species.^[51] For localized ocular or cutaneous manifestations, voriconazole is often preferred, given orally at 200-400 mg per day, owing to its favorable in vitro activity and tissue penetration.^[6] Alternative agents include oral itraconazole (200 mg twice daily) or fluconazole (200-400 mg daily) for mild or localized cases, particularly when azole susceptibility is confirmed.^[51] Adjunctive therapy with tetracyclines, such as doxycycline (100 mg twice daily), may be incorporated in combination regimens to enhance outcomes in refractory infections.^[6] Prototheca isolates generally exhibit high susceptibility to amphotericin B, with minimum inhibitory concentrations (MICs) typically below 1 μg/mL, but some strains of P. zopfii demonstrate resistance to azoles, underscoring the importance of species-specific in vitro testing prior to therapy initiation.^[4] Treatment duration is usually 4-12 weeks, tailored to clinical response and resolution of infection, with monitoring via repeat cultures or biopsies; combination therapy, such as amphotericin B plus an azole, is recommended for refractory or disseminated cases to improve clearance.^[51] In humans, cure rates for cutaneous protothecosis range from 60-80% with antifungal monotherapy or combinations, while disseminated forms achieve lower success at approximately 33%.^[6] In canines with disseminated disease, outcomes remain poor, with cure rates of approximately 10% overall and less than 2% for systemic cases, often necessitating prolonged or multimodal approaches despite limited overall efficacy.^[14]

Surgical Interventions

Surgical interventions are indicated for localized protothecosis in humans when infections, such as cutaneous lesions, olecranon bursitis, or abscesses, fail to respond to pharmacological therapy alone.^[37]^[52] In ocular cases, debridement may be performed for keratitis to remove infected corneal tissue.^[53] Common procedures include excision of infected tissue, such as bursectomy for olecranon bursitis to fully remove the affected bursa, and incision and drainage for subcutaneous abscess collections.^[54]^[55] For severe ocular involvement like endophthalmitis, pars plana vitrectomy is employed to clear protothecal organisms from the vitreous humor.^[56] These surgical approaches are typically adjunctive to antifungal therapy, enhancing clearance of the infection in localized cases.^[57] In humans, surgery combined with antifungals achieves success rates of approximately 73% for cutaneous lesions and 83% for olecranon bursitis.^[58] Incomplete excision of margins can lead to recurrence, while skin surgeries may result in cosmetic scarring.^[52] In veterinary medicine, surgical interventions mirror human approaches but are adapted to animal-specific presentations. For severe bovine mastitis caused by Prototheca, udder amputation may be performed in valuable animals to excise extensively damaged tissue and prevent systemic spread.^[59] In canine ocular protothecosis, enucleation is often indicated for painful, blind eyes to alleviate suffering and confirm diagnosis histologically.^[60]^[61]

Prevention and Control

In Humans

Protothecosis prevention in humans primarily focuses on minimizing exposure to environmental sources of Prototheca species, such as contaminated water, soil, and sewage, through personal hygiene practices.^[1] Proper wound care is essential, particularly after trauma, to prevent algal entry into the skin, as many cutaneous cases are linked to inoculation via open wounds.^[1] Individuals should avoid swimming or bathing in stagnant, swampy, or untreated water bodies in endemic areas, where Prototheca thrives.^[62] For at-risk occupations like aquaculture workers, farmers, and fishermen, who face frequent contact with potentially contaminated environments, wearing protective gear such as gloves, boots, and waterproof clothing is recommended to reduce skin exposure.^[1] In immunocompromised individuals, prophylactic antifungal therapy is not standard due to the rarity of the infection and lack of established protocols.^[6] However, patients on peritoneal dialysis should be monitored closely for signs of peritonitis, as Prototheca has been implicated in rare cases, emphasizing the importance of strict aseptic techniques during catheter care.^[63] Public health measures include ensuring water treatment and chlorination in hospitals to mitigate hospital-acquired infections, although Prototheca can survive standard chlorination levels.^[1] Routine screening for protothecosis is not recommended due to its low incidence, but early biopsy of suspicious skin lesions in at-risk individuals facilitates prompt diagnosis and intervention.^[1]

In Veterinary Practice

In veterinary practice, prevention of protothecosis focuses on environmental controls and biosecurity measures tailored to animal species and production systems to minimize exposure to Prototheca algae, which thrive in moist, organic-rich environments.^[12]^[23] For dairy cattle, rigorous hygiene protocols are essential to curb transmission, particularly in cases of mastitis, which accounts for the majority of bovine protothecosis infections. Key practices include thorough cleaning and disinfection of milking equipment using agents like peracetic acid or sodium hydroxide to remove biofilms, along with pre- and post-milking teat dips containing iodine, sodium hypochlorite, or chlorhexidine.^[64]^[12] Chlorination of water supplies and regular monitoring for contamination—such as checking for opacity, odor, or fecal matter—help limit algal growth in drinking water and wastewater from milking operations.^[23] Pasteurization of milk is effective in reducing or eliminating Prototheca species, helping to prevent zoonotic transmission.^[40] Infected animals should be segregated immediately and culled to prevent herd spread, as demonstrated in outbreak recoveries where removal of positive cows restored herd health.^[64]^[23] Broader farm management involves maintaining clean, dry housing with frequent bedding changes to reduce organic buildup, alongside biosecurity protocols like quarantining new stock and facility disinfection, which are particularly critical in endemic regions such as European countries and Japanese dairies where protothecal mastitis prevalence has been documented in bulk tank milk samples.^[12]^[23]^[65] In companion animals like dogs and cats, preventive strategies emphasize limiting environmental exposure, as Prototheca species are ubiquitous in sewage, soil, and wastewater. Owners should prevent pets from accessing contaminated areas and promptly clean any wounds to avoid algal entry, though no breed-specific screening programs exist for predisposed breeds such as Collies in dogs.^[12] Aquaculture operations, where protothecosis is rare but reported in species like carp, require water management to mitigate risks, though specific veterinary guidelines remain limited.^[66] No vaccines are currently available for protothecosis in animals, underscoring the reliance on hygiene and biosecurity for control.^[12]^[67]

