Mode Of Spread Research Articles

Empowerment and engagement of SHG women against HIV/AIDS in India: an interventional study

Background: Lack of access to information and education makes women more susceptible to acquire HIV/AIDS. Self-help groups (SHGs) are seen as instruments for empowering women in the community. Realizing this, it was hypothesized that if the strategy to train SHG women brings significant improvement in the knowledge of study population about HIV/AIDS; then this strategy may be a financially sustainable and practicable method in rural India.Objective: Empower and engage the SHG women against HIV/AIDS by creating awareness and sustaining interest through lesson plans in the IEC material.Methods: This was a 'Multi-centric Action Research Demonstration Study'. As an intervention, series of workshops were conducted with the help of pre-developed IEC material. 400 households (200 from each intervention and control sites) of SHG women were interviewed for baseline and end line each.Results: The planned intervention could make significant changes in level of awareness of the respondents about HIV/AIDS in terms of mode of spread, prevention and control measures and places to get tested for HIV/AIDS. This was also found effective to reduce the misconceptions regarding transmission of HIV/AIDS in the study area, thus in turn reducing the stigma attached with the disease.Conclusion: The awareness level about HIV/AIDS in rural areas among SHG women was very low and there is an urgent need and scope for development and implementation of effective interventions strategy to train local community worker which in turn can bring improvement in the knowledge of community by providing the information in culturally acceptable manner.

A Comparative Study: Knowledge and Practices amongst Post-Operative Patients Regarding Hospital Acquired Infections (HAI) between Private and Public Tertiary Care Setup in Pakistan

Abstract: Background: Hospital Acquired Infection (HAI) is a major global safety concern for the health system as it increases mortality, morbidity, and length of hospital stay and contributes to the economic burden. These infections are prevalent in hospitals of developing countries such as Pakistan, due to limited resources, unsafe infection control practices and under reporting. However, post-operative patients are more prone to these infections due to immunocompromised state, antibiotic resistance, and most importantly lack of awareness regarding HAIs and their respective preventive measures. Therefore, the objective of this study was to highlight some of the serious but avoidable aspects of this largely ignored but important issue of HAIs in public and private tertiary care hospitals by assessing and comparing the need of knowledge and awareness in post-operative patients to minimize risks which in turn will decrease incidence, morbidity and mortality. Materials and Methods: A descriptive cross sectional study was conducted among post-operative patients of Liaquat National Hospital and Civil Hospital (private and public tertiary care hospital, respectively), over a period of 1 year (July 2017-2018) in Karachi. Individual interviews following verbal consent were taken using a pre-coded questionnaire, which was divided into 3 sections to analyze the social and demographic, knowledge and practices of the patients. We excluded patients with impaired comprehension, less than 15 years of age and those who were reluctant to participate. Data was analyzed using SPSS v.22.0. Pearson’s chi-square was used as the primary statistical test. Results: Three-fifty post-operative patients from each, public and private hospital were enrolled. The mean age was found to be 38.41 ± 16.57 years and 40.3% of patients were uneducated. Knowledge regarding the modes of spread, types and risk factors for hospital acquired infections was significantly associated with patients admitted in private hospital, female gender and a higher education level.

Spoligotype Diversity of Mycobacterium tuberculosis over Two Decades from Tiruvallur, South India.

Geographically, most tuberculosis (TB) cases in 2018 were reported from India. This TB burden is compounded by MDR-TB and XDR-TB. The strategies for the management and control of TB in the community depend on an understanding of the mode of spread of the different strains of TB isolates in the community. To determine the distribution and trends of M. tb strains over the time period in the community due to treatment, we carried out the present study on changes over two decades. Design/Methods. A total of 1218 M. tb isolates (year: 2001–2018) from Tiruvallur, India, were genotyped by spoligotyping after DNA extraction and subjected to anti-TB drug susceptibility testing for the first-line anti-TB drugs. Results. On analysis with the SpolDB4 database, majority (2001–2003: 53.32% and 2015–2018: 46.3%) of the isolates belonged to East African Indian (EAI) lineage, and the orphans designated in comparison to SpolDB4 stood 33% among 2001–2003 strain collection and 46.3% among 2015–2018 strain collection. 10.2% (2001–2003) and 9.26% (2015 to 2018) of isolates were monoresistant to isoniazid (H). MDR strains were less common among EAI strains (3.2%) compared to non-EAI strains (10.32%). Conclusions. EAI is the most predominant lineage in Tiruvallur, despite the presence of highly transmissible lineages like Beijing for the last two decades. The prevalence of MDR-TB is below the national average of 2-3% among the new TB cases in the last two decades. The reason can be attributed to the well-established nature of the locally circulating strains in this region which are not associated with drug resistance.

