Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial.

BACKGROUND: Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. METHODS AND FINDINGS: An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. CONCLUSIONS: Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900022409.

Development of SARS-CoV-2 packaged RNA reference material for nucleic acid testing.

Nucleic acid tests to detect the SARS-CoV-2 virus have been performed worldwide since the beginning of the COVID-19 pandemic. For the quality assessment of testing laboratories and the performance evaluation of molecular diagnosis products, reference materials (RMs) are required. In this work, we report the production of a lentiviral SARS-CoV-2 RM containing approximately 12 kilobases of its genome including common diagnostics targets such as RdRp, N, E, and S genes. The RM was measured with multiple assays using two different digital PCR platforms. To measure the homogeneity and stability of the lentiviral SARS-CoV-2 RM, reverse transcription droplet digital PCR (RT-ddPCR) was used with in-house duplex assays. The copy number concentration of each target gene in the extracted RNA solution was then converted to that of the RM solution. Their copy number values are measured to be from 1.5 × 105 to 2.0 × 105 copies/mL. The RM has a between-bottle homogeneity of 4.80-8.23% and is stable at 4 °C for 1 week and at -70 °C for 6 months. The lentiviral SARS-CoV-2 RM closely mimics real samples that undergo identical pre-analytical processes for SARS-CoV-2 molecular testing. By offering accurate reference values for the absolute copy number of viral target genes, the developed RM can be used to improve the reliability of SARS-CoV-2 molecular testing.

A blueprint for academic laboratories to produce SARS-CoV-2 quantitative RT-PCR test kits.

Widespread testing for the presence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise, and/or instrumentation necessary to detect the virus by quantitative RT-PCR (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages. The Georgia Tech COVID-19 Test Kit Support Group, composed of faculty, staff, and trainees across the biotechnology quad at Georgia Institute of Technology, synthesized multiplexed primers and probes and formulated a master mix composed of enzymes and proteins produced in-house. Our in-house kit compares favorably with a commercial product used for diagnostic testing. We also developed an environmental testing protocol to readily monitor surfaces for the presence of SARS-CoV-2. Our blueprint should be readily reproducible by research teams at other institutions, and our protocols may be modified and adapted to enable SARS-CoV-2 detection in more resource-limited settings.

Delayed Laboratory Response to COVID-19 Caused by Molecular Diagnostic Contamination.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) created an exceptional situation in which numerous laboratories in Europe simultaneously implemented SARS-CoV-2 diagnostics. These laboratories reported in February 2020 that commercial primer and probe batches for SARS-CoV-2 detection were contaminated with synthetic control material, causing delays of regional testing roll-out in various countries.

Can We Test Our Way Out of the COVID-19 Pandemic?

Frequent, low-cost, universal testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with quarantine of those with a positive result has been suggested as a strategy to address the coronavirus disease 2019 (COVID-19) pandemic in the United States. Specifically, home or community use of tests that use paper strip detection devices, which may have reduced sensitivity for SARS-CoV-2, has been advocated. There are several potential challenges or problems with this strategy, including the limited availability of such tests, consequences of incorrect test results, difficulties with adherence to testing, and the questionable accuracy of such tests for detection of infectious people. Because of these, we think it is premature to strongly advocate for such a testing strategy, as the adverse consequences may outweigh any benefits. High-quality outcome data demonstrating the efficacy of this testing strategy are needed before widespread implementation.

Risks of emergency use authorizations for medical products during outbreak situations: a COVID-19 case study.

