Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Promising developments in gonococcal vaccines.

PURPOSE OF REVIEW: While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades. This review highlights recent progress in the field. RECENT FINDINGS: Vaccines containing outer-membrane vesicles (OMV) have been used to manage outbreaks of the serogroup B N. meningitidis in a number of countries. Epidemiologic studies indicate these vaccination campaigns were associated with reductions in reported N. gonorrhoeae infections. Recently, a serogroup B N. meningitidis vaccine containing both recombinant antigens and OMV has been licensed through much of the world. Epidemiologic studies also demonstrate associations between 4CMenB immunization and reduced N. gonorrhoeae infections. Additionally, mathematical modeling studies have begun to identify potential strategies for vaccine deployment to maximize reduction of infections. SUMMARY: After several decades with little progress towards an effective gonococcal vaccine, large observational studies have provided evidence that a new generation of group B N. meningitidis vaccines containing OMV have serendipitously restarted the field. Ongoing clinical trials will soon provide definitive evidence regarding the efficacy of these vaccines in preventing N. gonorrhoeae infection.

Efficacy of Two Evidence-Based Alcohol Consumption Interventions on Positive, Negative, and Neutral Days Among Hazardous Alcohol Users Living with HIV in Vietnam.

Social events and stressful settings can be catalysts for alcohol consumption. Motivational enhancement therapy (MET) and cognitive behavioral therapy (CBT) are widely used in alcohol interventions. We assessed how alcohol consumption varied across three types of days (positive/social, negative/stressful, and neutral) among hazardous alcohol users living with HIV in Vietnam. We further evaluated how those consumption patterns changed after two MET/CBT alcohol reduction interventions versus the standard of care (SOC). The 'combined' intervention offered 6 individual sessions and 3 group sessions; the 'brief' intervention offered 2 individual sessions and 2 phone calls. A 30-day timeline follow-back was administered at study visits, detailing daily drinks and events. Days were categorized as neutral, positive/social, or negative/stressful; negative binomial models and generalized estimating equations were used to estimate drinks consumed by type of day at baseline and 12 months. Prior to intervention, more drinks were consumed on positive/social days (5.2 drinks; 95% Confidence Interval [CI]:4.8, 5.7) than negative/stressful (1.5; 95% CI:1.3, 1.9) and neutral days (2.2; 95% CI: 1.9, 2.5). After the brief intervention, drinks consumed decreased on neutral days (ratio: 0.5: 95% CI: 0.4, 0.7). After the combined intervention, drinks consumed decreased on neutral days (ratio: 0.4; 95% CI: 0.3, 0.6), positive/social days (ratio: 0.6; 95% CI: 0.5, 0.7) and negative/stressful days (ratio: 0.3; 95% CI: 0.2, 0.6). No reductions in consumption were observed in the SOC group. Social/positive days had the highest alcohol consumption prior to intervention, and the combined intervention showed the greatest decrease in consumption on those days. CLINICAL TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT02720237).

Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20.

OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.

Dramatic Shift in the Etiology of Genital Ulcer Disease Among Patients Visiting a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Genital ulcer diseases (GUDs) are a common syndrome associated with sexually transmitted infections. Genital ulcer diseases increase the risk of HIV transmission, necessitating appropriate diagnosis and treatment. We provide an updated GUD etiology assessment in Malawi to guide diagnostic development and treatment algorithms. METHODS: We enrolled patients 18 years or older presenting with GUD at a sexually transmitted infection clinic in Lilongwe, Malawi, between May and October 2021. We purposively sampled by HIV status. Swabs of ulcers were tested for Treponema pallidum, herpes simplex virus (HSV)-1 and HSV-2, Haemophilus ducreyi, and Chlamydia trachomatis using polymerase chain reaction. Blood was collected for syphilis and HSV-2 serologies and acute HIV testing. Participants were treated per Malawi guidelines. Ulcer resolution (size reduced by >50%) was evaluated 14 days later. RESULTS: Fifty participants enrolled (30 without HIV, 2 with acute HIV infection, 18 with HIV seropositivity; 32 men, 18 women). Forty-six (92%) had an etiology identified. Syphilis was more common among those without HIV (22 of 30 [73%]) than participants with HIV (PWH; 8 of 20 [40%]; P = 0.04). Herpes simplex virus was more common among PWH (11 of 20 [55%]) than participants without (2 of 30 [7%]; P = 0.0002). One-fifth (9 of 50 [18%]) had H. ducreyi. Among those who returned for follow-up (n = 45), 9 (20%) had unresolved ulcers; persistent GUD was slightly more common in PWH (6 of 19 [32%]) than participants without (3 of 26 [12%]; P = 0.14). CONCLUSIONS: We observed a dramatic increase in syphilis ulcer proportion in a population whose GUDs were previously HSV predominant. Observed differences in etiology and resolution by HIV status could play an important role in the ongoing transmission and treatment evaluation of GUD.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Effects of Urethritis on Human Immunodeficiency Virus (HIV) in Semen: Implications for HIV Prevention and Cure.

BACKGROUND: Prior to the widespread availability of antiretroviral therapy (ART), men living with human immunodeficiency virus (HIV) with urethritis had increased concentrations of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and its implications for the cure of HIV. METHODS: Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits at 1, 2, 4, 8, 12, 24, 36, and 48 weeks after urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. RESULTS: There were 111 men enrolled in the study between January 2017-March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. During nonurethritis follow-up, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. CONCLUSIONS: An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field.

Outcomes From Re-Treatment and Cerebrospinal Fluid Analyses in Patients With Syphilis Who Had Serological Nonresponse or Lack of Seroreversion After Initial Therapy.

BACKGROUND: We conducted an observational study to determine whether patients with syphilis who do not demonstrate serological cure or lack of seroreversion in nontreponemal (NT) antibody titers after initial therapy benefit from re-treatment and cerebrospinal fluid (CSF) analysis. METHODS: We enrolled patients with syphilis from sexually transmitted disease clinics in Guangzhou, China, who had persistent NT titers after therapy. Serological nonresponse was defined as a <4-fold decline in baseline NT titers after therapy. Lack of seroreversion was defined as demonstrating a ≥4-fold NT titer decline but without seroreversion to negative, or having persistent low-level titers (i.e., 1:1-1:2) after therapy. After consent, we abstracted medical record data regarding syphilis diagnoses, initial and re-treatment regimens, and serological outcomes. Nontreponemal titers were obtained from participants at enrollment and follow-up. We evaluated CSF findings among a subgroup of participants relative to re-treatment. RESULTS: From March 2012 to February 2016, we enrolled 135 HIV-negative patients with syphilis with persistent NT titers after initial therapy. Among 116 participants with ≥12 months of follow-up, 60 (52%) received re-treatment of syphilis. Overall, there were no significant differences in serological response between those who were re-treated and those who were not among serological nonresponders (29% vs. 27%; P = 1.0) or among participants without seroconversion (41% vs. 37%; P = 0.8). Of 60 participants who underwent CSF analyses, 8 (13%) had CSF abnormalities, but only 2 (3%) met the neurosyphilis criteria after re-treatment. CONCLUSIONS: Most HIV-negative patients with syphilis who have serological nonresponse or lack of seroreversion after therapy do not benefit from re-treatment in the short term, and neurosyphilis is uncommon.

Syndromes Associated with Sexually Transmitted Infections in Lilongwe, Malawi: Burden and Trends, 2006 to 2015.

ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.

Real-world experience using hydroxyurea in children with sickle cell disease in Lilongwe, Malawi.

INTRODUCTION: Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region-specific evidence for safety and efficacy. METHODS: We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10-20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy). RESULTS: Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow-up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (-4.1 per 1000 person-days; -7.2, -1.0; P = .004), fevers (-4.2 per 1000 person-days; -7.2, -1.1; P = .002), transfusions (-2.3 per 1000 person-days; 95% confidence interval: -4.9, 0.3; P = .06), and annual school absenteeism (-51.2 per person-year; -60.1, -42.3; P < .0001) within 6 months of hydroxyurea commencement. CONCLUSION: We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high-risk children. This highlights the importance of continued widespread scale-up of hydroxyurea within SCD programs across SSA.

High rates of transmitted NNRTI resistance among persons with acute HIV infection in Malawi: implications for first-line dolutegravir scale-up.

