infections in homeless : a marker of poverty

Lice and insecticide resistance ESCMID European Course

Marseille 2014

Pr Philippe BROUQUI & Rezack DRALI Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes

URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095,

IHU Méditérranée Infection , Marseille

ESCMID Online Lecture Library

© by author

Executive summary

• Human Lice – Biology

• Definition and life style • Impact and epidemiology

– History • Ancient and modern history

– Medical importance • Typhus, recurrent fever, trench fever

– Pest control • Toward eradication

– Hygiene – Ivermectine – perythroid

– Resistance • Clinical resistance • Biology and genomic resistance

– Future direction – Evaluation of the presentation

2


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The Louse biology

3


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The Human Louse

– Head louse • Lives in hair

• Nits are glued to hair

– Body Louse • Morphologically identical

• Lives in clothes

– Crab Louse • Pubis

• Armpits

• Eyelashes


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FILM/pou me mvt diapor.mpg

Body Louse

• Reproductive Biology • Females lay about 8 eggs a day

• Daily mating is needed as there is no spermatheca

• A pair of mating lice can generate 200 lice during their live


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The Body louse

• Biology • Eggs laid in the folds of clothing

• Eggs hatch on day 6-9

• Eggs live never exceed 16 days

• Growing louse molts 3 times L1,L2,L3, at D3, D5 and D10

• Adults lives another 20 days

• Optimal temperature 29-32°C

• Optimal humidity 70-90%

• Feed exclusively on human – five times a day

6


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The Body Louse :diagnosis

• Homeless interview – Most of them denied be infested

by louse

• Look for scratch skin lesion – On the neck and trunk

• Search for nits, larvae and adults – In clothes folds

– Infestation can rank from few to more than 300 individuals


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The Body louse

• Epidemiology – Consequently

• Louse lives in clothes and not onto the skin

• Louse leaves febrile host

– Presence of lice are determined by

• Climate

– Low temperature

– Poverty

– Promiscuity

• The lack of clothing hygiene – which does not allow to change clothes

– War, refugee camps and homeless

8


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The Body Louse in the Laboratory

• Laboratory colony

– Breed on human skin

– Rabbit

– Bloody cotton


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FILM/Pou mange sur DR.mpg

FILM/Pou mange sur lapin.mpg

The Head louse

• Factors for head louse infestation • Sex, age, socioeconomic status, poverty,

crowding but not length of hair.

• Prevalence of simultaneous Body/Head infection in Nepalese street Childs as high as 60%

• Ex vivo breeding

– Human Skin

10


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The Head louse

• Not yet recognized to transmit Infectious agent

• Bartonella quintana DNA in adults and nits

• Trans-ovarial transmission ?

11


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The Human Louse

• History and phylogenetics – Up to 3000 louse species

– Head lice prevalent in humans for thousand of years

– Body louse found in textile from Jewish revolt against Roman AD 66-73

– Found in pre-Columbian mummies

12


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The Body Louse Origin Debate

13


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18S rRNA

Peru B1

Peru B2

France H1

France H2

Thailand H1

Thailand H2

Portugal H1

Portugal H2

China H1

China H2 95

62

57

87

84

100

100

76

44

Algeria B2

Algeria B1

FranceB2

Russia B2

Russia B1

USAB2

FranceB1

USAB1

91

64

77

Zimbabwe B1

Zimbabwe B2

Rwanda B1

Burundi B1

Burundi B2

Rwanda B2

Burundi H1

Burundi H2

Rwanda H1

Rwanda H2 65

100

89

0.002

Bo

dy

lice

H

ead

lice

Sub

Sah

aran

lice

Li

ce f

rom

all

are

as e

xce

pt

sub

Sah

aran

Afr

ica

[Yong et al. 2003. C R Biol]

[Raoult et al. 2008. J.Infect.Dis] [Veracx et al. 2012. PLoS.One]

[Li et al. 2010. PLoS.Negl.Trop.Dis.]

Classification of Human Louse


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15


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16


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17

Four and five genes were missing from the body and head louse respectively. Control PCR was not able to recovered PHUM540560 in the head louse and the gene was expected to be present in the body louse only


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Are Head and body lice

distinguishable ?

