Projecting the development of antimicrobial resistance in Neisseria gonorrhoeae from antimicrobial surveillance data: a mathematical modelling study.

BACKGROUND: The World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when ≥ 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae. METHODS: We used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000-2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution. RESULTS: The single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected ≥ 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7-44.8%) among HMW and 19.6% (95%CrI: 2.6-54.4%) among MSM by 2030. CONCLUSIONS: New first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.

Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Decreased Neisseria gonorrhoeae genotypic diversity following COVID-19 restrictions in Queensland, Australia 2020.

We investigated the potential effects of COVID-19 public health restrictions on the prevalence and distribution of Neisseria gonorrhoeae (NG) genotypes in our Queensland isolate population in the first half of the year 2020. A total of 763 NG isolates were genotyped to examine gonococcal strain distribution and prevalence for the first 6 months of 2020, with 1 January 2020 to 31 March 2020 classified as 'pre' COVID-19 restrictions (n = 463) and 1 April 2020 to 30 June 2020 classified as 'post' COVID-19 restrictions (n = 300). Genotypes most prevalent 'pre' restrictions remained proportionally high 'post' restrictions, with some significantly increasing 'post' restrictions. However, genotype diversity was significantly reduced 'post' restrictions. Overall, it seems public health restrictions (9-10 weeks) were not sufficient to affect rates of infection or reduce the prevalence of well-established genotypes in our population, potentially due to reduced access to services or health-seeking behaviours.

Conductive Ink-Coated Paper-Based Supersandwich DNA Biosensor for Ultrasensitive Detection of Neisseria gonorrhoeae.

Herein, we report results of the studies relating to the development of an impedimetric, magnetic bead-assisted supersandwich DNA hybridization assay for ultrasensitive detection of Neisseria gonorrhoeae, the causative agent of a sexually transmitted infection (STI), gonorrhea. First, a conductive ink was formulated by homogenously dispersing carboxylated multiwalled carbon nanotubes (cMWCNTs) in a stable emulsion of terpineol and an aqueous suspension of carboxymethyl cellulose (CMC). The ink, labeled C5, was coated onto paper substrates to fabricate C5@paper conductive electrodes. Thereafter, a magnetic bead (MB)-assisted supersandwich DNA hybridization assay was optimized against the porA pseudogene of N. gonorrhoeae. For this purpose, a pair of specific 5' aminated capture probes (SCP) and supersandwich detector probes (SDP) was designed, which allowed the enrichment of target gonorrheal DNA sequence from a milieu of substances. The SD probe was designed such that instead of 1:1 binding, it allowed the binding of more than one T strand, leading to a 'ladder-like' DNA supersandwich structure. The MB-assisted supersandwich assay was integrated into the C5@paper electrodes for electrochemical analysis. The C5@paper electrodes were found to be highly conductive by a four-probe conductivity method (maximum conductivity of 10.1 S·cm-1). Further, the biosensing assay displayed a wide linear range of 100 aM-100 nM (109 orders of magnitude) with an excellent sensitivity of 22.6 kΩ·(log[concentration])-1. The clinical applicability of the biosensing assay was assessed by detecting genomic DNA extracted from N. gonorrhoeae in the presence of DNA from different non-gonorrheal bacterial species. In conclusion, this study demonstrates a highly sensitive, cost-effective, and label-free paper-based device for STI diagnostics. The ink formulation prepared for the study was found to be highly thixotropic, which indicates that the paper electrodes can be screen-printed in a reproducible and scalable manner.

Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study.

BACKGROUND: In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission. METHODS: Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model. RESULTS: We included 366 participants. Median follow-up was 47 months (IQR 43-50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)). CONCLUSION: Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.

Increased clonality among Neisseria gonorrhoeae isolates during the COVID-19 pandemic in Amsterdam, the Netherlands.

