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April 8 marks a year since China's lifting of the 76-day lockdown in Wuhan—the epicentre of the COVID-19 outbreak. Since the reopening of Wuhan, efforts to control the pandemic in China have thus far successfully prevented resurgence and importation of new cases, while re-establishing the country's social and economic activities. Although China has since had sporadic outbreaks of COVID-19 in several areas, including Beijing and Qingdao, they were all contained. How has China managed to control COVID-19? And is the global scientific community in a position to benefit from China's experiences?…

In the past few months, the results of several phase 3 studies showing high vaccine efficacy against SARS-CoV-2 and the subsequent rapid regulatory approval and roll-out of several vaccines have ignited much optimism. However, this optimism has been dampened by the emergence of several new virus variants that are more transmissible and less sensitive to vaccine-induced antibodies.1–6 The extent to which emerging variants affect the efficacy of vaccines appears to vary considerably between vaccines and variants.

Maternal and child undernutrition is a pervasive problem that has grown during the COVID-19 pandemic. Rising food prices combined with disruptions to livelihoods have put millions of people at greater risk of food and nutrition insecurity.1 These impacts are especially pronounced in low-income and middle-income countries (LMICs), where existing health system infrastructure is weak and access to life-saving interventions has been interrupted by the COVID-19 pandemic.2…

People with disabilities have been differentially affected by COVID-19 because of three factors: the increased risk of poor outcomes from the disease itself, reduced access to routine health care and rehabilitation, and the adverse social impacts of efforts to mitigate the pandemic. 10 years ago, WHO's World Report on Disability noted that people with disabilities were more likely to be older, poorer, experience comorbidities, and be female.1 Older age, deprivation, and comorbidities are also associated with increased risk of severe outcomes from COVID-19.

As focus shifts to the next phase of research on the origins of SARS-CoV-2, calls for data sharing and more rigorous studies intensify. John Zarocostas reports.

We are delighted to see Sophie Harman and colleagues1 advocating the clinical and logistical considerations for the equitable and safe development, delivery, and administration of the COVID-19 vaccine to women. Additionally, there exists an area of gendered vaccine inequality, concerningly neglected to date, relating to the prioritisation of vaccines for survivors of gender-based violence (GBV).

Pedro Hallal1 describes how Brazil's President Bolsonaro has ridiculed the COVID-19 pandemic, hindered scientists, and implemented unreasonable policies. One point, holding the president's policies accountable for the death of 156 582 people, warrants a closer look. The estimate is based on the premise that Brazil should have COVID-19 death rates equal to the world average. However, there are substantial limitations to that assumption. Many of the countries reporting death rates that are less than the world average have authoritarian governments that typically control and censor information.

The current vaccination campaign against SARS-CoV-2 has many challenging aspects, one of which is maintaining the cold chain for the distribution, delivery, and storage of available vaccines and guaranteeing that their full titre is retained for administration. Although outstanding technology for vaccine development has enabled products to be put on the market in 1 year, it is difficult to understand why approximately the same length of time is taken to roll out their administration, thus jeopardising the effect of the campaign.

In the past few months, we have seen emergence of clinically important mutations that alter infectivity, severity, or immune susceptibility of SARS-CoV-2.1 Prominent examples include Asn501Tyr, His69_Val70del, and Glu484Lys mutations in the spike protein that have emerged independently in many global strains, such as those from the UK, South Africa, and Brazil, possibly driving resurgence of the pandemic when it appeared to be coming under control.2 Some of these variants are likely to be resistant to vaccines and capable of reinfections.

by Oh Joo Kweon, Yong Kwan Lim, Hye Ryoun Kim, Yoojeong Choi, Min-Chul Kim, Seong-Ho Choi, Jin-Won Chung, Mi-Kyung Lee We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.

by Agajie Likie Bogale, Tilahun Teklehaymanot, Jemal Haidar Ali, Getnet Mitike Kassie Background To establish successful strategies and increasing the utilization of preventive services, there is a need to explore the extent to which the general female population is aware and use the service for cervical cancer-screening among women infected with HIV in Africa. Available evidences in this regard are controversial and non-conclusive on this potential issue and therefore, we estimated the pooled effect of the proportion of knowledge, attitude and practice of HIV infected African women towards cervical cancer screening to generate evidence for improved prevention strategies. Methods We applied a systematic review and meta-analysis of studies conducted in Africa and reported the proportion of knowledge, attitude and practice towards cervical cancer screening. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Web of science, Cumulative Index of Nursing and allied Health Sciences (CINAHL) and Google scholar databases to retrieve papers published in English language till August 2020. We used random-effects model to estimate the pooled effect, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42020210879. Results In this review, we included eight published papers comprising 2,186 participants. The estimated pooled proportion of knowledge of the participants was 43.0% (95%CI:23.0–64.0) while the pooled estimates of attitudes and practices were 38.0% (95%CI: 1.0–77.0) and 41.0% (95%CI: 4.0–77.0), respectively. The proportion of the outcome variables were extremely heterogeneous across the studies with I2> 98%). Conclusion The pooled estimates of knowledge, attitude and practice were lower than other middle income countries calls for further activities to enhance the uptake of the services and establish successful strategies.