18 Comparison of the transcriptional profiles of head and body lice [Olds et al. 2012]

4112 bp 14514 bp

1283054 130512522071 bp

1798 bp

752 bp898 bpP

HU

M5

40

560

PH

UM

54

05

50

PH

UM

54

05

70

PHUM540560 • 3 exons, 752 bp • non conserved hypothetic protein • 89 a.a • 8288 Da • unknown fonction


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19

Are Head and body lice distinguishable ?


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Both head and body louse are infested with B quintana

20


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Table 1: Head lice haplotypes distribution identified in this study within different haplogroups

Polymorphisms specific to haplogroup A

Polymorphisms Specific to haplogroup B

Polymorphisms specific to haplogroup C

Nonsynonymous mutations

Haplotypes A

Haplotypes X

Haplotypes B

Haplotypes C

376379384385393397405414415423426429444445447453465468475477480483486492501502505506507508510513516519525540543546549550555557564565570582591597601608609619621623624637639

X37 A G A A G A T G T T A T A C A T T A G C A A A T T G A T T C T C T G C G G G T T C G A G T C A T T G T T A T T G T

A1 A G A A G A G G T T A T G C G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T C A T C G T T A T T A T

A5 A G A A G A G G T T A T G C G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A52 - G A A G A G G T T A T G C G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A15 A G A A G A G G T T A T G C G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T T A T T G T T A T T A T

A16 A G A A G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A T A A A T T T G A G T C A T T G T T A T T A T

A17 A G A A G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A18 - G A A G A G G T T A T G T G T T A G C A G G T C A A C T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A19 A G A A G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A T A A G T T T A A G T C A T T G T T A T T A T

A53 - G A A G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A12 A G A A G A G G T T A T G C G T T A G C A G A T C A A T T C C C C A T A A G T T T G A G T C A T T G T T A T T A T

A24 A G A A G A G G T T A T G T G C T A G C A G G T C A A T T C C C C A T G A G T T T G A G T C A T T G T T A T T A T

A21 A G A G G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A C A A G T T T G A G T C A T T G T T A T T A T

A22 A G A A G A G G T T A T G T G T T A G C A G G T C A A T T C C C C A T G A G G T T G A G T T A T T G T T A T T A T

A23 A G A A G A G G T T A T G T G C T A G C A G G T C A A T T C C C C A T G A G T T T G A G T T A T T G T T A T T A T

X25 A G A G G A G G T T A T G T G C T A G C G G G T C A A T T C T C C A C G G G G C T G A G T C A T T G T T A T T A T

X27 A G A A G A G G T T A T G T G C T A A C G G G T C A A T T C T T C A C G A G G C T G A G T C A T T G T T A T T A T

X28 A G A G G A G G T T A T G T G C T A A C G G G T C A A T T C T T C A C G A G G C T G A G T C A T T G T T A T T A T

X26 A G A G G A G G T T A T A T G C T A G C G G G T C A A T T C C C C A C G G G G C T G A G T T A T T G T T A T T A T

X29 A G A G G A G G T T A T A T G T T A A C G G A T C A A T T C T T T A C G G G G C T G A G T C A T T G T T A T T A T

X30 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T C T T C A C G G G G C T G A G T T A T T G T T A T T A T

B32 A G A G G A G G T T A T A T G C T A A C A G A T C A A T T C T T T A C G G G G T T G G G T T A T T T T T G T T G C

B33 A G A G G A G G T T A T A T G C T A A C A G A T C A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T G C

B34 A G A G G A G G T T A T A T G C T A A C A G A T T A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T G C

B31 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T G T T A T T A C

B47 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T G T T G T T G C

B48 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T A C

B36 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T G C

B49 A G A G G A G G T T A T A T G C T A A C G G A T C A A T T T T T T A C G G G G C T G G G T T A T T T T T G T T G C

B35 A G A G G A G G T T A A A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T G C

