Essay: Unearthing the Truth Behind Lyme Disease: The Global Epidemiology, Diagnosis & Manifesations



Abstract:

Introduction:

Lyme disease is the fastest growing vector borne illness in the world. It is a multisystem illness with a multitude of syndromes. There are no epidemiological figures or studies carried out for Lyme disease in Ireland but it is estimated there are about 200 serological diagnoses a year. It is an underreported and often misunderstood disease that is wrought with controversies regarding diagnosis and manifestations.

Objective:

The aim of this systematic review is to evaluate the existing literature, and gain an insight into the epidemiological situation in other countries, the criteria followed for diagnosis and the syndromes associated with the disease.

Methods:

A search of the PubMed database was carried out and 10 studies were selected based on a precise range of inclusion and exclusion criteria. The 10 studies selected are the most relevant to the objective in question.

Results:

The individual epidemiological findings of the studies varied immensely due to a multitude of factors. The median age of incidence was roughly approximate for the studies that examined it, and ranged from 41-65. Geographical location was another conclusive finding, outbreaks occur in clusters, and are of increased incidence in flatter, more densely forested regions. A clinical and laboratory two-tiered approach are commonly used in diagnosis. Erythema migrans and Lyme arthritis appear to be the most common syndromes reported.

Introduction:

Lyme borreliosis is a multi-system disease transmitted following a bite from an infected Ixodes tick (black-legged). (1) In the US, the infection is caused exclusively by Borrelia burgdorferi bacteria, however in Eurasia, and more importantly Ireland, it is caused by a variety, including Borrelia burgdorferi, garinii, and afzelii.(2) It is the most commonly reported vector-borne disease in the Northern Hemisphere. (3) It is subdivided into 3 stages. The acute phase usually presents as a cutaneous rash, known as erythema migrans or a Bullseye rash. (4) If the cutaneous rash or bite is left untreated it can develop in stage 2 and 3. (5) Stage 2 is known as the early disseminated stage of the disease and it causes widespread systemic symptoms. It can manifest as neuroborreliosis causing syndromes like meningitis, cranial neuritis, and radiculoneuritis, or carditis. (5) The late disseminated disease, stage 3, is localised and does not cause systemic symptoms. It usually is reported to present as arthritis and acrodermatitis chronica atrophicans (5) Lyme disease can be easily treated at any of the stages by the administration of antibiotics, varying in nature, but selected based on the manifestations. (5) Cases of Lyme disease are typically reported to occur in clusters in well-defined endemic regions, with 93% of cases between 1992-2006 occurring in only 10 states in the US. (6) Lyme disease awareness and knowledge is currently quite low and thus it is estimated by the CDC to be underreported by as much as 10-fold in certain regions. (7) Diagnosis of Lyme disease is a topic that is highly controversial and subject to much debate. Certain physicians believe diagnosis should be made on the manifestations of clinical symptoms alone, whilst others believe a laboratory diagnosis alongside this is needed to confirm infection. (8) A two-tiered approach using immune enzyme assay and IgG western blot is commonly accepted as best practise for laboratory confirmation however questions regarding sensitivity and specificity arise. (8)

Objectives:

The purpose of carrying out this systematic review of the literature is to examine and analyse the pre-existing information regarding:

1. the epidemiological state of Lyme disease worldwide

2. the diagnostic criteria used in carrying out these studies and what constitutes a diagnosis

3. the syndromes and the presentation of different Lyme disease stages and their symptoms

Method:

Study Selection:

An online search of the clinical journal database Pubmed was carried out to identify studies which could be used to answer the research objectives. On Pubmed I initially typed “Lyme Disease Epidemiology” into the searchbar. This yielded 2965 studies. In order to narrow down the literature I applied the following inclusion criteria:

1) Free full text (740 studies remaining)

2) Publication date within last 5 years (300 studies remaining)

3) Human based studies (215 studies remaining)

4) Published in English (207 studies remaining)

I then screened the abstracts of the remaining 207 studies. I narrowed my studies down to 10 studies. The selection process is outlined in Figure 1, and the exclusion criteria listed in Table 1.

