**14. Conclusions**

*Animal Models in Medicine and Biology*

**Epidemic/ Pandemic Disease**

**Table 1.**

*organism.*

**13. Future perspective**

**12. Disadvantages of Drosophila model for drug screening**

Haemorrhagic fever Ebola virus glycoprotein GP expressed in S2

Plague Yersinia pestis — Yellow fever Yellow fever virus —

*Drosophila melanogaster* being ectothermic organism unlike humans are endothermic homeotherms maintains physiological temperature constantly at 37°C, making it difficult to infect flies with bacteria like *Mycobacterium tuberculosis* grows strictly at 37°C [36, 122]. Several pathogenic viruses capable of infecting humans cannot naturally infect *Drosophila melanogaster* [55, 67]. The fungal dose response in flies is difficult to measure in oral infection model therefore this model is limited to study only the anti-fungal drug efficacy [64]. The presence of symbiotic microbes like Wolbachia a gram negative bacteria associate mostly with drosophila gut, improves the fly immunity against viral infection [123]. Superinfection like viral pneumonia cannot be studied at present to undertake preclinical trial using fly as a model.

**Microbes Vaccine/Drugs screened or** 

Haemorrhagic fever Marburg Virus MR191 expressed in S2 cell line [118]

West Nile Fever West Nile Virus WN-80E expressed in S2 cell line [116, 120]

*List of Drugs/vaccines screened or developed against Infectious diseases in* Drosophila melanogaster *as a model* 

**in-vivo)**

cell line

**derived out of fly model (in-vitro/**

**References**

[121]

Irrespective of multiple disadvantages flies could be used for studying drug efficacy. Multi-drug resistance tuberculosis infection could be studied in flies. The ART medication impairs human heart by causing prolonged QT, prolonged arrhythmic condition leads to myocardial infraction, *Drosophila* could be a suitable model to study the effect of anti retroviral therapy on fly heart [124–126]. Shockingly infection induced in flies by vesicular stomatitis virus in toll-7 depleted flies where 50% flies displayed death after 18 days, suggesting HIV infection could also kill toll7 mutant flies, as toll mutant flies displayed fungal invasion, this yet to be confirmed [44]. Alternative to this only viral DNA had been shown in a recent study to evoke immune activation in Drosophila by injecting it in thoracic region [87]. Kaposi sarcoma associated Herpesvirus (KSHV) needs a model which is yet to be studied in flies, however the KSHV viral gene latent nuclear antigen (LANA) interacts with RING3 of human which is homologous to drosophila female sterile homeotic (fsh) has already been identified [127]. Drosophila wound healing an important concern while inducing bacterial infection currently it is well understood and was found regulated by EGFR/ERK pathway essential for tissue repair [128]. The RNAi screens against Dengue or Influenza virus infection in cell culture could not identify Jak–STAT, ImD and toll dependent gene activation suggesting possible alternative pathway associated in infection modulation and no stimulation of inflammatory cytokine activation [40]. The food borne *Salmonella typhimurium* causes stomach flu (*gastroenteritis*) is well studied in Drosophila, but not epidemic

**118**

pathogen *Salmonella typhi*.

Currently the existing models of infection in drosophila are capable of causing infection using viruses, bacteria (gram negative and gram positive) and fungi. These models are of great use since the efficacy of a drug capable of modifying diseased condition could be studied in detail in live *Drosophila* or in-vitro S2 cell. In this detailed review on epidemiology of infectious disease, it could be predicted that infection alone is a threat to overall population imposing death to more than 5 million individuals. Diseases like influenza, HIV, pneumonia, tuberculosis and cholera could be studied in flies. Currently there are 20 diseases which caused epidemic worldwide [2], 13 of the pathogens were studied in *Drosophila melanogaster* and diseases caused by yellow fever virus, Nipah virus, MERS, Hepatitis C virus, Salmonella typhi, Crimean congo hemorrhagic fever virus, chikungunya virus, monkeypox virus, Nipah virus and shigellosis bacteria are yet to be studied in-vitro/in-vivo. These diseases are of pandemic and epidemic criteria it causes huge number of deaths globally. Controlling the epidemic and pandemic diseases should be the main focus of the healthcare sector in the next decade.
