Neurological Complications Caused by Human Immunodeficiency Virus (HIV) and Associated Opportunistic Co-infections: A Review on their Diagnosis and Therapeutic Insights.

Neurocognitive disorders associated with human immunodeficiency virus (HIV) infected individuals increase the risk of mortality and morbidity that remain a prevalent clinical complication even in the antiretroviral therapy era. It is estimated that a considerable number of people in the HIV community are developing neurological complications at their early stages of infection. The daily lives of people with chronic HIV infections are greatly affected by cognitive declines such as loss of attention, learning, and executive functions, and other adverse conditions like neuronal injury and dementia. It has been found that the entry of HIV into the brain and subsequently crossing the blood-brain barrier (BBB) causes brain cell damage, which is the prerequisite for the development of neurocognitive disorders. Besides the HIV replication in the central nervous system and the adverse effects of antiretroviral therapy on the BBB, a range of opportunistic infections, including viral, bacterial, and parasitic agents, augment the neurological complications in people living with HIV (PLHIV). Given the immuno-compromised state of PLHIV, these co-infections can present a wide range of clinical syndromes with atypical manifestations that pose challenges in diagnosis and clinical management, representing a substantial burden for the public health system. Therefore, the present review narrates the neurological complications triggered by HIV and their diagnosis and treatment options. Moreover, coinfections that are known to cause neurological disorders in HIV infected individuals are highlighted.

Implementation of drone based delivery of medical supplies in North-East India: experiences, challenges and adopted strategies.

Timely delivery of medical supplies is essential in the healthcare sector, which is hampered by factors such as poor transportation network, traffic and adverse environmental conditions. Alternatively, drone operations can leapfrog the last mile logistic solutions in hard-to-reach terrains. The present paper elucidates the implementation process of drone-based delivery of medical supplies, operational challenges and innovations adopted by scientists in Manipur and Nagaland. Three districts, Bishnupur, Imphal West and Churachandpur from Manipur and two districts, Mokokchung and Tuensang from Nagaland, were selected for the study. Regulatory and ethical approvals and coordination with state health and administrative authorities were accorded. Implementation and operational challenges faced by the research team were recorded elaborately in the field diaries and assessed qualitatively. The experiences encountered by the team for case-to-case based permission and coordination with the central and state aviation authorities, district administration and health authorities were observed. The drone-related technical and logistic challenges were identified as the deployment of suitable drones, payload capacity, time management for operations, and transportation of drones. The officials adopted mitigation strategies to overcome field-based challenges. Drone-based deliveries of medical supplies are proving to be time efficient, however, overcoming operational challenges could provide an effective long-term deployment strategy.

Assessment of Community Behavior and COVID-19 Transmission during Festivities in India: A Qualitative Synthesis through a Media Scanning Technique.

In India during the first wave of COVID-19 infection, the authorities were concerned about the advent of the festive season, which could lead to a surge in cases of SARS-CoV-2 infection. The present study attempted to assess the socio-behavioral aspects of COVID-appropriate behavior (CAB) at individual and community levels, and their impact on the transmission of COVID-19 during festivities in India. Media scanning was conducted to qualitatively assess CAB by analyzing 284 news reports from across India; quantitative data on COVID-19 daily cases from March 2020 to December 2020 were used to determine the trends of the adjusted test positivity (ATP) ratio for six cities. Peaks in ATP were observed in Chandigarh, Delhi-NCR in North India during and after Dussehra and Deepavali, and in Mumbai, in the west, after Navratri. Additionally, a surge in ATP was observed in Trivandrum after Onam and in Chennai around Deepavali in the south; meanwhile, in the eastern city of Kolkata, cases increased following Durga Puja. The major challenges were adherence to CAB viz. social distancing, hygiene, and compliance with the mask mandate. Microlevel CAB indicated relatively higher laxity in maintaining hand hygiene in all cities. Observations from the current study indicate that innovative community-driven initiatives during festivals in each geographical zone are key to the large-scale implementation of disease prevention measures.

Patterns of human immunodeficiency virus drug resistance mutations in people living with human immunodeficiency virus in India: A scoping review.