by Hailing Chang, Jiayin Guo, Zhongqiu Wei, Zheng Huang, Chuning Wang, Yue Qiu, Xuebin Xu, Mei Zeng Diarrhoea remains a major cause of childhood morbidity and mortality worldwide. This study aimed to monitor the aetiology of acute diarrhoea in children in Shanghai. Paediatric outpatients with acute diarrhoea were enrolled in the study from Jan 2015 to Dec 2018. Faecal samples were collected for testing. Enteric bacteria were identified and typed by culture and serotyping, respectively. Enteric viruses were identified by real-time PCR. Enteric pathogens were identified in 1572 (58.4%) of the 2692 enrolled children with acute diarrhoea. Viruses were detected more frequently than bacteria (41.3% versus 25.0%). Nontyphoidal Salmonella spp. (NTS) was the most common (10.3%) bacteria isolated, followed by enteropathogenic Escherichia coli (EPEC) (6.5%), enteroaggregative Escherichia coli (EAEC) (6.2%), Campylobacter spp. (3.6%), enterotoxigenic Escherichia coli (ETEC) (1.1%), Shigella spp. (0.2%), and enterohemorrhagic Escherichia coli (EHEC) (0.1%). Rotavirus was the most common (16.0%) virus detected, followed by norovirus (15.5%), adenovirus (7.2%), sapovirus (3.0%) and astrovirus (2.7%). Rotavirus, norovirus and NTS were the major pathogens responsible for diarrhoea in Shanghainese children. Improving uptake of the rotavirus vaccine and strengthening foodborne-pathogen prevention will aid in reducing the burden of diarrhoeal disease in children in Shanghai.

by Sing Chen Yeo, Clin K. Y. Lai, Jacinda Tan, Joshua J. Gooley The COVID-19 pandemic led to widespread closure of universities. Many universities turned to e-learning to provide educational continuity, but they now face the challenge of how to reopen safely and resume in-class learning. This is difficult to achieve without methods for measuring the impact of school policies on student physical interactions. Here, we show that selectively deploying e-learning for larger classes is highly effective at decreasing campus-wide opportunities for student-to-student contact, while allowing most in-class learning to continue uninterrupted. We conducted a natural experiment at a large university that implemented a series of e-learning interventions during the COVID-19 outbreak. The numbers and locations of 24,000 students on campus were measured over a 17-week period by analysing >24 million student connections to the university Wi-Fi network. We show that daily population size can be manipulated by e-learning in a targeted manner according to class size characteristics. Student mixing showed accelerated growth with population size according to a power law distribution. Therefore, a small e-learning dependent decrease in population size resulted in a large reduction in student clustering behaviour. Our results suggest that converting a small number of classes to e-learning can decrease potential for disease transmission while minimising disruption to university operations. Universities should consider targeted e-learning a viable strategy for providing educational continuity during periods of low community disease transmission.

by Degu Ashagrie, Chalachew Genet, Bayeh Abera Background Vancomycin resistant enterococci (VRE) and vancomycin resistance coagulase negative staphylococci (VRCoNS) are common pathogens causing difficult to treat health care associated infections (HAI). Hence, the World Health Organization listed VRE as one of the high priority pathogens for new antibiotic discovery and antimicrobial resistance surveillance. Despite this, data on the prevalence of VRE and VRCoNS in Ethiopia is scarce. Thus, the present study determined prevalence of VRE and VRCoNS among patients attending Felege-Hiwot comprehensive specialized hospital, Ethiopia. Methods A hospital based cross-sectional study was conducted on 384 patients selected conveniently from February to March 2020. Data on demographic and clinical variables were collected using a structured questionnaire by face-to-face interview. Simultaneously urine, venous blood and wound swab were collected and processed following standard bacteriological technique. Antimicrobial susceptibility test was performed by minimum inhibitory concentration method using E-test for vancomycin and Kirby-Bauer disc diffusion method for other classes of antibiotics. Data was entered and analyzed using SPSS version 23. Logistic regression was performed to identify factors associated with VRE infection. P. value < 0.05 was considered as statistically significant. Results The prevalence of enterococci and CoNS were 6.8% and 12% respectively. The prevalence of VRE was 34.61% (9/26), while all CoNS (46 isolates) were susceptible to vancomycin. The majority (66.7%) of VRE was isolated from blood samples. Furthermore all VRE (100%), 58.8% of vancomycin susceptible enterococci and 45.7% of CoNS were multidrug resistant (MDR). Having educational level of secondary school and below (AOR = 12.80, CI = 1.149–142.5), previous exposure to catheterization (AOR = 56.0, CI = 4.331–724.0) and previous antibiotic use practice (AOR = 26.25, CI = 3.041–226.2) were a significant associated explanatory factor for VRE infection. Conclusions The prevalence of vancomycin resistance enterococci, which is also multidrug resistant, was significantly high. Though no vancomycin resistance CoNS detected, the MDR level of CoNS was high. Thus to limit enterococci and CoNS infections and MDR development, focused infection prevention measures should be implemented.

