Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

BACKGROUND: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants. METHODS: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization. RESULTS: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without. CONCLUSIONS: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.

Impact of respiratory viral infections on nasopharyngeal pneumococcal colonization dynamics in children.

PURPOSE OF REVIEW: Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory infections caused by important pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, respiratory syncytial virus and pneumococcus are advancing, increasing evidence suggests that these and other respiratory viruses and pneumococci may exhibit interactions that are associated with altered colonization and disease dynamics. We aim to review recent data evaluating interactions between respiratory viruses and pneumococci in the upper respiratory tract and their potential impact on pneumococcal colonization patterns and disease outcomes. RECENT FINDINGS: While interactions between influenza infection and subsequent increased susceptibility and transmissibility of colonizing pneumococci have been widely reported in the literature, emerging evidence suggests that human rhinovirus, SARS-CoV-2, and other viruses may also exhibit interactions with pneumococci and alter pneumococcal colonization patterns. Additionally, colonizing pneumococci may play a role in modifying outcomes associated with respiratory viral infections. Recent evidence suggests that vaccination with pneumococcal conjugate vaccines, and prevention of colonization with pneumococcal serotypes included in these vaccines, may be associated with reducing the risk of subsequent viral infection and the severity of the associated illnesses. SUMMARY: Understanding the direction and dynamics of viral-pneumococcal interactions may elucidate the potential effects of existing and emerging viral and bacterial vaccines and other preventive strategies on the health impact of these important respiratory pathogens.

The Coronavirus Disease 2019 Pandemic Unmasked the Challenges Faced by Early-Stage Faculty in Infectious Diseases: A Call to Action.

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.

Antibiotic prescribing practices for acute respiratory illness in children less than 24 months of age in Kenema, Sierra Leone: is it time to move beyond algorithm driven decision making?

BACKGROUND: Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over-prescribing of unnecessary antibiotics. The aims of this study were to describe the antibiotic prescribing practices for children less than 24 months of age with symptoms of ARI, that were admitted to Kenema Government Hospital (KGH) in the Eastern Province of Sierra Leone, and to identify the number of children empirically prescribed antibiotics who were admitted to hospital with ARI, as well as their clinical signs, symptoms, and outcomes. METHODS: We conducted a prospective study of children < 24 months of age admitted to the KGH pediatric ward with respiratory symptoms between October 1, 2020 and May 31, 2022. Study nurses collected data on demographic information, medical and medication history, and information on clinical course while hospitalized. RESULTS: A total of 777 children were enrolled. Prior to arrival at the hospital, 224 children (28.8%) reported taking an antibiotic for this illness without improvement. Only 15 (1.9%) children received a chest radiograph to aid in diagnosis and 100% of patients were placed on antibiotics during their hospital stay. CONCLUSIONS: Despite the lives saved, reliance on clinical decision-support tools such as IMCI and ETAT + for pediatric ARI, is resulting in the likely over-prescribing of antibiotics. Greater uptake of implementation research is needed to develop strategies and tools designed to optimize antibiotic use for ARI in LMIC settings. Additionally, much greater priority needs to be given to ensuring clinicians have the basic tools for clinical diagnosis, as well as greater investments in essential laboratory and radiographic diagnostics that help LMIC clinicians move beyond the sole reliance on algorithm based clinical decision making.

Assessing the Impact of Acute Respiratory Illnesses on the Risk of Subsequent Respiratory Illness.

