<p>Adolescents and young adults (AYA, ages 10-24 years) comprise a uniquely important but understudied population in global efforts to end tuberculosis (TB), the leading infectious cause of death by a single agent worldwide prior to the COVID-19 pandemic. While TB prevention and care strategies often overlook AYA by grouping them with either children or adults, AYA have particular physiologic, developmental, and social characteristics that require dedicated approaches. This review describes current evidence on the prevention and control of TB among AYA, including approaches to TB screening, dynamics of TB transmission among AYA, and management challenges within the context of unique developmental needs. Challenges are considered for vulnerable groups of AYA such as migrants and refugees; AYA experiencing homelessness, incarceration, or substance use; and AYA living with HIV. We outline areas for needed research and implementation strategies to address TB among AYA globally.</p>

<p><strong>BACKGROUND: </strong>Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type b (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings.</p>

<p><strong>METHODS: </strong>We collected data on children 1 to 59 months of age at three hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. We compared pneumonia hospitalizations and deaths pre-vaccine (January 2009 to October 2010) to post-vaccine (January 2013 to December 2017) using seasonally-adjusted interrupted time-series analyses.</p>

<p><strong>FINDINGS: </strong>We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths. In the pre-vaccine period, pneumonia hospitalizations and deaths increased by 24% (rate: 1.24; 95% CI: 0.94, 1.64) and 59% (rate: 1.59; 95% CI: 0.87, 2.90) per year, respectively. Vaccine introduction was associated with a 48% (95% CI: 29%, 62%) decrease in the number of pneumonia hospitalizations and a 50% (95% CI: 1%, 75%) decrease in the number of pneumonia deaths between the end of the pre-vaccine period (October 2010) and the beginning of the post-vaccine period (January 2013). During the post-vaccine period, pneumonia hospitalizations and deaths declined by 6% (rate 0.94; 95% CI: 0.89, 0.99) and 22% (rate: 0.78; 95% CI: 0.67, 0.92) per year, respectively.</p>

<p><strong>INTERPRETATION: </strong>Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than five years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in Botswana.</p>

<p>Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana. To evaluate the challenges encountered, healthcare worker (HCW) approaches, and supported interventions in TB and TB-HIV (human immunodeficiency virus) care for adolescents and young adults (AYA, aged 10-24 years). Semi-structured interviews with HCW in TB clinics, analyzed using thematic analysis. Sixteen HCWs were interviewed. AYA developmental needs included reliance on family support for care, increasing autonomy, attending school or work, building trust in HCWs, and intensive TB education and adherence support. Stigma strongly influenced care engagement, including clinic attendance and HIV testing. Health system barriers to optimal AYA TB care included limited staffing and resources to follow-up or support. HCWs utilized intensive education and counseling, and transitioned AYA to community-based directly observed therapy whenever feasible. HCWs supported implementation of youth-friendly services, such as AYA-friendly spaces or clinic days, training in AYA care, use of mobile applications, and peer support interventions, in addition to health system strengthening. HCWs utilize dedicated approaches for AYA with TB, but have limited time and resources for optimal care. They identified several strategies likely to improve care and better retain AYAs in TB treatment. Further work is needed to study interventions to improve AYA TB care and outcomes.</p>

<p>This retrospective study investigated outcomes among lost to follow-up (LTFU) adolescents and young adults (AYAs: 10-24 years of age) with tuberculosis (TB) registered from 2008 to 2014 in Gaborone, using surveillance data. Of 68 LTFU AYAs, 16 repeated treatment; 8 completed and 6 were again LTFU. Of 4 confirmed deaths, 3 had TB/HIV coinfection. Approaches to improve AYA retention in TB care are needed.</p>

