Predisposing factors for excessive loss of weight in exclusively breastfed term and late preterm neonates - a case control study.

BACKGROUND: Exclusively breastfed healthy neonates can lose weight excessively due to poor milk production, inadequate enteral intake or due to poor milk transfer. The studies assessing risk factors for infants to lose weight excessively are diverse and results are highly varied. OBJECTIVES: We aimed to determine the risk factors for weight loss of over 10% in term and late preterm newborns who were exclusively breastfed. METHODS: This was a case-control study which was conducted in a tertiary care hospital. Exclusively breastfed neonates of ≥34 weeks having weight loss of >10% in the first 14 days of life comprised the study group with gestational age and weight-matched neonates without significant weight loss forming the control group. Demographic details, LATCH score, maternal EPDS (Edinburg postpartum depression score) and neonatal morbidities were assessed. RESULTS: Of the 53 mother-infant dyad in each group, baseline characteristics were similar. Gestational Diabetes Mellitus (GDM), Lower segment Caesarean section (LSCS) delivery, higher EPDS score, low LATCH score, absence of immediate skin to skin contact were associated with excessive weight loss and was found to be significant statistically. Babies in the study group had higher incidence of jaundice and hypernatremia and had longer duration of stay in hospital. CONCLUSION: Lack of early skin to skin contact, higher EPDS scores and lower LATCH scores are predisposing factors for exclusively breastfed infants to lose weight excessively.

Naturally occurring antibodies that recognize linear epitopes in the amino terminus of the hepatitis C virus E2 protein confer noninterfering, additive neutralization.

Chronic hepatitis C virus (HCV) infection can persist even in the presence of a broadly neutralizing antibody response. Various mechanisms that underpin viral persistence have been proposed, and one of the most recently proposed mechanisms is the presence of interfering antibodies that negate neutralizing responses. Specifically, it has been proposed that antibodies targeting broadly neutralizing epitopes located within a region of E2 encompassing residues 412 to 423 can be inhibited by nonneutralizing antibodies binding to a less conserved region encompassing residues 434 to 446. To investigate this phenomenon, we characterized the neutralizing and inhibitory effects of human-derived affinity-purified immunoglobulin fractions and murine monoclonal antibodies and show that antibodies to both regions neutralize HCV pseudoparticle (HCVpp) and cell culture-infectious virus (HCVcc) infection albeit with different breadths and potencies. Epitope mapping revealed the presence of overlapping but distinct epitopes in both regions, which may explain the observed differences in neutralizing phenotypes. Crucially, we failed to demonstrate any inhibition between these two groups of antibodies, suggesting that interference by nonneutralizing antibodies, at least for the region encompassing residues 434 to 446, does not provide a mechanism for HCV persistence in chronically infected individuals.

Determination of the human antibody response to the epitope defined by the hepatitis C virus-neutralizing monoclonal antibody AP33.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and there is a pressing need for the development of a preventative vaccine as well as new treatments. It was recently demonstrated that the mouse monoclonal antibody (mAb) AP33 potently neutralizes infectivity of HCV pseudoparticles (HCVpp) carrying E1E2 envelopes representative of all of the major genotypes of HCV. This study determined the prevalence of human serum antibodies reactive to the region of HCV E2 recognized by AP33. Antibodies recognizing this region were present in less than 2.5 % of sera obtained from individuals with chronic HCV infection. A similar prevalence was found in a smaller cohort of individuals who had experienced an acute infection, suggesting that AP33-like antibodies do not play a major role in natural clearance of HCV infection. Sera exhibited different patterns of reactivity to a panel of peptides representing circulating variants, highlighting the presence of distinct epitopes in this region. Only two sera contained antibodies that could recognize a specific AP33-reactive peptide mimotope. AP33-like antibodies made a measurable contribution to the ability of these sera to inhibit E2-CD81 interaction, but not to the overall neutralization of cell entry. Together, these data show that antibodies to the AP33 epitope are not commonly generated during natural infection and that generation of such antibodies via vaccination may require modified immunogens to focus the generation of specific antibodies. Importantly, individuals harbouring AP33-like antibodies are an important potential source of human mAbs for future therapeutic development.