by Adrian Galido, Jerina Jean Ecleo, Atina Husnayain, Emily Chia-Yu Su Public health agencies have suggested nonpharmaceutical interventions to curb the spread of the COVID-19 infections. The study intended to explore the information-seeking behavior and information needs on preventive measures for COVID-19 in the Philippine context. The search interests and related queries for COVID-19 terms and each of the preventive measures for the period from December 31, 2019 to April 6, 2020 were generated from Google Trends. The search terms employed for COVID-19 were coronavirus, ncov, covid-19, covid19 and “covid 19.” The search terms of the preventive measures considered for this study included “community quarantine”, “cough etiquette”, “face mask” or facemask, “hand sanitizer”, handwashing or “hand washing” and “social distancing.” Spearman’s correlation was employed between the new daily COVID-19 cases, COVID-19 terms and the different preventive measures. The relative search volume for the coronavirus disease showed an increase up to the pronouncement of the country’s first case of COVID-19. An uptrend was also evident after the country’s first local transmission was confirmed. A strong positive correlation (rs = .788, p < .001) was observed between the new daily cases and search interests for COVID-19. The search interests for the different measures and the new daily cases were also positively correlated. Similarly, the search interests for the different measures and the COVID-19 terms were all positively correlated. The search interests for “face mask” or facemask, “hand sanitizer” and handwashing or “hand washing” were more correlated with the search interest for COVID-19 than with the number of new daily COVID-19 cases. The search interests for “cough etiquette”, “social distancing” and “community quarantine” were more correlated with the number of new daily COVID-19 cases than with the search interest for COVID-19. The public sought for additional details such as type, directions for proper use, and where to purchase as well as do-it-yourself alternatives for personal protective items. Personal protective or community measures were expected to be accompanied with definitions and guidelines as well as be available in translated versions. Google Trends could be a viable option to monitor and address the information needs of the public during a disease outbreak. Capturing and analyzing the search interests of the public could support the design and timely delivery of appropriate information essential to drive preventive measures during a disease outbreak.

by Sumudu Hewage, Noel Somasundaram, Vithiya Ratnasamy, Ishara Ranathunga, Amitha Fernando, Indika Perera, Udara Perera, Dhammika Vidanagama, Mizaya Cader, Poorna Fernando, Nirupa Pallewatte, Lakmal Rathnayaka, Dushani Jayawardhana, Manjula Danansuriya, Nalika Gunawardena End TB strategy by the WHO suggest active screening of high-risk populations for tuberculosis (TB) to improve case detection. Present study generates evidence for the effectiveness of screening patients with diabetes mellitus (DM) for Pulmonary TB (PTB). A study was conducted among 4548 systematically recruited patients over 45 years attending DM clinic at the National Hospital of Sri Lanka. The study units followed an algorithm specifying TB symptom and risk factor screening for all, followed by investigations and clinical assessments for those indicated. Bacteriologically confirmed or clinically diagnosed PTB were presented as proportions with 95% CI. Mean (SD) age was 62·5 (29·1) years. Among patients who completed all indicated steps of algorithm, 3500 (76·9%) were investigated and 127 (2·8%) underwent clinical assessment. Proportion of bacteriologically confirmed PTB patients was 0·1% (n = 6,95%CI = 0·0–0·3%). None were detected clinically. Analysis revealed PTB detection rates among males aged ≥60 years with HbA1c ≥ 8 to be 0·4% (n = 2, 95%CI = 0·0–1·4%). The study concludes that active screening for PTB among all DM patients at clinic settings in Sri Lanka, to be non-effective measure to enhance TB case finding. However, the sub-category of diabetic males with uncontrolled diabetics who are over 60 years of age is recommended as an option to consider for active screening for PTB.

