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Background Strongyloides stercoralis is considered to be historically endemic in Appalachia and the American South, but recent surveillance data, especially data evaluating strongyloidiasis associated with hospitalization, are lacking in most parts of the United States. Methods We performed a population-based retrospective analysis on strongyloidiasis using the National Inpatient Sample from 2003 to 2018. Geographic distribution of strongyloidiasis associated hospitalization was assessed. Logistic regression was used to identify risk factors associated with strongyloidiasis. Results We identified 6931 hospitalizations associated with strongyloidiasis during the study period (11.8 per million hospitalizations). The rate of strongyloidiasis was highest in the Northeast US region, including the Middle Atlantic division (47.1 cases per million population; adjusted odds ratio, 2.00 [95% confidence interval: 1.58–2.53]), and the East South Central division (27.5 cases per million; adjusted odds ratio, 2.77 [2.02–3.80]). Older age, male sex, nonwhite race/ethnicity (particularly Hispanic and Asian), nonprivate insurance, and residence in neighborhoods with low median income were also associated with strongyloidiasis. Immunocompromising conditions, particularly human immunodeficiency virus infection, were present in 41.3% of hospitalizations with strongyloidiasis. In-hospital death occurred in 7.8% of patients with strongyloidiasis-associated hospitalization. Conclusions Strongyloidiasis-associated hospitalization is rare in the United States but can be associated with increased mortality rate/mortality risk . It occurs more frequently in poor and marginalized populations. Immunocompromised conditions were common among hospitalized patients with strongyloidiasis. Enhanced surveillance efforts are needed to inform health policies for improving the health of at-risk populations.

The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age.We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative).A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated.Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).

Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19.Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients7 days to1 year old hospitalized with symptomatic acute COVID-19.We report 232 infants7 days to1 year of age hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients7 days to18 years old, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and1% died.Infants accounted for over a fifth of children18 years of age hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.

As of December 14, 2020, children and adolescents aged

Laparoscopic appendectomy is a preferred approach in children with appendicitis. Patient characteristics associated with open appendectomy are poorly characterized, although such information can help optimize the care.To characterize the factors associated with open appendectomy, we performed a retrospective analysis using the 2014 Nationwide Readmissions Database, capturing 49.3% of US hospitalizations. We identified surgically managed appendicitis using International Classification of Diseases, Ninth Revision, Clinical Modification among patients aged 18 or younger. Factors associated with open appendectomy, 30-d readmission rate, and hospitalization length were assessed using logistic regression, Cox proportional hazards regression, and Poisson regression, respectively.Of 46,147 children with surgically managed appendicitis, 85.2% had laparoscopic appendectomy. Low-volume hospitals (odds ratio, OR: 3.01 [95% confidence interval, CI: 1.81-5.01]), rural hospitals (OR: 2.36 [95%CI: 1.63-3.40]), public insurance (OR: 1.19 [95%CI: 1.03-1.36]), lower-income neighborhood residence (OR: 1.40 [95%CI: 1.06-1.86]), younger age (OR: 5.00 [95%CI: 3.64-6.86] in5 year-old), and abscess complicating appendicitis (OR: 1.91 [95%CI: 1.58-2.31]) were associated with open appendectomy. Laparoscopic appendectomy was associated with shorter hospitalization (incidence rate ratio: 0.77 [95%CI: 0.69-0.87]) and less readmission with wound infection, but not with 30-d readmission, or readmission with intraabdominal abscess.Along with clinical factors, non-clinical factors including appendicitis volume and rural/teaching status of the treating hospitals play a role in the choice of surgical approach. Awareness of the patient- and hospital-level factors associated with open appendectomy may allow for future resource distribution or improvement in access to care, resulting in population-level impact.

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5)

ImportanceMinimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C).ObjectivesTo evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C.Design, Setting, and ParticipantsThis retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months.ExposuresGlucocorticoid treatment.Main Outcomes and MeasuresMain outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness.ResultsAmong 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91).Conclusions and RelevanceIn this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

Ocular toxocariasis can be vision threatening, and is commonly reported from tropical or subtropical regions. Knowledge of clinical manifestations from the United States, particularly in underserved areas such as the American South, is lacking. We report three cases of ocular toxocariasis in individuals from the Mississippi Delta, a rural community with prevalent poverty. Visual acuity was severely affected in two of the three cases. Increased awareness of ocular toxocariasis, which may have under-recognized frequency, will contribute to prompt diagnosis and treatment, which will ultimately improve patient health in the region.