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic still exists as a major global public health burden, especially in the middle- and low-income countries. Antiretroviral therapy (ART) remains a sole option to reduce the mortality and morbidity associated with this disease as no approved vaccine candidates are available. About 67% of the people living with HIV (PLHIV) have received the ART in 2019 worldwide. As a consequence of increased ART regimes, the prevalence of drug resistance mutations (DRM) also has been escalating and it would become a significant barrier in achieving the United Nations Programme on HIV/AIDS goal of eliminating HIV by 2030. So far, nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitor-(PI) associated DRM have been reported across the globe with a considerable escalation in the annual prevalence rate of pretreatment NNRTI DRM. Conversely, NRTI-associated DRM is still under 5%, with a few scattered reports of significant increase from few countries such as southern and eastern Africa. Likewise, in India, the propositions of NRTI and NNRTI-associated DRM have increased since the commencement of the nationwide ART program in 2004. In agreement to the global trend, M1841/V, a type of NNRTI, remains as a dominant DRM among PLHIV. In this review, we tried to collate various mechanisms of DRM in PLHIV. In addition, patterns of HIV DRM in India and their future challenges on drug-related mutations have been discussed.

Emerging and re-emerging sexually transmitted diseases: A review of epidemiological evidences.

Substantial increase in the outbreaks of sexually transmitted infections (STIs) and associated mortalities have raised international concerns. Concurrent with the escalation of established STIs, developing epidemics and outbreaks of newly emerging sexually transmissible pathogens pose serious problems for people and added burden and challenges for public health practitioners and researchers. Importantly, most of the emerging STIs are frequently found among vulnerable groups, such as men having sex with men and human immunodeficiency virus patients, which may result in large outbreaks in the near future. Furthermore, enhanced spread of antimicrobial resistance among these pathogens ever more limits treatment options for STIs. Thus, it is the optimal time to consider whether an infectious agent is sexually transmissible and develop treatment protocol for handling new STIs with pandemic potential. In this review, we explore emerging STIs, their current epidemiological status, and future perspective.

Sexually Transmitted Infections (STIs) and Its Changing Scenario: A Scoping Review.

Sexually Transmitted Infections (STIs) and reproductive tract infections (RTIs) have existed worldwide since ancient times, causing significant morbidity and mortality. To maintain healthy sexual and reproductive life, it is highly essential to prevent STIs, RTIs and related illnesses. STIs are transmitted by transaction of body fluids among people during sexual intercourse. The etiological agents for STIs are bacteria, viruses and parasites in most cases, but proportions by different aetiology are varying. Various studies have shown that STIs are increasing, and their primary aetiology is changing worldwide, which should be considered seriously and needs necessary actions. Several factors related to hosts and disease-causing agents have been identified to influence STIs' current strategies in the prevention and control program. The present study attempts to review the history, changing aetiology and antimicrobial resistance in STIs. This review has also highlighted the prevalence of STIs at the global level and their past and present trends in India, emphasizing future challenges and perspectives for making effective public health policies to prevent and control STIs.

Association between ambient air pollutants and meteorological factors with SARS-CoV-2 transmission and mortality in India: an exploratory study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic poses a serious public health concern worldwide. Certain regions of the globe were severely affected in terms of prevalence and mortality than other. Although the cause for this pattern is not clearly understood, lessons learned from previous epidemics and emerging evidences suggest the major role of ecological factors like ambient air pollutants (AAP) and meteorological parameters in increased COVID-19 incidence. The present study aimed to understand the impact of these factors on SARS-CoV-2 transmission and their associated mortality in major cities of India. METHODS: This study used secondary AAP, meteorological and COVID-19 data from official websites for the period January-November 2020, which were divided into Pre-lockdown (January-March 2020), Phase I (April to June 2020) and Phase II (July to November 2020) in India. After comprehensive screening, five major cities that includes 48 CPCB monitoring stations collecting daily data of ambient temperature, particulate matter PM2.5 and 10 were analysed. Spearman and Kendall's rank correlation test was performed to understand the association between SARS-CoV-2 transmission and AAP and, meteorological variables. Similarly, case fatality rate (CFR) was determined to compute the correlation between AAP and COVID-19 related morality. RESULTS: The level of air pollutants in major cities were significantly reduced during Phase I compared to Pre-lock down and increased upon Phase II in all the cities. During the Phase II in Delhi, the strong significant positive correlation was observed between the AAP and SARS-CoV-2 transmission. However, in Bengaluru, Hyderabad, Kolkata and Mumbai AAP levels were moderate and no correlation was noticed. The relation between AT and SARS-CoV-2 transmission was inconclusive as both positive and negative correlation observed. In addition, Delhi and Kolkata showed a positive association between long-term exposure to the AAP and COVID-19 CFR. CONCLUSION: Our findings support the hypothesis that the particulate matter upon exceeding the satisfactory level serves as an important cofactor in increasing the risk of SARS-CoV-2 transmission and related mortality. These findings would help public health experts to understand the SARS-CoV-2 transmission against ecological variables in India and provides supporting evidence to healthcare policymakers and government agencies for formulating strategies to combat the COVID-19.

Native Wolbachia influence bacterial composition in the major vector mosquito Aedes aegypti.

Bacterial species that inhabit mosquito microbiota play an essential role in determining vector competence. In addition to critical factors such as host genotype, feeding habit and geography, intracellular endosymbiont Wolbachia pipientis modulates microbial composition considerably. In the present study, we assessed the midgut bacterial diversity of Aedes aegypti mosquitoes that is either naturally carrying Wolbachia (wAegB+) or antibiotic cured (wAegB-) through a culture-independent approach. Towards this, 16S rRNA gene libraries were constructed from midgut bacterial DNA of laboratory-reared larvae and adult female mosquitoes fed with sugar or blood. Among them 33 genera comprising 65 distinct species were identified, where > 75% of bacterial taxa were commonly shared by both groups (wAegB+ and wAegB-), implying a subtle shift in the bacterial composition influenced by Wolbachia. Though the change was mostly restricted to minimally represented species, predominant taxa were observed unaltered except for certain genera. While Serratia sp. was abundant in Wolbachia carrying mosquitoes, Pseudomonas sp. and Acinetobacter sp. were predominant in Wolbachia free mosquitoes. This result demonstrates the influence of Wolbachia that could modulate the colonization of certain resident bacterial taxa through competitive interactions. Overall, this study shed more light on the impact of wAegB in altering the gut microbiota of Ae. aegypti mosquito, which might challenge host fitness and vector competence.

In Vitro Detoxification Studies of p-Cresol by Intestinal Bacteria Isolated from Human Feces.

p-Cresol is a neurotoxic and nephrotoxic carcinogenic aromatic substance produced as a result of microbial fermentation in the intestine. The derivatives of p-cresol (p-cresyl sulphate or p-cresyl glucuronide) have a deleterious effect on renal failure patients undergoing hemodialysis. Human gut seems to be inhabited with a diverse microbial population capable of detoxifying many aromatic compounds. However, the knowledge on the role of gut microbes in metabolizing p-cresol is limited. Hence, the present study aims to investigate p-cresol detoxification by intestinal bacteria isolated from human feces. Three potential p-cresol tolerant isolates were selected and identified as Enterococcus faecalis strains (UTD-1, UTD-2 and UTD-3) by 16SrRNA gene sequencing. All three E. faecalis isolates decreased the p-cresol concentration (30 µg/ml) at a higher rate with extracellular extracts (2.58-9.53 µg/ml) as compared to intracellular (0.55-5.28 µg/ml) extract. These three potential isolates also exhibited tolerance to gastrointestinal conditions for up to 60 min. Added to its potential, the expression of virulent genes (esp, gelE, and cyl) was found to be suppressed when subjected to bile stress under in vitro conditions. HPLC analysis displayed transformed products from extracellular extract treated samples were comparable to the metabolite standard of the p-cresol degradation pathway. Infrared spectral analysis too showed the spectrum similarity with metabolite standard. Thus, conclusively, intestinal isolates E. faecalis (UTD-1, UTD-2 and UTD-3) might be a promising candidate for mitigating p-cresol detoxification in uremic patients.

Evidence for the natural occurrence of Wolbachia in Aedes aegypti mosquitoes.

Wolbachia, a Gram-negative bacterium, is widely known to be present in arthropods and nematodes. Of late, great impetus is given to employ this intracellular bacterium, as an alternative to conventional biocontrol agents for the control of mosquitoes because of its inherent ability to induce sperm-egg incompatibility, feminisation etc. By employing molecular tools, we have shown the presence of Wolbachia from Aedes aegypti mosquito population collected from Coimbatore, India by PCR amplifying the Ae. aegypti mosquito genome with Wolbachia specific 16S rRNA, wsp and ftsZ gene primers. The phylogenetic analysis of these gene sequences incorporating MLST and GenBank reference sequences has confirmed the occurrence of Wolbachia supergroup B in Ae. aegypti. In addition, qRT-PCR results have shown the dynamics of Wolbachia across the developmental stages of mosquito. The absence of Wolbachia in tetracycline-treated Ae. aegypti mosquitoes evidenced by transmission electron microscopy reinforced our finding conclusively. After confirming their persistence through generations, we have designated Wolbachia from Ae. aegypti as wAegB. In our considered view, wAegB could play a dynamic role in impeding mosquito multiplication and consequently impinging transmission of the dreadful dengue.