Infectious Disease and Microbiology - Alphavirus Group and Alternaria Species

Alphavirus Group

Alphaviruses are mosquito-borne viruses within the arbovirus group. Important members include Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Ross River virus, chikungunya virus, Mayaro virus, O’nyong-nyong virus, Sindbis virus, Barmah Forest virus, and several related viruses. These infections are generally uncommon but can cause important neurologic or rheumatologic syndromes.

Microbiologic Characteristics

Alphaviruses are enveloped viruses with icosahedral symmetry. Their genome consists of single-stranded, positive-sense RNA.

Because they are arboviruses, their natural transmission cycles usually involve arthropod vectors, particularly mosquitoes.

Epidemiology

Alphavirus infections occur in different geographic regions according to the distribution of their mosquito vectors and animal reservoirs.

Ross River virus is found mainly in Australia, Tasmania, Papua New Guinea, Indonesia, and islands of the South Pacific. Sindbis virus occurs across parts of Africa, Europe, Asia, and Australia. Barmah Forest virus is primarily associated with Australia.

Chikungunya virus has historically circulated in sub-Saharan Africa and Asia and has also caused outbreaks in many other regions. O’nyong-nyong virus occurs mainly in sub-Saharan Africa, while Mayaro virus is associated particularly with forested areas of Central and South America.

Transmission

Human infection most commonly follows the bite of an infected mosquito.

Depending on the specific virus, natural transmission cycles may involve:

• Mosquitoes

• Birds

• Rodents

• Nonhuman primates

• Horses or other vertebrate hosts

The geographic distribution of disease therefore closely follows the distribution of competent mosquito vectors.

Major Clinical Patterns

Alphavirus infections can be divided broadly into two major clinical groups.

The equine encephalitis viruses primarily cause neurologic disease, while chikungunya and several related alphaviruses more often cause acute febrile illnesses dominated by rash and severe joint symptoms.

Encephalitic Alphaviruses

Eastern equine, Western equine, and Venezuelan equine encephalitis viruses can cause central nervous system disease.

Patients may present with:

• Fever

• Headache

• Altered mental status

• Seizures

• Meningitis or encephalitis

• Coma in severe cases

Eastern equine encephalitis is particularly important because neurologic disease can be severe and may leave survivors with permanent neurologic deficits.

Arthritogenic Alphaviruses

Chikungunya, Ross River, Mayaro, O’nyong-nyong, Sindbis, and Barmah Forest viruses commonly produce a syndrome characterized by:

• Acute fever

• Macular or maculopapular rash

• Severe polyarthralgia

• Polyarthritis

• Myalgias

• Fatigue

Joint manifestations may be prolonged and can persist beyond the acute febrile illness.

Chikungunya

Chikungunya is one of the best-known arthritogenic alphavirus infections.

Patients typically develop abrupt high fever accompanied by intense joint pain, often involving multiple peripheral joints. A maculopapular rash is also common.

Although most patients recover from the acute illness, joint pain or inflammatory arthritis can persist for weeks, months, or occasionally longer.

Diagnosis

Diagnosis is based on a combination of clinical presentation, epidemiologic exposure, and laboratory testing.

Available methods include:

• PCR or RT-PCR

• Serologic testing

• Cell culture in specialized laboratories

PCR is particularly useful early in illness when viremia is present. Serology becomes more helpful later as virus-specific antibodies develop.

Treatment

There is no established specific antiviral treatment for routine alphavirus infection.

Management is primarily supportive and may include:

• Fluid replacement

• Antipyretics

• Analgesics

• Treatment of severe arthritis symptoms

• Seizure control

• Intensive neurologic and respiratory support for encephalitis

Ribavirin has shown some activity against alphaviruses in laboratory studies, but this has not translated into a routinely established clinical treatment.

Prevention

Prevention depends largely on limiting mosquito exposure.

Important measures include:

• Mosquito-control programs

• Elimination of standing water

• Insect repellents

• Long sleeves and protective clothing

• Window screens

• Mosquito nets where appropriate

Control of arthropod vectors remains the main preventive strategy for most alphavirus infections.

High-Yield Alphavirus Pattern

Mosquito exposure

• ●

Fever

• ●

Severe joint pain and rash

→ Think chikungunya or another arthritogenic alphavirus.

Mosquito exposure

• ●

Fever

• ●

Seizures or encephalopathy

→ Think Eastern, Western, or Venezuelan equine encephalitis virus.

Infectious Disease and Microbiology - Alternaria Species

Basics

Alternaria is a genus of darkly pigmented filamentous fungi that can cause superficial, localized, or invasive infections. Important species include Alternaria alternata, A. longipes, and A. tenuissima, although several other species can occasionally cause human disease.

Alternaria infections are generally uncommon and are especially important in immunocompromised patients.

Microbiologic Characteristics

Alternaria species are dematiaceous fungi, meaning that they contain dark melanin pigment within their cell walls.

They are filamentous molds with septate hyphae.

In tissue specimens, Alternaria may appear in several forms, including:

• Pigmented septate hyphae

• Pseudohyphal forms

• Yeast-like structures

In culture, the organism grows predominantly as hyphae.

Epidemiology

Alternaria species occur worldwide and are common environmental fungi.

They may be found in:

• Soil

• Plants

• Airborne organic material

• Agricultural environments

Human infection generally follows traumatic inoculation, inhalation, or opportunistic invasion in patients with impaired immunity.

Phaeohyphomycosis

One of the most characteristic infections caused by Alternaria is phaeohyphomycosis.

This term describes infection caused by darkly pigmented fungi that form pigmented hyphae or yeast-like elements in tissue.

