Editorial: Emerging and reemerging neglected tropical diseases: Epidemiology, transmission, mitigation, and vaccines and chemotherapy advancements

Ranjan K. Mohapatra ^1* Snehasish Mishra ² Dr. Venkataramana Kandi Ph.D., MAMS, FAGE, FRCPath (London) ³ Chandra Sekhar Sirka ⁴ Lawrence Sena Tuglo ⁵

• ¹ Government College of Engineering, Keonjhar, Keonjhar, India
• ² KIIT University, Bhubaneswar, Odisha, India
• ³ Prathima Institute of Medical Sciences, Karimnagar, Andhra Pradesh, India
• ⁴ All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India
• ⁵ University of Health and Allied Sciences, Ho, Volta, Ghana

Neglected tropical diseases (NTDs) are bacterial, viral, fungal and parasitic infectious diseases including ectoparasites like mites and fleas [1,2,3]. NTD is a perpetual challenge to global public healthcare and community health. The major reason why such diseases collectively remain neglected is that they are considered as the ‘diseases of the poor’, the people primarily in the low and medium income countries (LMICs) with modest purchasing capacity. As a result of this, the commercial diagnostic, therapeutic and prophylactic efforts by the pharmaceutical companies are only skeletal as they don’t envision a profitable market. Thus, although treatable, these diseases ultimately manifest as the terminal diseases for the have-nots. The World Health Organisation (WHO) has enlisted the globally prevalent NTDs, and updates it from time-to-time. Currently, there are twenty-one aetiologically, epidemiologically and clinically unique forms of diseases (or groups of diseases) enlisted as NTDs by the WHO [4]. The WHO has devised public health strategies and has proposed a roadmap to eliminate NTDs by 2030 [5]. However, as the majority of the NTDs affected subjects live in financially constrained third world countries it seems to be an uphill task and achieving it is not a cakewalk by any means. Lack of NTDs related awareness and limited diagnostics resources in these regions severely affect their foolproof identification. This fact is evident from constantly rising instances of the diseases that fit into the NTDs criteria as delineated by the WHO. Various NTDs reemerged in the wake of the coronavirus disease 2019 (COVID-19) pandemic by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), striking the healthcare infrastructure hard worldwide and exposing the underbelly. It suggests the need for heightened collaborative research efforts to improve the diagnosis, control and prevention of NTDs possibly through special benevolent funding by the global health agencies and charitable trusts for the sake of the humanity. In wake of this, there is a constant need to keep the scientific community aware and updated about these ‘diseases of the poor’, and sensitise the numerous global stakeholders about the universal wellbeing and economic consequences far beyond the international borders. This editorial highlights the contributions of the various authored articles that are included in our special issue dedicated to research topics on NTDs. Figure 1 depicts the numerous perpetual social, economic and technical challenges faced to curb the NTDs in a nutshell for the readers to comprehend better. This special issue research topic was an attempt to decipher the best-case scenario to devise a unified global response to contain the diseases across borders, and save precious human lives.DiscussionGlobal impact of a tick-borne apicomplexan bovine babesiosis parasite, Babesia bovis has been underappreciated, particularly in the tropical and subtropical regions. Using Texas T2Bo strain of Babesia bovis in an US study, Cardiollo et al. compared the potency of imidocarb dipropionate (ID) and buparvaquone (BPQ) in vitro. The study evaluated the effect of the two drugs at varying concentrations against the lab-cultured infected cells. They revealed that the parasite could be completely eliminated at 150 nM of BPQ and 300 nM of ID, and thus BPQ was superior in efficacy as compared to ID. Thus the data suggested that BPQ was effective and seemed superior to ID as the first-line drug to treat the global menace of bovine babesiosis.The 2015 Zika virus (ZIKV) outbreak in Brazil attracted the global research community as the epidemic spread throughout the Americas. Over 5,00,000 ZIKV confirmed cases were reported in the Americas by 2016 end. Due to its serious public health threats, the WHO declared ZIKV infection a public health emergency of international concern (PHEIC). Till date, 86 countries and territories have reported ZIKV infection, while no effective treatments or vaccines against ZIKV are there yet. Among the several vector-borne viral infections, ZIKV is a mosquito-borne infection transmitted through the bite of Aedes aegypti. ZIKV belonged to Flaviviridae family of RNA viruses that also includes other human infectious viruses like yellow fever virus, dengue virus and Japanese B encephalitis. Feng reviewed a list of drugs and natural compounds with alleged anti-viral activities against ZIKV. Among these, protein inhibitor groups like LAS 52154459, LAS 52154463 and LAS 52154474 