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Frontiers in Public Health 2020Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a...
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. 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. The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.
Topics: Case-Control Studies; Humans; Isoniazid; Malawi; Pellagra; Tuberculosis
PubMed: 33324593
DOI: 10.3389/fpubh.2020.551308 -
The American Journal of Tropical... Apr 2021In mid-June 2019, 3 months after cyclone Idai landfall in Mozambique, health authorities of Nhamatanda district reported an outbreak of Pellagra. Applying a mixed-method...
In mid-June 2019, 3 months after cyclone Idai landfall in Mozambique, health authorities of Nhamatanda district reported an outbreak of Pellagra. Applying a mixed-method protocol, we carried out an investigation to characterize cases of pellagra, identify the associated factors for the outbreak using a case-control study, and explore the perceived impact on food security (availability, access, and usage) before and after Idai. We collected data from 121 cases and 121 controls and conducted in-depth interviews with 69 heads of households. The cases were more likely to be female (P < 0.01) and less educated (P < 0.01) than controls. Insufficient consumption of chicken and peanut before cyclone Idai arrival were statistically associated with pellagra (P < 0.05). From interviewed households' heads, 51% were experiencing food shortages even before the cyclone hit. Cyclone Idai served as a trigger to reduce niacin consumption below the threshold that protected Nhamatanda population from pellagra and caused a ≈2,300 case (707.9/100,000 inhabitants) outbreak.
Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Cyclonic Storms; Disease Outbreaks; Female; Humans; Infant; Infant, Newborn; Male; Mozambique; Odds Ratio; Pellagra; Skin
PubMed: 33844647
DOI: 10.4269/ajtmh.20-1321 -
The Pan African Medical Journal 2021Niacin or tryptophan deficiency causes pellagra. Isoniazid interferes with the absorption of niacin and individuals on Isoniazid (INH) are at risk of pellagra. Isoniazid...
Niacin or tryptophan deficiency causes pellagra. Isoniazid interferes with the absorption of niacin and individuals on Isoniazid (INH) are at risk of pellagra. Isoniazid preventive therapy (IPT) is the administration of isoniazid to immunosuppressed individuals to prevent active tuberculosis (TB). IPT, in sub-Saharan Africa, the region worst hit by HIV and with a high TB prevalence, is recommended. A 40-year-old, HIV+ Zambian woman on Antiretroviral therapy for five years and IPT for three months presented with a four-day history of constipation, generalised body weakness and irrelevant talk. She complained of a generalised rash, sloughing off, and darkening of the skin on the face, neck, forearms, and dorsum of both feet. A physical examination revealed features of pellagra, and rapid response to oral niacin reaffirmed the diagnosis of pellagra. Unlike typical cases of pellagra presenting with the classic 3 Ds of Diarrhoea, Dementia and Dermatitis, our patient presented with constipation instead of diarrhoea. A consideration of Pellagra in HIV+ patients on IPT whose diet is mostly maize-based will be beneficial, even if the classic 3 Ds of diarrhoea, dementia, and dermatitis are not wholly present. A timely diagnosis and prompt treatment of pellagra can be lifesaving.
Topics: Adult; Anti-HIV Agents; Antitubercular Agents; Constipation; Dementia; Dermatitis; Female; HIV Infections; Humans; Isoniazid; Niacin; Pellagra; Tuberculosis
PubMed: 34422196
DOI: 10.11604/pamj.2021.39.73.28072 -
European Journal of Nutrition Feb 2022Vitamin B provides nicotinamide adenine dinucleotide (NAD), an essential coenzyme in oxidoreductase reactions. Severe vitamin B deficiency leads to the disease Pellagra,...
PURPOSE
Vitamin B provides nicotinamide adenine dinucleotide (NAD), an essential coenzyme in oxidoreductase reactions. Severe vitamin B deficiency leads to the disease Pellagra, while mild vitamin B deficiency has been linked to age-related and metabolic diseases. Mild vitamin B deficiency is understudied, especially in females. Therefore, we examined how female mice responded to a diet that induced mild vitamin B deficiency in male mice.
METHODS
Female C57BL/6RccHsd mice were subjected for 18 weeks to a diet without vitamin B and low but sufficient tryptophan (0.115%) (0NR) and were compared to control female mice on the same diet with the reference dose of vitamin B (30NR, 30 mg nicotinamide riboside/ kg diet).
RESULTS
In the female mice, no differences between the two dietary groups were found in liver nicotinamide mononucleotide (NMN) levels, body composition, whole body energy and substrate metabolism measured by indirect calorimetry, or liver triacylglycerol metabolism. Expression of seven genes that previously were shown to respond to mild vitamin B deficiency in male white adipose tissue were not differentially expressed between the female dietary groups, neither was insulin sensitivity.
CONCLUSION
We concluded that the female 0NR mice were not vitamin B deficient; the role of age, sex and health status is discussed. Demonstrated by clear differences between females and males, the latter showing mild deficiency under the same conditions, this study highlights the importance of studying both sexes.
Topics: Adipose Tissue, White; Animals; Female; Liver; Male; Mice; Mice, Inbred C57BL; NAD; Niacinamide; Sex Factors; Vitamin B Deficiency; Vitamins
PubMed: 34338868
DOI: 10.1007/s00394-021-02651-8 -
Bioscience of Microbiota, Food and... 2023Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We...
Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of BB536 on pellagra-related nausea caused by pirfenidone in our mouse model. Our pharmacological data indicated that pirfenidone (PFD) causes modulation of the gut microbiota profile, which appeared to play an important role in the development of pellagra-related nausea. A gut microbiota-mediated protective effect of BB536 against nausea caused by PFD was also identified. Finally, the urinary ratio of nicotinamide/N-methylnicotinamide was shown to be a biomarker of pellagra-like adverse effects induced by PFD, and it may contribute to the prevention of these effects in patients with idiopathic pulmonary fibrosis.
PubMed: 37404569
DOI: 10.12938/bmfh.2022-042 -
Journal of Investigative Medicine High... 2020The triad of diarrhea, dementia, and dermatitis constitutes the clinical diagnosis of pellagra. However, most reported cases of pellagra have occurred without all...
The triad of diarrhea, dementia, and dermatitis constitutes the clinical diagnosis of pellagra. However, most reported cases of pellagra have occurred without all components of the triad. Pellagra was declared eradicated in the United States after an outbreak in the 1920s, and is now considered to be an exceedingly rare diagnosis in developed countries. In this article, we present a case of a 56-year-old man who presented with a significant history of alcohol use and chronic diarrhea. Pellagra was clinically diagnosed based on the triad of diarrhea, cognitive dysfunction, and dermatitis in this malnourished, alcoholic patient. The patient was treated and clinically improved with resolution of his diarrhea and cognitive dysfunction.
Topics: Alcoholism; Cognitive Dysfunction; Dermatitis; Diarrhea; Humans; Male; Middle Aged; Niacin; Pellagra; Vitamin B Complex
PubMed: 32646238
DOI: 10.1177/2324709620941305 -
Cells Jul 2020Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure....
Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of -mediated hepatotoxicity and the systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B deficiency), peripheral neuropathy, and vitamin B deficiency. However, the mechanisms by which isoniazid administration leads to these states are unclear. To elucidate the mechanism of rifampicin- and isoniazid-induced liver and systemic injury, we performed tandem mass tag mass spectrometry-based proteomic screening of and mice treated with combinations of rifampicin and isoniazid. Proteomic profiling analysis suggested that the liver proteome is affected by antitubercular therapy to disrupt [Fe-S] cluster assembly machinery, [2Fe-2S] cluster-containing proteins, cytochrome P450 enzymes, heme biosynthesis, homocysteine catabolism, oxidative stress responses, vitamin B metabolism, and vitamin B metabolism. These novel findings provide insight into the etiology of some of these processes and potential targets for subsequent investigations. Data are available via ProteomeXchange with identifier PXD019505.
Topics: Animals; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Heme; Homocysteine; Iron-Sulfur Proteins; Isoniazid; Liver; Mice; Mice, Inbred C57BL; Niacinamide; Oxidative Stress; Proteome; Rifampin; Vitamin B 6
PubMed: 32660103
DOI: 10.3390/cells9071654 -
Movement Disorders Clinical Practice Aug 2021
PubMed: 34514050
DOI: 10.1002/mdc3.13292 -
BMJ Case Reports Sep 2019The case involves a 62-year-old female native of the USA with a history of bipolar disorder and chronic obstructive pulmonary disease who presented with intractable...
The case involves a 62-year-old female native of the USA with a history of bipolar disorder and chronic obstructive pulmonary disease who presented with intractable diarrhoea. Prior to the index admission, she was admitted to the intensive care unit and required pericardiocentesis for an idiopathic pericardial effusion with tamponade physiology. Following discharge, she suffered intractable diarrhoea and represented for medical evaluation. She had a painful, swollen tongue as well as persistent hypoglycaemia and required glucose infusions. She had adrenal function testing which revealed adrenal insufficiency. Vitamin testing revealed normal B and folate levels but undetectable levels of thiamine, riboflavin and niacin. Her symptoms and signs resolved entirely with appropriate vitamin supplementation. Niacin (vitamin B) is essential for multiple metabolic pathways, and severe deficiency may cause clinical syndrome of pellagra which is most commonly associated with diarrhoea, delirium and dermatitis. Additional physiological derangements may include adrenal insufficiency, insulin hypersensitivity and pericarditis.
Topics: Diarrhea; Female; Humans; Middle Aged; Niacin; Pellagra; Recurrence; Thiamine; Tongue; Treatment Outcome; Vitamin B Complex
PubMed: 31570356
DOI: 10.1136/bcr-2019-230972 -
Journal of the American College of... Dec 2023
PubMed: 38029019
DOI: 10.1002/emp2.13065