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Protothecosis is a rare infectious disease caused by nonphotosynthetic algae belonging to the genus Prototheca, which is closely related to the green algae ...
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Identification of Prototheca species from bovine milk samples by ...
The aim of this study was to develop a rapid method to differentiate P. zopfii genotype 2, responsible for bo- vine mastitis, from other microalgae. Polymerase ...
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Prototheca spp. in Bovine Infections - MDPI
Sep 8, 2023 · Bovine mastitis represents the most important form of Prototheca infection in animals and consists of clinical or subclinical forms. Dairy- ...
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New approaches for risk assessment and management of bovine ...
The first reported human case of protothecosis was diagnosed in 1964, in Sierra Leone, on the foot of a rice farmer. The lesion started as a depigmented ...
[23]
Human Disseminated Protothecosis: The Skin is the “Window”?
Jun 13, 2022 · Human disseminated protothecosis is a rare infection caused by members of the genus Prototheca, an achlorophyllic algae always associated with debilitated ...
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Protothecosis - an overview | ScienceDirect Topics
Protothecosis is an uncommon cutaneous or systemic disease caused by Prototheca species, which are unicellular algae. Prototheca spp. lack chlorophyll, and as a ...Missing: taxonomy | Show results with:taxonomy
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Cutaneous protothecosis: contrasting case presentations - Pathology
Aug 14, 2023 · Two cases of cutaneous protothecosis: unique histopathological findings with crystal violet staining and the therapeutic effect of itraconazole.
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Prototheca wickerhamii causing toe infection presenting initially as ...
Sep 4, 2025 · This report describes a rare case of Prototheca wickerhamii toe infection in a 78-year-old Chinese male, presenting initially as gouty arthritis ...
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Successful treatment of cutaneous protothecosis with fluconazole: A ...
Mar 13, 2024 · We describe this case and 29 cases of prototheca infections in China. At present, Prototheca wickerhamii (Pw) infection is the most common ...
[28]
[PDF] GRAS Notice 673, Algal fat derived from Prototheca moriformis ...
Sep 23, 2016 · a total of 160 cases of human protothecosis reported from the first diagnosis of human protothecosis(1964)until 2012(Todd et al,2012).
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Successful Treatment of Cutaneous Protothecosis Due to Prototheca ...
Apr 24, 2024 · We present a case of cutaneous protothecosis effectively cured through a three-month course of terbinafine treatment.<|control11|><|separator|>
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Disseminated protothecosis: Case report and review of the literature
Jun 11, 2024 · Results: Overall, 54 cases of disseminated protothecosis were evaluated, 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and ...Missing: total | Show results with:total
[31]
A survey on the incidence of Prototheca mastitis in dairy herds in ...
The prevalence of protothecal mastitis in individual herds ranged from 0% (farms I, VI, and IX) to 25% (IV) with a mean of 4.6%. Prototheca spp. were detected ...
[32]
Prevalence of Prototheca spp. on dairy farms in Poland - NIH
Prototheca mastitis most often presents as a chronic process characterized by a permanent increase in somatic cell count and dramatic decline in milk yield ( ...
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[PDF] Protothecosis in Dogs: A Narrative Review | AlergoVet
Jan 31, 2025 · We present a synthesis of the current literature on protothecosis, with special emphasis on disease features in the dog. Five open- access ...
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What Is Protothecosis? - iCliniq
Feb 10, 2023 · Medical Care: Protothecosis can be hard to eradicate. Successful treatment is seen with Ketoconazole, Fluconazole, and Itraconazole.
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Successful treatment of Prototheca peritonitis ... - PubMed
We describe the second reported case of peritonitis caused by the alga Prototheca wickerhamii in a patient on continuous ambulatory peritoneal dialysis (CAPD).Missing: prevention | Show results with:prevention
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Long Term Follow-Up of Prototheca keratitis: A Case Report - PMC
Oct 9, 2020 · Corneal smears and contact lens swabs were positive for Prototheca spp. He required a continuous treatment with amphotericin B (AMPH-B) ointment ...Missing: prevention | Show results with:prevention
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New approaches for risk assessment and management of bovine ...
Protothecosis is a potential zoonosis related to bovine mastitis. In several countries, a higher incidence of protothecal bovine mastitis that is being recorded ...Missing: overview | Show results with:overview
[38]
Protothecosis and chlorellosis in sheep and goats: a review - PMC
Protothecosis and chlorellosis are sporadic algal diseases. In goats, protothecosis causes nasal lesions, while in sheep, chlorellosis causes green lesions in ...
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https://ijdvl.com/cutaneous-protothecosis-in-an-immunocompetent-host/
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Phenotypic and molecular characterization of Prototheca ...
Nov 4, 2024 · Prototheca species survive in wet environments, including tap water and other natural sources of water, vegetables, saprophytic niches as sewage ...Missing: temperature fermentation
