Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06–0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07–0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting

Comparison of stool collection and storage on Whatman FTA Elute cards versus frozen stool for enteropathogen detection using the TaqMan Array Card PCR assay.

The use of Polymerase Chain Reaction (PCR) assays for pathogen detection in travelers' diarrhea (TD) field studies is limited by the on-site processing and storage requirements for fecal specimens. The objectives of this investigation were to i) characterize the pathogen distribution in deployed military personnel with TD using the TaqMan® Array Card PCR (TAC) on frozen stool and diarrheal smears on Whatman FTA Elute cards (FTA cards), and to ii) compare TAC detection of enteropathogen targets using smeared FTA cards and frozen stool, using TAC on frozen stool as the 'reference standard'. Stool samples, obtained from active duty personnel with acute TD enrolled in a field trial, were smeared onto FTA cards and stored at room temperature. A corresponding aliquot of stool was frozen in a cryovial. FTA cards and frozen stool samples were tested at a central lab, using a customized TAC for detection of TD pathogens. 187 paired frozen stool samples and smeared FTA cards were stored for a median of 712 days (IQR 396-750) before testing. Overall detection rates were 78.6% for frozen stool and 73.2% for FTA cards. Diarrheagenic Escherichia coli were the most common bacteria identified. Using the TAC results on frozen stool as the reference, the overall sensitivity and specificity of TAC on FTA cards was 72.9% and 98.0% respectively. TAC on FTA cards demonstrated a decrease in sensitivity with increasing frozen stool quantification cycle (Cq) (90.0% in FTA cards with a corresponding frozen stool Cq < 30, and 72.9% in samples with a corresponding frozen stool Cq < 35). Our findings support the use and further development of FTA cards in combination with a quantitative PCR assay for enteropathogen detection in TD field studies

Antimicrobial resistance of <i>Klebsiella pneumoniae</i> stool isolates circulating in Kenya

<div><p>We sought to determine the genetic and phenotypic antimicrobial resistance (AMR) profiles of commensal <i>Klebsiella</i> spp. circulating in Kenya by testing human stool isolates of 87 <i>K</i>. <i>pneumoniae</i> and three <i>K</i>. <i>oxytoca</i> collected at eight locations. Over one-third of the isolates were resistant to ≥3 categories of antimicrobials and were considered multidrug-resistant (MDR). We then compared the resistance phenotype to the presence/absence of 238 AMR genes determined by a broad-spectrum microarray and PCR. Forty-six genes/gene families were identified conferring resistance to β-lactams (<i>ampC</i>/<i>bla</i>_DHA, <i>bla</i>_CMY/LAT, <i>bla</i>_LEN-1, <i>bla</i>_OKP-A/OKP-B1, <i>bla</i>_OXA-1-like family, <i>bla</i>_OXY-1, <i>bla</i>_SHV, <i>bla</i>_TEM, <i>bla</i>_CTX-M-1 and <i>bla</i>_CTX-M-2 families), aminoglycosides (<i>aac(3)-III</i>, <i>aac(6)-Ib</i>, <i>aad</i>(A1/A2), <i>aad</i>(A4), <i>aph</i>(AI), <i>aph3/str</i>(A), <i>aph6/str</i>(B), and <i>rmtB</i>), macrolides (<i>mac</i>(A), <i>mac</i>(B), <i>mph</i>(A)<i>/mph</i>(K)), tetracyclines (<i>tet</i>(A), <i>tet</i>(B), <i>tet</i>(D), <i>tet</i>(G)), ansamycins (<i>arr</i>), phenicols (<i>catA1/cat4</i>, <i>floR</i>, <i>cmlA</i>, <i>cmr</i>), fluoroquinolones (<i>qnrS</i>), quaternary amines (<i>qacE</i>Δ<i>1</i>), streptothricin (<i>sat2</i>), sulfonamides (<i>sul1</i>, <i>sul2</i>, <i>sul3</i>), and diaminopyrimidines (<i>dfrA1</i>, <i>dfrA5</i>, <i>dfrA7</i>, <i>dfrA8</i>, <i>dfrA12</i>, <i>dfrA13/21/22/23</i> family, <i>dfrA14</i>, <i>dfrA15</i>, <i>dfrA16</i>, <i>dfrA17</i>). This is the first profile of genes conferring resistance to multiple categories of antimicrobial agents in western and central Kenya. The large number and wide variety of resistance genes detected suggest the presence of significant selective pressure. The presence of five or more resistance determinants in almost two-thirds of the isolates points to the need for more effective, targeted public health policies and infection control/prevention measures.</p></div

Summary of AMR genes in the tested population.

<p>Summary of AMR genes in the tested population.</p

Summary of antimicrobial phenotypic susceptibility for diarrheal and control isolates.

<p>Summary of antimicrobial phenotypic susceptibility for diarrheal and control isolates.</p

Metadata and phenotypic antimicrobial susceptibility for individual isolates.

<p>Metadata and phenotypic antimicrobial susceptibility for individual isolates.</p