Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

Persuasive COVID-19 vaccination campaigns on Facebook and nationwide vaccination coverage in Ukraine, India, and Pakistan.

Social media platforms have a wide and influential reach, and as such provide an opportunity to increase vaccine uptake. To date, there is no large-scale, robust evidence on the offline effects of online messaging campaigns. We aimed to test whether pre-tested, persuasive messaging campaigns from UNICEF, disseminated on Facebook, influenced COVID-19 vaccine uptake in Ukraine, India, and Pakistan. In Ukraine, we deployed a stepped-wedge randomized controlled trial (RCT). Half of the 24 oblasts (provinces) received five weeks of the intervention, the other half ten weeks of the intervention. In India, an RCT with an augmented synthetic control was conducted in five states (Bihar, Chhattisgarh, Jharkhand, Madhya Pradesh, Rajasthan), whereby 40 out of 174 districts were randomized to receive six weeks of intervention. In Pakistan we deployed a pre-post design, whereby 25 city districts received six weeks of the intervention. Weekly COVID-19 vaccination data was sourced through government databases. Using Poisson regression models, the association between the intervention and vaccine uptake was estimated. In Ukraine we conducted a survey among Facebook users at three time points during the RCT, to ascertain vaccination intentions and trust in vaccines. The campaigns reached more than 110 million Facebook users and garnered 2.9 million clicks. In Ukraine, we found that the intervention did not affect oblast-level vaccination coverage (Relative Risk (RR): 0.93, 95% Confidence Interval (CI) 0.86-1.01). Similarly, in India and Pakistan we found no effect of our intervention (India: RR 0.85, 95% CI 0.70-1.04; Pakistan: RR 0.64, 95% CI 0.01-29.9). The survey among Facebook users in Ukraine showed that trust in vaccines and information sources was an important predictor of vaccination status and intention to get vaccinated. Our campaigns on Facebook had a wide reach, which did not translate in shifting behaviours. Timing and external events may have limited the effectiveness of our interventions.

Behavioral interventions for vaccination uptake: A systematic review and meta-analysis.

BACKGROUND: Human behavior and more specifically behavioral insight-based approaches to vaccine uptake have often been overlooked. While there have been a few narrative reviews indexed in Medline on behavioral interventions to increase vaccine uptake, to our knowledge, none have been systematic reviews and meta-analyses covering not just high but also low-and-middle income countries. METHODS: We included 613 studies from the Medline database in our systematic review and meta-analysis categorizing different behavioral interventions in 9 domains: education campaigns, on-site vaccination, incentives, free vaccination, institutional recommendation, provider recommendation, reminder and recall, message framing, and vaccine champion. Additionally, considering that there is variability in the acceptance of vaccines among different populations, we assessed studies from both high-income countries (HICs) and low- to middle-income countries (LMICs), separately. FINDINGS: Our results showed that behavioral interventions can considerably improve vaccine uptake in most settings. All domains that we examined improved vaccine uptake with the highest effect size associated with provider recommendation (OR: 3.4 (95%CI: 2.5-4.6); Domain: motivation) and on-site vaccination (OR: 2.9 (95%CI: 2.3-3.7); Domain: practical issues). While the number of studies conducted in LMICs was smaller, the quality of studies was similar with those conducted in HICs. Nevertheless, there were variations in the observed effect sizes. INTERPRETATION: Our findings indicate that "provider recommendation" and "on-site vaccination" along with other behavioral interventions can be employed to increase vaccination rates globally.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Two Clinical Prediction Tools to Inform Rapid Tuberculosis Treatment Decision-making in Children.

Background: In the absence of bacteriologic confirmation to diagnose tuberculosis (TB) in children, it is suggested that treatment should be initiated when sufficient clinical evidence of disease is available. However, it is unclear what clinical evidence is sufficient to make this decision. To identify children who would benefit from rapid initiation of TB treatment, we developed 2 clinical prediction tools. Methods: We conducted a secondary analysis of a prospective intensified TB patient-finding intervention conducted in Pakistan in 2014-2016. TB disease was determined through either bacteriologic confirmation or a clinical diagnosis. We derived 2 tools: 1 uses classification and regression tree (CART) analysis to develop decision trees, while the second uses multivariable logistic regression to calculate a risk score. Results: Of the 5162 and 5074 children included in the CART and prediction score, respectively, 1417 (27.5%) and 1365 (26.9%) were eligible for TB treatment. CART identified abnormal chest radiographs and family history of TB as the most important predictors (area under the receiver operating characteristic curve [AUC], 0.949). The final prediction score model included age group (0-4, 5-9, 10-14), weight <5th percentile, cough, fever, weight loss, chest radiograph suggestive of TB disease, and family history of TB; the identified best cutoff score was 9 (AUC, 0.985%). Conclusions: Use of clinical evidence was sufficient to accurately identify children who would benefit from treatment initiation. Our tools performed well compared with existing algorithms, though these results need to be externally validated before operationalization.