High rates of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was a key consideration in the WHO policies transitioning first-line regimens to include integrase inhibitors (dolutegravir [DTG]). However, recent data suggests a relationship between DTG and neural tube defects among women exposed during conception, giving providers and policymakers pause regarding the planned regimen changes. We examined HIV drug resistance among a cohort of 46 acutely infected persons in Malawi. Our data demonstrates high levels of transmitted resistance, 11% using standard resistance surveillance mutations and 20% when additional NNRTI polymorphisms that may affect treatment response are included. High resistance rates in this treatment-naïve patient population reinforces the critical nature of DTG-based options in the context of public-health driven treatment programs.

Primary Care Providers' Beliefs and Recommendations and Use of Screening Mammography by their Patients.

BACKGROUND: Revised breast cancer screening guidelines have fueled debate about the effectiveness and frequency of screening mammography, encouraging discussion between women and their providers. OBJECTIVE: To examine whether primary care providers' (PCPs') beliefs about the effectiveness and frequency of screening mammography are associated with utilization by their patients. DESIGN: Cross-sectional survey data from PCPs (2014) from three primary care networks affiliated with the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium, linked with data about their patients' mammography use (2011-2014). PARTICIPANTS: PCPs (n = 209) and their female patients age 40-89 years without breast cancer (n = 30,233). MAIN MEASURES: Outcomes included whether (1) women received a screening mammogram during a 2-year period; and (2) screened women had >1 mammogram during that period, reflecting annual screening. Principal independent variables were PCP beliefs about the effectiveness of mammography and their recommendations for screening frequency. KEY RESULTS: Overall 65.2% of women received >1 screening mammogram. For women 40-48 years, mammography use was modestly lower for those cared for by PCPs who believed that screening was ineffective compared with those who believed it was somewhat or very effective (59.1%, 62.3%, and 64.7%; p = 0.019 after controlling for patient characteristics). Of women with PCPs who reported they did not recommend screening before age 50, 48.1% were nonetheless screened. For women age 49-74 years, the vast majority were cared for by providers who believed that screening was effective. Provider recommendations were not associated with screening frequency. For women ≥75 years, those cared for by providers who were uncertain about effectiveness had higher screening use (50.7%) than those cared for by providers who believed it was somewhat effective (42.8%). Patients of providers who did not recommend screening were less likely to be screened than were those whose providers recommended annual screening, yet 37.1% of patients whose providers recommended against screening still received screening. CONCLUSIONS: PCP beliefs about mammography effectiveness and screening recommendations are only modestly associated with use, suggesting other likely influences on patient participation in mammography.

Inadequate Systems to Support Breast and Cervical Cancer Screening in Primary Care Practice.

BACKGROUND: Despite substantial resources devoted to cancer screening nationally, the availability of clinical practice-based systems to support screening guidelines is not known. OBJECTIVE: To characterize the prevalence and correlates of practice-based systems to support breast and cervical cancer screening, with a focus on the patient-centered medical home (PCMH). DESIGN: Web and mail survey of primary care providers conducted in 2014. The survey assessed provider (gender, training) and facility (size, specialty training, physician report of National Committee for Quality Assurance (NCQA) PCMH recognition, and practice affiliation) characteristics. A hierarchical multivariate analysis clustered by clinical practice was conducted to evaluate characteristics associated with the adoption of practice-based systems and technology to support guideline-adherent screening. PARTICIPANTS: Primary care physicians in family medicine, general internal medicine, and obstetrics and gynecology, and nurse practitioners or physician assistants from four clinical care networks affiliated with PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium research centers. MAIN MEASURES: The prevalence of routine breast cancer risk assessment, electronic health record (EHR) decision support, comparative performance reports, and panel reports of patients due for routine screening and follow-up. KEY RESULTS: There were 385 participants (57.6 % of eligible). Forty-seven percent (47.0 %) of providers reported NCQA recognition as a PCMH. Less than half reported EHR decision support for breast (48.8 %) or cervical cancer (46.2 %) screening. A minority received comparative performance reports for breast (26.2 %) or cervical (19.7 %) cancer screening, automated reports of patients overdue for breast (18.7 %) or cervical (16.4 %) cancer screening, or follow-up of abnormal breast (18.1 %) or cervical (17.6 %) cancer screening tests. In multivariate analysis, reported NCQA recognition as a PCMH was associated with greater use of comparative performance reports of guideline-adherent breast (OR 3.23, 95 % CI 1.58-6.61) or cervical (OR 2.56, 95 % CI 1.32-4.96) cancer screening and automated reports of patients overdue for breast (OR 2.19, 95 % CI 1.15-41.7) or cervical (OR. 2.56, 95 % CI 1.26-5.26) cancer screening. CONCLUSIONS: Providers lack systems to support breast and cervical cancer screening. Practice transformation toward a PCMH may support the adoption of systems to achieve guideline-adherent cancer screening in primary care settings.