Although the epidemiology of immunocompromising condition in children has evolved over time, updated epidemiology of pediatric pneumocystis infection in the United States is not available.We performed a retrospective analysis using the Kids' Inpatient Database, a nationally representative sample of US pediatric hospital discharges collected in 1997, 2000, 2003, 2006, 2009 and 2012. Pneumocystis cases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification, code 136.3 among children 0-18 years of age. Demographic data of cases with and without mortality were compared.We identified 1902 [standard error (SE): 95] pneumocystis cases during the study period. The pneumocystis hospitalization rate decreased from 7.5 (SE: 0.91) to 2.7 (SE: 0.31) per a million US children from 1997 to 2012 (63.2% decrease). Cases with HIV infection decreased from 285 (SE: 56) cases in 1997 to 29 (SE: 7) cases in 2012, whereas hematologic malignancy and primary immunodeficiency became more prominent. Infants were the most commonly affected [510 cases (SE: 40)]. All-cause in-hospital mortality was 11.7% (SE: 1.3%) and was particularly high among cases with hematopoietic stem cell transplant [32.4%(SE: 7.1%); P0.001].Pneumocystis infection in children showed a marked decrease from 1997 to 2012 in the United States, largely driven by the reduction in HIV-associated cases, and cases with non-HIV illnesses became more prominent. Hematopoietic stem cell transplant-associated cases had particularly high mortality. Clinicians should be aware of high-risk groups that may benefit from chemoprophylaxis, particularly in infancy.

Background Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced significant serum functional activity in both US and Malian adults. However, antibody titers declined rapidly, and transmission-reducing activity required four vaccine doses. Functional immunogenicity and durability must be improved before advancing TBV further in clinical development. We hypothesized that the pre-fertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity. Methods Transmission-blocking vaccine candidates based on gamete antigen Pfs230 or Pfs25 were conjugated with Exoprotein A, formulated in Alhydrogel, and administered to mice, rhesus macaques, and humans. Antibody titers were measured by ELISA and transmission-reducing activity was assess by the Standard Membrane Feeding Assay. Results Pfs25-EPA/Alhydrogel and Pfs230D1-EPA/Alhydrogel induced similar serum functional activity in mice, but Pfs230D1-EPA induced significantly greater activity in rhesus monkeys that was enhanced by complement. In U.S. adults, two vaccine doses induced complement-dependent activity in 4 of 5 Pfs230D1-EPA/Alhydrogel recipients but no significant activity in five Pfs25-EPA recipients, and combination with Pfs25-EPA did not increase activity over Pfs230D1-EPA alone. Conclusion The complement-dependent functional immunogenicity of Pfs230D1-EPA represents a significant improvement over Pfs25-EPA in this comparative study. The rhesus model is more predictive of the functional human immune response to Pfs230D1 than is the mouse model. Trial registration ClinicalTrials.gov NCT02334462Funding. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P

Laboratory data and prior pediatric reports indicate that HIV protease inhibitor (PI)–based antiretroviral therapy (ARV) kills gametocytes and reduces rates of gametocytemia, but not asymptomatic parasitemia, in a high malaria-transmission area. To determine whether ARV regimen impacts these rates in areas with less-intense malaria transmission, we compared asymptomatic parasitemia and gametocytemia rates in HIV-infected children by ARV regimen in Lilongwe, Malawi, an area of low-to-moderate transmission intensity. HIV PI lopinavir–ritonavir (LPV–rtv) ARV– or non-nucleoside reverse transcriptase inhibitor nevirapine ARV–treated children did not differ in the rates of polymerase chain reaction-detected asymptomatic parasitemia (relative risk [RR] 0.43 95% confidence interval [CI] [0.16, 1.18], P value 0.10) or microscopically detected gametocytemia with LPV–rtv ARV during symptomatic malaria (RR 0.48 95% CI [0.22,1.04] P value 0.06). LPV–rtv ARV was not associated with reduced rates of asymptomatic parasitemia, or gametocytemia on days of symptomatic malaria episodes, in HIV-infected children. Larger studies should evaluate whether ARV impacts transmission.