were found to be the potential candidates as they could efficiently contain the disease and were less toxic. The review summarised the role of NS2B-NS3 protease inhibitors like peptide derivatives, repurpose drugs and synthetic small molecules that restricted the viral development and reproduction. NS5 protein inhibitors like MTase inhibitors, RdRp inhibitors, nucleoside analogs also were reviewed for their anti-ZIKV potentials. In wake of this, continued research in this area to develop ZIKV medications is recommended as the most suggestive and effective approach.Dermatomycosis or dermatophytosis is a superficial fungal infection condition of the skin, hair and nails. Despite the mildness of the clinical presentations, such infections are severely debilitating. Adequate knowledge of the predisposing factors behind such infections and the preventive measures could contribute to low infection rates. In this context, Dhakal et al. evaluated the knowledge, hygiene practices and prevalence of dermatophytosis among prisoners in Nepal in their original survey-based study. In this cross-sectional study, 184 Nepali prisoners were included whose dermatophytosis data were collected using a validated questionnaire. The results demonstrated that the knowledge on dermatophytosis among the prisoners was moderate. The results also revealed significant knowledge gap on the transmission of the infections and the recommended preventive measures. Despite being aware of the available treatments, there were misconceptions about re-infections and the role of personal hygiene in controlling the spread of the infections. Given the crowded nature of the prisons, and sometimes overcrowding, it was important to implement measures to improve the understanding and awareness about dermatophytosis and preventive strategies among such population.Opisthorchis viverrine is a helminthic parasite fluke of the liver belonging to the Platyhelminthes group. It is one of the many NTDs that are endemic to the Great Mekong Subregion of Thailand. The humans infected with O. viverrine would suffer from cholangiocarcinoma. Although the infection could be treated by anti-helminthic praziquantel, O. viverrine reinfection due to antimicrobial resistance development severely limit the treatment option. Therefore, focused research directed toward the development of vaccines to prevent this parasitic infection was essential. Kafle and Ojha elucidated the application of Omics approaches and computational tools in developing advanced countermeasures against O. viverrine infection. The applications of cutting-edge tools and techniques based on Omics approaches like genomics (genome repeat and non-coding element identification, sequencing, genome assembly, protein-encoding gene identification and functional annotation), transcriptomics (differential gene expression analysis, RNA sequencing, transcriptome assembly and functional annotation), and proteomics (protein extraction, mass spectroscopy, protein identification, immunoreactive band excision and functional annotation), and the potential therapeutic targets have been elaborately discussed in their report. The approaches based on computational tools including Artificial Intelligence will be very much helpful to accelerate the NTDs related research and discovery of novel biologics with limited available funds, offering new vistas to effectively combat not only such neglected diseases as the carcinogenic human liver fluke O. viverrine infection but also other NTDs of global concerns.Arboviral infection is a significant threat to community health due to the associated morbidity and mortality. Arboviral infectious diseases are transmitted through the active involvement of arthropod vectors such as mosquitoes. These infections usually spread during the monsoon when the mosquito vectors breed and multiply exponentially. Compounded by climate change and increasing global movements, Italy faces a growing threat of arboviral infections due to presence of competent mosquito vectors like A. albopictus. Branda et al. have discussed about the Arboltaly and the utility of computerised tools in this context, to effectively carryout genomic surveillance of arboviruses in Italy. Their suggested approaches included data collection, its classification, dataset processing and online publication of the results of the analyses for access of the general public and the consumption of the scientific community. They have elaborately discussed the environmental and socioeconomic factors that were responsible for the spread of arboviral infections, controlling these infections through integrated strategies and furthering the research advances in developing vaccines against them. They observed that the chikungunya virus (CHIKV) vaccine currently in the Phase I clinical trials prepared using the pre-membrane (prM) and envelope (E) glycoproteins of CHIKV were more than 90% efficient, and a recombinant yellow fever vaccine using the same proteins demonstrated similar efficacy. Although Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur and Qdenga® (TAK-003) developed by Takeda are vaccines against Dengue virus (DENV) licensed for human use, there was no approved vaccine against CHIKV for human use. Therefore, enhanced vector control measures and public healthcare interventions to curb the widespread transmission of arboviral infections particularly in the high-risk regions was urgently needed, especially in the absence of effective preventive and therapeutic countermeasures.Among the various other arboviral infections, DENV is extremely prevalent in the tropical and subtropical Asia and America. DENV is transmitted by Aedes aegypti mosquito-bites. There are four DENV types (DENV 1–4) around the globe, of which DENV-2 serotype infection was fatal. With over 100 million illnesses and 25,000 deaths each year, it has significantly impacted the global healthcare and wellbeing measures. Hossain et al. evaluated the phytochemical compounds sourced from V. cinerea for their antiviral properties against DENV. Based on the thermodynamic properties, electrostatic potentials and the molecular screening of -amyrin, -amyrin acetate, chrysoeriol, isoorientin and luteolin as test compounds, these could potentially inhibit NS1 protein of DENV-2. Their study demonstrated that there was no cytotoxicity, hepatotoxicity, immunotoxicity, mutagenicity and carcinogenicity of the five test compounds that they studied. The authors have suggested through their article that chrysoeriol was the most effective against DENV-2, which could be evaluated further as a therapeutic agent to manage DENV-2 infections.The COVID-19 by the SARS-CoV-2 virus still existed and was round the corner since its discovery in 2019. Although it resulted in severe morbidity and mortality during the initial phases when the information about the aetiological agent SARS-CoV-2 was low, early introduction of vaccines could control its further spread and reduced the severity of the disease later. As evidenced from the variants like Alpha, Beta, Delta, Omicron, etc., SARS-CoV-2 is constantly emerging and thriving with its genetic variants. COVID-19 patients have frequently reported post-recovery sequelae, termed as ‘long COVID-19’, wherein they suffered from chronic symptomatic manifestations in internal organs like lungs. Chhotaray et al. evaluated the cardiovascular complications associated with SARS-CoV-2 infections by the JN.1 subvariant. JN.1 was identified in September 2023 and was initially labelled as the variant of interest (VoI) by the WHO. It was more prevalent in Canada, France, Sweden, Singapore, the UK and the USA. The unique mutations observed in JN.1 are R3821K in ORF1a, L455S in the spike protein, and F19l in ORF7b. Evidence suggested that since SARS-CoV-2 infection was facilitated by the ACE2 receptors on the human cells, affected the renin-angiotensin system (RAS) that were also involved in hypertension, and it could result in complication of the cardiovascular system. The authors also suggested close monitoring of the emergence of novel variations and their severe outcomes. They also emphasised on the development of novel monoclonal antibodies and next-generation vaccines to counter the adverse impact.With the emergence of mpox disease initiating as an endemic in the Democratic Republic of the Congo and developing as the next potential pandemic, the focus of the public health administrators, researchers and clinicians has shifted to MPXV (causal agent behind the mpox infection). MPXV, causing infections in vertebrate hosts like humans, cattle and monkeys, belongs to the pox virus lineage consisting of Orthopoxviruses. Of the MPXV clades, Clade I was more pathogenic than Clade II. However, Clade I was confined to the West African countries until recently where the virus was reported for the first time. Clade II reemerged in 2022 that spread to the US, and later expanded worldwide to more than 120 countries. The clear evidence of the recent spread of Clade I beyond the endemic regions and the emergence of the novel Clade Ib lineage has threatened global public health, and certainly a wake-up call. In this context, Srivastava et al. elaborated the geographical distribution, transmission characteristics, mutation rate and public healthcare impact of all the MPXV clades. They have explored the benefits of artificial intelligence in the diagnosis and surveillance of MPXV infections which could assist to predict and prevent outbreaks in future.The collection of research topic in this special issue on NTDs would certainly address the knowledge gaps and enhance the comprehension to effectively mitigate the transmission of these NTDs, particularly in the low-and-medium-income countries (LMICs). Further, the use of advanced computational tools like DL, ML and AI, along with the ‘One Health’ approaches, could facilitate forging solutions to contain these diseases. The frequently encountered numerous other infectious NTDs (such as tuberculosis) and non-infectious NTDs (such as noma) could debatably find more promising solutions through such investigative research interventions. The Editors envisage and wish to come up with a fresh special issue later covering some of these diseases too.