A Survey to Assess Serological Prevalence of Poliovirus Antibodies in Areas With High-Risk for Vaccine-Derived Poliovirus Transmission in Chad

Abstract

Currently, 5 out of the 6 World Health Organization (WHO) regions have been certified wild poliovirus-free [1, 2], including the African region, where the last case of wild poliovirus type 1 (WPV1) was detected in Nigeria in August 2016 [3]. However, complete polio eradication involves eradication of all polioviruses including those emanating from the use of live oral poliovirus vaccine (OPV) in recipients or their close contacts, referred to as vaccine-associated paralytic poliomyelitis or by genetic reversion through extensive replication, referred to as vaccine-derived polioviruses (VDPVs) [4]. In rare circumstances, the extensive transmission of Sabin-like strains in under-immunized communities allows genetic reversion that leads to outbreaks of paralytic poliomyelitis due to circulating VDPVs (cVDPVs) [5]. Therefore, the continuous use of Sabin strain OPV is not compatible with poliovirus eradication; OPV needs to be ultimately withdrawn and gradually replaced by inactivated poliovirus vaccine (IPV) [6]. The first phase of withdrawal was the global removal of the Sabin type 2 strain from trivalent OPV (tOPV), switching to bivalent OPV (bOPV; types 1 and 3) in April 2016 [7] for all immunization activities. Outbreaks of cVDPVs have been increasing in recent years [8], predominantly of serotype 2 (cVDPV2) [9], of which, 77% of cases from July 2018 to March 2020 were on the African continent [8]. While many outbreaks after the switch were controlled promptly, some have taken multiple supplementary immunization activities using monovalent OPV type 2 (mOPV2) to control or stop spread and some continue. New emergent cVDPV2 outbreaks, seeded during low-quality mOPV2 outbreak responses, are also on the rise as the time since the switch has progressed.

Sub-Saharan African countries have experienced 49 outbreaks of cVDPV2 between April 2016 (when tOPV was replaced by bOPV) and the end of 2020 [8]. There were 3 outbreaks reported from Chad—one cVDPV2 importation from Nigeria in 2019, a new emergence of cVDPV2 detected in Chad in 2019, and one importation from Central African Republic in 2020 [10]. Chad responded to the cVDPV2 outbreak with mOPV2 campaigns. One such campaign targeting all children below 5 years of age was conducted in July 2019, just prior to this survey. Most of the cases in Chad were detected in the western and southern areas of the country considered as high risk.

Chad introduced 1 dose of IPV in routine immunization, in 2015 and continues to administer bOPV in their immunization schedule (the routine immunization schedule includes bOPV at birth, 6, 10, and 14 weeks of age; and IPV at 14 weeks of age). The estimated national vaccination coverage in Chad with IPV and the third bOPV dose has been around 50% [11].

Seroprevalence surveys have been serving as a tool to assess population immunity gaps. Several seroprevalence surveys carried out in Nigeria, other West African countries, India, and Pakistan have well demonstrated their utility [12–14]. To better understand the immunity in areas and populations at high risk of polio in Chad and to assess the risk of future paralytic outbreaks of VDPVs, we conducted a community-based poliovirus seroprevalence survey in Chad. In our analysis, we focused primarily on type 2 seroprevalence because of the risk of cVDPV2 outbreaks.

METHODS

A community-based, cross-sectional survey was conducted in September 2019 that included areas of Hadjer-Lamis, Lac, and Kanem provinces of Chad. These selected areas have a great inflow of internally displaced persons and refugees from neighboring Nigeria, Niger, and the conflict areas of the Lake Chad region due to the Boko Haram and other rebel groups’ insurgency; thereby, they were considered as high-risk areas of Chad.

Using ArcGIS software, a sampling frame of settlements in these selected provinces was obtained. Settlements were plotted onto a map over satellite imagery and structures or households were manually digitized within these settlements. Households were then randomly selected within each of the settlements using computer-generated random numbers. One child, 12-59 months of age, living in each candidate household was eligible to be enrolled in the survey. If a household had 2 or more children aged 12-59 months, only one child was randomly selected using dice or other means.

