Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi
Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin s...
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| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2020.551308/full |
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| author | Scott A. Nabity Kelvin Mponda Steve Gutreuter Diya Surie Anne Williams Anne Williams Andrea J. Sharma Elizabeth R. Schnaubelt Rebekah E. Marshall Hannah L. Kirking Suzgo B. Zimba Joram L. Sunguti Laphiod Chisuwo Mabvuto J. Chiwaula Jesse F. Gregory Robin da Silva Michael Odo Andreas Jahn Thokozani Kalua Rose Nyirenda Belaineh Girma James Mpunga Nicole Buono Alice Maida Evelyn J. Kim Laurence J. Gunde Tigest F. Mekonnen Andrew F. Auld Adamson S. Muula John E. Oeltmann |
| author_facet | Scott A. Nabity Kelvin Mponda Steve Gutreuter Diya Surie Anne Williams Anne Williams Andrea J. Sharma Elizabeth R. Schnaubelt Rebekah E. Marshall Hannah L. Kirking Suzgo B. Zimba Joram L. Sunguti Laphiod Chisuwo Mabvuto J. Chiwaula Jesse F. Gregory Robin da Silva Michael Odo Andreas Jahn Thokozani Kalua Rose Nyirenda Belaineh Girma James Mpunga Nicole Buono Alice Maida Evelyn J. Kim Laurence J. Gunde Tigest F. Mekonnen Andrew F. Auld Adamson S. Muula John E. Oeltmann |
| author_sort | Scott A. Nabity |
| collection | DOAJ |
| description | Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi.Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3–25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim.Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis. |
| first_indexed | 2024-12-17T01:12:08Z |
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| issn | 2296-2565 |
| language | English |
| last_indexed | 2024-12-17T01:12:08Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Public Health |
| spelling | doaj.art-9fe800dec569443791b842a1af1ea5062022-12-21T22:09:07ZengFrontiers Media S.A.Frontiers in Public Health2296-25652020-11-01810.3389/fpubh.2020.551308551308Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in MalawiScott A. Nabity0Kelvin Mponda1Steve Gutreuter2Diya Surie3Anne Williams4Anne Williams5Andrea J. Sharma6Elizabeth R. Schnaubelt7Rebekah E. Marshall8Hannah L. Kirking9Suzgo B. Zimba10Joram L. Sunguti11Laphiod Chisuwo12Mabvuto J. Chiwaula13Jesse F. Gregory14Robin da Silva15Michael Odo16Andreas Jahn17Thokozani Kalua18Rose Nyirenda19Belaineh Girma20James Mpunga21Nicole Buono22Alice Maida23Evelyn J. Kim24Laurence J. Gunde25Tigest F. Mekonnen26Andrew F. Auld27Adamson S. Muula28John E. Oeltmann29Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesSchool of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, MalawiDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesNational Center for Chronic Disease Prevention and Health Promotion, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesMcKing Consulting Corporation, Atlanta, GA, United StatesNational Center for Chronic Disease Prevention and Health Promotion, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesElizabeth Glaser Pediatric AIDS Foundation, Lilongwe, MalawiElizabeth Glaser Pediatric AIDS Foundation, Lilongwe, MalawiNational Public Health Reference Laboratory, Public Health Institute of Malawi, Lilongwe, MalawiNational Public Health Reference Laboratory, Public Health Institute of Malawi, Lilongwe, MalawiDepartment of Food Science and Human Nutrition, University of Florida, Gainesville, FL, United StatesDepartment of Food Science and Human Nutrition, University of Florida, Gainesville, FL, United StatesDepartment of HIV and AIDS, Malawi Ministry of Health, Lilongwe, MalawiDepartment of HIV and AIDS, Malawi Ministry of Health, Lilongwe, MalawiDepartment of HIV and AIDS, Malawi Ministry of Health, Lilongwe, MalawiDepartment of HIV and AIDS, Malawi Ministry of Health, Lilongwe, MalawiNational Tuberculosis Control Program, Malawi Ministry of Health, Lilongwe, MalawiNational Tuberculosis Control Program, Malawi Ministry of Health, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, Malawi0Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lilongwe, MalawiSchool of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, MalawiDivision of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United StatesBackground: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi.Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3–25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim.Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.https://www.frontiersin.org/articles/10.3389/fpubh.2020.551308/fullisoniazidtuberculosis preventive treatmenttuberulosishuman immuno defficiency virus (HIV)pellagraniacin (nicotinic acid) |
| spellingShingle | Scott A. Nabity Kelvin Mponda Steve Gutreuter Diya Surie Anne Williams Anne Williams Andrea J. Sharma Elizabeth R. Schnaubelt Rebekah E. Marshall Hannah L. Kirking Suzgo B. Zimba Joram L. Sunguti Laphiod Chisuwo Mabvuto J. Chiwaula Jesse F. Gregory Robin da Silva Michael Odo Andreas Jahn Thokozani Kalua Rose Nyirenda Belaineh Girma James Mpunga Nicole Buono Alice Maida Evelyn J. Kim Laurence J. Gunde Tigest F. Mekonnen Andrew F. Auld Adamson S. Muula John E. Oeltmann Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi Frontiers in Public Health isoniazid tuberculosis preventive treatment tuberulosis human immuno defficiency virus (HIV) pellagra niacin (nicotinic acid) |
| title | Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi |
| title_full | Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi |
| title_fullStr | Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi |
| title_full_unstemmed | Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi |
| title_short | Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi |
| title_sort | protocol for a case control study to investigate the association of pellagra with isoniazid exposure during tuberculosis preventive treatment scale up in malawi |
| topic | isoniazid tuberculosis preventive treatment tuberulosis human immuno defficiency virus (HIV) pellagra niacin (nicotinic acid) |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2020.551308/full |
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