It was found that bulls roamed more widely across the park and were more tolerant in their habitat requirements than mixed herds.

It was of particular significance that resources in areas fre- quented by both mixed herds and bull groups were more similar to resources in areas where only mixed herds occurred, but differed Diversity and Distributions, 13, 225-236, Journal compilation © 2007 Blackwell Publishing Ltd from resources in areas that were used only by bulls.

Also, it was possible to delineate areas exclusively roamed by bulls in the dry season, but no comparable exclusive mixed herds area could be found.

This implies that bulls share space with mixed herds, but additionally have exclusive access to other areas and resources that are not available for mixed herds to utilize.

These 'bull areas' occur in almost every studied elephant population (e.g. Moss, 1988) and we have shown this to be the case in Kruger as well.

Bulls spend most of their adult lives living in peaceful harmony with other bulls, and only move out into the breeding herd areas when in musth.


During the dry season, mixed herds occurred more frequently in areas with abundant tree cover and close to rivers.

Although bulls were also attracted to rivers, they occurred, on average, far- ther from them than mixed herds.

Furthermore, artificial water- holes might potentially have opened up previously unutilized areas for bulls in the dry season, especially on the grassy basaltic plains in the north of the park.

Elephant bulls show a distinct preference for drinking at artificial waterholes' reservoirs, appar- ently preferring the clean water that they can easily access with their trunks.

However, natural surface water did not seem to be a scarce enough resource for artificial waterholes to lure mixed herds away from the rivers where they could meet their forage, water and habitat requirements.

The feeding and water require- ments hypotheses proposed and examined in this study should be further tested in the field, tracking individual herds for extended periods and over different seasons.


Elephant management is highly controversial and any elephant-related study is quickly seen as a pro or con for one of the usual elephant management practices (culling, contraception or metapopulation management).

Managing water sources has also been suggested as one option, even though no experimental data exist.

In a recent issue of Diversity and Distributions, Smit et al. ( 2007) rejected this management tool as an efficient method to control elephant distribution and dynamics in Kruger National Park, South Africa.

However, we believe that (1) Smit et al. 's conclusion is poorly supported by the available data, and (2) that this non-intrusive management tool has the potential for being one of the few practices able to reconcile managers, scientists, and the public opinion in the never-ending ‘elephant problem’.

For these reasons, we believe that the strong conclusions of Smit et al. should be moderated.

Finding a management tool, on which there is a consensus, to control elephant impacts seems to be harder than the quest for the Holy Grail.

In a recent issue of Diversity and Distributions, Smit et al. ( 2007) questioned the idea that surface-water management could help in managing elephant distribution in the famous Kruger National Park (KNP, South Africa), specifically stating that ‘considering (1) the results presented here (preference of mixed herds for areas close to rivers as opposed to areas close to artificial waterholes during the dry season); (2) the fact that the population growth rate did not decrease post-1997 when more than half of the waterholes in Kruger were permanently closed (Pienaar et al., 1997; Whyte, 2005); (3) the abundance of natural surface water in Kruger (Redfern et al., 2005); and (4) the abundance of elephants in parks with no or little artificial water provision (Barnes et al., 1999), it is unlikely that closure of artificial waterholes will affect the elephant population in the KNP significantly’.

While we accept Smit et al. 's results of a closer vicinity of elephant herds to rivers than to artificial waterholes (and distance to river, not to artificial waterholes, being a significant predictor of elephant presence), we strongly disagree with the management-related conclusions of the authors.

Our work in Hwange National Park (HNP, Zimbabwe) has been leading us to think that artificial surface-water management remains a highly promising, overlooked, elephant management practice (Chamaillé-Jammes et al., 2007), and that this may hold true for most other parks and specifically for KNP.

Building on our experience, we here offer a re-interpretation of Smit et al. 's arguments, discussing the four above points backward.


(4) Is there any ecological basis to consider that artificial water provision must be necessary to reach high elephant abundance? We believe not.

Elephants need to access water to survive the dry season, however, there is yet no demonstration that natural or artificial water have different ability to sustain elephant presence, and global water distribution across the landscape is likely to be the major factor affecting elephant abundance.

Comparison of elephant densities with respect to surface-water origin should only be conducted after having accounted for this overall availability of water, and such analysis remains to be conducted.

Historical information from individual parks, however, show that artificial water provision indeed increased elephant densities where surface-water was low or inexistent in the dry season.

In HNP, elephant abundance increased from a guestimate of 1000 individuals in 1928 to more than 8000 in 1971 following the creation of over 60 boreholes during this period (Davidson, 1967; Williamson, 1975), and went on growing despite population control through culling (Cumming, 1981).

Unhopefully, the potential historical effect of artificial water supply on elephant in Kruger cannot be disentangled from the recovery of past hunting, and may only be inferred from surface-water availability across the landscape.


(3) Redfern et al. ( 2005) suggested that boreholes in KNP had a negligible effect on the general vicinity to water due to numerous ponds or river pools linked to dry season rainstorms or carry-over effects of previous rainfall.

However, the importance of these small sources for elephant distribution and demography remains unknown, and the absence of these types of water sources in the analysis of Smit et al. suggests that these authors did not consider them relevant.

Actually, it has been shown that ‘removing all boreholes during dry years [below-median] increases the percentage of area beyond 10 km of persistent water sources from 1% to 50% in the northern region and from 1% to 38% in the southern region’ (Redfern, 2002 p. 85; see also fig. 4 in Redfern et al., 2005).

Therefore, approximately 40% of KNP remains further than 10 km of water during dry years in a natural situation, and could be considered inaccessible for elephant herds.

Thus, can one really say that natural surface-water availability in Kruger is abundant?

Conversely, artificial waterholes clearly open space for elephant herds in KNP.


(2) Not only elephant population growth rates did not decline post-1997 when the water provision policy was revised and half of the artificial waterholes were closed, but the population went on increasing at the same rate for at least six more years, recovering from the culling control ceased in 1994.

However, one should expect population growth rates to respond to changes in resource availability only when a population approaches the so-called carrying capacity mainly determined by such resource, especially in such long-lived species where density dependence is likely to be highly convex (Sinclair, 2003).

Has the Kruger elephant population ever reached levels at which resources will affect elephant demography noticeably?

We believe it has not.

The KNP elephant population has been around 12,500 individuals at its highest (Blanc et al., 2007).

Is this that much? It is not.

In HNP, only three-quarters the size of KNP, the elephant population has been estimated to be over 25,000 individuals for over a decade, reaching up to 44,492 animals in 2001 (Dunham & Mackie, 2002).

Although Kruger and Hwange NP experience similar annual rainfall, surface-water availability is much lower in HNP, with less than 60% of the park being within 10 km of water when all artificial waterholes are active (Chamaillé-Jammes et al. in press).

Considering the KNP elephant population as a low-density population would be of a shock for some, but it has to be reminded that the often stated sustainable threshold of 7000 individuals for KNP has been based on elephant impacts (Van Wyk & Fairall, 1969), not elephant demography per se.

It is not surprising, and in any case not an argument to reject potential later effects of surface-water management, that closure of half the artificial waterholes had no noticeable effect on elephant dynamics in KNP.


(1) What Smit et al. 's study showed is that elephant herds tend to be closer on average from rivers than artificial waterholes (respectively approximately 3.7 and 4.3 km) at the time aerial censuses were conducted, obviously during daylight.

It is, however, known that elephants drink mainly at dusk or night (Owen-Smith, 1988), day being mostly spent foraging and resting.

It is therefore expected that, even if case elephants would heavily use waterholes at night, they should not be found close to waterholes during the day, especially as food quantity is likely to be lower in the vicinity of permanent water sources (Thrash, 1998; Brits et al., 2002).

This is also probably why more generally elephant locations in Smit et al. 's study were not in the close vicinity of water.

Artiﬁcial waterholes could have been vital to elephants in KNP, results would not have been different.

The relevance of only an approximate 500 m difference in the average distance to water could also be discussed for such a large ranging animal.

Lastly, the extent to which habitat selection of elephants was affected by culling (conducted 4 months before censuses during 10 out of the 12 study years) remains unaccounted for (for large-scale effects of culling in KNP see Van Aarde et al., 1999).

Smit et al. 's study adds to the literature on elephant habitat use and suggests that increased cover and perennial rivers could be an important habitat for elephants.

It would have been more convincing in rejecting the importance of artificial waterholes if the analysis had investigated distribution changes when artificial water policy was revised.

We believe that the demonstration that surface-water management would be ineffective in limiting the KNP elephant population remains to be made.

We showed elsewhere that surface-water has been a key-driver of changes in elephant densities in one of the world’s largest elephant populations (Chamaillé-Jammes et al., 2007).

However, we acknowledge that controlling elephant numbers and mitigating elephant influence on ecosystems may at times have to be distinguished to achieve some specific management objectives.

Contradictory opinions may often simply highlight lack of knowledge.

We therefore urge ecologists to investigate under which environmental conditions various non-intrusive, low cost surface-water management policies could control elephant distribution and abundance.

We hope that in suitable sites surface-water management could help in reaching a non-controversial way forward in elephant management, rather than facing again the cyclical management and public opinion crisis.


In a recent paper we demonstrated that elephant bull groups and mixed herds exhibited spatial and resource segregation across the Kruger National Park.

It was found, inter alia, that both bull groups and mixed herds occurred more frequently closer to rivers than expected if they were randomly distributed, but that only bull groups occurred more frequently closer to the artificial waterholes.

Although Chamaillé-Jammes et al. ( 2007) accepted these results, they disagreed with our interpretation regarding the potential effect that closure of artificial waterholes might have.

Here we address some of the specific concerns expressed and provide a broader context regarding water provision and elephant management.

Although water provision can influence elephant density and distribution, we argue that the effectiveness of surface-water manipulation as a management tool will depend on (1) natural surface-water availability, (2) forage quality, (3) elephant densities, (4) position of a population on its growth trajectory, and (5) management objectives.

Even though elephants are water-dependent, the effectiveness of water provision as a management tool will therefore be area- and population-specific and will depend on management objectives.


In a recent paper we considered the landscape-scale sexual segregation of elephant bulls and mixed herds in the Kruger National Park (KNP), South Africa, and compared the resources between the areas frequented by the mixed herds and bull groups, respectively [1].

