Despite representing a major health problem, either due to the difficulty in diagnosis or treatment, mycoses remain neglected

Recently, the incorporation of new antifungal drugs into the SUS was approved: anidulafungin, voriconazole, isavuconazole and the expansion of the use of liposomal amphotericin B, which in the last 10 years was exclusively used by the leishmaniasis program

Although endemic mycoses are not included in the national list of diseases and diseases of compulsory notification and are not subject to routine epidemiological surveillance, they represent an important public health problem. Dr. Maria Adelaide Millington, technical consultant of the General Coordination of Surveillance of Diseases of Respiratory Transmission of Chronic Conditions of the Department of Diseases of Chronic Conditions and Sexually Transmitted Infections (CGDR/DCCI/SVS/MS), focal point of the Technical Group of Endemic Mycoses, points out that the impact of the absence of regular registration of clinical and epidemiological data on mycoses is enormous, since without these data, the planning and implementation of public policies for surveillance and control of these diseases are unfeasible. As a basic example we can ask, how to plan the acquisition of antifungal drugs if we do not know the prevalence of endemic mycoses (implantation, systemic and opportunistic) in our country?, she asks.

Without a record of general mycosis data, knowledge about endemic areas, their prevalence, incidence and morbidity is based on case studies, isolated studies of the microorganism and its strains, and data from the Hospital Information System of the Unified Health System (SIH/SUS). According to Dr. Millington, mycoses have always been neglected in many ways, including the lack of an information system. Also according to her, the Ministry of Health brings together several information systems, however, the Notifiable Diseases Information System (Sinan), in which there is the notification of communicable and non-communicable diseases, does not contemplate endemic mycoses, despite numerous attempts by the technical area of mycoses for their inclusion, especially the main systemic mycoses: Paracoccidioidomycosis, Histoplasmosis,  Cryptococcosis, and Sporotrichosis – implantation mycosis and responsible for a serious outbreak of feline transmission, which has spread throughout the country since 2012 and has already  has crossed borders with other countries. Today, under the coordination of the CGDR/DCCI/SVS/MS, a specific information system for endemic mycoses is under development, whose main scope is the dispensing of antifungal drugs linked to the notification of the case. Pilot testing for this system are to begin later this year.

Asked about the main challenges in structuring and implementing surveillance of endemic mycoses, Dr. Millington mentions some factors, among them: the lack of knowledge by managers about the morbidity and mortality of fungal infections in Brazil (in February 2020 it was denied by the then Secretary of Health Surveillance, the inclusion of systemic mycoses in the list of Compulsory Notifiable Diseases); lack of knowledge of health professionals about the clinical and epidemiological management of fungal infections; lack of standardization of notification by the autonomy of the Federation Units in establishing the surveillance of certain diseases; lack of active surveillance of mycoses, with ignorance of real data of incidence and prevalence; lack of specific laboratory diagnostic network.

“Brazil has enormous potential for public health care in the Central Public Health Laboratories (Lacen). However, if managers do not understand the importance of endemic mycoses in the health scenario of the country, there will be no implementation and/or implementation of the diagnosis of fungal infections. The structuring of the diagnostic network in medical mycology is one of the fundamental axes for coping with these diseases, points out the medical specialist in Tropical Medicine and Medical Mycology. Also according to her, in the current administration of the federal government, fortunately it was possible to advance the proposal to include endemic mycoses on the agenda of the Ministry of Health and the achievements obtained are of the utmost importance. We are investing in the training of human resources (physicians and laboratory technicians) in Clinical Management and Laboratory Diagnosis of endemic mycoses, with online courses, acquisition of diagnostic and therapeutic inputs, in the preparation of an information system, in addition to the funding of a research project to implement the area of serological diagnosis in paracoccidioidomycosis, she adds.

Mycoses remained invisible for years

Although serious fungal infections are a major public health problem in Brazil, coping with these diseases has gone a long way that has dragged on for years. “Since 2006 we have tried to include endemic mycoses on the agenda of the Ministry of Health, without success. With great insistence, around 2008, we managed to incorporate at least two antifungal drugs (Lipid formulation of amphotericin B and itraconazole) into the SUS to treat these patients. From 2008 to 2011, we trained 105 multiplier health professionals (physicians and epidemiological surveillance technicians) in the clinical and epidemiological management of systemic mycoses. Lacen technicians were also trained in mycological and serological diagnosis, says Dr. Millington. Despite this, there was no evolution in the implementation of mycosis surveillance and they were never included as priorities in past administrations, in all spheres of government.

Additionally, according to her, the shortage of human resources of the State and Municipal Health Departments in the areas of epidemiological surveillance have always contributed to the mycoses remaining invisible. We cannot hold States and Municipalities responsible for the lack of coping with these diseases, since the federal government itself refrained from seeing them as real public health problems. In order to cope with these diseases, I consider it essential by the managers of the, a look at this group of diseases, because as well as in others of interest to surveillance, they affect individuals with severity, leading to death, reach individuals in the most productive phases of life, are incapacitating by the very serious sequelae that cause and cause outbreaks, she adds. Still according to Dr. Millington, non-confrontation is multifactorial, involves management, diagnosis, care, treatment, prevention and control.

Dr. Millington is categorical in stating that there is no confrontation yet and that it must happen in several ways, and of course, in an integrated way in the three spheres of government. For her, the specific diagnosis is in the vast majority of cases, late or not, treatments are limited by the lack of available drugs, in addition to the high cost and long duration of treatment, which often hinders adherence. The issue of prevention is much more based on actions that include information and education for the population. In addition, little or no importance is given to the topic of fungal infections in medical schools, and as a result, the impact on medical care is inevitable because, very rarely, physicians include endemic mycoses in the differential diagnosis of the most varied types of involvement, although they, in several situations, are indistinguishable from some diseases, such as tuberculosis, leishmaniasis, leprosy.

Incorporation of new technologies and medicines

The approval of public proposals has allowed advances in achievements for this group of diseases. In 2020, CrAg LFA was incorporated, a rapid, non-invasive test that allows the early diagnosis of cryptococcal meningitis, providing preemptive treatment, in order to reduce the morbidity and mortality of the disease. Likewise, the incorporation of flucytosine, an antifungal agent that makes up the treatment of choice for cryptococcal meningitis, was approved, whose attempt to incorporate it into the SUS had been underway since 2012. In addition, on June 9 this year, the incorporation of new antifungal drugs in the SUS was approved: anidulafungin, voriconazole, isavuconazole, and the expansion of the use of liposomal amphotericin B, which in the last ten years was exclusively used by the leishmaniasis program.

Dr. Millington adds that later this year, a request for the incorporation of new rapid tests – Histoplasma Urinary Antigen LFA (Lateral Flow Assay) and Elisa galactomannana for Histoplasma – will be sent to the National Commission for the Incorporation of Technologies in the Unified Health System (CONITEC). In addition to these inputs, two more antifungal drugs – terbinafine and posaconazole – will also be submitted for approval. Also, there is an expectation of incorporating new protocols and guidelines to CONITEC to open public proposals. As new drugs or diagnostic tests emerge that we can make available to our patients, and, on the other hand, when the proposals for surveillance and control of a certain disease are organized, we will request the incorporation of diagnostic tests or new antifungal drugs, or even the expansion of the use of a certain drug, thus seeking to qualify the care provided to patients with endemic mycoses, she points out. Finally, Dr. Millington stresses that among the priorities of the Technical Group of Mycoses of the CGDR, is the referral to the Tripartite Intermanagement Commission (CIT), of the request for a new agreement, among the three spheres of government, so that People Living with HIV (PLHIV), carriers of fungal infections, are included in the dispensation of antifungal drugs by the Ministry of Health.