Awareness on Ebola Virus among Undergraduate Dental Students in a Private Dental Institution, Chennai - A Questionnaire Survey

Ebola virus disease (EVD) is a deadly disease with occasional outbreaks that occur primarily on the Africancontinent. EVD most commonly affects people and nonhuman primates (such as monkeys, gorillas, andchimpanzees).The aim of the study to determine the awareness of Ebola virus among the undergraduatedental college students.This study involved the awareness of Ebola virus in the age group of 18 to 25 years. Awell structured questionnaire comprising 14 questions covering socio demographic information, knowledge,attitude, perception was framed and administered to the participants through an online google forms. Surveywas conducted among 100 college students. In that 30.39% male students and 69.61% of female studentshave taken this survey. The association between groups was assessed by Chi Square test where p < 0.05was considered statistically significant. We have observed that association between gender and responsesto awareness on the mode of spread of Ebola virus was statistically significant (p =0.020 ). The awarenesson ebola virus was analysed among the few college students by this survey and more awareness should becreated among the population about the ebola virus.

Importance of the Respiratory Tract in Carbapenemase-Producing Enterobacteriaceae Spread

Background: Carbapenemase-producing Enterobacteriaceae (CPE) causes infections associated with high mortality rates among hospitalized patients. CPE transmission occurs frequently, and prevention of patient-to-patient transmission is a priority. However, transmission pathways are not yet completely understood. The colonization of the respiratory tract with a CPE may lead to a higher risk of contamination of the patient’s environment increasing the spread of CPE. Objective: We estimated the rate of CPE spread when respiratory tract infection or colonization is present. Methods: We studied CPE dissemination analyzing a cohort of patients admitted between January 2013 and December 2018 at the university hospital complex of A Corua, a tertiary-care hospital. All patients who were hospitalized in the same room as a patient colonized or infected with a CPE (index case) for at least 24 hours were screened for CPE carriage. The microbiological screening was performed with conventional culture or polymerase chain reaction (PCR) to identified possible CPE patient-to-patient transmission. The screening test included several samples: rectal swab, perineal swab, wound or drainage swab, and low respiratory tract sample. Results: Active screening for CPE carriage was performed in 84 contact patients. Men represent 57.1% of the sample, and the mean age was 78.5 years (men, 68.0 years and women, 80.8 years), with significant differences between sexes (12.9; 95% CI, 19.6 to 6.1). The major group of cases (86.9%) were hospitalized in medical wards. Transmission confirmed by PCR occurred in 13 (15.5%) of 84 contact patients, after a mean exposure to the index case of 13.3 days. No significant differences were detected in terms of mean exposure to index cases between those contact patients who result negative and those who result positive. The 35 index cases (41.7%) tested positive for CPE on the respiratory sample, and exposure to them led to 8 positive contact patients (61.5%). Conclusions: CPE transmission in a tertiary-care hospital occurred frequently. The spread rate is even higher when CPE is present at the respiratory level. Understanding the mode of spread is important for designing effective control measures and adding a respiratory sample to CPE screening could be a key consideration.Funding: NoneDisclosures: None