Provider Attitudes and Screening Practices Following Changes in Breast and Cervical Cancer Screening Guidelines.

BACKGROUND: Changes to national guidelines for breast and cervical cancer screening have created confusion and controversy for women and their primary care providers. OBJECTIVE: To characterize women's primary health care provider attitudes towards screening and changes in practice in response to recent revisions in guidelines for breast and cervical cancer screening. DESIGN, SETTING, PARTICIPANTS: In 2014, we distributed a confidential web and mail survey to 668 women's health care providers affiliated with the four clinical care networks participating in the three PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium breast cancer research centers (385 respondents; response rate 57.6 %). MAIN MEASURES: We assessed self-reported attitudes toward breast and cervical cancer screening, as well as practice changes in response to the most recent revisions of the U.S. Preventive Services Task Force (USPSTF) recommendations. KEY RESULTS: The majority of providers believed that mammography screening was effective for reducing cancer mortality among women ages 40-74 years, and that Papanicolaou (Pap) testing was very effective for women ages 21-64 years. While the USPSTF breast and cervical cancer screening recommendations were widely perceived by the respondents as influential, 75.7 and 41.2 % of providers (for mammography and cervical cancer screening, respectively) reported screening practices in excess of those recommended by USPSTF. Provider-reported barriers to concordance with guideline recommendations included: patient concerns (74 and 36 % for breast and cervical, respectively), provider disagreement with the recommendations (50 and 14 %), health system measurement of a provider's screening practices that use conflicting measurement criteria (40 and 21 %), concern about malpractice risk (33 and 11 %), and lack of time to discuss the benefits and harms with their patients (17 and 8 %). CONCLUSIONS: Primary care providers do not consistently follow recent USPSTF breast and cervical cancer screening recommendations, despite noting that these guidelines are influential.

Take the money and run? Redemption of a gift card incentive in a clinician survey.

BACKGROUND: Clinician surveys provide critical information about many facets of health care, but are often challenging to implement. Our objective was to assess use by participants and non-participants of a prepaid gift card incentive that could be later reclaimed by the researchers if unused. METHODS: Clinicians were recruited to participate in a mailed or online survey as part of a study to characterize women's primary health care provider attitudes towards breast and cervical cancer screening guidelines and practices (n = 177). An up-front incentive of a $50 gift card to a popular online retailer was included with the study invitation. Clinicians were informed that the gift card would expire if it went unused after 4 months. Outcome measures included use of gift cards by participants and non-participants and comparison of hypothetical costs of different incentive strategies. RESULTS: 63.5% of clinicians who responded to the survey used the gift card, and only one provider who didn't participate used the gift card (1.6%). Many of those who participated did not redeem their gift cards (36.5% of respondents). The price of the incentives actually claimed totaled $3700, which was less than half of the initial outlay. Since some of the respondents did not redeem their gift cards, the cost of incentives was less than it might have been if we had provided a conditional incentive of $50 to responders after they had completed the survey. CONCLUSIONS: Redeemable online gift card codes may provide an effective way to motivate clinicians to participate in surveys.

Scaling up a brief alcohol intervention to prevent HIV infection in Vietnam: a cluster randomized, implementation trial.

BACKGROUND: Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians' attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians' knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use. METHODS: Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians' alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI. PARTICIPANTS: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months. OUTCOMES: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff's alcohol use and clinic-level alcohol expectations in the EBAI arm. DISCUSSION: This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases. TRIAL REGISTRATION: NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 .

Kusankha Pamodzi: Health Care Decision-Making Preferences Among Patients with Cancer in Malawi.

