Insights from paleomicrobiology into the indigenous peoples of pre-colonial America - A Review

This review investigates ancient infectious diseases in the Americas dated to the pre-colonial period and considers what these findings can tell us about the history of the indigenous peoples of the Americas. It gives an overview, but focuses on four microbial pathogens from this period: Helicobacter pylori, Mycobacterium tuberculosis, Trypanosoma cruzi and Coccidioides immitis, which cause stomach ulceration and gastric cancer, tuberculosis, Chagas disease and valley fever, respectively. These pathogens were selected as H. pylori can give insight into ancient human migrations into the Americas, M. tuberculosis is associated with population density and urban development, T. cruzi can elucidate human living conditions and C. immitis can indicate agricultural development. A range of methods are used to diagnose infectious disease in ancient human remains, with DNA analysis by polymerase chain reaction one of the most reliable, provided strict precautions are taken against cross contamination. The review concludes with a brief summary of the changes that took place after European exploration and colonisation.

Capítulo 2: coccidioidomicose / Chapter 2: coccidioidomycosis

A coccidioidomicose é uma micose sistêmica causada pelos fungos dimórficos Coccidioides immitis e Coccidioides posadasii. A infecção é adquirida pela inalação de artroconídios infectantes presentes no solo. Usualmente apresenta-se como infecção benigna de resolução espontânea em 60 por cento dos casos. A micose é encontrada em regiões áridas e semiáridas do continente americano entre os paralelos 40ºN e 40ºS, principalmente no sudoeste dos Estados Unidos e no norte do México. A coccidioidomicose foi diagnosticada recentemente na região semiárida do nordeste do Brasil em quatro estados: Piauí (100 casos), Ceará (20 casos), Maranhão (6 casos) e Bahia (2 casos). A micose se manifesta sob três formas clínicas principais: forma pulmonar primária, forma pulmonar progressiva ou forma disseminada. Os sintomas de infecção respiratória manifestam-se, em média, 10 dias após a exposição. O diagnóstico faz-se pelo isolamento do Coccidioides sp. em cultivo ou pelo exame direto positivo (hidróxido de potássio a 10 por cento) de qualquer material suspeito (escarro, líquido cefalorraquidiano, exsudato de tegumento, linfonodos, etc.), ou corados por ácido periódico de Schiff ou impregnação argêntea. A imunodifusão em gel de ágar é o teste imunológico mais empregado na rotina diagnóstica. As manifestações radiológicas e tomográficas mais frequentes são nódulos pulmonares múltiplos, a maioria escavados, distribuídos difusamente. As drogas indicadas para o tratamento são fluconazol e itraconazol, com doses médias variando de 200 a 400 mg/dia, podendo chegar a 1.200 mg/dia. Nos casos graves, a anfotericina B pode ser a droga de escolha inicial. Na manifestação neurológica, o fluconazol é a droga preferida na dose mínima de 400 mg/dia.

Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Infection is acquired by inhalation of infective arthroconidia that live in the soil. In 60 percent of cases, the infection is benign and resolves spontaneously. In the northern hemisphere, coccidioidomycosis is endemic to arid and semi-arid regions at latitudes between 40ºN and 40ºS, particularly in the southwestern United States and in northern Mexico. In the semi-arid northeastern region of Brazil, cases of coccidioidomycosis have recently been reported in four states: Piauí (100 cases); Ceará (20 cases); Maranhão (6 cases); and Bahia (2 cases). The illness manifests in one of three clinical forms: the primary pulmonary form; the progressive pulmonary form; or the disseminated form. On average, the symptoms of respiratory infection appear 10 days after exposure. The diagnosis is made by the isolation of Coccidioides sp. in culture or by positive results from smear microscopy (10 percent potassium hydroxide test), periodic acid-Schiff staining or silver staining of any suspect material (sputum, cerebrospinal fluid, skin exudate, lymph node aspirate, etc.) Agar gel immunodiffusion is the diagnostic test most widely used. The most common finding on X-rays and CT scans is diffuse distribution of multiple pulmonary nodules, most of which are cavitated. The recommended treatment is fluconazole or itraconazole, the mean dose ranging from 200 to 400 mg/day, although as much as 1,200 mg/day is used in certain cases. In severe cases, amphotericin B can be the drug of choice. In cases of neurological involvement, the recommended treatment is administration of fluconazole, at a minimum dose of 400 mg/day.