Distancing measures during the COVID-19 lockdown led to a temporary decrease of casual sex partners among clients of the Centre for Sexual Health (CSH) in Amsterdam, the Netherlands. We investigated the effect of this change on the genotypic and phenotypic distribution of Neisseria gonorrhoeae (Ng) isolates from CSH patients. From each Ng-positive patient we sequenced one isolate, resulting in 322 isolates which constituted two groups: 181 isolates cultured from 15 January to 29 February 2020 (before the first lockdown) and 141 cultured from 15 May to 30 June 2020 (during the first lockdown). Patient characteristics showed significantly more symptomatic patients and significantly fewer reported sex partners during the lockdown. Phenotypic data showed an increase in low-level azithromycin resistance and ceftriaxone susceptibility during the lockdown, and this remained after the study period. The diversity in sequence types (STs) decreased slightly during the lockdown. A shift occurred from ST 8156 being predominant before lockdown to ST 9362 during lockdown and a remarkably low median SNP distance of 17 SNPs was found between ST 9362 isolates obtained during lockdown. These findings reflect restricted travel and the change in sexual behaviour of CSH clients during the lockdown, with a potentially increased local transmission of the ST 9362 strain during this period, which led to genotypic and phenotypic changes in the Ng population. This shows that public health measures have far-reaching consequences and should be considered in the surveillance of other infectious diseases.

50. Creating Adolescent-centered Sexual and Reproductive Care for a Mobile Health Unit

Purpose: Exacerbated by the COVID-19 pandemic, adolescents from structurally marginalized communities face barriers to accessing sexual and reproductive health (SRH) care. Mobile health units (MHUs) may be effective in reaching these adolescents but few studies have assessed their feasibility in this population. Methods: We assessed the feasibility of an MHU to provide SRH care to adolescents in community settings. Adolescents were invited to community demonstrations of hypothetical MHU care ("Demonstration events”). Adolescents completed surveys (demographics, likelihood of future MHU-based care, and access to health care) and staff documented field notes. We then partnered with adolescents, health care providers, and community leaders to create adolescent-centered SRH care for MHU delivery ("Clinical events”). Free and confidential services provided on the MHU included contraceptive care, condoms, testing for pregnancy, Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), Syphilis, and Human Immunodeficiency virus (HIV). Initially, we provided electronic prescriptions for contraception during MHU visits. We later designed a system to dispense contraception [I.e., emergency contraception (EC) for future use, combined hormonal oral contraceptives (CHOCs), patches and Medroxyprogesterone] in the MHU. After MHU care, adolescents completed surveys to report satisfaction while staff documented feedback through field notes. Results: At 8 community "Demonstration events”, 98 teens (mean age 15.8 years, 67% female at birth, 17% Genderfluid/Non-Binary/Trans, 49% heterosexual, 24% Hispanic, 49% Black, 40% White) were enrolled. Most (70%) reported no previous vaginal/penile sex. Many (46%) had forgone needed health care in the previous year. Most (77%) said they were very/somewhat likely to get care on the MHU if available in the future and 82% would recommend it to friends. Most thought the MHU would be a great way to increase access to SRH care because it eliminated transportation obstacles and appointment delays. Many felt the MHU would provide adequate privacy and advised bringing the MHU to school or community events. Teens recommended collecting urine specimens in nearby restrooms and using a brown bag to transport them to the MHU. Utilizing their feedback, we partnered with teen-serving community organizations and schools to host the MHU. At two "Clinical events”, we provided care for five patients (4 biologic females, 1 biologic male). Accepted health services included condom provision (n=5) and, pregnancy (n=3), GC/CT (n=4), and Syphilis/HIV (n=2) testing. Two MHU patients received contraceptive prescriptions, one received contraception onsite (EC and CHOCs), and one with a positive CT test was contacted and treated. Four adolescents completed a post-care survey. All (100%) were very satisfied with MHU care and said they would recommend it to a friend. All (100%) agreed/strongly agreed they learned something new about SRH and reported the information was helpful. Field notes revealed patients communicated appreciation for the care, felt comfortable on the MHU, and found school-based SRH care acceptable. We plan to host five additional MHU "Clinical events” (Fall 2022). Conclusions: As COVID-19 continues to negatively impact adolescent SRH care-seeking, our work offers key insights to customizing MHU-based SRH care to meet the unique needs of adolescents from structurally marginalized communities. Sources of Support: Institutional expansion of NIH-funded KL2 program (RB), 3R21HD098086-02S1 (MM), K23HD098299 (KM).

