Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Nasopharyngeal carriage of otitis media pathogens in infants receiving 10-valent non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10), 13-valent pneumococcal conjugate vaccine (PCV13) or a mixed primary schedule of both vaccines: A randomised controlled trial.

BACKGROUND: Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? METHODS: Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. FINDINGS: At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). CONCLUSIONS: Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

Epidemiology and prospects for prevention of rotavirus disease in India.

CONTEXT: With rotavirus vaccines now available globally, it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India, in order to weigh the urgency of introducing a vaccine to help control rotavirus disease. EVIDENCE ACQUISITION: We reviewed published studies on rotavirus infection and genotype distribution in India, as well as safety and immunogenicity studies of currently available vaccines. PubMed was searched for papers published after 1990, and several authors who are experts in the field recommended papers of known significance. RESULTS: Rotavirus accounts for close to 40% of hospitalizations for diarrhea in India, with more recent studies showing an increased proportion compared with older studies. There is substantial serotype diversity in India, although there is less intra-country variation than previously thought. Two genotypes, G1P[8] and G2P[4], account for roughly 50% of symptomatic infections in non-neonates. Currently licensed vaccines are safe, and although the efficacy appears lower in developing countries, given the extremely high incidence of diarrhea these could still be cost-effective interventions. CONCLUSIONS: The epidemiology and burden of rotavirus diarrhea is fairly well characterized in India. Introducing rotavirus vaccine into the UIP, along with adequate surveillance, should be an important part of efforts to reduce diarrhea mortality, the third leading cause of death among Indian children, and achieve the country's MDG goals.

Supporting new vaccine introduction decisions: lessons learned from the Hib Initiative experience.

The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines.

Use of serology and urine antigen detection to estimate the proportion of adult community-acquired pneumonia attributable to Streptococcus pneumoniae.

Streptococcus pneumoniae is a common cause of community-acquired pneumonia (CAP) but existing diagnostic tools have limited sensitivity and specificity. We enrolled adults undergoing chest radiography at three Indian Health Service clinics in the Southwestern United States and collected acute and convalescent serum for measurement of PsaA and PspA titres and urine for pneumococcal antigen detection. Blood and sputum cultures were obtained at the discretion of treating physicians. We compared findings in clinical and radiographic CAP patients to those in controls without CAP. Urine antigen testing showed the largest differential between CAP patients and controls (clinical CAP 13%, radiographic CAP 17%, control groups 2%). Serological results were mixed, with significant differences between CAP patients and controls for some, but not all changes in titre. Based on urine antigen and blood culture results, we estimated that 11% of clinical and 15% of radiographic CAP cases were due to pneumococcus in this population.

Measuring the incidence of adult community-acquired pneumonia in a Native American community.

Few population-based studies have investigated the epidemiology of adult community-acquired pneumonia (CAP). We aimed to determine the incidence of CAP in a population at high-risk for pneumococcal disease and to evaluate a standardized method for interpreting chest radiographs adapted from the World Health Organization paediatric chest radiograph interpretation guidelines. We reviewed radiology records at the two healthcare facilities serving the White Mountain Apache tribe to identify possible pneumonia cases > or =40 years of age. We categorized patients with clinical criteria and a physician diagnosis of pneumonia as clinical CAP and those with clinical criteria and an acute infiltrate as radiographic CAP. We identified 100 (27/1000 person-years) and 60 (16/1000 person-years) episodes of clinical and radiographic CAP, respectively. The incidence of CAP increased with age. Both radiographic and clinical CAP were serious illnesses with more than half of patients hospitalized. Our case definitions and methods may be useful for comparing data across studies and conducting vaccine trials.

Impact of clean delivery kit use on clean delivery practices in Beni Suef Governorate, Egypt.

OBJECTIVE: A major factor contributing to neonatal and maternal infections is unhygienic delivery practices. This study explores the impact of clean delivery kit (CDK) use on clean delivery practices during home and facility deliveries. DESIGN: Kits were distributed from primary care facilities and mothers and birth attendants received training on kit importance and use. The study was designed as a cross-sectional cohort study. Raedat (community health workers) visited 349 women during the postpartum period to administer a structured questionnaire. SETTING: The study was conducted from mid-March through mid-July 2001 in two rural areas of Ihnasia district in Beni Suef Governorate (Upper Egypt). RESULT: In bivariate analysis, CDK users in the home were more likely to report that the birth attendant had clean hands (P<0.001), washed/wiped the mother's perineum (P<0.001), used a sterile cord tie (P=0.001), applied antiseptic to the cord after cutting (P<0.001), and used a sterile cord cover (P<0.001) as compared with non-CDK users. CDK users at the facility were more likely to report that the birth attendant washed/wiped the mothers perineum (P=0.049) and used a sterile cord cover (P=0.030) as compared with non-CDK users. CONCLUSION: In settings in which unhygienic practices during home as well as facility deliveries are prevalent, use of inexpensive CDKs can promote clean delivery practices.

Addition of isovitalex in chocolate agar for the isolation of Haemophilus influenzae.

BACKGROUND & OBJECTIVE: The reason for lack of data on burden of Haemophilus influenzae type b (Hib) in developing countries was mainly failure of detection of this fastidious organism in laboratories. Use of isovitalex (IVX) was suggested as an essential supplement for growing this organism. This study was carried out to investigate the impact of IVX supplementation to chocolate agar for detection of Hib. METHODS: Chocolate agar with and without supplementation of IVX was prepared. Clinical samples as well as reference strains of Hib were simultaneously cultured on both the media. RESULTS: H. influenzae isolates (N=194) were simultaneously grown on chocolate agar (CA) with and without isovitalex (IVX). Average colony size of H. influenzae on CA with IVX (CA-IVX) was larger only by 0.10 cm (range 0.05 to 0.16 cm) compared to CA alone. Addition of IVX to CA increased the cost of media by 2.1-fold. INTERPRETATION & CONCLUSION: Isovitalex is not essential for the isolation and growth of H. influenzae almost halving the cost.

Community perceptions of birth weight in rural Uttar Pradesh, India: implications for care of low-birth-weight infants.

Effective implementation of interventions targeting low birth weight (LBW) and preterm infants, who contribute 60 to 80% of all neonatal deaths, requires an understanding of local people's perceptions of birth weight. This study was conducted to understand how birth weight is perceived in a low-resource setting, including the etiology, signs and care given to infants of various weights. In this qualitative research study, in-depth interviews and focus group discussions were conducted with recently delivered women (RDW) and their families, as well as local health stakeholders in a rural North Indian community. Birth weight per se is not considered a determinant of newborn health. Instead, newborns are classified into types, and care is provided based on these types. Classification is based on observable criteria, including feeding, vigor and alertness, and interviewees did not always consider low weight a criterion for weak type. In communities that do not perceive birth weight to be an important determinant of health, public health programmes and practitioners must reframe messages regarding additional care for LBW infants at home and care seeking outside the home in locally relevant ways.

Vaccination greatly reduces disease, disability, death and inequity worldwide.

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

Validation of accuracy and community acceptance of the BIRTHweigh III scale for categorizing newborn weight in rural India.

OBJECTIVE: To determine the accuracy and acceptability of a handheld scale prototype designed for nonliterate users to classify newborns into three weight categories (>or=2,500 g; 2,000 to 2,499 g; and <2,000 g). STUDY DESIGN: Weights of 1,100 newborns in Uttar Pradesh, India, were measured on the test scale and validated against a gold standard. Mothers, family members and community health stakeholders were interviewed to assess the acceptability of the test scale. RESULT: The test scale was highly sensitive and specific at classifying newborn weight (normal weight: 95.3 and 96.3%, respectively; low birth weight: 90.4 and 99.2%, respectively; very low birth weight: 91.7 and 98.4%, respectively). It was the overall agreement of the community that the test scale was more practical and easier to interpret than the gold standard. CONCLUSION: The BIRTHweigh III scale accurately identifies low birth weight and very low birth weight newborns to target weight-specific interventions. The scale is extremely practical and useful for resource-poor settings, especially those with low levels of literacy.

Feasibility of community neonatal death audits in rural Uttar Pradesh, India.

OBJECTIVE: Medical audit is a widely promoted strategy in hospitals, but experience within community settings is scant. Community neonatal death audit is a form of audit, which involves a systematic analysis of the quality of care provided in the home, danger sign recognition and care seeking decision making for neonatal illness. This research was conducted in Uttar Pradesh, India, to investigate the feasibility and cultural acceptability of community neonatal death audits. STUDY DESIGN: During November-December 2004, we conducted three in-depth interviews with family members of deceased neonates, and six focus group discussions with family and community members. Three approaches were evaluated: in-depth interview with the family before engaging them in an audit with the community; preliminary meeting to build rapport with the family and community before conducting an audit; and audit with the family and community in a single focus group. Approaches were interactive processes, involving the community, to identify avoidable factors in a particular death and discuss solutions. RESULT: Carried out in a culturally sensitive and non-punitive manner, community neonatal death audit was found to be acceptable and feasible. All approaches provoked formal investigation by community members, and stimulated sharing of views, leading to the self-discovery that community perception was a cumulatively amplified effect of individual perceptions. Presence of an educated/experienced community member or health worker served as a catalyst. No one optimal approach was identified. CONCLUSION: Community neonatal audit is an acceptable approach that shows promise as an effective intervention for improving neonatal health outcomes.

Newborn care in rural Uttar Pradesh.

OBJECTIVES: To describe selected newborn care practices related to cord care, thermal care and breastfeeding in rural Uttar Pradesh and to identify socio-demographic, antenatal and delivery care factors that are associated with these practices. METHODS: A cross-sectional survey in rural Uttar Pradesh included 13,167 women who had a livebirth at home during the two years preceding data collection. Logistic regression was used to identify socio-demographic, antenatal and delivery care factors that were associated with the three care practices. RESULTS: Use of antenatal care and skilled attendance at delivery were significantly associated with clean cord care and early breastfeeding, but not with thermal care. Antenatal home visits by a community-based worker were associated only with clean cord care. Women who received counseling from health workers or other sources on each of the newborn care practices during pregnancy were more likely to report the respective care practices, although levels of counseling were low. CONCLUSION: The association between newborn care practices and antenatal care, counseling and skilled delivery attendance suggest that evidence-based newborn care practices can be promoted through improved coverage with existing health services.

Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programmes.

OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1-6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7-13 and 14-27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period.

Introduction of community-based skin-to-skin care in rural Uttar Pradesh, India.

OBJECTIVE: Two-thirds of women globally give birth at home, yet little data are available on use of skin-to-skin care (STSC) in the community. We describe the acceptability of STSC in rural Uttar Pradesh, India, and measured maternal, newborn, and ambient temperature in the home in order to inform strategies for introduction of STSC in the community. STUDY DESIGN: Community-based workers in intervention clusters implemented a community mobilization and behavior change communication program that promoted birth preparedness and essential newborn care, including adoption of STSC, with pregnant mothers, their families, and key influential community members. Acceptance of STSC was assessed through in-depth interviews and focus groups, and temperature was measured during home visits on day of life 0 or 1. RESULTS: Incidence of hypothermia (<36.5 degrees C) was high in both low birth weight (LBW) and normal birth weight (NBW) infants (49.2%, (361/733) and 43% (418/971), respectively). Mean body temperature of newborns was lower (P<0.01) in ambient temperatures <20 degrees C (35.9+/-1.4 degrees C, n=225) compared to > or =20 degrees C (36.5+/-0.9 degrees C, n=1450). Among hypothermic newborns, 42% (331/787) of their mothers had a lower temperature (range -6.7 to 0.1 degrees C, mean difference 0.4+/-1.2 degrees C). Acceptance of STSC was nearly universal. No adverse events from STSC were reported. STSC was perceived to prevent newborn hypothermia, enhance mother's capability to protect her baby from evil spirits, and make the baby more content. CONCLUSION: STSC was highly acceptable in rural India when introduced through appropriate cultural paradigms. STSC may be of benefit for all newborns and for many mothers as well. New approaches are needed for introduction of STSC in the community compared to the hospital.

Evaluation of the indirect effects of a pneumococcal vaccine in a community-randomized study.

When a sufficiently high proportion of a population is immunized with a vaccine, reduction in secondary transmission of disease can confer significant protection to unimmunized population members. We propose a straightforward method to estimate the degree of this indirect effect of vaccination in the context of a community-randomized vaccine trial. A conditional logistic regression model that accounts for within-randomization unit correlation over time is described, which models risk of disease as a function of community-level covariates. The approach is applied to an example data set from a pneumococcal conjugate vaccine study, with study arm and immunization levels forming the covariates of interest for the investigation of indirect effects.

Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries.

UNLABELLED: Topical therapy to enhance skin barrier function may be a simple, low-cost, effective strategy to improve outcome of preterm infants with a developmentally compromised epidermal barrier, as lipid constituents of topical products may act as a mechanical barrier and augment synthesis of barrier lipids. Natural oils are applied topically as part of a traditional oil massage to neonates in many developing countries. We sought to identify inexpensive, safe, vegetable oils available in developing countries that improved epidermal barrier function. The impact of oils on mouse epidermal barrier function (rate of transepidermal water loss over time following acute barrier disruption by tape-stripping) and ultrastructure was determined. A single application of sunflower seed oil significantly accelerated skin barrier recovery within 1 h; the effect was sustained 5 h after application. In contrast, the other vegetable oils tested (mustard, olive and soybean oils) all significantly delayed recovery of barrier function compared with control- or Aquaphor-treated skin. Twice-daily applications of mustard oil for 7 d resulted in sustained delay of barrier recovery. Moreover, adverse ultrastructural changes were seen under transmission electron microscopy in keratin intermediate filament, mitochondrial, nuclear, and nuclear envelope structure following a single application of mustard oil. CONCLUSION: Our data suggest that topical application of linoleate-enriched oil such as sunflower seed oil might enhance skin barrier function and improve outcome in neonates with compromised barrier function. Mustard oil, used routinely in newborn care throughout South Asia, has toxic effects on the epidermal barrier that warrant further investigation.

Nasopharyngeal carriage of resistant pneumococci in young South Indian infants.

Streptococcus pneumoniae is the leading bacterial cause of life-threatening infections in infants. Although antibiotic resistance affects management of pneumococcal infections, few data on patterns of resistance are available for India. We examined nasopharyngeal carriage of antibiotic-resistant pneumococci in 464 South Indian infants between 2 and 6 months. Newly acquired serotypes were screened for susceptibility to cotrimoxazole, erythromycin and penicillin using disk diffusion. Cumulative prevalence of pneumococcal carriage rose from 53.9% at 2 months to 70.2% at 6 months. The prevalence of strains that were not susceptible to penicillin, cotrimoxazole and erythromycin was 34, 81.1 and 37.2%, respectively. Carriage of erythromycin non-susceptible strains declined significantly between ages 4 months and 6 months (44.1 vs. 10.7%). More than 87% of the isolates screened were non-susceptible to > or = 1 antibiotic. Serogroups/types that were most frequently non-susceptible to 1 or more antibiotics were 6, 9, 14, 19 and 23. Less than 1% of the isolates were multi-drug resistant. Widespread use of antibiotics in South India has resulted in S. pneumoniae becoming non-susceptible to some commonly used antibiotics. Monitoring trends in antibiotic susceptibility and making antibiotics available only through prescription from a health care worker may slow the spread of resistant pneumococci and improve management of pneumococcal infections in South India.