Treatment
There is no known permanent cure or treatment for primary trimethylaminuria, only mitigation of the effects. For secondary trimethylaminuria, it depends on the cause; for precursor overload, reducing the intake of TMA and its precursors will end symptoms. For TMAU caused by hypothetical gut dysbiosis, clinical review by a doctor, a plant based diet and reduced precursor intake should return gut flora to a healthy state.Primary TMAU sufferers generally have some residual FMO3 activity in the liver which processes TMA, however this happens relatively slowly. According to a study by Al-Waiz M TMA filters through to the bladder at half the rate of TMAO, and a healthy functioning person passes 99% of TMAO in urine within 24 hours. Therefore its estimated that the majority of TMA would be filtered out within 48 hours if no additional TMA or precursor is ingested, regardless of liver function. The metabolic and clinical manifestations of TMAU are generally regarded as benign, as there is no associated organ dysfunction. This designation, and the fact that the condition is often unrecognised by doctors, misdiagnosed and can have important ramifications including missed or delayed diagnosis.Affected individuals experience shame and embarrassment, fail to maintain relationships, avoid contact with people who comment on their condition, and are obsessive about masking the odour with hygiene products and even smoking. The malodorous aspect can have serious and destructive effects on schooling, personal life, career and relationships, resulting in social isolation, low self-esteem, depression, paranoid behaviour, and suicide.
In protected soil environments, near water sources, that are disturbed either naturally or by human activity, P. brasiliensis has been epidemiologically observed (although not isolated). A known animal carrier is the armadillo. In the natural environment, the fungi are found as filamentous structures, and they develop infectious spores known as conidia.Human to human transmission has never been proven. Mechanism
Primary infection, although poorly understood due to lack of data, is thought to occur through inhalation of the conidia through the respiratory tract, after inhaling fungal conidia produced by the mycelial form of P. brasiliensis. This occurs predominantly in childhood and young adulthood, after exposure to agricultural activity. Infection may occur through direct skin inoculation, although this is rare.After inhalation into the alveoli, there is rapid multiplication of the organism in the lung tissue, sometimes spreading via the venous and lymphatic systems. Approximately 2% of people develop clinical features after the initial asymptomatic infection.The type of immune response determines the clinical manifestation of the infection, with children and HIV co-infected individuals most commonly developing the acute/subacute disseminated disease. Most of those infected develop a Type 1 T-cell (Th1) mediated immune response, resulting in fibrosing alveolitis and compact granuloma formation that control fungal replication, and latent or asymptomatic infection. It then is thought to remain dormant in residual lung lesions and mediastinal lymph nodes. A deficient Th1 cell response results in the severe forms of the disease.