DEVELOPMENT of A MOLECULAR POINT of CARE DETECTION KIT for NEISSERIA GONORRHOEAE

Neisseria gonorrhoeae (NG) is the etiological agent of gonorrhea, one of the four most prevalent sexually transmitted diseases worldwide. The diagnosis of this pathogen is carried out mainly by PCR methodologies, because it is accurate, sensitive and fast. However, it is an expensive technique that is difficult to perform in every health center. Thus, the development of rapid and affordable molecular point-of-care tests (POCT) is very important because it can be applied in isolated places or low complexity centers. Nucleic acid diagnostics generally have three steps: extraction, amplification and visualization. To solve the two last steps, we decided to use an isothermal nucleic acid amplification system coupled to a pH-sensitive dye. In our laboratory (LIGBCM-Laboratory of Genetic Engineering and Cellular and Molecular Biology, of the National University of Quilmes), an isothermal loop-based nucleic acid amplification methodology called Easy Loop Amplification (ELA) was developed. Its application for the diagnosis of both human and veterinary pathogens, showed a great adaptability to different organisms. One of our developed kits was for the detection of SARS CoV-2. In this way, the main objective of this research project is the development of a molecular POCT kit for NG with no need of complex equipment. The development of this kit for NG started with a bioinformatic analysis that allowed the molecular target selection from the genome of NG and afterwards the primer design. With one of the selected target sequences, a positive control was constructed de novo and used for the optimization of the isothermal amplification system. Different reaction parameters were evaluated and optimized (temperature, magnesium concentration, etc.). The specificity and detection limit of ELA were evaluated. The in silico analysis of the primers showed 100% specificity and the detection limit (analyzed by a calibration curve) resulted in less than 1000 molecules. ELA diagnostics of NG showed similar parameters to those found with qPCR techniques. This amplification method could be used with a portable device, allowing the diagnosis in low complexity centers and highlighting its capability to be exploited as a POCT system.

Investigation of Streptomyces sp. Strain EMB24 Secondary Metabolite Profile Has Unraveled Its Extraordinary Antibacterial Potency Against Drug-Resistant Bacteria.

With the overuse and misuse of antibiotics amid COVID-19 pandemic, the antimicrobial resistance, which is already a global challenge, has accelerated its pace significantly. Finding novel and potential antibiotics seems one of the probable solutions. In this work, a novel Streptomyces sp. strain EMB24 was isolated and found to be an excellent source of antimicrobials as confirmed by agar-plug assay. It showed antibacterial activity against infection-causing bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In addition, Streptomyces sp. strain EMB24 inhibited the growth methicillin-resistant Staphylococcus aureus (MRSA), tetracycline-resistant Neisseria gonorrhoeae, and ampicillin-resistant Neisseria gonorrhoeae. Furthermore, to get deep insights about the genome and biosynthetic gene clusters producing antibiotics, whole genome sequencing was done. The strain EMB24 is closely related to the Streptomyces longispororuber as revealed by phylogenetic analysis which is a potential source of antibiotics and pigments as undecylprodigiosin and metacycloprodigiosin belonging to the class prodigiosin. Naphthyridinomycin, alkylresorcinols, desferrioxamine B and E, venezuelin, aborycin, MS-271, and siamycin are potent therapeutics that shared 100% similarity with the reference strain as revealed by the online antiSMASH tool.

