10-year-old intact male rhesus macaque, (Macaca mulatta).This animal was part of a study at an outside research institution that was looking at neural recordings. The day after the first recording was made from the deep brainstem, vestibular signs were noted. The animal was treated and improved. About a month later a recording was made from the contralateral side of the brain stem. The next day, the animal was reported to be weak with conscious proprioceptive deficits. Over the next few days, the animal deteriorated and developed respiratory distress. Elective euthanasia was performed and lung and brain tissue were subsequently submitted for histologic evaluation.
The lungs are multifocally mottled dark red.Â The brain exhibits dark brown discoloration and cavitation around the 4th ventricle and near the hippocampal formation unilaterally.
Lung: In a section of lung, there are variably-sized aggregates of large foamy macrophages, lymphocytes, plasma cells, fewer neutrophils and scattered multinucleated giant cells typically centered on mildly to moderately ectatic bronchioles and less often alveoli and small to medium-caliber vessels.Â Inflammation infiltrates and expands the walls of affected bronchioles.Â These bronchioles are lined by severely attenuated to denuded epithelium and multiple coagula of fibrin, foamy macrophages, mature and degenerate neutrophils and multinucleated giant cells.Â Macrophages and giant cells often contain variable amounts of birefringent golden brown granular intracytoplasmic pigment.Â Smooth muscle and lymphoid tissue surrounding airways are multifocally and mildly to moderately hyperplastic.Â Within affected bronchioles and inflammation surrounding alveoli are variable numbers of partial to complete sections of 300-500 Î¼m diameter arthropods characterized by a thin golden chitinous exoskeleton, jointed appendages, a body cavity with striated musculature, and digestive and reproductive tracts (consistent with Pneumonyssus simicola).Â Some of these airways are close to the pleural surface and inflammation extends into and through the pleura, forming a nearly diffuse coagulum of fibrin, foamy macrophages, multinucleate giant cells and few lymphocytes and plasma cells on the pleural surface.Â The tunicae media and intima of few scattered medium-caliber vessels in the section are diffusely and severely expanded by large foamy macrophages and multinucleated giant cells, narrowing the lumen.Â The tunicae intima and media of other vessels are obscured by deeply eosinophilic fibrillar material and scattered foamy macrophages and multinucleated giant cells.Â Other scattered smaller caliber vessels are effaced by aggregates of fibrin, macrophages, lymphocytes and plasma cells.Â The adventitia of affected vessels is expanded by lymphocytes and fewer plasma cells.Â In less affected areas of the lung, there is multifocal moderate emphysema and the interstitium is multifocally and mildly expanded by infiltrates of macrophages and lymphocytes.Â There are scattered areas of mild hemorrhage.
1.Â Bronchiolitis, alveolitis and pleuritis, necrotizing, histiocytic, lymphoplasmacytic, multifocal, severe, chronic with bronchiolectasis, smooth muscle hyperplasia, lymphoid hyperplasia and intraluminal arthropods (Pneumonyssus simicola).Â
2.Â Vasculitis, multifocal, necrotizing to histiocytic, severe, chronic with multinucleated giant cells; lung.
While Pneumonyssus simicola, the lung mite of macaques, is no longer a routine finding in colony-housed animals, pulmonary acariasis occurs in up to 100% of wild rhesus monkeys and is still seen in research colonies that include wild-caught or imported animals.(1,2,4,6) In all affected macaques, P.Â simicola infection is usually subclinical, but can result in clinical respiratory signs and other complications including pneumothorax and pulmonary arteritis.(4,6) Arteritis characterized by fibrinoid degeneration, macrophages and multinucleate giant cells is present in this case, and the pleural inflammatory reaction and acute onset of respiratory distress suggest an acute pneumothorax was possible prior to euthanasia.Â
The exact lifecycle has not been fully elucidated, but adult mites are obligate endoparasites and adults feed on host erythrocytes, lymph and epithelial cells in the lung.Â Transmission requires close association with infected animals as it is likely through direct contact.Â
Gross lesions are generally multifocal, round, yellow to tan cystic foci up to several millimeters in diameter within the lung parenchyma.Â Mites occasionally can be visualized in the center of these lesions with the aid of a dissecting scope.Â Histopathologic findings typically include granulomatous and eosinophilic inflammation centered on the terminal air passages, pigment-laden macrophages, bronchiectasis, alveolar emphysema, bronchiolar smooth muscle hyperplasia and interstitial fibrosis.(1,4-6) Female mites are most commonly seen in the airways and can be up to approximately 700 Î¼m long with a thin chitinous exoskeleton, jointed appendages and a body cavity with a digestive tract and reproductive tract.(3-5) The characteristic birefringent crystalline pigment, regarded as a metabolite of the female mite, can be present in sections of tissue that lack mites and can be used to make a presumptive diagnosis.
