The diagnosis of fungal neglected tropical diseases (fungal NTDs) and the role of investigation and laboratory tests: An expert consensus report

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs

Central nervous system paracoccidioidomycosis. Report of a case successfully treated with Itraconazol Paracoccidioidomicose do sistema nervoso central. Apresentação de um caso tratado com êxito com itraconazole

Paracoccidioidomycosis (PCM) is a primary pulmonary infection that often disseminates to other organs and systems. Involvement of the central nervous system (CNS) is rare and due to the fact that both clinical alertness and establishment of the diagnosis are delayed, the disease progresses causing serious problems. We report here a case of neuroparacoccidioidomycosis (NPCM), observed in a 55 year-old male, who consulted due to neurological symptoms (left hemiparesis, paresthesias, right palpebral ptosis, headache, vomiting and tonic clonic seizures) of a month duration. Upon physical examination, an ulcerated granulomatous lesion was observed in the abdomen. To confirm the diagnosis a stereotactic biopsy was taken; additionally, mycological tests from the ulcerated lesion and a bronchoalveolar lavage were performed. In the latter specimens, P. brasiliensis yeast cells were visualized and later on, the brain biopsy revealed the presence of the fungus. Treatment with itraconazole (ITZ) was initiated but clinical improvement was unremarkable; due to the fact that the patient was taking sodium valproate for seizure control, drug interactions were suspected and confirmed by absence of ITZ plasma levels. The latter medication was changed to clonazepam and after several weeks, clinical improvement began to be noticed and was accompanied by diminishing P. brasiliensis antigen and antibody titers. In the PCM endemic areas, CNS involvement should be considered more often and the efficacy of itraconazole therapy should also be taken into consideration.<br>A paracoccidioidomicose (PCM) é infecção pulmonar primária que algumas vezes pode se disseminar a outros órgãos e sistemas. O envolvimento do sistema nervoso central (SNC) é raro e devido ao fato que a alerta clínica e o estabelecimento do diagnóstico são tardios, a doença progride e o paciente piora. Aquí apresentamos caso de neuroparacoccidioidomicose (NPCM) observada em homem de 55 anos de idade que referia sintomas neurológicos (hemiparalisia esquerda, parestesias, ptose pálpebral direita, dor de cabeça, vômito e convulsões) de um mes de duração. Ao exame físico, foi achada lesão ulcerada e granulomatosa no abdômen. Como o diagnóstico era duvidoso, foi indicada biopsia estereotáxica; além disso provas micológicas a partir da lesão ulcerada e um lavado broncoalveolar foram realizados. Nas últimas amostras P. brasiliensis foi observado e depois a biopsia do cérebro revelou a presença do fungo. O tratamento com itraconazol foi iniciado mas a melhoria clínica não foi detectável; devido ao fato que o paciente estava tomando valproato de sódio para o controle das convulsôes, foi suspeita interação entre os dois medicamentos, que foi confirmada pela ausência do nível plasmático do antimicótico. Este último medicamento foi trocado por clonazepam e depois de algumas semanas a melhoria clínica foi percebida e acompanhada pela diminuição dos títulos de antígenos e anticorpos do P. brasiliensis. Em áreas endêmicas, o envolvimento do SNC deve ser considerado em doentes com PCM e a eficácia do itraconazole deve ser considerada