We found that bull groups and mixed herds exhibited both spatial as well as resource segregation.

Although Chamaillé-Jammes et al. ( 2007) accepted the results presented in Smit et al. ( 2007b), they disagreed with our interpretation of the implications of the paper regarding surface-water management.

We welcome their comments and believe that these provide useful context and alternative interpretations for the results presented in our original paper.

It is our opinion however, that the quote on which Chamaillé-Jammes et al. ( 2007) base their response does not reflect the broader context and conclusions of the original paper, which we believe provide some of the suggested moderation.

We therefore appreciate this opportunity to respond to the interpretation provided by Chamaillé-Jammes et al. ( 2007).

We agree that surface water is one of the primary drivers of elephant population dynamics and distribution patterns.

Hence, as stated by Chamaillé-Jammes et al. ( 2007), surface-water manipulation can potentially be a powerful tool for managing elephant populations.

This, however, will only be true for surface-water-limited populations.

In this communication we would like to emphasize that water scarcity and a whole suite of other factors need to be taken into account when considering the most appropriate options to achieve specific management objectives.


In our opinion, two conditions are crucial if the removal of artificial waterholes is to be a successful tool for managing elephant populations: 1.

The elephant population must be water limited (i.e. addition or removal of water should influence the density and distribution patterns).

2. The densities at which the impact of elephants exceed the impacts that are acceptable/desirable to managers must be similar or lower than the densities that would be achieved if no water was artificially provided.

Although these two conditions may hold true in certain parks, it is debatable whether it is the case in Kruger.

This was recognized by Owen-Smith et al. ( 2006), who suggested that the reduction of artificial waterpoints might potentially contribute towards restricting the dry season distribution of elephants, but at the same time acknowledged that it was debatable how effective this would be due to the fairly widespread natural water sources across the Kruger landscape.


We believe that one of the reasons for the response of Chamaillé-Jammes et al. ( 2007) may be the differences between the KNP (our study area) and Hwange National Park (study area on which Chamaillé-Jammes et al. ( 2007) based their experience) and their respective elephant populations.

These parks differ in terms of (1) surface-water availability (due to geology and distribution of rivers); (2) forage quality; (3) elephant densities; (4) position of the respective elephant populations on their population growth trajectories; and (5) management objectives/end points.

Due to these differences one would not expect similar responses from elephants to water provision in these systems.

Many of the issues listed above will be referred to in more detail throughout this communication.


Chamaillé-Jammes et al. ( 2007) suggest that surface-water may become limiting in the KNP during dry years, and hence artificial water may be an important source of water for elephants.

They base this statement on Redfern et al. ( 2005), who indicated that 40% of Kruger could occur beyond 10 km of persistent water sources in dry years if all boreholes were removed.

We do not believe that water sources persistent every year over 12 consecutive years, as defined by Redfern et al. ( 2005), give a reliable indication of surface-water availability for even the worst droughts in Kruger. To illustrate this, we re-analysed the data set Redfern et al. ( 2005) used and calculated the distance to the closest natural surface-water source for the 1991/1992 rainfall year (in the absence of boreholes).

The 1991/1992 rainfall season represented the lowest recorded rainfall in Kruger for a century (Zambatis & Biggs, 1995) and this was worsened by the fact that it occurred a few years into a dry cycle.

Considering the distribution of natural water in this unusually dry year, less than 8% of Kruger occurred further than 10 km from the closest natural water source, compared to 2.4% and 1% for the 1990/1991 and 1992/1993 rainfall years, respectively.

Thereafter, we simulated a drought that was even more severe than the 1991/1992 conditions by taking the furthest distance the centroid of each 1 km2 pixel occurred from the closest natural water source over a 12-year time series.

During this simulation of an extreme drought, only 26% of the KNP was further than 10 km from water and only 6% further than 15 km.

We propose that these scenarios, based on the driest year of the previous century, as well as a simulated drought that was based on combining the driest conditions experienced by each 1 km2 pixel over 12 years, provide a more realistic drought scenario than the 12-year persistence definition used in Redfern et al. ( 2005).

Furthermore, due to elephant’s mobility, Redfern et al. ( 2005) suggested that elephants might be less limited by perennial water sources and could potentially exploit ephemeral water sources more than other less-mobile species would be able to do. It is therefore not appropriate to discard the potential importance of ephemeral water sources as drinking source for elephants in Kruger.

The reason why Smit et al. ( 2007b) did not include ephemeral water sources, however, was the lack of good quality data on the distribution and size of the ephemeral water sources at the time the elephant surveys were flown, and not because it was considered unimportant.

Nonetheless, the omission of the ephemeral water sources in Smit et al. ( 2007b) would not have influenced the calculation of the distance that elephants occurred from artificial waterholes and the main rivers.


The lack of response of the Kruger elephant population to extensive artificial waterhole closure (Pienaar et al., 1997; Whyte, 2005) led us to suspect that the population was not operating close to a surface-water-driven density dependence.

Although the removal of water may have reduced the ultimate density-dependent ‘carrying capacity’, we suggest that Kruger may still be relatively far from that point.

Furthermore, the elephant density that may be achieved in the presence of only natural water may potentially still exceed acceptable densities.

‘ Acceptable densities’ in KNP are impact defined, rather than density, and are informed by ‘thresholds of potential concern’ (Biggs & Rogers, 2003).

Smit et al. ( 2007b) did not make it clear that surface-water management was considered from the perspective of avoiding exceeding specific elephant impact thresholds, and that these thresholds are associated with local densities that may potentially be lower than the density-dependent densities of the population, even in the absence of water provision.


Another concern expressed by Chamaillé-Jammes et al. ( 2007) was that the aerial census data were not collected when the elephants drink, but when they feed and rest.

Although the original paper by Smit et al. ( 2007b) acknowledged that mixed herds may utilize certain waterholes at night (p. 233), we find this rather unlikely for the large bull areas in the park.

For example, in one of the large bull areas of the northern basaltic plains, it was found that over the 12-year period of this study, bulls were recorded on 372 occasions and mixed herds only on 12 occasions (i.e. only 3% of all the recorded sightings were mixed herds) (based on snap-shot data from the dry season of 12 years).

In this specific area, where on average only one mixed herd was observed per yearly census over 12 years, in excess of 30 artificial waterholes were provided.

In our opinion it is unlikely that mixed herds will move in large numbers (even across rivers) into this area at night, if it is devoid of any mixed herds by day.

It is also questionable whether some of the boreholes with a windmill will be able to replenish water into the trough fast enough to provide for the needs of large mixed herds.

Therefore, although mixed herds will sometimes drink at artificial waterholes, also by night, we still consider, as proposed in Smit et al. ( 2007b), that the closure of waterholes in bull areas will potentially have a more pronounced effect on the bull population than on the mixed herd population.


Chamaillé-Jammes et al. ( 2007) stated that the average distance that mixed herds occurred from the closest artificial waterhole was not very different in absolute terms from the average distance to the closest main river.

Smit et al. ( 2007b) (p. 233) mentioned that the short distances between water sources would not pose difficulty for elephants to cross, and hence that the full expression of how elephants relate to surface-water would not be expressed in the Kruger context.

This further supports the notion expressed earlier that the Kruger population has not yet experienced water limitations.

However, the results did clearly indicate that the mixed herds were more biased towards the rivers than the artificial waterholes.

By expressing the observed distance to closest artificial waterhole and observed distance to closest main river as percentages of the average expected distance to closest waterhole and river, respectively, mixed herds in fact occurred 40% closer to rivers than expected assuming a distribution random with regard to rivers, and only 2% closer to waterholes than expected under a random distribution with regard to waterholes (compared to approximately 22% and 15%, respectively, for rivers and artificial waterholes for bull groups).

This illustrates that although the absolute difference in average distance to closest artificial waterhole and major river was small, mixed herds occurred randomly with regard to artificial waterholes, whereas they occurred closer to rivers than expected under a random distribution.


The KNP is mandated to protect biodiversity in all its natural facets and fluxes (Mabunda et al., 2003).

This mandate implies managing a complex heterogeneous system that supports a wide variety of organisms, some that benefit from the presence of elephant, and some that disappear even in the presence of very low numbers of elephant.

This necessitates the creation of a heterogeneous mosaic of elephant density and impact across the park that will favour all components of biodiversity along the elephant density/impact gradient.

In Smit et al. ( 2007b), it was stated that smaller, less mobile, water-dependent species with more specific habitat requirements than elephants would possibly be more affected than elephants if waterholes were closed within their home range.

This statement is supported by Redfern et al. ( 2005), Smit et al. ( 2007a), and classic allometric scaling theory relating body size to mobility (e.g. Stokke & du Toit, 2002).

In light of the KNP objectives, we have to caution against a single-species approach when considering surface-water manipulation as elephant management tool.

We consider the main contributions of Smit et al. ( 2007b) that it clearly identified the presence of large areas in Kruger that were used exclusively by bulls, and subsequently indicated that the resources in these areas differed from the resources in the areas where the mixed herds occurred.

These bull areas are likely to be differently impacted due to the size, feeding, and behaviour differences between the mixed herds and bull groups (Stokke & du Toit, 2002).

Managers should therefore take cognizance of these large bull areas when considering the different management options.

For example, increasing and decreasing artificial waterholes in these bull areas may potentially alter the resource base for the bull population directly, though it will probably not have any direct resource effect on the mixed herds that seem to avoid these areas.


We welcome the comments by Chamaillé-Jammes et al. ( 2007) and believe that these provide useful context and alternative interpretations for the results presented in Smit et al. ( 2007b).

In this communication, we suggest that several factors will influence the response of elephant populations to the addition (or removal) of artificial water sources.

These include, inter alia, (1) natural surface-water availability and distribution, (2) placement/context of artificial water sources, (3) other resources that may also be driving/limiting the population, (4) prevailing elephant densities, (5) position of the population on their density-dependent growth trajectory, and (6) the influence of sexual segregation in space and resource use.

The implication is that even though elephants are a water-dependent species, the influence of water provision will be area and population specific and it is cautioned to transfer conclusions between populations and areas.

As a consequence, we would encourage research on and debate about the importance of artificial surface-water manipulation as management tool in as many elephant populations in Africa as possible.

However, we would like to suggest a systems- rather than single-species approach in such studies.

