document_title: Cricket World Cup

question_text: which country has won the cricket world cup maximum number of times

text: Cricket World Cup

text: History[edit]

text: Before the first Cricket World Cup[edit]

text: The first international cricket match was played between Canada and the United States, on 24 and 25 September 1844.[2] However, the first credited Test match was played in 1877 between Australia and England, and the two teams competed regularly for The Ashes in subsequent years. South Africa was admitted to Test status in 1889.[3] Representative cricket teams were selected to tour each other, resulting in bilateral competition. Cricket was also included as an Olympic sport at the 1900 Paris Games, where Great Britain defeated France to win the gold medal.[4] This was the only appearance of cricket at the Summer Olympics.

text: The first multilateral competition at international level was the 1912 Triangular Tournament, a Test cricket tournament played in England between all three Test-playing nations at the time: England, Australia and South Africa. The event was not a success: the summer was exceptionally wet, making play difficult on damp uncovered pitches, and attendances were poor, attributed to a "surfeit of cricket".[5] Since then, international Test cricket has generally been organised as bilateral series: a multilateral Test tournament was not organised again until the triangular Asian Test Championship in 1999.[6]

text: The number of nations playing Test cricket increased gradually over time, with the addition of West Indies in 1928, New Zealand in 1930, India in 1932, and Pakistan in 1952. However, international cricket continued to be played as bilateral Test matches over three, four or five days.

text: In the early 1960s, English county cricket teams began playing a shortened version of cricket which only lasted for one day. Starting in 1962 with a four-team knockout competition known as the Midlands Knock-Out Cup,[7] and continuing with the inaugural Gillette Cup in 1963, one-day cricket grew in popularity in England. A national Sunday League was formed in 1969. The first One-Day International match was played on the fifth day of a rain-aborted Test match between England and Australia at Melbourne in 1971, to fill the time available and as compensation for the frustrated crowd. It was a forty over game with eight balls per over.[8]

text: In the late 1970s, Kerry Packer established the rival World Series Cricket (WSC) competition. It introduced many of the now commonplace features of One Day International cricket, including coloured uniforms, matches played at night under floodlights with a white ball and dark sight screens, and, for television broadcasts, multiple camera angles, effects microphones to capture sounds from the players on the pitch, and on-screen graphics. The first of the matches with coloured uniforms was the WSC Australians in wattle gold versus WSC West Indians in coral pink, played at VFL Park in Melbourne on 17 January 1979. The success and popularity of the domestic one-day competitions in England and other parts of the world, as well as the early One-Day Internationals, prompted the ICC to consider organising a Cricket World Cup.[9]

text: Prudential World Cups (1975–1983)[edit]

text: The inaugural Cricket World Cup was hosted in 1975 by England, the only nation able to put forward the resources to stage an event of such magnitude at the time. The 1975 tournament started on 7 June.[10] The first three events were held in England and officially known as the Prudential Cup after the sponsors Prudential plc. The matches consisted of 60 six-ball overs per team, played during the daytime in traditional form, with the players wearing cricket whites and using red cricket balls.[11]

text: Eight teams participated in the first tournament: Australia, England, India, New Zealand, Pakistan, and the West Indies (the six Test nations at the time), together with Sri Lanka and a composite team from East Africa.[12] One notable omission was South Africa, who were banned from international cricket due to apartheid. The tournament was won by the West Indies, who defeated Australia by 17 runs in the final at Lord's.[12]

text: The 1979 World Cup saw the introduction of the ICC Trophy competition to select non-Test playing teams for the World Cup,[13] with Sri Lanka and Canada qualifying.[14] The West Indies won a second consecutive World Cup tournament, defeating the hosts England by 92 runs in the final. At a meeting which followed the World Cup, the International Cricket Conference agreed to make the competition a quadrennial event.[14]

text: The 1983 event was hosted by England for a third consecutive time. By this stage, Sri Lanka had become a Test-playing nation, and Zimbabwe qualified through the ICC Trophy. A fielding circle was introduced, 30 yards (27 m) away from the stumps. Four fieldsmen needed to be inside it at all times.[15] The teams faced each other twice, before moving into the knock-outs. India, an outsider, quoted at 66–1 to win by bookmakers before the competition began, were crowned champions after upsetting the West Indies by 43 runs in the final.[9][16]

text: Different champions (1987–1996)[edit]

text: India and Pakistan jointly hosted the 1987 tournament, the first time that the competition was held outside England. The games were reduced from 60 to 50 overs per innings, the current standard, because of the shorter daylight hours in the Indian subcontinent compared with England's summer.[17] Australia won the championship by defeating England by 7 runs in the final, the closest margin in World Cup final history.[18][19]

text: The 1992 World Cup, held in Australia and New Zealand, introduced many changes to the game, such as coloured clothing, white balls, day/night matches, and a change to the fielding restriction rules. The South African cricket team participated in the event for the first time, following the fall of the apartheid regime and the end of the international sports boycott.[20] Pakistan overcame a dismal start in the tournament to eventually defeat England by 22 runs in the final and emerge as winners.[21]

text: The 1996 championship was held in the Indian subcontinent for a second time, with the inclusion of Sri Lanka as host for some of its group stage matches.[22] In the semi-final, Sri Lanka, heading towards a crushing victory over India at Eden Gardens after the hosts lost eight wickets while scoring 120 runs in pursuit of 252, were awarded victory by default after crowd unrest broke out in protest against the Indian performance.[23] Sri Lanka went on to win their maiden championship by defeating Australia by seven wickets in the final at Lahore.[24]

text: Australian treble (1999–2007)[edit]

text: In 1999 the event was hosted by England, with some matches also being held in Scotland, Ireland, Wales and the Netherlands.[25][26] Twelve teams contested the World Cup. Australia qualified for the semi-finals after reaching their target in their Super 6 match against South Africa off the final over of the match.[27] They then proceeded to the final with a tied match in the semi-final also against South Africa where a mix-up between South African batsmen Lance Klusener and Allan Donald saw Donald drop his bat and stranded mid-pitch to be run out. In the final, Australia dismissed Pakistan for 132 and then reached the target in less than 20 overs and with eight wickets in hand.[28]

text: South Africa, Zimbabwe and Kenya hosted the 2003 World Cup. The number of teams participating in the event increased from twelve to fourteen. Kenya's victories over Sri Lanka and Zimbabwe, among others – and a forfeit by the New Zealand team, which refused to play in Kenya because of security concerns – enabled Kenya to reach the semi-finals, the best result by an associate.[29] In the final, Australia made 359 runs for the loss of two wickets, the largest ever total in a final, defeating India by 125 runs.[30][31]

text: In 2007 the tournament was hosted by the West Indies and expanded to sixteen teams.[32] Following Pakistan's upset loss to World Cup debutants Ireland in the group stage, Pakistani coach Bob Woolmer was found dead in his hotel room.[33] Jamaican police had initially launched a murder investigation into Woolmer's death but later confirmed that he died of heart failure.[34] Australia defeated Sri Lanka in the final by 53 runs (D/L) in farcical light conditions, and extended their undefeated run in the World Cup to 29 matches and winning three straight championships.[35]

text: Hosts triumph (2011–2015)[edit]

text: India, Sri Lanka and Bangladesh together hosted the 2011 Cricket World Cup. Pakistan were stripped of their hosting rights following the terrorist attack on the Sri Lankan cricket team in 2009, with the games originally scheduled for Pakistan redistributed to the other host countries.[36] The number of teams participating in the World Cup dropped down to fourteen.[37] Australia lost their final group stage match against Pakistan on 19 March 2011, ending an unbeaten streak of 35 World Cup matches, which had begun on 23 May 1999.[38] India won their second World Cup title by beating Sri Lanka by 6 wickets in the final in Mumbai, and became the first country to win the final on home soil.[37] MS Dhoni later became the first captain in history to win all the major ICC tournaments - World T20 in 2007, Champions Trophy in 2013 and this edition of the World Cup.

text: Australia and New Zealand jointly hosted the 2015 Cricket World Cup. The number of participants remained at fourteen. Ireland was the most successful Associate nation with a total of three wins in the tournament. New Zealand beat South Africa in a thrilling first semi-final to qualify for their maiden World Cup final. Australia defeated New Zealand by seven wickets in the final at Melbourne to lift the World Cup for the fifth time.[39]

text: Format[edit]

text: Qualification[edit]

text: The Test-playing nations qualify automatically for the World Cup main event while the other teams have to qualify through a series of preliminary qualifying tournaments. A new qualifying format was introduced for the 2015 Cricket World Cup. The top two teams of the 2011–13 ICC World Cricket League Championship qualify directly. The remaining six teams join the third and fourth-placed teams of 2011 ICC World Cricket League Division Two and the top two teams of the 2013 ICC World Cricket League Division Three in the World Cup Qualifier to decide the remaining two places.[40][41]

text: Qualifying tournaments were introduced for the second World Cup, where two of the eight places in the finals were awarded to the leading teams in the ICC Trophy.[13] The number of teams selected through the ICC Trophy had varied throughout the years. The World Cricket League (administered by the International Cricket Council) is the qualification system provided to allow the Associate and Affiliate members of the ICC more opportunities to qualify. The name "ICC Trophy" has been changed to "ICC World Cup Qualifier".[42]

text: Under the current qualifying process, the World Cricket League, all Associate and Affiliate members of the ICC are able to qualify for the World Cup. Associate and Affiliate members must play between two and five stages in the ICC World Cricket League to qualify for the World Cup finals, depending on the Division in which they start the qualifying process.

