Infection In Young Infants Research Articles

Treatment of infections in young infants in low- and middle-income countries: a systematic review and meta-analysis of frontline health worker diagnosis and antibiotic access.

Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription? We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%-91%) and lower specificity (62%, 95% CI 48%-75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%-88%) and specificity of 69% (95% CI 54%-83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%-34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data. Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs. PROSPERO International prospective register of systematic reviews (CRD42013004586). Please see later in the article for the Editors' Summary.

Severe neonatal bacterial infections: when numbers matter

Severe neonatal bacterial infections: when numbers matter

The Changing Epidemiology of Serious Bacterial Infections in Young Infants

Management of febrile young infants suspected of having serious bacterial infections has been a challenge for decades. The impact of changes in prenatal screening for Group B Streptococcus and of infant immunizations has received little attention in population-based studies. This study analyzed all cultures of blood, urine and cerebrospinal fluid obtained from full-term infants 1 week to 3 months of age, who presented for care at Kaiser Permanente Northern California during a 7-year period utilizing electronic medical records. A total of 224,553 full-term infants were born during the study period. Of 5396 blood cultures, 129 bacteremic infants were identified (2%). Of 4599 urine cultures, 823 episodes of urinary tract infection (UTI) were documented in 778 infants (17%). Of 1796 CSF cultures, 16 infants had bacterial meningitis (0.9%). The incidence rate of serious bacterial infections (bacteremia, UTI and meningitis) and febrile serious bacterial infections was 3.75 and 3.1/1000 full-term births, respectively. Escherichia coli was the leading cause of bacteremia (78), UTI (719) and bacterial meningitis (7). There were 23 infants with Group B Streptococcus bacteremia including 6 cases of meningitis and no cases of Listeria infection. Nine percentage of infants had multiple sites of infection; 10% of UTIs were associated with bacteremia and 52% of bacteremia was associated with UTI. Compared with earlier studies, UTIs now are found significantly more often than bacteremia and meningitis with 92% of occult infections associated with UTIs. These data emphasize the importance of an urinalysis in febrile infants.

Effect of influenza A infection on maturation and function of neonatal monocyte-derived dendritic cells.

Dendritic cells (DC) are essential for the first-line innate defense against influenza infection. The greater susceptibility to severe influenza infection in young infants and neonates may be attributed in part to their defective DC function. We sought to investigate the effect of influenza A virus (IAV) infection on the maturation, apoptosis, and function of monocyte-derived dendritic cells (MoDCs) from umbilical cord blood (UCB) and compared this with responses from adult peripheral blood (APB). Our findings were as follows. First, MoDCs derived from UCB showed deficient CD40, CD80, CD86, and HLA-DR upregulation following IAV infection compared to APB MoDCs. Second, IAV induced a multiplicity of infection (MOI)-dependent increase of apoptosis in UCB MoDCs, similar to that observed with APB. Third, the ability of UCB MoDCs to uptake dextran is decreased following IAV infection. Fourth, deficient TNF-α, but not IL-6, IFN-α response was induced by IAV infection of UCB MoDCs. Fifth, the ability of UCB MoDCs to promote allogeneic CD3 T-cell proliferation is inhibited by IAV infection. Taken together, we demonstrated a differential response of UCB and APB MoDCs following IAV infection, which may contribute in part to the increased susceptibility to severe influenza infection observed in young infants and neonates.

Intention to accept Bordetella pertussis booster vaccine during pregnancy in Mexico City