BACKGROUND: Whether acute respiratory illnesses (ARIs), often associated with virus detection, are associated with lower risk for subsequent ARI remains unclear. We assessed the association between symptomatic ARI and subsequent ARI in young children. METHODS: In a prospective cohort of Peruvian children <3 years, we examined the impact of index ARI on subsequent ARI risk. Index ARI were matched with ≤3 asymptomatic observations and followed over 28 days. We compared risk of subsequent ARI between groups using conditional logistic regression adjusting for several covariates, accounting for repeat observations from individual children. RESULTS: Among 983 index ARI, 339 (34%) had an ARI event during follow-up, compared with 876/2826 (31%) matched asymptomatic observations. We found no significant association of index ARI and subsequent ARI risk during follow-up overall (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI], .98-1.23) or when limited to index ARI with respiratory viruses detected (aOR, 1.03; 95% CI, .86-1.24). Similarly, when the outcome was limited to ARI in which viruses were detected, no significant association was seen (aOR, 1.05; 95% CI, .87-1.27). CONCLUSIONS: ARIs were not associated with short-term protection against subsequent ARI in these children. Additional longitudinal studies are needed to understand drivers of recurrent ARI in young children.

Clinical presentations of adult and pediatric SARS-CoV-2-positive cases in a community cohort, Nashville, Tennessee.

Compared to adults, the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness in children has been lower and less severe. However, reports comparing SARS-CoV-2 infection among children and adults are limited. As part of our longitudinal cohort study of adults and children with SARS-CoV-2 infection and their household contacts in Nashville, Tennessee, we compared the clinical characteristics and outcomes of SARS-CoV-2 infections between children and adults. Children were more likely to be asymptomatically infected and had a shorter illness duration compared to adults. The differences observed in clinical presentation across ages may inform symptom-specific testing, screening, and management algorithms.

Clinical characteristics, outcomes, and seasonality of acute respiratory infection associated with single and codetected rhinovirus species among hospitalized children in Amman, Jordan.

Rhinovirus (RV)-specific surveillance studies in the Middle East are limited. Therefore, we aimed to study the clinical characteristics, outcomes, and seasonality of RV-associated acute respiratory infection among hospitalized young children in Jordan. We conducted a prospective viral surveillance study and enrolled children <2 years old admitted to a large public hospital in Amman, Jordan (2010-2013). Demographic and clinical data were collected by structured interviews and chart abstractions. Nasal and/or throat swabs were collected and tested for a panel of respiratory viruses, and RV genotyping and speciation was performed. At least one virus was detected in 2641/3168 children (83.4%). RV was the second most common virus detected (n = 1238; 46.9%) and was codetected with another respiratory virus in 730 cases (59.0%). Children with RV codetection were more likely than those with RV-only detection to have respiratory distress but had similar outcomes. RV-A accounted for about half of RV-positive cases (54.7%), while children with RV-C had a higher frequency of wheezing and reactive airway disease. RV was detected year-round and peaked during winter. In conclusion, though children with RV codetection had worse clinical findings, neither codetection nor species affected most clinical outcomes.

Parainfluenza Virus Types 1-3 Infections Among Children and Adults Hospitalized With Community-acquired Pneumonia.

BACKGROUND: Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia. METHODS: We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression. RESULTS: PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88-37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens. CONCLUSIONS: Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.

Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations.

BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. METHODS: Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression. RESULTS: HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43-9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59-.99) and atypical (OR, 0.39; 95% CI, .19-.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55-1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87-7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32-2.50) were more severe than HMPV (reference), but all other pathogens had similar severity. CONCLUSIONS: Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.

Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children.

OBJECTIVE: To determine the frequency of neurologic complications associated with influenza in hospitalized children. STUD DESIGN: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. RESULTS: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). CONCLUSIONS: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Epidemiologic trends and characteristics of SARS-CoV-2 infections among children in the United States.

PURPOSE OF REVIEW: To review the epidemiological characteristics and clinical features associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children in the United States. RECENT FINDINGS: In the United States, the majority of SARS-CoV-2 infections in children have been mild illnesses, with those 5-17 years of age having the highest frequency. Specifically, the incidence of SARS-CoV-2 in children is two times higher in adolescents (12-17 years) than younger school-aged children (5-11 years). Despite the higher case counts in older children, 10% of pediatric hospitalizations have been in infants less than one year. In addition, severe respiratory and renal complications, hospitalization, and even death have been documented in children. SUMMARY: Clinical manifestations of SARS-CoV-2 infection in children range from asymptomatic to severe respiratory distress, with mild nonspecific symptoms being the most commonly reported. The broad clinical presentation and the frequency of asymptomatic or minimally symptomatic infections in children pose challenges for controlling and detecting SARS-CoV-2. However, severe disease has been noted in children with associated medical complications and death. Thus, additional active surveillance and research is needed to understand the burden children contribute to the SARS-CoV-2 pandemic in the United States.