<p><strong>BACKGROUND: </strong>Children who develop malaria after returning to a setting in which the disease is not endemic are at high risk for critical delays in diagnosis and initiation of antimalarial therapy. We assessed the clinical impact of the implementation of malaria rapid diagnostic testing (RDT) on the management of children with malaria at an urban US children's hospital that serves a large immigrant population.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of all children diagnosed with laboratory-confirmed malaria at the Children's Hospital of Philadelphia (CHOP) between 2000 and 2014. RDT using a US Food and Drug Administration-approved immunochromatographic assay was introduced at CHOP on August 1, 2007. We compared clinical management and outcomes of patients with malaria diagnosed before and after RDT introduction.</p>

<p><strong>RESULTS: </strong>We analyzed 82 pediatric malaria cases (32 before and 50 after RDT implementation). The majority of these patients had traveled to West Africa (91.5%) and were infected with Plasmodium falciparum (80.5%). The mean time to a positive result decreased from 10.4 to 0.9 hours (P &lt; .001) after the introduction of RDT for patients with P falciparum. The mean time to antimalarial therapy decreased from 13.1 to 6.9 hours (P =; .023) in hospitalized patients. We found no significant reduction in the mean number of clinical signs of severe malaria between 0 and 48 hours of hospitalization and no difference in the need for exchange transfusion, time to resolution of parasitemia, or length of hospital stay.</p>

<p><strong>CONCLUSIONS: </strong>Implementation of RDT for malaria was associated with shorter times to malaria diagnosis and initiation of antimalarial therapy. The results of this study support RDT in the optimal management of patients with malaria who present in settings in which the disease is not endemic.</p>

High mortality among adolescents with HIV reflects delays and failures in the care cascade. We sought to elucidate critical missed opportunities and barriers to care among adolescents hospitalized with HIV at Botswana's tertiary referral hospital. We enrolled all HIV-infected adolescents (aged 10-19 years) hospitalized with any diagnosis other than pregnancy from July 2015 to January 2016. Medical records were reviewed for clinical variables and past engagement in care. Semi-structured interviews of the adolescents (when feasible) and their caregivers explored delays and barriers to care. Twenty-one eligible adolescents were identified and 15 were enrolled. All but one were WHO Clinical Stage 3 or 4. Barriers to diagnosis included lack of awareness about perinatal HIV infection, illness or death of the mother, and fear of discrimination. Barriers to adherence to antiretroviral therapy included nondisclosure, isolation, and mental health concerns. The number of hospitalized HIV-infected adolescents was lower than expected. However, among those hospitalized, the lack of timely diagnosis and subsequent gaps in the care cascade elucidated opportunities to improve outcomes and quality of life for this vulnerable group.

<p><strong>SETTING: </strong>Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana.</p>

<p><strong>OBJECTIVE: </strong>To describe clinical characteristics and outcomes among adolescents with TB and compare loss to follow-up (LTFU) rates with that among youth and adult cases.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study of TB cases registered from 2012 to 2014. Clinical characteristics and treatment outcomes were compared among adolescents (age 10-19 years), youth (20-24 years) and a systematic sample of adults (⩾25 years).</p>

<p><strong>RESULTS: </strong>We analyzed 120 adolescent, 210 youth, and 548 adult cases. Adolescents had twice the risk of LTFU over adults (RR 2.0, 95%CI 1.1-3.7, P = 0.03), and higher LTFU than youth; this was not significant (RR 1.4, 95%CI 0.7-2.9, P = 0.32). Of those with human immunodeficiency virus (HIV) infection, 8/35 (22.9%) adolescents were LTFU, compared with 3/51 (5.9%) youth, and 25/407 (6.1%) adults (P = 0.001). In a multivariable model, adolescence (OR 3.0, 95%CI 1.3-6.5, P &lt; 0.01), HIV positivity (OR 2.2, 95%CI 1.1-4.5, P = 0.02), and extra-pulmonary TB (OR 2.2, 95%CI 1.2-4.0, P = 0.01) were each associated with LTFU.</p>

<p><strong>CONCLUSION: </strong>Adolescents treated for TB had greater LTFU than youth and adults, particularly in the setting of TB-HIV coinfection. Further work should clarify the generalizability of these findings and investigate poor outcomes among adolescents with TB.</p>