**5. Leprosy**

with chronic kidney disease, dengue is associated with high mortality [18]. Among renal transplant patients, dengue fever also presents favorable outcomes and does not significantly

Chikungunya infection is another arbovirosis that has been responsible for large epidemic in recent years, causing self-limited disease in most cases, with predominant symptoms being fever and arthralgias [22, 23], but renal involvement has been reported in fatal cases [22, 24]. A series of 10 autopsies from Colombia evidenced that renal involvement is frequent, with serum creatinine at admission varying from 1.2 to 8.9 mg/dl (median 2.8 mg/dl), and the main histopathological findings were glomerular involvement (glomerular edema, nephrosclerosis, and membranoproliferative glomerulonephritis) and acute tubular necrosis [22, 24]. Similar to what is seen in dengue infection, transplanted patients who acquire Chikungunya infection seem to have a milder disease, with less severe arthralgia, and this could be due to immunosuppressant drug effects [25]. The acute viral infection also seems not to significantly

Zika is another arbovirosis that usually causes a mild infection, which is predominated by fever, arthralgias (milder than in dengue and chikungunya), and a typical rash with pruritus, which was brought to the attention of the Public Health authorities in 2015—the outbreak occurred in Brazil affecting a large number of people and causing neurologic disturbances in newborns, including microcephaly [26, 27]. Renal involvement has been recently described in experimental studies, which demonstrated that the Zika virus has the potential to infect different types of kidney cells, including podocytes, endothelial and mesangial cells, and the virus can also be detected in the urine, which is an evidence of the kidneys as reservoirs of the virus and a potential source for the transmission [26, 27]. These findings also suggest that patients infected with Zika virus are at risk of developing glomerulonephritis, as expected in the other arbovirosis.

There is no specific treatment for dengue, as well as for the other arbovirosis, so it consists in supportive measures and depends on clinical manifestations [40]. Treatment basis include hydration (oral or venous, depending on disease severity), resting and symptomatic medication (antipyretics, analgesics), and avoiding the use of anti-inflammatory drugs. Correction of metabolic and electrolyte disturbances is crucial and if instituted early can prevent complications [18]. Dengue vaccines are under research and the available ones present good results in

Leishmaniasis is the tropical disease caused by the parasites from the genus *Leishmania*, transmitted by mosquitoes *Phlebotomus* and *Lutzomyia*, with the majority of cases concentrated in Latin America, South East Asia, East Africa, and, less frequently, Europe [42, 43]. There are 12–15 million infected people in the world, and 350 million are at risk [43]. Approximately, 1.5 –2 million new cases of leishmaniasis are registered in the world each year [43], and 90%

of cases are concentrated in India, Ethiopia, Somalia, Sudan, and Brazil [44–46].

affect the allograft function [39].

34 Current Topics in Tropical Emerging Diseases and Travel Medicine

affect the renal allograft [25].

**4. Leishmaniasis**

individuals with previous exposure to the virus [41].

Leprosy is a chronic disease caused by the *Mycobacterium leprae*, an acid-fast bacillus, characterized to be incapacitating and to cause organ failure in some cases, including kidney disease [49, 65, 66]. The disease is highly contagious, but few people develop the disease once there is natural resistance to the bacillus [65]. This is one of the oldest diseases known to affect humankind, with reports in the Bible [67].

**6. Schistosomiasis**

important infection-associated cause of death [81].

Schistosomiasis is the parasitic disease caused by organisms of the genus *Schistosoma*, which affects more than 200 million people in the world and is endemic in some tropical areas of the globe [79, 80]. It is the second most frequent parasitic disease, after malaria, and is still an

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The definitive host is the men, where the adult parasite reproduces and eliminates its eggs, which contaminated water resources [79]. In nature, disease transmission depends on the presence of snails from the family *Planorbidae* and genus *Biomphalaria*, and the men acquire the infection when the cercariae penetrate through the skin. The presence of the parasite in the human organism is relatively harmless, and the manifestations depend on immune response to different stages of the parasite in the body [82]. The disease can manifest as an acute syndrome, also known as Katayama syndrome, which is more common among travelers or immigrants in endemic areas with no immunity to *Schistosoma* and is characterized by fever, malaise, myalgia, headache, and abdominal pain, which can last from 2 to 10 weeks [80]. Depending on the patient's immune system response, the disease can progress to the chronic forms, in which predominate the intestinal form, in the case of *S. mansoni*, *S. japonicum* and *S. mekongi* infections. Patients with poor immune regulation develop severe fibrosis and hepatosplenic disease with periportal fibrosis [80]. The species *S. haematobium*, which occurs in some parts of Africa, affects the urogenital system, manifesting mainly by hematuria [80–82]. Other symptoms described in the infection by *S. haematobium* include hematospermia and inflammation in other structures in men—epididymis, testicles, spermatic cord and prostate,

and women—hypertrophic/ulcerative lesions of the vulva, vagina, and cervix [82].

Kidney involvement in schistosomiasis is described and predominates in the form of glomerulonephritis [79]. In schistosomiasis, there are circulating antigens of adult parasite, and its eggs can be found in different organs, including the kidneys [79]. Acute kidney injury (AKI) is also described, with high prevalence in endemic areas, affecting as high as more than 40% of patients with the chronic forms of the disease [79]. Schistosomal glomerulonephritis is classically associated with the hepatosplenic form and ranges from asymptomatic disease to nephrotic syndrome [79]. Renal histopathological analysis evidences immune complex deposition, with schistosomal antigens in the glomerular basement membrane, as well as the presence of schistosomal eggs and granulomas. The mechanism of these lesions includes immunological phenomena, with response directed against parasite's antigens and immune complex formation and deposition in the glomeruli [83–86]. There is also evidence of polyclonal B-lymphocytes activation [87], but it is not sufficient to induce the process of nephritis, so more recent studies suggest the participation of autoimmune mechanisms [88]. The most common pattern of glomerular disease in schistosomiasis is mesangial proliferative and membranoproliferative glomerulonephritis [89, 90]. There are deposits of IgM, IgG, and C3 [91]. Amyloidosis has also been described [79, 92] but is less frequent, although it is always a possible pattern of kidney disease in any infectious disease with chronic evolution. Schistosomal glomerulonephritis can be classified in five types: mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, focal and segmental glomerulosclerosis, exudative glomerulonephritis, and amyloidosis [91]. Granuloma formation in the kidney is also a possible but rare complication of schistosomiasis [92]. Tubular

There are reports of leprosy in 138 countries, with world prevalence of 0.2 cases per 10,000 inhabitants in 2015 [68]. The number of new cases in this same year was 211,973 cases, evidencing continued transmission (2.9 cases per 100,000 inhabitants). India and Brazil are responsible for the highest majority of cases in the world [68].

The spectrum of manifestations depends on the host's immunity and response to M. leprae, and the incubation period is long, going from 6 months to 10–20 years [65, 66]. During the course of the disease, there are "reactional states," in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. The disease can be classified as paucibacillary and multibacillary, according to the number of skin lesions and bacilli found in skin smears [65, 66]. Besides affecting the skin, leprosy characterizes to cause peripheral nerve damage [65] and can complicate with systemic involvement, including nephropathy [49].

Kidney involvement in leprosy has been described for the first time a long time ago in autopsy studies and includes different types of glomerular lesions, such as epithelioid granulomas, and also Hansen's bacillus in renal parenchyma [49]. It is found in all forms of the disease but is more frequent in multibacillary forms [69, 70]. The most common leprosy-associated glomerular disease is mesangial proliferative glomerulonephritis and other histologic types are also found: acute proliferative glomerulonephritis, membranous glomerulonephritis, rapidly progressive glomerulonephritis, and others. Chronic tubulointerstitial nephritis and amyloidosis have also been described in the course of leprosy, leading to chronic kidney disease [71, 72]. The mechanics by which *M. leprae* infection leads to kidney disease are not completely understood [49], and it is probably associated with immunological phenomena. Complement reduction and immune complex deposition in glomerular basement membrane have been described [73–75]. Oxidative stress also plays a role in leprosy nephropathy. There is evidence of subclinical kidney damage even in patients with controlled infection. The levels of urinary MCP-1 are increased in leprosy patients and are associated with microalbuminuria levels and amount of bacilli of skin smears [76]. Renal tubular disturbances have also been described in leprosy, including concentration and acidification defects [77]. AKI can also occur in leprosy and seems to be associated to glomerulonephritis complications or secondary to the use of nephrotoxic drugs, mainly anti-inflammatory drugs and rifampicin, which are used in leprosy therapeutic scheme. Leprosy nephropathy seems to have changed in recent years, becoming a milder disease, characterized by micro-hematuria and mild proteinuria, which tends to recover after specific treatment [78].

Treatment consists of specific multi-drug therapy, reactional state treatment, prevention of disabilities, and psychosocial support. Specific therapy includes rifampicin and dapsone for paucibacillary patients (for 6 months) and rifampicin, dapsone, and clofazimine for multibacillary patients (for 12 months). Corticosteroids may be used for reactional states. Leprosyassociated end-stage kidney disease may require renal replacement therapy, which includes dialysis or transplantation, and immunosuppression for renal transplanted patients seems not to alter the response to leprosy-specific treatment [49].
