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Leptospirosis in New Zealand pig herds : an epidemiological study and a computer simulation model of endemic leptospiral infection in New Zealand with particular reference to Leptospira interrogans serovar pomona : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University

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LEPTOSPIROSIS IN NEW ZEALAND PIG HERDS An epidemiological s tudy and a computer simulation model

of endemic leptospiral infection in New Zealand pig herds,

with

p a r ticula r reference t o

Leptospira interrogans serovar pomona .

A thesis p resented i n p a rtial fulfilment of t h e requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University.

Ingeborg Bolt 1 990

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ABSTRACT

A serological s urvey of pig sera from six regional areas throughout New Zealand indicated that 60% h a d titres to Leptospira interrogans serovar pomona and 1 3 % to serovar tarassovi. Pig sera fro m the North Island districts had higher titres to pomona than t hose fro m the South Island districts, however the converse was true for titres to tarassovi. A serological s urvey of bacon weight pigs a t slaughter revealed that 60% had titres to pomona, 53% to bratislava, while titres to tarassovi were undetectable. The¥e

was no significant linear association between the magnitude of corresponding pomona and bratislava titres. Pomona was isolated from 53% of pigs

kidneys, however attempts to isolate bratislava were unsuccessful. The median prevalence of infection in bacon pigs from fa rms with endemic pomona infection, a t the time of slaughter was 80%. A retrospective s tudy of farming practices revealed that vaccination of breeding pigs had no effect o n the infection status o f their grower pigs at slaughter. It was also found that farms which reared their grower pigs to pork weight for slaughter were free o f leptospiral infection, as were farms with less than fifty breeding sows.

Cross s ectional serological and cultural p revalence studies o f grower pigs on farms with endemic pomona infection revealed that pigs less than ten weeks o f age were not leptospi ruric and had low or undetectable ti tres to pomona.

Pigs b etween ten and twenty weeks of age showed an increasing p revalence o f both leptospiru ria and pomona titres. Fu rther p rospective studies indicated that piglets acquire passive immunity from their dams, which h as a half life o f a round sixteen d ays. The majority of pigs less than fou rteen weeks of age appear to be resistant to infection, thereafter the level o f their p assive immunity wanes and they become infected and leptospiruric. The weekly incidence of leptospiruria for pigs in an infected grower house was usually between 10% and 20%. Following infection, the intensity of leptospiruria was greatest in the first three to fou r weeks and it l as ted for at least s ix weeks . Infection is bel ieved to occur by both d irect and indirect transmission of leptospires between infected and susceptible pigs. I t was s hown that grower pigs are a t the centre of the endemic cycle o f infection which is perpetuated by the trans mission of infection fro m older infected pigs to you nger s usceptible pigs . This cycle o f endemic infection can persist independen tly o f the breeding herd.

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iii Experimental evidence following the artificial exposure o f grower p igs to e i t he r serovar pomona or bratislava supported an hypothesis that the occurrence o f bratislava titres were associated with early i n fection of p igs w i t h serovar pomona . The heterologous t itres were believed to be a s erological cross reaction with homologous IgM antibody to which p igs had been exposed .

Experimental evidence demonstrated that leptospires could survive i n droplets of less t h a n 50 urn, however hamsters exposed to a leptospiral a e rosol containing droplets o f less than 50 urn failed t o become infected.

Infection via the intranasal route i n both hamsters and p igs showed that the i n fective dose of pomona was between 104 and 1 06 leptospires, i ndicating the intranasal route as a natural route for infection. Transmission o f infection could therefore occur d irectly by infective droplets lodging in the nasal cavity.

The vaccination of pigs, com m encing at ten weeks of age o n a farm with endemic pomona infection, revealed t h a t m ultiple i noculations o f a commercially available b acterin can be used to control the level of endemic i n fection within a grower pig herd. There was evidence to suggest t h a t persistent passive immunity i n young pigs could interfere w i t h t h e efficacy o f vaccination.