English

Pests and diseases greatly contribute to the decline in banana yields, food and income insecurity in the Great Lakes region of Africa. Understanding people’s role in pest and disease spread at landscape level is crucial for effective pest and disease management. To determine this, focus group discussions (FGDs) targeting 10 experienced farmers (50% female and 50% male) were conducted in 27 villages along four banana trade routes in western Burundi and eastern DR Congo. FGDs determined the presence and risk of spread of key banana pests and diseases via the movement of banana bunches, planting material and other products, labourers, traders and farm tools. Black leaf streak (BLS), Fusarium wilt and banana bunchy top disease (BBTD) were reported to have been in the landscape for over 40 years while Xanthomonas wilt (XW) was a more recent introduction (1-7 years). BBTD, XW and weevils were the most prevalent constraints. BBTD was observed at previously unsuitable high-altitude zones, which should be a cause of concern, especially with the current risk of climate change. Climate change, and linked temperature increases, could also worsen the prevalence of XW, weevils, nematodes and BLS. Movement of farming tools by labourers and traders, of planting material/suckers and banana bunches emerged as the most common human practices potentially responsible for the spread and/or build-up of banana pests/diseases. Strengthening farmer’s knowledge and institutional capacities of actors on these different modes of disease spread in banana value chains in the region is recommended. Key words: Black leaf streak, bunchy top disease, Fusarium wilt, nematodes, weevils, Xanthomonas wilt. &nbsp

Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae

Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.

A brief review on history, transmission and management of corona virus outbreaks

Over the year’s world had seen mainly viral outbreak, some of them became epidemic and others pandemic. Recent outbreak of COVID-19 is one of the examples. The present work is a review on the different viral outbreaks that took place in the history. Review mainly focuses on the outbreak caused by coronavirus family that comes under superfamily of Nidovirus. Here we have described in detail about the genetic composition of different corona viruses like Middle East Respiratory Syndrome-Corona-Virus (MERSCoV), severe acute respiratory syndrome-corona-virus (SARS-CoV) and Novel corona virus (COVID-19) along with their mode of spread and their effect on the human population. This work explains the about the research that either has been done or going on for the management and treatment of the disease. COVID-19 being the recent outbreak, a detail about its origin, cause, symptoms, transmission and its effect on the economy as well as environment has been explained here.

Covid 19- An Orthodontists’ perspective

COVID 19 has created havoc in the entire world in past few months. Starting from Wuhan, China the disease has spread to the entire world in couple of months. The highly contagious and notorious nature of the disease has made WHO declare it as a pandemic and sixth public health emergency of international concern. The nature and course of disease is constantly being upgraded by the researchers all over the world. Amongst all the health professionals, Dental fraternity is at utmost risk due to the mode of spread of infection via respiratory droplets. The fact has lead to increased anxiety amongst the fraternity and orthodontists are not an exception to it. In this article, an effort has been taken to summarise and review the cause and effects of SARS CoV 2, the precautions to be taken by the orthodontists and patients during the pandemic and smooth re opening of the practice post lockdown so as to minimise the anxiety and serve the patients in a safer way.

Managing rheumatic diseases during COVID-19.

Rheumatology practice, during Coronavirus Disease 2019 (COVID-19) pandemic, has faced multifaceted challenges. Rheumatologists routinely prescribe immunosuppressant medications to their patients with multisystem autoimmune rheumatic diseases who are concerned about the increased risk of acquiring COVID-19 infection and are anxious to know if they should continue or hold these medications. Rheumatologists are often inundated by calls from their patients and physician colleagues caring for COVID-19 patients in hospitals, about how to manage the immunosuppression. Physicians face the challenging task of keeping up with the most up-to-date information on COVID-19. There are uncertainties about the mode of spread, clinical features, management options as well as long-term complications of COVID-19. Data are rapidly evolving and different studies on treatment options are showing contradictory results. It is known that viral illnesses can trigger a flare-up of underlying rheumatic disease that was previously in remission. To further complicate the scenario, some of the immunosuppressants have shown to have antiviral properties. This has created dilemma in the light of current COVID-19 crisis, as whether to continue or stop the immunosuppressive agents which could be essential to prevent complications of the rheumatic diseases including organ failure but also there is concern about acquiring COVID-19 or developing serious infection. Until we get an effective vaccine, immunosuppressant management for rheumatic diseases as well as other autoimmune diseases and transplants will pose difficult questions. This article is an attempt to review and understand COVID-19 and its impact on the immune system with special emphasis on managing medications used for autoimmune rheumatic diseases. We have provided general guidance about decision making, in regards to the immunosuppressive agents used in rheumatology practice with an understanding that this may change in near future.

Awareness and knowledge of ocular prophylactic measures and hand hygiene among medical students in the wake of the pandemic- COVID 19

Objective: To assesses the awareness and knowledge of ocular prophylaxis, hand hygiene, and ocular surface as a mode of spread of SARS-CoV-2 among medical students, in the wake of the pandemic COVID-19. Methods: A cross-sectional questionnaire-based study was conducted on 248 medical students. The questionnaire is constructed based on previous publications related to hand hygiene and ocular hygiene. The answers to all the questions were assessed and results were analyzed. Results: Out of the 248 people who were included in the study, 99.2% were aware of the importance of handwashing and 97.6% of them agreed that handwashing is required after examining every patient. 85.5% of the participants agreed that the ophthalmologist needs to wear N95 masks during the slit-lamp examination and 92.9% of the students were aware of the need for protective eye goggles. 85.9% agreed that the patients also need to wear protective masks while being examined.74.3% of the participants knew the moments of handwashing, 60.2% knew the correct number of steps of handwashing. 87.6% answered that the slit lamp should be cleaned after every patient. Only 36.5% of the students who participated knew that non-contact tonometry will produce aerosols. The Internet was the most important source of information in about 27% of the participants. Conclusion: Medical students’ knowledge about COVID-19 and the prophylactic measures needs reinforcement. This is essential to safeguard the health of the medical professionals against less understood and remote routes of viral spread.

AN INSIGHT INTO AYURVEDIC VIEW OF SARS -COVID – 19

The Covid - 19 pandemic is defining the global health crisis of our time and occurs to be the greatest chal-lenge. The number of people getting affected and deaths are raising daily throughout the world. COVID-19 is the infectious disease caused by the most recently discovered Corona virus. The situation is much more than a health crisis with a potential to create devastating situations at social, economic, and political levels. Till date, no effective management to address this infection has been identified and attempts are being made to integrate a few traditional interventions along with standard treatment protocols of COVID-19. Ayurveda’s extensive knowledge is based on preventive care, health measures and boosting immunity. Contribution of Ayurveda in the management of various communicable and non-communicable diseases cannot be undermined. Through its wider concepts and treatment modalities, it has greater potential to ad-dress such situations. Awareness about the mode of spread of this disease is recommended highly to pre-vent oneself from falling prey to the disease. The large resource of time-tested traditional knowledge has to be used for the benefit of mankind. In addition to the personal hygiene and social distancing measures, it is of immense importance to improve individual’s natural defence system (immunity). Ayurveda can play a major role in mitigating the spread of COVID -19 by implementing some lifestyle changes along with sim-ple herbal medications and procedures by properly classifying and distinguishing the stage of the disease.

Armamentarium for Reduction of Transmission of COVID-19 Infection in Dental Operatory

The Pandemic of Novel Corona Virus Disease which emerged in December 2019 in WUHAN city is having an overshadowing impact on everyone’s life. Its mode of spread is primarily through droplets of saliva or discharge from the nose when an infected person coughs or sneezes. Research labs are joining forces to find a therapy and a preventive vaccine. Preventive and extraordinary safety measures are crucial to reducing the spread of SARS-CoV-2(severe acute respiratory syndrome coronavirus 2) among health care professionals (HCP). HCP performing or assisting aerosol-generating procedures are classified as ‘very high exposure risk’ workers. Dentists are one among higher risk HCP as they deal with oral cavity problems. This is because most of the procedures are involved with aerosol production in dentistry and saliva is the best medium for the dwelling of Covid-19. So, along with the use of standard preventive measures in reducing the transmission of COVID -19 it is essential for dental offices to change the operating modes. As we all know ‘Prevention is better than cure’ In this article, we reviewedauxiliary armamentariums required for prevention of transmission of Covid-19 infection to be used by dental health care professionals while providing urgent dental care to the patients. Currently, in the absence of a rapid diagnostic device with high sensitivity/ specificity and without an effective therapy or vaccine against SARS-CoV2, it is strongly recommended to treat each patient as a COVID-19 positive. So that Appropriate safety measures will protect both dental professionals and patients in transmitting this pandemic disease.