A sample size of 334 children was calculated in order to detect, at a 95% confidence level, a seroprevalence point estimate with a precision of approximately ±5% assuming >80% seroprevalence and the proportion of non-consenting parents <10%. Assuming that in approximately 2 out of 3 identified structures there would be at least 1 child in the targeted age group, 500 households were planned to be selected for inclusion in the study. GPS coordinates of the visited households were recorded. We assumed that seroprevalence will be distributed homogeneously across this area.

A simple demographic questionnaire including poliovirus vaccination history was administered to the parent or legal guardian, and children’s weight and height were recorded. Acute and chronic malnutrition was defined as weight-for-age Z-score ≤-2 and height-for-age Z-score ≤-2 standard deviations from mean Z-score, respectively. Vaccination card was requested, and documented vaccination history was recorded; if a vaccination card was available or not, the caretaker was asked if mOPV2 was received during a campaign in 2019. Trained phlebotomists collected dried blood spot (DBS) on Whatman 903tm cards using a finger prick technique. The DBS cards were shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, USA and tested for the presence of poliovirus neutralizing antibodies using a standard neutralization assay. Seroprevalence or seropositivity was defined as reciprocal titers of poliovirus neutralizing antibodies >8, with the highest reported antibody titer of >1:1448 (no further dilution made). Titers were reported in log₂ scale [15].

Seroprevalence against all 3 poliovirus types was expressed as percentages with 95% confidence intervals. Risk factors for type 2 seroprevalence were assessed using Fisher’s exact test or chi-square test, as appropriate. Cochrane-Armitage trend test was applied to test for trend in seroprevalence by age of the child. A multivariable logistic regression was applied using factors that were significant at 0.25 level in the bivariate analysis or unadjusted analysis for type 2 seroprevalence. The reciprocal titers were presented using median for all 3 serotypes. A P value <.05 was considered as significant. The data were analyzed using R software (v.3.4.3).

The study protocol was reviewed and approved by the Chad’s National Committee of Bioethics and by WHO’s Ethics Review Committee.

RESULTS

A total of 285 children were enrolled from 727 visited households. In 2 of the 285 children, blood was not collected due to refusal; in 47 of 285 children, the collected blood was not sufficient in volume for analysis, leading to the study population of 236, representing 83% of enrolled children.

Sociodemographic indicators and vaccination histories are presented in Tables 1 and 2, respectively. Nomadic population constituted about 4% (10/236) of the study population. Most parents indicated that their child received mOPV2 dose in a vaccination campaign in July 2019 (215/236, 91.5%, Table 2). Only 8% (19/236) of families presented an immunization card. Of those with the vaccination card, 79% (15/19) had received third dose of OPV and 61.1% (11/18) received IPV. Among the enrolled children in the survey, 37% (137/218) had chronic malnutrition while 20% (44/218) were acutely malnourished.

Seroprevalence was 91% (95%CI: 86.2-94.1) (214/236), 61% (95%CI: 54.9-67.7) (145/236), and 83% (95%CI: 77.6-87.6) (196/236) against poliovirus types 1, 2, and 3, respectively (Figure 1). The seroprevalence was stratified by age of the child categorized into 4 groups of 12 months each from 12 to 59 months. There was a significant increasing trend in seroprevalence with increase in the age of a child for serotypes 1 (P = .003) and 2 (P < .001). For type 1 seroprevalence was 86.7% (95%CI: 68.2-100) for children 12-23 months compared to 98.3 (95%CI: 91.1-99.9) for 48-59 months; for type 2, it was 36.7% (95%CI: 19.2-54.3) for 12-23 months compared to 83.3% (95%CI: 71.8-92.4) for 48-59 months.

Figure 1.

Overall and age groups wise seroprevalences against all 3 poliovirus types.

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The median reciprocal titers of antibodies were significantly different across the age groups for serotype 2 only (P = .006) (Figure 2). The cumulative distribution plots for titers of all 3 types in log₂ scale are presented in Figure 3.

Figure 2.

Median poliovirus type-specific titers (in log₂ scale) by age.

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Figure 3.

Reverse cumulative distribution plots of reciprocal titers in log₂ scale against all 3 poliovirus types.

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The design effect was calculated to be 1.01 indicating homogenous distribution of seroprevalence.

Bivariate analysis of risk factors for type 2 seronegativity is presented in Table 3. Risk factors included in multivariable regression (Table 4) were gender, age, chronic malnutrition, being born before the switch from tOPV to bOPV vaccine, and type of toilet. The odds of type 2 seropositivity were 3 times higher among those children born before switch as compared to children born after switch (OR = 3; 95% CI: 1.56-7.14). Children with chronic malnutrition were less likely to be type 2 seropositive (OR = 0.55; 95% CI: 0.31-0.98).

DISCUSSION AND CONCLUSION

Routine immunization national coverage estimates (which don’t include doses given during supplementary campaigns) for the third dose of polio in Chad have been sub-optimal since 1990 until the latest available estimate for 2019 [11]. Yet the seroprevalence of antibodies against poliovirus of types 1 and 3 was found to be high in our survey—91% and 83%, respectively. This is likely a result of 14-16 rounds of bOPV supplementary immunization campaigns carried out in Chad since the April 2016 replacement of tOPV with bOPV vaccine, no IPV campaigns have been conducted during this period. In contrast, type 2 seroprevalence was low overall (61%). Children born after the switch had limited opportunity to receive type 2 containing vaccine—one opportunity was during the mOPV2 campaign conducted in July 2019, the other opportunity was through IPV provided in routine immunization, as well as possible exposure for some children to cVDPV2 transmission. The identified type 2 immunity gap likely was present in non-sampled areas and greatly contributed to the spread of cVDPV2 in late 2019 and 2020 across the region.

The risk of future cVDPV2 outbreaks and spread remains high; and as time since the switch to bOPV increases, population immunity to type 2 polio continues to decrease [8, 16]. Chad shares borders with countries that recently reported type 2 outbreaks (Nigeria, Cameroon, Niger, and Central African Republic), and population movement between these countries and Chad is well documented [17, 18]. Exacerbating the situation is the ongoing insecurity due to Boko Haram insurgency resulting in the disruption of vaccination services and population displacement [17–19]. This increases the chance of cVDP2 importation again into Chad or from Chad into neighboring countries and further international transmission. Lastly, Chad has areas of insecurity which limits the quality of response SIAs in those areas.

This survey demonstrated association between seronegativity and chronic malnutrition. This finding is in agreement with previously reported results of studies in Pakistan [14], Morocco [20], and India [13].

Our study had some limitations. A long delay in laboratory testing of the DBS samples made it difficult to provide timely feedback to the polio program in Chad. Furthermore, we have not collected vaccination history by recall and therefore we have vaccination history only from a very small subset of children whose parents kept the vaccination cards (~8%). In reporting the total number of OPV doses received, we were unable to distinguish what type of OPV was administered. We estimated sample size assuming type 2 seroprevalence of 80%, however, in our sample, it was 61% which may have resulted in wider confidence intervals than what we had originally intended.

Our survey provides further evidence that poor routine immunization coverage may lead to spread of paralytic disease caused by VDPV if importation events or seeding of VDPVs occurs.

Notes

Acknowledgments. We wish to acknowledge the Ministry of Health in Chad, the traditional and administrative authorities of Lac, Kanem, and Hadjer-Lamis provinces for their support. We also thank the following CDC staff from the Polio and Picornavirus Laboratory Branch for performing the neutralization testing: Sharla McDonald, Deborah Moore, Mario Nicolas, William Hendley, and Yiting Zhang; and CDC consultants David Mekontso and Mahamat Abdoulaye. We thank Rotary International for providing financial support to implement this survey. Most of all, we wish to acknowledge the children and their parents for agreeing to participate in the survey.

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the contributing agencies.

Financial support. This work was supported by grants from the World Health Organization and the Rotary International.

Potential conflicts of interest. All authors: No reported conflicts.

All authors have submitted the ICMJE Form for Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References