A computer s imulation model of endemic pomona infection in a pig herd [Simulated Leptospiral Infection within a Pig herd, S LIP89] was d eveloped using the results of invest igations described in this thesis by sequentially breo.king down the cycle of endemic pomona infection into a series o f logical events. The model repeats a number o f p redetermined i ndependent and dependant even ts for each pig within a simulated herd. The o u tcome of each even t is randomly determined fro m an appropriately selected probability distribution. Each cycle o f repetition represents one week in time. The o utcome generated by the s i m u l ation can be used to obse rve varying patterns o f i n fection which a re due to either the element of chance o r the alteration o f k ey variables within the model . The results generated by the SLIP89 must b e viewed with the s tructure and l imitations of the model i n mind.

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ACKNOWLEDGEMENTS

I wish to acknowledge the fin a ncial s upport given by the Wom e n 's D ivision of Federated Farmers who funded this research, the P hyllis Irene Grey Fel lowship Fund which provided a computer and the Muriel Caddie Schol a rs h i p for personal funding. The p rovision of animal remedies fro m Coop ers Animal Health is appreciated .

I would l ike to thank my supervisors D r Roger Marshall for his encouragement, enthusiasm and patienc� throughout the period o f research and documentation, Professor Roger Mo r ris for his guidance throughout the development of the computer simulation model, and to Professor D avid Blackmore for his initiation o f the rese a rch p roj ect, his interest, constructive criticism and advice during his final years at Massey Universi ty.

Spec i a l tha nks to friends and eo-workers Ray Corner and Steve Flint for their help with the collection o f sam ples and for providing valid a rgument and d iscussion. I thank Wendy Gable for her support in the laboratory, Jan Schr a m a for her work i n the media preparation room, Peter Wildbore for ordering a l l materials, Pam Slack for the preparing h is to logical sections, Faris S h arpe for incinerating infective tissue and material, D r . Ram adass for the B R E NDA typing of leptospires, and the help of Fio na D icki nson with preparation of the final draft of this thesis.

I a m grateful to the management and employees of the Kiwi Bacon Comp any o f L ongburn for their co-operation in allowing the collection o f samp les fro m t h e i r abattoir. I wo uld l ike to thank t h e managers and workers o f all the p i g farms which were contacted througho u t t h i s study, with special thanks to P h i l Weber, N e i l Managh a n d A l a n Taylo r for their long t e r m assistance.

Finally, I wish to thank my husband B rad Bridges for his encouragement and support, his sense of humour and love, all o f which helped sustain me throughout this study. I am grate fu l that our son, Bear n a rd , who was born i n t h e later stages o f the prep aration of this thesis, proved to be a h a p py and contented child, and one who accept ed my divided attention.

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V

TAB LE OF C O NTENTS

Abs tract . . . i i

Acknowledgements . . . iv

Table of contents . . . v

List of Tab les . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi

List of Figures . . . xi

Chapter O n e Introduction . . . 1

Chapter Two Chapter Three Chapter Fou r Chapter Five Materials and Methods. . . 24

Prevalence Studies of Lep tospiral Infection in Pigs . . . 48

Observational Studies . . . 74

Experimental Studies . . . 1 20 Chapter Six Vaccination Trials . . . 160

Chapter S even A Computer Simul ation Model of Endemic Appendix I Appendix 11 Appendix Ill Appendix I V Appendix V Appendix VI Leptospiral Infection i n a Pig Herd . . . 2 1 2 Preparation o f Media Conversion of Titres 253 257 Questionnaire to Farmers . . . 258

Procedure for using S LIP89 . . . 260

List of SLIP89 data files . . . 278

Program Units i n S LIP89 . . . 279

References . . . 3 2 1

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Chapter O n e 1 . 1

Chapter Two 2 . 1

2.2

2 . 3

2 . 4

C hapter Three 3 . 1

3 .2

3 . 3

3 .4

3 .5

3 . 6

3 .7

LIST O F TABLES

Maintenance hosts for leptospiral serovars

found in New Zealand . . . 1 8

Fina l test dilutions o f s e r u m samples i n the

microtitre plates used for t he MAT . . . . . . . . . . . 3 7 Leptospiral serovars main tained for the

