JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

BACKGROUND: JYNNEOSTM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. METHODS: Effectiveness of a single dose of JYNNEOSTM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEPL) and first (PEPF) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. RESULTS: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEPL was 7 days (range 1-16). Time to PEPL receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEPL and PEPF effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. CONCLUSIONS: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.

Exploring COVID-19 vaccine hesitancy and uptake in Nairobi's urban informal settlements: an unsupervised machine learning analysis of a longitudinal prospective cohort study from 2021 to 2022.

OBJECTIVES: To illustrate the utility of unsupervised machine learning compared with traditional methods of analysis by identifying archetypes within the population that may be more or less likely to get the COVID-19 vaccine. DESIGN: A longitudinal prospective cohort study (n=2009 households) with recurring phone surveys from 2020 to 2022 to assess COVID-19 knowledge, attitudes and practices. Vaccine questions were added in 2021 (n=1117) and 2022 (n=1121) rounds. SETTING: Five informal settlements in Nairobi, Kenya. PARTICIPANTS: Individuals from 2009 households included. OUTCOME MEASURES AND ANALYSIS: Respondents were asked about COVID-19 vaccine acceptance (February 2021) and vaccine uptake (March 2022). Three distinct clusters were estimated using K-Means clustering and analysed against vaccine acceptance and vaccine uptake outcomes using regression forest analysis. RESULTS: Despite higher educational attainment and fewer concerns regarding the pandemic, young adults (cluster 3) were less likely to intend to get the vaccine compared with cluster 1 (41.5% vs 55.3%, respectively; p<0.01). Despite believing certain COVID-19 myths, older adults with larger households and more fears regarding economic impacts of the pandemic (cluster 1) were more likely to ultimately to get vaccinated than cluster 3 (78% vs 66.4%; p<0.01), potentially due to employment requirements. Middle-aged women who are married or divorced and reported higher risk of gender-based violence in the home (cluster 2) were more likely than young adults (cluster 3) to report wanting to get the vaccine (50.5% vs 41.5%; p=0.014) but not more likely to have gotten it (69.3% vs 66.4%; p=0.41), indicating potential gaps in access and broader need for social support for this group. CONCLUSIONS: Findings suggest this methodology can be a useful tool to characterise populations, with utility for improving targeted policy, programmes and behavioural messaging to promote uptake of healthy behaviours and ensure equitable distribution of prevention measures.

Infectious disease dynamics and restrictions on social gathering size.

Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain size. While it is generally agreed that such restrictions reduce contacts, the specific size threshold separating "allowed" from "prohibited" gatherings often does not have a clear scientific basis, which leads to dramatic differences in guidance across location and time. Building on the observation that gathering size distributions are often heavy-tailed, we develop a theoretical model of transmission during gatherings and their contribution to general disease dynamics. We find that a key, but often overlooked, determinant of the optimal threshold is the distribution of gathering sizes. Using data on pre-pandemic contact patterns from several sources as well as empirical estimates of transmission parameters for SARS-CoV-2, we apply our model to better understand the relationship between restriction threshold and reduction in cases. We find that, under reasonable transmission parameter ranges, restrictions may have to be set quite low to have any demonstrable effect on cases due to relative frequency of smaller gatherings. We compare our conceptual model with observed changes in reported contacts during lockdown in March of 2020.

Infectious disease dynamics and restrictions on social gathering size.

Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain size. While it is generally agreed that such restrictions reduce contacts, the specific size threshold separating "allowed" from "prohibited" gatherings often does not have a clear scientific basis, which leads to dramatic differences in guidance across location and time. Building on the observation that gathering size distributions are often heavy-tailed, we develop a theoretical model of transmission during gatherings and their contribution to general disease dynamics. We find that a key, but often overlooked, determinant of the optimal threshold is the distribution of gathering sizes. Using data on pre-pandemic contact patterns from several sources as well as empirical estimates of transmission parameters for SARS-CoV-2, we apply our model to better understand the relationship between restriction threshold and reduction in cases. We find that, under reasonable transmission parameter ranges, restrictions may have to be set quite low to have any demonstrable effect on cases due to relative frequency of smaller gatherings. We compare our conceptual model with observed changes in reported contacts during lockdown in March of 2020.

