{"id":225460,"date":"2016-10-04T12:45:11","date_gmt":"2016-10-04T15:45:11","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/en\/?p=225460"},"modified":"2016-10-04T17:29:43","modified_gmt":"2016-10-04T20:29:43","slug":"the-silent-attack-of-the-fungi","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/the-silent-attack-of-the-fungi\/","title":{"rendered":"The silent attack of the fungi"},"content":{"rendered":"
\"Candida

L\u00c9O RAMOS<\/span>Candida sp.<\/em> in a Petri dish: infecting almost three million people per year in BrazilL\u00c9O RAMOS<\/span><\/p><\/div>\n

It’s not a freezer, it’s a cage full of dangerous creatures. In metal boxes inside, at negative 80 degrees Celsius, in a laboratory at the Federal University of S\u00e3o Paulo (Unifesp), infectologist Arnaldo Colombo maintains a collection of roughly 4,000 yeasts and 1,000 filamentous fungi sampled from patients treated in hospitals across Brazil. These fungi were considered harmless up to a few years ago, but became aggressive as people’s natural defenses declined due to illness or drugs. Now, they are silently spreading severe, antifungal-resistant, potentially fatal infections.<\/p>\n

Almost four million people in Brazil are likely to get a fungal infection each year, according to a survey conducted by Juliana Giacomazzi at the Federal University of Health Sciences in the city of Porto Alegre. Out of that total, 2.8 million are caused by Candida<\/em> and one million by Aspergillus<\/em>, which take hold mainly in people whose bodily defenses have been weakened \u2013 usually by drugs to prevent rejection of a transplanted organ, treatments for cancer or AIDS, intensive antibiotic use or invasive procedures, such as catheterizations in intensive care units (ICUs).<\/p>\n

Worldwide, reported cases of meningitis caused by Cryptococcus neoformans<\/em> and C<\/em>. gattii<\/em> have grown from a few hundred in the 1950s to a million per year today, particularly among HIV\/AIDS patients. Fungal pathogens cause an estimated 11.5 million severe infections and recurring superficial mycoses per year, 1.5 million of them fatal \u2013 more than the total annual death toll of malaria and tuberculosis.<\/p>\n

\u201cDo you know what happened in this case?\u201d asked Colombo, pointing to a Petri dish where various drugs had been applied on samples of a fungus variety, which had recently arrived at his laboratory for identification and analysis. \u201cNone of the drugs worked and the patient died from the infection.\u201d Many species of fungi have been proving resistant to the handful of drugs used to combat them. In 2013, the research team at Unifesp pinpointed Candida<\/em> glabrata <\/em>as a top concern among hospital-acquired infections because it has proven resistant to almost all antifungal drugs, starting with fluconazole, the most commonly used. This type of yeast infection now has a mortality rate of almost 50% for patients admitted into ICUs. Two species of fungi, Aspergillus fumigatus<\/em> and Fusarium solani<\/em>, were isolated in 36 out of 164 samples of water used in the pediatric oncology ward of a hospital in the city of S\u00e3o Paulo. This is an indication that the water supply itself could be a source of contamination, since fungal propagules or spores \u2013 reproductive structures similar to seeds \u2013 could be transmitted via faucet or shower use.<\/p>\n

\"Aspergillus

L\u00c9O RAMOS<\/span>Aspergillus niger<\/em>: in the laboratory for genetic identification and drug susceptibility testingL\u00c9O RAMOS<\/span><\/p><\/div>\n

The average person inhales an estimated 200 to 2,000 spores every day.\u00a0 They are found not only dispersed in the air, but also inside the human body. \u201cWe have millions of colonies of Candida albicans<\/em> in our mouths and intestines and on our skins, but they only grow and make trouble when our defenses are compromised,\u201d said infectologist M\u00e1rcio Nucci from the Federal University of Rio de Janeiro (UFRJ). Nucci participated in a study that assessed the occurrence of abdominal infections, caused mostly by C. albicans<\/em> and C. glabrata<\/em>, in 481 patients admitted to 13 hospitals in Italy, Spain, Greece and Brazil, from 2011 to 2013. Most of them (85%) had candidiasis. The mortality rate was 60%, which Nucci attributes to the fact that this type of infection normally only afflicts patients who are terminally ill or who have had a late diagnosis of the source of infection, delaying the start of adequate treatment.<\/p>\n

In people who have had tuberculosis, fungal infections are easily mistaken for bacterial ones. \u201cLittle consideration is given to the possibility of chronic pulmonary aspergillosis, which appears in 10% to 15% of patients with pulmonary cavities or bronchial dilation as complications of tuberculosis, who are usually just given another course of antibiotics,\u201d said Colombo. He then presented an X-ray of a 51-year-old man who had lost weight and suffered for months from a chronic cough and fever, and who was treated for tuberculosis until it was discovered he actually had chronic pneumonia associated with the fungus Histoplasma capsulatum<\/em>, a frequent cause of hard-to-treat pneumonias. Another species, Paracoccidioides brasiliensis<\/em>, causes pneumonia even in people whose defenses are functioning normally, if they live in areas where this type of mycosis is common.<\/p>\n

To make matters worse, a single fungus can cause different diseases, depending on the defense capacity of the organism that it infects. Aspergillus <\/em>causes two types of pneumonia: acute and chronic. It is almost an established fact that these are no longer as rare as they were a few decades ago \u2013 the acute form will manifest in up to 12% of people with acute myeloid leukemia, according to estimates from a survey conducted in eight Brazilian public hospitals. The International Society for Human and Animal Mycology (ISHAM, its.mycologylab.org), an international, open-access database, currently holds 3,200 fungal DNA sequences that permitted the molecular identification of 524 species that cause diseases in humans, among more than 500,000 described species of fungi.<\/p>\n