Further research in Kruger should, inter alia, consider the role of water provision in determining elephant densities and distribution (including home range sizes) under increased elephant densities, especially if serious droughts ensue and, coupled to this, if rivers dry up due to increased pressure on these resources from outside the boundaries of the park.

The seasonal importance of waterholes and the effect of waterholes on all aspects of biodiversity should also receive further attention.


Reactive arthritis (ReA) is classically considered a sub-type of spondyloarthritis (SpA) that is precipitated after a gastro- intestinal or genitourinary infection [1].

The usual presen- tation is monoarticular or oligoarticular arthritis involving large joints that occurs around 2-4 weeks after an infection [2].

However, the term has been used in a wider context of an immune-mediated arthritis that may occur after any infec- tion.

The primary concept is that there is no direct invasion of the joints by any pathogen but the arthritis occurs as a result of induced changes in the immune system.


The proposed definitions of ReA have under the umbrella of SpA, be it under the Amor or the European Spondyloar- thropathy Study Group (ESSG) proposed criteria for "Spon- dyloarthropathy" [3] or the currently used ASAS (ASsess- ment in Ankylosing Spondylitis working group) criteria for peripheral SpA [4].

According to these definitions, the pathognomic features of SpA are required to label a patient as having ReA. These include sacroiliitis, uveitis, dactylitis, enthesitis, and HLA-B27 or family history of SpA, psoriasis, or uveitis [4, 5].


ReA allows us a distinctive opportunity to scrutinize and learn how an infective trigger precipitates an autoim- mune phenomenon.

A majority of ReA resolves within a few weeks to a few months.

The rest assume a chronic form indistinguishable from other chronic autoimmune arthritides [6].

Thus, it also provides an opening to understand how the autoimmune process becomes self-sustaining and chronic.


ReA is a predominant problem of low-to-middle income countries where gut and urinary tract infections abound.

Though it is reported from high-income countries, the phenotype is usu- ally limited to arthralgia, tenosynovitis, dactylitis or often not- so-severe arthritis.

The phenotype seen in the tropics is much different with the rapid development of secondary osteoarthri- tis or even evolution into ankylosing spondylitis [7].

However, with the COVID-19 pandemic, there are a lot of reports of post- COVID-19 ReA, re-igniting interest in this entity worldwide.


This perspective aims to explore how the concept of ReA has evolved over the last century, touching upon similar enti- ties and finally how the COVID-19 pandemic is coercing us to re-look into the definitions of this enigmatic malady.


We have adhered to recommendations for narrative review searches [8].

We searched through Scopus and LitCovid/Pub- Med databases [9].

Non-English sources have not been con- sulted.

Conference abstracts or non-peer reviewed sources were not included.

To avoid confusion, we used the MeSH keyword "reactive arthritis" that includes "post infectious arthritis" for searches through LitCovid/PubMed.

For Scopus, we used "reac- tive arthritis" OR "post infectious arthritis" in the search string.


The first descriptions of a post-infectious arthritis were made during the time of the First World war by Fiessinger and Leroy [10].

However, it was more commonly known with the eponym from a Nazi doctor who had first described a triad of urethritis, conjunctivitis, and arthritis.

However, since he was convicted of war crimes, the eponym is not encouraged [11].

Also, a similar triad had already been described almost a century ago by Sir Benjamin Brodie in five cases [12].


More than half a century after the First World War, the concept of ReA was established as a non-purulent arthri- tis that occurred after a gastrointestinal infection without the direct invasion of the bacteria into the joints [13].

This concept was first contradicted by the finding of Chlamydia elementary bodies in the synovial cells of patients with ReA [14].

The tug of war over this concept has kept on going for a few decades.

Now, it is clear that the entire live organism is not found in the joint but some antigen or genetic material, possibly carried by endosomes, may persist in the joint and lead to a sustained inflammatory reaction [15].


As the definition of ReA evolved, more and more entities were proposed for inclusion such as Lyme disease, gono- coccal arthritis, post-streptococcal reactive arthritis, and rheumatic fever [16].

While it is true that Lyme disease and gonococcal arthritis may not fulfil the classical Koch's postulates to be defined as an "infection," both have unique characteristics clinical features.

Clubbing them with ReA will neither help in the management nor further research.

Similarly, the differences between ReA and post-streptococ- cal reactive arthritis are elaborated elsewhere [17].


The most commonly used definition of ReA has been pro- vided by Braun and associates [18, 19].

This definition requires monoarthritis or oligoarthritis preceded by symptomatic diar- rhoea or urethritis.

For "definite" ReA to be diagnosed by the Braun criteria, an organism with known association with ReA needs to be demonstrated by culture or PCR.

Even while these classification criteria were formulated, there was a lack of agree- ment on various points like the relationship of HLA-B27 with ReA, the existence of ReA without arthritis, or whether it should include only spondyloarthritis presentations or any arthritis [18].

More and more organisms are being added to the list of potential precipitants of ReA [20].

Also, the definition by Braun et al. does not consider the entity of "post-vaccination ReA."


The American College of Rheumatology (ACR) or the Euro- pean Alliance of Associations for Rheumatology(EULAR) do not have separate practice guidelines pertaining to ReA as possibly the rheumatologists in Europe or the United States do not see severe cases of ReA[21-23].

The incidence is apparently declining in most high-income countries [24].

However, the rest of the world that depend on the ACR and EULAR recommendations may find this gap challenging.

For example, Latin America had the largest proportion of patients with "peripheral spondyloarthritis" [25].

ReA from India has arthritis as the predominant feature in 95% of patients [26] while a report from Finland showed only arthralgia in two and arthritis in none of 17 patients with post-Escherichia coli musculoskeletal conditions [23].

Thus, there seem to be great differ- ences in how clinicians from different parts of the world view ReA.


Only a small percentage of patients who have infections with organisms such as Campylobacter, Salmonella, Shigella, or Yersinia develop ReA [27].

Similarly, amongst millions who have developed SARS-CoV-2 infection, only a minor propor- tion develops arthritis.

Understanding this may help unearth new verities about the immune system and tolerance mechanisms.


Post COVID-19 arthritis more commonly has a rheuma- toid like phenotype affecting the wrists, ankles, and small 1642 Clinical Rheumatology (2022) 41:1641-1652 joints of hands and feet.

However, a spondyloarthritis-like presentation with axial involvement has also been reported [28].

It can also present as classical ReA with lower limb predominant oligoarthritis [29].

Isolate monoarthritis of a single metacarpophalangeal joint has also been reported [30].

Table 1 summarizes the different phenotypes, treat- ments given, and outcomes in various case reports of post- COVID-19 reactive arthritis from across the world.


The initial reports of post-COVID-19 ReA were in men past 50 years of age [31-33, 35].

This is in contrast to the clas- sical ReA that is most common between 15 and 40 years of age.

Again, at least three cases of post-COVID-19 ReA have also been reported in the paediatric age group [41, 45].

Unlike classical ReA, gender distribution appears equal between males and females.

However, the total number of reported cases is too small for conclusive comments.


The majority of the patients had responded to non-steroidal anti-inflammatory drugs (NSAIDs) while some received intra-articular steroids or rapidly tapered oral steroids (Table 2).

Where outcomes are reported, usually, there was a response within the first week and the steroids /NSAIDs could be tapered down after 4 weeks.

Only patients with rheumatoid arthritis-like phenotype with anti-citrullinated peptide antibodies had a chronic course and had to be given methotrexate [48-50].


Thus, the phenotype and outcomes of post-COVID-19 ReA appear to be different from those of classical ReA. These differences are summarized in Table 2.


Vaccination-induced autoimmunity is a concern since vac- cines stimulate the immune system [51].

The first published case of ReA post-COVID-19 vaccination was reported in a 23-year-old woman after the inactivated Sinovac-CoronaVac vaccine [52].

We could identify a total of seven cases of inflammatory arthritis reported post-vaccination (Table 3).


We have reviewed post-COVID-19 rheumatic diseases at an earlier stage of the pandemic [57].

Post-COVID-19 periph- eral nerve entrapment syndromes like carpal tunnel or tarsal tunnel syndromes have been hypothesized to be either due to localized demyelination, microangiopathy involving the vasa nervosum or an immune phenomenon targeting the adjacent synovial sheath [58].

An interesting group is the patients who have clinical phenotype and antibodies sug- gestive of rheumatoid arthritis developing post-COVID-19.

These patients developed anti-cyclic citrullinated peptide antibody-positive arthritis after documented COVID-19 infection [48-50].


One concern was whether vaccination would cause a flare in persons with pre-existing autoimmune diseases [51].

Cases with flares of RA temporarily related to vacci- nation have been reported [59].

However, in a cohort of 724 patients with autoimmune rheumatic disease, only 4 patients had complained of a flare in joint pain.

This was managed with NSAIDs and lasted less than a week [60].


In a cohort of 5493 RA patients from Hong Kong, a pro- pensity-score weighted multivariate analysis did not show any association with COVID-19 vaccination and flare of RA [61].


Several viruses are associated with acute polyarthritis that lasts less than 6-8 weeks [62].

In a small proportion of cases, such viral arthritis may become chronic such as in the case of HIV (Human Immunodeficiency Virus), Hepatitis B and C viruses [63, 64], parvovirus B19, and Chikungunya [65].

Some authors have argued that it may be better to label "COVID-19 associated arthritis" rather than "COVID-19 ReA" [66].

COVID-19 can also possibly precipitate arthritis in a susceptible individual.


There is a case report of a lady with psoriasis and inflammatory bowel disease who devel- oped arthritis post-COVID-19 infection [67].

Post-chikungunya or Parvovirus B-19 there can be an onset of arthritis indistinguishable from rheumatoid arthri- tis [68, 69].

A similar phenomenon has been reported post- COVID-19 too [48-50].

However, such anti-citrullinated antibody-positive RA has been reported only in 3 cases to date.


The possibility of a coincidence cannot be excluded looking at the high incidence of COVID-19 infections and the not uncommon incidence of RA, but the point in support of a "reactive" arthritis is that the arthritis is seen after the acute COVID-19 infection.

It is self-limiting.

Had it been a direct viral arthritis, the synovitis should have occurred dur- ing the seroconversion phase.

In acute COVID-19 infection, though arthralgia is common, documented arthritis has been rarely reported.