text: Process summary in chronological order (2011-2014):

text:
2011 ICC World Cricket League Division Two: 6 Teams – Top 2 were promoted to the 2011–13 ICC World Cricket League Championship. The third and fourth-placed teams qualified for the 2014 Cricket World Cup Qualifier. The fifth and sixth-placed teams were relegated to the Division Three for 2013.
2011–13 ICC World Cricket League Championship: 8 Teams – Top 2 automatically qualified for the 2015 Cricket World Cup. The remaining six teams qualified for the 2014 Cricket World Cup Qualifier.
2013 ICC World Cricket League Division Three: 6 Teams – Top 2 were qualified for the 2014 Cricket World Cup Qualifier. The fifth and sixth-placed teams were relegated to the Division Four for 2014.
2014 Cricket World Cup Qualifier: 10 Teams – Top 2 qualified for the 2015 Cricket World Cup and the 2015–17 ICC World Cricket League Championship. The third and fourth-placed teams qualified for the 2015–17 ICC World Cricket League Championship. The fifth, sixth, seventh, and eighth-placed teams remained in the Division Two for 2015. The ninth and tenth-placed teams were relegated to the Division Three for 2014

tag: ol

text: Tournament[edit]

text: The format of the Cricket World Cup has changed greatly over the course of its history. Each of the first four tournaments was played by eight teams, divided into two groups of four.[43] The competition consisted of two stages, a group stage and a knock-out stage. The four teams in each group played each other in the round-robin group stage, with the top two teams in each group progressing to the semi-finals. The winners of the semi-finals played against each other in the final. With South Africa returning in the fifth tournament in 1992 as a result of the end of the apartheid boycott, nine teams played each other once in the group phase, and the top four teams progressed to the semi-finals.[44] The tournament was further expanded in 1996, with two groups of six teams.[45] The top four teams from each group progressed to quarter-finals and semi-finals.

text: A distinct format was used for the 1999 and 2003 World Cups. The teams were split into two pools, with the top three teams in each pool advancing to the Super 6.[46] The Super 6 teams played the three other teams that advanced from the other group. As they advanced, the teams carried their points forward from previous matches against other teams advancing alongside them, giving them an incentive to perform well in the group stages.[46] The top four teams from the Super 6 stage progressed to the semi-finals, with the winners playing in the final.

text: The format used in the 2007 World Cup involved 16 teams allocated into four groups of four.[47] Within each group, the teams played each other in a round-robin format. Teams earned points for wins and half-points for ties. The top two teams from each group moved forward to the Super 8 round. The Super 8 teams played the other six teams that progressed from the different groups. Teams earned points in the same way as the group stage, but carried their points forward from previous matches against the other teams who qualified from the same group to the Super 8 stage.[48] The top four teams from the Super 8 round advanced to the semi-finals, and the winners of the semi-finals played in the final.

text: The format used in the 2011 and 2015[49] World Cups featured two groups of seven teams, each playing in a round-robin format. The top four teams from each group proceeded to the knock out stage consisting of quarter-finals, semi-finals and ultimately the final.[50]

text: It is proposed that in 2019 World Cup, the number of teams participating will go down to 10 and all the teams will play against each other once in round robin format, before entering the semifinals. This would be similar to the one used in 1992 World Cup.

text: Trophy[edit]

text: The ICC Cricket World Cup Trophy is presented to the winners of the World Cup. The current trophy was created for the 1999 championships, and was the first permanent prize in the tournament's history. Prior to this, different trophies were made for each World Cup.[51] The trophy was designed and produced in London by a team of craftsmen from Garrard & Co over a period of two months.

text: The current trophy is made from silver and gilt, and features a golden globe held up by three silver columns. The columns, shaped as stumps and bails, represent the three fundamental aspects of cricket: batting, bowling and fielding, while the globe characterises a cricket ball.[52] The seam is tilted to symbolize the axial tilt of the Earth. It stands 60 centimetres high and weighs approximately 11 kilograms. The names of the previous winners are engraved on the base of the trophy, with space for a total of twenty inscriptions. The ICC keeps the original trophy. A replica differing only in the inscriptions is permanently awarded to the winning team.[53]

text: Media coverage[edit]

text: The tournament is the world's third largest[54] with only the FIFA World Cup and the Summer Olympics exceeding it. The 2011 Cricket World Cup final was televised in over 200 countries to over 2.2 billion television viewers.[55][56][57] Television rights, mainly for the 2011 and 2015 World Cup, were sold for over US$1.1 billion,[58] and sponsorship rights were sold for a further US$500 million.[59] The 2003 Cricket World Cup matches were attended by 626,845 people,[60] while the 2007 Cricket World Cup sold more than 672,000 tickets.[61][62]

text: Successive World Cup tournaments have generated increasing media attention as One-Day International cricket has become more established. The 2003 World Cup in South Africa was the first to sport a mascot, Dazzler the zebra.[63] An orange mongoose known as Mello was the mascot for the 2007 Cricket World Cup.[64] Stumpy, a blue elephant was the mascot for the 2011 World Cup.[65]

text: On 13 February, the opening of the 2015 tournament was celebrated with a Google Doodle.[66]

text: Selection of hosts[edit]

text: The International Cricket Council's executive committee votes for the hosts of the tournament after examining the bids made by the nations keen to hold a Cricket World Cup.[67]

text: England hosted the first three competitions. The ICC decided that England should host the first tournament because it was ready to devote the resources required to organising the inaugural event.[10] India volunteered to host the third Cricket World Cup, but most ICC members preferred England as the longer period of daylight in England in June meant that a match could be completed in one day.[68] The 1987 Cricket World Cup was held in India and Pakistan, the first hosted outside England.[69]

text: Many of the tournaments have been jointly hosted by nations from the same geographical region, such as South Asia in 1987, 1996 and 2011, Australasia in 1992 and 2015, Southern Africa in 2003 and West Indies in 2007.

text: Tournament history[edit]

text:
Year
Host(s)
Final venue
Result

Winner
Margin
Runner-up

1975
Details
 England
London
 West Indies
291/8 (60 overs)
West Indies won by 17 runs
Scorecard
 Australia
274 all out (58.4 overs)

1979
Details
 England
London
 West Indies
286/9 (60 overs)
West Indies won by 92 runs
Scorecard
 England
194 all out (51 overs)

1983
Details
 England [a]
London
 India
183 all out (54.4 overs)
India won by 43 runs
Scorecard
 West Indies
140 all out (52 overs)

1987
Details
 India
 Pakistan
Kolkata
 Australia
253/5 (50 overs)
Australia won by 7 runs
Scorecard
 England
246/8 (50 overs)

1992
Details
 Australia
 New Zealand
Melbourne
 Pakistan
249/6 (50 overs)
Pakistan won by 22 runs
Scorecard
 England
227 all out (49.2 overs)

1996
Details
 Pakistan
 India
 Sri Lanka
Lahore
 Sri Lanka
245/3 (46.2 overs)
Sri Lanka won by 7 wickets
Scorecard
 Australia
241/7 (50 overs)

1999
Details
 England
 Wales [b]
London
 Australia
133/2 (20.1 overs)
Australia won by 8 wickets
Scorecard
 Pakistan
132 all out (39 overs)

2003
Details
 South Africa [c]
Johannesburg
 Australia
359/2 (50 overs)
Australia won by 125 runs
Scorecard
 India
234 all out (39.2 overs)

2007
Details
 West Indies [d]
Bridgetown
 Australia
281/4 (38 overs)
Australia won by 53 runs (D/L)
Scorecard
 Sri Lanka
215/8 (36 overs)

2011
Details
 India
 Sri Lanka
 Bangladesh
Mumbai
 India
277/4 (48.2 overs)
India won by 6 wickets
Scorecard
 Sri Lanka
274/6 (50 overs)

2015
Details
 Australia
 New Zealand
Melbourne
 Australia
186/3 (33.1 overs)
Australia won by 7 wickets
Scorecard
 New Zealand
183 all out (45 overs)

2019
Details
 England
 Wales
London

2023
Details
 India
Kolkata

text:
Jump up ^ England was the sole designated host, but matches were also played in Wales.
Jump up ^ The England and Wales Cricket Board was the sole designated host, but matches were also played in Scotland, Ireland, and the Netherlands.
Jump up ^ Cricket South Africa was the sole designated host, but matches were also played in Zimbabwe and Kenya.
Jump up ^ Eight member countries of the West Indies Cricket Board hosted matches – Antigua and Barbuda, Barbados, Grenada, Guyana, Jamaica, Saint Kitts and Nevis, Saint Lucia, and Trinidad and Tobago.

text: Results[edit]

text: Twenty nations have qualified for the Cricket World Cup at least once (excluding qualification tournaments). Seven teams have competed in every finals tournament, five of which have won the title.[9] The West Indies won the first two tournaments, Australia has won five, India has won two, while Pakistan and Sri Lanka have each won once. The West Indies (1975 and 1979) and Australia (1999, 2003 and 2007) are the only nations to have won consecutive titles.[9] Australia has played in seven of the eleven final matches (1975, 1987, 1996, 1999, 2003, 2007, 2015). England has yet to win the World Cup, but has been runners-up three times (1979, 1987, 1992). The best result by a non-Test playing nation is the semi-final appearance by Kenya in the 2003 tournament; while the best result by a non-Test playing team on their debut is the Super 8 (second round) by Ireland in 2007.[9]

text: Sri Lanka as a co-host of the 1996 Cricket World Cup was the first host to win the tournament though the final was held in Pakistan.[9] India won in 2011 as host and was the first team to win in a final played in their own country.[70] Australia repeated the feat in 2015.[39] England is the only other host to have made the final, in 1979. Other countries which have achieved or equalled their best World Cup results while co-hosting the tournament are New Zealand as finalists in 2015; Zimbabwe who reached the Super Six in 2003; and Kenya as semi-finalists in 2003.[9] In 1987, co-hosts India and Pakistan both reached the semi-finals, but were eliminated by Australia and England respectively.[9] Australia in 1992, England in 1999, South Africa in 2003, and Bangladesh in 2011 have been the host teams that were eliminated in the first round.

