An Integrated Mother-Child Intervention on Child Development and Maternal Mental Health.

OBJECTIVES: To evaluate an integrated, low-cost, facility-based group intervention designed to promote child care, boost maternal mental-wellbeing, reduce harsh discipline, and improve children's health, nutrition, and early development. METHODS: In Dhaka, 30 neighborhood clusters of a low-income urban community were randomized to intervention or control groups. Mothers with children between 6 and 24 months (n = 300) who self-reported negative discipline were identified and enrolled. A 1-year group intervention included integration of responsive caregiving, nutritional supplementation, caregivers' mental health, child protection, and health advice. Child outcomes were cognition (primary) and language, motor and behavioral development, growth, and hemoglobin and iron status (secondary). Maternal outcomes were depressive symptoms, self-esteem, negative discipline, and child care knowledge and practices. RESULTS: Overall, 222 (74%) mother-child dyads participated in the 1-year follow-up. Intervention and control groups differed on wealth, with no other significant differences. The intervention resulted in a 0.75 SD effect on cognition, 0.77 SD on language, 0.41 SD on motor, and 0.43 to 0.66 SDs on behavior during testing (emotion, cooperation, and vocalization) in the intervention arm. Mothers in the intervention group had fewer depressive symptoms (effect size: -0.72 SD), higher self-esteem (0.62 SD), better child care knowledge (2.02 SD), fewer harsh discipline practices (0.25 SD), and better home stimulation (0.73 SD). The intervention showed no effect on child growth or hemoglobin, but significantly improved serum iron status (-0.36 SD). CONCLUSIONS: A comprehensive intervention, delivered through group sessions in health facilities, was effective in promoting child development and reducing maternal depressive symptoms among mothers who reported using negative or harsh discipline.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

Epidemiology of the Rhinovirus (RV) in African and Southeast Asian Children: A Case-Control Pneumonia Etiology Study.

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing.

Considerations for design and implementation of vaccine field trials for novel foot-and-mouth disease vaccines.

Vaccines are commonly used to control Foot-and-Mouth Disease (FMD) in endemic regions and form an important part of contingency plans for FMD-free countries. Conventional FMD vaccines have numerous limitations, and the U.S. government supports the development of next-generation vaccines. In the U.S., vaccine efficacy is typically demonstrated through experimental vaccination and challenge of animals using the World Organization for Animal Health (OIE) standards. Although conventional challenge and immunogenicity studies provide useful information, they have limitations and results do not always accurately predict field performance. Consequently, there is a need to test next-generation vaccines under field conditions to gain a better understanding of field performance to inform policy decisions and support their viability as a commercial product. In June 2017, an expert consultation was organised to discuss and define an optimal field study design for novel FMD vaccines. Cattle were the primary species considered, although parallel strategies for swine and small ruminants were also discussed. Many methodological and logistical considerations in the study design were identified, including: (1) study site selection and the importance of baseline studies to understand exposure risk, (2) ethics of using a placebo and assessing equivalence with conventional vaccines, (3) merits of using individual randomised versus cluster randomised trials, (4) preventive versus reactive vaccination, and (5) methods of randomisation and blinding. The proposed optimal study design was a multicentre (i.e. farm), three-arm, double-blind randomised controlled trial comparing groups receiving the novel vaccine to a conventional vaccine group and a placebo group. Large farms in areas of high exposure risk were identified as ideal study sites, and the primary study outcome was susceptibility to disease or infection, during a six-month observation period, following a single dose of vaccine. This report provides a summary of the important issues to consider when designing a field efficacy study in livestock and proposes a study design that could be utilised for novel FMD vaccines.

Monitoring influenza virus susceptibility to oseltamivir using a new rapid assay, iART.

A new rapid assay for detecting oseltamivir resistance in influenza virus, iART, was used to test 149 clinical specimens. Results were obtained for 132, with iART indicating 41 as 'resistant'. For these, sequence analysis found known and suspected markers of oseltamivir resistance, while no such markers were detected for the remaining 91 samples. Viruses isolated from the 41 specimens showed reduced or highly reduced inhibition by neuraminidase inhibition assay. iART may facilitate broader antiviral resistance testing.

Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

BACKGROUND: Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. METHODS: As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. PRINCIPAL FINDINGS: We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. CONCLUSIONS: This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children.

Influenza-associated mortality in 2009 in four sentinel sites in Bangladesh.

OBJECTIVE: To estimate influenza-associated mortality in Bangladesh in 2009. METHODS: In four hospitals in Bangladesh, respiratory samples were collected twice a month throughout 2009 from inpatients aged < 5 years with severe pneumonia and from older inpatients with severe acute respiratory infection. The samples were tested for influenza virus ribonucleic acid (RNA) using polymerase chain reaction. The deaths in 2009 in five randomly selected unions (the smallest administrative units in Bangladesh) in each hospital's catchment area were then investigated using formal records and informal group discussions. The deaths of those who had reportedly died within 14 days of suddenly developing fever with cough and/or a sore throat were assumed to be influenza-associated. The rate of such deaths in 2009 in each of the catchment areas was then estimated from the number of apparently influenza-associated deaths in the sampled unions, the proportion of the sampled inpatients in the local hospital who tested positive for influenza virus RNA, and the estimated number of residents of the sampled unions. FINDINGS: Of the 2500 people known to have died in 2009 in all 20 study unions, 346 (14%) reportedly had fever with cough and/or sore throat within 14 days of their deaths. The estimated mean annual influenza-associated mortality in these unions was 11 per 100,000 population: 1.5, 4.0 and 125 deaths per 100,000 among those aged < 5, 5-59 and > 59 years, respectively. CONCLUSION: The highest burden of influenza-associated mortality in Bangladesh in 2009 was among the elderly.

Early detection of pandemic (H1N1) 2009, Bangladesh.

To explore Bangladesh's ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June-July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.

Incidence of influenza-like illness and severe acute respiratory infection during three influenza seasons in Bangladesh, 2008-2010.

OBJECTIVE: To determine how much influenza contributes to severe acute respiratory illness (SARI), a leading cause of death in children, among people of all ages in Bangladesh. METHODS: Physicians obtained nasal and throat swabs to test for influenza virus from patients who were hospitalized within 7 days of the onset of severe acute respiratory infection (SARI) or who consulted as outpatients for influenza-like illness (ILI). A community health care utilization survey was conducted to determine the proportion of hospital catchment area residents who sought care at study hospitals and calculate the incidence of influenza using this denominator. FINDINGS: The estimated incidence of SARI associated with influenza in children < 5 years old was 6.7 (95% confidence interval, CI: 0-18.3); 4.4 (95% CI: 0-13.4) and 6.5 per 1000 person-years (95% CI: 0-8.3/1000) during the 2008, 2009 and 2010 influenza seasons, respectively. The incidence of SARI in people aged ≥ 5 years was 1.1 (95% CI: 0.4-2.0) and 1.3 (95% CI: 0.5-2.2) per 10,000 person-years during 2009 and 2010, respectively. The incidence of medically attended, laboratory-confirmed seasonal influenza in outpatients with ILI was 10 (95% CI: 8-14), 6.6 (95% CI: 5-9) and 17 per 100 person-years (95% CI: 13-22) during the 2008, 2009 and 2010 influenza seasons, respectively. CONCLUSION: Influenza-like illness is a frequent cause of consultation in the outpatient setting in Bangladesh. Children aged less than 5 years are hospitalized for influenza in greater proportions than children in other age groups.

