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.

Utility of RSV rapid diagnostic assays in hospitalized children in Amman, Jordan.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children worldwide and a frequent cause of hospitalization. Rapid diagnostic assays (RDAs) are available for RSV and they help guide management; however, they are underutilized in developing countries. We compared molecular diagnostics to RSV RDA in hospitalized children in Amman, Jordan. MATERIALS AND METHODS: Children under 2 years of age, admitted with fever and/or respiratory symptoms were enrolled prospectively from March 2010 to 2012. Demographic and clinical data were collected through parent/guardian interviews and medical chart abstraction. RSV RDAs were performed, and nasal/throat swabs were tested for RSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: RSV RDA and PCR were performed on specimens from 1271 subjects. RSV RDA had a sensitivity of 26% and a specificity of 99%, with positive and negative predictive values of 98.6% and 43%, respectively. RDA-positive patients had fewer days of symptoms at presentation and were more likely to have a history of prematurity, lower birth weight, require supplemental oxygen, and a longer hospitalization as compared with subjects with negative RDA. Multivariate analysis showed only lower birth weight, lack of cyanosis on examination, and lower cycle threshold to be independently associated with positive RDA (p ≤ .001). CONCLUSION: RSV RDAs had high specificity, but low sensitivity as compared with qRT-PCR. Positive RDA was associated with patients with a more severe disease, as indicated by oxygen use, longer length of stay, and higher viral load. Implementation of RDAs in developing countries could be an inexpensive and expedient method for predicting RSV disease severity and guiding management.

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.

High prevalence of Group B Streptococcus colonization among pregnant women in Amman, Jordan.

BACKGROUND: Little is known of the burden of Group B Streptococcus (GBS) colonization among pregnant women in Jordan. We conducted a pilot study to determine the prevalence of GBS among pregnant women in Amman, Jordan, where GBS testing is not routine. We also explored GBS serotypes and the performance of a rapid GBS antigen diagnostic test. METHODS: We collected vaginal-rectal swabs from women who presented for labor and delivery at Al-Bashir Hospital. Three methods were used to identify GBS: Strep B Rapid Test (Creative Diagnostics), blood agar media (Remel) with confirmed with BBL Streptocard acid latex test (Becton Dickinson), and CHROMagar StrepB (Remel). Results were read by a senior microbiologist. We defined our gold standard for GBS-positive as a positive blood agar culture confirmed by latex agglutination and positive CHROMagar. PCR testing determined serotype information. Demographic and clinical data were also collected. RESULTS: In April and May 2015, 200 women were enrolled with a median age of 27 years (IQR: 23-32); 89.0% were Jordanian nationals and 71.9% completed secondary school. Median gestational age was 38 weeks (IQR: 37-40); most women reported prenatal care (median 9 visits; IQR: 8-12). Median parity was 2 births (IQR: 1-3). Pre-pregnancy median BMI was 24.1 (IQR: 21.5-28.0) and 14.5% reported an underlying medical condition. Obstetric complications included gestational hypertension (9.5%), gestational diabetes (6.0%), and UTI (53.5%), of which 84.5% reported treatment. Overall, 39 (19.5%) of women were GBS-positive on blood agar media and CHROMagar, while 67 (33.5%) were positive by rapid test (36% sensitivity, 67% specificity). Serotype information was available for 25 (64%) isolates: III (48%), Ia (24%), II (20%), and V (8%). No demographic or clinical differences were noted between GBS+ and GBS-negative women. CONCLUSIONS: Nearly one in five women presenting for labor in Jordan was colonized with GBS, with serotype group III as the most common. The rapid GBS antigen diagnostic had low sensitivity and specificity. These results support expanded research in the region, including defining GBS resistance patterns, serotyping information, and risk factors. It also emphasizes the need for routine GBS testing and improved rapid GBS diagnostics for developing world settings.

Recurrent meningitis in children: etiologies, outcome, and lessons to learn.