While P.Â simicola is most frequently described in rhesus macaques, it has also been reported in other macaque species and a baboon.(3) Pulmonary acariasis is not limited to nonhuman primates; there are numerous species of mites that can be found in nasal passages and lungs of other animals including but not limited to Rhinophaga sp.Â in non-human primates, Pneumonyssoides caninum in dogs, Entonyssus sp.Â and Entophionyssus sp.Â in snakes, Cephenemyia sp.Â in wild cervids, Cytodites nudus in poultry, and Sternostoma tracheacolum in Gouldian finches.
1.Â Lung: Bronchiolitis, granulomatous and necrotizing, chronic, multifocal, severe, with bronchiolar smooth muscle hyperplasia, bronchiolectasis and intrabronchiolar arthropods and mite pigment.Â
2.Â Pleura: Serositis, granulomatous, multifocal, moderate, with epithelial hyperplasia.Â
3.Â Subpleural vasculature, smooth muscle: Hyperplasia, diffuse, mild to moderate.Â
This is an exceptional example of pulmonary acariasis with well preserved sections of adults, eggs and often mite fragments within multinucleated giant cells scattered throughout conducting airways and occasionally within alveoli.Â Bronchiolar walls are often replaced by fibrin and abundant granulomatous inflammation.Â We observed fibrinoid change in widely scattered vessel in several slides, but it was not constant over the distributed sections, so we have elected not include it in our diagnosis.Â
The term acariasis equates with a mite infection and is derived from the Order Acari in which all mites are classified.Â While most mite infections are localized to the skin, there are at least ten species of lung mites which infect the lungs of Old World monkeys, all of the genus Pneumonyssus.(7)
Conference participants debated on possible causes of the evident granulomatous inflammation with multinucleated cells lining the outside of the pleura in this case.Â Most agreed with the contributors suspicions of a secondary pneumothorax, possibly a sequela of ruptured mite houses.Â Additional Gram, fungal and acid-fast stains did not elucidate any additional infectious organisms.Â Without definitive causal evidence, we elected to separate out the diagnoses of serositis and the prominent smooth muscle hyperplasia of subpleural vessels.Â
As nicely described by the contributor, mite pigment is present in abundance in many sections.Â This is a golden brown to black pigment usually found within macrophages.Â This pigment does not contain carbon or melanin, but rather is iron-positive and likely the result of breakdown and excretion of the hosts blood proteins.(7)
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2.Â Andrade, MCR, Marchevsky, RS.Â Histopathologic findings of pulmonary acariasis in a rhesus monkeys breeding unit.Â [Aspectos histopatolÂ³gicos da acar+ï¿½-ï¿½ase pulmonar em uma cria+ï¿½-ï¿½+ï¿½-ï¿½o de maca-cos rhesus.] Revista Brasileira de Parasitologia Veterin+ï¿½-ï¿½ria.Â 2007;16(4):229-234.
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5.Â Ogata T, Imai H, Coulston F.Â Pulmonary acariasis in rhesus monkeys: electron microscopy study.Â Experimental and Molecular Pathology. 1971;15(2):137-47.
6.Â Osborn K, Lowenstein L.Â Respiratory diseases.Â In: Bennett B, Abee C, Henrickson R, eds.Â Nonhuman Primates in Biomedical Research: Diseases. 1st ed.Â Vol.Â 2.Â San Diego, CA: Academic Press; 1998:302-303.Â
7.Â Strait K, Else JG, Eberhard ML.Â Parasitic diseases of nonhuman primates.Â In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed.Â Vol.Â 2.Â San Diego, CA: Academic Press; 2012:268-270.