• Improving rotavirus vaccine coverage: Can newer-generation and locally produced vaccines help?

      Deen, Jacqueline; Lopez, Anna Lena; Kanungo, Suman; Wang, Xuan-Yi; Anh, Dang Duc; Tapia, Milagritos D.; Grais, Rebecca F. (Taylor & Francis, 2017-12-21)
      There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare then with Rotarix and Rotateq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed.
    • Low birth weight: Case definition & guidelines for data collection, analysis, and presentation of maternal immunization safety data

      Cutland, Clare L.; Lackritz, Eve M.; Mallett-Moore, Tamala; Bardaji, Azucena; Chandrasekaran, Ravichandran; Lahariya, Chandrakant; Nisar, Muhammed Imran; Tapia, Milagritos D.; Pathirana, Jayani; Kochhar, Sonali; et al. (Amsterdam: Elsevier, 2017-12-04)
    • Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali, and South Africa

      Omer, Saad B.; Clark, Dayna R.; Aqil, Anushka R.; Tapia, Milagritos D.; Nunes, Marta C.; Kozuki, Naoko; Steinhoff, Mark C.; Madhi, Shabir A.; Wairagkar, Niteen (Lippincott Williams & Wilkins, 2018)
      Background: To evaluate the effect of antenatal influenza vaccination on all-cause severe infant pneumonia, we performed pooled analysis of three randomized-controlled trials conducted in Nepal, Mali, and South Africa. Methods: The trials were coordinated from the planning phase. The follow-up period was 0–6 months post-partum in Nepal and Mali, and 0-24 weeks in South Africa. Pregnant women with gestational age 17-34 weeks in Nepal, ≥28 weeks in Mali, and 20-36 weeks in South Africa were enrolled. Trivalent Inactivated Influenza Vaccine (IIV). was compared with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal conjugate vaccine (MCV) (Mali). In South Africa, cases were hospitalized, and were therefore considered to have severe pneumonia. In Nepal and Mali, severe infant pneumonia diagnosis was based on the WHO Integrated Management of Childhood Illness (IMCI) definition. Results: A total of 10,002 mothers and 9,801 live-born eligible infants were included in the present analysis. Incidence rate of severe pneumonia was 31% lower in the IIV group compared to the control group (incidence rate ratio [IRR]: 0.69, 95% CI: 0.50 - 0.94, P = 0.02). During periods with high influenza circulation there was lower incidence of severe pneumonia among the IIV group (IRR: 0.20, 95% CI: 0.06 - 0.74, P = 0.02), however, there was no difference in pneumonia incidence between study groups during periods of low and no influenza circulation. Conclusions: Maternal influenza immunization may reduce severe pneumonia episodes among infants –particularly those too young to be completely vaccinated against S. pneumoniae and influenza.
    • A randomized, placebo-controlled, double-blind Phase 2 trial comparing the reactogenicity and immunogenicity of a single ≥2x108 colony forming units [cfu] standard-dose versus a ≥2x109 cfu high-dose of CVD 103-HgR live attenuated oral cholera vaccine, with Shanchol inactivated oral vaccine as an open label immunologic comparator

      Sow, Samba O.; Tapia, Milagritos D.; Chen, Wilbur H. (2017-10-11)
      Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically-naïve individuals during “virgin soil” epidemics would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (VaxchoraTM) containing >2x108 colony forming units (cfu) induces vibriocidal antibody seroconversion (correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required >2x109 cfu to elicit high seroconversion in developing country populations. We compared vibriocidal responses of Malians (18-45 years old) randomized to ingest a single >2x108 cfu standard-dose (N=50) or >2x109 cfu high-dose (N=50) of PaxVax CVD 103-HgR with buffer, or two doses (N=50) of ShancholTM inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice, 2 weeks apart; CVD 103-HgR recipients ingested placebo weeks before or after ingesting vaccine. Seroconversion (>4-fold vibriocidal titer rise) between baseline and 14 days after CVD 103-HgR, and following the first and second dose of Shanchol were the main outcomes measured. By day 14 post-vaccination, seroconversion after a single standard-dose of CVD 103-HgR was 71.7% (33/46) and 83.3% (40/48) after high-dose. Seroconversion following first-dose Shanchol 56.0% (28/50) was significantly lower compared with high-dose CVD 103-HgR (p=0.003). High-dose CVD 103-HgR vibriocidal geometric mean titer (GMT) exceeded standard-dose GMT at day 14 (214 vs 95, p=0.045) and was ~2-fold higher than day 7 and day 14 GMT following the first Shanchol dose (p>0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess efficacy and practicality in field situations. (ClinicalTrials.gov number, NCT02145377)