Microscopic Agglutination Test . . . 40

T h e o r e t i c a l n u m b e r of l e p t o s p i r e s inoculated into five cul ture dilutions of

u rine . . . . . . . 41 Number of th ree u rine cultures from which

leptospires were isolated a fter two and fou r

weeks o f incuba tion . . . 42

Serological results for serovar pomona o f pigs from s i x MAF admin istrative dist ricts

of New Zealand . . . 55 Serological results for serovar tarassovi of

pigs from s ix MAF administra tive dis tricts

of New Zealand . . . 56 Distribution of pomona a nd bratislava titres

of grower p igs at slaughter . . . 59 Serological and cultu ral res ults of twenty­

two bacon weight p igs sampled at

slaughter . . . 60 A comparison of some farm p ractises and

the infection status o f their pigs, for twelve

farms . . . . . . . . . . . . . . . . . . . . . . . . 64 Sizes of twelve farms in comparison with the

infectious status o f their grower pigs at sla ughter and the vaccination s tatus of their

breeding pigs . . . 65 Number of fa rms wi thin each district with

near equal or u neven ratios o f

pomona:tarassovi titres . . . 67

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Chapter Fou r 4. 1

4 . 2

4 . 3

4 . 4

4 . 5

4 . 6

4 . 7

4 . 8

4 . 9

4 . 10

Chapter Five 5 . 1

5.2

Serological and cultural prevalence o f i nfection with pomona i n g rower pigs fro m

vii

Farm B . . . . . . 85 Serological and cultural prevalence of infection

with pomona in grower pigs fro m Farm D . . . 86

Schedule of sero logical and cultural examination of fou r age cohorts over an

eleven week period . . . 90 Serological results to serovar pomona of two

sows and five of their piglets between five

and thirty-fo u r d ays of age . . . 9 1 Serological results to serovar pomona o f

pigs between six a n d fifteen weeks of a g e i n

the "weaner coho rt" . . . 93 Serological and cultural results to serovar

pomona of pigs between e leven and twenty­

one weeks of age in the "young grower

cohort" . . . 95 Serological and cultural results to serovar

pomona of p igs between s ixteen and twenty­

six weeks of a ge in the "older grower

cohort" . . . 98 Mixing and movement of pigs between pens,

and the infectious status of pigs in adj acen t pens . . . . Onset and duratio n o f leptospiruria i n grower p igs fro m Farm B

Culture results and location of gilts o n Far m

. . . 1 0 1

. . . 1 02 - 1 0 3

B a t the t ime o f exa mination . . . 1 04

Homologous pomona t itres of pigs exposed to serovar pomona by intramuscul a r

inoculation or v i a the i n tranasal route . . . 1 27 Heterologous bratislava t itres of p igs

exposed to serovar pomona by intramuscul a r

i noculation or via the i ntranasal route . . . 1 2 9

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5 . 3

5 .4

5 .5

5 .6

5 . 7

5 . 8

5 . 9

5 . 1 0 5 . 1 1

5 . 1 2

5 . 1 3

Chapter Six 6 . 1

6.2

6.3

Geometric mean t i tres [GMT] of pigs

artificially exposed t o serovar pomona . . . 129 Homologo us bratislava titres of p igs exposed

to serovar bratislava by intramuscular

inocu l a tion or via the i n tranasal route . . . 1 3 0 Heterologous pomona t i tres o f pigs exposed

to serovar bratislava by intramuscular

inoculation or via the intranasal route . . . 1 3 0 Geometrical mean t it res [GMT] of pigs

artificially exposed to serovar bratislava . . . 1 3 1 Homogenous and heterologous heat treated

and untreated titres o f pigs exposed to

pomona and bratislava . . . 1 3 2 O n s e t , d u r a t i o n a n d i n te n s i ty o f

leptos piruria determined by cultural

examination . . . 1 3 3

Diameter o f droplets formed by spinning

disc . . . . 1 48 Diameter of droplets by nebuliser . . . . 1 49 Minimum infective dose of pomona for pigs

via the intranasal route . . . 150 Minimum infective dose of pomona for

hamsters via the i n tranasal route . . . 1 5 1

Results o f exposing o f h amsters t o pomona

via the res piratory route using an aerosol . . . 152

Regimes of inoculation tested in grower

pigs . . . . . . . 1 7 1

Number o f p igs examined i n each inoculation group fro m Farm B throughout the period o f s ampling and a t the time of

slaughter . . . 173

Reciprocal titres o f p igs inoculated with vaccine i n the first week [Group 1 ] which were raised o n the far m free of leptospiral

i nfection [Farm A] . . . 1 77

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6 . 4

6 . 5

6.6

6.7

6.8

6.9

6 . 1 0

Chapter Seven

7 . 1 7.2

7.3

Recip rocal t i tres and kidney culture results for p igs inoculated with vaccine i n the first week [Gro u p 1] and u nvaccinated pigs [con trol group] which were raised on the farm with endemic pomona infection [Farm

ix

B] . . . 1 78 Recip rocal titres o f pigs inoculated with

vaccination in the first and fifth week [Group 2] which were r a ised on the far m

free of leptospiral i n fection [Farm A] . . . 1 82

Reciprocal t itres and kidney culture results for pigs inoculated i n the first and fifth week [ Group 2] and u nvaccinated pigs [contro l group] which were fro m the farm

with endemic pomona i n fection [Farm B] . . . 183 Reciprocal titres o f pigs inoculated with

vaccine in the first, third and fifth week [Group 3 ] which were from the farm free o f

leptospiral infection [Farm A] . . . 187 Reciprocal titres and kid ney culture results

for p igs inocul ated with vaccine i n the first, third and fifth week [Group 3] and unvaccinated p igs [co ntrol group] which were from the farm with endemic pomona

infection [Farm B] . . . 188

Reciprocal titres of pigs inoculated with vaccine in the first, second and third week [Group 4] which were from the farm free of

leptospiral infection [Fa rm A] . . . 192 Reciprocal titres and kidney culture resu lts

for pigs inoculated with vaccine in the first, second and third week [ Group 4] and u nvaccinated p igs [control group] which were from the fa rm with endemic pomona

infection [Farm B] . . . 1 9 3

Age related m ating frequency for boars . . . 22 1 The average p revalence of leptospiral

i n fection for grower p igs in SLIP89, using

the default sett ings . . . 23 9

S LIP89 results o f the average prevalence o f

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7 . 4

7 . 5

7 . 6

7 . 7

leptospiral infection i n grower pigs, when

validating for weaning age . . . 240

SLIP89 results of the average prevalence of leptospiral infection in grower pigs, when

validating for the d uration of leptospiruria . . . . . . 242 SLIP89 results of the aver age p revalence of

leptospiral i nfection i n grower pigs, when

validating for the i ntensity of leptospiruria . . . 243 SLIP89 results of the average prevalence o f

leptospiral infection i n g rower pigs, when validating for the contamination division

factors . . . 245 SLIP89 results of the aver age prevalence o f

infection for validation o f contact between

pigs . . . 246

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Chapter 2

2. 1

2.2

2.3 2 . 4

2 . 5

Chapter 3 3 . 1

3 .2

3 . 3

3 . 4

3 .5

Chapter 4

4 . 1 4 . 2 4 . 3 4 . 4

xi LIST OF FIGURES

Collection o f a blood sample by jugular

bleeding . . . 27 Collection of a midstream urine sample . . . . . . . 28

Kidn ey culture p rocedure . . . 3 2 Urine culture procedure . . . . 3 3 Equ ations to convert reciprocal titre to a

