CROI 2023: Epidemiology, Diagnosis, and Management of MPox.

The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) emphasized emerging infectious diseases such as COVID-19 and mpox. Despite emerging from countries in which it was endemic only 9 months before the conference, mpox was well covered, with more than 60 presentations addressing various topics. There was a focus on the rapid development and implementation of tests to reduce the time to diagnosis, as well as multiplex panels to increase the accuracy of differential diagnosis. Presenters also highlighted the ability to diagnose mpox from multiple compartments, such as with rectal and pharyngeal swabs, and provided crucial information on the duration of positivity that may impact isolation requirements. Clinical experiences were described, including risk factors for severe disease and syndemic management. High rates of concomitant sexually transmitted infection (STI) were reported. Finally, prevention was a key topic, with presenters pointing to the contributions of individual behavioral changes and vaccine efficacy to reducing new cases.

Research Note: Simultaneous detection of infectious laryngotracheitis virus, fowlpox virus, and reticuloendotheliosis virus in chicken specimens.

Infectious laryngotracheitis (ILT), fowlpox (FP), and reticuloendotheliosis are important poultry diseases caused by gallid herpesvirus 1 (ILTV), fowlpox virus (FWPV), and reticuloendotheliosis virus (REV), respectively. Coinfections with ILTV and FWPV occur naturally in chickens, and FP in its more virulent wet form is characterized by diphtheritic lesions and easily confused with ILT. Moreover, the insertion of only partial REV-LTR or a nearly full-length REV into the FWPV genome, located between the ORF 201 and ORF 203, has increased recently in wild-type field FWPV isolates. Therefore, it is critical to detect ILTV, FWPV, REV-integrated FWPV, and REV early and accurately. In this study, we successfully developed a multiplex PCR assay for the simultaneous detection of ILTV, FWPV, REV-integrated FWPV, and REV, and the detection limits was 1 × 54 copies/tube. When used to test clinical samples, the results of the multiplex PCR were in 100% agreement with singleplex PCRs and sequencing. This new multiplex PCR is a simple, rapid, sensitive, specific, and cost-effective method for detection of 4 viruses in clinical specimens.

Virtual CROI 2020: Highlights of Epidemiology, Public Health, and Prevention Research.

At the 2020 Conference on Retroviruses and Opportunistic Infections, held virtually as a result of the emerging COVID-19 pandemic, trends in the HIV epidemic were highlighted, with decreasing HIV incidence reported across several countries, although key regions remain heavily impacted, including the US South. Adolescent girls and young women, men who have sex with men (MSM), transgender persons, and people who inject drugs continue to experience a high burden of new infections. Sexually transmitted infections during pregnancy can lead to a number of adverse outcomes in infants; novel strategies to detect and treat these infections are needed. Innovative HIV testing strategies, including self-testing and assisted partner services, are expanding the reach of testing; however, linkage to care can be improved. Novel preexposure prophylaxis (PrEP) delivery strategies are increasing uptake of PrEP in different groups, although adherence and persistence remain a challenge. Use of on-demand PrEP is increasing among MSM in the US. Strategies are needed to address barriers to PrEP uptake and persistence among cis- and transgender women. Several novel regimens for postexposure prophylaxis show promise.

Assessment of porcine endogenous retrovirus transmission across an alginate barrier used for the encapsulation of porcine islets.

BACKGROUND: Subcutaneous implantation of a macroencapsulated patch containing human allogenic islets has been successfully used to alleviate type 1 diabetes mellitus (T1DM) in a human recipient without the need for immunosuppression. The use of encapsulated porcine islets to treat T1DM has also been reported. Although no evidence of pathogen transfer using this technology has been reported to date, we deemed it appropriate to determine if the encapsulation technology would prevent the release of virus, in particular, the porcine endogenous retrovirus (PERV). METHODS: HEK293 (human epithelial kidney) and swine testis (ST) cells were co-cultured with macroencapsulated pig islets embedded in an alginate patch, macroencapsulated PK15 (swine kidney epithelial) cells embedded in an alginate patch and free PK15 cells. Cells and supernatant were harvested at weekly time points from the cultures for up to 60 days and screened for evidence of PERV release using qRT-PCR to detect PERV RNA and SG-PERT to detect reverse transcriptase (RT). RESULTS: No PERV virus, or evidence of PERV replication, was detected in the culture medium of HEK293 or pig cells cultured with encapsulated porcine islets. Increased PERV activity relative to the background was not detected in ST cells cultured with encapsulated PK15 cells. However, PERV was detected in 1 of the 3 experimental replicates of HEK293 cells cultured with encapsulated PK15 cells. Both HEK293 and ST cells cultured with free PK15 cells showed an increase in RT detection. CONCLUSIONS: With the exception of 1 replicate, there does not appear to be evidence of transmission of replication competent PERV from the encapsulated islet cells or the positive control PK15 cells across the alginate barrier. The detection of PERV would suggest the alginate barrier of this replicate may have become compromised, emphasizing the importance of quality control when producing encapsulated islet patches.

Epidemiologic survey of feline leukemia virus in domestic cats on Tsushima Island, Japan: management strategy for Tsushima leopard cats.

The Tsushima leopard cat (TLC) Prionailurus bengalensis euptilurus, a subspecies of P. bengalensis, is designated a National Natural Monument of Japan, and lives only on Tsushima Island, Nagasaki Prefecture, Japan. TLCs are threatened by various infectious diseases. Feline leukemia virus (FeLV) causes a serious infectious disease with a poor prognosis in cats. Therefore, the transmission of FeLV from Tsushima domestic cats (TDCs) to TLCs may threaten the TLC population. We investigated the FeLV infection status of both TDCs and TLCs on Tsushima Island by screening blood samples for FeLV p27 antigen and using PCR to amplify the full-length FeLV env gene. The prevalence of FeLV was 6.4% in TDCs and 0% in TLCs. We also demonstrated that the virus can replicate in the cells of TLCs, suggesting its potential cross-species transmission. The viruses in TDCs were classified as genotype I/clade 3, which is prevalent on a nearby island, based on previous studies of FeLV genotypes and FeLV epidemiology. The FeLV viruses identified on Tsushima Island can be further divided into 2 lineages within genotype I/clade 3, which are geographically separated in Kamijima and Shimojima, indicating that FeLV may have been transmitted to Tsushima Island at least twice. Monitoring FeLV infection in the TDC and TLC populations is highly recommended as part of the TLC surveillance and management strategy.

Differences in the Prediction of Area Under the Curve for a Protease Inhibitor Using Trough Versus Peak Concentration: Assessment Using Published Pharmacokinetic Data for Indinavir.

In the present day antiretroviral therapy, Ctrough is a key tool for efficacy assessment. The present work explored the feasibility of using Ctrough or Cmax in the area under the concentration-time curve (AUC) prediction of indinavir. A simple unweighted linear regression model was developed to describe the relationship between Cmax versus AUC (r = 0.8101, P < 0.001) and Ctrough versus AUC (r = 0.8127, P < 0.001) for indinavir. The regression lines were used to predict the AUC values from literature Cmax or Ctrough data of indinavir in HIV and healthy subjects. The fold difference, defined as the quotient of the observed and predicted AUC values, was evaluated along with statistical comparison, including root mean square error (RMSE) prediction for the 2 models. The correlation between Cmax versus AUC and Ctrough versus AUC was established. Majority of the predicted values for Cmax versus AUC were within 0.75- to 1.5-fold differences. However, the Ctrough versus AUC model showed larger variability with approximately one-third of the predictions within 0.75- to 1.5-fold differences. The r value and %RMSE for observed versus predicted AUC for Ctrough (r = 0.5925, n = 65, P < 0.001, and RMSE: 67%) were inferior to the Cmax (r = 0.8773, n = 86, P < 0.001, and RMSE: 46%). In conclusion, Cmax versus AUC and Ctrough versus AUC relationships were established for indinavir showing the utility of a single concentration time point for therapeutic drug monitoring purpose. The Cmax model for indinavir may be more relevant for AUC prediction as determined by the statistical criteria.

Assessment of antiretroviral treatment (ART) care service provision in Tigray Region health centers, North Ethiopia.

BACKGROUND: Client satisfaction is a vital component and main concern intertwined with strategic decisions in service provisions. To improve efficiency of services, eliciting the opinion of users about the available services and identifying factors associated with dissatisfaction is very critical. Thus, the main objective of this study was to assess the perceived levels of clients' satisfaction with health services at ART clinic level in health centres of Tigray Region in Ethiopia. METHODS: Cross sectional study was conducted from May to June 2013 in Tigray Region ART clinics. A total of 714 ART care user were included in the study using both purposive and probability sampling technique. Data was collected by using structured questionnaire and the collected data was analysed using Statistical Package for the Social Sciences (SPSS) version 16.0. Crude and Adjusted logistic regression analyses were carried out to identify the associated factors underlying perceived levels of clients' overall satisfaction. Finally, the results were presented with table as well as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 714 study participants were enrolled in this study. An overall satisfaction level of 89.6% was reported by ART care service users. Higher scores of satisfaction of services provisions were reported for courtesy and respect (95.80%) followed by privacy (93.28%). On the other hand, respondents' dissatisfaction was rated 35.32% for toilet cleanliness followed by 26.19% for availability of additional drugs. As for overall satisfaction and associated factors, adjusted logistic regression analyses showed that marital status [AOR = 2.01 (95% CI: 1.11, 3.60)], educational status [AOR = 3.13 (95% CI: 1.15, 8.53)], travel distance to reach health centre [AOR = 3.59 (95% CI: 1.23, 10.50)], toilet cleanliness [AOR = 2.22 (95% CI :1.62, 6.32)], and ART drug availability [AOR = 2.60 (95% CI :1.18, 6.52)] were found to have influence on overall ART service satisfaction status. CONCLUSIONS: This study revealed high level of client satisfaction rate and were associated with preventable and modifiable factors such as marital status, educational status, travel distance to reach health centre, toilet cleanliness and ART drug availability. Therefore, countermeasures such as increasing access to ART service, availing clean toilet and ART drugs may further increase client satisfaction level in the region.

The ecology of primate retroviruses - an assessment of 12 years of retroviral studies in the Taï national park area, Côte d׳Ivoire.

The existence and genetic make-up of most primate retroviruses was revealed by studies of bushmeat and fecal samples from unhabituated primate communities. For these, detailed data on intra- and within-species contact rates are generally missing, which makes identification of factors influencing transmission a challenging task. Here we present an assessment of 12 years of research on primate retroviruses in the Taï National Park area, Côte d'Ivoire. We discuss insights gained into the prevalence, within- and cross-species transmission of primate retroviruses (including towards local human populations) and the importance of virus-host interactions in determining cross-species transmission risk. Finally we discuss how retroviruses ecology and evolution may change in a shifting environment and identify avenues for future research.

The use of preliminary scientific evidence in public health: a case study of XMRV.

Kumanan Wilson and colleagues explain how the rapid response to XMRV as a novel pathogen has highlighted some challenges pertaining to policy-making and editorial responsibilities. The impact on policy and the propagation of the initial scientific information may not cease if the evidence is disproven and retracted from the peer-reviewed literature, which creates a challenge for regulators and scientific journals. Please see later in the article for the Editors' Summary.

Occurrence of antibodies against Maedi-Visna in Santa Inês sheep in the State of Sergipe, Brazil / Ocorrência de anticorpos contra o virus Maedi-Visna em ovinos Santa Inês, no Estado de Sergipe, Brasil

Small Ruminant Lentiviruses (SRLV) are infectious diseases of viral etiology caused by retroviruses, characterized for being a slowly progressive degenerative disease. The aim of this study was to determine the occcurrence of antibodies against lentivirus in the flock of Santa Inês sheep in Sergipe, Brazil. A minimum number of samples was analyzed by the Astudillo calculation, with an expected prevalence (p) of 10%, error rate (;) of 20% and confidence level of 95% (g = 1.96) obtaining the minimum number of samples (n) of 861. Finally, 941 serum samples were collected, derived from 54 properties and 19 municipalities distributed in three regions of the State, and the number of collected samples was proportional to the sheep flock of each municipality. The serum was placed at -20°C until the Agar Gel Immunodiffusion test (AGID), and results considered as positive or suspicious in AGID were assessed by the Western blotting technique. Out of sampled animals, 194 (20.62%) were male and 747 (79.38%) were female. From the stratification by age, 300 were young sheep (31.88%), aged between six months and one year old, 308 (32.73%) were young adults, aged between 1 and 3 years old, and 333 (35.39%) were estimated to be older than three years old. Results showed that antibodies against the Maedi-Visna virus in the sheep flock occcurred in the State of Sergipe at low frequency (0.11%). Thus, the occcurrence of Maedi-Visna infection in sheep in the State of Sergipe is reported, and emphasizes the participation of the transit of animals in the epidemiology of the disease.

As Lentiviroses de Pequenos Ruminantes (LVPR) são enfermidades infecciosas de etiologia viral causadas por retrovírus, caracterizadas por uma doença de degeneração progressiva e lenta. O objetivo deste estudo foi determinar a ocorrência de anticorpos contra o lentivírus no rebanho ovino Santa Inês, de Sergipe. Para analisar o número mínimo de amostras utilizou-se o cálculo de Astudillo, com prevalência esperada (p) de 10%, margem de erro (;) de 20% e grau de confiança de 95% (g = 1,96), obtendo-se o número mínimo de amostras (n) de 861. Foram colhidas 941 amostras de soro ovino oriundas de 54 propriedades e 19 municípios distribuídos nas três mesorregiões do Estado, sendo o número de amostras proporcional ao efetivo ovino do município. O soro foi acondicionado a -20°C até a realização do teste de Imunodifusão em Gel de Ágar (IDGA). Os resultados considerados positivos ou suspeitos na IDGA foram reavaliados através da técnica de Western blotting. Dos animais amostrados, 194 (20,62%) eram machos e 747 (79,38%) eram fêmeas. Quanto à estratificação por idade, 300 ovinos eram jovens (31,88%), entre seis meses e um ano, 308 (32,73%) eram jovens adultos, entre 1 e 3 anos, e 333 (35,39%) tinham idade estimada superior a 3 anos. Os resultados obtidos demonstraram que anticorpos contra o vírus Maedi-Visna (MVV) ocorrem no rebanho ovino do estado de Sergipe em baixa frequência (0,11%). Assim, relata-se a ocorrência da infecção por Maedi-Visna em ovinos no estado de Sergipe e ressalta-se a participação do trânsito de animais na epidemiologia da doença.

Within-host demographic fluctuations and correlations in early retroviral infection.

In this paper we analyze the demographic fluctuations and correlations present in within-host populations of viruses and their target cells during the early stages of infection. In particular, we present an exact treatment of a discrete-population, stochastic, continuous-time master equation description of HIV or similar retroviral infection dynamics, employing Monte Carlo simulations. The results of calculations employing Gillespie's direct method clearly demonstrate the importance of considering the microscopic details of the interactions which constitute the macroscopic dynamics. We then employ the τ-leaping approach to study the statistical characteristics of infections involving realistic absolute numbers of within-host viral and cellular populations, before going on to investigate the effect that initial viral population size plays on these characteristics. Our main conclusion is that cross-correlations between infected cell and virion populations alter dramatically over the course of the infection. We suggest that these statistical correlations offer a novel and robust signature for the acute phase of retroviral infection.

Simian foamy virus infection in humans: prevalence and management.

Simian foamy viruses (SFVs) are highly prevalent in all nonhuman primate species and can infect humans following occupational and non-occupational exposure to infected animals and their tissues, blood or body fluids. Virus transmission results in a stable, persistent infection that seems to be latent. SFV infections are thus far nonpathogenic, with no evidence of adverse clinical outcome in their natural nonhuman primate hosts or by experimental injection in animals and upon cross-species transmission in humans. Since the emergence of pathogenic viruses from nonpathogenic viruses upon cross-species infection is well-documented for several retroviruses, it is prudent to take necessary precautions to deter SFV infections in humans. These steps will help prevent the emergence of a novel pathogen and reduce the risk of transmission of another potential pathogenic human retrovirus.

Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro.