Identidad genética del hongo causante del primer caso de coccidioidomicosis descripto por Alejandro Posadas en 1892 / Genetic characterization of the fungus involved in the first case of coccidioidomycosis described by Alejandro Posadas in 1892

En 1892, Alejandro Posadas documentó el primer caso mundial de coccidioidomicosis en un paciente argentino de nombre Domingo Escurra. Con el objetivo de identificar la especie de Coccidioides involucrado en ese caso, analizamos una pieza de necropsia del paciente, conservada en el Museo de Patología de la Facultad de Medicina de la Universidad de Buenos Aires, Argentina. La porción del tejido con mayor número de endosporas del hongo libres e integras fue elegida utilizando una coloración inmunohistoquímica específica. El ADN fúngico fue amplificado usando una PCR anidada que reconoce un fragmento del gen Ag2/PRA cuyo polimorfismo diferencia Coccidioides immitis y C. posadasii. Se amplificó además, el ADN de dos cepas de referencia: C. immitis (M38-05) y C. posadasii (1-NL) y de cuatro aislamientos de Coccidioides de pacientes argentinos. Los fragmentos amplificados fueron secuenciados en ambas hebras. Las secuencias fueron editadas, alineadas y comparadas con las depositadas en GenBank C. posadasii (Acceso N° AY536446, cepa Silveira) y C. immitis (Acceso N° AY536445). Las secuencias del Coccidioides del caso Escurra, de los aislamientos argentinos y de la cepa 1-NL fueron idénticos entre sí y mostraron una mutación puntual de C→G en la posición 1228 en comparación con la secuencia de C. posadasii, cepa Silveira. Este es el primer trabajo donde se busca ADN de Coccidioides en una pieza anatómica de museo con más de 100 años de antigüedad. Los resultados confirman que el primer caso de coccidioidomicosis o enfermedad de Posadas documentado mundialmente fue producido por el recientemente descripto C. posadasii.

In 1892 Alejandro Posadas described the first worldwide case of coccidioidomycosis in a patient named Domingo Escurra. A preserved necropsy piece from the patient's remains is conserved in the Museum of Pathology of the Medical School, Buenos Aires University. Paraffin-embedded specimens obtained from this piece served to identify the fungus involved in the case. Histological slices from different lesion sites were submitted to a genus-specific immunohistochemical staining in order to select the more suited areas in terms of abundance/integrity of fungal esporangia and endospora. Fungal DNA was amplified from selected deparaffinated slices using a nested PCR designed to amplify a segment of the gen Ag2/PRA and differentiate C. immitis from C. posadasii. This PCR was also applied to two reference strains (C. immitis M38-05, C. posadasii 1-NL) and isolates obtained from four recent coccidioidomycosis cases occurred in Argentina. Amplified products were submitted to sequencing of both DNA strands. The obtained sequences were edited, aligned and compared with C. posadasii (Access N° AY536446, strain Silveira) and C. immitis (Access N° AY536445) deposited in GenBank. DNA sequences from Escurra's lesions were 100% homologous to the recent Argentinean cases and the reference strain 1-NL. A single point C→G difference in position 1228 was observed with respect to sequence of strain C. posadasii Silveira. For the first time, Coccidioides DNA is recovered from a museum piece which is more than 100-year-old. Our results confirm that the original case of Posadas's disease was caused by the recently described C. posadasii.

Detección de infección por Coccidioides immitis en zonas del estado de Coahuila, México / Detection of Coccidioides immitis infection in Coahuila, Mexico

La coccidioidomicosis es una micosis inicialmente pulmonar causada por Coccidioides immitis; puede diseminarse principalmente a sistema nervioso central, huesos y piel. En México se desconoce la frecuencia exacta de esta enfermedad. Nuestro objetivo fue determinar, por intradermorreacción y por serología, los casos de infección por C. immitis en 12 comunidades (10 rurales y dos urbanas) atendidas en el Hospital Rural Nº 79 del Instituto Mexicano del Seguro Social (IMSS) del estado de Coahuila, México. Se estudiaron 668 individuos adultos de ambos sexos; se les aplicó 0,1 ml de coccidioidina por vía intradérmica; después de 72 hs. se midió el diámetro de induración. Fueron seleccionados 180 individuos y a partir del suero se determinaron los niveles de inmunoglobulinas anti-C. immitis por ELISA. Fueron positivos a la coccidioidina 621 sujetos (93%), frecuencia mucho mayor a la reportada previamente en Coahuila. De los 180 sueros estudiados los promedios de densidad óptica (DO) fueron: IgG1, 1,55; IgG2, 0,94; IgG total, 0,33; IgG3, 0,29; IgG4, 0,27; IgM, 0,08. Los valores de IgG1, IgG2 e IgM comparados con las otras inmunoglobulinas fueron estadísticamente significativos. Los valores de IgG1 e IgG2 sugieren contacto frecuente con los antígenos e incluso probables casos de enfermedad no diagnosticada.

