The role of stigma in cannabis use disclosure: an exploratory study.

BACKGROUND: Although cannabis use incidence, societal acceptance, and legislation all trend positively, cannabis remains federally illegal in the USA. Prior studies have revealed that patients are reluctant to disclose their cannabis use history in the healthcare system, which can negatively impact patient care. This study reports the frequency of cannabis use disclosure with special considerations for stigmatization. To better understand the limitations, providers face in providing collaborative, comprehensive, and informed care, this study evaluated four domains of stigma: perceived, anticipated, enacted, and internalized. METHODS: This study used a descriptive exploratory design. Data collection occurred using an anonymous, online national survey with a convenience sample in the USA. Recruitment relied on electronic media and occurred between July and December 2022. Participants were adults older than 21 years and self-identified as having used cannabis and accessed the healthcare system within the last five years. The survey measured demographic characteristics, cannabis use, and disclosure patterns. Stigma was measured using the Stigma Use Stigma Mechanism Scale (SU-SMS) and Substance Abuse Use Self-Stigma Scale (SASSS) with language modifications for cannabis. Ordinal logistic regression models were performed to evaluate associations between the frequency of cannabis use disclosure patterns and each stigma category. Associations were assessed using Chi-squared or Fisher's exact tests. RESULTS: Data were available for 249 respondents. Most participants (57.1%) reported initiating a conversation about cannabis with their healthcare provider; 27.8% of the time, cannabis is never discussed, and healthcare providers initiate only 15.1% of related discussions. Anticipated stigma [95% CI 1.045-1.164] and total stigma [95% CI 1.001-1.039] had statistically significant associations with nondisclosure. Annual household income (p = .04), chronicity of cannabis use (p = .03), frequency of cannabis use (p = .02), and a known amount of CBD in products consumed (p = .01) had statistically significant associations with the frequency of cannabis use disclosure. CONCLUSIONS: Patients who use cannabis experience stigmatization in the healthcare setting that may limit disclosure of cannabis use history. Future studies would be well served to explore anticipated stigma more deeply. Healthcare providers should be knowledgeable to lead such conversations relating to cannabis while maintaining an unbiased perspective.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Qualitative assessment of infant sleep practices and other risk factors of sudden infant death syndrome (SIDS) among mothers in Lusaka, Zambia.

BACKGROUND: There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia. METHODS: FGDs involved 35 purposively sampled mothers aged 18-49 years. FGDs were conducted using a semi-structured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12. RESULTS: Six FGDs were conducted with 35 mothers in April-May 2021 across two study sites. FGD Participants were generally aware of sudden unexplained infant deaths, with several describing stories of apparent SIDS in the community. The side sleeping position was preferred and perceived to be safer for the infant with most believing the supine position posed an aspiration or choking risk to the infant. Bedsharing was also preferred and perceived to be convenient for breastfeeding and monitoring of the infant. Experienced family members such as grandmothers and mothers-in-law, and health care workers were frequently cited as sources of information on infant sleep position. A heightened awareness of the infant's sleeping environment was suggested as a mechanism to prevent SIDS and smothering. CONCLUSIONS: Decisions about bedsharing and infant sleep position were guided by maternal beliefs and perceptions about what is convenient for breastfeeding and safer for the infant. These concerns are vital to designing tailored interventions to address sleep-related sudden infant losses in Zambia. Public health campaigns with tailored messages that address these concerns are likely to be effective at ensuring optimal uptake of safe sleep recommendations.

Assessing infant sleep practices and other risk factors of SIDS in Zambia: a cross-sectional survey of mothers in Lusaka, Zambia.