Case report: post-Covid-19 arthritis and peri arthritis

We present the case of a 63 years old male patient known for type 2 diabetes and sleep apnoea. He was admitted as inpatient for a nontraumatic severe and disabling left hip pain. The pain started progressively one month ago. The medical history was otherwise irrelevant, with no general symptoms nor other symptoms suggestive of an inflammatory disease. To mention a history of an asymptomatic SARS-COV2 infection, diagnosed by a naso-pharyngial PCR, approximately 10 days before the onset of the pain. On physical examination, the patient was afebrile. The palpation of the inguinal region was tender on palpation with marked limitation of the hip range of motion. The spine and other peripheral joints were painless without inflammatory sign. Moreover, there was no skin lesion nor inguinal lymph nods enlargement. Due to the importance of pain with marked functional limitation, the patient is hospitalized for investigations and pain-management. On blood sample there was a mild increase of inflammatory markers (CRP 25mg/l, VS 20mm/h) with normal cell count. Standard X-rays of the pelvis and hip were normal. The MRI of the hip showed a mild coxo-femoral arthritis with marked inflammation of the surrounding musculature. An arthrocentesis was performed and 2ml of serous fluid was aspirated. There were no crystals. The cellularity could not be tested due to small amounts of fluid. The synovial culture showed a polymicrobious growth compatible with contamination. In summary, we were facing a patient with an acute and very painful hip monoarthritis. There was no history of gastrointestinal or urinary tract infection, the search for C. trachomatis and N. gonorrhoea in urines was negative. An extensive serologic testing (HIV, HBV, HCV, HBV, HCV, HIV, Lyme, Syphilis, Coxiella, Bartonella, Brucella & Quantiferon) and the search for T. whipplei were negative as well. There was no HLA-B27 and rheumatoid factor, ACPA, ANA, ANCA and specific antibodies related to polymyositis were negative. The chest-abdomen-pelvis scan showed no sign of neoplasia. To rule out a vasculitis we proceeded to a PET-CT, which showed no sign of vasculitis or myositis. Considering the timing of the onset of the symptoms and the absence of any other diagnosis, the patient was diagnosed with reactive arthritis caused by SARS-COV2. The patient was treated with Diclofenac 150 mg/day and opioids. The clinical evaluation one month after discharge showed a spontaneous significant improvement.

SORE THROAT SAGA: A TALE OF A MISDIAGNOSED PERSIST SORE THROAT DURING THE COVID-19 PANDEMIC

CASE: A 24-year-old male without past medical history aside from high-risk sexual activity (multiple female sexual partners complicated by a distant history of chlamydia) however with frequent negative testing (recent negative HIV, syphilis RPR, and urinary gonorrhea/chlamydia RNA tests) and consistent condom use presents to an urgent care visit for 1 week history of sore throat with difficulty swallowing. The symptoms presented gradually with reported lymph node swelling of upper neck without associated cough, congestion, or fever. He denies sick contacts however there is high local transmission of COVID-19. Exam shows bilateral tonsillar swelling with right-sided white exudate and midline uvula;bilateral tender anterior cervical lymphadenopathy is present. COVID-19 PCR and Strep antigen/culture tests are negative. Patient is advised to treat symptomatically with ibuprofen and saltwater gargles for a likely viral upper respiratory tract infection. Symptoms persist without improvement;he presents again 1 week later. He now reveals that prior to this sore throat he had receptive oral intercourse with a female partner of unknown sexual history. Exam is unchanged. Repeat COVID-19 PCR test is negative. Monospot and HIV RNA tests are negative but gonorrhea RNA pharyngeal swab results positive. Patient is given IM ceftriaxone and symptoms resolve;patient tests negative on repeat swab 10 days later. IMPACT/DISCUSSION: This case demonstrates the difficulty in expeditious diagnosis of gonococcal pharyngitis without high index of suspicion. Spread primarily through receptive oral intercourse, most oropharyngeal infections with N. gonorrhoeae are asymptomatic, although symptoms shared with other common upper respiratory infections like sore throat, exudate, and cervical lymphadenopathy as well as fever may occur. Management is a single 500mg IM injection of ceftriaxone, notification of relevant partners, as well as a test of cure 7-14 days after initial treatment due to challenges of effective treatment when at this site. Expeditious diagnosis and eradication are important as pharyngeal gonococcal infections can contribute to high level of gonococcal transmission, uneradicated gonococcal infection could disseminate, and the pharynx is thought to be where horizontal transfer of gonococcal antimicrobial resistance genes commonly occurs. Given the increasing prevalence of gonococcal infections nationally and increasing rates of antimicrobial-resistant gonococcal infections, which were estimated to be 550,000 infections in 2019 and increasing when studied from 2000-2017 as per the CDC's 2019 Antibiotic Resistance Threats Report, this concern becomes increasingly urgent with time. CONCLUSION: -A high index of suspicion is required for expeditious diagnosis of gonococcal pharyngitis -A test of cure is recommended after treatment given the challenge of eradication at the pharynx -Eradication is important to decrease gonorrhea transmission and horizontal transfer of antimicrobial resistance genes.