Personal risk or societal benefit? Investigating adults' support for COVID-19 childhood vaccination.

Parental hesitancy poses a serious threat to the success of the COVID-19 childhood vaccination campaign. We investigate whether adults' opinions on childhood vaccination can be influenced via two survey experiments in Italy (n = 3,633 participants) and the UK (n = 3,314 participants). Respondents were randomly assigned to: a "risk treatment" that highlighted the potential risks of COVID-19 to a child, a "herd immunity treatment" that emphasized the community benefits of pediatric vaccination, or a control message. Participants' probability of supporting COVID-19 childhood vaccination was then assessed on a 0-100 scale. We find that the "risk treatment" reduced the proportion of Italian parents strongly against vaccination by up to 29.6 %, while increasing the proportion of neutral parents by up to 45.0 %. The "herd immunity treatment", instead, was only effective among non-parents, resulting in a lower proportion of individuals against pediatric vaccination and a higher proportion of individuals in favor (both shifted by around 20 %).

Presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients in a tertiary care hospital in Pakistan-A cross-sectional study.

BACKGROUND: The aim of this study was to investigate the presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients in a tertiary care hospital in the metropolitan city of Lahore, Pakistan from September 2020 till July 2021. METHODS: We retrospectively collected data of Covid-19 patients hospitalized from September 2020 till July 2021. Only those patients who tested PCR positive through a nasopharyngeal swab, were enrolled in the study. Patients' whose data were missing were excluded from this study. Our exclusion criteria included patients who tested negative on Covid-19 PCR, patients with comorbidities that may cause enlarged mediastinal lymphadenopathies such as haemophagocytic lymphohistiocytosis, neoplasia, tuberculosis, sarcoidosis or a systemic disease. The extent of lung involvement in Covid-19 patients was quantified by using a 25-point visual quantitative assessment called the Chest Computed Tomography Score. This score was then correlated with the presence of mediastinal lymphadenopathy. FINDINGS: Of the 210 hospitalized patients included in the study, 131 (62.4%) had mediastinal lymphadenopathy. The mean and median Severity Score of Covid-19 patients with mediastinal lymphadenopathy (mean: 17.1, SD:5.7; median: 17, IQR: 13-23) were higher as compared to those without mediastinal lymphadenopathy (mean: 12.3, SD:5.4; median: 12, IQR:9-16). INTERPRETATION: Our study documents a high prevalence of mediastinal lymphadenopathy in hospitalized patients with Covid-19 with the severity score being higher in its presence representing a more severe course of disease.

Using geographic information system to track children and optimize immunization coverage and equity in Karachi, Pakistan.

BACKGROUND: Despite the potential of geospatial technologies to track and monitor coverage, they are underutilized for guiding immunization program strategy and implementation, especially in low-and-middle-income countries. We conducted geospatial analysis to explore the geographic and temporal trends of immunization coverage, and examined the pattern of immunization service access (outreach and facility based) by children. METHODOLOGY: We extracted data to analyze coverage rates across different dimensions (by enrolment year, birth year and vaccination year) from 2018 till 2020 in Karachi, Pakistan using the Sindh Electronic Immunization Registry (SEIR). We conducted geospatial analysis to assess variation in coverage rates of BCG, Pentavalent (Penta)-1, Penta-3, and Measles-1 vaccines using Government targets. We also analyzed the proportion of children receiving their routine vaccinations at fixed centers and outreach and examined whether children received vaccinations at the same or multiple immunization centers. RESULTS: A total of 1,298,555 children were born, enrolled or vaccinated from 2018 till 2020. At the district level, analysis by enrollment and birth year showed coverage increased between 2018 and 2019 and declined in 2020, while analysis by vaccination year showed consistent increase in coverage. However, micro-geographic analysis revealed pockets where coverage persistently declined. Notably 27/168, 39/168 and 3/156 Union councils showed consistently declining coverage when analyzing by enrollment, birth and vaccination year respectively. More than half (52.2%, 678,280/1,298,555) of the children received all their vaccinations exclusively through fixed centers and, 71.7% (499,391/696,701) received all vaccinations from the same centers. CONCLUSION: Despite overall improving vaccination coverage between 2018 and 2020, certain geographic areas have consistently declining coverage rates, which is detrimental for equity. Making immunization inequities visible through geospatial analysis is the first step to ensure resources are allocated optimally. Our study provides impetus for immunization programs to develop and invest in geospatial technologies, harnessing its potential for improved coverage and equity.