coded titre unit [CTU] and CTU to a

reciprocal titre . . . 3 8

The six MAF administrative districts o f New Zealand used in the serological survey o f pomona a n d tarassovi ti tres of pigs

thro ughout New Zealand . . . 52 Serological resu lts for s erovar pomona of

pigs from six MAF administrative districts

of New Zealand . . . 53 Serological resu lts for serovar tarassovi of

pigs from s ix MAF administrative districts

of New Zealand . . . . . . . 54 Frequency distribution of pomona and

bratislava titres in 140 b acon weight pigs at

slaughter . . . 58 Distribution of pomona t itres in grower p igs

at slaughter fro m farms which either do or

do not vaccinate their b reeding pigs . . . 63

Design of piggery o n farm B . . . . . . . . . . . . . 8 1 Design o f p iggery o n fa rm D . . . . . . . 82 Design of piggery o n farm E . . . 83 Intensity of leptospiruria in naturally

infected pigs over a ten week period o f

examination . . . . . . . 97

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4.5

4.6

4.7

4.8

4.9

4 . 1 0

4. 1 1

4 . 1 2

Chapter 5 5 . 1

5.2

5.3

5.4

5 . 5

5.6

Geometric mean t itre of pomona i n grower pigs fro m Farm C with endemic pomona

infection . . . 97 Schematic representation of movement of a

grou p of pigs througho u t the grower shed

on Far m B over a period of 1 6 weeks . . . 1 05

Schematic representatio n of the movement of two individual p igs BG- 1 and BB-2 throughout the grower s hed o n Fa rm B for

a period of 1 6 weeks . . . 1 06- 1 07

Average prevalence of leptospiruria i n 3

groups of n aturally infected grower pigs . . . 1 08 Prevalence of leptospiruria i n the pig herd

fro m Farm B with endemic pomona

infection . . . 1 09 Decline of matern al antibody titres i n p igs . . 1 1 1 Age of onset of leptospiruria i n grower p igs

of Farms B and C . . . 1 1 2 Cycle of maintenance of infection with

pomona in a grower pig herd . . . 1 16

Pom ona and bratislava titres of pigs

artificially exposed to s erovar pomona . . . 1 28 Bratislava and pomona titres

artificially exposed to bratislava of p igs Homogenous and heterologous pomona and bratislava titres o f heat treated and u ntreated sera

Spinn ing disc used for the formation of

. . . 128

. . . 1 3 1

d rops greater t h a n 5 0 JL m i n d i ameter . . . 1 43 Nebuliser used for the formation of droplets

less than 50 JLm i n d i a meter . . . 144 S ize of droplets landing in pen adj acent to

pen which was spray hosed . . . 150

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5 . 7

5 . 8

5 . 9 5 . 10

Chapter 6

6 . 1

6 . 2

6.3

6.4

6.5

6.6

6.7

xiii Theoretical m aximum n umber of leptospires

in a drop of known d i ameter . . . 1 54 Theoretical percentage o f drops formed

from two leptospiral concentrations which contain at least one leptospira . . . . Pigs "rooting" amongst i n fective effluent . . . Pigs "urine sniffing", a behaviour allowing

1 5 5 156

i nfection via the intranasal route . . . 1 57

Serological results o f p igs raised on the farm free of leptosp i ral infection [Farm A]

which were inocula ted with vaccine in the

first week only [Group 1] . . . 1 76 Serological resu lts o f pigs raised on the

farm with endemic pomona infection [Farm B] which were inocul ated with vaccine i n

t h e first week [Gro u p 1 ] . . . 1 76 Serological results of pigs raised on the

farm free of leptospiral infection [Farm A]

which were inocu l ated with vaccine i n the

first and fifth week [Group 2] . . . 1 8 1 Serological results of pigs raised o n the

far m with endemic pomona infection [Farm B] which were inocul ated in the first and

fifth week [Group 2] . . . 1 8 1 Serological resu l ts o f p igs raised o n the

farm fre e o f leptospiral i nfection [Farm A]