PURPOSE: Recurrent meningitis in children is a rare condition. However, its early recognition is important in order to prevent serious complications. This study aims to review cases of recurrent meningitis in children. METHODS: This is a retrospective study that included children diagnosed with recurrent meningitis and who were followed at child neurology clinic at the Jordan University Hospital from January 2001 to June 2017. RESULTS: Thirteen patients were included (nine males and four females). Age of first episode of meningitis ranged from 2 months to 9.5 years. The delay in diagnosis of the underlying cause after the first episode ranged from 6 months to 2.5 years. Underlying causes included inner ear malformation in one patient, skull fractures in two, and dermal sinuses (thoracic spinal and occipital dermal sinus) in two patients. No identifiable cause was found in eight patients. Streptococcus pneumoniae was identified in four (31%) patients, Staphylococcus aureus in two (15%), and no organism was isolated in seven (54%). Three patients (23.1%) developed neurological sequel including developmental delay, limb spasticity, and epilepsy. Two patients had sensorineural hearing loss related to meningitis, and two patients had sensorineural hearing loss mostly related to their original disease. CONCLUSION: A detailed history, examination, and thorough investigations are necessary to determine the underlying cause of recurrent meningitis. In addition, in patients with positive CSF bacterial culture, finding the underlying etiology is very likely.

Kawasaki disease in Jordan: demographics, presentation, and outcome.

Kawasaki disease is the leading cause of acquired coronary artery disease in young children. There is a lack of data on Kawasaki disease and its effect on coronary arteries in Jordan and other developing countries. We report clinical and demographic data of Kawasaki disease in Jordan from a single institution, with emphasis on cardiac involvement and short to intermediate follow-up. Review of the medical records of 34 patients with Kawasaki disease from 1997 to 2010 was done for clinical and demographic variables. Echocardiographic and angiographic images were reviewed for patients at presentation and follow-up. The median age at presentation was 19 months, ranging from 2 months to 8 years, with a male to female ratio of 3.9:1. In all, 12 patients (35%) had incomplete Kawasaki disease. There was a high incidence of coronary artery involvement (41%), where 20.5% had aneurysms and 20.5% had ectasia without aneurysm. Most coronary aneurysms were present at the time of diagnosis. The only independent variable for prediction of coronary involvement was age, with an odds ratio of 0.63 per year (95% confidence interval 0.41-0.95).

Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions. The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports. Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.

Adenovirus Infection in Hospitalized Children with Acute Respiratory Infection in Jordan.

BACKGROUND: The most common clinical manifestation of adenovirus (AdV) infection is acute respiratory illness (ARI). Specific AdV species associated with ARI hospitalizations are not well defined in the Middle East. METHODS: A viral surveillance study was conducted among children <2 years hospitalized in Amman, Jordan, from March 2010 to March 2013. Nasal and throat respiratory specimens were obtained from enrolled children and tested for viruses using a real-time reverse-transcription quantitative polymerase chain reaction. AdV-positive specimens were typed by partial hexon gene sequencing. Demographic and clinical features were compared between AdV detected as single pathogen versus co-detected with other respiratory viruses, and between AdV-B and AdV-C species. RESULTS: AdV was detected in 475/3168 (15%) children hospitalized with ARI; of these, 216 (45%) specimens were successfully typed with AdV-C as the most common species detected (140/216; 65%). Children with AdV-single detection (88/475; 19%) had a higher frequency of fever (71% vs. 56%; P=0.015), diarrhea (18% vs. 11%; p=0.048), and/or seizures/abnormal movements (14% vs. 5%; p=0.003). Children with AdV co-detected with other viruses more likely required oxygen support [adjusted odds ratio (aOR) 1.91 (95% CI: 1.08, 3.39), P = 0.027] than those with AdV-single detection. Children with AdV-C had higher odds of co-detections with other viruses compared with those with AdV-B [aOR 4.00 (95% CI: 1.91, 8.44), P < 0.001]. CONCLUSION: Clinical differences were identified between AdV-single and AdV co-detected with other viruses, and between AdV-B and AdV-C. Larger studies with AdV typing are needed to determine additional epidemiological and clinical differences between specific AdV species and types.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Respiratory Viruses Associated With Acute Wheezing in Hospitalized Young Children in Jordan.

A cross-sectional viral surveillance study of hospitalized children less than 2 years of old in Amman, Jordan, noted that respiratory syncytial virus and human metapneumovirus, but not human rhinovirus, were associated with higher odds of acute wheezing. Future longitudinal studies are needed to evaluate the association between early childhood viral acute respiratory infections and recurrent wheezing later in childhood.