ObjectiveAdult booster vaccination against pertussis can help prevent severe infections in young infants. We examined influences on intention to accept pertussis booster vaccination among pregnant women in Mexico City. MethodsWe conducted a cross-sectional survey, recruiting convenience samples of pregnant women receiving prenatal care from three public healthcare centers between March and May 2012. Our primary outcome was intention to accept pertussis vaccination during pregnancy. We examined socio-demographic factors, vaccination history, pertussis knowledge, perceptions of vaccine information sources, and other potential influences on vaccine decision-making. ResultsA total of 402 pregnant women agreed to participate, of which 387 (96%) provided their intention to accept or decline pertussis vaccination. Among respondents, 57% intended to accept a pertussis booster vaccine if offered, but only 16% had ever heard of pertussis, and only 2% knew someone who had contracted this disease. Over 80% of respondents would accept pertussis vaccination if recommended by an obstetrician-gynecologist. The most frequently selected reasons to refuse pertussis vaccination were concerns that the vaccine might harm the unborn baby or pregnant woman. In multivariate analysis, rating doctors and nurses as good sources of vaccine information, and having ever heard of pertussis, were independently associated with intention to accept pertussis vaccination. ConclusionsPromoting patient awareness about pertussis disease and vaccine safety, and encouraging general practitioners, nurses and obstetricians to recommend pertussis booster vaccine, may increase vaccine uptake among pregnant women.

Fc gamma receptors in respiratory syncytial virus infections: implications for innate immunity

RSV infections are a major burden in infants less than 3 months of age. Newborns and infants express a distinct immune system that is largely dependent on innate immunity and passive immunity from maternal antibodies. Antibodies can regulate immune responses against viruses through interaction with Fc gamma receptors leading to enhancement or neutralization of viral infections. The mechanisms underlying the immunomodulatory effect of Fc gamma receptors on viral infections have yet to be elucidated in infants. Herein, we will discuss current knowledge of the effects of antibodies and Fc gamma receptors on infant innate immunity to RSV. A better understanding of the pathogenesis of RSV infections in young infants may provide insight into novel therapeutic strategies such as vaccination.

Ongoing Trials of Simplified Antibiotic Regimens for the Treatment of Serious Infections in Young Infants in South Asia and Sub-Saharan Africa

Background:The current World Health Organization (WHO) recommendation for treatment of severe infection in young infants is hospitalization and parenteral antibiotic therapy. Hospital care is generally not available outside large cities in low- and middle-income countries and even when available is not acceptable or affordable for many families. Previous research in Bangladesh and India demonstrated that treatment outside hospitals may be possible.Research:A set of research studies with common protocols testing simplified antibiotic regimens that can be provided at the lowest-level health-care facility or at home are nearing completion. The studies are large individually randomized controlled trials that are set up in the context of a program, which provides home visits by community health workers to detect serious illness in young infants with assessment and treatment at an outpatient health facility near home. This article summarizes the policy implications of the research studies.Policy Implications:The studies are expected to result in information that would inform WHO guidelines on simple, safe and effective regimens for the treatment of clinical severe infection and pneumonia in newborns and young infants in settings where referral is not possible. The studies will also inform the inputs and process required to establish outpatient treatment of newborn and young infant infections at health facilities near the home. We expect that the information from research and the resulting WHO guidelines will form the basis of policy dialogue by a large number of stakeholders at the country level to implement outpatient treatment of neonatal infections and thereby reduce neonatal and infant mortality resulting from infection.

Simplified Antibiotic Regimens for the Management of Clinically Diagnosed Severe Infections in Newborns and Young Infants in First-level Facilities in Karachi, Pakistan

Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. Timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. This trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of once-daily (OD) intramuscular (IM) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, Pakistan. The reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. The 2 comparison arms are (1) IM gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) IM penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. The primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. This trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of IM procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths.

Safety and Efficacy of Simplified Antibiotic Regimens for Outpatient Treatment of Serious Infection in Neonates and Young Infants 0–59 Days of Age in Bangladesh

Background:Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7–10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections.Methods:We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant’s home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013.Discussion:The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

An Innovative Multipartner Research Program to Address Detection, Assessment and Treatment of Neonatal Infections in Low-resource Settings