text: Teams' performances[edit]

text: An overview of the teams' performances in every World Cup:

text:
Team \ Host
1975
(8)
1979
(8)
1983
(8)
1987
(8)
1992
(9)
1996
(12)
1999
(12)
2003
(14)
2007
(16)
2011
(14)
2015
(14)
2019
(10)
2023
(10)

 Afghanistan

GP

 Australia
2nd
GP
GP
1st
GP
2nd
1st
1st
1st
QF
1st
Q

 Bangladesh

GP
GP
S8
GP
QF
Q

 Bermuda

GP

 Canada

GP

GP
GP
GP

 East Africa†
GP

 England
SF
2nd
SF
2nd
2nd
QF
GP
GP
S8
QF
GP
Q

 India
GP
GP
1st
SF
GP
SF
S6
2nd
GP
1st
SF
Q

 Ireland

S8
GP
GP

 Kenya

GP
GP
SF
GP
GP

 Namibia

GP

 Netherlands

GP

GP
GP
GP

 New Zealand
SF
SF
GP
GP
SF
QF
SF
S6
SF
SF
2nd
Q

 Pakistan
GP
SF
SF
SF
1st
QF
2nd
GP
GP
SF
QF
Q

 Scotland

GP

GP

GP

 South Africa

SF
QF
SF
GP
SF
QF
SF
Q

 Sri Lanka
GP
GP
GP
GP
GP
1st
GP
SF
2nd
2nd
QF
Q

 United Arab Emirates

GP

GP

 West Indies
1st
1st
2nd
GP
GP
SF
GP
GP
S8
QF
QF

 Zimbabwe

GP
GP
GP
GP
S6
S6
GP
GP
GP

text: †No longer exists.

text: Before the 1992 World Cup, South Africa was banned due to apartheid.

text: The number of wins followed by Run-rate is the criteria for determining the rankings till the 1987 World Cup.

text: The number of points followed by, head to head performance and then net run-rate is the criteria for determining the rankings for the World Cups from 1992 onwards.

text: Legend

text:
1st – Winner
2nd – Runner up
SF – Semi-finals
S6 – Super Six (1999–2003)
S8 – Super Eight (2007)
QF – Quarter-finals (1996, 2011–2015)
GP – Group – First round

text: Debutant teams[edit]

text:
Year
Teams

1975
 Australia, East Africa†,  England,  India,  New Zealand,  Pakistan,  Sri Lanka,  West Indies

1979
 Canada

1983
 Zimbabwe

1987
none

1992
 South Africa

1996
 Kenya,  Netherlands,  United Arab Emirates

1999
 Bangladesh,  Scotland

2003
 Namibia

2007
 Bermuda,  Ireland

2011
none

2015
 Afghanistan

2019
TBD

text: †No longer exists.

text: Overview[edit]

text: The table below provides an overview of the performances of teams over past World Cups, as of the end of group stage of the 2015 tournament. Teams are sorted by best performance, then by appearances, total number of wins, total number of games, and alphabetical order respectively.

text:
Appearances

Statistics

Team
Total
First
Latest
Best result
Mat.
Won
Lost
Tie
NR
Win%*

 Australia
11
1975
2015
1.1 !Champions (1987, 1999, 2003, 2007, 2015)
84
62
20
1
1
75.30

 India
11
1975
2015
1.3 !Champions (1983, 2011)
75
46
27
1
1
62.83

 West Indies
11
1975
2015
1.3 !Champions (1975, 1979)
71
41
29
0
1
58.57

 Sri Lanka
11
1975
2015
1.5 !Champions (1996)
73
35
35
1
2
50.00

 Pakistan
11
1975
2015
1.5 !Champions (1992)
71
40
29
0
2
57.97

 England
11
1975
2015
2.3 !Runners-up (1979, 1987, 1992)
72
41
29
1
1
58.45

 New Zealand
11
1975
2015
2.5 !Runners-up (2015)
79
48
30
0
1
61.53

 South Africa
7
1992
2015
3.2 !Semi-finals (1992, 1999, 2007, 2015)
55
35
18
2
0
65.45

 Kenya
5
1996
2011
3.5 !Semi-finals (2003)
29
6
22
0
1
21.42

 Zimbabwe
9
1983
2015
5.4 !Super 6 (1999, 2003)
57
11
42
1
3
21.29

 Bangladesh
5
1999
2015
7.4 !Quarter-finals (2015), Super 8 (2007)
32
11
20
0
1
35.48

 Ireland
3
2007
2015
7.5 !Super 8 (2007)
21
7
13
1
0
35.71

 Netherlands
4
1996
2011
9.2 !Group Stage (1996, 2003, 2007, 2011)
20
2
18
0
0
10.00

 Canada
4
1979
2011
9.2 !Group Stage (1979, 2003, 2007, 2011)
18
2
16
0
0
11.11

 Scotland
3
1999
2015
9.3 !Group Stage (1999, 2007, 2015)
14
0
14
0
0
0.00

 United Arab Emirates
2
1996
2015
9.4 !Group Stage (1996, 2015)
11
1
10
0
0
9.09

 Afghanistan
1
2015
2015
9.5 !Group Stage (2015)
6
1
5
0
0
16.66

 Namibia
1
2003
2003
9.5 !Group Stage (2003)
6
0
6
0
0
0.00

 Bermuda
1
2007
2007
9.5 !Group Stage (2007)
3
0
3
0
0
0.00

 East Africa†
1
1975
1975
9.5 !Group Stage (1975)
3
0
3
0
0
0.00

Last Updated: 29 March 2015
Source: Cricinfo[71]

text: The Win percentage excludes no results and counts ties as half a win.

text: †No longer exists.

text: Awards[edit]

text: Man of the tournament[edit]

text: Since 1992, one player has been declared as "Man of the Tournament" at the end of the World Cup finals:[72]

text:
Year
Player
Performance details

1992
 Martin Crowe
456 runs

1996
 Sanath Jayasuriya
221 runs and 7 wickets

1999
 Lance Klusener
281 runs and 17 wickets

2003
 Sachin Tendulkar
673 runs and 2 wickets

2007
 Glenn McGrath
26 wickets

2011
 Yuvraj Singh
362 runs and 15 wickets

2015
 Mitchell Starc
22 wickets

text: Man of the Match in the Final[edit]

text: There were no Man of the Tournament awards before 1992 but Man of the Match awards have always been given for individual matches. Winning the Man of the Match in the final is logically noteworthy, as this indicates the player deemed to have played the biggest part in the World Cup final. To date the award has always gone to a member of the winning side. The Man of the Match award in the final of the competition has been awarded to:[72]

text:
Year
Player
Performance details

1975
 Clive Lloyd
102 runs

1979
 Viv Richards
138*

1983
 Mohinder Amarnath
3/12 and 26

1987
 David Boon
75 runs

1992
 Wasim Akram
33 and 3/49

1996
 Aravinda de Silva
107* and 3/42

1999
 Shane Warne
4/33

2003
 Ricky Ponting
140*

2007
 Adam Gilchrist
149

2011
 Mahendra Singh Dhoni
91*

2015
 James Faulkner
3/36

text: Tournament records[edit]

text:
World Cup records[73]

Batting

Most runs
 Sachin Tendulkar
2,278 (1992–2011)

Highest average (min. 20 inns.) [74]
 AB de Villiers
63.52 (2007–2015)

Highest score
 Martin Guptill v West Indies
237* (2015)

Highest partnership
 Chris Gayle & Marlon Samuels
(2nd wicket) v Zimbabwe
372 (2015)

Most runs in a tournament
 Sachin Tendulkar
673 (2003)

Most hundreds
 Sachin Tendulkar
6 (1992–2011)

Bowling

Most wickets
 Glenn McGrath
71 (1996–2007)

Lowest average (min. 1000 balls bowled)
 Glenn McGrath
18.19 (1996–2007)

Best strike rate (min. 1000 balls bowled)
 Lasith Malinga
23.8 (2007–2015)

Best economy rate (min. 1000 balls bowled)
 Andy Roberts
3.24 (1975–1983)

Best bowling figures
 Glenn McGrath v Namibia
7/15 (2003)

Most wickets in a tournament
 Glenn McGrath
26 (2007)

Fielding

Most dismissals (wicket-keeper)
 Kumar Sangakkara
54 (2003–2015)

Most catches (fielder)
 Ricky Ponting
28 (1996–2011)

Team

Highest score
 Australia v Afghanistan
417/6 (2015)

Lowest score
 Canada v Sri Lanka
36 (2003)

Highest win % [75]
 Australia
74% (Played 84, Won 62)

Most consecutive wins [76]
 Australia
27 (20 Jun 1999–19 Mar 2011, one N/R excluded)

Most consecutive tournament wins
 Australia
3 (1999–2007)


document_title: Crooked House (film)

question_text: where was the film the crooked house filmed

root

text: Crooked House (film)

text: Plot[edit]

text: The granddaughter of late business tycoon Aristide Leonides, Sophia Leonides, visits private investigator Charles Hayward in his office. Sophia hires Charles to investigate Aristide's death, for she believes he was murdered by a member of his sprawling and idiosyncratic family. Sophia notes that Leonides' regular insulin injection had been laced with eserine from his eye drops, the resulting chemicals in them causing him to die. Sophia believes this to have been a deliberate switch rather than accidental. Charles begrudgingly agrees to take on the case as a result of his feelings for Sophia as the two had enjoyed a brief love affair when they had met sometime prior in Cairo. Charles seeks the consent of Chief Inspector Taverner of Scotland Yard to look into the case, utilising his personal connection with Taverner, who had served with Charles's father, a decorated former Assistant Commissioner who was murdered.

