Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi.

BACKGROUND: The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi. METHODS: Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%. RESULTS: The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25-49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23-42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15-24 years, individuals aged 25-49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35-0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20-0.58), indicating a 67% decreased likelihood compared to the youngest age group 15-24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation. CONCLUSION: This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15-24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens.

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.

Enhancing SARS-CoV-2 surveillance in Malawi using telephone syndromic surveillance from July 2020 to April 2022.

INTRODUCTION: Monitoring the SARS-CoV-2 pandemic in low-resource countries such as Malawi requires cost-effective surveillance strategies. This study explored the potential utility of phone-based syndromic surveillance in terms of its reach, monitoring trends in reported SARS-CoV-2-like/influenza-like symptoms (CLS/ILS), SARS-CoV-2 testing and mortality. METHODS: Mobile phone-based interviews were conducted between 1 July 2020 and 30 April 2022, using a structured questionnaire. Randomly digital dialled numbers were used to reach individuals aged ≥18 years who spoke Chichewa or English. Verbal consent was obtained, and trained research assistants with clinical and nursing backgrounds collected information on age, sex, region of residence, reported CLS/ILS in the preceding 2 weeks, SARS-CoV-2 testing and history of household illness and death. Data were captured on tablets using the Open Data Kit database. We performed a descriptive analysis and presented the frequencies and proportions with graphical representations over time. FINDINGS: Among 356 525 active phone numbers, 138 751 (38.9%) answered calls, of which 104 360 (75.2%) were eligible, 101 617 (97.4%) consented to participate, and 100 160 (98.6%) completed the interview. Most survey respondents were aged 25-54 years (72.7%) and male (65.1%). The regional distribution of the respondents mirrored the regional population distribution, with 45% (44%) in the southern region, 41% (43%) in the central region and 14% (13%) in the northern region. The reported SARS-CoV2 positivity rate was 11.5% (107/934). Of the 7298 patients who reported CLS/ILS, 934 (12.8%) reported having undergone COVID-19 testing. Of the reported household deaths, 47.2% (982 individuals) experienced CLS/ILS 2 weeks before their death. CONCLUSION: Telephonic surveillance indicated that the number of SARS-CoV-2 cases was at least twice as high as the number of confirmed cases in Malawi. Our findings also suggest a substantial under-reporting of SARS-CoV-2-related deaths. Telephonic surveillance has proven feasible in Malawi, achieving the ability to characterise SARS-CoV-2 morbidity and mortality trends in low-resource settings.

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.