which were inocul a ted with vaccine i n the

first, third and fifth week [Group 3] . . . 1 86 Serological results o f pigs raised on the

farm with endemic pomona infection [Fa r m B] which were inoculated with vaccine i n

t h e first, third and fifth week [Group 2 ] . . . 1 86 Serological results o f p igs raised o n the

far m free o f leptospiral infection [Farm A]

which were inoculated with vaccine i n the

first, second and third week [Group 4] . . . 1 9 1

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6 . 8

6 . 9 a - d

6. 1 0

6 . 1 1

6 . 1 2

6 . 1 3

6 . 1 4

6 . 1 5

6 . 1 6

Chapter 7 7 . 1

7 . 2 7 . 3 a

7 .3b

Serological results of p igs r aised on the farm with endemic pomona i n fection [Farm B] which were inoculated with vaccine i n

the first, second and third week [Group 4] . . . 1 9 1 Proportion o f kidneys from v accinated and

u nvaccinated p igs fro m which leptospires

were isolated . . . 1 94 Percentage of pigs i n a p opulation with

residual m a ternal antibody . . . 200 Nomograph indicating optimum times for

the commencement of vaccination of p igs with a pomona vaccine, based on the a ntibody ti tre of the dam and a half life of

s ixteen days . . . 201

" Windows o f s usceptibility" for a population o f pigs, indicating the optimum age r ange

for the commencement o f vaccination . . . 202 Distribution of pomona titres of p igs

i noculated once and of u nvaccinated pigs at

s laughter . . . 204 Distribution of pomona titres of pigs

i noculated twice, and of u nvaccinated pigs

at slaughter . . . 204

Distribution of pomona ti tres of pigs inoculated three times at two weekly intervals, and of u nvaccinated pigs at

slaughter . . . 205 Distribution of pomona titres of pigs

inoculated t hree times at weekly intervals,

and of unvaccinated pigs a t slaughter . . . 205

Pathways for the transm ission of infection between pigs in SLIP89 . . . . Flow D iagram of S LIP89 . . . . SLIP89 data records for sows and boars . . . SLIP89 d a t a records for grower pigs . . .

2 1 6 2 1 8

220 222

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7 . 4

7 . 5 a 7 .5b

7 . 6

7 . 7

7 . 8

7 . 9

7 . 1 0

7 . 1 1

Appendix IV A4 . 1

A4.2

A4.3

A4.4

A4. 5 A4.6 A4. 7

A4.8

A4.9

XV

Floor plan of weaner and grower houses i n

SLIP89 . . . 223 Normal distribution o f post-infection titres

The distribution of post-infection titres after a pp lying minimum and m aximum titre

224

restrictions . . . 225 The simulated increase o f p igs titres

following infection in S LIP89 . . . 226

P a t hw a ys fo r d i re c t a n d i n d i r e c t t r ansmission of infection between pigs i n

SLIP89 . . . 229 The preval ence of infection in grower p igs

for SLIP89 d a t a and field d a t a . . . 236 The pomona t itres of grower pigs for

S LIP89 data and field d a t a . . . 237 The prevalence o f lep tospiruria for

popu lations of pigs i n S LIP89 data and field

d a ta . . . 238

P revalence of infection in grower p igs

following simulated vaccination . . . 250

Main menu and sub-menus of SLIP89 . . . 261 Reproductive variables s ubmenu option of

SLIP89 . . . 262 Epidemiological variables sub-menu o p tion

o f SLIP89 . . . 263 SLIP89 sub-menu option for executing

SLIP89 . . . 266 Output Files submenu o f SLIP89 . . . 270 Cohort Data submenu o f S LIP89 . . . 272 Time Series Display submenu option of

SLIP89 . . . 274

Age Data submenu option of SLIP89 275

Pen D a t a submenu option of SLIP89 276

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Appendix VI A6. 1

A6. 1

Flow Chart of interaction between SLIP89

p rogram units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 Summary of the interaction of program

p rocedures within the WKUPDATE and

R UNSLIP units . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307

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