Chikungunya virus (CHIKV) seroprevalence in the South Pacific populations of the Cook Islands and Vanuatu with associated environmental and social factors

Background Arthropod-borne diseases pose a significant and increasing risk to global health. Given its rapid dissemination, causing large-scale outbreaks with severe human infections and economic loss, the Chikungunya virus (CHIKV) is one of the most important arboviruses worldwide. Despite its significance, the real global impact of CHIKV remains underestimated as outbreak data are often incomplete and based solely on syndromic surveillance. During 2011–2016, the South Pacific Region was severely affected by several CHIKV-epidemics, yet the area is still underrepresented in arboviral research. Methods 465 outpatient serum samples collected between 08/2016 and 04/2017 on three islands of the island states Vanuatu (Espiritu Santo) and the Cook Islands (Rarotonga, Aitutaki) were tested for anti-CHIKV specific antibodies using Enzyme-linked immunosorbent Assays. Results A total of 30% (Cook Islands) and 8% (Vanuatu) of specimens were found positive for anti-CHIKV specific antibodies with major variations in national and intranational immunity levels. Seroprevalence throughout all age groups was relatively constant. Four potential outbreak-protective factors were identified by comparing the different study settings: presence of Ae. albopictus (in absence of ECSA E1-A226V-mutation CHIKV), as well as low levels of human population densities, residents’ travel activity and tourism. Conclusion This is the first seroprevalence study focussing on an arboviral disease in the Cook Islands and Vanuatu. It highlights the impact of the 2014/2015 CHIKV epidemic on the Cook Islands population and shows that a notable part of the Vanuatu test population was exposed to CHIKV although no outbreaks were reported. Our findings supplement the knowledge concerning CHIKV epidemics in the South Pacific Region and contribute to a better understanding of virus dissemination, including outbreak modifying factors. This study may support preventive and rapid response measures in affected areas, travel-related risk assessment and infection identification in returning travellers. Trial registration ClinicalTrials.gov Aachen: 051/16_09/05/2016 Cook Islands Ref.: #16-16 Vanuatu Ref.: MOH/DG 10/1/1-GKT/lr.


Methods
-Are the objectives of the study clearly articulated with a clear testable hypothesis stated? -Is the study design appropriate to address the stated objectives? -Is the population clearly described and appropriate for the hypothesis being tested? -Is the sample size sufficient to ensure adequate power to address the hypothesis being tested? -Were correct statistical analysis used to support conclusions? -Are there concerns about ethical or regulatory requirements being met?

Reviewer #1:
The objectives are pretty well described, however I would suggest as per PLOSNTD 'suggestions' to: a) relocate sentences 105-109 to Methods section, -Sentences were relocated as desired b) amend formulation > To assess the seroprevalence of CHIKV a study has been conducted in the local / (or [apparently not as expatriates were not excluded]? -age limitations?) population of the Cook Islands, which had been affected by an outbreak in 2014/15 and Vanuatu, which had never reported such an outbreak. In both study setting specific environmental variables were assessed … (specify why?).
-formulation is amended as desired we added the term "permanent inhabitants" to describe the study population more accurately -for sample collections there was no age limitation -we added a statement why environmental variables were assessed (influence on vector spread) c) consider to add a sentence on why you selected these two islands except for the yes/no reason. There would have been many other options.
-we added a statement, why the Cook Islands and Vanuatu were chosen (comparison of a Polynesian to a Melanesian country) With such additional information the objective will be crystal-clear, the population clearly described. The sample size is sufficient for the simple statistical analysis needed here, except that on Vanuatu the sample size is too small apparently lacking cases in small children to show that seroprevalence has recently been acquired. No concerns about ethics or regulatory issues.

Results
-Does the analysis presented match the analysis plan? -Are the results clearly and completely presented? -Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1:
Essentially well described. Particularly appreciated that the results in the text and figures / tables were complimentary and not repetitive. DETAIL: 206 Why was age group 0-9y excluded? No data? Would have been relevant, see above.
-as described in the Method section, the age group 0-9 was excluded from analysis due to low case numbers (in the Cook Islands collective there were only 2 patients in this age group) 213 25.0?
-We do not fully understand this comment 220-226 As the Cook Island outbreak has not been part of the study per se I would rather move that to the Discussion (or Introduction).
-the section was moved to Discussion

Reviewer #2:
Analysis matches the plan, results clear, tables to be slightly modified (as indicated) - Table was modified as

Conclusions
-Are the conclusions supported by the data presented? -Are the limitations of analysis clearly described? -Do the authors discuss how these data can be helpful to advance our understanding of the topic under study? -Is public health relevance addressed?

Reviewer #1:
Essentially agree with the conclusions presented from 293. Suggest to add the word 'international' on line 302 to more clearly differ from local mobility.
-We added the word "international" Limitations are clearly described, possibly an addition should be made relating to the pediatric population.
-We added a sentence emphasizing that the age group 0-9 years was excluded from some parts of the analysis.
-We further added that information concerning the role of Ae. hebrideus in CHIKV transmission are missing Suggest to add a final conclusive sentence on the public health relevance and the need of further assessment in the SPR. Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend "Minor Revision" or "Accept".

Reviewer #1:
Suggest to modify the title: Chikungunya virus seroprevalence in the South Pacific populations of the Cook Islands and Vanuatu with associated environmental and social factors. > delete the second sentence which does not offer much additional information.
-We deleted the second sentence While the English is pretty good, sometimes the wording is a bit clumsy (possibly from German background) > suggest to have a native British or American speaker with epidemiological knowledge check the manuscript.
-The manuscript was checked by a native British speaker with epidemiological knowledge and several linguistic corrections were carried out PLOS NTD does not publish any titles like 'full professor', 'MD' > delete. Anyhow you have been inconsistent. See instructions for authors.
-All titles were deleted 59. Suggest 'Arboviral' instead of 'mosquito-borne viral' -The term was changed 95. Are subregions essential for this paper? Rather not.
-Yes, they are important as there are major differences in terms of population mobility as described below 98. Are natural disasters essential for this seroprevalence study?
-Yes, they are important as they are an important characteristic of the SPR, add to the challenges health systems must face, and make populations more vulnerable to infectious diseases Suggest you review the manuscript only keeping the essential elements.
50, 107, 293: no need to perseverate on 'first study' in these two islands. After all there was a seroprevalence of about 3% in French Polynesia possibly before 2014.
-The term was deleted in lines 107 and 293.
-The first sentence was moved to the end of the paragraph and the discussion starts as suggested -Changed as suggested