To describe the rate and risk factors of deep neck space involvement of Kawasaki disease.We performed a retrospective analysis using the Kids' Inpatient Database from 2006, 2009, 2012, and 2016. Kawasaki disease and deep neck space involvement cases were identified using International Classification of Diseases codes among children aged12 years. Demographic and outcome data of Kawasaki disease cases with and without deep neck space involvement were compared.Of 20 787 patients with Kawasaki disease, 0.6% (130 cases) had deep neck space involvement. On multivariable analysis, children aged ≥4 years (OR 8.41; 95% CI 3.79-18.7 in those aged 6-11 years), Asian or Pacific Islanders (OR 3.72; 95% CI 1.90-7.27), non-Hispanic black children (OR 2.39; 95% CI 1.34-4.28), and Northeast hospital region (OR 2.32; 95% CI 1.21-4.46) were associated with deep neck space involvement. Surgical drainage was performed in 21.7% of patients with deep neck space involvement. Deep neck space involvement was associated with longer hospital stay and greater costs.Approximately 0.6% of patients with Kawasaki disease present with deep neck space involvement in the US. Deep neck space involvement of Kawasaki disease occurs primarily in older (≥4 years old), non-white, non-Hispanic children. Deep neck space involvement is associated with operative procedures for presumed abscess, longer hospital stay, and greater costs. In caring for children with suspected deep neck space abscess, particularly when they are not responding to antibiotics, clinicians should evaluate them for the possibility of Kawasaki disease.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age

BACKGROUND. We previously used mathematical modeling to predict reduced malaria incidence in children with protease inhibitor- (PI), compared with non-nucleoside reverse transcriptase inhibitor (NNRTI-), based highly-active antiretroviral therapy (HAART), in moderate to high malaria transmission areas. These effects were accounted for, in part, by pharmacokinetic (PK) interactions between PIs and artemether-lumefantrine (AL). OBJECTIVE: Because of potentially reduced malaria transmission reservoirs in HIV-infected children due to PI/AL PK interactions impacting non-HIV-infected children, we estimate the antimalarial benefit of PI-based HAART in all children, and in HIV-infected children only residing in low to moderate malaria transmission areas. DESIGN: A dynamic model of malaria transmission was developed to evaluate the pharmacokinetic interaction of PI-based HAART with the antimalarial, artemether-lumefantrine (AL) for preventing malaria. METHODS. To evaluate the benefit of HIV PI-based HAART on malaria incidence, a malaria transmission model with varying degrees of HIV newborn prevalence was developed using recent pediatric clinical trial data in Lilongwe Malawi. RESULTS. Comparing situations of low to high HIV newborn prevalence, and low to moderate malaria transmission intensities, our model predicts the combination of PI-based HAART with AL-treated malaria prevents 0.04-24.8, and 0.05-34.5 annual incidences of malaria overall per 1000 children, and saves 0.003-1.66, and 0.003-2.30 DALYs per 1000 children, respectively. When incorporating seasonality, 0.01-7.3, and 0.01-5.9 annual incidences of malaria overall per 1000 children, and 0.0-0.5, and 0.001-0.41 DALYs per 100 children, are prevented, respectively. CONCLUSIONS. In low to moderate malaria transmission intensity areas, PI-based HAART may reduce malaria events in children when AL is used.

Objective To assess whether symptomatic congenital cytomegalovirus infection (cCMV) is associated with bronchopulmonary dysplasia (BPD) and mortality in very preterm infants (gestational age ≤32 weeks). Study design We performed a retrospective study using the Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Diagnoses of BPD and symptomatic cCMV were determined using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among patients with in-hospital birth at ≤32 weeks of gestation, cases of symptomatic cCMV were matched with infants without cCMV using propensity score matching at 1:2 ratio. Outcomes of BPD and in-hospital mortality were assessed using conditional logistic regression. Results Of 204 818 in-hospital births with gestational age ≤32 weeks, we identified 208 cases of symptomatic cCMV, 177 of which underwent matching. Symptomatic cCMV was associated with higher odds of BPD (OR, 2.34; 95% CI, 1.41-3.87), but was not significantly associated with in-hospital all-cause mortality (OR, 1.18, 95% CI, 0.64-2.17). Conclusions Symptomatic cCMV was associated with BPD but not with in-hospital mortality among very preterm infants. Further study is needed to determine the risk of BPD among infants with cCMV to allow for evaluation of possible preventive measures.

Trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3–12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP–SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP–SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below half maximal inhibitory concentrations (IC50) for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations reported in Uganda. With TMP–SMX prophylaxis, suboptimal adherence is concerning. Sulfamethoxazole levels below IC50s required to overcome malaria parasites with multiple antifolate resistance mutations may be significant. Further study of TMP–SMX in this context is needed.

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8+ T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis.

Objective To assess risk factors, geographic distribution, length of stay, and total charges per case of symptomatic congenital cytomegalovirus infection (cCMV). Study design We performed retrospective analyses of serial cross-sectional data using the Kids' Inpatient Database, a nationally representative sample of US pediatric hospital discharges, from 2000, 2003, 2006, 2009, and 2012. Symptomatic cCMV was identified via use of the International Classification of Diseases, Ninth Revision, Clinical Modification code 771.1 among records with in-hospital birth that were accompanied by 1 or more characteristic symptoms. Demographic characteristics were compared with multivariable logistic regression. Temporal trend was assessed using linear regression. Charges were adjusted for inflation to 2012 US dollars. Results We identified 1349 cases of symptomatic cCMV (SE 56). Symptomatic cCMV was associated with non-Hispanic black race (OR 1.70; 95% CI 1.37-2.10), government-sponsored insurance (OR 1.95; 95% CI 1.34-2.83), and birth in the American South and West (OR 1.68, 95% CI 1.35-2.09 and OR 1.61, 95% CI 1.23-2.09, respectively). In-hospital mortality and preterm birth rate ranged from 3.2%-6.8% and 50.4%-59.2%, respectively, without temporal changes. The geometric mean of total charges per case doubled from $45 771 (SE $8509) in 2000 to $89 846 (SE $10 358) in 2006 (P = .002) but did not change from 2006 to 2012. Length of stay in days was 15 (IQR 8-22) in 2000, 27 (IQR, 9-51) in 2009, and 18 (IQR, 8-47) in 2012. Conclusions Symptomatic cCMV was associated with non-Hispanic black race, low socioeconomic status, and birth in the American South and West and resulted in substantial healthcare burden.

BackgroundHIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed.MethodsThirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor.ResultsWe found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03).ConclusionsLPV-rtv in combination with malaria treatment was associated with lower risk of recurrent positive BS, but not CCM, in HIV-infected children. Larger, randomized studies are needed to confirm these findings which may permit ART optimization for malaria-endemic settings.Trial registrationClinicalTrials.gov NCT00719602.

Antiretroviral therapy in children has expanded dramat- ically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recom- mend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. vivax relapses. HIV and P. vivax malaria geographically overlap in many areas of the world, including South America and Asia. Despite the increasing body of knowledge regarding HIV protease inhibitors (HIV PIs) on P. falciparum malaria, there are no data regarding the effects of these treatments on P. vivax's hypnozoite form and clinical relapses of malaria. We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium actively dividing liver stages in rodent malarias and in vitro in P. falciparum, but effect against Plasmodium dormant hypnozoite forms remains untested. Separately, although other antifolates have been tested against hypnozoites, the antibiotic trimethoprim sulfamethoxazole, commonly used in HIV infection and exposure management, has not been evaluated for hypnozoite-killing activity. Since Plasmodium cynomolgi is an established animal model for the study of liver stages of malaria as a surrogate for P. vivax infection, we investigated the antimalarial activity of these drugs on Plasmodium cynomolgi relapsing malaria in rhesus macaques. Herein, we demonstrate that neither TMP-SMX nor LPV-RTV kills hypnozoite parasite liver stage forms at the doses tested. Because HIV and malaria geographically overlap, and more patients are being managed for HIV infection and exposure, understanding HIV drug impact on malaria infection is important.