Genetic analyses have shown that samples once believed to be composed of a single species can sometimes include several types of fungi, with different levels of drug resistance. This was the case of Candida parapsilosis<\/em>, which has been reclassified into three species: C. parapsilosis sensu stricto<\/em>, C. orthopsilosis<\/em> and C. metapsilosis<\/em>. All three species can be found on the hands of medical personnel in hospitals and result in infections associated with handling catheters and other devices commonly used in intensive care units.<\/p>\n

\"Fungi

L\u00c9O RAMOS<\/span>Fungi collection: fungi immersed in mineral oil after being collected from hospital patientsL\u00c9O RAMOS<\/span><\/p><\/div>\n

It is no simple task to find out how fungi acquire virulence (the ability to cause infection) and drug resistance. In his laboratory at the University of S\u00e3o Paulo (USP) School of Pharmaceutical Sciences in the city of Ribeir\u00e3o Preto, Gustavo Goldman, a biologist by training, verified that Aspergillus fumigatus<\/em> can use different strategies to proliferate in the lungs, due to its ability to evade the body’s defenses as well as the most widely used antifungal drugs, known as azoles. According to Goldman, resistance to azoles might be explained by the use of fungicides to eliminate agricultural pest species in areas near cities, favoring the selection and dissemination of varieties that can cause disease in humans.\u00a0 \u201cFungi are essentially opportunistic organisms,\u201d he says. \u201cVarieties that are important in carbon recycling in nature can cause disease if they find a debilitated host. They also have high genotypic plasticity and strong adaptability to different environments.\u201d<\/p>\n

Groups of fungi can show increased resistance and virulence, says Maria Jos\u00e9 Giannini, professor of mycology at the S\u00e3o Paulo State University (Unesp) School of Pharmaceutical Sciences, in the city of Araraquara. Together with her team, she found that fungal agglomerations \u2013 or biofilms \u2013 of Cryptococcus<\/em> are more virulent and drug-resistant, both in vitro<\/em> and in<\/em> vivo<\/em>, than isolated forms, as had already been observed for species of other genera, including Paracoccidioides brasiliensis<\/em> and Histoplasma capsulatum<\/em>. Biofilm formation may be why the research team in Araraquara found it so hard to eliminate onichomycosis, or nail fungus, caused by Candida<\/em> and Cryptococcus.<\/em> It can also explain the resistance shown by Trichosporon<\/em> to triazole and amphotericin B, two drugs widely used against skin or internal infections, in a study by the group at Unifesp.<\/p>\n

The results achieved by public policies designed to measure and deter fungal infections are not as consistent as those observed in basic research, says Giannini. \u201cAs a result, we may face serious problems related to an increase in fungal diseases,\u201d she says. \u201cThe at-risk population has grown \u2013 especially the immunosuppressed \u2013, as has the use of invasive medical procedures like catheters, which can facilitate fungal transmission. But this has not led to increased response capacity in the healthcare system, which should be alert and ready to deter this situation,\u201d says Colombo. To exemplify, he mentions that no specific system is in place to diagnose post-tuberculosis fungal pneumonias, a measure that would be relatively easy to implement.<\/p>\n

Worried about the situation, the researchers offer recommendations to other professionals in the field (see sidebar<\/a><\/em>) and try to act in unison to disseminate information about these health concerns. Unifesp has been working with a research team at the University of Manchester, in England, and with medical centers in the states of S\u00e3o Paulo, Paran\u00e1, Rio de Janeiro and Esp\u00edrito Santo, to determine how far-reaching acute and chronic fungal pneumonias are among the population, and the best alternatives for their diagnosis and treatment. As an additional initiative, the Brazilian branch of the Global Action Fund for Fungal Infections (GAFFI, gaffi.org) was established in 2015 to provide constant updates to the healthcare professionals responsible for identifying or treating these diseases.<\/p>\n

\"Fungi\"<\/a><\/p>\n

Project<\/strong>
\nPulmonary Aspergillosis and correlation between clinical forms and differential expression of virulence attributes in Aspergillus fumigatus<\/em> (n\u00ba 2014\/50294-3<\/a>); Grant Mechanism:<\/strong> Regular Research Grant; Principal Investigator:<\/strong> Arnaldo L. Colombo (Unifesp); Investment:<\/strong> R$42,905.00<\/p>\n

Scientific articles<\/em>
\nBENADUCCI, T. et al<\/em>. Virulence of Cryptococcus<\/em> sp. biofilms in vitro<\/em> and in vivo<\/em> using Galleria mellonella<\/em> as an alternative model<\/a>. Frontiers in Microbiology<\/strong>. V. 7, p. 290. 2016.
\nCOLOMBO, A.L. et al<\/em>. Candida glabrata<\/em>: An emerging pathogen in Brazilian tertiary care hospitals<\/a>. Medical Mycology<\/strong>. V. 51, No. 1, pp. 38-44. 2013.
\nGIACOMAZZI, J. et al<\/em>. The burden of serious human fungal infections in Brazil<\/a>. Mycoses<\/strong>.\u00a0V. 59, No. 3, pp. 145-50. 2016.<\/p>\n","protected":false},"excerpt":{"rendered":"Species of fungi cause drug-resistant infections","protected":false},"author":17,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[206,242,247,260],"coauthors":[5968],"class_list":["post-225460","post","type-post","status-publish","format-standard","hentry","category-science","tag-biodiversity","tag-immunology","tag-medicine","tag-public-health"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/225460","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/17"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=225460"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/225460\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=225460"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=225460"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=225460"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=225460"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}