Coccidioidomycosis is a mycosis firstly pulmonar caused by Coccidioides immitis; it can be disseminated to central nervous system, bones and skin, principaly. In Mexico, the real frequency of the disease is unknown. The aim of this work was to determine, by skin test and by serology, the infection cases by C. immitis in twelve communities (10 rural and two urban), attended in the Hospital Rural Nº 79 at the Instituto Mexicano del Seguro Social (IMSS) from the Coahuila State, Mexico. Six hundred and sixty eight adult individuals of both sexes were studied, to whom 0.1 ml of coccidioidin by intradermal route was applied; 72 h after, the induration diameter was measured. One hundred eighty individuals were selected and seric anti-C. immitis immunoglobulins levels were determined by ELISA. Six hundred twenty one individuals (93%) were positive to coccidioidin, the frequency was much higher than that previously reported in Coahuila. From 180 sera studied, the means of optical density (OD) were: IgG1, 1.55; IgG2, 0.94; total IgG, 0.33; IgG3, 0.29; IgG4, 0.27; IgM, 0.08. The values of IgG1, IgG2 and IgM compared with the other immunoglobulins were statistically significant. The high values of IgG1 and IgG2 suggest frequent contact with the antigen, and probable cases of undiagnosed disease.

The first imported case of pulmonary coccidioidomycosis in Korea

Coccidioidomycosis is an endemic disease found in the southwestern part of North America. Travellers who visit the endemic area may carry the infection. We report a case of pulmonary coccidioidomycosis in a 74-year-old woman. She was healthy before visiting Arizona, U.S.A twice. After returning home, she began to complain of intermittent dry coughing. The symptom was mild, however, and she was treated symptomatically. Later a chest radiograph, which was taken 4 years after the onset of the symptom, showed a solitary pulmonary nodule in the right upper lobe. By percutaneous needle aspiration, a few clusters of atypical cells were noted in the necrotic background. A right upper and middle lobectomy was done. A 1.5 x 1.5 x 1.2 cm sized tan nodule was present in otherwise normal lung parenchyma. Microscopically, the nodule consisted of aggregates of multiple solid granulomas inside of which was mostly necrotic. Neutrophils and nuclear debris were scattered along the periphery of the necrotic foci. Numerous multinucleated giant cells were associated with the granulomas. In the necrotic area, mature spherules of Coccidioides immitis, which were 30-100 microm in diameter, were present. They contained numerous endospores which ranged from 5 to 15 microm and were also noted in multinucleated giant cells. The diagnosis of coccidioidomycosis was made. She is doing well after the resection.

Coccidioidomicose: novo caso brasileiro / Coccidioidomycosis: a new brazilian case

A case of pulmonary coccidioidomycosis from the rural zone of Bertolinia, PI, is reported. The patient, a farm worker, attributed his illness to the dust inhaled while digging a water well during the dry season of the year, some weeks before the onset of the clinical manifestations. The main symptoms of the disease were severe chest pain and moderate fever. The diagnosis was made histopathologically: tissue phase fungal organisms--immature spherules and spherules with endospores--were observed in histological sections of a lung fragment obtained by open chest biopsy. This is the twelfth autochthonous case of coccidioidomycosis found so far in Brazil. All of them involved native inhabitants of the semi-arid part of Northeastern Brazil. The hot and dry environment of the region seems to favor the development of C. immitis in the soil. Humans and animals probably acquire the infection by digging the soil, when they become exposed to the conidium-bearing dust raised by this activity.

É descrito um caso de coccidioidomicose pulmonar oriundo da zona rural de Bertolínia, PI. A manifestação clínica principal consistiu em dor torácica e o diagnóstico teve por base o achado do agente ¾ Coccidioides immitis ¾ em cortes histológicos. Formas teciduais do microrganismo ¾ esférulas imaturas e maduras ¾ estavam presentes nas lesões observadas em fragmento pulmonar removido do paciente por biópsia a céu aberto. Este novo caso autóctone da doença, como os outros anteriormente descritos no Brasil, procedia do interior semi-árido da Região Nordeste. O ambiente quente e seco do sertão nordestino oferece, sem dúvida, condições propícias ao desenvolvimento de C. immitis, um habitante do solo. As pessoas e animais do local devem adquirir a infecção ao revolver a terra, ato que os expõe à poeira contendo os propágulos do fungo.