tag: p

text: Charles visits the Leonides estate and proceeds to interview the various members of the family, finding various motives from each. Charles begins with Lady Edith De Haviland, the sister of Leonides's first wife, who despised her brother-in-law and his callous attitude towards her grandchildren. Leonides's eldest son, Philip, hated his father for passing him over to run the family business and for refusing to take interest in a new play he'd written for his wife, Magda, a fading theatre actress. Philip and Magda provided Leonides with three grandchildren, namely Sophia and the precocious younger children Eustace and Josephine. Eustace takes a dislike to Charles and seeks to hamper him where possible whilst Josephine makes clear to Charles that she eavesdrops on everyone around the house, makes notes about their private lives and dislikes most of her family except for Edith and Sophia.

text: Charles subsequently finds that Leonides' younger son, Roger, the emotionally immature managing director of the family's flagship business, was reliant upon his father bailing out the business numerous times due to his poor management. The fact that Leonides was so willing to bail Roger out did not sit well with either Roger, due to his pride, or his domineering wife Clemency. Charles further finds that Leonides' second wife, Brenda, a much younger former Las Vegas casino dancer, is suspected by the rest of the family as having committed the murder. Evidence seems to back this up due to the facts that Brenda had been having an affair with Laurence Brown, the private tutor for the Leonides children, as well as that she administered the fatal dose of drugs to Leonides and that she stood to inherit the entirety of the Leonides estate due to him not having signed a will, meaning he died intestate and thus his estate passed to her.

text: Charles's investigations and questions are met with hostility by most of the family whilst Josephine cryptically hints at clues along the way, to Charles's irritation, as he finds her treating the investigation as a game to be tiresome. Events take a new, horrific turn when the ladder to Josephine's treehouse is sabotaged and she falls from the tree, being hospitalised as a result. Charles suspects that this was due to Josephine's habit of spying on the other family members and the killer thus wanting to silence her. In the aftermath, Charles's suspicions are heightened and even extend to Sophia after a new will is discovered in which Leonides had left his estate to her, with some arguing that Sophia hired Charles to investigate the murder due to their personal history, knowing he would never accuse her due to their romantic past.

text: After those developments, Taverner arrives in person to take charge of the case as he feels Charles' romantic history with Sophia does not make him objective enough to solve it. The discovery of love letters between Brenda and Laurence gives Taverner enough evidence to arrest them for Leonides' murder and the attempt on Josephine, to the delight of most of his family members who had always hated both. Charles, however, remains unconvinced that Brenda and Laurence are guilty, noting Brenda's childlike intelligence and Laurence's pacifist, left-wing views as making them unlikely candidates for being a murderer. Sophia and Edith seem to agree, with Sophia noting how the letters could have been forged and Edith paying for a top rate lawyer to represent Brenda and Laurence in court. In the meantime, however, Charles returns to London and only returns to the estate when Josephine's nanny dies after being poisoned by drinking a mug of hot chocolate that she had made for Josephine.

text: Charles implores Josephine to tell her who the killer is as he has worked out she knows their identity. Again, Josephine refuses to tell. After it is established that the nanny died of cyanide poisoning, Charles begins to suspect Edith as he knew she had been using cyanide to remove moles in the estate garden. His search of Edith's garden shed finds a bottle of cyanide as well as Josephine's missing notebook, complete with her notes on each member of the family. Edith drives out of the family estate with Josephine, having also left a note for Charles to find. Charles and Sophia take off in pursuit of Edith in a car chase to try and stop them. In the car, Sophia reads the note that Edith had left in which she confesses to the murder but Charles argues that he believes Edith is not the killer.

text: Sophia reads extracts from Josephine's notebook in which the child admits to murdering Leonides purely because he had refused to pay for her ballet lessons. The notebook further reveals that Josephine had also faked the attack on herself and had poisoned her nanny when the latter began to suspect Josephine. Lady Edith had worked out that Josephine was the killer and planted evidence and wrote the confession note to spare Josephine a life in psychiatric institutions and exonerate Brenda and Laurence. Edith had earlier been informed that she was dying of cancer and so decided to sacrifice herself to protect Josephine and the rest of the family. Edith realises that Charles and Sophia are pursuing her and so she drives her car over the clifftop of a quarry, killing herself and Josephine. The film ends as Charles comforts a shocked Sophia at the edge of the cliff.

text: Cast[edit]

text:
Glenn Close as Lady Edith de Haviland
Terence Stamp as Chief Inspector Taverner
Max Irons as Charles Hayward
Stefanie Martini as Sophia Leonides
Julian Sands as Philip Leonides
Honor Kneafsey as Josephine Leonides
Christian McKay as Roger Leonides
Amanda Abbington as Clemency Leonides
Gillian Anderson as Magda Leonides
Christina Hendricks as Brenda Leonides
Preston Nyman as Eustace Leonides
John Heffernan as Laurence Brown
Jenny Galloway as Nanny
David Kirkbride as Sergeant Glover
Tina Gray as Miss Ackroyd
Roger Ashton-Griffiths as Mr Gaitskill
Andreas Karras as Iannois Agrodopolous
Gino Picciano as Aristide Leonides

tag: ul

text: Production[edit]

text: This section needs expansion. You can help by adding to it. (December 2017)

tag: table

text: The mystery drama is based on Agatha Christie's novel of the same name. Principal photography began in September 2016.[2] Part of the filming was done at King's College London's Maughan Library. Other parts were filmed at Tyntesfield, near Bristol.[citation needed] Minley Manor near Fleet, Hampshire, was used as the location for the external shots of Crooked House.

text: Music[edit]

text: The film's original score is by Hugo de Chaire.[3]

text: Changes from source material[edit]

text: Whilst the film remains largely faithful to Christie's book, there were some changes, among them:

text:
Charles's father, Sir Arthur Hayward, is deceased. He is referred to as an Assistant Commissioner of Scotland Yard but was murdered. Chief Inspector Taverner assumes some of the qualities and the role played by Sir Arthur.
Charles and Sophia are no longer in a relationship. Their love affair beginning in Cairo ended when Sophia refused to introduce Charles to her family and after she found out he was spying on her for the Foreign Office due to their interest in Leonides's business affairs. The ending of the film is open-ended as to whether they will reconcile.
Nanny is poisoned by cyanide, not digitalis.
Lady Edith addresses her confession note to Charles instead of Taverner.
Lady Edith does not leave the second letter for Charles and Sophia outlining Josephine as the killer. Instead, Charles finds Josephine's notebook and that is used for Charles and Sophia as confirmation that Josephine is the killer.
The ages of Philip and Roger are switched around. Philip becomes the eldest son, this forming part of his motive to kill Aristide as he had been passed over to run the family business for his younger brother, Roger.
The story is set a decade later to 1950s London, as evidenced by one of the film's characters referencing the execution of the murderess Ruth Ellis in 1955.
The conversation with the lawyer mentioned that will was signed in 1957.

text: Reception[edit]

text: Critical response[edit]

text: On review aggregator website Rotten Tomatoes, the film has an approval rating of 69% based on 16 reviews, with an average rating of 5.8/10.[4] On Metacritic, which assigns a normalized rating to reviews, the film has a weighted average score of 59 out of 100, based on 8 critics, indicating "mixed or average reviews."[5]


document_title: Renal sodium reabsorption

question_text: where is most sodium reabsorbed in the kidney

text: Renal sodium reabsorption

text: Proximal tubule[edit]

text: Most of the reabsorption (65%) occurs in the proximal tubule. In the latter part it is favoured by an electrochemical driving force, but initially it needs the cotransporter SGLT and the Na-H antiporter. Sodium passes along an electrochemical gradient (passive transport) from the lumen into the tubular cell, together with water and chloride which also diffuse passively. Water is reabsorbed to the same degree, resulting in the concentration in the end of the proximal tubule being the same as in the beginning. In other words, the reabsorption in the proximal tubule is isosmotic.

text: Loop of Henle[edit]

text: Sodium is reabsorbed in the thick ascending limb of loop of Henle, by Na-K-2Cl symporter and Na-H antiporter. It goes against its chemical driving force, but the high electrical driving force renders the overall electrochemical driving force positive anyway, availing some sodium to diffuse passively either the transcellular or paracellular way..

text: Distal tubule[edit]

text: In the distal convoluted tubule sodium is transported against an electrochemical gradient by sodium-chloride symporters.

text: Collecting duct[edit]

text: The principal cells are the sodium-transporting cells in the collecting duct system.

text: Regulation[edit]

text: Although only a fragment of total reabsorption happens here, it is the main part of intervention. This is e.g. done by endogenous production of aldosterone, increasing reabsorption. Since the normal excretion rate of sodium is ~100mmoles/day, then a regulation of the absorption of still more than 1000 mmoles/day entering the collecting duct system has a substantial influence of the total sodium excreted.

text: Overview table[edit]

text:
Characteristics of Na+ reabsorption

Characteristic
proximal tubule
loop of Henle
Distal convoluted tubule
Collecting duct system

S1
S2
S3
descending limb
thin ascending limb
thick ascending limb
connecting tubule
initial collecting tubule
cortical collecting ducts
medullary collecting ducts

reabsorption (%)
67%[2]

25%[2]
5%[2]
3%[2]

reabsorption (mmoles/day)
~17,000[2]

~6,400[2]
~1,300[2]
~700[2]

Concentration (mM)
142[3]

142[3]

100[3]
70[3]

40[3]

electrical driving force (mV)
-3[3]

+3[3]

+15[3]
-5 to +5[3]

-40[3]

chemical driving force (mV)
0[3]

0[3]

-9[3]
-19[3]

-34[3]

electrochemical driving force (mV)
-3[3]

+3[3]

+6[3]
-24 to -14[3]

-74[3]

apical transport proteins
SGLT, Na-H antiporter[4]