Figure 1:

    

Table 1:

Reasons for Exclusion:

Review paper, overview

41

Newer version of study published

2

Studies carried out on ticks exclusively

6

Discusses other tick-borne illnesses or infectious diseases

49

Discusses tick ecology as opposed to human epidemiology

29

Exclusively discusses diagnostic techniques

28

Exclusively discusses prevention

9

Not representative of population

9

Discusses only one manifestation exclusively

24

Total:

196

Results:

In total, 10 studies were carefully chosen to be analysed, which were believed to adequately address the objectives of the literature review at hand. All the relevant significant findings in each individual study are summarized in more depth than the below paragraphs, in Table 2.

Epidemiology:

All the studies chosen were retrospective, which is to be expected given the rare nature of the disease in question. The studies gained their data regarding the incidence, gender, age, geographical location, occupation and lifestyle habits through a database of cases or a questionnaire. (9-18)

Incidence:

The results regarding the incidence of Lyme disease varied greatly throughout the studies. For example, in Holland in 2014 the rate was 488 per 100,000 compared to 33.2 per 100,000 in Poland in 2013. (11) (9) Not all studies were suited to calculate an accurate yearly incidence rate, as they were either too small scale or completed over a long time-frame. (10, 12, 15-18) The longer studies reported a steadily increasing rate in emergence of Lyme disease. (9,10,11,13,14) The increasing rates began plateauing in 2009 & 2010 in two of the selected studies. (13, 14) One of these studies even showed a decrease in incidence in 2014, the first reported decrease seen in the region in 20 years. (14)

Gender:

One study focused predominately on the gender disparities & reported that 59.3% of cases reported were female. (17) However, another study found that 76.9% of their cases were male, so no conclusive gender comparisons can be drawn. (10)

Age:

Only 4 studies had conclusive, significant results with regards to the age of cases. (10, 12, 15, 18) Three studies calculated the median age, they were 56, 61.5, and 41.9 respectively. (10, 12, 18) A survey carried out in Spain reported the highest incidence in the 41-50 age group. (15)

Geographical Location:

It is clear from all the studies which evaluated the geographical distribution of the disease, that it occurs predominately in clusters, in endemic regions. (9, 10, 12, 13, 14, 16, 18) A particular study found that the incidence increased in less mountainous regions. (16) Another reports that the incidence of Lyme disease increased in people whose properties had an increased shrub edge density. (12)

Occupation:

3 studies took occupational hazard into account. (15, 16, 18). One study carried out in the Beijing suburbs found a positive correlation between the participants’ occupation and the incidence of Lyme disease in the region. (16) It saw a large increase in the number of cases amongst farmers who were sowing and planting in the summer, as opposed to those who did not. (16)

Lifestyle Habits:

Out of 10, 4 studies inquired about the cases’ lifestyle habits and the effect they had on the Lyme disease infection rates. (12, 16, 17, 18) A Rhode Island based study solidified the belief that protective clothing has preventive properties against infection. (12) Another study reported that all their seropositive Lyme disease patients had contact with animals. (16) A correlation between outdoor activities, like gardening, and infection was highlighted in another study. (17) Travel is another risk factor, which was overlooked by the other studies, but in a particular study, cases acquired outside of Korea accounted for 5 out of 11 reported Lyme cases. (18)

Diagnosis:

All the studies, excluding one, used the two-tiered laboratory technique for laboratory diagnosis. (9, 10, 12, 13, 14, 15, 16, 17, 18) Several studies made a diagnosis based on a trip to an endemic region along with clinical manifestations, or a positive serological result, or both. (9, 10, 14, 18) The diagnostic technique used in one study was questionable, and may have resulted in a number of false positives to be included in the study. It relied solely on a queried tick bite and the appearance of erythema migrans, and no laboratory results were utilised or a trip to an endemic region considered. (11) Given the long study time of 2 of the studies, the case definition changed midway through the investigation, and this may have caused disparities to occur in the number of cases included before and after this change, questioning the validity of the studies at question. (10, 14)