B50 A G A G G A G G C T A T A T G C T A A C G G A T C A A T T C T T T A C G G G G C T G G G T T A T T T T T G T T G C

39C G G G A G A G A T C A C C T A T C G A T G G G G T A G T T C C T T G C A G G A T T G A G C T T C T G C C A C C A T

C51 A G G A A A G G T T G C C T A C C G A T G G G G C A A T C C C T T A C A G G A T T G A G C T A C T G T T A T C A T

40C A A G A G A G G T T G C C T A C C G A T G G G G T A A T T C C T T G C A G G A T T G A A C T C C T G T T A T C A T

41C A G G A A A G G T T G C C T A C C G A T G G G G T A A T C C C T T G C A G G A T T G A A C T C C T G T T A T C A T

42C A A G A G A A G T T G C C T A C C G A T G G G G T A A T C C C T T G C A G G A T T G A A C T C C T G T T A T C A T

43C A A G A G T G G T T G C C T A C C G A T G G G G T A A T C C C T T G C A G G A T T G A A C T C C T G T T A T C A T

44C A A G A G A G G T T G C C T A C C G A T G G G G T A A T C C C T T G C A G G A T T G A A C T C C T G T T A T C A T

Polymorphisms Positions on the targeted cytb gene fragment (nucleotide positions 370-642)

Haplotypes

Haplotyping the mitochondrial genes of human louse


© by author

Haplotyping the mitochondrial genes of human louse

• Paris is a cosmopolitan area

• Nucleotide recombination between mitochondrial genes ?

• African lice as well as those of Paris are found in all clade while Asian louse are found in clade A only and American one in clade A and B

• Identification of a new clade in “Pygmee” clade D

22

D37

A12

A18

A16

A16

A17

A5

A15 A1

A22

A23

A24

A21

X27

X28

X25

X26

X29

X30

B48

B47

B50

B49

B35

B32

B34

B33

B31

C51

C39 C42

C44

C43

C41

C40

A53

B36

A52

Africa

Asia

Europe

America

Oceania

Paris


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The new concepts on the origin and evolution of Human Louse

23


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THE HUMAN LOUSE AND LOUSE BORNE DISEASES

24


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Head Pediculosis

25


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Body Pediculosis


© by author

Louse borne diseases (Body louse only)

Bartonella quintana

Rickettsia prowazekii

Borrelia recurrentis

27


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Bartonella quintana

28


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Bartonella quintana (BQ)

• Bartonella quintana

Trench fever (IC individuals)

Bacillary angiomatosis and

peliosis

(ID individuals)

Endocarditis


© by author

Trench fever History

• Older disease than expected

– BQ in dental pulp of 4,000 Y-O man

– BQ in Napoleon soldiers in Vilnius

• Discover World War 1

– Estimated morbidity : • 1,000,000 soldiers

– Re emergence in World War 2

– Describe 1918

• Re discovered – homeless in Marseille

– homeless in Seattle

30

Excavations of mass graves in Vilnius, Lithuania.

CNRS


© by author

FILM/recovery of human dental pulp.mpg

Trench fever BQ primary infection

• Quintane fever – Incubation 6-22 days

– A typical pain in the shin

– Dizziness

– Headaches

– HG fever

• Last 2 to 4 days

• Relapse every 4-6 days


© by author

Trench fever Chronic bacteremia

• Recognized early 1950

• A third (5) of 14 the B.quintana infected louse feeders (typhus vaccine production) had prolonged bacteremia

• Among symptomatic carriers two third are infected de novo

• Asymptomatic carriers do not have antibodies

• In our experience • 5/11 homeless had prolonged chronic bacteremia

• Last up to 78 Weeks

• Without endocarditis ESCMID Online Lecture Library

© by author

Bartonella Quintana In immunocompromised

• Immunocompromised situations – AIDS

– Organ transplant and other

• Cutaneous Bacilliary Angiomatosis • Histology : endothelial cell proliferation with

clumps of bacilli

• Liver and spleen peliosis • Systemic disease with bacteremia, visceral

involvement : liver, spleen, lymph nodes, bone, brain…

• Lobular proliferation of hepatic sinusoids + clumps of bacilli

ESCMID Online Lectu

re Library

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Bartonella Quintana endocarditis

• Culture negative Endocarditis – No previous valvulopathy

– Alcohol consumption

– Body louse infestation

• Homeless

– Diagnostic often delayed

– High mortality rate / Others IE


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Epidemic typhus

35


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Epidemic typhus the agent

• Rickettsia prowazekii

– Obligate intracellular

• BSL3 handling

– Main reservoir

• Humans but Flying squirrel possible option in the USA

– Transmission by Body Louse

• Ticks suggested option

36


© by author

Epidemic typhus

• Epidemiology – Outbreaks associated with

• War famine, and refugee camps

• Cold weather poverty or gap in Public health management – In ancient time (Vilnius)

