1. Deworming improves current wheeze and temporarily deteriorates atopy: longitudinal anthelminthic treatment studies in Cuban schoolchildren Wördemann Meike, Menten Joris, Junco Diaz Raquel, Menocal Heredia Lenina, Ruiz Espinosa Aniran, Gryseels Bruno, Bonet Gorbea Mariano, Polman Katja Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium National Institute of Hygiene, Epidemiology and Microbiology, Havana, Cuba Institute Pedro Kouri, Havana, Cuba Congreso Higiene y Epidemiologia, Havana, 5-9 Nov 2007
9 May 2018

2. Rationale
Atopic diseases very common and helminth infections uncommon in developed countries, while inverse is true in many developing countries
Inverse relationship helminth infections and atopic diseases? (~hygiene hypothesis)
*Hygiene hypothesis: exposure to infections in early childhood reduces risk of developing allergies
Helminth infections  allergy  ?
Anthelminthic treatment  allergy  ?
---> scientific, clinical + PH consequences
9 May 2018

3. Objective Prospective intervention study
Investigate the effect of deworming and intestinal helminth (re)infections (Ascaris, Trichuris, hookworm) on atopy and atopic diseases (asthma, allergic rhinitis and atopic dermatitis)
9 May 2018

4. Methods
440 children (4-13yrs) from randomly selected primary schools in San Juan y Martinez, Pinar del Rio
Treatment follow up study six-monthly for 24 months
Helminth positive children treated with anthelminthics  untreated controls*
9 May 2018

5. asthma (current wheeze): affirmative answer to ISAAC question CW 2
International Study of Asthma and Allergies in childhood (ISAAC) questionnaire (atopic disease):
asthma (current wheeze): affirmative answer to ISAAC question CW 2
allergic rhinoconjunctivitis: affirmative answer to ISAAC question AR 2+3 (= definition Strachan)
atopic dermatitis: affirmative answer to ISAAC question AD 2+3 (= definition Williams)
9 May 2018

6. Presence of helminth eggs of A. lumbricoides, T. trichiura, hookworm
Stool examination by Kato-Katz & direct smear (intestinal helminth infection):
Presence of helminth eggs of A. lumbricoides, T. trichiura, hookworm
9 May 2018

7. Skin prick test (atopy):
Positive reaction to any of 7 international standard allergens tested
(Dermatophagoides pteronyssinus, D. farinae, cat dander, mixed tree, mixed grass, Alternaria alternata, and cockroach)
9 May 2018

8. Statistics Repeated measures logistic regression
time trend for atopic disease/atopy after treatment
Transition logistic regression model
 effect of helminth infection (after treatment failure or reinfection) on development/ retainment of atopic conditions
9 May 2018

9. Baseline data on age, sex, and helminth infection, atopy and atopic disease status for treated cohort
Treated
Cohort
Untreated
Control Group
Month 6
Month 12
Month 18
Control Group
Month 24 N
119
112 71 75 63
% Male
45%
44%
39%
53%
57%
Age: mean (SD)
8.0 (2.0)
8.8 (2.1)
7.9 (2.1)
8.8 (2.2)
8.1 (1.9)
Helminths (% positive)
A. lumbricoides
46%
50%
51%
60%
T. trichiura
28%
14%
hookworm
25%
11% 6% 5%
16%
Atopy/atopic disease (% positive)
Current wheeze
31%
20%
22%
Skin prick test positive 9%
15%
Allergic rhinitis
18%
10%
Atopic dermatitis 8%
12%
17% 4%
9 May 2018

10. Percentages of children with current wheeze (asthma) in treated and untreated helminth-positive children in San Juan y Martínez.
Significant decrease over time in percentage of children with wheeze for treated cohort, not for untreated control groups
9 May 2018

11. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for asthma by helminth infection
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Current wheeze
A. lumbricoides
18.1%
30.8%
2.02
( 0.97 , 4.22)
0.065
T. trichiura
17.4%
39.8%
3.65
( 1.49 , 8.92)
0.006
hookworm
21.7%
17.8%
0.54
( 0.17 , 1.77)
0.289
Any helminth
14.6%
27.5%
1.96
(1.05, 3.65)
0.033
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

12. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for asthma by helminth infection
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Current wheeze
A. lumbricoides
18.1%
30.8%
2.02
( 0.97 , 4.22)
0.065
T. trichiura
17.4%
39.8%
3.65
( 1.49 , 8.92)
0.006
hookworm
21.7%
17.8%
0.54
( 0.17 , 1.77)
0.289
Any helminth
14.6%
27.5%
1.96
(1.05, 3.65)
0.033
Children who were helminth-free after treatment are less likely to develop or retain current wheeze than those who remained infected or were reinfected
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

13. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for asthma by helminth infection
For A. lumbricoides and T. trichiura but not for hookworm, those who remained infected or were (re)infected after treatment were more likely to develop or retain wheeze than children who cleared their infection.
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Current wheeze
A. lumbricoides
18.1%
30.8%
2.02
( 0.97 , 4.22)
0.065
T. trichiura
17.4%
39.8%
3.65
( 1.49 , 8.92)
0.006
hookworm
21.7%
17.8%
0.54
( 0.17 , 1.77)
0.289
Any helminth
14.6%
27.5%
1.96
(1.05, 3.65)
0.033
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

14. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for allergic rhinitis by helminth infection
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Allergic Rhinitis
A. lumbricoides
8.9%
16.2%
2.44
( 1.01 , 5.85)
0.053
T. trichiura
19.3%
1.95
( 0.64 , 5.91)
0.258
hookworm
11.5%
5.5%
0.22
( 0.03 , 1.74)
0.077
Any helminth
8.1%
13.2%
1.36
(0.63, 2.92)
0.433
(Re)infection with A. lumbricoides positively associated and with hookworm negatively associated with the development or retention of allergic rhinitis
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

15. Percentages of skin prick test positive children (atopy) in treated and untreated helminth-positive children in San Juan y Martínez.
Significant change over time (temporary increase followed by gradual decrease to baseline) in percentage of skin prick test positive children for treated cohort, not for untreated control groups
9 May 2018

16. Percentages of skin prick test positive children (atopy) in treated and untreated helminth-positive children in San Juan y Martínez.
Significant change over time (temporary increase followed by gradual decrease to baseline) in percentage of skin prick test positive children for treated cohort, not for untreated control groups
Early strong reaction of immune system shortly after treatment
Repeated treatment  immune suppression
~ immunotherapy in allergy (repeated vaccinations with allergens) 
9 May 2018

17. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for atopy by helminth infection
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Skin Prick Test
A. lumbricoides
20.5%
12.0%
0.77
( 0.35 , 1.69)
0.510
T. trichiura
19.8%
12.1%
0.61
( 0.22 , 1.66)
0.316
hookworm
18.1%
20.6%
1.56
( 0.66 , 3.64)
0.317
Any helminth
22.3%
14.7%
0.82
(0.45, 1.48)
0.511
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

18. Sign/Symptom Prevalence
Frequencies and results from transition logistic regression model for atopy by helminth infection
Trend opposite to that observed for atopic diseases: (re)infection with A. lumbricoides or T. trichiura negatively associated and with hookworm positively associated with the development or retention of atopy
Sign/Symptom Prevalence
Odds-Ratio†
Helminth species
in non infected children‡
in infected children‡
Estimate
95% Confidence Interval
P-value
Skin Prick Test
A. lumbricoides
20.5%
12.0%
0.77
( 0.35 , 1.69)
0.510
T. trichiura
19.8%
12.1%
0.61
( 0.22 , 1.66)
0.316
hookworm
18.1%
20.6%
1.56
( 0.66 , 3.64)
0.317
Any helminth
22.3%
14.7%
0.82
(0.45, 1.48)
0.511
† Odds-ratio of developing atopy/atopic diseases (for children who did not have atopy/atopic diseases at previous visit) or retaining atopy/atopic diseases (for children who had atopy/atopic diseases at previous visit) in helminth infected versus non helminth infected children. Odds-ratio, 95% confidence interval, and p-value obtained from transition logistic regression model with adjustment for time, age, gender and rural/urban location of the school.
‡ After anthelminthic treatment, i.e. children with successful treatment versus children with unsuccessful treatment or reinfection.
9 May 2018

19. Conclusion Atopic diseases improve after anthelminthic treatment
Atopy increases after deworming, but
As this increase appears only temporarily, deworming of schoolchildren does not seem to be a risk factor for the development of atopy, nor for atopic disease
Effects of helminth (re)infections on atopy and atopic diseases appear to be species-specific
9 May 2018

20. Thank you for your attention
9 May 2018