Alternaria phaeohyphomycosis most often involves:

• Skin

• Subcutaneous tissue

Lesions may present as:

• Papules

• Nodules

• Plaques

• Ulcers

• Subcutaneous cysts

The course is often chronic and slowly progressive.

Skin and Subcutaneous Infection

Cutaneous Alternaria infection occurs particularly in immunocompromised patients, including those receiving corticosteroids or other immunosuppressive therapies.

The lesions may occur on exposed areas after minor trauma and can be mistaken for bacterial infection, atypical mycobacterial disease, or another fungal infection.

Biopsy and culture are usually required for diagnosis.

Sinusitis

Alternaria can occasionally cause fungal sinusitis, particularly in patients with impaired immunity.

Symptoms may include:

• Nasal obstruction

• Facial pain or pressure

• Headache

• Nasal discharge

• Fever in invasive disease

In severely immunocompromised patients, invasive sinus disease can extend into adjacent tissues and requires urgent treatment.

Osteomyelitis

Bone infection caused by Alternaria is uncommon but can occur, particularly after direct inoculation or extension from adjacent soft-tissue disease.

Patients may develop:

• Persistent localized pain

• Swelling

• Chronic drainage

• Bone destruction on imaging

Management generally requires both systemic antifungal therapy and surgical debridement.

Peritoneal Dialysis-Associated Peritonitis

Alternaria has been reported as a rare cause of peritonitis in patients receiving peritoneal dialysis.

Clinical manifestations can include:

• Abdominal pain

• Fever

• Cloudy peritoneal dialysis fluid

• Elevated peritoneal leukocyte count

Removal of the dialysis catheter may be required in addition to antifungal therapy.

Keratitis

Alternaria can cause fungal keratitis, often after corneal trauma involving plant or soil material.

Symptoms include:

• Eye pain

• Redness

• Photophobia

• Tearing

• Reduced visual acuity

Prompt ophthalmologic evaluation is important because fungal keratitis can progress and threaten vision.

Otitis Media

Alternaria has occasionally been reported as a cause of otic infection, particularly in agricultural workers with substantial exposure to soil and plant material.

This association likely reflects repeated environmental exposure.

Diagnosis

Diagnosis requires demonstration of the organism in appropriate clinical specimens.

Important approaches include:

• Direct microscopy

• Histopathologic examination

• Culture

• Species identification when available

Because Alternaria is also a common environmental mold, recovery from nonsterile specimens must be interpreted cautiously.

Demonstration of pigmented fungal elements invading tissue strongly supports true infection.

Histopathology

In tissue, Alternaria can appear as pigmented, septate hyphae or other fungal forms.

Special stains can help visualize the organism.

The presence of melanin pigmentation supports the diagnosis of a dematiaceous fungal infection.

Differential Diagnosis

Cutaneous Alternaria infection may resemble:

• Other causes of phaeohyphomycosis

• Sporotrichosis

• Nontuberculous mycobacterial infection

• Nocardiosis

• Bacterial abscesses

• Cutaneous malignancy

Keratitis should be differentiated from bacterial, viral, and other fungal causes.

Treatment

Treatment depends on the site and severity of infection.

Systemic antifungal agents with reported activity include:

• Itraconazole

• Voriconazole

• Amphotericin B

The choice should be individualized based on disease severity, site of infection, susceptibility results when available, and host immune status.

Itraconazole

Itraconazole has been used successfully in many localized cutaneous and subcutaneous Alternaria infections.

It is often favored when disease is chronic but not immediately life-threatening.

Treatment may need to continue for several weeks or months.

Voriconazole

Voriconazole is another important option, particularly for deeper or more serious infections.

Its good tissue penetration makes it useful in selected cases involving:

• Eye

• Bone

• Sinuses

• Disseminated disease

Clinical response should be monitored carefully.

Amphotericin B

Intravenous amphotericin B may be used for severe, invasive, or disseminated Alternaria infection.

Because of potential toxicity, lipid formulations are often preferred when prolonged treatment is required.

Surgical Management

Surgery can be an important part of treatment when localized infected tissue is accessible.

Potential procedures include:

• Excision of cutaneous or subcutaneous lesions

• Drainage of collections

• Debridement of infected bone

• Sinus surgery

• Removal of infected dialysis catheters

• Ophthalmologic intervention for severe keratitis

Combining surgery with antifungal therapy may improve outcomes in deep or refractory disease.

Prognosis

Localized skin and subcutaneous infections usually have a better prognosis than invasive disease.

Outcome is more guarded when infection involves:

• Bone

• Sinuses with tissue invasion

• Internal organs

• Severely immunocompromised patients

Reducing immunosuppression when medically possible can improve the likelihood of successful treatment.

High-Yield Alternaria Pattern

Immunocompromised patient

• ●

Chronic pigmented skin or subcutaneous lesions

• ●

Dematiaceous septate mold

→ Consider Alternaria phaeohyphomycosis.

Exam Essentials

Alphavirus

Genome:

→ Positive-sense single-stranded RNA

Envelope:

→ Present

Transmission:

→ Mosquitoes

Equine alphaviruses:

→ Encephalitis

Chikungunya and related viruses:

→ Fever + rash + polyarthralgia/polyarthritis

Diagnosis:

→ PCR and serology

Treatment:

→ Supportive

Prevention:

→ Mosquito control

Alternaria

Organism:

→ Dematiaceous filamentous fungus

Hyphae:

→ Pigmented and septate

Important species:

→ A. alternata, A. longipes, and A. tenuissima

Classic infection:

→ Phaeohyphomycosis

Other infections:

→ Sinusitis, osteomyelitis, keratitis, peritonitis, and otic infection

Diagnosis:

→ Histopathology and culture

Important antifungal agents:

→ Itraconazole, voriconazole, and amphotericin B

Important additional treatment:

→ Surgical excision or debridement when feasible