BACKGROUND: Having infants sleep with their parents and sleeping face down or on their sides are the two most proximate and modifiable risk factors for sudden infant death syndrome (SIDS). Little is known about the burden of SIDS or the prevalence of these risk factors in Africa. Our primary objective was to determine the prevalence of modifiable risk factors of SIDS in Lusaka, Zambia. METHODS: We conducted cross-sectional surveys with recent mothers of infants aged < 1 year across two busy urban clinic sites in Lusaka, Zambia. We used log-binomial regression analysis to identify factors predictive of bedsharing and prone sleeping. RESULTS: Surveys were conducted with 478 mothers between April-May 2021. The sleep-related risk factors, bedsharing and side sleeping, were widely prevalent. 89.5% of respondents indicated that they share a bed with the infant during sleep, 73.0% preferred putting their baby on its side, and 19.9% preferred the prone position. Only 6.7% of respondents described using the safer, supine position. Age of infant was the only factor which was predictive of prone sleeping. Infants > 2 months old were twice as likely to be put to sleep in a prone position compared to infants aged less than 2 months old. Mothers reported that they rarely (24.1%) received advice from medical caregivers to use the supine position. Maternal use of alcohol (12.0%) and tobacco (0.8%) during pregnancy were uncommon. CONCLUSIONS: Bedsharing and placing the infant to sleep on the side were commonly reported among the mothers we interviewed. Whether this represents an opportunity to reduce SIDS in Zambia is unclear since accurate data on the burden of SIDS in Zambia is not available. There is a need for increased awareness of SIDS and more prospective data collection on its burden and related risk factors in these African populations.

A Tale of 2 Pneumos: The Impact of Human Immunodeficiency Virus Exposure or Infection Status on Pediatric Nasopharyngeal Carriage of Streptococcus pneumoniae and Pneumocystis jiroveci: A Nested Case Control Analysis From the Pneumonia Etiology Research In Child Health Study.

BACKGROUND: The majority of pediatric human immunodeficiency virus (HIV) cases in Africa reflect maternal-to-child transmission. HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality when compared to HIV unexposed and uninfected (HUU) children. The mechanisms behind these unexpected trends are only partially understood but could be explained by the differences in the immune response to infections triggered by an altered immune system state. METHODS: Using quantitative reverse transcription polymerase chain reaction, we compared the nasopharyngeal carriage prevalence and density of Streptococcus pneumoniae (SP) and Pneumocystis jirovecii (PJ) between children living with HIV and HEU or HUU cases (pneumonia) and controls (without pneumonia). RESULTS: The cohort included 1154 children (555 cases and 599 matched controls). The SP carriage prevalence rates were similar between cases and controls. Among SP carriers with pneumonia, carriage density was increased among children living with HIV, versus HEU or HUU children (15.8, 4.7, and 3.6 × 105 copies/mL, respectively). The rate of PJ carriage was significantly higher among children living with HIV than among HEU and HUU children (31%, 15%, and 10%, respectively; P < .05), as was carriage density (63.9, 20.9, and 4.8 × 103 copies/mL, respectively; P < .05). CONCLUSIONS: Carriage prevalences and densities for SP and PJ show different kinetics in terms of their relationship with HIV exposure and clinical status, particularly for Pneumocystis jirovecii. This supports the theory that the increased morbidity and mortality observed among HEU children may reflect deficits not just in humoral immunity but in cell-mediated immunity as well.

Challenges of Assessing Community Mortality Due to Respiratory Viruses in Children Aged Less Than 5 Years.

BACKGROUND: Estimating the real impact of respiratory syncytial virus (RSV) disease is key for the development of vaccines and treatments. Ascertaining the burden of community mortality due to RSV is challenging due to the lack of primary data. Therefore, conducting observational studies to determine the factors associated with community mortality due to the virus in developing countries is important. OBJECTIVE: Our aim in this study was to describe the obstacles, gaps, and challenges that investigators face in low-income, vulnerable regions in 4 developing countries on 3 continents. RESULTS: The main obstacles and challenges of ascertaining community mortality due to RSV were defining strategies to consent families for testing before burial, sampling individuals at the household level, supporting bereaved parents with different cultural and religious backgrounds, establishing tailored strategies for studies in challenging settings, and integrating RSV mortality data from nasopharyngeal samples. CONCLUSION: Detailed logistical planning based on population sociodemographic information, grief counseling, staff training, and a multidisciplinary approach with adequate laboratory infrastructure is critical to successful observational community-based RSV studies.

Histopathological Evaluation of Deceased Persons in Lusaka, Zambia With or Without Coronavirus Disease 2019 (COVID-19) Infection: Results Obtained From Minimally Invasive Tissue Sampling.

BACKGROUND: Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. METHODS: We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. RESULTS: From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40-64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. CONCLUSIONS: Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.