– In the last decades Burundi/Rwanda 1996, Russia

– Individual cases reported

• Homeless of Marseille, Alger and Houston,TX

37

1812: La Grande Armée Napoléon


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Epidemic typhus re-emergence

• Body-louse as a cause of reemergence of typhus

Typhus

recover

« Healthy carrier »

Stress

Brill-Zinsser

OUTBREAK

R.prowazekii Infected Louse ESCMID Online Lecture Library

© by author

Epidemic Typhus

• Life-threatening acute exanthematic illness • Fever, myalgia, headaches, prostration (tuphos)

• Rash on day 5

• Mortality without treatment 10-40% – but lower in youth (5%)

• Treatment : One dose of 200mg of Doxycycline®

Niang, Brouqui, Raoult. Emerg Infect Dis 1999


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Relapsing Fever

• Borrelia recurrentis – Spirochete

• Almost Disappeared – But still endemic on highland of Ethiopia

• 25% hospitalization

– Outbreak notified • Sudan and rural Andean in Peru

– unnoticed cases in homeless

• Commonly reported – Slum dwellers – prisoners – and impoverished population

• Transmitted by the Body Louse

41


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Relapsing fever

• Clinical features

– Abrupt Chills, fever and headaches • Myalgia, arthralgia, abdominal pain , anorexia ,

• Prominent dry cough , hemoptysis and epitasis mimicking CAP

• Neurological involvement usual – Meningismus, encephalitis

– Physical signs

• Conjunctivitis, petechial skin rash of the trunk Jaundice


© by author

Relapsing fever • Evolution

– Bleeding : purpura and epistasis • Hematuria, cerebral hemorrhages, bloody diarrhea…

– Relapses • 1-2

• Duration and severity decrease

– Mortality • 10-40% without TTT

• 2-3% if TTT

– Treatment • Jarisch-Herxheimer 75%

• 3 fold risk in patient >14YO

43


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Others louse-associated bacteria

44

• Body Louse as a vector for Plague

– Classically : Xenopsylla cheopis • (Rat flea)

– Transmission by clothes • Observed first by Baltazar 1941

• Infected body louse collected from bacteriemic patient in Morocco 1940s

• Animal model

• Body Louse as vector for Acinetobacter baumanii?


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46

Delousing • Delousing

– Complete change of clothes – Clothes need to be washed up

to 50°C

– If not washed do not re-used until 6 days

– Powder dusting • 10%DDT,

• 1% malathion,

• 1% permethrin

Need for alternative treatment


© by author

Follow up of louse infestation:

a 12 years follow up

• Head and body louse prevalence in Homeless and louse-associated diseases

47

4,7 4,9

11,4

3,4

8,4

3,3

0

2

4

6

8

10

12

2000 2001 2002 2003

year of investigation

Perc

en

tag

e o

f p

osit

ive h

om

ele

ss

B quintana antibodies IgG>=100

B quintana bacteremia

R prowazekii antibodies IgG >=64

B recurrentis antibodies IgG >=100


© by author

48

Delousing with Ivermectin 1898

261

15

497

60

18,5

60,7

84,9

0

10

20

30

40

50

60

70

80

90

D-0 D-7 D-14 D-45

Pre

vale

nce o

f b

od

y l

ice i

nfe

ste

d i

nd

ivid

ual

(%)

0

200

400

600

800

1000

1200

1400

1600

1800

2000

Nu

mb

er

of

bo

dy l

ice i

n t

he c

om

mu

nit

y o

f h

om

ele

ss

number of lice Prevalence


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49

Permethrin resistance in the

body louse Is due to the presence of mutations in

the gene encoding the α-subunit of the sodium channel that provides the depolarization of nerve cells. Kdr : Knock Down


© by author

FILM/HBL effet KDR.wmv

Permethrin kdr haplotypes and allelic frequency before the study on 52 lice from 12 randomly sampled

homeless

51


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Clinical trial

52

0.4% Permethrin Under wear

0 % Permethrin Under wear

Double blind randomized clinical trail


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53

Characteristics Permethrin

(n = 40)

Placebo

(n = 33) P Value

Age, mean (SD), y 56.4 (14) 57.62 (12) .69

Men, No. (%) 37 (92) 33 (100) .24

MV Shelter 36 (90) 31 (94) .68

Marginal homelessa, No. (%) 20 (50) 20 (61) .36

Homeless with more than 50 lice, No. (%) 18 (45) 19 (58) .28

Duration of homelessness ≤24 months, No. (%) 15 (38) 19 (58) .08

Pruritus, No. (%) 40 (100) 33 (100) -

Intention-To-Treat population Per-Protocol population

Outcome Measures Permethri

n Placebo OR (95% CI)

P Value

Permethrin

Placebo OR (95% CI) P

Value

Body lice-free homeless after 14

days, No./Total (%) 11/40 (28) 3/33 (9) 3.79 (.95–

15.00) .04 11/32 (34) 3/28 (11) 4.36 (1.07–17.74) .03

Body lice-free homeless after 45

days, No./Total (%) 11/40 (28) 9/33 (27) 1.01 (.36–

2.84) .98 11/27 (41) 9/24 (38) 1.14 (.37–3.54) .81


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54

Permethrin Placebo

Haplotype Day 1 Day 45 P Value Day 1 Day 45 P Value

Year 1 RRRa, No./Total (%) 17/44 (39) 31/43 (72) .002 18/47 (38) 17/53 (32) .51

RRRa,b, % (95% CI) 41.9 (40.4–43.4)

67.4 (66.4–68.4) 21.1 (20.8–

21.4) 26.2 (25.3–

27.0)

Year 2 RRRa, No./Total (%) 22/32 (69) 41/56 (73) .65 18/35 (51) 34/61 (56) .68

RRRa,b, % (95% CI) 77.8 (76.1–79.6)

75.0 (74.1–76.0) 56.9 (55.1–

58.6) 59.9 (58.8–

61.0)

All RRRa, No./Total (%) 39/76 (51) 72/99 (73) .004 36/82 (44) 51/114 (45) .90

RRRa,b, % (95% CI) 62.8 (61.9–63.7)

71.8 (71.3–72.3) 34.3 (33.8–

34.9) 44.8 (44.3–

45.4) ESCMID Online Lecture Library

© by author

55

Permethrin Placebo

Mutation Day 1 Day 45 P Value Day 1 Day 45 P Value

M815I, No./Total

(%) 44/44 (100) 43/43 (100) - 47/47 (100) 53/53 (100) -

Year 1 T917I, No./Total

(%) 18/44 (41) 31/44 (72) .003 21/47 (45) 17/53 (32) .19

L920F, No./Total

(%) 43/44 (98) 43/44 (100) - 37/47 (79) 53/53 (100) P<.001

M815I, No./Total

(%) 32/32 (100) 56/56 (100) - 35/35 (100) 61/61 (100) -

Year 2 T917I, No./Total

(%) 22/32 (69) 45/56 (80) .21 18/35 (51) 34/61 (56) .68

L920F, No./Total

(%) 32/32 (100) 56/56 (100) - 34/35 (97) 61/61 (100) -

M815I, No./Total

(%) 76/76 (100) 99/99 (100) - 82/82 (100) 114/114 (100) -

All T917I, No./Total

(%) 40/76 (53) 76/99 (77) .008 39/82 (48) 51/114 (45) .69

L920F, No./Total

(%) 75/76 (99) 99/99 (100) - 71/82 (87) 114/114 (100) P<.001


© by author

Future direction

56

Bacterial Symbiotes, Their Presence in Head Lice, and Potential Treatment Avenues :J Cutan Med Surg. 2006 Jan-Feb;10(1):2-6. Within these insects reside symbiotic bacteria “Riesia pediculicola » that enable the insect to flourish on dietary sources of limited nutritional value. These symbiotic bacteria are essential to the survival of the insect. The symbiont is accessible as a target for pediculocidal and ovicidal therapy by altering its habitat and existence. Understanding of the nature of bacterial symbiotes of head lice might lead to alternative strategies for eradication or inhibition of these necessary bacteria, thereby controlling head lice with less toxic agents than conventional insecticides, to which the organism continues to increase its resistance.


© by author

http://www.ncbi.nlm.nih.gov/pubmed/17241564

57

Acknowledgement

To the medical doctors, fellows, students and nurses

who help in snapshot investigation

Dr Badiaga Sékéné

Dr H Tissot Dupont

Pr J M Rolain

Dr P Delauney

URMITE CNRS/IRD UMR 6236/198

Funded by PHRC ESCMID Online Lecture Library

© by author

infections in homeless : a marker of poverty

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