**7. Conclusion**

Control efforts for leishmaniasis (especially asymptomatic VL), particularly in endemic regions, need a detailed understanding of *Leishmania* ecology and epidemiology. Those infected with viscerotropic *Leishmania* species, on the other hand, may remain asymptomatic, which is the most typical result of infection in endemic regions. However, it is impossible to offer reliable estimates of the number of infected vs. those at risk. The number of persons infected but asymptomatic is far greater than the number of people infected and presenting with clinical disease. As a result, it is critical to understand how many infected people will acquire illness and how they may be identified before clinical symptoms appear. Different studied found that utilizing anti-rK39 ELISA to screen family members and contacts might be a very reliable technique for early diagnosis and planning preventive treatment of latently infected asymptomatic carriers in order to eradicate kala-azar. Although there have been isolated instances of parasite circulation in the peripheral blood of asymptomatic individuals with *L. donovani* and *Leishmania tropica* infection. Various study findings explain the immune response as tracked prospectively and its diagnostic value in predicting the fate of latent infection in a relatively large number of patients. Serologically positive state a relatively transient increase in serum antibodies caused by recent infection that lasts for months, whereas LST positive thought to indicate long-term cell-mediated immunity after asymptomatic infection or clinical cure of kala-azar. A favorable LST result may take months to years to manifest after effective kalaazar therapy, but it lasts for decades after exposure. There are few data on risk factors for asymptomatic leishmaniasis, and its epidemiology is unknown. Such knowledge is critical for efforts to prevent and control visceral leishmaniasis, such as the eradication programs. In a Brazilian research, sand flies fed on kala-azar patients were sick in 25% of cases, while none of the sand flies fed on asymptomatically afflicted individuals became infected. Seroepidemiologic data from disease-endemic areas of India are scarce and based on small sample sizes. Serologic status is not a good predictor for conversion to clinical VL. Studies confirmed that 33% persons were serologically positive, only 3.48% seropositive persons showed disease conversion. However, 2.57%seronegative persons at baseline showed disease conversion also [11]. Human instances of transfusion-transmitted visceral leishmaniasis (VL) have been reported in both endemic and non-endemic locations, with clinical characteristics and outcomes comparable to those of natural infection [81].

When innate immune cells from asymptomatic carriers were stimulated with antigens in vitro, they exhibited a regulated rise in cytokine production that differed from that seen in non-infected subjects. This implies that using more than one diagnostic approach makes it easier to identify a substantial proportion of asymptomatic carriers. One often mentioned flaw in these research is the difficulty in identifying those who are briefly and quietly infected with the parasite. A recent study of asymptomatic people' innate and adaptive immunity revealed that a mixed cytokine profile is crucial not just for parasite replication control, but also for the preservation of these individuals' immune state [51]. Only 20% of those infected with *L. chagasi* in endemic regions of VL develop classical VL, according to research. Even before extremely sensitive molecular diagnostic technologies became available, it was established that the majority of infected people living in an endemic region have asymptomatic self-cured illnesses [82]. Nonetheless, despite the PCR assays' excellent sensitivity and specificity in identifying *Leishmania* DNA in clinically sick patients' peripheral blood, a proportion of asymptomatic persons with positive serological tests had no detectable circulating *Leishmania* DNA. As a result, the co-positivity between the PCR assay and different serological assays was astonishingly low. It's conceivable that these apparent differences might be explained by how an illness develops in people. The parasite can be identified in the peripheral blood at a certain point (providing a positive PCR assay), followed by adaptive-mediated immunity with the generation of antibodies and a T lymphocytes-mediated immune response. Because these biological moments are never-ending, it's possible to analyze certain people when they are in a state of transition. Other non-invasive and extremely sensitive techniques, such as PCR in peripheral blood, have recently been available. This has made it possible to identify

#### *Visceral Leishmaniasis: Asymptomatic Facts DOI: http://dx.doi.org/10.5772/intechopen.101109*

asymptomatic carriers of *Leishmnia* who otherwise would not have been detected using just serological methods [83]. Research findings suggest that the method used to diagnose an infection may have an impact on infection-related variables including risk factors and treatment results [61]. At the moment, it is impossible to determine who among the asymptomatically infected persons will acquire VL illness and when. A research from Bangladesh further indicates that about 80% of asymptomatic individuals contribute to disease transmission, compared to 8–10% of VL and PKDL patients [13].

The question of why just a few exposed asymptomatic people acquire fullblown illness symptoms but not all remains unsolved. The major immunological variables that promote the conversion of asymptomatic patients to symptomatic stage of visceral leishmaniasis have been attempted to explicate in several research. It is crucial to note that the use of five diagnostic techniques as a regular strategy would be impractical in endemic situations. Before a particular recommendation can be made, more research is needed to confirm the optimal diagnostic method [61]. The important checkpoints for determining disease resistance or susceptibility are cytokines that control cellular immunity [84, 85]. Despite substantial understanding of host–parasite interactions and immunobiology, reliable protective immunity criteria have yet to be discovered. Asymptomatic instances of human VL can be diagnosed using qPCR using RNA targets. There are also questions about whether or not using RNA as a gene target can help discover asymptomatic instances of VL. By combining this methodology with epidemiological data analysis, it will be possible to improve the detection and treatment of asymptomatic cases. Priority should be given to stepping up efforts to better characterize asymptomatic illness in endemic areas and to develop a uniform case definition for leishmanial infection. Self-clearing infections vs. illness development must have all of their factors examined thoroughly. The problems in parasite and sand fly management methods, as well as changes in the epidemiology of VL in disease-endemic countries, are important threats to its eradication. In addition, the movement of infected but asymptomatic people from endemic areas has resulted in additional infections in non-endemic areas [86]. The xenodiagnosis approach validates whether asymptomatic infected people can be infectious to sand flies and might be a crucial step in determining whether or not to modify the existing VL management strategy. One study used xenodiagnosis to identify VL infection in HIV-positive people and found even asymptomatic patients in the early stages of the infection were able to infect others [87]. Although Xenodiagnosis findings from an Indian investigation indicate that neither asymptomatic nor treated patients were infected by vector sandflies [88]. Asymptomatic infected persons are not now the focus of drug research efforts. This is because the asymptomatic state is not clearly defined, but largely because an intervention is less of a priority as long as the role of asymptomatically infected people in transmission is not clarified. There have been significant gains in reducing infection rates thanks to the eradication programs, but there are still some obstacles to overcome along the way. Considering that humans are the sole reservoir for *Leishmania donovani*, the effectiveness of a control programme hinges heavily on treating both symptomatic and potentially asymptomatic persons, if such individuals are found to also function as a reservoir. The lack of techniques to identify live parasites in silent infections and their relationship to disease transmission, sterile cure characteristics, and PKDL development remains a serious danger to the disease's eradication. There has been tremendous progress in the control or elimination of tropical illnesses, with a large drop in the incidence of these diseases. Although it is critical to comprehend these underlying causes for each illness, asymptomatic

carriers are a common component that can contribute to resurgence; their effect in terms of population percentage and function in transmission must be established. More study is needed to completely understand the determinants.