Risk Factors for Respiratory Syncytial Virus-Associated Community Deaths in Zambian Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low- and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known. METHODS: Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs). RESULTS: We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2-7.1]). Compared with older infants, those aged 0-8 weeks had a 2.83 (95% CI, 1.30-6.15) increased risk of dying with RSV. The risk of RSV for the 0-8-week age group increased to 5.24 (1.56-33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22-3.27]). CONCLUSION: RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka.

Association of Respiratory Syncytial Virus Infection and Underlying Risk Factors for Death Among Young Infants Who Died at University Teaching Hospital, Lusaka Zambia.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections and child mortality. While RSV disease burden is highest in low- and middle-income countries, most knowledge about risk factors for fatal RSV disease comes from high-income settings. METHODS: Among infants aged 4 days to <6 months who died at University Teaching Hospital in Lusaka, Zambia, we tested nasopharyngeal swabs obtained postmortem for RSV using reverse transcriptase-quantitative polymerase chain reaction. Through a systematic review of death certificates and hospital records, we identified 10 broad categories of underlying medical conditions associated with infant deaths. We used backward-selection models to calculate adjusted and unadjusted risk ratios (RRs) for the association between each underlying condition and RSV status. RESULTS: From 720 infant deaths, 6% (44) were RSV-positive, 70% were <4 weeks old, and 54% were male. At least 1 underlying condition was found in 85% of infants, while 63% had ≥2. Prematurity/low birth weight (53% [384]) and complications of labor and delivery (32% [230]) were the most common conditions. Congenital cardiac conditions were significantly associated with an increased risk of RSV infection (4%, 32; adjusted RR: 3.57; 95% CI: 1.71-7.44). No other underlying conditions were significantly associated with RSV. CONCLUSIONS: Other than congenital cardiac conditions, we found a lack of association between RSV and underlying risk factors. This differs from high-income settings, where RSV mortality is concentrated among high-risk infants. In this population, birth-related outcomes are the highest mortality risk factors. Improved neonatal care remains crucial in the fight against neonatal mortality.

Global Respiratory Syncytial Virus-Related Infant Community Deaths.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

Use of eHealth for HIV Medical Education: a Narrative Review.

PURPOSE OF REVIEW: The complexity of HIV care and its expanding clinical workforce has created a need for new distance learning models to deliver medical education. We conducted a narrative review to assess the acceptability and effectiveness of recent eHealth HIV education interventions supporting HIV healthcare providers. RECENT FINDINGS: Evidence from 24 articles revealed that synchronous (real time), asynchronous (any time), and hybrid (combination) models of eHealth education are feasible and acceptable. Only two interventions (one asynchronous, one hybrid) of 19 included in the review utilized a randomized controlled design. Some studies showed improvement in confidence and perceived quality of case management, but few studies were designed to demonstrate impact. Successful eHealth education interventions require a thorough understanding of the target community's capacity and needs. Both synchronous and asynchronous strategies appear acceptable and potentially effective, but more studies are needed to assess impact on knowledge and practices to determine the most effective delivery models.

Cost and Impact of Dried Blood Spot Versus Plasma Separation Card for Scale-up of Viral Load Testing in Resource-limited Settings.

BACKGROUND: Routine plasma viral load (VL) testing is recommended for monitoring human immunodeficiency virus-infected patients on antiretroviral therapy. In Zambia, VL scale-up is limited due to logistical obstacles around plasma specimen collection, storage, and transport to centralized laboratories. Dried blood spots (DBSs) could circumvent many logistical challenges at the cost of increased misclassification. Recently, plasma separation cards (PSCs) have become available and, though more expensive, have lower total misclassification than DBSs. METHODS: Using a geospatial model created for optimizing VL utilization in Zambia, we estimated the short-term cost of uptake/correct VL result using either DBSs or PSCs to increase VL access on equipment available in-country. Five scenarios were modeled: (1) plasma only (status quo); (2) plasma at high-volume sites, DBS at low-volume sites; (3) plasma at high-volume sites, PSC at low-volume sites; (4) PSC only; (5) DBS only. RESULTS: Scenario 1 resulted in 795 342 correct results due to limited patient access. When allowing for full and partial adoption of dried specimens, access increases by 19%, with scenario 3 producing the greatest number of correct results expected (929 857). The average cost per correct VL result was lowest in the plasma + DBS scenario at $30.90 compared to $31.62 in our plasma + PSC scenario. The cost per correct result of using dried specimens only was dominated in the incremental analysis, due primarily to fewer correct results. CONCLUSIONS: Adopting the partial use of dried specimens will help achieve improved VL access for patients at the lowest cost per correct result.

Ear biometrics for patient identification in global health: a field study to test the effectiveness of an image stabilization device in improving identification accuracy.

BACKGROUND: In many low and middle-income countries (LMICs), difficulties in patient identification are a major obstacle to the delivery of longitudinal care. In absence of unique identifiers, biometrics have emerged as an attractive solution to the identification problem. We developed an mHealth App for subject identification using pattern recognition around ear morphology (Project SEARCH (Scanning EARS for Child Health). Early field work with the SEARCH App revealed that image stabilization would be required for optimum performance. METHODS: To improve image capture, we designed and tested a device (the 'Donut'), which standardizes distance, angle, rotation and lighting. We then ran an experimental trial with 194 participants to measure the impact of the Donut on identification rates. Images of the participant's left ear were taken both with and without use of the Donut, then processed by the SEARCH algorithm, measuring the top one and top ten most likely matches. RESULTS: With the Donut, the top one identification rate and top ten identification rates were 99.5 and 99.5%, respectively, vs. 38.4 and 24.1%, respectively, without the Donut (P < 0.0001 for each comparison). In sensitivity analyses, crop technique during pre-processing of images had a powerful impact on identification rates, but this too was facilitated through the Donut. CONCLUSIONS: By standardizing lighting, angle and spatial location of the ear, the Donut achieved near perfect identification rates on a cohort of 194 participants, proving the feasibility and effectiveness of using the ear as a biometric identifier. TRIAL REGISTRATION: This study did not include a medical intervention or assess a medical outcome, and therefore did not meet the definition of a human subjects research study as defined by FDAAA. We did not register our study under clinicaltrials.gov .

Incidence of Severe and Nonsevere Pertussis Among HIV-Exposed and -Unexposed Zambian Infants Through 14 Weeks of Age: Results From the Southern Africa Mother Infant Pertussis Study (SAMIPS), a Longitudinal Birth Cohort Study.

BACKGROUND: Maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (Tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by Bordetella pertussis To better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of Zambian infants. METHODS: Mother-infant pairs were enrolled at 1 week of life, and then seen at 2- to 3-week intervals through 14 weeks of age. At each visit, nasopharyngeal (NP) swabs were obtained from both, and symptoms were catalogued. Using polymerase chain reaction (PCR) to identify cases, and a severity scoring system to triage these into severe/nonsevere, we calculated disease incidence using person-time at risk as the denominator. RESULTS: From a population of 1981 infants, we identified 10 with clinical pertussis, for an overall incidence of 2.4 cases (95% confidence interval [CI], 1.2-4.2) per 1000 infant-months and a cumulative incidence of 5.2 cases (95% CI, 2.6-9.0) per 1000 infants. Nine of 10 cases occurred within a 3-month window (May-July 2015), with highest incidence between birth and 6 weeks of age (3.5 cases per 1000 infant-months), concentrated among infants prior to vaccination or among those who had only received 1 dose of Diphtheria Tetanus whole cell Pertussis (DTwP). Maternal human immunodeficiency virus (HIV) modestly increased the risk of infant pertussis (risk ratio, 1.8 [95% CI, .5-6.9]). Only 1 of 10 infant cases qualified as having severe pertussis. The rest presented with the mild and nonspecific symptoms of cough, coryza, and/or tachypnea. Notably, cough durations were long, exceeding 30 days in several cases, with PCRs repeatedly positive over time. CONCLUSIONS: Pertussis is circulating freely among this population of Zambian infants but rarely presents with the classical symptoms of paroxysmal cough, whooping, apnea, and cyanosis. Maternal HIV appears to increase the risk, while lack of effective exposure to DTwP increased the risk.

Novel Approaches for Visualizing and Analyzing Dose-Timing Data from Electronic Drug Monitors, or "How the 'Broken Window' Theory Pertains to ART Adherence".

Adherence to antiretroviral medications is usually expressed in terms of the proportion of doses taken. However, the timing of doses taken may also be an important dimension to overall adherence. Little is known about whether patients who mistime doses are also more likely to skip doses. Using data from the completed Adherence for Life randomized controlled trial, we created visual and statistical models to capture and analyze dose timing data collected longitudinally with electronic drug monitors (EDM). From scatter plots depicting dose time versus calendar date, we identified dominant patterns of dose taking and calculated key features [slope of line over calendar date; residual mean standard error (RMSE)]. Each was assessed for its ability to categorize subjects with 'sub-optimal' (<95 % of doses taken) using area under the receiver operating characteristic (AROC) curve analysis. Sixty eight subjects contributed EDM data, with ~300 to 400 observations/subject. While regression line slopes did not predict 'sub-optimal' adherence (AROC 0.51, 95 % CI 0.26-0.75), the variability in dose timing (RMSE) was strongly predictive (AROC 0.79, 95 % CI 0.62-0.97). Compared with the lowest quartile of RMSE (minimal dose time variability), each successive quartile roughly doubled the odds of 'sub-optimal' adherence (OR 2.1, 95 % CI 1.3-3.4). Patterns of dose timing and mistiming are strongly related to overall adherence behavior. Notably, individuals who skip doses are more likely to mistime doses, with the degree of risk positively correlated with the extent of dose timing variability.

Bottlenecks, barriers, and solutions: results from multicountry consultations focused on reduction of childhood pneumonia and diarrhoea deaths.

Millions of children still die unnecessarily from pneumonia and diarrhoea, mainly in resource-poor settings. A series of collaborative consultations and workshops involving several hundred academic, public health, governmental and private sector stakeholders were convened to identify the key barriers to progress and to issue recommendations. Bottlenecks impairing access to commodities included antiquated supply management systems, insufficient funding for drugs, inadequate knowledge about interventions by clients and providers, health worker shortages, poor support for training or retention of health workers, and a failure to convert national policies into action plans. Key programmatic barriers included an absence of effective programme coordination between and within partner organisations, scarce financial resources, inadequate training and support for health workers, sporadic availability of key commodities, and suboptimal programme management. However, these problems are solvable. Advocacy could help to mobilise needed resources, raise awareness, and prioritise childhood pneumonia and diarrhoea deaths in the coming decade.

Curated and Annotated Dataset of Lung US Images in Zambian Children with Clinical Pneumonia.

See also the commentary by Sitek in this issue. Supplemental material is available for this article.

Single-test syphilis serology: A case of not seeing the forest for the trees.

INTRODUCTION: There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. METHODS: Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. RESULTS: Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. CONCLUSION: Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Systematic review of current and emerging strategies for reducing morbidity from malaria in sickle cell disease.

Sickle cell disease (SCD) is a chronic debilitating disorder affecting erythrocytes, which is especially prevalent throughout Sub-Saharan Africa and among individuals of African descent. Because malaria is thought to be a significant cause of morbidity and mortality in patients with SCD, malaria chemoprophylaxis is often recommended for these patients. In SCD, malaria chemoprophylaxis reduces malaria parasite count, anaemia and the need for blood transfusion, and improves clinical outcomes. However, the effectiveness of malaria chemoprophylaxis in the setting of SCD is based on a few studies conducted prior to the emergence of widespread antimalarial drug resistance. Consequently, it is uncertain what the optimal strategy for managing patients with SCD in malarious areas should be. Despite the widespread use of hydroxyurea in non-malarious regions, little is known about its effect in malaria-endemic areas or on malaria-related outcomes. On the one hand, hydroxyurea upregulates intercellular cell adhesion molecule 1 (ICAM-1), the cell surface receptor for adhesion of Plasmodium falciparum-infected erythrocytes, and theoretically, it could enhance parasite replication. On the other hand, hydroxyurea increases levels of foetal haemoglobin, which is protective against malaria. We explore what is currently known about the interactions between SCD and malaria and review the published literature on the efficacy of malaria chemoprophylaxis in SCD. We also consider alternative strategies, including hydroxyurea, in the reduction of malaria-associated morbidity and mortality in patients with SCD.

Young Zambian infants with symptomatic RSV and pertussis infections are frequently prescribed inappropriate antibiotics: a retrospective analysis.

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis. Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.