Syndromes:

A multitude of manifestations were discussed throughout 7 of the studies. (9, 10, 11, 14, 15, 17, 18) These studies reported the occurrence of: erythema migrans, acrodermatitis chronica atrophicans, Lyme neuroborreliosis, Lyme arthritis, influenza-like symptoms, fatigue and fever. Erythema migrans was used as an aid in diagnostic criteria for several of the studies. (9, 10, 11, 14, 17, 18) Lyme arthritis was the most common finding in the Nova Scotia case review study with 32.5% of patients reporting it. (10) One particular study focused on the differences between male and female manifestations and had very interesting results. (17)

Abbreviations Used in Table:

LD: Lyme Disease

DX: Diagnosis

BB: Borrelia Burgdorferi

LA: Lyme Arthritis

NB: Neuroborreliosis

IEA: Immune Enzyme Assay

WB: Western Blot

EM: Erythema Migrans

DHA: District Health Authority

CDC: Centre for Disease Control

ELLD: Early Localized Lyme Disease

CI: Confidence Interval

ICD-9-CM: International Classification of Disease, Ninth Revision, Clinical Modification

RR: Relative Risk

OR: Odds Ratio

ACA: Acrodermatitis Chronica Atrophicans

LNB: Lyme Neuroborreliosis

Table 2.

Author (Date), Title, Location

Study Type, Sample Size, Population

Objective & Method

Key Relevant Findings

Strengths & Weaknesses

Paradowska-Stankiewicz I, Chrześcijańska I, (2015)

Lyme Disease in Poland 2013

Poland

Retrospective case review study from the database of the annual bulletin “Infectious diseases and poisonings in Poland in 2013”

N=12,773

All Polish citizens (approx. 38m in 2013)

Objective: to assess the epidemiological state of Poland with regards to LD in 2013, & compare it to previous year

Method:

• Only confirmed cases were included

• A case was confirmed based on definition given by Department of Epidemiology NIZP-PZH.

• A confirmed selected case either fulfils clinical criteria for early phase (no lab confirmation) or fulfils both lab & clinical criteria

• Lab criteria included:

1) Positive culture for BB

2) For LA: diagnostic levels of IgG

3) For NB: local antibodies in CNS &/or increase in serum levels

4) For CVS LD & lymphocytoma: significant increase of serum antibodies

** antibody presence detected by IEA confirmed via WB

• 12,773 cases reported in 2013

• 45% more cases of LD reported in 2013 than 2012

• incidence: 33.2 per 100,000 (10 greater than previous year)

• an increase was seen in every region studied

• substantial regional variation was noted

• cases reported peaked from May to November: when ticks most active

• 16.9% (2,155) of cases were hospitalised for treatment

Strengths:

• large sample studied

• clear definition of what constitutes a case, & inclusion criteria

• study of exact same format carried out in previous years, so accurate comparisons could be drawn.

Weaknesses:

• increases in incidence and cases reported may be due to improved surveillance and reporting and not a true increase

• gives no information regarding how many patients suffered with what LD syndrome & severity

Hatchette TF, Johnston BL, Schleihauf E, Mask A, Haldane D, Drebot M, Baikie M, Fleming S, Gould R, Lindsay R (2015)

Epidemiology of Lyme Disease, Nova Scotia, Canada

Nova Scotia, Canada

Retrospective case review study, from database of Population Health Assessment & Surveillance, & a Serosurvey

N=329 (LD cases)

N=1885 (serosuvery)

921,727 (Nova Scotia population 2011)

Objective: to explore the epidemiology of LD in Nova Scotia, the rate of people underdiagnosed and the syndromes

Method:

♣ LD cases were included based on:

1) 2002-2007: EM or other clinical evidence or lab results (CDC based)

2) 2007-2013: clinical evidence with visit to endemic region or lab results

♣ for serosurvey: residual serum from people seeking routine check-ups. Samples were stratified by age, sex & DHA. Serum was tested using 2-tiered approach in accordance with CDC

♣ median age of cases was  56 years old (range 0-85)

♣ 76.9% were male

♣ only 26.4% reported a known tick bite

♣ most reported ELLD: influenza like illness, EM or non EM rash

♣ 38% of cases had EDLD or LDLD with joint swelling & Bell’s palsy

♣ clinician diagnosed EM increased over time

♣ 13 patients hospitalised (unknown cause)

♣ 93% reported exposure to endemic region

♣ 80% of cases were seropositive

♣ incidence varied by DHA

♣ seroprevalence of LD using IgG WB in serosuvery was 0%

♣ most common manifestation was LA (32.5%)

♣ DHA 1 had an incidence of 200 per 100,000

Strengths:

♣ Large population size

♣ In serosurvery sample sizes for endemic DHAs were calculated within a 95% CI

♣ Endemic region clearly defined

♣ Incidences for each manifestation documented

♣ Long time frame allows temporal comparisons to be made

Weaknesses:

♣ Case review information limited & at times unspecific eg no clear definition of influenza like illness given

♣ Cases definition changed in 2007, creating disparities in inclusions

♣ Serosurvey may not be representative of population: inclusion bias- health aware population included  

Hofhuis A, Bennema S, Harms M, van Vliet AJH, Takken W, van den Wijngaard CC, van Pelt W (2016)

Decrease in tick bite consultations and stabilization of early Lyme borreliosis in the Netherlands in 2014 after 15 years of continuous increase

Netherlands

Cross-Sectional Retrospective Survey amongst GPs in the Netherlands

N=10.5m patients represented by 4203 GPs

16.8m (population of Netherlands in 2014)

Objective: to calculate an incidence of LD in the Netherlands, the no. of consultations for tick bites & EM, and compare year by year

Methods:

♣ Postal questionnaires distributed to all GPs

♣ Values assigned to precoded response categories based on best fit of assumed underlying negative binomial distribution

♣ Incidence rates calculated using bootstrap analysis (95% CI)

♣ Incidence estimates for consultations & EM DXs were compared & stratified for GPs that responded to some or all of the surveys

♣ Each year of survey a predicted incidence was calculated at a population coverage of 60, 75 & 90%, using statistical regression for each municipality with no. of reported LD cases, the population & response being the percentage of municipality covered

♣ From 1994-2009 there was a continuously rising number of consultations for tick bites & EM

♣ 2014 incidence of tick bite consultations was 488 per 100,000, the first decrease since 1994

Strengths:

♣ long study time allows for temporal incidences of LD to be examined

♣ allows geographical variation to be assessed

♣ huge sample of population included

Weaknesses:

♣ gives no information about individual variability of patients, eg age, sex etc

♣ recall bias possible- as physicians with increased exposure to LD may be more likely to respond to survey

♣ incidence of syndromes of LD not described apart from EM

Finch C, Al-Damluji MS, Krause PJ, Niccolai L, Steeves T, Folsom O’Keefe C, Diuk-Wasser MA (2014)

Integrated Assessment of Behavioural & Enviromental Risk Factors for Lyme Disease Infection on Block Island, Rhode Island

Block Island, RI

Retrospective Cohort Serosurvey from 2005-2011

N=486

12,000 (population of Block Island during summer)

Objective: to assess whether certain behaviours and location affect incidence rates for LD

Methods:

♣ assessed results of serum samples from participants 2005-2011

♣ participants excluded if LD DX within 2 years of initial serosurvey

♣ environmental exposure based on 2010 satellite image

♣ questionnaire filled out at time of blood draw to assess individual risks eg age, protective behaviours

♣ negative binomial regression used to measure association between landscape and tick density

♣ STATA/SE used to estimate individual & environmental risk factors

♣ First line in protection against LD is protective clothing- 27% of seropositive people claimed to wear it but 46% of the seronegative did

♣ Shrub edge density associated with definite increase in no. of human seropositive LD cases