by Leila Mekkaoui, Marie Hallin, Françoise Mouchet, Marie-Christine Payen, Evelyne Maillart, Philippe Clevenbergh, Aspasia Georgala, Sigi Van den Wijngaert Among the challenges in controlling tuberculosis, a rapid and accurate diagnostic test for the detection of Mycobacterium tuberculosis complex (MTBc) and its resistance to first line therapies is crucial. We evaluated the performance of the Xpert MTB/RIF Ultra assay (Xpert Ultra) for the rapid detection of MTBc and rifampicin resistance (RR) in 1120 pulmonary and 461 extra-pulmonary clinical specimens and compared it with conventional phenotypic techniques. The Xpert Ultra assay detected MTBc in 223 (14.1%) samples with an overall sensitivity and specificity, using culture as the “gold standard”, of 91.1% (95% CI, 85.6–95.1) and 94.5% (95% CI, 93.1–95.6), respectively. The sensitivity of the Xpert Ultra test for smear-negative extra-pulmonary specimens was high (87.1%), even higher than with smear-negative pulmonary specimens (81.8%). But this enhanced sensitivity came with a low overall specificity of smear-negative extra-pulmonary specimens (66.7%). For 73 patients, 79/1423 (3.4%) negative mycobacterial culture samples were found to be positive with Xpert Ultra. Clinical data was necessary to correctly interpret potential false-positive results, especially trace-positive results. Sensitivity of the Xpert Ultra to detect RR compared to drug susceptibility testing was 100% (95% CI, 29.2–100) and specificity was 99.2% (95% CI, 95.8–100). We concluded that the Xpert Ultra test is able to provide a reliable TB diagnosis within a significantly shorter turnaround time than culture. This is especially true for paucibacillary samples such as smear-negative pulmonary specimens and extra-pulmonary specimens.

by Benjamin Born, Alexander M. Dietrich, Gernot J. Müller While most countries imposed a lockdown in response to the first wave of COVID-19 infections, Sweden did not. To quantify the lockdown effect, we approximate a counterfactual lockdown scenario for Sweden through the outcome in a synthetic control unit. We find, first, that a 9-week lockdown in the first half of 2020 would have reduced infections and deaths by about 75% and 38%, respectively. Second, the lockdown effect starts to materialize with a delay of 3–4 weeks only. Third, the actual adjustment of mobility patterns in Sweden suggests there has been substantial voluntary social restraint, although the adjustment was less strong than under the lockdown scenario. Lastly, we find that a lockdown would not have caused much additional output loss.

by Sozinho Acácio, Tacilta Nhampossa, Llorenç Quintò, Delfino Vubil, Marcelino Garrine, Quique Bassat, Tamer Farag, Sandra Panchalingam, James P. Nataro, Karen L. Kotloff, Myron M. Levine, Sharon M. Tennant, Pedro L. Alonso, Inácio Mandomando Background Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0–59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1–3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85–37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02–25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.

by Reaz Mahmud, Md. Mujibur Rahman, Mohammad Aftab Rassel, Farhana Binte Monayem, S. K. Jakaria Been Sayeed, Md. Shahidul Islam, Mohammed Monirul Islam Background Post-coronavirus disease (COVID-19) syndrome includes persistence of symptoms beyond viral clearance and fresh development of symptoms or exaggeration of chronic diseases within a month after initial clinical and virological cure of the disease with a viral etiology. We aimed to determine the incidence, association, and risk factors associated with development of the post-COVID-19 syndrome. Methods We conducted a prospective cohort study at Dhaka Medical College Hospital between June 01, 2020 and August 10, 2020. All the enrolled patients were followed up for a month after clinical improvement, which was defined according the World Health Organization and Bangladesh guidelines as normal body temperature for successive 3 days, significant improvement in respiratory symptoms (respiratory rate 93% without assisted oxygen inhalation. Findings Among the 400 recruited patients, 355 patients were analyzed. In total, 46% patients developed post-COVID-19 symptoms, with post-viral fatigue being the most prevalent symptom in 70% cases. The post-COVID-19 syndrome was associated with female gender (relative risk [RR]: 1.2, 95% confidence interval [CI]: 1.02–1.48, p = 0.03), those who required a prolonged time for clinical improvement (p<0.001), and those showing COVID-19 positivity after 14 days (RR: 1.09, 95% CI: 1.00–1.19, p<0.001) of initial positivity. Patients with severe COVID-19 at presentation developed post-COVID-19 syndrome (p = 0.02). Patients with fever (RR: 1.5, 95% CI: 1.05–2.27, p = 0.03), cough (RR: 1.36, 95% CI: 1.02–1.81, p = 0.04), respiratory distress (RR: 1.3, 95% CI: 1.4–1.56, p = 0.001), and lethargy (RR: 1.2, 95% CI: 1.06–1.35, p = 0.003) as the presenting features were associated with the development of the more susceptible to develop post COVID-19 syndrome than the others. Logistic regression analysis revealed female sex, respiratory distress, lethargy, and long duration of the disease as risk factors. Conclusion Female sex, respiratory distress, lethargy, and long disease duration are critical risk factors for the development of post-COVID-19 syndrome.