Molecular characterization of respiratory syncytial viruses circulating in a paediatric cohort in Amman, Jordan.

Respiratory syncytial viruses (RSVs) are an important cause of mortality worldwide and a major cause of respiratory tract infections in children, driving development of vaccine candidates. However, there are large gaps in our knowledge of the local evolutionary and transmission dynamics of RSVs, particularly in understudied regions such as the Middle East. To address this gap, we sequenced the complete genomes of 58 RSVA and 27 RSVB samples collected in a paediatric cohort in Amman, Jordan, between 2010 and 2013. RSVA and RSVB co-circulated during each winter epidemic of RSV in Amman, and each epidemic comprised multiple independent viral introductions of RSVA and RSVB. However, RSVA and RSVB alternated in dominance across years, potential evidence of immunological interactions. Children infected with RSVA tended to be older than RSVB-infected children [30 months versus 22.4 months, respectively (P value = 0.02)], and tended to developed bronchopneumonia less frequently than those with RSVB, although the difference was not statistically significant (P value = 0.06). Differences in spatial patterns were investigated, and RSVA lineages were often identified in multiple regions in Amman, whereas RSVB introductions did not spread beyond a single region of the city, although these findings were based on small sample sizes. Multiple RSVA genotypes were identified in Amman, including GA2 viruses as well as three viruses from the ON1 sub-genotype that emerged in 2009 and are now the dominant genotype circulating worldwide. As vaccine development advances, further sequencing of RSV is needed to understand viral ecology and transmission, particularly in under-studied locations.

The Clinical Characteristics, Severity, and Seasonality of RSV Subtypes Among Hospitalized Children in Jordan.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in young children worldwide. Multiple factors affect RSV disease severity, and data regarding differences between RSV subtypes severity are controversial. This study aimed to evaluate the clinical characteristics, seasonality and severity of RSV subtypes in children. METHODS: As part of a prospective ARI surveillance study conducted from March 2010 to March 2013 in Amman, Jordan, children less than 2 years with fever and/or respiratory symptoms were enrolled. Demographic and clinical characteristics were collected through parental interviews and medical chart review. The treating physician collected severity score data at admission. Nasal and throat swabs were collected and tested. Multivariable regression models were used to compare the odds of increased disease severity across a priori selected predictors of interest. RESULTS: Overall, 1397/3168 (44%) children were RSV positive, with a mean age of 5.3 months (±4.8 SD), 59.7% were male, 6.4% had an underlying medical condition (UMC), 63.6% were RSV-A positive, 25.2% were RSV-B positive, 0.6% were positive for both, and 10.6% could not be typed. Both RSV subtypes peaked in January-March of each year. RSV A-positive children were more likely to present with decreased appetite but less likely to have viral co-detection than RSV B-positive children. Independent factors associated with RSV disease severity included cycle threshold value, vitamin D level, age, UMC, prematurity and severity score, but not RSV subtypes. CONCLUSION: RSV subtypes co-circulated and had similar severity profiles; future preventive and treatment measures should target both subtypes.

Antibiotic use for respiratory syncytial virus in the Middle East: A surveillance study in hospitalized Jordanian children.

INTRODUCTION: In developing countries where point-of-care testing is limited, providers rely on clinical judgement to discriminate between viral and bacterial respiratory infections. We performed a cross-sectional cohort study of hospitalized Jordanian children to evaluate antibiotic use for respiratory syncytial virus (RSV) infections. MATERIALS AND METHODS: Admitting diagnoses from a prior viral surveillance cohort of hospitalized Jordanian children were dichotomized into suspected viral-like, non-pulmonary bacterial-like, and pulmonary bacterial-like infection. Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) for antibiotic use during hospitalization. Sensitivity and specificity of admission diagnoses and research laboratory results were compared. RESULTS: Children with a suspected viral-like admission diagnosis, compared to those with suspected non-pulmonary bacterial-like, were 88% and 86% less likely to be administered an empiric/first-line antibiotic (male, aPOR: 0.12; female, aPOR: 0.14; p-value = <0.001). There were slight differences by sex with males having a lower prevalence than females in being administered an expanded coverage antibiotic; but they had a higher prevalence of macrolide administration than males with non-pulmonary bacterial-like infection. Overall, children with RSV had a 34% probability (sensitivity) of being assigned to a suspected viral-like diagnosis; whereas RSV-negative children had a 76% probability (specificity) of being assigned to a suspected pulmonary bacterial-like diagnosis. CONCLUSIONS: Hospitalized children with a suspected viral-like admission diagnosis were less likely to receive an empiric/first-line and expanded coverage antibiotic compared to suspected non-pulmonary and pulmonary infections; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.

Coronavirus Surveillance in a Pediatric Population in Jordan From 2010 to 2013: A Prospective Viral Surveillance Study.

BACKGROUND: Human coronaviruses (HCoVs) are a significant cause of acute respiratory illness (ARI) in children; however, the role of HCoVs in ARI among hospitalized children in the Middle East is not well defined. METHODS: Children under 2 years admitted with fever and/or respiratory symptoms were enrolled from 2010 to 2013 in Amman, Jordan. Nasal/throat swabs were collected and stored for testing. Demographic and clinical characteristics were collected through parent/guardian interviews and medical chart abstractions. Prior stored specimens were tested for HCoVs (HKU1, OC43, 229E and NL63) by qRT-PCR. RESULTS: Of the 3168 children enrolled, 6.7% were HCoVs-positive. Among HCoV-positive children, the median age was 3.8 (1.9-8.4) months, 59% were male, 14% were premature, 11% had underlying medical conditions and 76% had viral-codetection. The most common presenting symptoms were cough, fever, wheezing and shortness of breath. HCoVs were detected year-round, peaking in winter-spring months. Overall, 56%, 22%, 13% and 6% were OC43, NL63, HKU1 and 229E, respectively. There was no difference in disease severity between the species, except higher intensive care unit admission frequency in NL63-positive subjects. CONCLUSIONS: HCoVs were detected in around 7% of children enrolled in our study. Despite HCoV detection in children with ARI with highest peaks in respiratory seasons, the actual burden and pathogenic role of HCoVs in ARI merits further evaluation given the high frequency of viral codetection.

Assessing the epidemiology and seasonality of influenza among children under two hospitalized in Amman, Jordan, 2010-2013.

BACKGROUND: The disease burden of influenza-associated hospitalizations among children in Jordan is not well established. We aimed to characterize hospitalizations attributed to influenza in a pediatric population. METHODS: We conducted a cross-sectional study from our viral surveillance cohort in children under 2 years hospitalized with acute respiratory symptoms and/or fever from March 2010 to March 2013. We collected demographic and clinical characteristics, and calculated the frequency of children who met the severe acute respiratory illness (SARI) criteria. Nasal specimens were tested using real-time reverse transcriptase polymerase chain reaction to detect influenza A, B, or C. Further subtyping for influenza A-positive isolates was conducted. RESULTS: Of the 3168 children enrolled in our study, 119 (4%) were influenza-positive. Influenza types and subtypes varied by season but were predominantly detected between December and February. Codetection of multiple respiratory pathogens was identified in 58% of children with the majority occurring among those <6 months. Bronchopneumonia and rule-out sepsis were the most common admission diagnoses, with influenza A accounting for over 2/3 of children with a rule-out sepsis admission status. One-third of children under 6 months compared to 3/4 of children 6-23 months met the SARI criteria. CONCLUSIONS: Influenza was an important cause of acute respiratory illness in children under 2 years. Children <6 months had the highest burden of influenza-associated hospitalizations and were less likely to meet the SARI global surveillance case definition. Additional surveillance is needed in the Middle East to determine the true influenza burden on a global scale.

Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.

BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation.

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

BACKGROUND: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. METHODS: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. FINDINGS: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. INTERPRETATION: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Human metapneumovirus in hospitalized children in Amman, Jordan.