RAPID POINT-OF-CARE DIAGNOSIS OF CT/NG USING EXPAR DNA AMPLIFICATION COUPLED TO A NOVEL OPTICAL DETECTION SYSTEM

Introduction The Covid-19 pandemic has dramatically accelerated the point of care (POC) landscape, increasing awareness and demand for rapid diagnostics of other diseases. STIs are a major current health issue, with Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) being highly prevalent. Current diagnostic methods are not POC and the most rapid takes around 20 mins. We have developed a new molecular assay, taking < 10 minutes for a diagnostic result, and combined it with a novel, rapid detection mechanism to produce a fully integrated POC device. Methods Our assay will make use of the exponential amplification reaction (EXPAR), a rapid isothermal DNA amplification technique, to produce an output detectable by Linear Dichroism (LD). LD is a highly sensitive optical detection technique, relying on exploiting structural properties of a scaffold such as M13 bacteriophage. Adapting EXPAR and combining it with a DNA sensitive LD assay allows detection of specific DNA sequences, signalling the presence of CT and/or NG. A principal advantage of our system is it allows multiplexing on the same detection scaffold. Results Initial clinical trials using EXPAR show detection of CT/NG patient samples within 10 minutes of DNA amplification at a constant temperature. The sequences detected represent specific and well conserved regions of CT and NG. Large signal changes give M13 a high analytical sensitivity. Discussion Our systems will ensure faster and more accurate diagnosis and ultimately better patient health outcomes. We are currently focused on an expansion of the scope of diseases that we can detect, using our in-house sequence selection process. (Figure Presented).

OUTCOMES OF SELF-TAKEN GENITAL NEISSERIA GONORRHOEAE CULTURE SWABS IMPLEMENTED TO REDUCE DIRECT PATIENT CONTACT DURING THE COVID-19 PANDEMIC

Introduction Obtaining samples of Neisseria gonorrhoeae for antibiotic sensitivity testing is important for purposes of antimicrobial stewardship. While urethral and cervical gonorrhoea culture samples are usually taken by a healthcare professional, the Covid-19 pandemic necessitated a reduction in direct patient contact. In our service, patients with confirmed gonorrhoea who did not otherwise require examination were asked to take their own urethral or vaginal culture swabs. Methods GUMCAD coding was used to identify cases of cervical or male urethral Neisseria gonorrhoeae infection diagnosed on nucleic acid amplification testing, where the gonococcal culture result and the identity of the swab-taker (patient/healthcare professional) were recorded in the notes. 50 cases were selected in 2019, and 50 in 2020, after the onset of the Covid-19 pandemic. Proportions of patients taking their own swabs were calculated for the two periods. Culture positivity rates were compared between self-taken and healthcare professional-taken swabs. Results During the pandemic, use of self-taken culture samples increased ten-fold. Although positivity for Neisseria gonorrhoeae was lower for self-taken swabs, 38% of male self-taken urethral samples tested positive for gonorrhoea, and the organism was successfully cultured from a self-taken vaginal swab on one occasion. Discussion Although self-taken gonorrhoea cultures were less likely to grow Neisseria gonorrhoeae than those taken by healthcare professionals, they proved a useful tool in gathering sensitivity data in a time of restricted patient contact. The lower positivity rate of self-taken cultures may be partially attributable to their use in patients with fewer symptoms, and hence a lower bacterial load. (Table Presented).