Biphalin, a dimeric enkephalin analog, is under investigation as a potential, long-lasting medication of pain associated with chronic diseases, like cancer or AIDS. The role of cytokines, and splenocytes in anti-Friend leukemia virus (FLV) activity of biphalin, a synthetic opioid, and AZT was investigated in vitro. Mouse splenocytes inhibited FLV replication in Mus dunni (Dunni) cells when they were added to the cell culture. This inhibitory effect of splenocytes also was evident when cells were combined with biphalin and AZT as measured using a focus-forming assay. Under cell-free conditions, recombinant interferon gamma (IFNgamma), interleukin 2 (IL-2) and IL-4 directly inhibited the FLV reverse transcriptase (RT) activity by 27% to 36%. IFNgamma at 0.005 pg to 500 ng inhibited FLVRT activity by 61% to 80%. Acombination of 250 ng IFNgamma and 50 mug biphalin resulted in a 94% reduction of FLVRT activity, as compared with 61% inhibition by IFNgamma alone. The combination of AZT and IFNgamma, IL-2 or IL-4 also induced a stronger suppression of FLV RT activity than either cytokine or AZT used alone. In addition, cloned RT from Moloney murine leukemia virus (MMLV) was directly sensitive to inhibition by biphalin. Thus, the anti-FLV effects of splenocytes in combination with biphalin and AZT in cell culture are likely mediated to a large degree by the direct effect of cytokines. This antiviral activity of splenocytes or cytokines combined with chemotherapy, biphalin, and/or AZT, could be used as a complementary therapy to current approaches for retroviral infection and benefit acquired immunodeficiency syndrome (AIDS) patients. In conclusion, biphalin applied primarily as a new medicine for chronic pain treatment in AIDS patients may play a significant beneficial role as a component of antiviral HIV multidrug therapies.

Risk assessment: A model for predicting cross-species transmission of simian foamy virus from macaques (M. fascicularis) to humans at a monkey temple in Bali, Indonesia.

Contact between humans and nonhuman primates (NHPs) frequently occurs at monkey temples (religious sites that have become associated with free-ranging populations of NHPs) in Asia, creating the potential for NHP-human disease transmission. In March 2003 a multidisciplinary panel of experts participated in a workshop designed to model the risk of NHP-human pathogen transmission. The panel developed a risk assessment model to describe the likelihood of cross-species transmission of simian foamy virus (SFV) from temple macaques (Macaca fascicularis) to visitors at monkey temples. SFV is an enzootic simian retrovirus that has been shown to be transmitted from NHPs to humans. In operationalizing the model field data, laboratory data and expert opinions were used to estimate the likelihood of SFV transmission within this context. This model sets the stage for a discussion about modeling as a risk assessment tool and the kinds of data that are required to accurately predict transmission.

[Analysis of antiretroviral drugs-induced adverse effects]. / Analyse des effets indésirables des médicaments du VIH.

In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.

[Ecology and social organization of African tropical forest primates: aid in understanding retrovirus transmission]. / Ecologie et organisation sociale des primates de la forêt tropicale africaine: aide à la compréhension de la transmission des rétrovirus.

The risk of transmission of primate viruses to humans is great because of their genetic proximity. It is now clear that the HIV group of retroviruses came from primates and that the origin of HIV1 is the chimpanzee subspecies of Central Africa, Pan troglodytes troglodytes. Many African primates are natural hosts of retroviruses and details of the natural history of both hosts and viruses are essential to understand the evolution of the latter. Data on the demography, ecology and behaviour of three species of primates (gorillas, chimpanzees and mandrills), studied in the Lopé Reserve in Central Gabon since 1983, are analysed to identify the factors that allow, or favour, disease transmission within each species, between different species and between primates and humans. The comparison of the relative degree of risk suggests that of the three species, chimpanzees are the most susceptible to exposure to infection both from conspecifics and from other species. With respect to humans, the comparative analysis suggests greater exposure to viruses of mandrills and gorillas than to those of chimpanzees. For primates, major risk factors are: large social groups; bites inflicted in fights; social grooming; and predation on mammals. However, given that contacts between social groups of the same species are rare, the spread of a virus through a population will be slow and uncertain. Hunting wild animals is the behaviour most likely to provide transmission routes for primate viruses into human populations because of the high probability of blood-blood contact. Not only the hunters themselves, but also women who prepare bush meat for cooking and people involved in trade of carcasses are at high risk of transmission of pathogens. Hunting of bush meat is increasing in Central Africa due to the economic recession and the spread of logging into the forests of the interior of the region. To counter the significant risk of transmission of known, as well as new, diseases from primates to humans, urgent measures are needed to attack the root causes of commercial hunting which is not only risk to public health but also a serious threat to biodiversity in the region.