Human metapneumovirus (HMPV) has recently been identified as an important cause of acute respiratory infections (ARI) in children worldwide. However, there is little systematic data on its frequency and importance as a cause of ARI in the Middle East. We conducted a viral surveillance study in children <5 years of age admitted with respiratory symptoms and/or fever at two major tertiary care hospitals in Amman, Jordan from 1/18-3/29/07. Nose and throat swabs were collected and tested for HMPV and other respiratory viruses by real-time RT-PCR. A total of 743 subjects were enrolled. Forty-four (6%) subjects were positive for HMPV, 467 (64%) were positive for RSV and 13 (1.3%) had co-infection with both HMPV and RSV. The frequency of HMPV in January, February, and March was 4.1%, 3.0%, and 11.9% respectively. Clinical features associated with HMPV infection were similar to those of other respiratory viruses, except children with HMPV were more likely to present with fever than children not infected with HMPV. Children with HMPV and RSV co-infection were administered supplemental oxygen and were admitted to the ICU more frequently than children infected with HMPV alone or RSV alone, though these differences did not reach statistical significance. We conclude that HMPV is an important cause of acute respiratory infections in children in Amman, Jordan. Longer surveillance studies are needed to better understand the seasonal epidemiology of HMPV and to assess if co-infection with HMPV and RSV leads to more severe illness.

Burden of respiratory syncytial virus in hospitalized infants and young children in Amman, Jordan.

Acute respiratory infections (ARI) play a major role in hospitalizations in the Middle East, but the specific viral causes are unknown. We conducted prospective viral surveillance in children <5 y of age admitted with ARI and/or fever at 2 dissimilar hospitals in Amman, Jordan during peak respiratory syncytial virus (RSV) season. We collected prospective clinical and demographic data and obtained nose/throat swabs for testing for RSV by real-time polymerase chain reaction (RT-PCR). We obtained clinical and laboratory data for 728/743 (98%) subjects enrolled. The children's median age was 4.3 months, 58.4% were males, 87% were breastfed, 4% attended day care, 67% were exposed to smokers, 7% were admitted to the intensive care unit, and 0.7% died (n = 5). Out of 728 subjects, 467 (64%) tested positive by RT-PCR for RSV. Comparing RSV-positive with RSV-negative subjects, the RSV-positive subjects had lower median age (3.6 vs 6.4 months, p < 0.001) and fewer males (55% vs 64%, p = 0.02). RSV-positive children had higher rates of oxygen use (72% vs 42%, p < 0.001), a longer hospital stay (5 vs 4 days, p = 0.001), and higher hospital charges (US$538 vs US$431, p < 0.001) than RSV-negative children. In young hospitalized Jordanian infants, the medical and financial burden of RSV was found to be high. Effective preventive measures, such as an RSV vaccine, would have a significant beneficial impact.

The role of National Immunization Technical Advisory Groups (NITAG) in strengthening health system governance: Lessons from three middle-income countries-Argentina, Jordan, and South Africa (2017-2018).

INTRODUCTION: Toward the Global Vaccine Action Plan 2020 goal, almost 90% of countries have established a National Immunization Technical Advisory Group (NITAG). However, little is known about NITAG's contributions to governance. METHODS: In 2017-2018, a two-step, qualitative retrospective study was conducted. Jordan (JO), Argentina (AR), and South Africa (SA) were selected owing to government-financed NITAGs from middle-income countries (MICs), geographic diversity, and a vaccine introduction with NITAG support. Country case studies were developed, collecting data through desk review and face-to-face key informant interviews (KIIs) from Ministry of Health (MoH) and NITAG. Case studies were analyzed together, to assess governance applying the European Observatory on Health Systems and Policies framework focusing on transparency, accountability, participation, integrity, and policy capacity (TAPIC). RESULTS: Document review and 53 KII (22 AR, 20 SA, 11 JO) showed NITAGs played a pivotal role as advisors promoting a culture of evidence-informed policies. NITAGs strengthened governance, although practices varied among countries. Meetings were conducted behind-closed-doors, participation restricted to members, only in one country agendas, and recommendations were public (AR). To increase participation, policy capacity, and transparency, countries considered adding experts in communications, advocacy, and economics. AR and SA contemplated including community members. NITAGs functioned autonomously from the government, with no established internal or external monitoring or supervision. NITAG meeting minutes allowed the review of integrity, adherence to terms of reference, standard operating procedures, and conflict of interest (CoI). For the most part, NITAGs abided by their mandates. Significant issues were related to the level of MoH support and oversight of CoI declaration and documentation. CONCLUSIONS: Systematically implementing governance approaches could improve processes, better tailor policies, and implementation. The long-term survival and resilience of NITAGs in these countries showed they play a significant role in strengthening governance. Lessons learned could be useful to those promoting country-driven evidence-informed decision-making.