Background:In pursuit of innovative approaches for the management of severe infections in young infants, which is a major cause of mortality, a multipartner research program was conceptualized to provide right care in the right place. The primary objective was to generate evidence and identify a simple, safe and effective treatment regimen for young infants with severe infections that can be provided closer to home by trained health workers where referral is not possible.Research:Published and nonpublished data on community-based approaches for the management of neonatal sepsis were critically reviewed by an independent expert panel convened in 2007 by the World Health Organization in collaboration with the United States Agency for International Development and Save the Children/Saving Newborn Lives. These stakeholders agreed to 1) undertake research to improve the specificity of a diagnostic algorithm and revise World Health Organization/United Nations International Children’s Emergency Fund Integrated Management of Childhood Illness guidelines to identify sick young infants for referral, 2) develop research studies with common research designs (1 site in each Bangladesh and Pakistan and a multicentre site in Democratic Republic of Congo, Kenya and Nigeria) and oversight mechanisms to evaluate antibiotic regimens (when referral is not accepted by the family) that are safe and efficacious, appropriate to the severity of infection, and deployable on a large scale and 3) utilize existing program delivery structures incorporating community health workers, skilled health workers to deliver simple antibiotic treatment when referral is not possible.Conclusions:This research program facilitated innovative research in different geographical, cultural and administrative milieus to generate recommendations for policy.

Kinetics of procalcitonin and C-reactive protein and the relationship to postoperative infection in young infants undergoing cardiovascular surgery

BackgroundThe utility of procalcitonin and C-reactive protein (CRP) as infectious biomarkers following infant cardiothoracic surgery is not well defined.MethodsWe designed a prospective cohort study to evaluate procalcitonin and CRP after infant cardiothoracic surgery. Procalcitonin and CRP were drawn pre-operatively and 24/72 hours post-operation or daily in delayed sternal closure patients. Presence of infection within 10 days of surgery, vasoactive-inotropic scores at 24 and 72 hours, and length of intubation, intensive care unit stay, and hospital stay were documented.ResultsProcalcitonin and CRP were elevated at 24 hours. Procalcitonin then decreased while CRP increased in patients undergoing delayed sternal closure or cardiopulmonary bypass. In the delayed sternal closure group, procalcitonin was significantly higher on post-operative days 2–5 in patients who ultimately developed infection. Higher procalcitonin was independently associated with increased vasoactive-inotropic score at 72 hours. CRP did not correlate with infection or post-operative support.ConclusionsProcalcitonin rises after cardiothoracic surgery in infants but decreases by 72 hours while CRP remains elevated. Sternal closure may affect CRP but not procalcitonin. Procalcitonin is independently associated with circulatory support requirements at 72 hours post-operation and development of infection. Procalcitonin may have greater utility as a biomarker in this population.

Prevention of Invasive Cronobacter Infections in Young Infants Fed Powdered Infant Formulas

Prevention of Invasive Cronobacter Infections in Young Infants Fed Powdered Infant Formulas

1064 Neurological Involvement of Enterovirus Infection in Young Infants with Sepsis-Like Illness

IntroductionEnterovirus (EV) infection is common in young infants. Amongst those requiring intensive care seizures and cerebral white matter abnormalities with serious neurologic sequelae have been reported. We questioned whether similar...

Low prevalence of invasive bacterial infection in febrile infants under 3 months of age with enterovirus infection

Infants under 3 months of age with fever without source (FWS) generally undergo a full, invasive septic evaluation to exclude invasive bacterial infection (IBI). Enterovirus (EV) infections are mostly banal and self-limiting and show a high prevalence rate at this age. We aimed to investigate the prevalence of IBI in EV-infected and uninfected infants under 3 months of age with FWS. This was a prospective observational cohort study of infants aged <90 days who were admitted because of FWS. As per protocol, blood and urine analysis and culture were obtained in all cases, and RNA EV from blood and/or cerebrospinal fluid samples was determined by real-time PCR. Three hundred and eighty-one previously healthy infants with FWS were included. EV infection was diagnosed in 64 children (16.8%; 95% confidence interval, 13.2–20.9%) and showed an uneventful evolution in all cases. Laboratory markers of infection were consistently lower in EV-infected patients; only one case of IBI (1.6%) was observed in an EV-infected patient as compared with 25.2% in EV-negative infants (p <0.001). Intravenous antibiotic use and length of stay were no different in EV-infected and uninfected patients. In our study, febrile infants (<90 days) diagnosed with EV infection showed a low risk of IBI when compared with uninfected patients. The systematic investigation of EV infection in young infants with FWS may allow a more conservative approach to the management of these patients. Further studies on this diagnostic approach are needed.