IMPACT of COVID OUTBREAK on PREVENTION and CARE for HIV and STIs at A LARGE HOSPITAL

Background: Routine medical care was drastically affected by the overwhelming irruption of COVID-19 pandemic. We comprehensively assessed the impact of the COVID-19 pandemic on the prevention and care for HIV and other sexually transmitted infections at a large reference hospital providing preventive and clinical services for HIV infection and other sexually transmitted infections. Methods: We retrospectively compared clinical and laboratory data from March to December 2020 (first ten months of the SARS-CoV-2 epidemics in Spain) vs. the same period 2019 in the setting of Hospital Clínic of Barcelona which provides preventive and clinical services for HIV infection and other sexually transmitted infections for the region of Catalonia and is the largest of its kind in Spain. Monthly clinical data on HIV pre-exposure and post-exposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database. De novo HIV, hepatitis B, or hepatitis C diagnosis were considered whenever a person had a first known positive laboratory test. Results: There were less (28% reduction) but more advanced (mean [SD] CD4 cell counts per mm3 at HIV diagnosis 305 [167] vs. 370 [170], P<0.001;26 (18%) persons had AIDS-defining conditions at HIV diagnosis vs. 20 (10%), P=0.03) HIV cases and more gonorrhea (39% increase, P<0.001) and chlamydia (37% increase, P<0.001) infections in 2020 vs. 2019. In people with HIV, rates of viral load above the level of detection remained stable (11% vs 11%, P=0.147) despite less scheduled visits (25% reduction, P<0.001). However, they had less antiretroviral prescription changes (10% reduction, P=0.018), worse plasma lipids (mean total cholesterol 190 vs 185 mg/dL, P<0.001;mean LDL cholesterol 114 vs 110 mg/dL, P<0.001;mean triglycerides 136 vs 125 mg/dL, P<0.001;mean HDL cholesterol 47 vs 48 mg/dL, P=0.006), and an excess of mortality (29 deaths vs 11, 264% increase, P=0.006) due in great part to COVID-19 (n=11) but also to other non-COVID-19 causes. Conclusion: In the setting of a large Spanish reference hospital, SARS-CoV-2 epidemics was associated with an increase of some prevalent sexually transmitted infections, with less but more advanced de novo HIV infections, and with worse non-virologic healthcare outcomes and higher mortality in people living with HIV.

Informative Review on Pharmacognostic, Phytochemistry, Ethnopharmacological, and Phytopharmacological Actions of Tinospora cordifolia

Herbal drugs are medicinally and therapeutically active. From ancient times, Tinospora cordifolia belongs to Menispermaceae. This plant generally contains tinosporine, hydroxy ecdysone, furanoid diterpene, tinosponone, terpenoids, sinapic acid, and aliphatic compounds. Major phytopharmacological actions are significantly reported are against Diabetes Mellitus (DM), SARS-CoV-2 syndrome, boost immunity, treat influenza, viral infection, lymphoma, anticancer, antipyretic, effective against several bacteria such as Mycobacterium leprae, Mycobacterium tuberculosis, Neisseria gonorrhoeae and having diverse variety beneficial properties. This review is an endeavor on many isolated chemical components from T. cordifolia, medicinal utilization of this plant against several disorders, ethnopharmacology, phytopharmacological actions.

THE GREAT AORTIC VALVE DESTROYER: A CASE OF NEISSERIA GONORRHEA INFECTIVE ENDOCARDITIS

Background: With the advent of antibiotics to eradicate common sexually transmitted infections (STIs), such as those due to Neisseria gonorrhea, we do not often see their most severe complications. Disseminated gonococcal infection (DGI) occurs in 0.5-3% of all infections, with infective endocarditis (IE) being a complication in 1-2% of patients with DGI. Case: A 30-year-old male with no past medical history, presented for 2 weeks of progressively worsening midline pleuritic chest pain, fevers, chills, malaise and dyspnea. TTE on admission noted severe aortic regurgitation and mild to moderate mitral regurgitation. Follow-up TEE noted destruction of the aortic valve with evidence of para-aortic abscess and a small dissection of the aortic root. Empiric intravenous antibiotic coverage was subsequently initiated. These findings, coupled with 2 blood cultures positive for N. gonorrhea, led to the patient's transfer to our institution for surgical evaluation. Decision-making: There have been about 50 reported cases of N. gonorrhea infective endocarditis since 1949. Treatment of the offending pathogen is made difficult by the infected typically being asymptomatic, which is why the mortality rate remains at about 20%. In our case, the patient was treated empirically for chlamydial co-infection and maintained on IV ceftriaxone until 6 weeks post-operatively. Due to the patient's symptoms and degree of valvular destruction, urgent surgical aortic valve replacement (AVR) was undertaken. The 2015 European Society of Cardiology guidelines for IE management recommend either bioprosthetic or mechanical AVR. A mechanical valve was chosen based on 2020 data indicating that there may be an association between bioprosthesis and higher IE risk. Conclusion: Despite our current ability to eradicate STIs with oral antibiotics, complicated infections like IE are still seen. This is pervasive amongst the sexually active in our underserved populations, augmented by decreased healthcare contact due to the COVID-19 pandemic. Therefore, continued consideration of this diagnosis in patients like ours, as well as a multidisciplinary approach inclusive of surgical evaluation, is imperative.

Use of Mail-Out Sexually Transmitted Infection Test Kits in a Telehealth Pre-exposure Prophylaxis Clinic

Background. Standard of care for patients receiving pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) includes HIV screening and testing for sexually transmitted infections (STIs) at all sites of potential exposure every three months. We implemented a provider and pharmacist telehealth based PrEP program as part of the HIV, Hepatitis Specialty Telehealth Access Resource (H-START) Collaborative. Due to the COVID-19 pandemic and care via telehealth, we had limited ability to collect pharyngeal or rectal swabs in clinic. We created mail-out kits including swabs and instructions for self-collection to test for rectal and pharyngeal Neisseria gonorrhea and Chlamydia trachomatis. Methods. Kits were mailed out to patients between June 2020 and May 2021. Providers first confirmed patient comfort with self-swab collection during telehealth appointments. Kits included: an instruction sheet with visual diagrams for collection, swabs with appropriate labels;and a pre-paid envelope for patients to mail swabs back to our facility for laboratory testing. Prospective data collection included the date kits were mailed out to patients, the date of kit receipt at our facility and the test result. Charts were retrospectively reviewed to determine treatment completion. Results. 54 self-swab kits were mailed to patients. 53 of the patients were male and the average age was 41.3 years old. 38 (70.3%) swabs were returned. The median time for return of swabs was 21 days (Range 2-289). Of those returned, 5 (13.1%) were positive and all 5 patients were treated for their infection. Conclusion. Mail-out STI testing was effective in identifying STIs for a telehealth PrEP program and for maintaining standard of care practice during the COVID-19 pandemic. This model may increase rates of testing compliance for care provided via telehealth and decrease rates of STI transmission and complications. Better communication around returning kits in a timely-manner and understanding reasons for non-return warrant further investigation.