Corona Virus (COVID-19) Awareness Assessment - A Survey Study Amongst the Indian Population

Aim: The aim of this survey study was to assess the level of awareness amongst Indian population regarding the COVID-19. Method: A survey was conducted amongst 745 individuals to assess their level of awareness regarding COVID-19 and steps to be taken for its prevention. Result: The results revealed that a considerable percentage of individuals learned about the pandemic through social media and news and were aware of the mode of spread of the virus and also steps to be taken to prevent it from spreading. But considerable percentage of people was also not fully aware regarding the age groups this virus will be affecting. Conclusion: Upon understanding the percentage of people not aware about the age groups this virus will be affecting, keeping in mind good amount of knowledge amongst individuals about maintaining hygiene and social distancing, this survey would help the health care workers to create awareness regarding the effect of this virus on different age groups to help prevent carelessness amongst youth in following the regime.

Effects of Ambient Parameters and Sample Width on Upward Flame Spread over Thermally Thin Solids

Upward flame spread is the most rapid and hazardous of the different modes of flame spread. Moreover, studies on the effects of ambient parameters on flame spread are very important for fire safety on spacecraft systems. Therefore, the effects of pressure (0 kPa to 70 kPa), oxygen mole fraction (0.30 to 0.90) and sample width (0.3 cm to 2 cm) on upward flame spread over thin papers were studied. A flame break-off phenomenon over papers was firstly observed, which occurred more likely at high oxygen and high pressure conditions. Upward flame spread reached a steady state by varying the ambient parameters and using narrow samples. The smaller sample width narrowed the flammability limits. Differences in upward and downward flame spread were discussed. We found that a power law relationship between flame spread rate and pressure remained valid near the extinction limit for upward spread, while the power law broke down in the extinction region for downward spread. The controlling mechanism of upward spread was revealed by a pressure modeling method showing that the upward flame spread rate was proportional to the Grashof number raised to an exponent of 0.257. For upward flame spread over narrow solids, the gas phase kinetics and radiation effects are less important compared to the heat convection in the flame spread process, which is quite different from the downward spread. This study contributes to the fire safety of space vehicles and enhances the understanding of the controlling mechanism of flame spread.

Macrophage Cell-Cell Interactions Promoting HIV-1 Infection.

Many pathogens infect macrophages as part of their intracellular life cycle. This is particularly true for viruses, of which HIV-1 is one of the best studied. HIV-1 infection of macrophages has important consequences for viral persistence and pathogenesis, but the mechanisms of macrophage infection remain to be fully elucidated. Despite expressing viral entry receptors, macrophages are inefficiently infected by cell-free HIV-1 virions, whereas direct cell-cell spread is more efficient. Different modes of cell-cell spread have been described, including the uptake by macrophages of infected T cells and the fusion of infected T cells with macrophages, both leading to macrophage infection. Cell-cell spread can also transmit HIV-1 between macrophages and from macrophages to T cells. Here, we describe the current state of the field concerning the cell-cell spread of HIV-1 to and from macrophages, discuss mechanisms, and highlight potential in vivo relevance.

Two Months of COVID-19 Pandemic in Nigeria: Distribution and responses of the Nigerian Media

This study reviewed the distribution of and Nigerian Media responses to the COVID-19 pandemic within the first two months (February 27 to April 30 2020) of its outbreak in Nigeria. Using data collected from the websites of the Nigeria Centre for Disease Control, NCDC and Worldometer, and analysed in simple percentages and presented in tables and charts, the study showed that by April 30, 2020, the total confirmed, active, recovered and death cases stood at 1932, 1555, 319 and 58 respectively; an indication of an alarming spread. The distribution of the disease saw Lagos (epicentre of the disease), Kano and FCT collectively accounting for 71.07% of confirmed cases, 71.45% of active, 73.67% of death, and 46.55% of recovered cases. The initial mode of spread was through contact; however, as of April 30, 2020, 79% of new cases were through contact and incomplete epidemiological link; an indication of possible community transmission. The Nigerian media responded adequately and aggressively to the outbreak by setting the agenda and providing regular updates of government, private and individual efforts in containing the spread of the disease. By the conclusion of this study, over 40 healthcare workers had tested positive to SARS-CoV-2; thus, challenging the government to intensify efforts in curbing community transmission by ensuring effective contact tracing, testing, isolation and treatment. How to cite this article:Izah SC, Iniamagha I, Sylva L. Two Months of COVID-19 Pandemic in Nigeria: Distribution and responses of the Nigerian Media. Epidem Int 2020; 5(1): 32-44. DOI: https://doi.org/10.24321/2455.7048.202015