(passively)
Na-K-2Cl symporter
(Na-H antiporter[4] and passively)
sodium-chloride symporter[4]

ENaC[4]

basolateral transport proteins
Na+/K+-ATPase[4]

Other reabsorption features
isosmotic

by principal cells, stimulated by aldosterone


document_title: Lyme disease

question_text: where is lyme disease found in the us

question_tokens: where is lyme disease found in the us

text: Lyme disease

text: Signs and symptoms

text: Lyme disease can affect multiple body systems and produce a broad range of symptoms. Not all patients with Lyme disease have all symptoms, and many of the symptoms are not specific to Lyme disease, but can occur with other diseases, as well. The incubation period from infection to the onset of symptoms is usually one to two weeks, but can be much shorter (days), or much longer (months to years).[19]

text: Symptoms most often occur from May to September, because the nymphal stage of the tick is responsible for most cases.[19] Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States.[20] Asymptomatic infection may be much more common among those infected in Europe.[21]

text: Early localized infection

text: Early localized infection can occur when the infection has not yet spread throughout the body. Only the site where the infection has first come into contact with the skin is affected. The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans (EM), which occurs at the site of the tick bite three to 32 days after the tick bite.[2] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated (is thicker and firmer), the outer edge remains red, and the portion in between clears, giving the appearance of a bull's eye. However, partial clearing is uncommon, and the bull's-eye pattern more often involves central redness.[2]

text: The EM rash associated with early infection is found in about 70–80% of people infected.[1] It can have a range of appearances including the classic target bull's-eye lesion and nontarget appearing lesions. The 20–30% without the EM and the nontarget lesions can often cause misidentification of Lyme disease.[22] Affected individuals can also experience flu-like symptoms, such as headache, muscle soreness, fever, and malaise.[23] Lyme disease can progress to later stages even in people who do not develop a rash.[21][24]

text: Early disseminated infection

text: Within days to weeks after the onset of local infection, the Borrelia bacteria may begin to spread through the bloodstream. EM may develop at sites across the body that bear no relation to the original tick bite.[25] Another skin condition, apparently absent in North American patients, but found in Europe, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum.[26] Various acute neurological problems, termed neuroborreliosis, appear in 10–15% of untreated people.[23][27] These include facial palsy, which is the loss of muscle tone on one or both sides of the face, as well as meningitis, which involves severe headaches, neck stiffness, and sensitivity to light. Inflammation of the spinal cord's nerve roots can cause shooting pains that may interfere with sleep, as well as abnormal skin sensations. Mild encephalitis may lead to memory loss, sleep disturbances, or mood changes. In addition, some case reports have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis.[28] The disease may adversely impact the heart's electrical conduction system and can cause abnormal heart rhythms such as atrioventricular block.[29]

text: Late disseminated infection

text: After several months, untreated or inadequately treated patients may go on to develop severe and chronic symptoms that affect many parts of the body, including the brain, nerves, eyes, joints, and heart. Many disabling symptoms can occur, including permanent impairment of motor or sensory function of the lower extremities in extreme cases.[21] The associated nerve pain radiating out from the spine is termed Bannwarth syndrome,[30] named after Alfred Bannwarth.

text: The late disseminated stage is where the infection has fully spread throughout the body. Chronic neurologic symptoms occur in up to 5% of untreated patients.[23] A polyneuropathy that involves shooting pains, numbness, and tingling in the hands or feet may develop. A neurologic syndrome called Lyme encephalopathy is associated with subtle cognitive difficulties, insomnia, a general sense of feeling unwell, and changes in personality.[31] Other problems, however, such as depression and fibromyalgia, are no more common in people with Lyme disease than in the general population.[32][33]

text: Chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, brain fog, migraines, balance issues, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. In rare cases, untreated Lyme disease may cause frank psychosis, which has been misdiagnosed as schizophrenia or bipolar disorder. Panic attacks and anxiety can occur; also, delusional behavior may be seen, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome, where the patients begin to feel detached from themselves or from reality.[34][35]

text: Lyme arthritis usually affects the knees.[36] In a minority of patients, arthritis can occur in other joints, including the ankles, elbows, wrists, hips, and shoulders. Pain is often mild or moderate, usually with swelling at the involved joint. Baker's cysts may form and rupture. In some cases, joint erosion occurs.

text: Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe among the elderly.[26] ACA begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless.[37]

text: Cause

text: Lyme disease is caused by spirochetal bacteria from the genus Borrelia. Spirochetes are surrounded by peptidoglycan and flagella, along with an outer membrane similar to other Gram-negative bacteria. Because of their double-membrane envelope, Borrelia bacteria are often mistakenly described as Gram negative despite the considerable differences in their envelope components from Gram-negative bacteria.[38] The Lyme-related Borrelia species are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity.

text: B. burgdorferi sensu lato is made up of 21 closely related species, but only three clearly cause Lyme disease: B. burgdorferi sensu stricto (predominant in North America, but also present in Europe), B. afzelii, and B. garinii (both predominant in Eurasia).[39][40] Some studies have also proposed B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.[41][42]

text: Transmission

text: Lyme disease is classified as a zoonosis, as it is transmitted to humans from a natural reservoir among small mammals and birds by ticks that feed on both sets of hosts.[43] Hard-bodied ticks of the genus Ixodes are the main vectors of Lyme disease (also the vector for Babesia).[44] Most infections are caused by ticks in the nymphal stage, because they are very small and thus may feed for long periods of time undetected.[43] Larval ticks are very rarely infected.[45] Although deer are the preferred hosts of the adult stage of deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire Lyme disease spirochetes from deer. Rather, deer ticks acquire Borrelia microbes from infected small mammals and occasionally birds, including the white-footed mouse, Peromyscus leucopus.[46]

text: Within the tick midgut, the Borrelia's outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. When the tick feeds, the Borrelia downregulates OspA and upregulates OspC, another surface protein. After the bacteria migrate from the midgut to the salivary glands, OspC binds to Salp15, a tick salivary protein that appears to have immunosuppressive effects that enhance infection.[47] Successful infection of the mammalian host depends on bacterial expression of OspC.[48]

text: Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. However, transmission is quite rare, with only about 1% of recognized tick bites resulting in Lyme disease.

text: In Europe, the vector is Ixodes ricinus, which is also called the sheep tick or castor bean tick.[49] In China, Ixodes persulcatus (the taiga tick) is probably the most important vector.[50] In North America, the black-legged tick or deer tick (Ixodes scapularis) is the main vector on the East Coast.[45]

text: The lone star tick (Amblyomma americanum), which is found throughout the Southeastern United States as far west as Texas, is unlikely to transmit the Lyme disease spirochetes,[51] though it may be implicated in a related syndrome called southern tick-associated rash illness, which resembles a mild form of Lyme disease.[52]

text: On the West Coast of the United States, the main vector is the western black-legged tick (Ixodes pacificus).[53] The tendency of this tick species to feed predominantly on host species such as lizards that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West.[54][55]

text: Transmission across the placenta during pregnancy has not been demonstrated, and no consistent pattern of teratogenicity or specific "congenital Lyme borreliosis" has been identified. As with a number of other spirochetal diseases, adverse pregnancy outcomes are possible with untreated infection; prompt treatment with antibiotics reduces or eliminates this risk.[56][57]

text: While Lyme spirochetes have been found in insects, as well as ticks,[58] reports of actual infectious transmission appear to be rare.[59] Lyme spirochete DNA has been found in semen[60] and breast milk.[61] However, according to the CDC, live spirochetes have not been found in breast milk, urine, or semen and thus is not sexually transmitted.[62]

text: Tick-borne coinfections

text: Ticks that transmit B. burgdorferi to humans can also carry and transmit several other parasites, such as Theileria microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively.[63] Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis.[64] Ticks in certain regions, including the lands along the eastern Baltic Sea, also transmit tick-borne encephalitis.[65]

text: Coinfections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the coinfections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control and Prevention studied 100 ticks in rural New Jersey, and found 55% of the ticks were infected with at least one of the pathogens.[66]

text: Pathophysiology

text: B. burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system.[48][67] Many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues.[23]

text: B. burgdorferi is injected into the skin by the bite of an infected Ixodes tick. Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite.[68] This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis. The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion.[48] Neutrophils, however, which are necessary to eliminate the spirochetes from the skin, fail to appear in the developing EM lesion. This allows the bacteria to survive and eventually spread throughout the body.[69]

text: Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of the disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete.[70]

text: If untreated, the bacteria may persist in the body for months or even years, despite the production of B. burgdorferi antibodies by the immune system.[71] The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, antigenic variation of the VlsE surface protein, inactivating key immune components such as complement, and hiding in the extracellular matrix, which may interfere with the function of immune factors.[72][73]

text: In the brain, B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis), which may contribute to neurodysfunction.[74] The spirochetes may also induce host cells to secrete quinolinic acid, which stimulates the NMDA receptor on nerve cells, which may account for the fatigue and malaise observed with Lyme encephalopathy.[75] In addition, diffuse white matter pathology during Lyme encephalopathy may disrupt gray matter connections, and could account for deficits in attention, memory, visuospatial ability, complex cognition, and emotional status. White matter disease may have a greater potential for recovery than gray matter disease, perhaps because the neuronal loss is less common. Resolution of MRI white matter hyperintensities after antibiotic treatment has been observed.[76]

text: Tryptophan, a precursor to serotonin, appears to be reduced within the central nervous system in a number of infectious diseases that affect the brain, including Lyme.[77] Researchers are investigating if this neurohormone secretion is the cause of neuropsychiatric disorders developing in some patients with borreliosis.[78]

text: Immunological studies

text: Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response,[79] a form of pathogen-induced autoimmune disease.[80] The production of this reaction might be due to a form of molecular mimicry, where Borrelia avoids being killed by the immune system by resembling normal parts of the body's tissues.[81][82]

text: Chronic symptoms from an autoimmune reaction could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to rheumatic fever, but its wider application is controversial.[83][84]

text: Diagnosis

text: Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as EM, facial palsy, or arthritis), or a history of possible exposure to infected ticks, as well as serological blood tests. The EM rash is not always a bull's eye, i.e., it can be solid red. When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illnesses. Not all individuals infected with Lyme disease develop the characteristic bull's-eye rash, and many may not recall a tick bite.[85]

text: Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas.[44] The EM rash, which does not occur in all cases, is considered sufficient to establish a diagnosis of Lyme disease even when serologic blood tests are negative.[86][87] Serological testing can be used to support a clinically suspected case, but is not diagnostic by itself.[44]

text: Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator".[88] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, lupus, Crohn's disease, HIV, or other autoimmune and neurodegenerative diseases. As all people with later-stage infection will have a positive antibody test, simple blood tests can exclude Lyme disease as a possible cause of a person's symptoms.[89]

text: Laboratory testing

text: Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. The most widely used tests are serologies, which measure levels of specific antibodies in a patient's blood. These tests may be negative in early infection as the body may not have produced a significant quantity of antibodies, but they are considered a reliable aid in the diagnosis of later stages of Lyme disease.[90] Serologic tests for Lyme disease are of limited use in people lacking objective signs of Lyme disease because of false positive results and cost.[91]

text: The serological laboratory tests most widely available and employed are the Western blot and ELISA. A two-tiered protocol is recommended by the Centers for Disease Control and Prevention: the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run.[92] The reliability of testing in diagnosis remains controversial.[44] Studies show the Western blot IgM has a specificity of 94–96% for people with clinical symptoms of early Lyme disease.[93][94] The initial ELISA test has a sensitivity of about 70%, and in two-tiered testing, the overall sensitivity is only 64%, although this rises to 100% in the subset of people with disseminated symptoms, such as arthritis.[95]

text: Erroneous test results have been widely reported in both early and late stages of the disease, and can be caused by several factors, including antibody cross-reactions from other infections, including Epstein–Barr virus and cytomegalovirus,[96] as well as herpes simplex virus.[97] The overall rate of false positives is low, only about 1 to 3%, in comparison to a false-negative rate of up to 36% in the early stages of infection using two-tiered testing.[95]

text: Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. PCR tests are susceptible to false positive results from poor laboratory technique.[98] Even when properly performed, PCR often shows false negative results with blood and cerebrospinal fluid specimens.[99] Hence, PCR is not widely performed for diagnosis of Lyme disease, but it may have a role in the diagnosis of Lyme arthritis because it is a highly sensitive way of detecting ospA DNA in synovial fluid.[100]

text: Culture or PCR are the current means for detecting the presence of the organism, as serologic studies only test for antibodies of Borrelia. OspA antigens, shedded by live Borrelia bacteria into urine, are a promising technique being studied.[101] The use of nanotrap particles for their detection is being looked at and the OspA has been linked to active symptoms of Lyme.[102][103] High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.[104]

text: Western blot, ELISA, and PCR can be performed by either blood test via venipuncture or cerebrospinal fluid (CSF) via lumbar puncture. Though lumbar puncture is more definitive of diagnosis, antigen capture in the CSF is much more elusive; reportedly, CSF yields positive results in only 10–30% of affected individuals cultured. The diagnosis of neurologic infection by Borrelia should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.[105]

text: New techniques for clinical testing of Borrelia infection have been developed, such as LTT-MELISA,[106] although the results of studies are contradictory. The first peer reviewed study assessing the diagnostic sensitivity and specificity of the test was presented in 2012 and demonstrated potential for LTT to become a supportive diagnostic tool.[107] In 2014, research of LTT-MELISA concluded that it is "sensible" to include the LTT test in the diagnostic protocol for putative European-acquired Lyme borreliosis infections.[108] Other diagnostic techniques, such as focus floating microscopy, are under investigation.[109] New research indicates chemokine CXCL13 may also be a possible marker for neuroborreliosis.[110]

text: Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of B. burgdorferi, and lymphocyte transformation tests. The CDC does not recommend these tests, and stated their use is "of great concern and is strongly discouraged".[99]

text: Imaging

text: Neuroimaging is controversial in whether it provides specific patterns unique to neuroborreliosis, but may aid in differential diagnosis and in understanding the pathophysiology of the disease.[111] Though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a patient. Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) are two of the tests that can identify abnormalities in the brain of a patient affected with this disease. Neuroimaging findings in an MRI include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. The findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. Images produced using SPECT show numerous areas where an insufficient amount of blood is being delivered the cortex and subcortical white matter. However, SPECT images are known to be nonspecific because they show a heterogeneous pattern in the imaging. The abnormalities seen in the SPECT images are very similar to those seen in people with cerebral vacuities and Creutzfeldt–Jakob disease, which makes them questionable.[112]

text: Prevention

text: Protective clothing includes a hat, long-sleeved shirt, and long pants tucked into socks or boots. Light-colored clothing makes the tick more easily visible before it attaches itself. People should use special care in handling and allowing outdoor pets inside homes because they can bring ticks into the house. People who work in areas with woods, bushes, leaf litter, and tall grass are at risk of becoming infected with Lyme at work. Employers can reduce the risk for employees by providing education on Lyme transmission and infection risks, and about how to check themselves for ticks on the groin, armpits, and hair. Work clothing used in risky areas should be washed in hot water and dried in a hot dryer to kill any ticks.[113]

text: Permethrin sprayed on clothing kills ticks on contact, and is sold for this purpose. According to the CDC, only DEET is effective at repelling ticks.[114]

text: Host animals

text: Lyme and other deer tick-borne diseases can sometimes be reduced by greatly reducing the deer population on which the adult ticks depend for feeding and reproduction. Lyme disease cases fell following deer eradication on an island, Monhegan, Maine[115] and following deer control in Mumford Cove, Connecticut.[116] It is worth noting that eliminating deer may lead to a temporary increase in tick density.[117]

text: For example, in the U.S., reducing the deer population to levels of 8 to 10 per square mile (from the current levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates), may reduce tick numbers and reduce the spread of Lyme and other tick-borne diseases.[118] However, such a drastic reduction may be very difficult to implement in many areas, and low to moderate densities of deer or other large mammal hosts may continue to feed sufficient adult ticks to maintain larval densities at high levels. Routine veterinary control of ticks of domestic animals, including livestock, by use of acaricides can contribute to reducing exposure of humans to ticks.

text: Action can be taken to avoid getting bitten by ticks by using insect repellants, for example, those that contain DEET. DEET-containing repellants are thought to be moderately effective in the prevention of tick bites.[119]

text:
In Europe known reservoirs of Borrelia burgdorferi were 9 small mammals, 7 medium-sized mammals and 16 species of birds (including passerines, sea-birds and pheasants).[120] These animals seem to transmit spirochetes to ticks and thus participate in the natural circulation of B. burgdorferi in Europe. The house mouse is also suspected as well as other species of small rodents, particularly in Eastern Europe and Russia.[120]
"The reservoir species that contain the most pathogens are the European roe deer Capreolus capreolus;[121] "it does not appear to serve as a major reservoir of B. burgdorferi" thought Jaenson & al. (1992)[122] (incompetent host for B. burgdorferi and TBE virus) but it is important for feeding the ticks,[123] as red deer and wild boars (Sus scrofa),[124] in which one Rickettsia and three Borrelia species were identified",[121] with high risks of coinfection in roe deer.[125] Nevertheless, in the 2000s, in roe deer in Europe " two species of Rickettsia and two species of Borrelia were identified".[124]

text: Vaccination

text: A recombinant vaccine against Lyme disease, based on the outer surface protein A (ospA) of B. burgdorferi, was developed by SmithKline Beecham. In clinical trials involving more than 10,000 people, the vaccine, called LYMErix, was found to confer protective immunity to Borrelia in 76% of adults and 100% of children with only mild or moderate and transient adverse effects.[126] LYMErix was approved on the basis of these trials by the Food and Drug Administration (FDA) on 21 December 1998.

text: Following approval of the vaccine, its entry in clinical practice was slow for a variety of reasons, including its cost, which was often not reimbursed by insurance companies.[127] Subsequently, hundreds of vaccine recipients reported they had developed autoimmune and other side effects. Supported by some patient advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline, alleging the vaccine had caused these health problems. These claims were investigated by the FDA and the Centers for Disease Control, which found no connection between the vaccine and the autoimmune complaints.[128]

text: Despite the lack of evidence that the complaints were caused by the vaccine, sales plummeted and LYMErix was withdrawn from the U.S. market by GlaxoSmithKline in February 2002,[129] in the setting of negative media coverage and fears of vaccine side effects.[128][130] The fate of LYMErix was described in the medical literature as a "cautionary tale";[130] an editorial in Nature cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations."[17] The original developer of the OspA vaccine at the Max Planck Institute told Nature: "This just shows how irrational the world can be... There was no scientific justification for the first OspA vaccine LYMErix being pulled."[128]

text: New vaccines are being researched using outer surface protein C (OspC) and glycolipoprotein as methods of immunization.[131][132] Vaccines have been formulated and approved for prevention of Lyme disease in dogs. Currently, three Lyme disease vaccines are available. LymeVax, formulated by Fort Dodge Laboratories, contains intact dead spirochetes which expose the host to the organism. Galaxy Lyme, Intervet-Schering-Plough's vaccine, targets proteins OspC and OspA. The OspC antibodies kill any of the bacteria that have not been killed by the OspA antibodies. Canine Recombinant Lyme, formulated by Merial, generates antibodies against the OspA protein so a tick feeding on a vaccinated dog draws in blood full of anti-OspA antibodies, which kill the spirochetes in the tick's gut before they are transmitted to the dog.[133]

