Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Pneumococcal Antibody Concentrations and Carriage of Pneumococci more than 3 Years after Infant Immunization with a Pneumococcal Conjugate Vaccine

BACKGROUND: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38-52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6-8 weeks and 16-18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6-8 weeks after PCV-7, but only the 6B difference was sustained at 16-18 months. There was no significant difference in nasopharyngeal carriage between the two groups. CONCLUSIONS/SIGNIFICANCE: Pneumococcal antibody concentrations in Gambian children were high 34-48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months

Diet and asthma: looking back, moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant's immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma

Malaria parasitaemia among pregnant women in a rural community of eastern Nigeria; Need for combined measures

Malaria in pregnancy is a major contributor to adverse maternal and perinatal outcome. In hyper endemic areas like ours, it is a common cause of anaemia in pregnancy in both immune and non-immune individuals and is aggravated by poor socioeconomic circumstances. The aim of this study is to assess the prevalence of asymptomatic malaria parasitaemia among pregnant women in a rural setting. 272 pregnant women, aged between 18 and 40 years in some remote rural areas of Ebonyi State, Nigeria were recruited between January 2007 and March 2008.Their blood samples were collected and examined for malaria parasite, haemoglobin and packed cell volume using standard methods. Our results showed 59.9% prevalence of parasitaemia with the highest prevalence occurring in the first trimester (84.1%).Among the positive cases, mild parasitaemia was recorded in 47.2% moderate parasitaemia in 37.4% while severe parasitaemia was recorded in 15.3% of cases. These differences were statistically significant (P<0.016). Furthermore the distribution of malaria densities in different gravidity groups showed an inverse relationship, 45.4% in primigravidae, (31.9%) in secundigravidae and (10.4%) among people with more than five pregnancies. These findings were statistically significant (P< 0.0001). The prevalence of anaemia in pregnancy in this study was 62.4%. Apart from the use of nets, drugs and vector control, the prevention of malaria in pregnancy in very poor socioeconomic settings should make provision for nutritional support

Chain Peer Referral Approach for HIV Testing Among Adolescents in Kisumu County, Kenya

New HIV infections among adolescents continues to be a large public health burden in sub-Saharan Africa, with few adolescents accessing HIV testing and counseling (HTC) services. We evaluated the effect of a peer referral program among adolescents in Kisumu county, Kenya in accessing HTC. Female adolescents aged 15 to 19&nbsp;years were recruited from three health clinics in Kisumu County. They, in turn, recruited their peers for HTC by handing out referral cards. Referrals would then recruit their peers and this peer-referral repeated for approximately 5&nbsp;months. The 252 female index seeds showed a relatively higher-risk profile for HIV compared to the 792 referral participants. The referral system yielded an increased proportion of first-time adolescent testers from 13.1% among index seeds to 42.7% among the second wave of referrals. However, the peer referral system ultimately did not increase the absolute number of adolescents Queryaccessing HTC. Future strategies should consider these findings to better target those with undiagnosed HIV infection

Impact of universal antiretroviral treatment eligibility on rapid treatment initiation among young adolescents with HIV in sub-Saharan Africa.

BACKGROUND Young adolescents with perinatally-acquired HIV are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation following care enrollment among 10-14-year-olds in seven sub-Saharan African countries. METHODS Regression discontinuity analysis and data for 6,912 10-14-year-old patients were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) following adoption of Treat All policies in two groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). RESULTS There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016, compared with those adopting it in 2013: 23.4 percentage points (pp) (95%CI: 13.9-32.8) vs. 11.2pp (95%CI: 2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp afterwards. CONCLUSIONS Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All

Methods for identifying Neisseria meningitidis carriers: a multi-center study in the African meningitis belt.

OBJECTIVE: Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers. METHODS: We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U) to swabbing the posterior pharynx behind the uvula plus one tonsil (T). Swabs were cultured immediately and analyzed using molecular methods. RESULTS: One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6%) based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7%) versus 4.9% (95% CI: 3.6-6.4%) respectively (p=0.6)). The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73), indicating good agreement. CONCLUSIONS: These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence