Under-Reporting of Tuberculosis Disease among Children and Adolescents in Low and Middle-Income Countries: A Systematic Review.

Under-reporting of tuberculosis (TB) disease in children and adolescents is a significant global concern, as many children are missing from TB notification data. A systematic literature review was conducted to understand the global reporting gap of child and adolescent TB as well as current interventions to close this gap in Low- and Middle- Income Countries (LMIC). Our study found large and variable gaps in child and adolescent TB reporting, due to various factors. Interventions to close this gap exist but are limited. Future studies are necessary to improve global surveillance systems to improve TB care delivery for children and adolescents.

T-SPOT.TB Reactivity in Southern African Children With and Without in Utero Human Immunodeficiency Virus Exposure.

Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9-18 months using T-SPOT.TB. Prevalence of TB infection was low and did not differ by HIV exposure status.

Tuberculosis care models for children and adolescents: a scoping review.

Objective: To map which tuberculosis care models are best suited for children and adolescents. Methods: We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group < 20 years old. Findings: We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents. Conclusion: Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.

Age-specific Clinical Presentation and Risk Factors for Extrapulmonary Tuberculosis Disease in Children.

BACKGROUND: Clinical presentation for extrapulmonary tuberculosis (EPTB) in children can be variable and nonspecific, leading to delayed diagnosis, disease and death. We describe the age-specific clinical presentation and identify risk factors for EPTB among children in Pakistan. METHODS: In 2015-2016 in 4 facilities in Sindh, Pakistan, children were diagnosed with TB either through bacteriologic confirmation or clinical-radiologic criteria. EPTB comprised any form of TB disease that did not involve the lungs. Among children with TB disease, we report demographics, clinical characteristics and symptoms, family medical history and diagnostic test results for children with and without EPTB. We conduct age-specific regression analyses to identify factors associated with an EPTB diagnosis among children age 0-4, 5-9 and 10-14 years. RESULTS: A total of 1163 children were diagnosed with TB disease, of which 157 (13.5%) had EPTB. Of those, 46 (29.3%) were 0-4, 53 (33.8%) were 5-9 and 58 (36.9%) were 10-14 years old. Of children with EPTB, the most frequently reported sites were lymph node (113, 72.4%) and abdominal (31, 19.9%). Weight loss was associated with an increased risk of EPTB in the 0-4-year-old (adjusted odds ratio: 2.80, 95% confidence interval: 1.05-7.47) and 10-14-year-old (adjusted odds ratio: 2.79, 95% confidence interval: 1.28-6.07) groups, and the presence of cough was associated with a decreased risk of EPTB. CONCLUSIONS: This study provides new knowledge about age-specific clinical presentation and risk factors of EPTB in children in Pakistan. Our results can help to optimize clinical algorithms designed to achieve a timely diagnosis in children with EPTB along with improved treatment outcomes.

Comorbidities Associated with Hospitalization and Progression Among Adolescents with Symptomatic Coronavirus Disease 2019.

OBJECTIVE: To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19). STUDY DESIGN: We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. RESULTS: A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization. CONCLUSIONS: SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

Age-specific effectiveness of a tuberculosis screening intervention in children.

OBJECTIVE: To apply a cascade-of-care framework to evaluate the effectiveness-by age of the child-of an intensified tuberculosis patient-finding intervention. DESIGN: From a prospective screening program at four hospitals in Pakistan (2014-2016) we constructed a care cascade comprising six steps: screened, positive screen, evaluated, diagnosed, started treatment, and successful outcome. We evaluated the cascade by each year of age from 0 to 14 and report the age-specific mean proportion and standard deviation. RESULTS: On average across all ages, only 12.5% (standard deviation: 2.0%) of children with a positive screen were not evaluated. Among children who had a complete evaluation, the highest percentages of children diagnosed with tuberculosis were observed in children 0-4 (mean: 31.9%; standard deviation: 4.8%), followed by lower percentages in children 5-9 (mean: 22.4%; standard deviation: 2.2%), and 10-14 (mean: 26.0%; standard deviation:5.4%). Nearly all children diagnosed with tuberculosis initiated treatment, and an average of 93.3% (standard deviation: 3.3%) across all ages had successful treatment outcomes. CONCLUSIONS: This intervention was highly effective across ages 0-14 years. Our study illustrates the utility of applying operational analyses of age-stratified cascades to identify age-specific gaps in pediatric tuberculosis care that can guide future, novel interventions to close these gaps.

Tuberculosis in Pediatric Solid Organ and Hematopoietic Stem Cell Recipients.

Children undergoing solid organ and hematopoietic stem cell transplantation are at high risk of morbidity and mortality from tuberculosis (TB) disease in the post-transplant period. Treatment of TB infection and disease in the post-transplant setting is complicated by immunosuppression and drug interactions. There are limited data that address the unique challenges for the management of TB in the pediatric transplant population. This review presents the current understanding of the epidemiology, clinical presentation, diagnosis, management, and prevention for pediatric transplant recipients with TB infection and disease. Further studies are needed to improve diagnosis of TB and optimize treatment outcomes for these patients.

Non-SARS-CoV-2 Infections Among Patients Evaluated for MIS-C Associated With COVID-19.