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Molecular characterization of Prototheca in 11 symptomatic dogs
Dec 3, 2020 · Protothecosis is an uncommon disease caused by algae of the genus Prototheca. In dogs, the infection is usually first localized to the colon ...
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Olecranon Bursitis Workup: Approach Considerations, Gram Stain ...
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[43]
Cutaneous protothecosis in a solid organ transplanted patient - NIH
Arterial and venous Doppler ultrasound ... Prototheca infection ranges from indolent and localized skin involvement, soft tissue infection, olecranon bursitis ...
[44]
Cerebral protothecosis mimicking high-grade glioma - PMC
Jan 26, 2021 · We report the first UK case of cerebral protothecosis in an immunocompetent 56-year-old woman who presented with a 5-month history of intermittent fatigue.
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The first case of intracerebral lesions caused by Prototheca ...
Case Report. A 55 year old female presented with progressive neurology and multiple lesions on brain MRI scanning. Initial histology from a brain biopsy was ...
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Bilateral Choroiditis From Prototheca wickerhamii Algaemia
Aug 1, 2005 · Ocular involvement in the setting of disseminated protothecosis was confirmed by histopathological examination and PCR analysis. Although ...
[47]
Longitudinal Analysis of Prototheca zopfii-Specific Immune Responses
Both counterimmunoelectrophoresis tests and ELISA-based detection of anti-Prototheca IgG in serum showed poor sensitivity and specificity and thus are not ...
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Drug Susceptibility Profiling of Prototheca Species Isolated from ...
Mar 21, 2023 · At least five species have been implicated as the causative agents of opportunistic infections of men. Human protothecosis typically manifests ...
[49]
Successful treatment of cutaneous protothecosis with liposomal ...
Medical treatment for protothecosis most commonly includes antifungal agents and/or tetracyclines [1], [2]. Reported treatment success rates are higher for ...
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Cutaneous Protothecosis - Allen Press
Jul 1, 2011 · Cutaneous protothecosis is an uncommon indolent condition occurring primarily in immunocompromised individuals.
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Protothecal Olecranon Bursitis: An Unusual Algal Infection
More recently, itraconazole has been found to be curative. Surgical excision of the bursa remains the definitive treatment of protothecal olecranon bursitis.
[52]
Protothecosis in the Southeastern United States - PubMed
Most cases have involved the olecranon bursa, have occurred in otherwise healthy individuals, and were cured by simple excision. Intensive therapy with ...
[53]
Protothecal bursitis after simultaneous kidney/liver transplantation: a ...
Jan 18, 2016 · ... surgical resection can be curative for olecranon bursitis, even in the absence of antifungal therapy. Therefore, removal of the source of ...
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Diagnosis of Ocular Infections | Clinical Microbiology Reviews
Jun 2, 2021 · Acanthamoeba keratitis is associated with poor contact lens hygiene, soft contact lens use, and/or a history of trauma or exposure to water ...
[55]
Successful Treatment of Protothecal Tenosynovitis in an ...
Dec 1, 2017 · Conventional amphotericin B was administered according to antifungal susceptibility tests and the lesion completely resolved. Protothecosis ...<|separator|>
[56]
Case Report: Olecranon Bursitis from Prototheca wickerhamii
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[PDF] Urogenital Surgery, Including Mastectomy
Udder amputation is performed when an owner wishes to keep the animal (either for genetic potential or as a pet) after the udder has become beyond repair. In ...Missing: protothecosis | Show results with:protothecosis
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Disseminated canine protothecosis - Awanui Veterinary
Aug 8, 2024 · Enucleation of eye was performed and was submitted to the laboratory along with vitreous humour collected pre-fixation, fresh and fixed colonic ...
[59]
Full article: Protothecosis in four dogs in New Zealand
The four cases in this series provide evidence for the occurrence of protothecosis as a cause of ocular, gastrointestinal and cutaneous disease in dogs in New ...
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Eradication of Bovine Mastitis Caused by the Pathogenic Microalga ...
Sep 13, 2023 · Bovine mammary gland infection caused by members of the genus Prototheca has been reported with increasing incidence worldwide in recent decades ...
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Analysis of Prototheca and yeast species isolated from bulk tank ...
Analysis of Prototheca and yeast species isolated from bulk tank milk collected in Tokachi District, Japan. August 2022; Journal of Dairy Science 105(10). DOI: ...
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Isolation of infectious microalga Prototheca wickerhamii from a carp ...
Protothecosis is a rare infection caused by environmentally ubiquitous achlorophyllic microalgae of the genus Prototheca. Here, we describe a first case of ...Missing: prevention | Show results with:prevention
[63]
Protothecosis in Veterinary Medicine: a minireview - PubMed
Jun 1, 2023 · Our findings showed that protothecosis has been reported in various domestic and wild animal species, presenting diverse clinical manifestations ...Missing: sheep | Show results with:sheep