♣ Average age was 61.5

Strengths:

♣ Used two-tier serologic approach for LD DX

♣ First study to describe direct relationship between individual properties landscape & LD

♣ Assessed methods of preventative behaviours & which seem most effective

Weaknesses:

♣ no description of LD syndromes

♣ inability to assess where LD infection took place

♣ may miss ELLD cases as only serology used and no clinical DX made without serology

♣ geographical area small so bias may occur

Nelson CA, Saha S, Kugeler KJ, Delorey MJ, Shankar MB, Hinckley AF, Mead PS (2015)

Incidence of Clinician-Diagnosed Lyme Disease, United States, 2005-2010

United States

Retrospective case review from Truven Health MarketScan Commercial Claims and Encounters Database

N=45,430

All people Truven Health MarketScan customers who had a plan for a minimum of a full year between 2005-2010 whose drug information was available

Objective: to estimate LD incidence in US & its epidemiologic patterns

Methods:

♣ deidentified data was obtained from enrolees- demographics, outpatient visits, ED visits, admission & prescription drugs

♣ each patient encounter was assigned over 1 diagnostic code from ICD-9-CM

♣ principle DX: an inpatient event with ICD-9-CM code (088.81) for LD or 088.81 as a secondary DX with a DX for manifestation of LD

♣ analysed & compared results with CDC

♣ no. of clinician DXed LD cases estimated by applying age and county specific data to county populations (2010 census)

♣ only 2.2% of LD cases were inpatient admission

♣ average incidence was 44.8 per 100,000

♣ incidence peaked at 56.3 per 100,000 in 2009

♣ clinican DXed LD peaked in summer especially inpatient admissions

♣ no significant age distribution differences

♣ both inpatient & outpatient, male had higher rates particularly (5-9) & (60-64) age bracket.

♣ 15 states represented 80.6% of LD

Strengths:

♣ took possible coding errors and exclusion of true LD cases into account and multiplied by a correction factor

♣ all patients’ demographics given so incidence rates amongst denominations could be calculated

♣ identifies both outpatient and inpatient cases

♣ length of study allowed temporal associations to be made

Weaknesses:

♣ outpatient ICD-9-CM codes don’t differentiate between primary & secondary DXs

♣ only had patient records from aged <65 so this exclusion had to be adjusted for

♣ sensitivity analyses showed the correction factor for patients who weren’t coded 088.81 had huge impacts of final estimate

Li J, Kolivras KN, Hong Y, Duan Y, Seukep SE, Prisley SP, Campbell JB, Gaines DN (2014)

Spatial and Temporal Emergence Pattern of Lyme Disease in Virginia

Virginia, US

Retrospective Database Study of VDH

N=6,714

Population of Virginia from 1998-2011

(8m population in 2010)

Objective: to estimate and incidence rate for LD in the time frame and assess the spatial & temporal patterns occurring.

Methods:

♣ focused mainly on emergence of LD from northern counties to south

♣ cases obtained from VDH from 1989-2011

♣ from 1989-2008: LD case confirmed by EM alone or manifestation of 1 LDLD manifestation with lab DX

♣ from 2008-2011: EM only diagnostic in endemic region, otherwise lab results needed

♣ LD cases were mapped to geographical location using Centrus Software with latitude and longitude

♣ 1999 & 2002 were removed from study as no case data at centrus level available

♣ for low population tracts weighted average approach was used: kernel function smoothed rate by averaging neighbouring regions

♣ spatial scan statistics were used to identify disease clusters

♣ 6,714 cases reported in study period

♣ 2007-2011 accounted for 74% of cases

♣ LD incidence increased 2003-2006, started to plateau in 2006 and peaked in 2010

♣ Disease focuse shifted south to less populated areas by end of study

♣ Primary cluster in 2003 was sparsely populated rural area, in 2006 it expands to include more densely populated census tracts

♣ Spatial-temporal cluster from 2008-2011 includes 24.57% of population but has a RR of 6.71

Strengths:

♣ the focus of northern to southern counties allows us to address the role environment plays on emergence

♣ use of spatial-temporal clusters allows RR to be calculated for a time period within a region

♣ identification of clusters enable Public Health officials to approach endemic areas

Weaknesses:

♣ case definition changed in 2008 creating disparities in cases included although review was carried out on cases before 2008 & queried cases omitted false positives may still have been included

♣ not clear picture of 1989-2011 as 1999 & 2002 were excluded

♣ address used was home address and may not be indicative of where infection occurred.

