Factors associated with COVID-19 vaccine receipt among mobile phone users in Malawi: Findings from a national mobile-based syndromic surveillance survey, July 2021-April 2022.

Malawi recommended COVID-19 vaccines for adults aged ≥18 years in March 2021. We assessed factors associated with receiving COVID-19 vaccines in Malawi as part of a telephone-based syndromic surveillance survey. We conducted telephone-based syndromic surveillance surveys with questions on COVID-19 vaccine receipt among adults (≥18 years old) upon verbal consent from July 2021 to April 2022. We used random digit dialing to select mobile phone numbers and employed electronic data collection forms on secure tablets. Survey questions included whether the respondent had received at least one dose of a COVID-19 vaccine. We used multivariable analysis to identify factors associated with COVID-19 vaccine receipt. Of the 51,577 participants enrolled; 65.7% were male. Males were less likely to receive the COVID-19 vaccine than females (AOR 0.83, 95% CI 0.80-0.86). Compared to those aged 18-24 years, older age had increased odds of vaccine receipt: 25-34 years (AOR 1.32, 95% CI 1.24-1.40), 35-44 years (AOR 2.00, 95% CI 1.88-2.13), 45-54 years (AOR 3.02, 95% CI 2.82-3.24), 55-64 years (AOR 3.24, 95% CI 2.93-3.57) and 65 years+ (AOR 3.98, 95% CI 3.52-4.49). Respondents without formal education were less likely to receive vaccination compared to those with primary (AOR 1.30, 95% CI 1.14-1.48), secondary (AOR 1.76, 95% CI 1.55-2.01), and tertiary (AOR 3.37, 95% CI 2.95-3.86) education. Respondents who thought COVID-19 vaccines were unsafe were less likely to receive vaccination than those who thought it was very safe (AOR 0.26, 95% CI 0.25-0.28). Residents of the Central and Southern regions had reduced odds of vaccine receipt compared to those in the North (AORs 0.79, (95% CI 0.74-0.84) and 0.55, (95% CI 0.52-0.58) respectively). Radio (72.6%), health facilities (52.1%), and social media (16.0%) were the more common self-reported sources of COVID-19 vaccine information. COVID-19 vaccine receipt is associated with gender, age, education, and residence. It is important to consider these factors when implementing COVID-19 vaccination programs.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

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 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.