BACKGROUND: The world is facing an unprecedented outbreak affecting all aspects of human lives which is caused by the COVID-19 pandemic. Due to the virus novelty, healthcare systems are challenged by a high rate of patients and the shortage of medical products. To address an increased need for essential medical products, national authorities, worldwide, made various legislative concessions. This has led to essential medical products being produced by automotive, textile and other companies from various industries and approved under the emergency use authorizations or legal concessions of national regulatory bodies. This paper presents a narrative commentary of the available documentation on emergency use authorizations and legal concessions for medical products during COVID-19 pandemic. METHODOLOGY: The basis for narrative commentary includes scientific articles published in Web of Science, Scopus, PubMed and Embase databases, official publications of international organizations: Food and Drug Agency (FDA), World Health Organisation (WHO), World Bank and United Nations (UN), and national regulatory agency reports in native languages (English, German, Bosnian, and Croatian) published from November 1, 2019 to May 1, 2020. This paper focuses on three types of essential medical products: mechanical ventilators, personal protective equipment (PPE) and diagnostic tests. Evidence-informed commentary of available data and potential identified risks of emergency use authorizations and legal concessions is presented. DISCUSSION: It is recognized that now more than ever, raising global awareness and knowledge about the importance of respecting the essential requirements is needed to guarantee the appropriate quality, performance and safety of medical products, especially during outbreak situation, such as the COVID-19 pandemic. Emergency use authorizations for production, import and approval of medical products should be strictly specified and clearly targeted from case to case and should not be general or universal for all medical products, because all of them are associated with different risk level. CONCLUSION: Presented considerations and experiences should be taken as a guide for all possible future outbreak situations to prevent improvised reactions of national regulatory bodies.

Relationship Gender Equality and Couples' Uptake of Oral Human Immunodeficiency Virus Self-Testing Kits Delivered by Pregnant Women in Kenya.

BACKGROUND: Higher gender equality is associated with many human immunodeficiency virus (HIV) preventive behaviors, including HIV testing. HIV self-testing is a relatively new testing technology that could assist with HIV prevention. However, there are no studies examining gender equality and HIV self-testing. We examined the associations between gender equality and couples' uptake of HIV self-testing among heterosexual couples expecting a child in central Kenya. METHODS: This analysis used data from a HIV self-testing randomized intervention trial among pregnant women attending antenatal care and their male partners. The primary exposures were gender equality (measured by the male partner's attitudes toward intimate partner violence, and the woman's report on her household decision making power), and the primary outcome was couples' uptake of HIV self-testing. Generalized linear mixed models framework was used to account for site-level clustering. RESULTS: In comparison to male partners reporting high acceptance of intimate partner violence, couples with male partners reporting medium acceptance (odds ratio, 2.36; 95% confidence interval, 0.99-5.63) or low acceptance (odds ratio, 2.50; 95% confidence interval, 1.20-5.21) were significantly more likely to use HIV self-testing. Gender equality measured by decision making power was not associated with couples' uptake of HIV self-testing. CONCLUSIONS: This study is the first of its kind to examine the association between gender equality and couples' HIV self-testing. This holds important implications for HIV self-testing as we strive to achieve the United Nations Programme on HIV/acquired immune deficiency syndrome goal that 90% of individuals living with HIV should know their status.

Where are we now? A multicountry qualitative study to explore access to pre-antiretroviral care services: a precursor to antiretroviral therapy initiation.

OBJECTIVE: To explore barriers and facilitators to accessing postdiagnosis HIV care in five sub-Saharan African countries. METHODS: In-depth interviews were conducted with 77 people living with HIV (PLHIV) in pre-antiretroviral therapy care or not-yet-in care and 46 healthcare workers. Participants were purposely selected from health and demographic surveillance sites in Karonga (Malawi), Manicaland (Zimbabwe), uMkhanyakude (South Africa), Kisesa (Tanzania) and Rakai and Kyamulibwa (Uganda). Thematic content analysis was conducted, guided by the constructs of affordability, availability and acceptability of care.- RESULTS: Affordability: Transport and treatment costs were a barrier to HIV care, although some participants travelled to distant clinics to avoid being seen by people who knew them or for specific services. Broken equipment and drug stock-outs in local clinics could also necessitate travel to other facilities. Availability: Some facilities did not offer full HIV care, or only offered all services intermittently. PLHIV who frequently travelled complained that care was seldom available to them in places they visited. Acceptability: Severe pain or sickness was a key driver for accessing postdiagnosis care, whereas asymptomatic PLHIV often delayed care-seeking. A belief in witchcraft was a deterrent to accessing clinical care following diagnosis. Changing antiretroviral therapy guidelines generated uncertainty among PLHIV about when to start treatment and delayed postdiagnosis care. PLHIV reported that healthcare workers' knowledge, attitudes and behaviours, and their ability to impart health education, also influenced whether they accessed HIV care. CONCLUSION: Despite efforts to decentralise services over the past decade, many barriers to accessing HIV care persist. There is a need to increase sustained access to care for PLHIV not yet on treatment, with initiatives that encompass biomedical aspects of care alongside considerations for individual and collective challenges they faced. A failure to do so may undermine efforts to achieve universal access to antiretroviral therapy.

Availability, Accessibility, and Price of Rapid HIV Self-Tests, New York City Pharmacies, Summer 2013.

We conducted an in-person survey of New York City (NYC) pharmacies to assess the availability, accessibility, and price of the over-the-counter, rapid HIV self-test kit. NYC pharmacies were stratified into high, moderate and low morbidity neighborhoods by the HIV diagnosis rate of the neighborhood in which the pharmacy was located. A random sample of 500 pharmacies was taken [250 from high morbidity neighborhoods (HighMN) and 250 from low morbidity neighborhoods (LowMN)]. Pharmacies were excluded if: closed during survey, non-retail, or >10 min walk from subway. Project staff visited pharmacies to determine kit availability (in pharmacy on day of survey), accessibility (not locked/behind counter), and price (marked on shelf/product). Of 361 pharmacies (161 LowMN; 200 HighMN), kits were available in 27 % and accessible in 10 %; there was no difference by neighborhood. Kits were most often kept behind the pharmacy counter; this was more common in HighMN than in LowMN. Kits were kept solely behind the pharmacy counter in 52 %. Median price was US $42.99 without variability across neighborhoods. The rapid HIV self-test had limited availability and access in retail pharmacies. The high median price measured suggests that cost remained a barrier.

Willingness to distribute free rapid home HIV test kits and to test with social or sexual network associates among men who have sex with men in the United States.

Peer-driven HIV prevention strategies can be effective in identifying high-risk persons with undiagnosed infections. Besides individual self-testing, other potential uses of rapid home HIV test kits include distributing them, and testing with others within one's social or sexual networks. We sought to identify factors associated with the willingness to engage in these alternative activities among men who have sex with men (MSM) in the United States. From May to October 2014, we surveyed 828 HIV-negative or unknown status MSM about multiple aspects of rapid home HIV testing. A greater proportion indicated being likely to distribute free oral fluid (OF) tests compared to free finger-stick blood (FSB) tests (91% versus 79%), and almost three-fourths (72%) reported being likely to test with their friends or sex partners in the future. MSM not identifying as homosexual/gay were less willing to distribute OF tests, and those with lower educational attainment were more willing to distribute FSB tests. MSM unaware of their HIV status were less likely to report potentially testing with others using free rapid home HIV tests compared to those who were HIV-negative. Finally, MSM willing to self-test were more likely to report future test kit distribution, and those willing to distribute kits were more likely to report potentially testing with others. Engaging individuals with positive attitudes towards these strategies in prevention efforts could help increase HIV testing levels among MSM. A greater understanding of the potential public health impact of rapid home HIV test kits is necessary.

Notes from the Field: Baseline Assessment of the Use of Ebola Rapid Diagnostic Tests--Forécariah, Guinea, October-November 2015.

The Ebola virus disease (Ebola) epidemic in West Africa began in Guinea in early 2014. The reemergence of Ebola and risk of ongoing, undetected transmission continues because of the potential for sexual transmission and other as yet unknown transmission pathways. On March 17, 2016, two new cases of Ebola in Guinea were confirmed by the World Health Organization. This reemergence of Ebola in Guinea is the first since the original outbreak in the country was declared over on December 29, 2015. The prefecture of Forécariah, in western Guinea, was considerably affected by Ebola in 2015, with an incidence rate of 159 cases per 100,000 persons. Guinea also has a high prevalence of malaria; in a nationwide 2012 survey, malaria prevalence was reported to be 44% among healthy children aged ≤5 years. Malaria is an important reason for seeking health care; during 2014, 34% of outpatient consultations were related to malaria.

A cross-sectional study of the availability and price of anti-malarial medicines and malaria rapid diagnostic tests in private sector retail drug outlets in rural Western Kenya, 2013.

BACKGROUND: Although anti-malarial medicines are free in Kenyan public health facilities, patients often seek treatment from private sector retail drug outlets. In mid-2010, the Affordable Medicines Facility-malaria (AMFm) was introduced to make quality-assured artemisinin-based combination therapy (ACT) accessible and affordable in private and public sectors. METHODS: Private sector retail drug outlets stocking anti-malarial medications within a surveillance area of approximately 220,000 people in a malaria perennial high-transmission area in rural western Kenya were identified via a census in September 2013. A cross-sectional study was conducted in September-October 2013 to determine availability and price of anti-malarial medicines and malaria rapid diagnostic tests (RDTs) in drug outlets. A standardized questionnaire was administered to collect drug outlet and personnel characteristics and availability and price of anti-malarials and RDTs. RESULTS: Of 181 drug outlets identified, 179 (99 %) participated in the survey. Thirteen percent were registered pharmacies, 25 % informal drug shops, 46 % general shops, 13 % homesteads and 2 % other. One hundred sixty-five (92 %) had at least one ACT type: 162 (91 %) had recommended first-line artemether-lumefantrine (AL), 22 (12 %) had recommended second-line dihydroartemisinin-piperaquine (DHA-PPQ), 85 (48 %) had sulfadoxine-pyrimethamine (SP), 60 (34 %) had any quinine (QN) formulation, and 14 (8 %) had amodiaquine (AQ) monotherapy. The mean price (range) of an adult treatment course for AL was $1.01 ($0.35-4.71); DHA-PPQ was $4.39 ($0.71-7.06); QN tablets were $2.24 ($0.12-4.71); SP was $0.62 ($0.24-2.35); AQ monotherapy was $0.42 ($0.24-1.06). The mean AL price with or without the AMFm logo did not differ significantly ($1.01 and 1.07, respectively; p = 0.45). Only 17 (10 %) drug outlets had RDTs; 149 (84 %) never stocked RDTs. The mean RDT price was $0.92 ($0.24-2.35). CONCLUSIONS: Most outlets never stocked RDTs; therefore, testing prior to treatment was unlikely for customers seeking treatment in the private retail sector. The recommended first-line treatment, AL, was widely available. Although SP and AQ monotherapy are not recommended for treatment, both were less expensive than AL, which might have caused preferential use by customers. Interventions that create community demand for malaria diagnostic testing prior to treatment and that increase RDT availability should be encouraged.

Public readiness for HIV self-testing in Kenya.

High interest and a growing body of evidence suggest that HIV self-testing could help fill the HIV testing gap for populations who have been hesitant to access testing services through current mechanisms. Evidence from five of six studies funded by 3ie answers questions posed by the Kenyan government to understand the readiness of Kenyans for HIV self-testing. The findings suggest that Kenyans are generally ready for HIV self-testing. Most people would not only like to obtain self-test kits through public health facilities but also expect to be able to obtain them from pharmacies - easy access being a key factor for a distribution outlet. Respondents across the studies seem to understand the importance of counseling and confirmatory testing, although the decision to access services after an HIV self-test will certainly be influenced by the results of the test. Respondents do have some concerns about potential harms and abuses from HIV self-tests. These concerns are focused on what they expect others would do, rather than reflections of what they say they would do themselves. Additionally, most people believe that such concerns were mostly unwarranted and/or could be addressed.

The Cobas® EGFR Mutation Test v2 assay.

Paul Brown speaks to Gemma Westcott, Commissioning Editor: Paul Brown has served as the Head of Roche Molecular Diagnostics at Roche Diagnostics Corporation since February 2010 having previously held a variety of positions within Roche Pharma. After completing his doctorate in organic chemistry he was awarded a post-doctoral fellowship at the California Institute of Technology in Pasadena, CA, USA, but soon returned to his native UK to join Roche Pharma Research. Paul's first post within Roche was as group leader, doing drug discovery and making new small molecule drugs, but later moved into the business part of the company. Since then, he has enjoyed roles such as lifecycle leader for brands such as Tamiflu(®) and Xenical, vice president of sales and marketing of the pharmaceutical division and most recently general manager of Roche Pharma, Sweden.

