**9. Treatment**

As for lymphomas, histopathological and immunohistochemical exams will help to conclude the diagnosis. In the case of rhinophyma, there is usually a history of rosacea (acne-like lesions and telangiectasias, of long evolution). In the differential diagnosis with rhinosporidiosis what are important are: the origin (Piauí, Maranhão), the history of possible exposure to the fungus in stagnant water and dams, the presence of polyps in the nasal and ocular mucous membranes, and upper respiratory tracts. Histopathological examination shows the microorganism (sporangia of 6 to 300µm). Lesions of entomophthoromycosis present a hardened or woody consistency to palpation and histopathological and mycological exams demonstrate the presence of hyphae and isolation of the fungus in cultur medium. In the differential diagnosis with leprosy, skin sensibility tests, testing of skin bacilli in the lymph of the pinna or lesions and histopathological examination will help confirm the diagnosis. The clinical history is essential when seeking information on personal or family atopy (allergic rhinitis, bronchitis, migraine), on traumatic perforation and use of drugs. Wegner's granulomatosis and sarcoi‐ dosis are rarer diseases, and sometimes difficult to confirm. Diagnosis may be aided by observation of the involvement of other organs such as the lungs and kidneys, it being stressed

ATL can modify the progression of the disease due to HIV and immunosuppression caused by this virus facilitating progression of ATL [8]. Acquired immunodeficiency syndrome is caused by a retrovirus of the *Lentiviridae* family, HIV-1 and HIV-2. Those infected with the human immunodeficiency virus (HIV) progress to severe dysfunction of the immune system, as the CD4 + T lymphocytes, one of the major target cells of the virus, are being destroyed [19]. On destroying the immune system, the so-called "opportunistic infections" are manifested as this unfolds in which infections are included, namely infections by protozoa [4]. The assessment of the set of clinical manifestations of ATL in patients with HIV indicates that there is no definition of a clinical profile that may unarguably be associated with co-infection [8]. The exponential increase in the number of cases of coinfection of *Leishmania*/ HIV, especially in the late 1990s, has undergone modifications [4]. Unusual findings can be observed in co-infected patients, suchas, for example, finding *Leishmania spp* in intact skin, and overlying a Kaposi's sarcoma lesion, or *Herpes simplex* and *Herpes zoster* lesions. There may also be involvement of the gastrointestinal tract and the respiratory tract for the coinfection of ATL/AIDS [8]. The population of drug users who inject endovenously is the main group at risk of the co-infection of *Leishmania*/HIV in

Several thorough trials have been carried out on the production of anti- *Leishmania* vaccines: 1) "Leishmanization" has been used empirically since the distant past by people living in

that the histopathology will contribute to the diagnosis [8].

Southeast Europe, and form 72% of co-infected patients [4].

**8. Prevention**

**7. Co-infection** *Leishmania* **and HIV**

56 Leishmaniasis - Trends in Epidemiology, Diagnosis and Treatment

ENT activity is of primary importance [5]. The drug of first choice is the pentavalent antimonial one. With a view to standardizing the therapeutic regimen, WHO recommends that the dose of this antimonial be calculated in mg /SbV/ Kg day./ (SbV meaning a pentavalent antimonial).

There are two types of pentavalent antimonial that can be used, N-methylglucamine antimonate and sodium stibogluconate [10,16]. In all forms of mucosal involvement, the recommended dose is 20mg Sb+5/kg/day, for thirty consecutive days, preferably in a hospital environment. If healing is not complete within three months (twelve weeks) after treatment ends, the scheme should be repeated only once. Should there be no response, use one of the second choice drugs [16].

If there is no satisfactory response to the treatment with pentavalent antimony, the second choice drugs are amphotericin B and pentamidine isethionate. The injections must be made parenterally, intramuscularly (IM) or intravenously (IV), with rest after application. The IM may have the drawback of local pain. It is suggested, therefore, locations be alternated, the gluteal region being preferred.

In cases of malnourished patients with low muscle mass, and those with thrombocytopenia, the intravenous route should be given preference. This is the best route because it allows the application of large volumes without the inconvenience of local pain. The application should be slow (a minimum of 5 minutes), with a fine needle (gauge 25x7 or 25x8) and without needing to be diluted. To make it possible for rest after administration, it is generally advisable to apply the medication at the end of the day. It is worth noting that there is no difference between the IV and IM routes, with respect to the efficacy and safety of the drug [8].

The use of topical products such as paromomycin and imiquimod, associated or not with parenteral medication, have also presented preliminary satisfactory results, with cure rates ranging between 74% and 85% for the former drug, and 90% for the latter [9]. The imidazo‐ quinoline, approved for the treatment of genital warts, [17] stimulates the Th1 response by increasing the production of TNF- α, IFN-γ and IL-12. *In vitro*, presents anti Leishmanial activity because it also stimulates the production of nitric oxide by macrophages, thus decreasing the number of parasites. Paromomycin is an antibiotic that inhibits the mitochon‐ drial activity of *Leishmania*. rhGM-CSF is a glycoprotein that induces the growth of colonies of granulocytes and/or macrophages, by stimulating their phagocytic and metabolic functions. For this reason, it plays an important role in the immune response against intracellular pathogens. It has been used experimentally in the treatment of some inflammatory diseases as it has an inhibitory effect on TNF- α [18].

Local treatment of small lesions may not be necessary. Larger lesions may be treated with surgical excision, curettage or cryotherapy [13]. Secondary infection may occur in 54.2% of patients and the germ most frequently found is *Staphylococcus aureus* [21], which is why local care should be prescribed such as local cleansing with soap and water and if possible com‐ presses with KMnO (potassium permanganate in a dilution of 1/5000ml) [8, 16].

The cure criterion is defined by the regression of all signs and confirmed by ENT examination, up to 6 months after completion of the treatment regimen. In the absence of the specialist, the clinician must be trained to perform, at least, anterior rhinoscopy and oroscopy. Where there is no clinician, the patient should be referred to the service that evaluates healing. The patient should return monthly for a consultation for 3 consecutive months after the end of the treatment regimen so that the clinical cure can be evaluated.

Once cured, the patient should be monitored every 2 months, until 12 months after completing treatment [8]. The control of ATL should be tackled in a comprehensive way, in five respects: epidemiological surveillance, measures of performance in the transmission chain, educational measures, administrative measures and vaccine [9]. To reduce the lethality of these diseases, what is above all necessary is early diagnosis and the timely treatment of cases [14].

The current challenges for ATL are: a) to increase investments in seeking drugs with better efficacy, safety, low cost, ease of administration and sustainability; b) to continue to be vigilant about the adverse effects of medication; c) to expand the health network for early diagnosis and adequate treatment of cases; d) to investigate and evaluate deaths; e) to implement surveillance actions in territorial units; f) to expand the activities of epidemiological surveil‐ lance [19].