by Leshui He, Wen Zhou, Ming He, Xuanhua Nie, Jun He Along with the plight of the COVID-19 outbreak in 2020 come the xenophobic behaviors and hate crimes against people with Asian descent around the globe. The threat of a public health emergency catalyzed underlying xenophobic sentiments, manifesting them into racial discrimination of various degrees. With most discriminatory acts reported in liberal societies, this article investigates whether an economy more open to trade and migration can be more susceptible to xenophobia. Using our first-hand survey data of 1767 Chinese respondents residing overseas from 65 different countries during February of 2020, we adopt an instrumental variable strategy to identify the causal effect of openness to trade and migration of their residence country on the likelihood of them receiving discriminatory behaviors during the early stage of the COVID-19 outbreak. Our results show that greater openness to trade increases the likelihood of reported xenophobic behaviors, while openness to migration decreases it. On the other hand, stronger trade or immigration relationships with China are associated with less reported discrimination. And these effects primarily influence discriminatory behavior in interpersonal spaces, rather than through media outlets. Our findings highlight nuances of the effect of trade relations on the culture of a society.

by Isaiah Gwitira, Norbert Karumazondo, Munyaradzi Davis Shekede, Charles Sandy, Nicolas Siziba, Joconiah Chirenda Introduction Accurate mapping of spatial heterogeneity in tuberculosis (TB) cases is critical for achieving high impact control as well as guide resource allocation in most developing countries. The main aim of this study was to explore the spatial patterns of TB occurrence at district level in Zimbabwe from 2015 to 2018 using GIS and spatial statistics as a preamble to identifying areas with elevated risk for prioritisation of control and intervention measures. Methods In this study Getis-Ord Gi* statistics together with SaTscan were used to characterise TB hotspots and clusters in Zimbabwe at district level from 2015 to 2018. GIS software was used to map and visualise the results of cluster analysis. Results Results show that TB occurrence exhibits spatial heterogeneity across the country. The TB hotspots were detected in the central, western and southern part of the country. These areas are characterised by artisanal mining activities as well as high poverty levels. Conclusions and recommendations Results of this study are useful to guide TB control programs and design effective strategies which are important in achieving the United Nations Sustainable Development goals (UNSDGs).

by Lin Chen, Mingyu Luo, Yun Xu, Yan Xia, Xin Zhou, Wanjun Chen, Hui Wang, Tingting Jiang, Weiyong Chen, Yan Luo, Qiaoqin Ma, Jianmin Jiang, Xiaohong Pan To analyze the results of HIV screening and the HIV-positive rate based on different HIV detection strategies in Zhejiang Province, China. Data were downloaded from the AIDS Prevention and Control Information System on May 1, 2019. HIV screening, prevalence, and incidence data were analyzed from 2008 to 2018. The incidence of HIV was calculated from the results of BED testing. SPSS software (ver. 19.0) was used for the analysis. The number of people screened for HIV increased by 229.7% from 2008 to 2018, while the incidence of HIV increased from 1.14‱ (2010) to 1.67‱ (2018), peak by 2015 (2.28‱). The proportion of people screened for HIV in medical institutions increased from 62.0% in 2008 to 67.1% in 2018, while of all positive tests, 47.9% were conducted at medical institutions in 2008, which increased to 63.2% in 2018. VCT and STD clinic attendees, who had only 4.5% of all those undergoing HIV tests, accounted for 23.7% of all HIV positive in 2018. The rate of HIV-positive people and incidence of HIV both increased in Zhejiang Province between 2008 and 2015. The most effective strategy for detecting HIV new cases is screening visitors to VCT and STD clinics.

AbstractMost patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild COVID-19 react to severe acute respiratory syndrome coronavirus 2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels in 95 patients with COVID-19 during the infection’s acute phase and report that significantly higher interleukin 12 and 2 levels were induced in patients with asymptomatic or mild disease than in those with moderate or severe disease, indicating the key roles of these cytokines in the pathogenesis of asymptomatic or mild COVID-19.