Scale-Up of Rifapentine and Isoniazid for Tuberculosis Prevention Among Household Contacts in 2 Urban Centers: An Effectiveness Assessment.

BACKGROUND: Scaling up a shorter preventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tuberculosis (TB) preventive treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden-TB countries. METHODS: We scaled up 3HP from 2018 to 2021 in 2 cities in Pakistan. Eligible participants were household contacts of persons diagnosed with TB disease. Participants were prescribed 3HP after ruling out TB disease. Treatment was self-administered. We analyzed the proportion who completed 3HP. RESULTS: In Karachi, we verbally screened 22 054 household contacts of all ages. Of these, 83% were clinically evaluated and 3% were diagnosed with TB. Of household contacts without TB disease, 59% initiated the 3HP regimen, of which 69% completed treatment. In Peshawar, we verbally screened 6389 household contacts of all ages. We evaluated 95% of household contacts, of whom 2% were diagnosed with TB disease. Among those without TB disease, 65% initiated 3HP, of which 93% completed. Factors associated with higher 3HP completion included residence in Peshawar (risk ratio [RR], 1.35 [95% confidence interval {CI}: 1.32-1.37]), index patient being a male (RR, 1.03 [95% CI: 1.01-1.05]), and index patient with extrapulmonary TB compared to bacteriologically positive pulmonary TB (RR, 1.10 [95% CI: 1.06-1.14]). The age of the index patient was inversely associated with completion. CONCLUSIONS: We observed a high level of acceptance and completion of 3HP in programs implemented in 2 cities in Pakistan, with differences observed across the cities. These findings suggest that 3HP can be effectively scaled up in urban settings to improve the reach and impact of TPT.

COVID-19 Vaccine Acceptance and Hesitancy Among Health Care Workers in Lebanon.

BACKGROUND: Lebanon endured its worst economic and financial crisis in 2020-2021. To minimize the impact of COVID-19 pandemic, it is important to improve the overall COVID-19 vaccination rate. Given that vaccine hesitancy among health care workers (HCWs) affects the general population's decision to be vaccinated, our study assessed COVID-19 vaccine acceptance among Lebanon HCWs and identified barriers, demographic differences, and the most trusted sources of COVID-19 information. METHODS: A cross-sectional study was conducted between January and May 2021 among HCWs across nine hospitals, the Orders of Physicians, Nurses, and Pharmacists in Lebanon. Descriptive statistics were performed to evaluate the COVID-19 vaccine acceptance, and univariate and multivariable to identify their predictors. RESULTS: Among 879 participants, 762 (86.8%) were willing to receive the COVID-19 vaccine, 52 (5.9%) refused, and 64 (7.3%) were undecided. Males (226/254; 88.9%) and those ≥ 55 years (95/100; 95%) had the highest rates of acceptance. Of the 113 who were not willing to receive the vaccine, 54.9% reported that the vaccine was not studied well enough. Participants with a previous SARS-CoV-2 infection and those who did not know if they had a previous infection (p = 0.002) were less likely to accept the vaccine compared to those with no previous infection. The most trusted COVID-19 sources of information were WHO (69.3%) and healthcare providers (68%). CONCLUSION: Lebanese HCWs had a relatively high acceptance rate for COVID-19 vaccination compared to other countries. Our findings are important in informing the Lebanese health care authorities to establish programs and interventions to improve vaccine uptake among HCWs and the general population.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

Mental Health Impact of COVID-19 among Children and College Students: A Systematic Review.

The COVID-19 pandemic led to a worldwide lockdown and school closures, which have placed a substantial mental health burden on children and college students. Through a systematic search of the literature on PubMed and Collabovid of studies published January 2020-July 2021, our findings of five studies on children and 16 studies on college students found that both groups reported feeling more anxious, depressed, fatigued, and distressed than prior to the pandemic. Several risk factors such as living in rural areas, low family socioeconomic status, and being a family member or friend to a healthcare worker were strongly associated with worse mental health outcomes. As schools and researchers discuss future strategies on how to combine on-site teaching with online courses, our results indicate the importance of considering social contacts in students' mental health to support students at higher risk of social isolation during the COVID-19 pandemic.

Attitudes towards Monkeypox vaccination and predictors of vaccination intentions among the US general public.

Amidst an unprecedented Monkeypox outbreak, we aimed to measure knowledge, attitudes, practices and Monkeypox vaccination intentions among the U.S. adult population. We conducted an online cross-sectional survey, representative of the U.S. adult general public in June 2022. We asked participants whether they would receive a Monkeypox vaccine, if they were recommended to do so. Participants also answered questions on their self-assessed level of Monkeypox knowledge, risk perception, perceived exaggeration of the threat, and self-efficacy around Monkeypox. Furthermore, we asked about their trusted sources of information, COVID-19 vaccination status and administered the 6-item Vaccine Trust Indicator (VTI). Survey weights were created based on age, gender and race. We analyzed predictors of Monkeypox vaccination intentions using logistic regression, adjusted for education, age, race and ethnicity. A total of 856 respondents completed the survey, of which 51% (n = 436) were female and 41% (n = 348) had a college degree or higher. If recommended, 46% of respondents intended to get vaccinated against Monkeypox, 29% would not get vaccinated and 25% did not know. Almost half the respondents (47%) found their own knowledge level about Monkeypox poor or very poor. The most trusted sources of information about the outbreak were healthcare professionals and officials, but also known doctors and researchers with a large online following. Only 24% indicated that the U.S. Centers for Disease Control and Prevention should be in charge of the outbreak response. Being vaccinated against COVID-19 was a strong predictor of intention to receive a Monkeypox if recommended (adjusted Odds Ratio (aOR) 29.2, 95% Confidence Interval (CI) 13.1-65.3). Increased risk perception was positively associated with vaccination intentions (aOR 2.6, 95% CI 1.8-3.6), scoring high on the VTI as well (5.4, 95% CI (3.2-9.1). The low levels of self-assessed knowledge, vaccination intentions and influence of COVID-19 vaccination status point to a lack of clear communication.

Drug-Resistant Tuberculosis Treatment Outcomes among Children and Adolescents in Karachi, Pakistan.

BACKGROUND: Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan. METHODS: We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services. A physician assessed all children and adolescents (0-19 years) with presumptive DR-TB, including details of exposure to DR-TB, medical history, radiology, and laboratory results. All patients received treatment as per national DR-TB management guidelines based on WHO recommendations. RESULTS: There were 262 treatment episodes for 247 patients enrolled during the study period. The median age of the cohort was 16 years (IQR: 13-18 years) with 16 (6.1%) children being under 5 years; 237 (90.5%) patients had pulmonary TB. The majority of the patients (194 or 74.1%) experienced a favourable treatment outcome and 26 (9.9%) died while on treatment. Female patients (78.5%) were more likely to experience favourable outcomes compared to males (64.7%; chi-sqr p-value = 0.02). CONCLUSIONS: We found high rates of favourable outcomes in children and adolescents treated for DR-TB. However, there were few young children in our cohort and there was a considerable gender gap that enhanced efforts to diagnose DR-TB in young children and to elucidate and mitigate the reasons for poor outcomes amongst males.

Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study.

Background: Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. Methods: We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. Results: The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9-5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%-51%) and specificity of 79% (95% CI, 71%-86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. Conclusions: Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable.

Prevalence of Chronic Diseases, Depression, and Stress Among US Childcare Professionals During the COVID-19 Pandemic.