text: Valneva's hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was granted fast track designation by the U.S. Food and Drug Administration in July 2017 which will allow further study.[134]

text: Tick removal

text: Attached ticks should be removed promptly, as removal within 36 hours can reduce transmission rates.[135] Folk remedies for tick removal tend to be ineffective, offer no advantages in preventing the transfer of disease, and may increase the risks of transmission or infection.[136] The best method is simply to pull the tick out with tweezers as close to the skin as possible, without twisting, and avoiding crushing the body of the tick or removing the head from the tick's body.[137] The risk of infection increases with the time the tick is attached, and if a tick is attached for less than 24 hours, infection is unlikely. However, since these ticks are very small, especially in the nymph stage, prompt detection is quite difficult.[135] The Australian Society of Clinical Immunology recommends against using tweezers to remove ticks but rather to kill the tick first by using a product to rapidly freeze the tick to prevent it from injecting more allergen-containing saliva. In a tick allergic person, the tick should be killed and removed in a safe place (e.g. an emergency department of a hospital).[138]

text: Preventive antibiotics

text: The risk of infectious transmission increases with the duration of tick attachment.[139] It requires between 36 and 48 hours of attachment for the bacteria that causes Lyme to travel from within the tick into its saliva.[139] If a deer tick that is sufficiently likely to be carrying Borrelia is found attached to a person and removed, and if the tick has been attached for 36 hours or is engorged, a single dose of doxycycline administered within the 72 hours after removal may reduce the risk of Lyme disease. It is not generally recommended for all people bitten, as development of infection is rare: about 50 bitten people would have to be treated this way to prevent one case of erythema migrans (i.e. the typical rash found in about 70-80% of people infected).[2][139]

text: Occupational exposure

text: Outdoor workers are at risk of Lyme disease if they work at sites with infected ticks. In 2010, the highest number of confirmed Lyme disease cases were reported from New Jersey, Pennsylvania, Wisconsin, New York, Massachusetts, Connecticut, Minnesota, Maryland, Virginia, New Hampshire, Delaware, and Maine. U.S. workers in the northeastern and north-central States are at highest risk of exposure to infected ticks. Ticks may also transmit other tick-borne diseases to workers in these and other regions of the country. Worksites with woods, bushes, high grass, or leaf litter are likely to have more ticks. Outdoor workers should be extra careful to protect themselves in the late spring and summer when young ticks are most active.[140]

text: Treatment

text: Antibiotics are the primary treatment.[2][139] The specific approach to their use is dependent on the individual affected and the stage of the disease.[139] For most people with early localized infection, oral administration of doxycycline is widely recommended as the first choice, as it is effective against not only Borrelia bacteria but also a variety of other illnesses carried by ticks.[139] Doxycycline is contraindicated in children younger than eight years of age and women who are pregnant or breastfeeding;[139] alternatives to doxycycline are amoxicillin, cefuroxime axetil, and azithromycin.[139] Individuals with early disseminated or late infection may have symptomatic cardiac disease, refractory Lyme arthritis, or neurologic symptoms like meningitis or encephalitis.[139] Intravenous administration of ceftriaxone is recommended as the first choice in these cases;[139] cefotaxime and doxycycline are available as alternatives.[139]

text: These treatment regimens last from one to four weeks.[139] If joint swelling persists or returns, a second round of antibiotics may be considered.[139] Outside of that, a prolonged antibiotic regimen lasting more than 28 days is not recommended as no clinical evidence shows it to be effective.[139][141] IgM and IgG antibody levels may be elevated for years even after successful treatment with antibiotics.[139] As antibody levels are not indicative of treatment success, testing for them is not recommended.[139]

text: Prognosis

text: For early cases, prompt[specify] treatment is usually curative.[142] However, the severity and treatment of Lyme disease may be complicated due to late diagnosis, failure of antibiotic treatment, and simultaneous infection with other tick-borne diseases (coinfections), including ehrlichiosis, babesiosis, and immune suppression[citation needed] in the patient.

text: It is believed that less than 5% of people have lingering symptoms of fatigue, pain, or joint and muscle aches at the time they finish treatment.[143] These symptoms can last for more than 6 months. This condition is called post-treatment lyme disease syndrome. As of 2016 the reason for the lingering symptoms was not known; the condition is generally managed similarly to fibromyalgia or chronic fatigue syndrome.[144]

text: In dogs, a serious long-term prognosis may result in glomerular disease,[145] which is a category of kidney damage that may cause chronic kidney disease.[133] Dogs may also experience chronic joint disease if the disease is left untreated. However, the majority of cases of Lyme disease in dogs result in a complete recovery with, and sometimes without, treatment with antibiotics.[146][verification needed] In rare cases, Lyme disease can be fatal to both humans and dogs.[147]

text: Epidemiology

text: Lyme disease occurs regularly in Northern Hemisphere temperate regions.[148]

text: Africa

text: In northern Africa, B. burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.[149][150][151]

text: Lyme disease in sub-Saharan Africa is presently unknown, but evidence indicates it may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.[152] In East Africa, two cases of Lyme disease have been reported in Kenya.[153]

text: Asia

text: B. burgdorferi sensu lato-infested ticks are being found more frequently in Japan, as well as in northwest China, Nepal, Thailand and far eastern Russia.[154][155] Borrelia has also been isolated in Mongolia.[156]

text: Europe

text: In Europe, Lyme disease is caused by infection with one or more pathogenic European genospecies of the spirochaete B. burgdorferi sensu lato, mainly transmitted by the tick Ixodes ricinus.[157] Cases of B. burgdorferi sensu lato-infected ticks are found predominantly in central Europe, particularly in Slovenia and Austria, but have been isolated in almost every country on the continent.[158] Incidence in southern Europe, such as Italy and Portugal, is much lower.[159]

text: United Kingdom

text: In the United Kingdom the number of laboratory confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986[160] when 68 cases were recorded in the UK and Republic of Ireland combined.[161] In the UK there were 23 confirmed cases in 1988 and 19 in 1990,[162] but 973 in 2009[160] and 953 in 2010.[163] Provisional figures for the first 3 quarters of 2011 show a 26% increase on the same period in 2010.[164]

text: It is thought, however, that the actual number of cases is significantly higher than suggested by the above figures, with the UK's Health Protection Agency estimating that there are between 2,000 and 3,000 cases per year,[163] (with an average of around 15% of the infections acquired overseas[160]), while Dr Darrel Ho-Yen, Director of the Scottish Toxoplasma Reference Laboratory and National Lyme Disease Testing Service, believes that the number of confirmed cases should be multiplied by 10 "to take account of wrongly diagnosed cases, tests giving false results, sufferers who weren't tested, people who are infected but not showing symptoms, failures to notify and infected individuals who don't consult a doctor."[165][166]

text: Despite Lyme disease (Borrelia burgdorferi infection) being a notifiable disease in Scotland[167] since January 1990[168] which should therefore be reported on the basis of clinical suspicion, it is believed that many GPs are unaware of the requirement.[169] Mandatory reporting, limited to laboratory test results only, was introduced throughout the UK in October 2010, under the Health Protection (Notification) Regulations 2010.[160]

text: Although there is a greater incidence of Lyme disease in the New Forest, Salisbury Plain, Exmoor, the South Downs, parts of Wiltshire and Berkshire, Thetford Forest[170] and the West coast and islands of Scotland[171] infected ticks are widespread, and can even be found in the parks of London.[162][172] A 1989 report found that 25% of forestry workers in the New Forest were seropositive, as were between 2% and 4-5% of the general local population of the area.[173][174]

text: Tests on pet dogs, carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought.[175][176] It is thought that global warming may lead to an increase in tick activity in the future, as well as an increase in the amount of time that people spend in public parks, thus increasing the risk of infection.[177]

text: North America

text: Many studies in North America have examined ecological and environmental correlates of Lyme disease prevalence. A 2005 study using climate suitability modelling of I. scapularis projected that climate change would cause an overall 213% increase in suitable vector habitat by the year 2080, with northward expansions in Canada, increased suitability in the central U.S., and decreased suitable habitat and vector retraction in the southern U.S.[178] A 2008 review of published studies concluded that the presence of forests or forested areas was the only variable that consistently elevated the risk of Lyme disease whereas other environmental variables showed little or no concordance between studies.[179] The authors argued that the factors influencing tick density and human risk between sites are still poorly understood, and that future studies should be conducted over longer time periods, become more standardized across regions, and incorporate existing knowledge of regional Lyme disease ecology.[179]

text: Canada

text: Owing to changing climate, the range of ticks able to carry Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, southern New Brunswick, southwest Nova Scotia and limited parts of Saskatchewan and Alberta, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland.[180][181][182] A model-based prediction by Leighton et al. (2012) suggests that the range of the I. scapularis tick will expand into Canada by 46 km/year over the next decade, with warming climatic temperatures as the main driver of increased speed of spread.[183]

text: Mexico

text: A 2007 study suggests Borrelia burgdorferi infections are endemic to Mexico, from four cases reported between 1999 and 2000.[184]

text: United States

text: Each year, approximately 30,000 new cases are reported to the CDC however, this number is likely underestimated. The CDC is currently conducting research on evaluation and diagnostics of the disease and preliminary results suggest the number of new cases to be around 300,000.[185][186]

text: Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.[187][188][189]

text: Although Lyme disease has been reported in all states[185][190] about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central).[191] New 2011 CDC Lyme case definition guidelines are used to determine confirmed CDC surveillance cases.[192]

text: Effective January 2008, the CDC gives equal weight to laboratory evidence from 1) a positive culture for B. burgdorferi; 2) two-tier testing (ELISA screening and Western blot confirming); or 3) single-tier IgG (old infection) Western blot.[193] Previously, the CDC only included laboratory evidence based on (1) and (2) in their surveillance case definition. The case definition now includes the use of Western blot without prior ELISA screen.[193]

