**6. Schistosomiasis**

[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

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

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

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

humankind, with reports in the Bible [67].

36 Current Topics in Tropical Emerging Diseases and Travel Medicine

tends to recover after specific treatment [78].

not to alter the response to leprosy-specific treatment [49].

responsible for the highest majority of cases in the world [68].

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 important infection-associated cause of death [81].

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 dysfunction also occurs in schistosomiasis, mainly urinary concentration dysfunction, which can be found in as high as 85% of patients with the hepatosplenic form in endemic areas [93]. Even in patients infected with *S. mansoni*, without clinically significant disease, there is evidence of renal inflammation, which was shown through increased urinary levels of MCP-1 [94].

Treatment is based on specific drugs, the first choice being praziquantel [80, 82], which has action against all *Schistosoma* species and provides cure rates above 80% [82]. The recommended dose is 40 mg/kg for *S. haematobium* and *S. mansoni*, and 60 mg/kg for *S. japonicum* [82].

**Table 1** summarizes the main aspects of kidney involvement in the neglected tropical diseases discussed in this chapter.

**Figure 1** illustrates the general pathophysiology of kidney involvement in tropical infectious and parasitic diseases.


**7. Conclusion**

ery is possible if adequate management is provided.

Neglected tropical diseases represent a global public health problem, affecting billions of people and requiring billions of dollars to treat and control. Authorities should have in mind that the key approach to these diseases, including kidney disease itself, is prevention, which is far from ideal, mainly in the developing world. Governments should also have in mind that the main determinant factors for the perpetuation of the neglected tropical diseases in the world in the sum of poor living conditions (lack of sanitation, potable water, piped water, garbage collection, education, domestic animal control, disease-vector control, environmental problems, lack of urbanization plans, and many others), and they have responsibility for the control of these diseases [95]. Many complications can arise from these diseases, and one of the most frequent and severe is kidney disease. The main pathophysiologic factors include immunological phenomena and hemodynamic abnormalities. Endemic diseases, such as dengue, chikungunya, and Zika virus infection, which have affected millions of people in the last few years, are having increasing evidences of kidney involvement in severe cases. In the majority of cases, kidney involvement in these diseases develops as a complication when the patient has poor or delayed access to health care. Research is being conducted to better control these diseases, including vaccine development. Concerning tropical diseases-associated kidney injury, the current "hot-topic" research is to detect this complication through novel biomarkers in order to provide an early and more specific management aiming to avoid or stop renal function loss and then prevent permanent renal insufficiency. Physicians attending patients with tropical diseases should always evaluate renal function, once renal involvement is frequent, and renal recov-

Neglected Tropical Diseases with an Impact on Kidney Function

http://dx.doi.org/10.5772/intechopen.78981

39

**Figure 1.** General pathophysiology of kidney involvement in tropical infectious and parasitic diseases.

AKI: acute kidney injury; CKD: chronic kidney disease; NGAL: neutrophil gelatinase-associated lipocalin; MCP-1: monocyte chemoattractant protein-1.

**Table 1.** Kidney involvement in neglected tropical diseases.

**Figure 1.** General pathophysiology of kidney involvement in tropical infectious and parasitic diseases.