Afebrile pneumonia (whooping cough) syndrome in infants at Hospital Universitario del Valle, Cali, 2001-2007

Afebrile pneumonia syndrome in infants, also called infant pneumonitis, pneumonia caused by atypical pathogens or whooping cough syndrome is a major cause of severe lower respiratory infection in young infants, both in developing countries and in developed countries. To describe children with afebrile pneumonia syndrome. Through a cross-sectional study, we reviewed the medical records of children diagnosed with afebrile pneumonia treated at Hospital Universitario del Valle, a reference center in southwestern Colombia, between June 2001 and December 2007. We obtained data on maternal age and origin, prenatal care, the childs birth, breastfeeding, vaccination status, symptoms, signs, diagnosis, treatment, and complications. We evaluated 101 children with this entity, noting a stationary presentation: June-August and November- December. A total of 73% of the children were under 4 months of age; the most common symptoms were: cyanotic and spasmodic cough (100%), respiratory distress (70%), and unquantified fever (68%). The most common findings: rales (crackles) (50%), wheezing and expiratory stridor (37%); 66% were classified as mild and of the remaining 33%, half of them required attention in the intensive care unit. In all, there was clinical diagnosis of afebrile pneumonia syndrome in infants, but no etiologic diagnosis was made and despite this, 94% of the children received macrolides. These data support the hypothesis that most of these patients acquired the disease by airway, possibly caused by viral infection and did not require the indiscriminate use of macrolides.

Zinc treatment for serious infections in young infants

Zinc deficiency increases risk of infection and growth failure, and is a widespread problem for young children in countries of low and middle income. In countries such as India where consumption of animal protein is low, risk of deficiency is high during pregnancy and in children younger than 5 years.1 Routine zinc supplementation decreases occurrence, severity, and mortality of diarrhoea and pneumonia in children younger than 5 years living in areas where zinc deficiency is common.2–4

Perinatal cytomegalovirus hepatitis in Saudi infants: A case series

Background/Aim:Cytomegalovirus (CMV) is the most common congenital viral infection, occurring in 0.4%–2.3% of all live births. The clinical manifestations of CMV are multiorgan involvement. Currently, the numbers of studies of hepatic CMV infection in immunocompetent infants are insufficient and little information exists in the medical literature about the hepatic manifestations and complications of CMV.Patients and Methods:Nine infants diagnosed with hepatic CMV infection were included in the study. The diagnosis was based on the presence of IgM anti-CMV antibodies titer in serum and detection of CMV-DNA in blood. The authors identified clinical characteristics, biochemical characteristics, immunologic markers, and the outcome of hepatic CMV with or without treatment.Results:Jaundice was the most common clinical feature of CMV infection in infancy (100%). Hepatic abnormalities in the form of cholestasis (defined as a serum conjugated bilirubin concentration greater than 17.1 μmol/L or greater than 20% of the total serum bilirubin) were found in all patients (100%), hepatitis (77%), hypoalbuminemia (55%), elevated alkaline phosphatase, and gamma-glutamyltransferase (77%). Other findings showed hepatosplenomegaly (44%), thrombocytopenia (22%) and low birth weight (11%) The treatment of hepatic CMV infection was indicated in 66% and was not indicated in 33%. Both of them had resolved cholestasis and hepatitis.Conclusion:Jaundice and cholestasis were the most common clinical features of hepatic CMV infections. Hepatic CMV infection in young infants is often a self-limited illness that does not require antiviral therapy. Most of the patients with hepatic CMV infection had a favorable outcome.

Clinical manifestations of a cluster of rotavirus infection in young infants hospitalized in neonatal care units

To define the clinical manifestations of rotavirus (RV) infection in neonates and young infants hospitalized in neonatal care units, which are rarely reported. From October 2008 to September 2010, a total of 153 stool specimens positive for RV were detected from 100 neonates and young infants hospitalized in neonatal care units of our hospital. Four infants had two episodes of RV infection. Demographics and clinical presentations of these infants were collected and analyzed. The infants were further classified as having hospital-acquired (HA) or community-acquired (CA) RV infection. Of the 104 episodes from 100 patients, 76 (73%) were classified as HA. Fifty-six infants were male. The mean age of onset was 2 days. The most common presentations were loose stool passages (52.9%), abdominal distension (51.9%), blood or mucus in stool (42.3%), and unstable vital signs (32.7%). Watery character in stool passage was identified in 13.5% of the infants and vomiting in 21.2%. A picture suggestive of necrotizing enterocolitis (NEC) was identified in 22 episodes (21.1%), and 12 of these were stage II or above. The average number of hospitalization days from the onset of HA-RV infection was 23 days. Compared with those in the CA group, the infants in the HA group had a significantly higher rate of blood or mucus in stools (52.6% vs. 14.3%, p < 0.01) and unstable vital signs (39.5% vs. 14.3%, p = 0.02), but a lower rate of watery diarrhea (9.2% vs. 28.6%, p = 0.04) and fever (13.8% vs. 42.9%, p < 0.01). Overall, there were five deaths, but all of these infants had major diseases. Bloody, mucoid stools and unstable vital signs, instead of fever with watery diarrhea, are commonly seen in neonates and young infants with RV infection. A substantial proportion of these infants may present as NEC. Once introduced, RV appears to become a troublesome problem of HA infections in neonatal care settings.

Enterovirus infections in young infants: Are children still protected by maternal antibodies?

Enterovirus infections are frequent in childhood and may be involved in development of several chronic diseases including type 1 diabetes. Maternal antibodies have a protective effect in young infants. It has been proposed that this protection is now vanishing due to decreasing circulation of enteroviruses in Western countries. We aimed to analyse the occurrence of enterovirus infections in 55 infants and to assess the protection provided by maternal antibodies to these children and the development of enterovirus antibodies in a prospective cohort study. In addition, the presence of enteroviruses was detected in faeces using RT-PCR and their serotype identified using VP1 region sequencing. Our results showed that before polio vaccination 12 of 194 faecal samples were positive for enterovirus RNA (coxsackieviruses A4, A5, A16 or echoviruses 13 and 16). After vaccination Sabin 1, 2 and 3 poliovirus strains predominated in stool samples. From birth to 6 months of age polio IgG and IgA increased in most of children whereas the levels of other enterovirus antibodies started to increase from 6 months to 24 months age. The frequency of maternal neutralizing antibodies was generally quite high but still 3 out of 8 infants had no maternal antibodies against the enterovirus serotype which they had in stool sample. This study shows that enterovirus infections are relatively frequent already before the age of 3 months. Considerable proportion of infants lack maternal antibodies against the virus causing their infection. The significance of this phenomenon needs to be evaluated in larger studies.

Transmission intrafamiliale de Staphylococcus aureus sécréteur de toxine leucocidine Panton-Valentine responsable de deux cas de pneumopathies nécrosantes néonatales

Necrotizing Staphylococcus aureus Panton-Valentine leukocidin (SA-PLV+) accounts for less than 1% of community-acquired lung diseases in children and young adults. Neonatal cases are exceptional. We report the observations of two newborn female twins, who were not breastfed, presenting a necrotizing lung disease due to the same strain of SA-PVL+ despite nasal decolonization measures taken. These two cases are informative and bring to light (1) the possibility of severe SA-PVL+ lung infections in young infants and (2) their strictly intrafamilial mode of transmission for which eradication measures were ineffective.