Clinical features of parainfluenza infections among young children hospitalized for acute respiratory illness in Amman, Jordan.

BACKGROUND: Parainfluenza virus (PIV) is a leading cause of acute respiratory illness (ARI) in children. However, few studies have characterized the clinical features and outcomes associated with PIV infections among young children in the Middle East. METHODS: We conducted hospital-based surveillance for ARI among children < 2 years of age in a large referral hospital in Amman, Jordan. We systematically collected clinical data and respiratory specimens for pathogen detection using reverse transcription polymerase chain reaction. We compared clinical features of PIV-associated ARI among individual serotypes 1, 2, 3, and 4 and among PIV infections compared with other viral ARI and ARI with no virus detected. We also compared the odds of supplemental oxygen use using logistic regression. RESULTS: PIV was detected in 221/3168 (7.0%) children hospitalized with ARI. PIV-3 was the most commonly detected serotype (125/221; 57%). Individual clinical features of PIV infections varied little by individual serotype, although admission diagnosis of 'croup' was only associated with PIV-1 and PIV-2. Children with PIV-associated ARI had lower frequency of cough (71% vs 83%; p < 0.001) and wheezing (53% vs 60% p < 0.001) than children with ARI associated with other viruses. We did not find a significant difference in supplemental oxygen use between children with PIV-associated infections (adjusted odds ratio [aOR] 1.12, 95% CI 0.66-1.89, p = 0.68) and infections in which no virus was detected. CONCLUSIONS: PIV is frequently associated with ARI requiring hospitalization in young Jordanian children. Substantial overlap in clinical features may preclude distinguishing PIV infections from other viral infections at presentation.

The first 1000 symptomatic pediatric SARS-CoV-2 infections in an integrated health care system: a prospective cohort study.

BACKGROUND: The spectrum of illness and predictors of severity among children with SARS-CoV-2 infection are incompletely understood. METHODS: Active surveillance was performed for SARS-CoV-2 by polymerase chain reaction among symptomatic pediatric patients in a quaternary care academic hospital laboratory beginning March 12, 2020. We obtained sociodemographic and clinical data 5 (+/-3) and 30 days after diagnosis via phone follow-up and medical record review. Logistic regression was used to assess predictors of hospitalization. RESULTS: The first 1000 symptomatic pediatric patients were diagnosed in our institution between March 13, 2020 and September 28, 2020. Cough (52 %), headache (43 %), and sore throat (36 %) were the most common symptoms. Forty-one (4 %) were hospitalized; 8 required ICU admission, and 2 required mechanical ventilation (< 1 %). One patient developed multisystem inflammatory syndrome in children; one death was possibly associated with SARS-CoV-2 infection. Symptom resolution occurred by follow-up day 5 in 398/892 (45 %) patients and by day 30 in 443/471 (94 %) patients. Pre-existing medical condition (OR 7.7; 95 % CI 3.9-16.0), dyspnea (OR 6.8; 95 % CI 3.2-14.1), Black race or Hispanic ethnicity (OR 2.7; 95 % CI 1.3-5.5), and vomiting (OR 5.4; 95 % CI 1.2-20.6) were the strongest predictors of hospitalization. The model displayed excellent discriminative ability (AUC = 0.82, 95 % CI 0.76-0.88, Brier score = 0.03). CONCLUSIONS: In 1000 pediatric patients with systematic follow-up, most SARS-CoV-2 infections were mild, brief, and rarely required hospitalization. Pediatric predictors of hospitalization included comorbid conditions, Black race, Hispanic ethnicity, dyspnea and vomiting and were distinct from those reported among adults.

AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells.

BACKGROUND: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. METHODS: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. RESULTS: AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. CONCLUSIONS: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.

Nasopharyngeal Pneumococcal Density during Asymptomatic Respiratory Virus Infection and Risk for Subsequent Acute Respiratory Illness.

Increased nasopharyngeal pneumococcal (Streptococcus pneumoniae) colonization density has been associated with invasive pneumococcal disease, but factors that increase pneumococcal density are poorly understood. We evaluated pneumococcal densities in nasopharyngeal samples from asymptomatic young children from Peru and their association with subsequent acute respiratory illness (ARI). Total pneumococcal densities (encompassing all present serotypes) during asymptomatic periods were significantly higher when a respiratory virus was detected versus when no virus was detected (p<0.001). In adjusted analyses, increased pneumococcal density was significantly associated with the risk for a subsequent ARI (p<0.001), whereas asymptomatic viral detection alone was associated with lower risk for subsequent ARI. These findings suggest that interactions between viruses and pneumococci in the nasopharynx during asymptomatic periods might have a role in onset of subsequent ARI. The mechanisms for these interactions, along with other potentially associated host and environmental factors, and their role in ARI pathogenesis and pneumococcal transmission require further elucidation.

Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer cells, T cells, and B cells after administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA class I proteins was increased in the Adjuvant System 03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches.

Measuring Health Literacy Among Adults with HIV Infection in Mozambique: Development and Validation of the HIV Literacy Test.

The role of health literacy on HIV outcomes has not been evaluated widely in Africa, in part because few appropriate literacy measures exist. We developed a 16-item scale, the HIV Literacy Test (HIV-LT) to assess literacy-related tasks needed to participate in HIV care. Items were scored as correct or incorrect; higher scores indicated higher literacy skill (range 0-100 %). We tested internal reliability (Kuder-Richardson coefficient) of the HIV-LT in a convenience sample of 319 Portuguese-speaking, HIV infected adults on antiretroviral treatment in Maputo, Mozambique. Construct validity was assessed by a hypothetical model developed a priori. The HIV-LT was reliable and valid to measure participants' literacy skills. The mean HIV-LT score was 42 %; literacy skills applicable to HIV care were challenging for many participants. The HIV-LT could be used to assess the relationship of literacy and HIV-related outcomes in diverse settings, and evaluate interventions to improve health communication for those in HIV care.

Norovirus infections in young children in Lusaka Province, Zambia: clinical characteristics and molecular epidemiology.

BACKGROUND: The burden, clinical features, and molecular epidemiology of norovirus infection in young children in southern Africa are not well defined. METHODS: Using data from a health facility-based surveillance study of children <5 years in Lusaka Province, Zambia presenting with diarrhea, we assessed the burden of norovirus infection. A convenience sample of 454 stool specimens was tested for norovirus using reverse-transcriptase polymerase chain reaction (RT-PCR). RT-PCR positive samples underwent additional nucleotide sequencing for genogroup and genotype identification. Clinical features and severity of diarrheal illnesses were compared between norovirus-positive and -negative subjects using Chi-squared and t-tests. RESULTS: Norovirus was detected in 52/454 (11.5%) specimens tested. Abdominal pain, fever, and vomiting were the most common presenting features in norovirus-associated illnesses. However, there were no significant differences in the clinical features of norovirus-positive compared to norovirus-negative illnesses. Of 43 isolates that were available for sequencing, 31 (72.1%) were genogroup II (GII) and 12 (27.9%) were genogroup I (GI). The distribution of genotypes was diverse. CONCLUSIONS: Noroviruses were detected in approximately 10% of young children with diarrhea in the Lusaka Province of Zambia, with GII representing the majority of infections. These findings support the role of norovirus in symptomatic diarrhea disease in Africa. Further studies are needed to confirm these observations and to evaluate prevention strategies.