AbstractWe evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3–28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct <30, indicating high viral load; of these, 40% (6 of 15) were asymptomatic. Using this Ct threshold (<30) for Binax-CoV2 evaluation, the sensitivity of Binax-CoV2 was 93.3% (95% confidence interval, 68.1%–99.8%) (14 of 15) and the specificity was 99.9% (99.4%–99.9%) (855 of 856).

AbstractBackgroundThere is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2–infected patients.MethodsWe studied 1122 patients (mean age, 46 years) diagnosed by polymerase chain reaction (PCR). URT viral load, measured by PCR cycle threshold, was categorized as high, moderate, or low.ResultsThere were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, more often had comorbidities, developed Symptomatic disease (COVID-19), were intubated, and died. Patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (P values < .05 for all comparisons). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity, and chronic neurological disease more often had high viral load (P value < .05 for all comparisons). In multivariate analysis high viral load was associated with COVID-19. Level of viral load was not associated with any other outcome.ConclusionsURT viral load could be used to identify patients at higher risk for morbidity or severe outcome.

AbstractBackgroundTo determine how serologic antibody testing outcome links with virus neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluated individuals for SARS-CoV-2 antibody level and viral neutralization.MethodsWe compared serum Ig levels across platforms of viral antigens and antibodies with 15 positive and 30 negative SARS-CoV-2 controls followed by viral neutralization assessment. We then applied these platforms to a clinically relevant cohort of 114 individuals with unknown histories of SARS-CoV-2 infection.ResultsIn controls, the best-performing virus-specific antibody detection platforms were SARS-CoV-2 receptor binding domain (RBD) IgG (sensitivity 87%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 94%), spike IgG3 (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%), and nucleocapsid protein (NP) IgG (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%). Neutralization of positive and negative control sera showed 100% agreement. Twenty individuals with unknown history had detectable SARS-CoV-2 antibodies with 16 demonstrating virus neutralization. Spike IgG3 provided the highest accuracy for predicting serologically positive individuals with virus neutralization activity (misidentified 1/20 unknowns compared to 2/20 for RBD and NP IgG).ConclusionsThe coupling of virus neutralization analysis to a spike IgG3 antibody test is optimal to categorize patients for correlates of SARS-CoV-2 immune protection status.

To the Editor—We read with interest the review article by Burke et al [1] on the evidence of a link between rotavirus and type 1 diabetes (T1D) and wish to report our experience in Israel showing a correlation between the introduction of free, universal childhood rotavirus vaccination and a reduction in the rate of annual increase in the incidence of T1D in children aged 0–4 years.

AbstractBackgroundVaricella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid.MethodsAβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin’s function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated.ResultsCompared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA.ConclusionsVZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

AbstractInvasive group A Streptococcus (GAS) in immunocompetent individuals is largely linked to hypervirulent strains. Congenital immunodeficiencies and those acquired from chronic disease or immunosuppressant drugs also increase risk of severe illness. We recovered GAS from the blood of a patient receiving a biologic inhibitor of interleukin 6 (IL-6). Growth of this serotype M4 isolate in human blood or a murine bacteremia model was promoted by interleukin 1 or IL-6 inhibition. Hyperinvasive M1T1 GAS was unaffected by IL-6 in both models. These findings based on a natural experiment introduce IL-6 signaling deficiencies as a risk factor for invasive GAS.

AbstractBackgroundFractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV.MethodsA community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months.ResultsSeroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B.ConclusionsThere was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing.Clinical Trials RegistrationNCT03286803.

AbstractBackgroundInvasive candidiasis (IC) is a growing concern among US healthcare facilities. A large-scale study evaluating incidence and trends of IC in the United States by species and body site is needed to understand the distribution of infection.MethodsAn electronic medical record database was used to calculate incidence and trends of IC in the United States by species and infection site from 2009 through 2017. Hospital incidence was calculated using total unique inpatient hospitalizations in hospitals reporting at least 1 Candida case as the denominator. IC incidence trends were assessed using generalized estimating equations with exchangeable correlation structure to fit Poisson regression models, controlling for changes in hospital characteristics and case mix over time.ResultsCandida albicans remains the leading cause of IC in the United States, followed by Candida glabrata. The overall incidence of IC was 90/100 000 patients, which did not change significantly over time. There were no changes in incidence among C. albicans, C. glabrata, C. parapsilosis, or C. tropicalis; the incidence of other Candida spp. as a whole increased 7.2% annually. While there was no change in candidemia 2009–2017, abdominal and nonabdominal sterile site IC increased significantly.ConclusionsNonbloodstream IC is increasing in the United States. Understanding the epidemiology of IC should facilitate improved management of infected patients.