Resectional surgery for malignant disease of abdominal digestive organs is not surgery of the organ itself, but also that of the mesenteric organ

Despite large strides in molecular oncology, surgery remains the bedrock in the management of visceral cancer. The primacy of surgery cannot be understated and a mesenteric (i.e. ontogenetic) approach is particularly beneficial to patients. Heald greatly advanced the management of rectal cancer with his description of the anatomical foundation of total mesorectal excision (TME), dramatically improving outcomes worldwide with this mesenteric-based approach. Moreover, complete mesocolic excision (CME) based on similar principles is becoming popular. Introduced by Hohenberger, CME resembles TME insofar as it emphasises strictly anatomical dissection along embryological planes to detach an intact (i.e. “complete”) mesentery with peritoneal envelope. CME also incorporates “central” vascular ligation (CVL) which broadly correlates with the “D3 lymphadenectomy” of Eastern literature. As many surgeons already practise anatomical and mesenteric-based surgery, it is unclear how the putative benefits of CME (including CVL) arise. Herein, we argue that these may relate to a more extensive resection of the mesentery, and thus mesenteric tumour deposits within the connective tissue lattice of the mesentery, and not necessarily the lymphadenectomy alone. We believe the connective tissue interface between the bowel wall and mesentery provides an alternative mode of spread of pathogenic elements. Whilst this remains a suggestion only, it would explain the histological independence of tumour deposits and why a greater mesenterectomy could be associated with benefits in survival. If this argument holds, it follows that resectional surgery for digestive organ malignancy is not surgery of the organ itself (or lymphatics only), but also that of the contiguous mesentery.

MicroRNA-200 family governs ovarian inclusion cyst formation and mode of ovarian cancer spread.

Epidemiologic and histopathologic findings and the laying hen model support the long-standing incessant ovulation hypothesis and cortical inclusion cyst involvement in sporadic ovarian cancer development. MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. Herewith, we show that ovarian surface epithelial (OSE) cells with ectopic miR-200 expression formed stabilized cysts in three-dimensional (3D) organotypic culture with E-cadherin fragment expression and steroid hormone pathway activation, whereas ovarian cancer 3D cultures with miR-200 knockdown showed elevated TGF-β expression, mitotic spindle disorientation, increased lumenization, disruption of ROCK-mediated myosin II phosphorylation, and SRC signaling, which led to histotype-dependent loss of collective movement in tumor spread. Gene expression profiling revealed that epithelial-mesenchymal transition and hypoxia were the top enriched gene sets regulated by miR-200 in both OSE and ovarian cancer cells. The molecular changes uncovered by the in vitro studies were verified in both human and laying hen ovarian cysts and tumor specimens. As miR-200 is also essential for ovulation, our results of estrogen pathway activation in miR-200-expressing OSE cells add another intriguing link between incessant ovulation and ovarian carcinogenesis.

Effect of synaptic cell-to-cell transmission and recombination on the evolution of double mutants in HIV.

Recombination in HIV infection can impact virus evolution in vivo in complex ways, as has been shown both experimentally and mathematically. The effect of free virus versus synaptic, cell-to-cell transmission on the evolution of double mutants, however, has not been investigated. Here, we do so by using a stochastic agent-based model. Consistent with data, we assume spatial constraints for synaptic but not for free-virus transmission. Two important effects of the viral spread mode are observed: (i) for disadvantageous mutants, synaptic transmission protects against detrimental effects of recombination on double mutant persistence. Under free virus transmission, recombination increases double mutant levels for negative epistasis, but reduces them for positive epistasis. This reduction for positive epistasis is much diminished under predominantly synaptic transmission, and recombination can, in fact, lead to increased mutant levels. (ii) The mode of virus spread also directly influences the evolutionary fate of double mutants. For disadvantageous mutants, double mutant production is the predominant driving force, and hence synaptic transmission leads to highest double mutant levels due to increased transmission efficiency. For advantageous mutants, double mutant spread is the most important force, and hence free virus transmission leads to fastest invasion due to better mixing. For neutral mutants, both production and spread of double mutants are important, and hence an optimal mixture of free virus and synaptic transmission maximizes double mutant fractions. Therefore, both free virus and synaptic transmission can enhance or delay double mutant evolution. Implications for drug resistance in HIV are discussed.