text: The number of reported cases of the disease has been increasing, as are endemic regions in North America. For example, B. burgdorferi sensu lato was previously thought to be hindered in its ability to be maintained in an enzootic cycle in California, because it was assumed the large lizard population would dilute the prevalence of B. burgdorferi in local tick populations; this has since been brought into question, as some evidence has suggested lizards can become infected.[194]

text: Except for one study in Europe,[195] much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated lizards are able to infect ticks feeding upon them.[194][196][197][198] As some experiments suggest lizards are refractory to infection with Borrelia, it appears likely their involvement in the enzootic cycle is more complex and species-specific.[55]

text: While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice, Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, and Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association.[citation needed]

text: Several similar but apparently distinct conditions may exist, caused by various species or subspecies of Borrelia in North America. A regionally restricted condition that may be related to Borrelia infection is southern tick-associated rash illness (STARI), also known as Masters' disease. Amblyomma americanum, known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so patients in these regions experiencing Lyme-like symptoms—especially if they follow a bite from a lone-star tick—should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment.[citation needed]

text: In recent years there have been 5 to 10 cases a year of a disease similar to Lyme occurring in Montana. It occurs primarily in pockets along the Yellowstone River in central Montana. People have developed a red bull's-eye rash around a tick bite followed by weeks of fatigue and a fever.[190]

text: Lyme disease prevalence is comparable among males and females. A wide range of age groups is affected, though the number of cases is highest among 10- to 19-year-olds. For unknown reasons, Lyme disease is seven times more common among Asians.[199]

text: South America

text: In South America, tick-borne disease recognition and occurrence is rising. In Brazil, a Lyme-like disease known as Baggio–Yoshinari syndrome was identified, caused by microorganisms that do not belong to the B. burgdorferi sensu lato complex and transmitted by ticks of the Amblyomma and Rhipicephalus genera.[200] The first reported case of BYS in Brazil was made in 1992 in Cotia, São Paulo.[201] B. burgdorferi sensu stricto antigens in patients have been identified in Colombia and Bolivia.[citation needed]

text: History

text: The evolutionary history of Borrelia burgdorferi genetics has been the subject of recent studies. One study has found that prior to the reforestation that accompanied post-colonial farm abandonment in New England and the wholesale migration into the mid-west that occurred during the early 19th century, Lyme disease was present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest.[202]

text: John Josselyn, who visited New England in 1638 and again from 1663–1670, wrote "there be infinite numbers of tikes hanging upon the bushes in summer time that will cleave to man's garments and creep into his breeches eating themselves in a short time into the very flesh of a man. I have seen the stockins of those that have gone through the woods covered with them."[203]

text: This is also confirmed by the writings of Peter Kalm, a Swedish botanist who was sent to America by Linnaeus, and who found the forests of New York "abound" with ticks when he visited in 1749. When Kalm's journey was retraced 100 years later, the forests were gone and the Lyme bacterium had probably become isolated to a few pockets along the northeast coast, Wisconsin, and Minnesota.[204]

text: Perhaps the first detailed description of what is now known as Lyme disease appeared in the writings of Reverend Dr. John Walker after a visit to the Island of Jura (Deer Island) off the west coast of Scotland in 1764.[205] He gives a good description both of the symptoms of Lyme disease (with "exquisite pain [in] the interior parts of the limbs") and of the tick vector itself, which he describes as a "worm" with a body which is "of a reddish colour and of a compressed shape with a row of feet on each side" that "penetrates the skin". Many people from this area of Great Britain emigrated to North America between 1717 and the end of the 18th century.

text: The examination of preserved museum specimens has found Borrelia DNA in an infected Ixodes ricinus tick from Germany that dates back to 1884, and from an infected mouse from Cape Cod that died in 1894.[204] The 2010 autopsy of Ötzi the Iceman, a 5,300-year-old mummy, revealed the presence of the DNA sequence of Borrelia burgdorferi making him the earliest known human with Lyme disease.[206]

text: The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Breslau, Germany (now Wrocław, Poland), where physician Alfred Buchwald described a man who had suffered for 16 years with a degenerative skin disorder now known as acrodermatitis chronica atrophicans.[207]

text: At a 1909 research conference, Swedish dermatologist Arvid Afzelius presented a study about an expanding, ring-like lesion he had observed in an older woman following the bite of a sheep tick. He named the lesion erythema migrans.[207] The skin condition now known as borrelial lymphocytoma was first described in 1911.[208]

text: The modern history of medical understanding of the disease, including its cause, diagnosis, and treatment, has been difficult.[209]

text: Neurological problems following tick bites were recognized starting in the 1920s. French physicians Garin and Bujadoux described a farmer with a painful sensory radiculitis accompanied by mild meningitis following a tick bite. A large, ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. In 1930, the Swedish dermatologist Sven Hellerström was the first to propose EM and neurological symptoms following a tick bite were related.[210] In the 1940s, German neurologist Alfred Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

text: Carl Lennhoff, who worked at the Karolinska Institute in Sweden, believed many skin conditions were caused by spirochetes. In 1948, he used a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM.[211] Although his conclusions were later shown to be erroneous, interest in the study of spirochetes was sparked. In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin.[212] In the 1950s, the relationship among tick bite, lymphocytoma, EM and Bannwarth's syndrome was recognized throughout Europe leading to the widespread use of penicillin for treatment in Europe.[213][214]

text: In 1970, a dermatologist in Wisconsin named Rudolph Scrimenti recognized an EM lesion in a patient after recalling a paper by Hellerström that had been reprinted in an American science journal in 1950. This was the first documented case of EM in the United States. Based on the European literature, he treated the patient with penicillin.[215]

text: The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns Lyme and Old Lyme, which gave the disease its popular name.[216] This was investigated by physicians David Snydman and Allen Steere of the Epidemic Intelligence Service, and by others from Yale University, including Dr. Stephen Malawista, who is credited as a co-discover of the disease.[217] The recognition that the patients in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe.[218]

text: Before 1976, the elements of B. burgdorferi sensu lato infection were called or known as tick-borne meningopolyneuritis, Garin-Bujadoux syndrome, Bannwarth syndrome, Afzelius' disease,[219] Montauk Knee or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease,[220][221] Lyme borreliosis or simply borreliosis.[citation needed]

text: In 1980, Steere, et al., began to test antibiotic regimens in adult patients with Lyme disease.[222] In the same year, New York State Health Dept. epidemiologist Jorge Benach provided Willy Burgdorfer, a researcher at the Rocky Mountain Biological Laboratory, with collections of I. dammini [scapularis] from Shelter Island, NY, a known Lyme-endemic area as part of an ongoing investigation of Rocky Mountain spotted fever. In examining the ticks for rickettsiae, Burgdorfer noticed "poorly stained, rather long, irregularly coiled spirochetes." Further examination revealed spirochetes in 60% of the ticks. Burgdorfer credited his familiarity with the European literature for his realization that the spirochetes might be the "long-sought cause of ECM and Lyme disease." Benach supplied him with more ticks from Shelter Island and sera from patients diagnosed with Lyme disease. University of Texas Health Science Center researcher Alan Barbour "offered his expertise to culture and immunochemically characterize the organism." Burgdorfer subsequently confirmed his discovery by isolating, from patients with Lyme disease, spirochetes identical to those found in ticks.[223] In June 1982, he published his findings in Science, and the spirochete was named Borrelia burgdorferi in his honor.[224]

text: After the identification of B. burgdorferi as the causative agent of Lyme disease, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics, amoxicillin, cefuroxime axetil, intravenous and intramuscular penicillin and intravenous ceftriaxone.[225][226] The mechanism of tick transmission was also the subject of much discussion. B. burgdorferi spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands.[227]

text: Society and culture

text: Urbanization and other anthropogenic factors can be implicated in the spread of Lyme disease to humans. In many areas, expansion of suburban neighborhoods has led to gradual deforestation of surrounding wooded areas and increased border contact between humans and tick-dense areas. Human expansion has also resulted in a reduction of predators that hunt deer as well as mice, chipmunks and other small rodents—the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission of the disease has greatly increased.[228][229] Researchers are investigating possible links between global warming and the spread of vector-borne diseases, including Lyme disease.[230]

text: Controversy

text: The term "chronic Lyme disease" is controversial and not recognized in the medical literature,[231] and most medical authorities advise against long-term antibiotic treatment for Lyme disease.[91][232][233] Studies have shown that most people diagnosed with "chronic Lyme disease" either have no objective evidence of previous or current infection with B. burgdorferi or are people who should be classified as having post-treatment Lyme disease syndrome (PTLDS), which is defined as continuing or relapsing non-specific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a person previously treated for Lyme disease.[234]

text: Other animals

text: Prevention of Lyme disease is an important step in keeping dogs safe in endemic areas. Prevention education and a number of preventative measures are available. First, for dog owners who live near or who often frequent tick-infested areas, routine vaccinations of their dogs is an important step.[235]

text: Another crucial preventive measure is the use of persistent acaricides, such as topical repellents or pesticides that contain triazapentadienes (Amitraz), phenylpyrazoles (Fipronil), or permethrin (pyrethroids).[236] These acaricides target primarily the adult stages of Lyme-carrying ticks and reduce the number of reproductively active ticks in the environment.[235] Formulations of these ingredients are available in a variety of topical forms, including spot-ons, sprays, powders, impregnated collars, solutions, and shampoos.[236]

text: Examination of a dog for ticks after being in a tick-infested area is an important precautionary measure to take in the prevention of Lyme disease. Key spots to examine include the head, neck, and ears.[237]

text: Research

text: The National Institutes of Health have supported research into bacterial persistence.[238]