The Impact of the Coronavirus Pandemic on Vaccination Coverage in Latin America and the Caribbean

Round 1

Reviewer 1 Report

I thing this is a very important analysis of the impact of pandemic on the decline of vaccination coverage in the Region of The Americas. The fact that inequality is an important driver of the effect of the pandemic in the vaccination coverage may provide an additional input to the voices that advocate for more redistributive justice in Latin America and the Caribbean. I have some especifics comments on specific aspects of the paper:

1. The summary should include that school closure was one of the driver of the coverage fall. This is important because Latin America was the Region where children lasted more time out of the schools and this mistake should not be committed again.

2. In the summary authors stated that DPT coverage decreased for 39 countries. However I understood that the decrease was not significant for many of them. I recommend that the summary stated that very clearly. 

3.In methods the authors mentioned that they performed an initial analysis to compare DPT vaccination levels between 2019 and 2021. But it is not clear why was that analysis neccesary and what was the meaning of the results because, a decline for that short period of time, do not demostrate that the decrease could be fully attributed to the pandemic.  I thing that analysis would have been more informative if it were included monthly variation of the vacciantion rate especially for 2020. It is a limitation that should be recognized in the discussion.

4. Changes in DPT coverage should have been described by the different subregions of LATAM and The Caribbean. I strongly recommend including that. 

5. In discussion. Authors mentioned that some countries were able to keep vaccination coverage unaffected during the pandemic period. It would be very useful to propose which hypothesis are about the cuases of that success. 

6. In discussion, line 211, authors mentioned that they are laying out some recommendations based on their findings. I thing it is not the case because they recommended to intervene several factors that were not analysed in this study. Only school closures and inequality were found statistically associated to vaccination decrease.

7. In discussion authors should recognise additional limitations of the analysis such as the statsitical power that the time series analysis may have for those countries with small population. For countries with small population, small changes in coverage may not be detected as statistically signficant but still they may be public health significant

Author Response

Reviewer 1 comments

I thing this is a very important analysis of the impact of pandemic on the decline of vaccination coverage in the Region of The Americas. The fact that inequality is an important driver of the effect of the pandemic in the vaccination coverage may provide an additional input to the voices that advocate for more redistributive justice in Latin America and the Caribbean. I have some especifics comments on specific aspects of the paper:

1. The summary should include that school closure was one of the driver of the coverage fall. This is important because Latin America was the Region where children lasted more time out of the schools and this mistake should not be committed again.

We agree that this finding should be emphasized and have included the following sentence in the abstract: “We also observed a trend between school closures and greater-than-predicted declines in DTPcv3 coverage that approached statistical significance (p=0.06) (lines 39-41).”

Based on this finding, we make the following recommendation: “Countries must also develop contingency plans to reach children who missed vaccines and to minimize disruptions during future public health emergencies [12]. Strategies, such as campaigns and periodic outreach activities, must be in place to maintain routine immunization in schools and integrate immunization with all essential health services across primary health care” (lines 206-208).

2. In the summary authors stated that DPT coverage decreased for 39 countries. However, I understood that the decrease was not significant for many of them. I recommend that the summary stated that very clearly.

Thank you for the comment. The sentence, as previously written, could be misleading. Please see modifications to the abstract (lines 34-35).

At the same time, it’s important to highlight the clear trend observed in most countries. In the discussion section, we note, “While only nine and 12 LAC countries and territories, respectively, experienced statistically significant greater-than-predicted declines in DTPcv1 and DTPcv3 coverage, there was a clear trend toward lower-than-predicted coverages” (lines 153-155). In our view, the public health significance of the general trend should not be overshadowed by the fact that statistical significance was not reached in every instance. As the reviewer astutely notes in comment 7, this may be particularly relevant for countries with small populations.

3.In methods the authors mentioned that they performed an initial analysis to compare DPT vaccination levels between 2019 and 2021. But it is not clear why was that analysis neccesary and what was the meaning of the results because, a decline for that short period of time, do not demostrate that the decrease could be fully attributed to the pandemic.  I thing that analysis would have been more informative if it were included monthly variation of the vacciantion rate especially for 2020. It is a limitation that should be recognized in the discussion.

We first conducted a simple analysis of absolute declines in DTPcv1 and DTPCv3 coverages to have a baseline for our predictive model (i.e., to compare observed versus predicted values). Please see lines 90-98 in the methodology section. We agree that decreases over a short period could not necessarily be attributed to the pandemic. For this reason, we used time-series modeling to distinguish between pre-existing coverage trends and the effect of the pandemic.

Monthly data would strengthen the analysis. Unfortunately, these data were not available. We have added this limitation to the discussion (lines 234-235).

4. Changes in DPT coverage should have been described by the different subregions of LATAM and The Caribbean. I strongly recommend including that. 

Thank you for this comment. We discussed among ourselves and explored potential ways to include an analysis by subregion. While we are happy to discuss further, we are concerned that the proposed sub-analysis would be difficult for several reasons. First, it is not clear how countries would be subdivided. The Region of the Americas includes countries with very small populations (e.g., Caribbean Island nations) and countries with very large populations (e.g., Mexico and Brazil) that themselves might be considered a “subregion.” These countries may be near one another, but it is not clear that geography in itself, independent of other factors measured in this study (e.g., inequality), is likely to predict changes in coverage.

More substantially, we are concerned that sub-dividing countries into small sets would severely limit or preclude us from conducting a secondary analysis. This is due to the existing small sampling size and limited data availability for select variables.

5. In discussion. Authors mentioned that some countries were able to keep vaccination coverage unaffected during the pandemic period. It would be very useful to propose which hypothesis are about the causes of that success. 

Reasons why some countries may have more capably responded to the pandemic include strong infrastructure for immunization (reference 24 cited in the discussion in line 164), relatively milder income inequality (supported by this study), as well as factors not fully evaluated in this study (e.g., trust in the health system). We do not want to speculate about the latter category of factors because they were not the focus of this manuscript. With that said, we agree with the reviewer that the “success stories” of the pandemic deserve further attention. This might be a fruitful avenue for further research. Please see changes in lines 167-168.

6. In discussion, line 211, authors mentioned that they are laying out some recommendations based on their findings. I thing it is not the case because they recommended to intervene several factors that were not analysed in this study. Only school closures and inequality were found statistically associated to vaccination decrease.

Thank you for the careful read of our study. We should more carefully explain that our recommendations are based on the study, our review of the literature, and expert opinion. Please see changes to line 188. We do make some recommendations based on the study itself. For example, since inequality was found to be associated with declines in coverage, we recommend focusing on social determinants of health (see lines 189). Given the likely association between school closures and greater-than-expected declines in DTPcv3 coverages, we also recommended contingency plans to mitigate the negative impact of future healthcare crises (lines 205-210).

7. In discussion authors should recognise additional limitations of the analysis such as the statsitical power that the time series analysis may have for those countries with small population. For countries with small population, small changes in coverage may not be detected as statistically signficant but still they may be public health significant.

We agree with the reviewer. This is indeed part of the reason that we wish to highlight the trend toward greater-than-expected declines in 31 of 39 countries for DTPcv1 and DTPcv3, even if statistical significance was not reached in most countries. To better explain our reasoning and per the reviewer’s recommendation, we have added further explanation to the discussion section. Please see lines 236-239.

Reviewer 2 Report

This is a well-written and interesting manuscript on vaccination coverage in Latin America and Caribbean. Even though the findings on the relation of inequality gaps and the effects of the Covid-19 pandemic on vaccination rates can be explained also by the resilience issues of different health systems, the analysis is very interesting and definitively worth of publishing in Vaccines. I have no suggestions for any revisions of the text.

Author Response

We greatly appreciate the reviewers’ careful read of our manuscript.

Reviewer 3 Report

Summary:

This manuscript examines data from the PAHO/WHO/UNICEF Joint Reporting Form database relating to DTPcv1 and DTPcv3 vaccinations immediately before (2020) and immediately after the COVID-19 pandemic in Latin American and Caribbean countries. The data reveal decreases in vaccination rates for DTPcv1 and DTPcv3. They do not address whether or not vaccinations for other conditions were altered. The data do suggest a gradual recovery in vaccination rates for DTPcv1 and DTPcv3 in the countries examined with some countries reporting recovery to pre-pandemic levels and other countries lagging a bit behind. There is some evidence that socioeconomic status may influence the recovery to pre-pandemic vaccination rates for DTPccv1 and DTPcv3.

Comments to Authors:

This is a well-written paper. It could be published in its’ current form. However, the authors may want to consider addressing some points to improve the manuscript before publication.

The study focuses on changes in DTPcv1 and DTPcv3 coverage. It compares vaccination rates before and after the COVID pandemic. There is no mention or discussion of whether or not there were changes in the prevalence (number of cases) of diphtheria, tetanus, or pertussis in any of the countries examined during the interval in which vaccination rates declined. In other words, did the observed decrease in vaccination rates have any disease or medical consequences for the people living in any of the counties examined? In other words, the authors do not address the differences  between statistical significance and practical significance in the analysis mentioned above or anywhere else in the manuscript.

Table 1 shows the Gini index was the only statistically significant factor examined with the statistics showed  this was significant for DTPcv1 and not for DTPcv3. The data in Table 2 show observed and predicted vaccination rates broken down by quintiles of income per capita. It is interesting that the lowest two quintiles of income showed the greatest differences in observed and predicted vaccination coverage for both the DTPcv1 and DTPcv3 vaccines. It is not known if the lowest quintiles in income are the same or different in relative currency values (purchasing power in each country) in the various countries examined. The combining of all the countries into single values masks such considerations.

Overall, the data seem to suggest (see Figure 3) vaccination rates for DTPcvc1 and DTPcv3 are recovering in LAC countries. It is possible that different countries are recovering post pandemic at different rates. It might be predicted that eventually all the countries will vaccinate at pre-pandemic levels. If this is the case, the authors Discussion points on vaccine hesitancy, although valid, might not be relevant to the collected data or the trends presented.

Are DTPccv1 and DTPcv3 the only vaccines influenced by the COVID-19 pandemic? There are probably others, such as MMR and polio, that might be similarly altered by the pandemic? This manuscript is very specific to DTPcv1 and DTPcv3 and the possibility of other standardized vaccines is not addressed.

Author Response

This is a well-written paper. It could be published in its’ current form. However, the authors may want to consider addressing some points to improve the manuscript before publication.

The study focuses on changes in DTPcv1 and DTPcv3 coverage. It compares vaccination rates before and after the COVID pandemic. There is no mention or discussion of whether or not there were changes in the prevalence (number of cases) of diphtheria, tetanus, or pertussis in any of the countries examined during the interval in which vaccination rates declined. In other words, did the observed decrease in vaccination rates have any disease or medical consequences for the people living in any of the counties examined? In other words, the authors do not address the differences  between statistical significance and practical significance in the analysis mentioned above or anywhere else in the manuscript.

We agree that the main goal of increasing coverages is to prevent morbidity and mortality from vaccine-preventable diseases. However, this manuscript does not address prevalence directly because changes in prevalence may lag significantly behind coverage for some VPDs. To address this point, we added the following phrase in lines 211-213.

Table 1 shows the Gini index was the only statistically significant factor examined with the statistics showed  this was significant for DTPcv1 and not for DTPcv3. The data in Table 2 show observed and predicted vaccination rates broken down by quintiles of income per capita. It is interesting that the lowest two quintiles of income showed the greatest differences in observed and predicted vaccination coverage for both the DTPcv1 and DTPcv3 vaccines. It is not known if the lowest quintiles in income are the same or different in relative currency values (purchasing power in each country) in the various countries examined. The combining of all the countries into single values masks such considerations.

As mentioned in the Methods, we conducted analyses with income per capita estimates expressed in Geary-Khamis (i.e., international) dollars—i.e, a hypothetical unit of currency with the same purchasing power parity of US dollars. These values were expressed in constant units of currency to avoid the distortion of inflation. It should be emphasized that the Gini index measured within-country income inequality, but the quintile partition of countries according to their mean income per capita measured between-country income inequality. The ranking of countries by Gini and by income per capita may differ, but our findings highlight the disproportionate concentration of lower DTP coverage among those with higher income inequality.

In addition, it should be noted that the statistical comparison of the Gini index in Table 1 (between ‘less unequal’ and ‘more unequal’) refers to two groups separated by the median (see Supplementary Table 1) rather than to quintiles.

Overall, the data seem to suggest (see Figure 3) vaccination rates for DTPcvc1 and DTPcv3 are recovering in LAC countries. It is possible that different countries are recovering post pandemic at different rates. It might be predicted that eventually all the countries will vaccinate at pre-pandemic levels. If this is the case, the authors Discussion points on vaccine hesitancy, although valid, might not be relevant to the collected data or the trends presented.

We appreciate the comment and agree that clarifications are needed regarding the basis for our recommendations. Please see changes to the discussion section in line 188.

Are DTPccv1 and DTPcv3 the only vaccines influenced by the COVID-19 pandemic? There are probably others, such as MMR and polio, that might be similarly altered by the pandemic? This manuscript is very specific to DTPcv1 and DTPcv3 and the possibility of other standardized vaccines is not addressed.

Thank you for the comment. In the second paragraph of the methodology (lines 85-89), we explain that these DTPcv1 and DTPcv3 were chosen as proxy vaccines for access to health service and routine immunization program performance. We think it is likely that the pandemic similarly affected coverage of other vaccines.

Round 2

Reviewer 1 Report

I have no further suggestions