Introducing ROTAVAC® to the occupied Palestinian Territories: Impact on diarrhea incidence, rotavirus prevalence and genotype composition

Abstract

Background: Rotavirus infection remains an important cause of morbidity and mortality in children. The introduction of vaccination programs in more than 100 countries has contributed to a decrease in hospitalizations and mortality. This study investigates the epidemiological impact of the rotavirus vaccine ROTAVAC® in the Palestinian Territories, the first country to switch from ROTARIX® to this new vaccine.

Methods: Clinical surveillance data was collected fromchildren younger than 5attendingoutpatient clinics throughout Gaza withdiarrhea between 2015 and 2020. The incidence of all-cause diarrhea was assessed using an interrupted time-series approach. Rotavirus prevalence was determined at the Caritas Baby Hospital in the West Bank usingELISA on stool specimen of children younger than 5with diarrhea. Genotyping was performed on 325 randomly selected rotavirus-positive samples from January 2015 through December 2020 using multiplex PCR analysis.

Results: Average monthly diarrhea casesdropped by 16.7% annually fromintroduction of rotavirus vaccination in May 2016 to the beginning of the SARS-CoV-2 epidemic in March 2020 for a total of 53%. Case count declines were maintained afterthe switchto ROTAVAC® in October 2018. Rotavirus positivity in stool samples declined by 67.1% over the same period without change followingthe switch to ROTAVAC®. The distribution of predominant genotypes in rotavirus-positive stool samples changed from a pre-vaccination G1P [8] to G9P[8] and G12P[8] during the ROTARIX® period and G2P[4] after the introduction of ROTAVAC®.

Conclusion: ROTAVAC® has shown epidemiological impact on par with ROTARIX® after its introduction to the national immunization schedule in the Palestinian Territories. A molecular genotype shift from a pre-vaccination predominance of G1P[8] to a current predominance of G2P[4] requires more long-term surveillance.

Keywords: Genotyping; Rotavirus; Vaccine impact.

Fig. 1

Monthly outpatient clinic visits for well and sick children throughout MoH and UNRWA clinic networks in Gaza 2015 through 2020. Note the significant drop in clinic visits after March 2020.

Fig. 2

Monthly births and ROTAVAC® doses given 2 (RV1), 4 (RV2) and 6 (RV3) months later for all infants born in the West Bank and Gaza during 2019 and 2020. The months indicated on the horizontal axis reflect birth dates rather than vaccination dates.

Fig. 3

(a) Monthly average diarrhea cases in children under 5 in Gaza comparing pre-immunization period (Jan 2015 - Apr 2016, n = 16), ROTARIX® period (May 2016 – Sep 2018, n = 29), and ROTAVAC® period (Oct 2018 – Mar 2020, n = 18, illustrating means, highs, lows, and quartiles. (b) ITS with LOESS demonstrating diarrhea incidence before rotavirus vaccine (left of first dotted line), during ROTARIX® period (between dotted lines), and after transition to ROTAVAC® (right of second dotted line).

Fig. 4

(a) Monthly average RV positive cases in children under 5 at Caritas Baby Hospital comparing pre-vaccination period (Jan 2015 - Apr 2016, n = 16), ROTARIX® period (May 2016 – Sep 2018, n = 29), and ROTAVAC® period (Oct 2018 – Mar 2020, n = 18 illustrating means, highs, lows, and quartiles. (b) Monthly diarrhea case averages in children younger than 5 at Caritas Baby Hospital indicating RV positive (red bars), RV negative (gray bars) stool samples, as well as RV positivity rates (black line) between 2015 and 2020. Dotted lines indicate the introduction of ROTARIX® and ROTAVAC® vaccines, respectively. Seasonal variations of RV positivity are demonstrated. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Proportional G and P genotype representation in RV positive stool samples randomly collected from 2015 through 2020 indicating the pre-vaccination, ROTARIX® and ROTAVAC® periods respectively.

Fig. 6

A (top) and b (bottom): transition of VP7 G genotypes (top) and VP4 P genotypes (bottom) from 2015 through 2020 in response to ROTARIX® introduction in 2016 and transition to ROTAVAC® in 2018.

Fig. 7

Age distribution in months of intussusception cases in infants presenting at Shifa Hospital in Gaza (2019–2020) and Caritas Baby Hospital in the Southern West Bank (2015–2020) in relation to ROTARIX® doses given at 2 and 4 months (blue) and ROTAVAC® doses given at 2, 4 and 6 months (orange), respectively.