Problems with evidence assessment in COVID-19 health policy impact evaluation: a systematic review of study design and evidence strength.

INTRODUCTION: Assessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. METHODS: We included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on 26 November 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation. RESULTS: After 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-sectional), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DISCUSSION: The reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigour to be actionable by policy-makers. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

Problems with Evidence Assessment in COVID-19 Health Policy Impact Evaluation: A systematic review of study design and evidence strength.

INTRODUCTION: Assessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. This study systematically reviewed the strength of evidence in the published COVID-19 policy impact evaluation literature. METHODS: We included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on November 26, 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation, assessing what impact evaluation method was used, graphical display of outcomes data, functional form for the outcomes, timing between policy and impact, concurrent changes to the outcomes, and an overall rating. RESULTS: After 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. The majority (n=23/36) of studies in our sample examined the impact of stay-at-home requirements. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-section), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 1/27 studies passed all of the above checks, and 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DISCUSSION: The reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigor to be actionable by policymakers. This was largely driven by the circumstances under which policies were passed making it difficult to attribute changes in COVID-19 outcomes to particular policies. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

The evaluation of the Woman's Condom marketing approach: What value did peer-led interpersonal communication add to the promotion of a new female condom in urban Lusaka?

During a mass media campaign accompanying the launch of the Maximum Diva Woman's Condom (WC) in Lusaka, Zambia, a cluster-randomized evaluation was implemented to measure the added impact of a peer-led interpersonal communication (IPC) intervention on the awareness and uptake of the new female condom (FC). The WC and mass media campaign were introduced simultaneously in 40 urban wards in April 2016; half of the wards were randomly assigned to the treatment (IPC intervention) with cross-sectional surveys conducted before (n = 2,364) and one year after (n = 2,430) the start of the intervention. A pre-specified intention-to-treat (ITT) analysis measured the impact of randomization to IPC at the community level. In adjusted ITT models, there were no statistically significant differences between intervention and control groups. Due to significant implementation challenges, we also conducted exploratory secondary analyses to estimate effects among those who attended an IPC event (n = 66) using instrumental variable and inverse probability weighting analyses. In addition to increases in FC identification (IPC attendees had higher reported use of any condom, improved perceptions of FC's, and were more likely to have discussed contraceptive use with their partner as compared to non-attendees). The introduction of a new FC product combined with an IPC intervention significantly increased general knowledge and awareness in the community as compared to media alone, but did not lead to detectable community level impacts on other primary outcomes of interest. Observational evidence from our study suggests that IPC attendance is associated with increased use and negotiation. Future studies should explore the intensity and duration of IPC programming necessary to achieve detectable community level impacts on behavior. Trial Registration: AEARCTR-0000899.

Exploring gender and partner communication: Theory of planned behavior predictors for condom use among urban youth in Zambia.

OBJECTIVE: To understand how knowledge and perceptions of condoms and partner communication influence use of condoms in a high HIV prevalence setting and gender-specific differences. METHODS: A cross-sectional study was conducted in Zambia from 2015 to 2016. The survey included questions on demographics, sexual behavior, contraceptive perceptions, and behaviors. We constructed multivariate regression models using the Theory of Planned Behavior to determine associations between knowledge, perceptions, and perceived control with intended, communicated, and reported use of condoms by gender. RESULTS: The participants were 2388 sexually active urban residents aged 18-24 years. In the sample, 1646 (69%) were female, 841 (35%) married, and 1894 (61%) unemployed. Partner communication was the predictor most associated with use of condoms. Among women, partner communication was associated with over three times higher odds of condom use (odds ratio [OR] 3.51, 95% confidence interval [CI] 2.65-4.65) but being married reduced the odds of condom use by 76% (OR 0.24, 95% CI 0.17-0.33). For men, a network of friends that was supportive of the use of contraception was associated with increased odds of 55% for use of condoms (OR 1.55, 95% CI 1.10-2.18). CONCLUSION: Public health programs aimed at increasing safer sexual behavior and use of condoms must consider improving gender equity and partner communication, as knowledge of contraceptives and positive perceptions are not enough to ensure their use.

The child survival impact of the Ghana Essential Health Interventions Program: A health systems strengthening plausibility trial in Northern Ghana.

BACKGROUND: The Ghana Health Service in collaboration with partner institutions implemented a five-year primary health systems strengthening program known as the Ghana Essential Health Intervention Program (GEHIP). GEHIP was a plausibility trial implemented in an impoverished region of northern Ghana around the World Health Organizations (WHO) six pillars combined with community engagement, leadership development and grassroots political support, the program organized a program of training and action focused on strategies for saving newborn lives and community-engaged emergency referral services. This paper analyzes the effect of the GEHIP program on child survival. METHODS: Birth history data assembled from baseline and endline surveys are used to assess the hazard of child mortality in GEHIP treatment and comparison areas prior to and after the start of treatment. Difference-in-differences (DiD) methods are used to compare mortality change over time among children exposed to GEHIP relative to children in the comparison area over the same time period. Models test the hypothesis that a package of systems strengthening activities improved childhood survival. Models adjusted for the potentially confounding effects of baseline differentials, secular mortality trends, household characteristics such as relative wealth and parental educational attainment, and geographic accessibility of clinical care. RESULTS: The GEHIP combination of health systems strengthening activities reduced neonatal mortality by approximately one half (HR = 0.52, 95% CI = 0.28,0.98, p = 0.045). There was a null incremental effect of GEHIP on mortality of post-neonate infants (from 1 to 12 months old) (HR = 0.72; 95% CI = 0.30,1.79; p = 0.480) and post-infants (from 1 year to 5 years old) -(HR = 1.02; 95% CI = 0.55-1.90; p = 0.940). Age-specific analyses show that impact was concentrated among neonates. However, effect ratios for post-infancy were inefficiently assessed owing to extensive survival history censoring for the later months of childhood. Children were observed only rarely for periods over 40 months of age. CONCLUSION: GEHIP results show that a comprehensive approach to newborn care is feasible, if care is augmented by community-based nurses. It supports the assertion that if appropriate mechanisms are put in place to enable the various pillars of the health system as espoused by WHO in rural impoverished settings where childhood mortality is high, it could lead to accelerated reductions in mortality thereby increasing survival of children. Policy implications of the pronounced neonatal effect of GEHIP merit national review for possible scale-up.

Why don't urban youth in Zambia use condoms? The influence of gender and marriage on non-use of male condoms among young adults.

BACKGROUND: Zambia experiences high unmet need for family planning and high rates of HIV, particularly among youth. While male condoms are widely available and 95% of adults have heard of them, self-reported use in the past 12 months is low among young adults (45%). This study describes factors associated with non-use of male condoms among urban young adults in Zambia. METHODS: A household cross-sectional survey in four urban districts was conducted from November 2015 to January 2016 among sexually active young adults ages 18-24 years. A random walk strategy was implemented in urban areas; eligible, enrolled participants were administered a survey on household characteristics, health access, and knowledge, attitudes and practices related to contraception. Relative risk regression models were built to determine factors associated with the decision to not use a male condom (non-use) at most recent sexual intercourse. RESULTS: A total of 2,388 individuals were interviewed; 69% were female, 35% were married, and average lifetime sex partners was 3.45 (SD±6.15). Non-use of male condoms was 59% at most recent sexual intercourse. In a multivariate model, women were more likely to report non-use of a male condom compared with men (aRR = 1.24 [95% CI: 1.11, 1.38]), married individuals were more likely to report non-use compared with unmarried individuals (aRR = 1.59 [1.46, 1.73]), and those residing in the highest poverty wards were more likely to report non-use compared with those in the lowest poverty wards (aRR = 1.31 [1.16, 1.48]). Those with more negative perceptions of male condom use were 6% more likely to report non-use (aRR = 1.06 [1.03, 1.09]). Discussion regarding contraception with a partner decreased non-use 13% (aRR = 0.87 [0.80, 0.95]) and agreement regarding male condom use with a partner decreased non-use 16% (aRR = 0.84 [0.77, 0.91)]). DISCUSSION: Non-use of male condoms is high among young, married adults, particularly women, who may be interested in contraception for family planning but remain at risk of STI infection. Effective marketing strategy of dual protection methods to this population is critical.

Benefits and Limitations of a Community-Engaged Emergency Referral System in a Remote, Impoverished Setting of Northern Ghana.

Although Ghana has a well-organized primary health care system, it lacks policies and guidelines for developing or providing emergency referral services. In 2012, an emergency referral pilot-the Sustainable Emergency Referral Care (SERC) initiative-was launched by the Ghana Health Service in collaboration with community stakeholders and health workers in one subdistrict of the Upper East Region where approximately 20,000 people reside. The pilot program was scaled up in 2013 to a 3-district (12-subdistrict) plausibility trial that served a population of approximately 184,000 over 2 years from 2013 to 2015. The SERC initiative was fielded as a component of a 6-year health systems strengthening and capacity-building project known as the Ghana Essential Health Intervention Program. Implementation research using mixed methods, including quantitative analysis of key process and health indicators over time in the 12 intervention subdistricts compared with comparison districts, a survey of health workers, and qualitative systems appraisal with community members, provided data on effectiveness of the system as well as operational challenges and potential solutions. Monitoring data show that community exposure to SERC was associated with an increased volume of emergency referrals, diminished reliance on primary care facilities not staffed or equipped to provide surgical care, and increased caseloads at facilities capable of providing appropriate acute care (i.e., district hospitals). Community members strongly endorsed the program and expressed appreciation for the service. Low rates of adherence to some care protocols were noted: referring facilities often failed to alert receiving facilities of incoming patients, not all patients transported were accompanied by a health worker, and receiving facilities commonly failed to provide patient outcome feedback to the referring facility. Yet in areas where SERC worked to bypass substandard points of care, overall facility-based maternal mortality as well as accident-related deaths decreased relative to levels observed in facilities located in comparison areas.

The Astronomy of Africa's Health Systems Literature During the MDG Era: Where Are the Systems Clusters?

Growing international concern about the need for improved health systems in Africa has catalyzed an expansion of the health systems literature. This review applies a bibliometric procedure to analyze the acceleration of scientific writing on this theme. We focus on research published during the Millennium Development Goal (MDG) era between 1990 and 2014, reporting findings from a systematic review of a database comprised of 17,655 articles about health systems themes from sub-Saharan African countries or subregions. Using bibliometric tools for co-word textual analysis, we analyzed the incidence and associations of keywords and phrases to generate and visualize topical foci on health systems as clusters of themes, much in the manner that astronomers represent groupings of stars as galaxies of celestial entities. The association of keywords defines their relative position, with the size of images weighted by the relative frequency of terms. Sets of associated keywords are arrayed as stars that cluster as "galaxies" of concepts in the knowledge universe represented by health systems research from sub-Saharan Africa. Results show that health systems research is dominated by literature on diseases and categorical systems research topics, rather than on systems science that cuts across diseases or specific systemic themes. Systems research is highly developed in South Africa but relatively uncommon elsewhere in the region. "Black holes" are identified by searching for terms in our keyword library related to terms in widely cited reviews of health systems. Results identify several themes that are unexpectedly uncommon in the country-specific health systems literature. This includes research on the processes of achieving systems change, the health impact of systems strengthening, processes that explain the systems determinants of health outcomes, or systematic study of organizational dysfunction and ways to improve system performance. Research quantifying the relationship of governance indicators to health systems strengthening is nearly absent from the literature. Long-term experimental studies and statistically rigorous research on cross-cutting themes of health systems strengthening are rare. Studies of organizational malaise or corruption are virtually absent. Trend analysis shows the emergence of organizational research on specific priority diseases, such as on HIV/AIDS, malaria, and tuberculosis, but portrays a lack of focus on integrated systems research on the general burden of disease. If health systems in Africa are to be strengthened, then organizational change research must be a more concerted focus in the future than has been the case in the past.