INTRODUCTION: Given their central role in supporting children's development, childcare professionals' overall physical and mental health is important. We evaluated the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among US childcare professionals. METHODS: Data were obtained from US childcare professionals (N = 81,682) through an online survey from May 22, 2020, through June 8, 2020. We used multivariable logistic and linear regression models to assess the association of sociodemographic characteristics with 4 physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. RESULTS: For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) obesity. For mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and sex/gender disparities were found for physical health conditions but not mental health of childcare professionals during the COVID-19 pandemic. CONCLUSION: Our findings highlighted that childcare professionals' depression rates during the pandemic were higher than before the pandemic, and depression, stress, and asthma rates were higher than rates among US adults overall during the pandemic. Given the essential work childcare professionals provided during the pandemic, policy makers and public health officials should consider what can be done to support their physical and mental health.

Brief Report: Performance of Tuberculosis Symptom Screening Among Hospitalized ART-Naive Children With HIV in Kenya.

BACKGROUND: The World Health Organization (WHO) recommends tuberculosis (TB) diagnostic evaluation for children with HIV (CHIV) who have history of TB contact, poor weight gain, cough, or fever. These screening criteria were developed based on studies of symptomatic CHIV with incomplete microbiologic confirmation. We performed routine TB microbiologic evaluation of hospitalized CHIV with and without symptoms to develop a data-driven TB symptom screen. METHODS: Among hospitalized antiretroviral therapy-naive Kenyan CHIV enrolled in the Pediatric Urgent Start of Highly Active Antiretroviral Therapy (PUSH) trial, we performed Xpert MTB/RIF and mycobacterial culture of respiratory and stool specimens independent of TB symptoms. We evaluated performance of WHO and other published pediatric TB screening criteria and derived optimized criteria using a combination of symptoms. RESULTS: Of 168 CHIV who underwent TB microbiologic evaluation, 13 (8%) had confirmed TB. WHO TB symptom screening had 100% sensitivity and 4% specificity to detect confirmed TB. Published TB screening criteria that relied on prolonged symptoms missed cases of confirmed TB (sensitivity 85%-92%). An optimized symptom screen including weight loss, cough, anorexia, or TB contact had 100% sensitivity and improved specificity (31%) compared with the WHO pediatric TB symptom screen. CONCLUSIONS: The WHO TB symptom screen was highly sensitive but resulted in a high proportion of hospitalized CHIV who would require TB diagnostic evaluation. Other published TB screening criteria missed CHIV with confirmed TB. Our optimized screening tool increased specificity while preserving sensitivity. Future multicenter studies are needed to improve TB screening tools for CHIV in both inpatient and outpatient settings.

Overcoming Vaccine Hesitancy for Future COVID-19 and HIV Vaccines: Lessons from Measles and HPV Vaccines.

BACKGROUND: The discovery of vaccines significantly reduced morbidity and mortality of infectious diseases and led to the elimination and eradication of some. Development of safe and effective vaccines is a critical step to the control of infectious diseases; however, there is the need to address vaccine hesitancy because of its potential impact on vaccine uptake. METHODS: We conducted a narrative review of studies on interventions to address measles and human papillomavirus vaccine hesitancy. We discussed how lessons learned from these studies could be applied towards COVID-19 and future human immunodeficiency virus vaccines. RESULTS: We found that there are several successful approaches to improving vaccine acceptance. Interventions should be context specific and build on the challenges highlighted in various settings. CONCLUSION: Strategies could be used alone or in combination with others. The most successful interventions directly targeted the population for vaccination. Use of financial incentives could be a potential tool to improve vaccine uptake.

Improving Tuberculosis Case Detection in Children: Summary of Innovations and Findings From 18 Countries.

Despite a growing focus on the plight of tuberculosis (TB) among children, 56% of the 1.2 million children who develop TB annually are not detected and notified. TB REACH is a platform of the Stop TB Partnership that supports innovative interventions to improve TB case detection and preventative treatment. We present summary findings from 27 TB REACH-supported projects in 18 countries. Interventions were designed around intensified case-finding approaches (facility-based systematic screening and contact investigation), capacity building (including decentralized care delivery and supported decision-making), and improving diagnostic methods (ie, introduction of alternative respiratory specimens and new tools to aid the diagnosis). These interventions were evaluated on how they worked to identify children with TB, prevent further transmission of TB among children, and strengthen the health system involved with childhood TB care. Overall, 13 715 children were detected with TB, improving case notifications by 34%. In addition, nearly 5000 eligible contacts were enrolled on TB preventive treatment through these interventions. Focusing efforts and funding on childhood TB can produce marked improvements in case detection.