AbstractAfter 7-valent pneumococcal conjugate vaccine introduction in the United States in 2000, invasive pneumococcal disease (IPD) due to serotype 4 greatly decreased in children and adults. Starting in 2013, serotype 4 IPD incidence increased among adults within 3 of 10 Active Bacterial Core surveillance sites. Of 325 serotype 4 cases among adults in 2010–2018, 36% were persons experiencing homelessness (PEH); incidence of serotype 4 IPD among PEH was 100–300 times higher than in the general population within these 3 areas. Genome sequencing for isolates recovered 2015–2018 (n = 246), revealed that increases in serotype 4 IPD were driven by lineages ST10172, ST244, and ST695. Within each lineage, clusters of near-identical isolates indicated close temporal relatedness. Increases in serotype 4 IPD were limited to Colorado, California, and New Mexico, with highest increases among PEH, who were at increased risk for exposure to and infections caused by these strains.

AbstractBackgroundIt is not known whether reductions in socioeconomic and racial disparities in incidence of invasive pneumococcal disease (defined as the isolation of Streptococcus pneumoniae from a normally sterile body site) noted after pneumococcal conjugate vaccine (PCV) introduction have been sustained.MethodsIndividual-level data collected from 20 Tennessee counties participating in Active Bacterial Core surveillance over 19 years were linked to neighborhood-level socioeconomic factors. Incidence rates were analyzed across 3 periods—pre–7-valent PCV (pre-PCV7; 1998–1999), pre–13-valent PCV (pre-PCV13; 2001–2009), and post-PCV13 (2011–2016)—by socioeconomic factors.ResultsA total of 8491 cases of invasive pneumococcal disease were identified. Incidence for invasive pneumococcal disease decreased from 22.9 (1998–1999) to 17.9 (2001–2009) to 12.7 (2011–2016) cases per 100 000 person-years. Post-PCV13 incidence (95% confidence interval [CI]) of PCV13-serotype disease in high- and low-poverty neighborhoods was 3.1 (2.7–3.5) and 1.4 (1.0–1.8), respectively, compared with pre-PCV7 incidence of 17.8 (15.7–19.9) and 6.4 (4.9–7.9). Before PCV introduction, incidence (95% CI) of PCV13-serotype disease was higher in blacks than whites (17.3 [15.1–19.5] vs 11.8 [10.6–13.0], respectively); after introduction, PCV13-type disease incidence was greatly reduced in both groups (white: 2.7 [2.4–3.0]; black: 2.2 [1.8–2.6]).ConclusionsIntroduction of PCV13 was associated with substantial reductions in overall incidence and socioeconomic and racial disparities in PCV13-serotype incidence.

AbstractBackgroundThis is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG.MethodsCMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI.ResultsA total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1–53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL.ConclusionsMore than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

AbstractBackgroundGlobally, decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae is rising. We aimed to compile a global collection of N. gonorrhoeae strains and assess the genetic characteristics associated with decreased susceptibility to ceftriaxone.MethodsWe performed a literature review of all published reports of N. gonorrhoeae strains with decreased susceptibility to ceftriaxone (>0.064 mg/L minimum inhibitory concentration) through October 2019. Genetic mutations in N. gonorrhoeae genes (penA, penB, mtrR, and ponA), including determination of penA mosaicism, were compiled and evaluated for predicting decreased susceptibility to ceftriaxone.ResultsThere were 3821 N. gonorrhoeae strains identified from 23 countries and 684 (18%) had decreased susceptibility to ceftriaxone. High sensitivities or specificities (>95%) were found for specific genetic mutations in penA, penB, mtrR, and ponA, both with and without determination of penA mosaicism. Four algorithms to predict ceftriaxone susceptibility were proposed based on penA mosaicism determination and penA or non-penA genetic mutations, with sensitivity and specificity combinations up to 95% and 62%, respectively.ConclusionMolecular algorithms based on genetic mutations were proposed to predict decreased susceptibility to ceftriaxone in N. gonorrhoeae. Those algorithms can serve as a foundation for the development of future assays predicting ceftriaxone decreased susceptibility within N. gonorrhoeae globally.