Viruses have been long implicated in the breakdown of immune tolerance and precipitation of autoimmune dis- ease [70].

SARS-CoV-2 activates CD14 + monocytes and PD-L1 + neutrophils via the Osteopontin-mediated inhibi- tion of Interleukin-10.

This pathway is involved in rheuma- toid arthritis and thus provides a common pathway for the Interferon (IFN)-related pathways have been implicated in COVID-19 [73, 74] and these have a role in the initiation of rheumatoid arthritis.

The TNF (Tumor Necrosis Factor)- induced animal models of rheumatoid arthritis are dependent on IFN and IFN response elements such as the IRF1 (inter- feron regulatory factor 1) transcription factor [75].


Also, various autoantibodies have been reported in COVID-19 [76].

Some of these might have pathological potential and if they persist after the infection, they may lead to rheumatic manifestations like arthritis.

At least 15 different autoantibodies have been described in COVID-19 and 34 human peptides have similarities with SARS-CoV-2 proteins [77].

This may have implications for molecular mimicry in COVID-19.


Classical ReA is self-limiting in two-thirds of cases, but can damage the joints even in such a short period.

Chronic ReA can have much worse sequelae.

In the case of post- COVID-19 ReA, the manifestations appear more transient and self-limiting.

This appears more similar to post-strepto- coccal ReA rather than classical ReA [17].

Also, some cases of post-COVID-19 ReA have different antibodies.

There is a possibility that these may evolve into classifiable rheumatic diseases such as rheumatoid arthritis or lupus [57].


It is not necessary that all arthritis occurring post- COVID-19 should be reactive arthritis.

The alternative is that it may be late-onset viral arthritis with actual invasion of the synovial space with the virus [78].

We could identify one study that reported the detection of SARS-CoV-2 RNA in a patient with wrist arthritis that had appeared 15 days after diarrhoea and upper respiratory tract symptoms [79].

However, other cases have not found such evidence [80].

Moreover, a post-mortem study also failed to find any viral RNA in synovial fluid or bone tissue in five patients who had died of COVID-19 [81].


One limitation of this review is that the search strategy could miss cases of SARS-CoV-2 associated arthritis if the words "reactive" or "post-infectious" were not used.

However, the main focus of the review was to assess how clinicians per- ceive and use the concept of reactive arthritis rather than only assessing SARS-CoV-2 associated arthritis.


The definitions of ReA have been evolving gradually over the last half-century.

Nevertheless, an ideal working defi- nition still eludes us.

Since this entity is not very com- mon in high-income countries, there are possibly limited guidelines for this entity.

The evidence base for treatment is also weak.

The first and foremost requirement to fill in these deficiencies is a strong and universal definition of ReA. The advent of ultrasound in the detection of enthesitis can ena- ble a more objective definition [82].

Also, radiographic features such as new bone formation at the site of enthesitis can be a possi- ble marker [83].

Radiographic changes are late but ultrasound diag- nosis can be early with validated OMERACT (Outcome Measures in Rheumatology Clinical Trials) definitions available [84].


The emergence of post-COVID-19 ReA and possibly post- vaccination ReA is forcing a paradigm shift in how we per- ceive this entity.

Post-vaccination autoimmune diseases are being reported [85].

This leads to the question of whether individuals with genetic predisposition such as HLA-B27 positivity need to be segregated for different vaccines [52].


As the SARS-CoV-2 pandemic is transformed into an endemic due to wide-spread vaccination and emergence of less virulent strains, it will be interesting to study how this affects emergence of COVID-19 associated autoimmune conditions including ReA.


Finally, post-infectious arthritis may hold the key to understanding how the chronicity of arthritis develops.

This may help in future preventive strategies.

The first step has to be a coordinated effort across nations and various rheumatology societies to set up working definitions and enumerate thrust areas of research for ReA.


All co-authors contributed substantially to the concept formulation, searches of relevant articles, and revisions.

They approve the final version of the manuscript and take full responsibility for all aspects of the work.


SA has received honorarium as speaker from Pfiz- er, DrReddy's, Cipla, and Novartis (outside of the current work).

All other authors declare no competing interests.


Dear Editor,


We read with interest the published manuscript by Bekaryssova et al. [ 1] summarizing cases of post-COVID-19 reactive arthritis (ReA).

In their manuscript, the authors started their review by discussing the definition of ReA and its progression over time.

Then, they summarized cases of COVID-19 ReA and those of COVID-19 vaccination-induced arthritis.

They described clinical features, therapeutic management of ReA, and outcomes of these patients.


Twenty-two cases of COVID-19 ReA were summarized [1].

Several studies showed that COVID-19 infection is not only responsible for ReA but also viral arthritis.

Thus, it is necessary to specify whether articular manifestations are due to ReA or viral arthritis.


Viral arthritis is characterized by an early onset and is commonly associated with symptoms of disseminated viral infection.

This diagnosis remains possible in cases of early onset of articular symptoms.

In this review, two cases of early arthritis associated with signs of disseminated viral infection were considered ReA [2, 3].

Indeed, Houshmand et al. described the case of a 10-year-old boy who presented with a concomitant fever, urticaria, and arthritis.

Urticarial lesions tended to appear simultaneously with systemic viral symptoms.

They have been reported in 11 to 19% of patients with COVID-19 infections [4].


These findings support the diagnosis of viral arthritis rather than post-COVID-19 ReA in this patient.

The post-COVID-19 ReA diagnosis can be established based on the occurrence of rheumatological manifestations with a delay between the onset of these manifestations and the confirmed diagnosis of COVID-19 and nasopharyngeal real-time polymerase chain reaction (RT-PCR) negativation at the time of articular signs onset [5].

It is important to emphasize that RT-PCR positivity can persist in patients who have already been in remission [6].


In this review, the authors did not specify the delay between the COVID-19 infection diagnosis and articular manifestations onset [1].


Besides, the authors did not describe the treatments received during the COVID-19 infection [1].

Indeed, articular manifestations can be triggered by several drugs prescribed during COVID-19 infection.

Favipiravir may induce hyperuricemia and even acute gouty arthritis [7].

Likewise, interferon β1 treatment may be responsible for inflammatory rheumatic disease occurrence [8, 9].


There is no agreement on the ReA criteria.

Therefore, we believe that ruling out differential diagnoses such as viral arthritis related to COVID-19, drug-induced arthritis, crystal-induced flares, or a recent onset of another inflammatory rheumatic disease is necessary before making the ReA diagnosis [10].


The authors included seven cases of ReA after COVID-19 vaccination with corona VAC, Sinovac, and SPUTNIK-V.


While some authors consider joint manifestations induced by anti-COVID vaccination a form of ReA, others consider it an autoimmune or inflammatory syndrome induced by adjuvants.

Adjuvants are components added to subunit and inactivated vaccines to stimulate innate and adaptive immune responses.

This stimulation increases the effectiveness of subunit and inactivated vaccines, but it can be responsible for autoimmune/inflammatory syndrome induced by adjuvant (ASIA) [11].

Diagnosis criteria have been suggested for ASIA.

The first major criterion is exposure to external stimuli such as a vaccine, and the second is the appearance of typical clinical manifestations such as arthritis [11].

These manifestations typically occur 2 to 5 days after COVID-19 vaccination [12].

The detection of autoantibodies or anti-adjuvant antibodies is possible and considered a minor diagnosis criterion [12].

It is not clear whether articular manifestations occurring after COVID-19 vaccination correspond to ReA or ASIA [11].


ReA post-COVID-19 infection or post-COVID-19-vaccination is a matter of concern that must support increased research into the pathophysiology of ReA.


We are grateful to Slouma and associates for mirroring our thought processes in the letter [1] in response to our review on reactive arthritis (ReA) before and after COVID-19 [2]. They have reiterated the need to differentiate infective viral arthritis from post-viral reactive arthritis.

The initial concept of ReA was that it was a para-infectious arthritis due to an autoimmune phenomenon without direct invasion of the infectious agents into the synovium.

However, the demonstration of Chlamydial elementary bodies [3] or bacterial DNA [4] in joints of “ReA” has blurred this distinction.

The time period between the infection and the onset of arthritis may be important, but in post-streptococcal reactive arthritis, this gap is very small [5].

Even in the case of COVID-19, this time gap is not known and our review included all cases labelled as the authors by post-COVID ReA to demonstrate how variable the interpretation could be.

Ultimately, the immunopathogenesis of post-COVID ReA must be understood to be able to differentiate it from acute viral arthritis [6].


Slouma and associates are correct that certain drugs may precipitate or unmask rheumatic symptoms.

However, if they check Table 1 in the review, they will see that most patients have received only non-steroidal anti-inflammatory drugs, and oral, parenteral or intra-articular steroids [2].

Also, in most of the case reports, the respective authors have specified how they have excluded other diagnoses before making a diagnosis of post-COVID ReA.


Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) can be considered a differential diagnosis for post-vaccination ReA. Most of the post-vaccination autoimmune phenomena will meet the criteria for ASIA [11].

However, there are some controversies raised about this entity [12] and the mere swapping of names will not leave anyone the wiser.


This letter has helped bring out the message from our review.

The various controversies related to ReA diagnosis are summarized in Table 1.

Whether the concept of post-COVID ReA should be treated as a separate entity needs to be explored.

Large online surveys of treating physicians and multi-national cohort studies of reactive arthritis are required to analyse the concept of viral arthritis and post-COVID-19 joint involvement during the pandemic.

This should be a clarion call to clinicians and rheumatology societies worldwide to get together to update and craft better classification criteria enabling better understanding of this enigmatic entity.


The annual incidence of venous thromboembolism (VTE) in the United States is approximately 1 per 1,000 adults.

Among nonfatal VTEs, approximately 60% are cases of deep vein thrombosis (DVT) and 40% are cases of nonfatal pul- monary embolism (PE) (1).

Arterial thrombosis and venous thrombosis share multiple risk factors, the strongest of which are age, obesity, cigarette smoking, and hypertension (2-4).

However, little is known about the relation between diet and VTE.


A relation between diet and VTE was suggested as early as World War II (5).

However, to our knowledge, there have only been 2 prospective epidemiologic studies-the Athero- sclerosis Risk in Communities (ARIC) Study and the Iowa Women's Health Study (IWHS)-in which investigators have systematically examined the role of dietary patterns in the development of VTE (6, 7), and the results of those studies conflicted.

There have been 8 studies in which investigators have explored the relation between alcohol and VTE; in 4 of those studies, an inverse association was reported (7-10), whereas no relation was found in the other 4 (11-14).

The relation between specific nutrients and coagulation factor levels has been evaluated more broadly (6, 7, 15-17).

Vitamins B 6 and B 12 have been shown to reduce elevated homocysteine 114 Am J Epidemiol.

2012;175(2):114-126 levels, which are associated with an increased VTE risk; omega-3 fatty acids decrease platelet aggregation and factor VII and fibrinogen levels (18); and vitamin E might inhibit the biologic activity of vitamin K and vitamin K-dependent clotting factors (19).

However, little is known about the potential role of these nutrients in the development of VTE.


The aim of the present study was to better define the association between dietary intake and the risk of VTE by analyzing cohort data from approximately 130,000 US women and men.


The Nurses' Health Study (NHS) began in 1976, when 121,701 female nurses who were 30-55 years old and living in 11 US states (California, Connecticut, Florida, Maryland, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, and Texas) responded to a mailed health questionnaire (20).

The Health Professionals Follow-up Study (HPFS) began in 1986, when 51,529 male US health professionals who were 40-75 years old responded to a de- tailed mailed questionnaire that included a diet survey and questions about lifestyle practices and medical history.

In both cohorts, follow-up questionnaires were sent every 2 years thereafter to acquire updated information on lifestyle factors and to query participants about newly diagnosed medical conditions.

Women in the NHS also completed a 126-item food frequency questionnaire (FFQ) in 1984, and men in the HPFS completed a 131-item FFQ at baseline (i.e., in 1986).

Similar FFQs were sent every 2-4 years thereafter.

The Partners Institutional Review Board (Partners HealthCare, Boston, Massachusetts) ap- proved the NHS and the HPFS protocols.

The studies are being conducted according to the ethical guidelines of Part- ners HealthCare.


We excluded participants who did not complete an FFQ at baseline from the analysis.

Likewise, we excluded partici- pants with extremely high energy intakes (>3,500 kcal/day for women and >4,200 kcal/day for men) or extremely low energy intakes (<500 kcal/day for women and <800 kcal/day for men), as well as those who left more than 70 questions blank.

Subjects who reported a history of VTE at baseline also were excluded from the present analysis.

The final baseline population (in 1984 for women from the NHS and in 1986 for men from the HPFS) included 80,192 women and 49,238 men.

In the NHS, the active follow-up rate (the number of person-years in the cohort when participants are censored after their last questionnaire response) from 1984 to 2008 was 92.2%, and in the HPFS, the follow-up rate from 1986 to 2008 was 88.0%.


Dietary intake information was collected using an FFQ designed to assess average food intake over the previous 12 months.

Standard portion sizes were listed with each food.

For each food item, participants indicated their average fre- quency of consumption over the past year in terms of the specified serving size by checking 1 of 9 frequency categories that ranged from ''almost never'' to ''6 times/day.''


To prepare for factor analysis, food items were grouped into 38 predefined food groups as previously described (21).

Using principal component analysis, dietary patterns were identified from FFQs administrated in 1984, 1986, 1990, 1994, 1998, and 2002 in the NHS and 1986, 1990, 1994, 1998, and 2002 in the HPFS.

We rotated the factors using an orthogonal transformation to achieve structure with greater interpretability and determined the number of factors to be retained using the diagram of eigenvalues.

Foods with a cor- relation of at least 0.30 were considered to be making a con- tribution to the factor.


On the basis of prior published reports and biologic plausi- bility, we selected some specific food groups (fruits, vegetables, fish, red and processed meats, and alcohol) and nutrients (omega-3 fatty acids, trans fatty acids, total fiber, vitamin K 1 , vitamin B 6 , vitamin B 12 , and vitamin E) to assess their association with the risk of VTE.

We assessed both dietary and total (diet plus supplements) intakes.

Nutrient intakes were computed by multiplying the frequency response by the nutrient content of the specified portion sizes.

Food com- position values were obtained from the Harvard University Food Composition Database (Boston, Massachusetts), which was derived from US Department of Agriculture sources and supplemented with information from manufacturers.

All di- etary factors were adjusted for total energy using the residual method (22).


To reduce measurement error and represent long-term dietary intake, the cumulative averages of pattern scores, foods, and nutrients were calculated and then divided into quintiles.

We also examined the consistency of the association between dietary patterns and VTE by using the most recent dietary intakes as predictors of VTE risk.


Participants who reported a physician-diagnosed PE on a biennial questionnaire but did not have a prior history of malignancy received a follow-up letter requesting medical records from the facility in which they were diagnosed with a PE.

A detailed review of these records was undertaken, and cases were coded.

Incident cases for which the medical record included imaging that was diagnostic of a PE were considered confirmed.

Imaging was considered diagnostic if the radiologist reading the study noted a ventilation/perfusion lung scan that indicated a high probability of a PE, a filling defect on a contrast-enhanced computed tomographic scan of the pulmonary vasculature, or a filling defect on a catheter- based pulmonary angiograph.


Over the follow-up period, we identified 956 women and 353 men with an incident PE.

Participants also reported physician-diagnosed DVT on the biennial questionnaire.

Men were considered to have incident DVT if they reported a physician-diagnosed DVT between 2 consecutive questionnaires, and women were if they reported ''phlebitis and thrombophlebitis'' as another major illness (code 451 according to the International Classification of Diseases, Eighth Revision).

A total of 584 women and 999 men were classified as having DVT under these definitions.


Overall, 1,540 women and 1,352 men reported VTE.


When possible, data on covariates were obtained from the baseline questionnaire (1984 in NHS and 1986 in HPFS) and updated every 2 years.

Variables included age, physical activity level, physical inactivity level, body mass index (BMI, mea- sured as weight (kg)/height (m) 2 ), total caloric intake, smoking status, pack-years of smoking, race/ethnicity, spouse's high- est educational attainment (only in the NHS), parity (only in the NHS), menopausal status (only in the NHS), nonaspirin nonsteroidal antiinflammatory drug use, warfarin use, mul- tivitamin use, hypertension, coronary heart disease, and rheumatologic disease.


Physical activity, including a variety of activities such as walking, bicycling, swimming, or playing tennis, was mea- sured in metabolic equivalents per week and categorized in quintiles.

Physical inactivity was defined as the number of hours spent sitting at home per day and was categorized in 6 categories (from the lowest amount of time to the highest).

BMI was updated biennially and categorized in 4 categories: less than 25.0, 25.0-29.9, 30.0-34.9, and 35 or higher.

Total caloric intake was estimated through the FFQ, expressed in


Our strategy for analysis was to study the association between dietary intake and the risk of VTE (DVT and PE) in both men and women.

Each dietary variable was analyzed using the Cox proportional hazards model.

A test for trend across the quintiles of each dietary variable was calculated by treating the categories as ordinal variables in a propor- tional hazards model.

After calculating sex-specific relative risks, we combined the ln relative risks weighted by the inverse of their variances using a random-effects model (23).

We tested for between-study heterogeneity using the Q To assess whether age-related physiologic differences might modify the association between diet and VTE (9), we further stratified our analysis according to the median age at baseline (50 years in women and 53 years in men).

We also stratified analyses according to obesity (BMI 30) and level of physical activity (median).

In addition, we performed sensitivity analyses by excluding participants with prior co- morbid conditions (cancer or cardiovascular diseases).

All analyses were conducted using SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina).


Through the use of principal component analysis, we iden- tified 2 distinct major dietary patterns among both women and men.

The first pattern was defined by high intakes of fruit, vegetables, fish, poultry, whole-grain products, and low- fat dairy products.

The second pattern was defined by high intakes of refined grains, cured and red meats, desserts, sweets, French fries, and high-fat dairy products.

In accordance with what was done in previous studies of dietary patterns in this population, we labeled the first pattern the ''prudent pat- tern'' and the second pattern the ''Western pattern.'' Tables 1 and 2 show baseline characteristics of the participants, which were adjusted for age and stratified according to each dietary pattern among women and men.

Compared with participants with the lowest intake of foods from the prudent diet (the lowest quintile), participants with the highest intake of foods from the prudent diet (the highest quintile) were older, more physically active, less likely to be current smokers, and more frequent users of multivitamin supplements.

Compared with participants with the lowest intake of foods from the Western diet, participants with the highest intake of foods from the Western diet had a higher BMI, were less physically active, were more likely to smoke, and took fewer multivitamin supplements.

When the population was restricted to participants without prior cancer or cardiovascular disease (n ¼ 112,658 women and men), the results did not differ materially (for the highest quintile of Western diet vs. the lowest, multivari- able pooled RR ¼ 1.24, 95% CI: 0.91, 1.80; P for trend < 0.001; P for between-study heterogeneity ¼ 0.06).


We performed several subanalyses of the association between dietary patterns and VTE.

First, we stratified our analyses according to the median age at baseline (Figures 1 and 2).

Among both the youngest participants (women aged 38-49 years at baseline and men aged 40-52 years at base- line) and the oldest participants (women aged 50-63 years at baseline and men aged 53-75 years at baseline), no Regarding food groups (Table 4) and nutrients (Table 5), there was a consistent inverse association between vitamin E intake and the risk of VTE in women (P for trend ¼ 0.02), in men (P for trend ¼ 0.07), and in the pooled analysis (P for trend ¼ 0.004).

For fiber and vitamin B 6 intakes, there was a significant inverse association with the risk of VTE in the pooled analysis, with no significant heterogeneity between men and women, although the associations were significant only in men (Table 5).

For intakes of red and processed meat and of trans fatty acids, no association with VTE was found in women, whereas a significant positive association was found in men (the percentages of total variance between studies were 88% and 84% for red and processed meat and trans fatty acids, respectively).

The association in the pooled analysis was not significant for trans fatty acid intake (for the Dietary Patterns, Foods, Nutrients, and VTE 121 Am J Epidemiol.

2012;175(2):114-126 highest quintile of trans fatty acid intake vs. the lowest, mul- tivariable RR ¼ 1.14, 95% CI: 0.84, 1.53; P for trend ¼ 0.33; P for between-study heterogeneity ¼ 0.01) and was border- line significant for red and processed meat intake (for the highest quintile of red and processed meat intake vs. the lowest, multivariable RR ¼ 1.38, 95% CI: 0.92, 2.06; P for trend ¼ 0.07; P for between-study heterogeneity ¼ 0.004).

Analyses in which we used the most recent dietary intakes or nutrient intakes derived from foods only (not supplements) had similar results (data not shown).

No associations were found between the risk of VTE and the intakes of fruit, vegetables, fish, alcohol, omega-3 fatty acids, vitamin K 1 , and vitamin B 12 (Tables 4 and 5).


In a pooled analysis of men and women, we found a weak association between diet and risk of VTE.

No relation was found between the prudent diet pattern and the risk of VTE; however, we did find a weak positive association between the Western diet pattern and the risk of VTE.

Stratification according to age, BMI, and physical activity level led to similar results.

Regarding specific foods or nutrients, no associations were found between the risk of VTE and the intakes of fruits, vegetables, fish, alcohol, omega-3 fatty acids, vitamin K 1 , and vitamin B 12 .

Vitamin E had a protective association, as did fiber and vitamin B 6 , particularly in men.

Similarly, we found that increased intakes of red and pro- cessed meat and trans fatty acids might be associated with VTE in men.

These sex differences should be considered with caution, as issues of sample size and multiple testing could have influenced the results.


Our use of data from 2 large prospective cohorts of health professionals who were 38-73 years of age at baseline and followed for more than 20 years enabled us to establish a temporally correct relation between dietary intake and VTE and to control for many potential confounders in our analyses.


To our knowledge, there have been only 2 previous cohort studies in which dietary patterns and the risk of idiopathic VTE were examined (6, 7).

Steffen et al. ( 6) studied 14,962 middle-aged (45-64 years old) men and women from the ARIC Study.

Although the investigators found no association between the prudent pattern and idiopathic VTE, they found that a greater consumption of the Western pattern was as- sociated with an increased risk of idiopathic VTE.

The latter finding appeared to be driven by persons in the high- est quintile, which suggests a threshold effect rather than a dose-response relation between the Western pattern and idiopathic VTE.

Lutsey et al. ( 7) studied 37,393 white women aged 59-65 years from the IWHS and reported no association between either dietary pattern and the risk of VTE.


Data relating food groups/nutrients to VTE are scant, and in the few published epidemiologic studies of this relation, investigators reported conflicting results (6, 7, 11).

Our find- ings regarding vitamin B 6 and red and processed meat intakes are consistent with those from the ARIC Study (6); of the 6 food groups and 5 nutrients investigated, only intakes of vitamin B 6 and fruits and vegetables were significantly as- sociated with a decreased risk of VTE, and only red and processed meat intake was associated with an increased risk of VTE (6).

A borderline-significant negative association was reported for folate intake (6).

However, in 2 large randomized trials, supplementation with vitamins B 6 and B 12 and folic acid did not reduce VTE incidence (16) or recurrence (15).

In the IWHS, of the 11 food groups and 6 nutrients investi- gated, only alcohol intake was associated with a reduced risk of VTE (7).

Recently, in a case-control study of 292 Asian men and women, 6 food groups were investigated, and only a high vegetable intake was negatively associated with VTE (11).

Our finding regarding vitamin E is consistent with a previous long-term trial in the Women's Health Study, in which intake of 600 IU of natural-source vitamin E on al- ternate days was associated with a significant 21% reduction in the hazard of VTE (17).


There are several possible explanations for the different findings in the ARIC Study, the IWHS, and our study.

To explain the contrary findings between the ARIC Study and the IWHS, Lutsey et al. ( 7) hypothesized that diet may play a bigger etiologic role in the development of VTE in younger people than in older people.

In the present study, we found similar results in strata of younger and older participants, although this limited the power of our study.

Another pos- sible explanation is race/ethnicity; approximately 25% of participants in the ARIC Study were black, whereas most ).

Tang et al. ( 26) recently reported that, compared with whites, blacks experienced 3 times more frequent fatal out-of-hospital PE in the New York City area and died at an age that was 10 years younger in the case of fatal PE, but they did not carry factor V Leiden and the prothrombin G20210A mutation (27).

However, the impact of these black/white differences on the diet-PE association is not clear.


Another possible explanation for the discrepant findings is that the primary outcome differed across studies.

In the ARIC Study, the main outcome was non-cancer-related VTE In conclusion, we found a weak association between diet and the risk of VTE in US women and men.

Nutritional factors of possible etiologic relevance include the Western dietary pattern and intakes of vitamins E and B 6 , fiber, red and processed meat, and trans fatty acids.

Other nutritional fac- tors were not associated with VTE in our 2 large cohorts.

The unique characteristics of our cohorts might limit generaliz- ability of the results to individuals of nonwhite race/ethnicity or lower socioeconomic status or persons with limited access to medical care.

Further studies are warranted in these vulnerable populations.


Recently, there has been interest in determining whether diet is associated with the risk of venous thromboembolism.

The article by Varraso et al. ( Am J Epidemiol.

2012;175(2):114–126) published in this issue of the Journal is an important contribution to this literature.

In this commentary, the author discusses the findings of Varraso et al. within the context of the existing literature and posits epidemiologic explanations for why investigators might have failed to identify strong associations between diet and venous thromboembolism.


In this issue of the Journal, Varraso et al. [ 1] report the results of a comprehensive assessment of the associations between diet and incident venous thromboembolism (VTE) in a sample of 129,430 male and female health professionals.

Dietary intake was represented by dietary patterns (prudent diet vs. Western diet) and intakes of various food groups and nutrients.

Despite the large number of VTEs reported (n = 2,892) and the use of analytic methods that attempted to reduce dietary measurement error by taking advantage of multiple dietary assessments, overall there was little suggestion of a relation between diet and VTE.

Of the 14 dietary patterns, food groups, and nutrients evaluated, only vitamin E, vitamin B6, and fiber were associated with a lower risk of VTE in the gender-pooled analysis.

Higher Western dietary pattern scores and greater consumption of red and processed meats and trans fatty acids were associated with a greater risk of VTE in men but not in women.

In the present commentary, prior studies that explored the relation between diet and VTE are summarized, and potential reasons why strong associations between diet and VTE have not been consistently observed are outlined.


Etiologic data from Norway gathered during World War II (1940–1944) provided the first suggestion of a relation between diet and VTE [2, 3].

In recent years, possible relations have been examined in several epidemiologic studies [1, 4–19].

As shown in Table 1, some studies, but not all, showed that VTE risk was inversely associated with intakes of fruits and vegetables, alcohol, vitamin E, vitamin B6, and fiber but positively associated with adherence to a Western dietary pattern and intakes of red and processed meat and trans fatty acids.

Overall, the results of Varraso et al. [ 1] are consistent with those of previous investigators, who have generally failed to report strong associations between diet and VTE.

Given the lack of consistent and strong associations between diet and VTE, it is important to evaluate 1) the mechanisms underlying the hypothesized associations and 2) the methodological factors that might be impairing our ability to detect relations between diet and VTE if they are present.


Physiologically, diet might affect VTE risk by altering levels of hemostatic and fibrinolytic factors and/or by influencing an individual’s propensity for obesity.

Epidemiologic associations between VTE and specific dietary components are inconsistent, but many of the food groups and nutrients with the strongest evidence for an association with VTE—including vitamin E, the B vitamins, fruits and vegetables, red and processed meat, and alcohol—act on the hemostatic system.

For example, red and processed meats are high in saturated fatty acids, which have been shown to increase platelet aggregation [20].

Moderate alcohol consumption might have antithrombotic effects [21–23], although it is unclear whether these effects are due to ethanol or other compounds [24] such as resveratrol, which is present in red wine [25], or hops, which are found in beer [26].

However, effects of diet on hemostatic pathways have not always translated into risk of VTE in controlled trials.

B vitamin supplementation did not reduce the risk of incident VTE [5] or recurrent VTE [6], despite the apparent inverse relation with homocysteine levels [27].

However, supplementation with vitamin E, which has been shown to have anticoagulant effects in humans [28, 29] and animals [30, 31], was associated with a 21% lower risk of incident VTE in the Women’s Health Study clinical trial [4].

Although numerous statistically significant associations have been observed between dietary intake and hemostatic factor levels, it must be acknowledged that the magnitudes of these associations were generally very modest.

Furthermore, associations between hemostatic factors and VTE incidence are also often of modest magnitude.

Given this compilation of modest physiologic associations, it is unlikely that acting through hemostatic factors, diet would have a strong impact on the absolute risk of VTE.


Diet may also influence VTE risk through its relation to obesity, which is a well-established strong risk factor for VTE [32].

Obesity is associated with venous stasis and also with venous damage and varicosity [11].

Further, obesity may promote thrombosis through increased activity of the coagulation cascade and decreased activity of the fibrinolytic cascade [33].

Particularly when thinking about the positive associations among Western dietary patterns, red and processed meat, and VTE, it is important to be cognizant of the possibility of residual confounding by total caloric intake and obesity.

Caloric intake is poorly estimated by food frequency questionnaires, and estimates are known to be differential by overweight status [34].


In addition to the potential issue of small effects between diet and hemostatic factor levels, dietary measurement error may make it difficult to detect associations between diet and VTE.

In many of the publications presented in Table 1, diet was assessed only once, and follow-up was often long.

Given the imprecision of dietary assessment and the possibility of an individual’s diet changing over time, dietary measurement error might have muddied the results.

To reduce dietary measurement error, Varraso et al. [ 1] utilized data from a biennial food frequency questionnaire in a cumulative average diet analytic approach.

Further, to address the issue of change in dietary intake over time, they conducted sensitivity analyses in which they used the most recent dietary intake as the predictor of VTE risk.

Given their careful analytic approach, dietary measurement should be less of a concern in the article by Varraso et al. [ 1] than in others in which the relation between diet and VTE was explored.


Another issue to keep in mind when reviewing this (and any) literature is the possibility of publication bias.

Given that many of the published studies have yielded null results, one has to question whether publication bias may also be present.

It is possible that some authors have chosen not to publish papers with null results.


In summary, the evidence suggesting a relation between dietary intake and the risk of VTE is relatively weak overall.

The article by Varraso et al. [ 1] is an important contribution to this body of literature, given the large number of cases and the analytic approach, which was intended to reduce dietary measurement error.

Questions still remain regarding whether diet has an important impact on VTE risk.

However, given the small magnitude of the associations between diet and hemostatic factor levels, combined with the relatively weak epidemiologic findings between diet and VTE, current data do not support a major role for diet in the development of VTE.


Although exploring the relations between diet and VTE is etiologically interesting, it is also important to ask: What are the potential public health and clinical implications of this work? Given that VTE is a relatively rare condition with an incidence rate of approximately 1 per 1,000 person-years [35–37], it is unlikely that public health messages will promote adherence to a healthy diet for VTE prevention, especially as the foods hypothesized to be beneficial are also advantageous for more common conditions, such as coronary heart disease and cancer.

Recurrence of VTE is common, however, with approximately 8% of individuals experiencing a recurrent event within 1 year of their initial diagnosis [35] and one-third experiencing a recurrent event in the decade after their incident event [37–39].

Therefore, identifying dietary factors that are effective at preventing VTE recurrence may have clinical value.


We appreciate the thoughtful comments by Dr. Lutsey [1] about our analysis [2] of data from the Nurses’ Health Study and the Health Professional Follow-up Study.

We agree with her conclusion that the association between diet and the risk of venous thromboembolism (VTE) is likely weak.

In the invited commentary [1], Dr. Lutsey discussed the potential for dietary measurement error.

We agree that measurement of dietary intakes is difficult, especially because they change over time.

However, in addition to considering errors in the measurement of the dietary exposures, one might also examine the heterogeneity of the outcome (in this case, VTE).

In most of the studies cited in Table 1 of the invited commentary [1], the authors investigated all VTEs (i.e., all cases of pulmonary embolism (PE) or deep vein thrombosis) without differentiating between idiopathic and provoked VTE.

If one studies all types of VTE, he or she also studies the risk factors for VTE (e.g., cancer).

Thus, if one wants to study novel risk factors for VTE, one might preferentially study cases of idiopathic VTE (i.e., cases that were unrelated to classic risk factors for malignancy, recent surgery, and trauma).

Although our data did not permit us to distinguish between idiopathic and provoked VTE, we could specifically analyze idiopathic PEs.


Over the follow-up period, we identified 308 women and 109 men who had an incident idiopathic PE.

After adjusting for 17 potential confounders (age, total physical activity level, physical inactivity level, body mass index (weight (kg)/height (m)2), total caloric intake, smoking, pack-years of smoking, race/ethnicity, spouse’s educational attainment (in women only), parity (in women only), menopausal status (in women only), nonaspirin nonsteroidal antiinflammatory drug use, warfarin use, multivitamin supplement use, hypertension, coronary heart disease, and rheumatologic disease), we found no association among dietary patterns, foods, or nutrients and the risk of idiopathic PE in either women or men.

The pooled relative risk of PE for persons in the highest quintile of prudent diet intake compared with persons in the lowest was 0.85 (95% confidence interval (CI): 0.42, 1.72; P for trend = 0.78); for Western diet intake, the corresponding relative risk was 1.14 (95% CI: 0.53, 2.45; P for trend = 0.94).

These results provide further evidence that there is little (if any) association between diet and VTE.


In our study [2], we investigated several foods and nutrients in relation to VTE, but we did not study coffee intake.

A recent study in which it was reported that moderate coffee consumption might be associated with a reduced risk of VTE [3] led us to conduct further analyses regarding the potential role of coffee intake in the development of VTE.

However, we found no association between coffee intake and the risk of VTE (for the highest quintile of coffee intake compared with the lowest, relative risk (RR) = 1.02, 95% CI: 0.87, 1.22) or idiopathic PE (RR = 0.94, 95% CI: 0.44, 1.18).

As mentioned by Dr. Lutsey, diet may also influence VTE risk through its relation to obesity, which is a strong risk factor for VTE.

We previously showed that increasing body mass index had a strong linear association with the risk of idiopathic PE in the Nurses’ Health Study [4].

This association remained statistically significant after further adjustment for dietary patterns (for each 1-unit increase in body mass index, RR = 1.09, 95% CI: 1.07, 1.10; P < 0.001).

In addition to obesity, physical activity or inactivity might also modulate the association of diet, obesity, and VTE.

Recently, we reported that in the Nurses’ Health Study, the risk of idiopathic PE was more than 2-fold higher in women who spent the most time sitting than in women who spent the least time sitting, independent of obesity, diet, and other factors [5].

The interrelations between nutritional factors and lifestyle factors (diet, obesity, physical activity, and physical inactivity) provide important challenges for epidemiologic researchers.

Accordingly, there is a need for further research to disentangle the independent effect of each nutritional factor on VTE risk by using, for example, causal models [6].

This analytic approach allows for testing of different models of causality in the epidemiology of disease arising out of environmental factors and analysis of the interplay between these factors.

Such an approach might help us find a stronger scientific basis to support nutritional recommendations that lower the risk of VTE.


Atmospheric ionization events break N 2 chemical bonds, enabling nitrogen oxides [NO(y)] formation, normally at low atmospheric abundance [e.g. Thomas et al., 2005].

There has been controversy whether NO(y) deposition in ice cores, primarily as nitrate (NO 3 ), can be used as a proxy for very large solar proton events (SPEs).

Based on the impulsive nitrate events identified in polar ice by Dreschhoff and Zeller [1990, 1994, 1998] McCracken et al. [ 2001a] established a calibration between impulsive nitrate deposition in the 415-year GISP2-H ice core obtained from the top of the ice sheet divide at Summit, Greenland, in 1991 by Dreschhoff and Zeller [1994, 1998] and extremely large SPEs between 1956 and 1989.


These authors identified 70 impulsive nitrate events in the GISP2-H core and concluded that they could be used as proxies to identify past extremely large SPEs.

One of the largest impulsive nitrate events was dated as late 1859 and associated with the well-documented but poorly quantified September 1859 Carrington event [Clauer and Siscoe, 2006].


Wolff et al. [ 2012] analyzed several central Greenland ice cores, including their D4 [McConnell et al., 2007] and Zoe [Wolff et al., 2012] cores for a 40-year time period (1840-1880) and suggested that the impulsive nitrate event identified by McCracken et al. [ 2001a] as the 1859 Carrington event most likely resulted from biomass burning in 1863.


It is the hard spectra solar cosmic ray ground-level events that have sufficient >300 MeV fluence to penetrate to and through the ozone layer (30 to 17 km altitude).

The large fluence of these particles produces the ionization that provides the energy to ionize N 2 in the lower stratosphere or even the troposphere [Atri et al., 2010; Usoskin et al., 2011].

When NO(y) is generated at these lower altitudes, there is the possibility of moving quickly into the troposphere, either by downward advection or by incorporation into polar stratospheric clouds and gravitational settling, where it will be deposited as NO(y) in snow events.

The softer spectra events will deposit the ionization energy at higher altitudes, and the resulting NO(y) must be transported downward by mechanisms such as the upper branch of the Brewer-Dobson circulation.

These well-established transport mechanisms acting over longer time periods should significantly broaden the deposition timescale as the material diffuses down into the troposphere making any nitrate signal in the ice much harder to identify.


The problem with using the Carrington event to dispute all SPE effects in polar ice nitrate profiles as done by Wolff et al. [ 2012] is that while this was clearly a major solar event (white light central meridian solar flare) with subsequent associated extreme geomagnetic storm and low-latitude aurora, it is only a single example and little quantitative information exists with respect to a SPE.

Hence, it may not represent the type of high-energy SPE needed to produce an impulsive nitrate event and is not the ideal test case.

A careful inspection of Figure 1 in McCracken et al. [ 2001a] shows a complex structure of several events occurring in the 1859 dated GISP2-H core, which is not seen in the 1863 Zoe and D4 data.

It is simply not possible at this time to state conclusively whether the large nitrate spike dated to 1859 or 1860 in the GISP2-H core and to or 1863 in other Greenland cores resulted from the Carrington event or if a smaller, or no, impulsive nitrate enhancement should be expected.


In an effort to understand the different interpretations between McCracken et al. [ 2001a] and Wolff et al. [ 2012], we concluded that a correlation test between impulsive nitrate spikes in polar ice and SPEs could be conducted by examining ice core nitrate deposition during the only years when both well-documented extremely large hard spectrum relativistic solar cosmic ray events occurred and ultrafine-resolution nitrate measurements in consolidated firn exist, namely the 14- year interval 1937 to 1951.

We use this time period to ascertain if the ice core data available for analysis contain evidence of short-duration impulsive nitrate enhancements that could be time associated with these large relativistic solar cosmic ray events.

Using spectral analysis we also determine the resolutions of sampling schemes using these nitrate enhancements.

In this study we will show that finer than 0.08 year (sub-monthly) resolution is necessary for impulsive nitrate event detection in ice cores and conclude that the data used by Wolff et al. [ 2012] were inadequate to differentiate short-duration nitrate enhancements that might be indicative of an extremely large solar proton event.


We note that Schrijver et al. [ 2012] also discuss reasons to question the validity of nitrate spikes.

We comment briefly on those here.

( 1) The conventional nitrate transport processes from the middle stratosphere and above is very slow, so it is hard to make spikes in the ice.

The problem with this is an assumption that substantial deposition cannot occur at lower altitudes.

This can be shown to be incorrect by examining tables in Atri et al. [ 2010] or balloon data in Nicoll and Harrison [2014].


(2) Nitrate interference from biomass burning is a serious concern but can be filtered out by examining other species (e.g., black carbon, ammonium and vanillic acid), at comparable resolution.

Similarly, post-depositional variations could be detectable by examining the concentration of other species.

Ionization events should only involve impulsive nitrate increases although conductivity may increase also as nitrate is highly ionic in water and is the second largest contributor to Greenland ice conductivity after sulfate.


There appears to be disagreement as to what constitutes an "impulsive nitrate event" in the ice core data.

In fact, for years, these features either were not observed due to insufficient time resolution or were attributed to contamination [e.g., Herron, 1982; Delmas et al., 1982; Dreschhoff et al., 1983; Legrand and Delmas, 1986].

The amount of nitrate found in polar ice and snow from generally accepted background sources (biogenic decay, biomass burning, lightning, anthropogenic emissions, and stratosphere-troposphere exchange) [e.g., Ehhalt and Drummond, 1982; Chameides et al., 1977; Neftel et al., 1985; Hameed et al., 1981; Hastings et al., 2004] and from proposed extreme SPEs is dependent on many factors that tend to vary in an annual cycle (e.g., source strength, atmospheric processes, and transport mechanisms to the ice).


The impulsive nitrate enhancement definition used by McCracken et al. [ 2001a,b] was an extremely short duration nitrate impulse that was at least three standard deviations above and superimposed on the temporal, highly variable nitrate background.

The smoothed temporal profile was subtracted from the short-duration impulse event amplitude to obtain the additional accumulated NO(y) contained in the impulsive nitrate event.


An illustrative example is the impulsive nitrate event contained in samples 1133-1136 of the GISP2-H data shown in Figure 1 that is time associated with the 23 February 1956 solar cosmic ray ground-level event [Meyer et al., 1956; Pfotzer, 1958; Shea and Smart, 2012].

This is the largest relativistic solar cosmic ray event observed in the history of cosmic ray measurements with relativistic solar particles impacting the Earth's polar regions for more than 24 hours (Švestka and Simon, 1975).

The duration of this impulsive nitrate deposition event in the ice was about 2 cm water equivalent at Summit, or 1 month.


The data used in this analysis are from four ice cores identified by the following names: Zoe, D4, GISP2-H, and BU.

The Zoe, GISP2-H and BU cores were obtained at Summit (72.6°N, 38.3°W, 3216 m elevation, 24.6 cm average annual water equivalent accumulation [Meese et al., 1994; Albert and Schultz, 2002]), and the D4 core was drilled 237 km away in central Greenland (71.4°N, 44.0°W, 2713 m elevation, 41.4 cm average annual water equivalent accumulation [Banta and McConnell, 2007]).

E. W. Wolff and J. R. McConnell (personal communication, 2012) have generously provided their Zoe and D4 ice core data.

GISP2-H [Dreschhoff and Zeller, 1994; 1998] and BU [Kepko et al., 2009] data were provided by G. A. M. Dreschhoff (personal communication, 2000) and L. Kepko (personal communication, 2009) respectively.


Figure 2 presents the 14 year time series of nitrate concentrations from 1937 to 1951 for all four cores.

The nitrate profiles look very similar when plotted in terms of water equivalent depth and are not shown here.


The Zoe and D4 curves obtained from continuous flow analysis (CFA) of multiple species actually show coarser effective resolution compared to GISP2-H and BU, despite the finer resolutions listed in Table 1 of Wolff et al. [ 2012].


Discretely sampled and co-located nitrate and conductivity values were identified each 1.5 cm of firn or ice along the entire GISP2-H core yielding approximately 20 discrete samples per year (~1.25 cm water equivalent per sample).

For the BU core, Kepko et al. [ 2009] developed a simplified CFA procedure that concentrated on obtaining only co-located nitrate and conductivity measurements through a single flow line, resulting in an approximately 0.063 cm water equivalent sampling interval, thus reducing dispersion effects and achieving a sampling frequency in excess of 284 (cycles) year -1 (per year) for 1937 to 1951.


To ensure the accuracy and repeatability of the data acquired, Kepko et al. also divided the initial core into four parallel sections and analyzed each section independently before averaging.

This resulted in an ultrafine- resolution nitrate and conductivity data set that could be dated using the Hekla eruption volcanic tie point, annual layer counting, and the consensus Summit depth/time profile [Meese et al., 1994].


In contrast, the multi-species CFA conducted on the Zoe and D4 cores used sampling intervals ranging from 0.4 to 0.9 cm water equivalent.

While this CFA design enabled many geochemical species in the ice cores to be characterized in parallel, this approach, coupled with dispersion effects, inherently sacrificed effective depth resolution [Breton et al., 2012] and reduced the time resolution of the Zoe and D4 data compared to those of GISP2-H and BU as shown in Figure 2.


Nearly any mathematical function can be represented as the sum of a series of sinusoids; examining the nature of these has become a standard method in many fields, in this case time and depth series.

For an introduction, see Muller and MacDonald [2002] and Melott and Bambach [2011].

The power spectrum is a way of showing the strength of fluctuations at various frequencies.

In order to represent a sudden change over time T, frequencies up to 1/(2T), the Nyquist frequency, must be included.

When considering a depth interval D, an analogous Nyquist frequency 1/(2D) is obtained.

Smoothing data, which involves averaging over neighboring points, may happen by mixing the data at different times or depths.

It is equivalent to removing high frequencies from the data, which can be seen in the power spectrum.


The Lomb-Scargle Method [Scargle, 1982] was developed to analyze irregularly spaced data directly without interpolation.

It is equivalent to doing a least-squares fit to sine waves of various wavelengths [Cornette, 2007].


In Figure 3 we show the results of a Lomb-Scargle analysis of the four nitrate data sets in terms of time.

A spectral analysis of all four data sets was also obtained in terms of water equivalent depth.

The depth power spectra gave similar results and are not shown, but the resulting depth resolutions are reported here.

Significance levels are assigned assuming a "red noise" AR(1) background.

All the data in Figure 3 show a peak near 1, corresponding to the annual nitrate cycle in polar ice that is well preserved at Summit.


The discretely sampled GISP2-H data show significant power right up to the largest sampled frequency.

In contrast, the CFA-sampled Zoe, D4, and BU data show a distinct drop of significance at the higher frequencies, far below the putative Nyquist frequency.

We recognize that there may be some mild nonlinearities in the correspondence between time and depth scales, but these will average out over the 14-year interval with the result that there is some mixing of power for adjacent frequencies.

In any case, shorter depth intervals will correspond on average to shorter times and higher frequencies.


The narrowness of the peak at 1 year -1 sets a limit of a few percent in the variation in annual snowfall rate.


The Zoe and D4 nitrate data show that even at the 50% confidence level, there is no significant power at frequencies greater than about 3 year -1 .

The depth analysis of the observed nitrate pattern in the Summit Zoe data corresponds to a depth resolution that is closer to 8 cm water equivalent rather than 1 cm water equivalent, suggesting that these are at best seasonal features (i.e., the annual nitrate cycles) that are being resolved.

The actual depth resolution in the D4 ice core nitrate data from 1937 to 1951 with power exceeding the 95% confidence interval is no better than 9.4 cm water equivalent at Summit.

In contrast, the GISP2-H nitrate data show significant power at the 99.9% confidence level up to about 12 year -1 (1 month period) and have a 1.9 cm water equivalent depth resolution, and the more finely depth sampled BU core nitrate data show significant power at the 99.9% confidence level up to about 36 year -1 (~10 days period or ~0.67 cm water equivalent depth resolution).

This suggests strongly but does not prove that there is a meaningful signal in the Summit ice at about a 10-day resolution that has not been consistently compromised by post-depositional processes.

This resolution limit is most probably determined by the high frequency of episodic snowfall events ~88 year -1 (~7.3 per month or roughly one snowfall event every 4 days, corresponding to ~0.28 cm water equivalent per event [Dibb and Fahnestock, 2004]) in combination with winds and subsequent migration of nitrate in the firn and applies to other species as well.

The question we are left with then is, "What is the effective sub-annual resolution of nitrates in ice cores at Summit; i.e., how fine a resolution in the ice cores at Summit will yield useful information from multi-parameter (as well as possibly SPE/nitrate deposition) studies?"


It is not sufficient to show the presence of high frequencies, as in the GISP2-H and BU core power spectra (Figure 3).

Noise in the data could introduce high-frequency power.

In order to demonstrate that they show fine-resolution sampling, power must be correlated in such a way as to generate high peaks on a corresponding fine depth or time scale.


In Figure 4 we show the five highest nitrate peaks for the interval 1937-1951 in each of these data sets.

The full width at half- maximum (FWHM) was calculated by plotting each peak out to its first local minimum on either side.

Peak heights and half maximum widths were plotted and calculated relative to the average nitrate concentration of each pair of local minima as the zero point.

An average FWHM (FWHM av ) was then calculated from all five peaks for each core.


The FWHM av of each core corresponds closely to the resolution limits given by the power spectra in Figure 3, but we note that the D4 core FWHM av of 3.5 year -1 (3.4 months) is slightly better than the 2.7 year -1 (4.5 months) resolution indicated by the power spectrum analysis.

We therefore have good overall agreement and an independent confirmation of the resolution in the nitrate data sets.


Summit is an optimal location for preserving the seasonal geochemical depositional record including nitrates because the relatively high snow accumulation of 0.65 m year -1 at the surface (0.246 m year -1 water equivalent) [Meese et al., 1994; Albert and Schultz, 2002] is not dominated by wind erosion drifting features or sastrugi, and post-depositional processing effects are minimal [Hastings et al., 2004].

Summit is also not subject to katabatic winds that re-arrange the snow at down-slope locations.

Furthermore, and most importantly, any mixing of episodic snowfall events by winds will on average have the effect of reducing nitrate spike amplitudes relative to the background.


In a major study of nine soluble ions involving multiple snow pit and daily surface samples covering three years, Dibb et al. [ 2007] concluded that at least on a seasonal basis "...post- depositional changes do not greatly impact the glaciochemical records preserved at Summit." Dibb et al. [ 2007] went on to say that nitrate loss due to volatility "...is a minor (≤ 5% up to perhaps 25%) fraction of the total that is deposited..." Their findings are consistent with a previous surface and snow pit study focused on nitrates by Burkhart et al. [ 2004], who also observed impulsive nitrate features within one year of deposition at the depth and time scales discussed here and concluded that, "Over 90% of the measured nitrate in the surface snow is preserved in the pits indicating that photochemistry and temperature-dependent uptake and release from the snow do not play as important a role with preservation at Summit…" While the Burkhart et al. study did not observe a clear annual cycle and a consistent preservation of impulsive nitrate events, their nitrate study was limited to one year, and their results must be interpreted accordingly.

These findings do not, of course, prove that impulsive nitrate features at the fine resolution indicated in the current study will be preserved at depth.

However, the presence of both highly significant nitrate power spectra and consistent behavior in FWHM nitrate spikes in the BU core down to approximately 0.67 cm water equivalent depth (10 day) intervals from our results strongly support limited interference by post-depositional processes and are a validation of this analytical approach.