Summary of national data of class A, B and C communicable diseases in China, October 2021

In October 2021 (from 00: 00, 1 October to 24: 00, 31 October), a total of 523 006 cases of notifiable communicable diseases, including 2 040 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, 2 cases of cholera were reported without death. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A (H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 249 605 cases were reported, a decrease of 8% compared with last month (272 332 cases) and a decrease of 3% compared with the same period in 2020 (258 591 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and AIDS, accounting for 95% of the total reported cases in class B. A total of 2 039 deaths were reported, a decrease of 6% (133 deaths) compared with last month (2 172 deaths) and an increase of 17% compared with the same period in 2020 (1 737 deaths). According to the website of the National Health Commission of China, a total of 1 081 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00: 00, 1 October to 24: 00, 31 October, 2021. In class C communicable diseases, a total of 273 399 cases were reported, an increase of 20% compared with last month (228 597 cases) and a decrease of 13% compared with the same period in 2020 (315 366 cases). The first 3 diseases in terms of reported case number were hand foot and mouth disease (HFMD), other infectious diarrhea and influenza, accounting for 95% of the total reported cases in class C. Compared with last month, except filariasis which had no incidences in both months, the diseases with reported cases increases were HFMD (45 435 cases, 52%), influenza (17 811 cases, 50%) and rubella (11 cases, 12%), but the reported cases of other diseases all decreased, the diseases with obvious case decreases were other infectious diarrhea (16 519 cases, 18%), mumps (1 490 cases, 12%) and acute hemorrhagic conjunctivitis (327 cases, 14%). Compared with the same period in 2020, except filariasis which had no incidences in both years, the diseases with reported case increases were influenza (33 177 cases, 164%), typhus fever (15 cases, 9%), rubella (8 cases, 9%) and leprosy (3 cases, 17%), but the diseases with reported case decreases were HFMD (65 002 cases, 33%), other infectious diarrhea (4 111 cases, 5%) and mumps (1 574 cases, 12%). One death caused by class C communicable diseases was reported, an increase of 1 death compared with last month and a decrease of 1 death compared with the same period in 2020 (2 deaths).

Summary of national data of class A, B and C communicable diseases in China, September 2021

In September 2021 (from 00:00, 1 September to 24: 00, 30 September), a total of 500 929 cases of notifiable communicable diseases, including 2 172 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, no case and no death were reported. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A(H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 272 332 cases were reported, a decrease of 0.9% compared with last month (274 917 cases) and a decrease of 5% compared with the same period in 2020 (287 923 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and brucellosis, accounting for 94% of the total reported cases in class B. A total of 2 172 deaths were reported, an increase of 5% (95 deaths) compared with last month (2 077 deaths) and a decrease of 5% compared with the same period in 2020 (2 291 deaths). According to the website of the National Health Commission of China, a total of 1 264 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00:00, 1 September to 24: 00, 30 September, 2021. In class C communicable diseases, a total of 228 597 cases were reported, an increase of 10% compared with last month (207 153 cases) and a decrease of 7% compared with the same period in 2020 (247 112 cases). The first 3 diseases in terms of reported case number were other infectious diarrhea, hand foot and mouth disease (HFMD) and influenza, accounting for 93% of the total reported cases in class C. Compared with last month, except filariasis, visceral leishmaniasis, leprosy and other infectious diarrhea which decreased by 1 case, 11 cases (39%), 12 cases (33%) and 12 747 cases (12%) respectively, the reported cases of all other diseases increased, the diseases with obvious case increases were HFMD (15 352 cases, 22%), influenza (14 160 cases, 66%) and mumps (4 253 cases, 51%). Compared with the same period in 2020, the diseases with reported case increases were influenza (17 269 cases, 95%), visceral leishmaniasis (4 cases, 31%), rubella (19 cases, 27%) and typhus fever (32 cases, 18%), filariasis had no incidences in both years, and the diseases with obvious reported case decreases were HFMD (26 506 cases, 23%). other infectious diarrhea (5 628 cases, 6%) and mumps (523 cases, 4%). No death caused by class C communicable diseases was reported, same to the last month and a decrease of 3 deaths compared with the same period in 2020 (3 deaths).