AbstractBackground We investigated whether higher-intensity exercise provided greater decrease in markers of inflammation, and whether responses differed by HIV serostatus.MethodsPeople with HIV (PWH; n = 32) and controls (n = 37) aged 50–75 years completed 12 weeks moderate-intensity exercise, then were randomized to moderate- or high-intensity exercise for 12 additional weeks (n = 27 and 29, respectively). Inflammation biomarkers were measured at 0, 12, 24 weeks. Mixed and multiple regression models were adjusted for baseline inflammation, age, and body mass index.ResultsBaseline tumor necrosis factor-α (TNF-α), soluble TNF receptor 2 (sTNFR2), and soluble CD14 (sCD14) were significantly higher among PWH than controls (P < .04). From week 0–12, changes in interleukin-6 (IL-6), TNF-α, and sTNFR1 were not significantly different by HIV serostatus. We found no significant interaction between HIV serostatus/exercise intensity on week 12–24 changes in IL-6, TNF-α, and sTNFR1. Among high-intensity exercisers, PWH and controls had significant increases in sCD14 (P ≤ .003), controls significant increases in IL-10 (P = .01), and PWH nonsignificant decrease in highly sensitive C-reactive protein (P = .07). Other markers were not significantly different by serostatus or intensity.ConclusionsModerate and high-intensity exercise elicited similar effects on inflammation among PWH and controls, with additional beneficial effects seen among high-intensity exercisers. Increase in sCD14 and attenuated IL-10 increase (PWH only) merit further study.Clinical Trials RegistrationNCT02404792.

AbstractBackgroundInfluenza vaccination has been suggested to protect against death and recurrent events among patients with cardiovascular disease or chronic obstructive respiratory disease, but there is limited evidence in older adults, who have higher risks of influenza-associated hospitalization and mortality.MethodsPatients aged ≥60 years hospitalized for cardiovascular or respiratory diseases from the Beijing Urban Employee Basic Medical Insurance database during 3 influenza seasons (2013–2014 through 2015–2016) were pooled to estimate the effects of influenza vaccination on hospitalization outcomes. Vaccination status was ascertained through cross-referencing the Beijing Elderly Influenza Vaccination database. The summer months (June–August) were used as a reference period to adjust for unmeasured confounders during influenza seasons.ResultsAfter adjustment for both measured and unmeasured confounders, influenza vaccination was associated with lower risks of in-hospital deaths among patients hospitalized for cardiovascular (odds ratio [95% confidence interval], 0.85 [.68–1.06]) or respiratory diseases (0.66 [.54–.82]). Influenza vaccination was associated with a lower risk of readmission among patients with cardiovascular (odds ratio [95% confidence interval], 0.81 [.69–.95]) but not respiratory diseases (1.12 [.92–1.35]). Influenza vaccination was also associated with lower direct medical costs, but not with length of stay.ConclusionsInfluenza vaccination protected against hospitalization outcomes among older adults with cardiovascular or respiratory diseases.

AbstractDirect acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK-cell memory formation following HCV clearance by examining NK-cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post therapy (SVR12). NK-cell phenotype at SVR12 differed significantly from paired pretreatment samples, with an increase in maturation markers CD16, CD57, and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV-infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCV-specific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.

AbstractA successful Staphylococcus aureus vaccine remains elusive, and one controversy in the field is whether humans generate a protective adaptive immune response to infection. We developed a bacterial challenge murine assay that directly assesses the protective capacity of adoptively transferred human serum samples. We first validated the model by showing that postpneumococcal vaccine serum samples from humans induced effective clearance of Streptococcus pneumoniae in mice. We then found that human serum samples adoptively transferred from children with invasive S. aureus infections exhibited protection from disease in a murine model, with some samples conferring near complete protection. These findings demonstrate that human serum samples are capable of conferring a protective adaptive response generated by humans during invasive staphylococcal disease, allowing for the study of protective factors in a murine model. Identification of the protective factors present in the most efficacious serum samples would be of high interest as potential staphylococcal vaccine candidates or passive therapeutics.

AbstractBackgroundImmune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management.MethodsPlasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model.ResultsWe identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort.ConclusionsSystemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART.Clinical Trials Registration NCT00286767.

AbstractBackgroundAntibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein (GP) antibodies suggest that Fc-dependent activation of effector cells, including natural killer (NK) cells, could play a role in vaccination against Ebola virus disease.MethodsWe analyzed the effect on primary human NK cell activation of anti-Ebola GP antibody in the serum of United Kingdom–based volunteers vaccinated with the novel 2-dose heterologous adenovirus type 26.ZEBOV, modified vaccinia Ankara–BN-Filo vaccine regimen.ResultsWe demonstrate primary human NK cell CD107a and interferon γ expression, combined with down-regulation of CD16, in response to recombinant Ebola virus GP and post-vaccine dose 1 and dose 2 serum samples. These responses varied significantly with vaccine regimen, and NK cell activation was found to correlate with anti-GP antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive.ConclusionsThese findings highlight the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses.