Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

Introduction

Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).

Methods

420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.

Results

Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).

Conclusion

Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.     

The Economic Burden Attributable to a Child’s Inpatient Admission for Diarrheal Disease in Rwanda

Background

Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction.

Methods

This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child’s caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$.

Results

Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 ± 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 ± $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction.

Conclusion

Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.     

A revisited phylogeography of Nautilus pompilius

The cephalopod genus Nautilus is considered a “living fossil” with a contested number of extant and extinct species, and a benthic lifestyle that limits movement of animals between isolated seamounts and landmasses in the Indo‐Pacific. Nautiluses are fished for their shells, most heavily in the Philippines, and these fisheries have little monitoring or regulation. Here, we evaluate the hypothesis that multiple species of Nautilus (e.g., N. belauensis, N. repertus and N. stenomphalus) are in fact one species with a diverse phenotypic and geologic range. Using mitochondrial markers, we show that nautiluses from the Philippines, eastern Australia (Great Barrier Reef), Vanuatu, American Samoa, and Fiji fall into distinct geographical clades. For phylogenetic analysis of species complexes across the range of nautilus, we included sequences of Nautilus pompilius and other Nautilus species from GenBank from localities sampled in this study and others. We found that specimens from Western Australia cluster with samples from the Philippines, suggesting that interbreeding may be occurring between those locations, or that there is limited genetic drift due to large effective population sizes. Intriguingly, our data also show that nautilus identified in other studies as N. belauensis, N. stenomphalus, or N. repertus are likely N. pompilius displaying a diversity of morphological characters, suggesting that there is significant phenotypic plasticity within N. pompilius.     

Characterization of an anaerobic marine microbial community exposed to combined fluxes of perchlorate and salinity

Applied Microbiology and Biotechnology - The recent recognition of the environmental prevalence of perchlorate and its discovery on Mars, Earth’s moon, and in meteorites, in addition to its...     

Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however, the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp‐expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp‐deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre‐incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1; this outcome supported augmented adherence of Tfp‐expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp‐targeted vaccine for NTHI‐induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role.