Resumen OBJETIVO: Determinar en qué medida contribuye la gripe a la enfermedad respiratoria aguda grave (ERAG), una de las principales causas de muerte infantil, en personas de todas las edades en Bangladesh. MÉTODOS: Los médicos tomaron muestras de exudado nasal y faríngeo para realizar la prueba del virus de la gripe en pacientes que estuvieron hospitalizados en los 7 días posteriores al inicio de la infección respiratoria agua grave (IRAG) o que acudieron a consulta como pacientes ambulatorios por síndrome gripal (SG). Se llevó a cabo un estudio sobre el uso de la asistencia sanitaria comunitaria para determinar la proporción de residentes del área de cobertura del hospital que solicitaron asistencia médica en hospitales pertenecientes al estudio y se calculó la incidencia de la gripe con este denominador. RESULTADOS: La incidencia estimada de la IRAG asociada con la gripe en niños menores de 5 años fue del 6,7 (95% de intervalo de confianza, IC: 0-18,3); 4,4 (95% IC: 0-13,4) y 6,5 por 1000 años-persona (95% IC: 0-8,3/1000) durante las temporadas de gripe de 2008, 2009 y 2010, respectivamente. La incidencia de la IRAG en las personas con una edad igual o superior a 5 años fue del 1,1 (95% IC: 0,4- 2,0) y 1,3 (95% IC: 0,5-2,2) por 10 000 años-persona durante 2009 y 2010, respectivamente. La incidencia de la gripe de temporada tratada médicamente y confirmada en laboratorio en pacientes ambulatorios con SG fue de 10 (95% IC: 8-14); 6,6 (95% IC: 5-9) y 17 por 100 años-persona (95% IC: 13-22/1000) durante las temporadas de gripe de 2008, 2009 y 2010, respectivamente. CONCLUSIÓN: El síndrome gripal es una causa frecuente de consulta en los centros ambulatorios en Bangladesh. La proporción de niños menores de 5 años hospitalizados por gripe es mayor que la de niños en otros grupos de edad.

Résumé OBJECTIF: Déterminer l'impact de la grippe sur le syndrome respiratoire aigu sévère (SRAS), une cause majeure de la mortalité chez les enfants, chez les personnes de tous les âges au Bangladesh. MÉTHODES: Les médecins ont obtenu des écouvillons de prélèvement de nez et de gorge afin de tester le virus de la grippe chez des patients qui avaient été hospitalisés dans les 7 jours suivants l'apparition de l'infection respiratoire aiguë sévère (SRAS) ou qui avaient eu une consultation déambulatoire pour un syndrome de type grippal (STG). Une enquête sur l'utilisation des soins de santé communautaires a été effectuée afin de définir la proportion des riverains de la circonscription hospitalière, qui avaient reçu des soins dans les hôpitaux universitaires, et afin de calculer l'incidence de la grippe à l'aide de ce dénominateur. RÉSULTATS: L'estimation de l'incidence du SRAS associé à la grippe chez les enfants de moins de 5 ans était de 6,7 (intervalle de confiance de 95%, IC: 0-18.3); de 4,4 (IC de 95%: 0-13.4) et de 6,5 pour 1 000 personnes-années (IC de 95%: 0-8.3/1000) lors des saisons de la grippe de 2008, 2009 et 2010, respectivement. L'incidence du SRAS chez les personnes âgées de plus de 5 ans était de 1,1 (IC de 95%: 0.4-2.0) et 1,3 (IC de 95%: 0.5-2.2) pour 10 000 personnes-années en 2009 et 2010, respectivement. L'incidence de la grippe saisonnière traitée médicalement et confirmée en laboratoire chez les patients en consultation ambulatoire souffrant du STG était de 10 (IC de 95%: 8-14), 6,6 (IC de 95%: 5-9) et de 17 pour 100 personnes-années (IC de 95%: 13-22) lors des saisons de la grippe de 2008, 2009 et 2010, respectivement. CONCLUSION: Le syndrome de type grippal est une cause fréquente de consultation dans la configuration de la consultation ambulatoire au Bangladesh. Les enfants de moins de 5 ans sont hospitalisés pour la grippe dans des proportions supérieures aux enfants des autres groupes d'âge.

An evaluation of emerging vaccines for childhood pneumococcal pneumonia.

BACKGROUND: Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%). CONCLUSIONS: Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.

Prevalence and risk factors of hepatitis B and C virus infections in an impoverished urban community in Dhaka, Bangladesh.

BACKGROUND: Viral hepatitis is a serious global public health problem affecting billions of people globally, and both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are rapidly spreading in the developing countries including Bangladesh due to the lack of health education, poverty, illiteracy and lack of hepatitis B vaccination. Also there is lack of information on their prevalence among the general population. So, a population-based serological survey was conducted in Dhaka to determine the prevalence and risk factors of HBV and HCV infections. METHODS: Healthy individuals were selected for demographic and behavioural characteristics by stratified cluster sampling and blood tested for hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (anti-HBc), and anti-HCV antibodies (anti-HCV). RESULTS: From June 2005-November 2006, 1997 participants were screened for HBsAg, anti-HBc and anti-HCV, 738 (37%) were males with mean (SD) age of 24 (14) years. HBV-seropositivity was documented in 582 (29%) participants: 14 (0.7%) were positive for HBsAg, 452 (22.6%) for anti-HBc and 116 (5.8%) for both HBsAg and anti-HBc. Four (0.2%) participants were positive for anti-HCV, and another five (0.3%) for both anti-HBc and anti-HCV. Ninety-six/246 (39%) family members residing at same households with HBsAg positive participants were also HBV-seropositive [74 (30.1%) for anti-HBc and 22 (8.9%) for both HBsAg and anti-HBc], which was significantly higher among family members (39%) than that of study participants (29%) (OR 1.56; p < 0.001). In bivariate analysis, HBV-seropositivity was significantly associated with married status (OR 2.27; p < 0.001), history of jaundice (OR 1.35; p = 0.009), surgical operations (OR 1.26; p = 0.04), needle-stick injuries (OR 2.09; p = 0.002), visiting unregistered health-care providers (OR 1.40; p = 0.008), receiving treatment for sexually transmitted diseases (STD) (OR 1.79; p = 0.001), animal bites (OR 1.73; p < 0.001); ear-nose-body piercing in females (OR 4.97; p < 0.001); circumcision (OR 3.21; p < 0.001), and visiting community barber for shaving in males (OR 3.77; p < 0.001). In logistic regression analysis, married status (OR 1.32; p = 0.04), surgical operations (OR 1.39; p = 0.02), animal bites (OR 1.43; p = 0.02), visiting unregistered health-care providers (OR 1.40; p = 0.01); and ear-nose-body piercing in females (OR 4.97; p < 0.001) were significantly associated with HBV-seropositivity. CONCLUSIONS: The results indicate intermediate level of endemicity of HBV infection in Dhaka community, with much higher prevalence among family members of HBsAg positive individuals but low prevalence of HCV infections, clearly indicating need for universal hepatitis B vaccination. The use of disposable needles for ear-nose-body piercing need to be promoted through public awareness programmes as a preventive strategy.

Conjugate vaccines for enteric fever: proceedings of a meeting organized in New Delhi, India in 2009.

Enteric fever is responsible for significant morbidity in South Asia and high prevalence of severe disease is seen in children under two years of age. Effective typhoid vaccines are available, but they cannot be used for children under two years of age and also have some limitations in older age groups. Participants supported development of a Salmonella Typhi conjugate vaccine able to induce effective, long-lasting immunity in young children. The role of Salmonella Paratyphi A as a cause of enteric fever was discussed and consensus reached that a bivalent S. Typhi-S. Paratyphi A conjugate vaccine is highly desirable; however, considering disease epidemiology and the advanced status of vaccine development, rapid introduction of monovalent S. Typhi conjugate vaccine into vaccination programs of South Asia was recommended. Prevention should be emphasized, available vaccines used, and efforts toward improving sanitation continued. Success of the new vaccine will depend on several factors, including delivery costs and governmental ability to adopt and implement suitable immunization programs. To ensure good immunization coverage, the conjugate vaccine could be administered either to young infants, concomitantly with infant EPI vaccines, or to older infants, concomitantly with measles vaccine, currently given at 9 to 12 months. The need for new combination vaccines, containing both EPI and typhoid antigens, was discussed as a tool to increase coverage and reduce the number of injections and priority conflicts in a crowded infant vaccination schedule. However, stand-alone enteric fever conjugate vaccines would allow more flexibility to immunize different age groups and therefore should be rapidly developed.