Clinical features of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 are nonspecific. In this retrospective cohort study of 39 patients evaluated for MIS-C, 11 had non-SARS-CoV-2 infections, 3 of whom were also diagnosed with MIS-C. Clinical features were similar in patients with MIS-C and patients with non-SARS-CoV-2 infections. Clinicians should consider non-SARS-CoV-2 infections in patients undergoing MIS-C evaluation.

Integrating childhood TB: applying the care delivery value chain to improve pediatric HIV/TB services in Togo, West Africa.

The World Health Organization has prioritized integrating tuberculosis (TB) and human immunodeficiency virus (HIV) services. Diagnosis of HIV/TB coinfection in children remains a challenge worldwide for numerous reasons. The care delivery value chain (CDVC) is an effective tool that can be applied as a systemic framework for assessing health care delivery. Our objective was to apply the CDVC framework to improve pediatric HIV/TB care at an HIV center in northern Togo that serves over 130 children and 1000 adults living with HIV. Using the CDVC framework, gaps in HIV/TB care were identified, and services related to screening and diagnosis were prioritized to implement 3 distinct quality improvement cycles. Primary outcomes included percentage of children screened for TB by medical providers and percentage of diagnostic sample results received at the HIV clinic for children and adults. Improvements in the TB diagnostic process were observed, resulting in a change of sputum sample results received for both children and adults from 25% at baseline to >88% at 3 months. Given the relative low associated costs, this QI approach may be applicable and feasible in other settings to target screening and diagnosis of TB for children living with HIV worldwide.

Off-Stream Watering Systems and Partial Barriers as a Strategy to Maximize Cattle Production and Minimize Time Spent in the Riparian Area.

A study was conducted in 2009 at two locations in Manitoba (Killarney and Souris), Canada to determine the impact of off-stream waterers (OSW) with or without natural barriers on (i) amount of time cattle spent in the 10 m buffer created within the riparian area, referred to as the riparian polygon (RP), (ii) watering location (OSW or stream), and (iii) animal performance measured as weight gain. This study was divided into three 28-day periods over the grazing season. At each location, the pasture-which ranged from 21.0 ha to 39.2 ha in size-was divided into three treatments: no OSW nor barriers (1CONT), OSW with barriers along the stream bank to deter cattle from watering at the stream (2BARR), and OSW without barriers (3NOBARR). Cattle in 2BARR spent less time in the RP in Periods 1 (p = 0.0002), 2 (p = 0.1116), and 3 (p < 0.0001) at the Killarney site compared to cattle in 3NOBARR at the same site. Cattle in 2BARR at the Souris site spent more time in the RP in Period 1 (p < 0.0001) and less time in Period 2 (p = 0.0002) compared to cattle in 3NOBARR. Cattle did use the OSW, but not exclusively, as watering at the stream was still observed. The observed inconsistency in the effectiveness of the natural barriers on deterring cattle from the riparian area between periods and locations may be partly attributable to the environmental conditions present during this field trial as well as difference in pasture size and the ability of the established barriers to deter cattle from using the stream as a water source. Treatment had no significant effect (p > 0.05) on cow and calf weights averaged over the summer period. These results indicate that the presence of an OSW does not create significant differences in animal performance when used in extensive pasture scenarios such as those studied within the present study. Whereas the barriers did not consistently discourage watering at the stream, the results provide some indication of the efficacy of the OSW as well as the natural barriers on deterring cattle from the riparian area.

Reaction of rosmarinic acid with nitrite ions in acidic conditions: discovery of nitro- and dinitrorosmarinic acids as new anti-HIV-1 agents.

Rosmarinic acid was reacted with nitrite ions under acidic conditions to give 6'-nitro- and 6',6''-dinitrorosmarinic acids according to the reaction time. Both compounds were active as HIV-1 integrase inhibitors at the submicromolar level. They also inhibited the viral replication in MT-4 cells with modest and similar selectivity indexes. The nitration of rosmarinic acid strongly improves the anti-integrase inhibition and the antiviral activity without increasing the cellular toxicity.

Can general dentists produce successful implant overdentures with minimal training?

OBJECTIVES: This study was carried out to determine whether inexperienced dentists can provide two-implant overdentures that are as satisfactory and of the same cost as those provided by experienced prosthodontists. METHODS: Edentulous elders were enrolled in a randomized controlled clinical trial to compare the effects of mandibular conventional and two-implant overdentures on nutrition. They were randomly assigned to groups that were treated by either an experienced prosthodontist or by a newly-graduated dentist with minimal training in implant treatment. Data for this study were obtained during the treatment of the first 140 subjects enrolled. The change in patient ratings of satisfaction after treatment, laboratory costs and the number of unscheduled visits up to 6 months following prosthesis delivery were compared. RESULTS: Satisfaction was significantly higher with implant overdentures than with conventional dentures, but there were no differences in scores for either prosthesis between the groups treated by experienced specialists or new dentists. Furthermore, six of the seven inexperienced dentists reported that they found the mandibular two-implant overdenture easier to provide than the conventional denture. CONCLUSIONS: The results of this study suggest that general dentists can provide successful mandibular two-implant overdentures with minimal training.