Background: Oncology teams are encouraged to include patient preferences and goals of care in determining appropriate treatment courses. There are no existing data from Malawi exploring decision-making preferences among cancer patients. Methods: In the oncology clinic in Lilongwe, Malawi, 50 patients were surveyed for decision making. Results: Most participants (70%, n = 35) preferred to engage in shared decision making regarding cancer treatment. About half (52%, n = 24) did not feel that their medical team involved them in decision making and 64% (n = 32) felt that they were never or only sometimes listened to by the medical team. Nearly all (94%, n = 47) preferred to have their medical team inform them how likely treatments are to lead to cure. Conclusions: Shared decision making was the preferred mode of treatment decision making by the majority of the surveyed cancer patients in Malawi. Cancer patients in Malawi may have similar preferences to cancer patients in other low-resource settings regarding decision making and communication.

Characterizing Network-Based HIV Testing Interventions to Guide HIV Testing and Contact Tracing at STI Clinics in Lilongwe, Malawi.

BACKGROUND: Understanding heterogeneity across patients in effectiveness of network-based HIV testing interventions may optimize testing and contact tracing strategies, expediting linkage to therapy or prevention for contacts of persons with HIV (PWH). SETTING: We analyzed data from a randomized controlled trial of a combination intervention comprising acute HIV testing, contract partner notification (cPN), and social contact referral conducted among PWH at 2 STI clinics in Lilongwe, Malawi, between 2015 and 2019. METHODS: We used binomial regression to estimate the effect of the combination intervention vs. passive PN (pPN) on having any (1) contact, (2) newly HIV-diagnosed contact, and (3) HIV-negative contact present to the clinic, overall and by referring participant characteristics. We repeated analyses comparing cPN alone with pPN. RESULTS: The combination intervention effect on having any presenting contact was greater among referring women than men [prevalence difference (PD): 0.17 vs. 0.10] and among previously vs. newly HIV-diagnosed referring persons (PD: 0.20 vs. 0.11). Differences by sex and HIV diagnosis status were similar in cPN vs. pPN analyses. There were no notable differences in the intervention effect on newly HIV-diagnosed referrals by referring participant characteristics. Intervention impact on having HIV-negative presenting contacts was greater among younger vs. older referring persons and among those with >1 vs. ≤1 recent sex partner. Effect differences by age were similar for cPN vs. pPN. CONCLUSION: Our intervention package may be particularly efficacious in eliciting referrals from women and previously diagnosed persons. When the combination intervention is infeasible, cPN alone may be beneficial for these populations.

Phosphatidylethanol and self-reported alcohol consumption among people living with HIV in Thai Nguyen, Vietnam.

BACKGROUND: Phosphatidylethanol (PEth) is a biomarker for recent alcohol consumption that would ideally validate self-reported alcohol consumption behaviors. We assessed the relationship between PEth and several self-reported alcohol consumption metrics among hazardous alcohol users living with HIV in Vietnam. METHODS: Participants in a three-arm randomized controlled trial assessing two alcohol interventions reported recent alcohol consumption on a 30-day timeline follow-back interview and had a PEth assessment at enrollment, 3 months, and 12 months of the study follow-up. We examined the relationship between self-reported alcohol consumption and quantitative PEth results using Spearman rank correlation and receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC). We assessed associations between categorical PEth results and self-reported drinking behaviors using prevalence ratios calculated with regression models and generalized estimating equations. RESULTS: Among 1221 study visits (n = 439 participants; 425 (97%) men), the median PEth result was 71 ng/mL (Interquartile range (IQR): 20, 212), and participants reported a median of 11 (IQR: 4, 24) drinking days and 25 (IQR: 8, 71) standard drinks in the previous 28 days. Quantitative PEth results were moderately correlated with drinking days (ρ = 0.26-0.35) and standard drinks consumed (ρ = 0.23-0.38) in the same period. AUCs ranged from 0.54 (any binge drinking in the past 28 days) to 0.82 (any alcohol consumed in the past 21 days). Positive PEth results (≥50 ng/mL) were 2.24 (95% Confidence Interval [CI]: 1.49, 3.35) times as prevalent among participants who reported drinking in the previous 28 days compared with those who did not. CONCLUSIONS: Although PEth values and self-reported alcohol use were correlated, the observed associations were modest. Additional research into the dynamics of PEth production and elimination is warranted across diverse populations to better understand how PEth assessments can best be integrated into research and clinical care.