Implementation of repeat HIV testing during pregnancy in Kenya: a qualitative study.

BACKGROUND: Repeat HIV testing in late pregnancy has the potential to decrease rates of mother-to-child transmission of HIV by identifying mothers who seroconvert after having tested negative for HIV in early pregnancy. Despite being national policy in Kenya, the available data suggest that implementation rates are low. METHODS: We conducted 20 in-depth semi-structured interviews with healthcare providers and managers to explore barriers and enablers to implementation of repeat HIV testing guidelines for pregnant women. Participants were from the Nyanza region of Kenya and were purposively selected to provide variation in socio-demographics and job characteristics. Interview transcripts were coded and analyzed in Dedoose software using a thematic analysis approach. Four themes were identified a priori using Ferlie and Shortell's Framework for Change and additional themes were allowed to emerge from the data. RESULTS: Participants identified barriers and enablers at the client, provider, facility, and health system levels. Key barriers at the client level from the perspective of providers included late initial presentation to antenatal care and low proportions of women completing the recommended four antenatal visits. Barriers to offering repeat HIV testing for providers included heavy workloads, time limitations, and failing to remember to check for retest eligibility. At the facility level, inconsistent volume of clients and lack of space required for confidential HIV retesting were cited as barriers. Finally, at the health system level, there were challenges relating to the HIV test kit supply chain and the design of nationally standardized antenatal patient registers. Enablers to improving the implementation of repeat HIV testing included client dissemination of the benefits of antenatal care through word-of-mouth, provider cooperation and task shifting, and it was suggested that use of an electronic health record system could provide automatic reminders for retest eligibility. CONCLUSIONS: This study highlights some important barriers to improving HIV retesting rates among pregnant women who attend antenatal clinics in the Nyanza region of Kenya at the client, provider, facility, and health system levels. To successfully implement Kenya's national repeat HIV testing guidelines during pregnancy, it is essential that these barriers be addressed and enablers capitalized on through a multi-faceted intervention program.

Challenges encountered in providing integrated HIV, antenatal and postnatal care services: a case study of Katakwi and Mubende districts in Uganda.

BACKGROUND: Integration of sexual and reproductive health (SRH), HIV/AIDS and maternal health (MH) services is a critical strategy to confront the HIV/AIDS epidemic, high maternal mortality and the unmet need for contraception. In 2011 the AIDS Information Centre (AIC) in partnership with the Ministry of Health implemented SRH, HIV/AIDS and MH integration services in the districts of Katakwi and Mubende in Uganda. This paper documents challenges encountered in providing these integrated services in the two districts. METHODS: This was a cross-sectional qualitative study conducted in Mubende and Katakwi districts in Uganda. Data were collected using 10 focus group discussions with 89 women attending ANC and postnatal care and 21 key informant interviews with district managers and health workers who were involved in the integrated service delivery. Content thematic approach was used for data analysis. RESULTS: The study findings indicate that various challenges were encountered in integrating HIV, ANC and PNC services. Major challenges included inadequate staff, gaps in knowledge of service providers especially with regard to provision of long-term family planning, limited space, shortage of critical supplies such as HIV test kits, drugs and gloves. CONCLUSION: These findings indicate that the delivery of integrated HIV, SRH and MH services is hampered greatly by health system challenges and depict the need for additional staffing in health facilities, capacity building of health workers and health managers as well as ensuring sufficient supplies to health facilities for smooth implementation of integrated SRH, HIV and MH services.

Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda: lessons learned and policy implications.

BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons learned and policy implications. RESULTS: Introducing RDTs into drug shops was feasible. To scale-up this intervention however, drug shop practices need to be regulated since the registration process was not clear, supervision was inadequate and record keeping was poor. Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome, but at evaluation this was not found to be a constraint. This presents an important lesson for introducing health management information system into drug shops. Involving stakeholders, especially the district health team, in the design was important for ownership and sustainability. The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions. CONCLUSION: Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy. It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector.