Helminth - Mycobacterium leprae co-infections: Facilitators of leprosy transmission and morbidity or innocent bystanders? Open Access

Abstract

Background: The immune derangements of helminth infections and evidence that co-infections may shift the presentation of leprosy to the lepromatous end of the spectrum suggest that they could be risk factors for both leprosy transmission and for the serious immunologic reactions. Methods: We conducted two investigations: a case-control study on helminth co-infections and leprosy reactions and a geospatial study on spatial associations of schistosomiasis and leprosy in Minas Gerais, Brazil. Adult patients with multibacillary disease were recruited from a leprosy clinic in Belo Horizonte. Cases included those with active Type 1 (T1R) or Type 2 reaction (T2R) and controls included those without reactions. Data were abstracted from charts and questionnaires, and stool and blood tested for helminth infections. Adjusted odds ratios were calculated with helminth infection as the main exposure and T1R or T2R as the outcomes. For the geospatial study, all new cases of M. leprae and Schistosoma mansoni infections from 2007-2014 were retrieved from SINAN, the Brazilian national notifiable disease network, for seven municipalities. Cases were mapped to municipality and neighborhood levels. A stratified analysis was conducted to identify spatial associations between the two infections. Results: Seventy-three patients were recruited to the case-control study. Helminth infections were found in 4 patients with reactions and 1 patient without reaction, with total prevalence of 6.9%. Helminth co-infections were not found to be associated with T1R (aOR =3.5; 95% CI 0.17, 73.15) nor T2R (aOR = 0.07; 95% CI <0.001, 80.49). The geospatial analysis found a RR of 6.80 (95% CI 1.46, 31.64) of finding new cases of leprosy in neighborhoods with schistosomiasis in one municipality. Incidence rates of leprosy per neighborhood increased with corresponding incidence rates of schistosomiasis. Conclusion: While the pilot study did not show a statistically significant association with helminth infections and reactions, the total numbers of co-infections were low. However, we found an association between leprosy and schistosomiasis on the spatial analysis, suggesting a possible role of co-infections propagating leprosy transmission. These findings call for further research with prospective studies on reactions as well as epidemiologic and immunologic studies on co-infections in areas with higher helminth endemicity.

Table of Contents

Chapter I: Introduction……………………………….………………………………….1

Chapter II: Literature Review……………………………….………………………….3

Mycobacterium leprae infection and "reactions"…...…………......……………..3

Risk factors for Type 1 and Type 2 reactions………..……………………………..4

Co-infections and risk of reactions………….……………………………………....7

Helminth-leprosy co-infections...…………………..……………………………....8

Geographic information systems and leprosy…...…...………..…………………9

Helminth infection epidemiology in Minas Gerais……..………………..……..10

Goals of this study………………...………………………………...…………….......11

Chapter III: Manuscript…………………………..…………………………………….12

I. Abstract ………………………………………….………………………………........13

II. Introduction…………………………………..…………………………………......14

III. Methods………………………………….……….……………………………….....17

a. Reactions Study………………………….…………………………………….........17

Study site and population……….……………………………………………….......17

Data collection…………………………………………………………………...........18

Infection diagnosis….………………………………..…………………………........19

Statistical analysis………………………………………...…………………….........20

Multivariate analysis…………………………………………...……………….........21

b. GIS Study…………………..…………………………………………………...........22

Study area………………..…..…………………………………………………...........22

GIS mapping……………………………………...……………………………...........23

Statistical analysis……………………………………...………………….……........24

c. Ethical approval…………………………………………..…………………….......25

IV. Results……………………………………….…………………….…………….......25

a. Reactions study……………………………….……………………………............25

Participant characteristics……………………………………………………….......25

Results of the multivariate analysis……………………………………………......26

b. GIS study………………………………………………………………………..........28

V. Discussion………………………………………………………………………........30

VI. Tables and Figures………………………………………………………………....35

Chapter IV: Summary and Future Directions……………………………………..43

References………………………………………………………………………………..46

Appendices……………………………………………………………………………….53

Appendix A: Additional Figures………………………………………………….....53

Appendix B: Additional Tables…………………………………………………......54

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Keyword	morbidity leprosy helminths co-infection transmission
Committee Chair / Thesis Advisor	Kitron, Uriel, Emory University
Partnering Agencies	University, college or educational institution (other than Emory)

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