Lldeo L, Gegundez MI, Gimenez-Pardo C, Alamo R, Fernande-Soto P, Nuncio MS, Saz JV (2014)

A Seventeen-Year Epidemiological Surveillance Study of Borrelia burgdorferi Infections in Two Provinces of Northern Spain

Palencia & Burgos Provinces, Northern Spain

Retrospective cohort study on those bitten by ticks presenting to healthcare in Palenica & Burgos

N=1,179 serum samples from 623 patients

Population of Palencia & Burgos 1996-2013

Objective: to assess epidemiological state of LD in Palencia & Burgos

Methods:

1179 serum samples were collected from patients presenting to primary care with a tick bite over a 17-year period

♣ blood was taken:

1) once from 225 patients (first presentation)

2) twice from 240 (presentation & 30 days)

3) thrice from 158 patients (presentation, 30 days & 90 days)

♣ information demographics were taken: age, sex, occupation, residence, symptomatology, contact with cattle & nature of tick bite

♣ samples tested with two-tiered approach

♣ analysed using chi-squared test

♣ 83 samples tested positive (13.3% of patients), 12.46% of males & 14.38% of females

♣ All seropositive people had contact with animals

♣ No differences between occupation, & no relationship between province

♣ For patients with >1 serum sample raising IgG levels were seen

♣ Some cases remained asymptomatic while others complained of fever, fatigue, LA & headaches

♣ Highest seroprevalence was 16.9% in 41-50 age group

Strengths:

♣ Length of study shows clear timeline of temporal nature of emergence

♣ Multiple blood tests allow us to examine how IgG & IgM levels develop overtime

♣ All demographic info collected us enables clear epidemiological picture to be drawn

Weaknesses:

♣ Small population sample

♣ Inclusion bias- inclusion of those health-conscious or likely to present to primary care setting

♣ True incidence rates may have been masked by early treatment

Xiang Feng D, Yan Ning L, Yi J, Chang Ying L, Li Li T, Quan Yi W, Yu Song Y, Chao L, Yu Lan S, Zeng Zhi G, Xiu Chun Z, Xin Yu L (2014)

Lyme Borreliosis- Associated Risk Factors in Residents of Beijing Suburbs: A Preliminary Case-control Study

Beijing Suburbs

Preliminary Population Based Case-Control Study

N=306

Population of unknown Beijing suburbs

Objective: to assess the epidemiology of Lyme borreliosis in Beijing suburbs & the lifestyles which increase the likelihood of DX

Methods:

♣ 34 cases & 272 controls enrolled in 28 endemic villages

♣ cases were local farmers with DX of LD by the two-tiered test

♣ each case matched by age (+/-)5 and sex for 8 controls

♣ areas of interest were:

1) agricultural works & outdoor activities

2) environment

3) personal protective behaviours

4) tick bite prevention

♣ serosurvey was carried out

♣ data set developed by EpiData software & statistical analysis completed.

♣ Inter-person variables transformed into a percentage & analysed using conditional logistic regression.

♣ Incidence of seropositive LD was higher in flat land than mountainous land (OR=3.496)

♣ Gardening, weeding in particular also markedly increased seropositivity (OR=2.567)

♣ No other environmental factor had a significant impact

♣ Farmers sowing in summer had increased risk (OR=3.054)

♣ Tick awareness was very limited only 26.2% knew they could be bitten by a tick, only 2.3% knew LD was trasmissable and none knew how to remove ticks safely

Strengths:

♣ no prior similar studies published

♣ cases & controls were carefully matched

♣ assessed several demographic variables

♣ statistical analysis was precisely carried out

Weaknesses:

♣ Exact population and name of suburbs not given

♣ May not be relevant regarding awareness and preventative measures given cultural differences

♣ Only carried out on farmers not representative of entire population in area although majority are of agricultural background

Strle F, Wormser GP, Mead P, Dhaduvai K, Longo MV,  Adenikinju O Soman S, Tefera Y, Maraspin V, Lotric-Furlan S, Ogrinc K, Cimperman J, Ruzic-Sabljic E, Stupica D (2013)

Gender Disparity between Cutaneous & Non-Cutaneous Manifestations of Lyme Borreliosis

Ljubljana, Slovenia

Retrospective Case Review Study on database in University Medical Centre Ljubljana

N=10,539

Number of people attending University Medical Centre Ljubljana

Objective: to assess disparities between gender in terms of manifestations of LD

Methods:

♣ case charts were reviewed on patients with LD >15 years who attended the centre between 1990-2012

♣ EM was defined by the CDC as an erythematous skin lesion 5cm in diameter

♣ ACA DX required clinical findings, histological & serum IgG

♣ LA: objective swelling in 1/+ large joints, serum IgG & no alternative arthritis reasoning

♣ LNB: CSF pleocytosis & one or more of

1) Concomitant EM

2) Borreia bacteria in CSF

3) Intrathecal synthesis of antibody

Overall sex ratio male biased so clinical group were normalised using direct standardization technique, 5 year age grouping & data for 2010 census

♣ 10,539 patients were diagnosed with LD from 1990-2009

♣ 6245 were female (59.3&)

♣ female majority in EM DX also (57.7%)

♣ 506 ACA DX, 68.6% of these were female

♣ statistically significant predominance in male LA (75%)

♣ patients with LA & EM (22): 17 were male

♣ females predominate cutaneous LD manifestations

♣ male predominate LA

LNB DX were predominately male

Strengths:

♣ gave clear definition of each manifestation & the incidences

♣ allowed clear comparisons to be made between genders

♣ long time frame

Weaknesses:

♣ changes in data collection methods meant certain manifestations were only collected during periods, meaning different manifestations have different time frames.

♣ Data only collected from one hospital

True ACA rates may not indicate higher rates in women as older population in Slovenia are female biased and most of the ACA DX were of the older subsets

Moon S, Hong Y, Hwang KJ, Kim S, Eom J, Kwon D, Park JH, Youn SK, Sohn A (2015)

Epidemiological Features & Clinical Manifestations of Lyme Borreliosis in Korea during Period 2005-2012

Korea

Retrospective Database Study of KNIH

N=16

71 possible cases of LD

Objectives: to assess the epidemiology of cases of LD in Korea & their manifestations

Methods:

♣ Since 2011 LD became notifiable so 14 possible LD cases were studied

♣ From 2005-2011 possible cases were identified from KNIH

♣ Variables collected from each patient: gender, age, address, occupation, travel history (6m prior to onset), tick bite history, clinical manifestations, lab findings

♣ Case definition: clinical & lab findings

♣ Clinical findings: EM, erythematous lesion & tick bite, ACA, neurological incl LNB, musculoskeletal incl LA, CVS symptoms

♣ Lab: two-tiered approach

♣ 16 cases identified

♣ Autochthonous LD (11 cases):

1. mean age of 41.9

2. majority lived in Seoul metropolitan region

3. 7 did not work outdoors

4. past exposure in 62.5%

5. 5 cases had EM

6. 4 cases had neurological abnormalities

♣ Cases outside of Korea (5):

1. 4 had EM

2. none had any neurological symptoms

Strengths:

♣ wide range of demographic variables compared

♣ clear breakdown of manifestations identified

♣ identified cases occurring outside of Korea

Weaknesses:

♣ sample size very small any inferences could be due to chance

♣ disparities between case inclusions as LD only become notifiable in 2011

♣ travel history of 6 months prior to manifestations limits likelihood of LDLD cases

Discussion:

The objective of this systematic review was to gain an insight into the current and preceding epidemiological states of Lyme disease around the globe, as there is no existing literature on its current existence in Ireland. It aimed to discover what diagnostic tools and techniques were most commonly used, and the ones which proved most effective in previous studies. The review was also carried out with the intention of identifying the manifestations of the Borreliosis bacterial infection, and the most common syndromes and the stages they present at with in patients.

Epidemiology:

In terms of the epidemiological variance of Lyme disease, the results from the literature vary from region to region. The incidence rates calculated in the reviewed studies fluctuate due to a multitude of factors, like, the density of infected ticks in a region, the exposure of the patient to the outdoors or an endemic region, the awareness of the patient to ticks and Lyme preventive techniques, the diagnosis used in their vicinity and the treatment and standard of care given. (5, 12, 19) The results in terms of sex, were contradicting and no definitive answers arose, apart from the increased incidence of cutaneous manifestations that were reported in women. (17)  In terms of age all the results were reasonably uniform with the median ages reported ranging from 41.9 to 61.5. (10, 12, 18) Clustering of cases occurs, in both spatial and temporal terms. (14) The disease outbreak endemic occurs in well-defined regions then tends to spread to surrounding regions. (14) Location plays a vital role in Lyme disease contraction risk. (20) Flatter land and areas with shrubs appear to increase the risk. (12, 16) It is clear from the studies that an increased amount of time spent outdoors, particularly in the summer months, increases rates of the infection amongst humans. (16, 17) The literature also supports an association with animal exposure and increased incidence rates. (16) Travel, to endemic regions in particular, plays an enormous role in exposure and can affect incidence rates in a non-endemic region, if the non-autochthonous cases are not exposed, like they were in the Korean study. (18)

Diagnosis:

Regarding diagnostic techniques, the majority of the studies analysed used the two-tiered laboratory diagnostic technique. (9, 10, 12, 13, 14, 15, 16, 17, 18) This approach was the most commonly used method for diagnosing the infection in the articles, and the two-tiered approach is reported to result in higher sensitivity for Lyme disease. (8, 21) A two-tiered approach consists of an initial enzyme immunoassay test, and if it is found to be positive a second test is run on the same sample. (8)  The second test comprises of a Western Blot technique. If the symptoms have existed for less than a month only an IgG Western Blot is carried out, however if they have persisted for longer, both IgG and IgM are carried out. (8) Both tests must return positive for a definitive two-tiered diagnosis to be given. (8)

Syndromes:

Lyme disease is multi-system disease, with numerous syndromes, the most common presentation is diverse erythema migrans. (3) Acrodermatitis chronica atrophicans is another common cutaneous manifestation in Europe. (5, 17) Lyme arthritis and neuroborreliosis are also reported, with varying incidence rates. (4, 10, 12, 17) It is vital to recognise the different symptoms and the stages they appear at, as they are so varying in nature.

Conclusion:

The research which has been carried out on the topic of Lyme disease, its epidemiology, its diagnosis and its manifestations is vast and far-reaching. After, extensive researching, no studies have been carried out in Ireland, and very little of significance carried out in the nearest geographical region of the UK. (3)  The research that has been carried out has been focused in endemic regions of Europe, America, Canada and Asia. (7, 9-20) It gave a clear insight into the most likely age of occurrence, and that outdoor exposure increases the risk, but all other epidemiological variables would play an unpredictable role in the occurrence of Lyme disease in Ireland.  

 With this in mind, it is apparent a case-review study carried out in Ireland would be an invaluable study which would successfully carry out the objectives of this review in an Irish setting. An approach should be taken that combines all the positives findings from the results of the 10 closely analysed studies. Each case should have demographics like age, sex, geographical location, occupation, travel, outdoor activities clearly identified and analysed. A two-tiered approach alongside clinical manifestations should be used for diagnosis and identification for inclusion in the study. Each syndrome and its associated disease stage should be clearly outlined, and the type of treatment received documented.

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