Protocol to implement a syndromic surveillance survey of COVID-19 in Malawi.

Introduction: Malawi experienced two waves of COVID-19 between April 2020 and February 2021. A High negative impact of COVID-19 was experienced in the second wave, with increased hospital admissions that overwhelmed the healthcare system. This paper describes a protocol to implement a telephone-based syndromic surveillance system to assist public health leaders in the guidance, implementation, and evaluation of programs and policies for COVID-19 prevention and control in Malawi. Study design: This is a serial cross-sectional telephonic-based national survey focusing on the general population and People living with HIV and AIDS. Methods: We will conduct a serial cross-sectional telephone survey to assess self-reported recent and current experience of influenza-like illness (ILI)/COVID-19-like-illness (CLI), household deaths, access to routine health services, and knowledge related to COVID-19. Structured questionnaires will be administered to two populations: 1) the general population and 2) people living with HIV (PLHIV) on antiretroviral therapy (ART) at EGPAF-supported health facilities. Electronic data collection forms using secure tablets will be used based on randomly selected mobile numbers from electronic medical records (EMR) for PLHIV. We will use random digit dialing (RDD) for the general population to generate phone numbers to dial respondents. The technique uses computer-generated random numbers, using the 10-digit basic structure of mobile phone numbers for the two existing mobile phone companies in Malawi. Interviews will be conducted only with respondents that will verbally consent. A near real-time online dashboard will be developed to help visualize the data and share results with key policymakers. Conclusion: The designed syndromic surveillance system is low-cost and feasible to implement under COVID-19 restrictions, with no physical contact with respondents and limited movement of the study teams and communities. The system will allow estimation proportions of those reporting ILI/CLI among the general population and PLHIV on ART and monitor trends over time to detect locations with possible COVID-19 transmission. Reported household deaths in Malawi, access to health services, and COVID-19 knowledge will be monitored to assess the burden and impact on communities in Malawi.

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.

Assessing treatment outcomes among peer educators living with HIV in Kenya.

BACKGROUND: People living with HIV (PLHIV) often face barriers in accessing quality and comprehensive HIV care, including stigma and discrimination, which results in poor retention and viral non-suppression. Peer-led interventions can help address these barriers. In Kenya, peer educators (PEs) are PLHIV who support other PLHIV to adhere to clinic schedules and antiretroviral medication uptake. In spite of their status as role models and their key role in supporting clients receiving HIV care and treatment, little is known about the characteristics and treatment outcomes of PEs themselves, specifically viral suppression. METHODS: This is a retrospective descriptive analysis of program data on treatment outcomes of PEs engaged in active patient support activities between October 2010 and January 2017. All eligible PEs from 140 health facilities located in 23 counties of Kenya were included in the study. Data from 230 PEs were abstracted from the electronic medical records, patient files, and registers between June and August 2017. Study variables included key sociodemographic characteristics (sex, marital status, and age), duration on antiretroviral therapy (ART), WHO clinical staging, baseline CD4 count, current antiretroviral regimen and uptake of isoniazid preventive therapy (IPT). The outcome variable was viral suppression, defined as a viral load <1000 copies/ml. RESULTS: Overall, 173/230 (75%) of the PEs were female, 144/230 (63%) were married, and median age (LQ, UQ) was 38.5 (33.0, 42.0) years. The PEs had been on ART for a median (LQ, UQ) duration of 76.0 (37.0, 105.0) months. Six months IPT completion was high at 97%. Of the 222 (97%) PEs with an up-to-date viral load taken within the last one year, 211 (95%) were virally suppressed. CONCLUSION: Our study showed that peer educators actively engaged in patient support activities have achieved high viral suppression rates.

Impact of a Comprehensive Adolescent-Focused Case Finding Intervention on Uptake of HIV Testing and Linkage to Care Among Adolescents in Western Kenya.

BACKGROUND: Low HIV testing uptake prevents identification of adolescents living with HIV and linkage to care and treatment. We implemented an innovative service package at health care facilities to improve HIV testing uptake and linkage to care among adolescents aged 10-19 years in Western Kenya. METHODS: This quasi-experimental study used preintervention and postintervention data at 139 health care facilities (hospitals, health centers, and dispensaries). The package included health worker capacity building, program performance monitoring tools, adolescent-focused HIV risk screening tool, and adolescent-friendly hours.The study population was divided into early (10-14 years) and late (15-19 years) age cohorts. Implementation began in July 2016, with preintervention data collected during January-March 2016 and postintervention data collected during January-March 2017. Descriptive statistics were used to analyze the numbers of adolescents tested for HIV, testing HIV-positive, and linked to care services. Preintervention and postintervention demographic and testing data were compared using the Poisson mean test. χ testing was used to compare the linkage to care rates. RESULTS: During the preintervention period, 25,520 adolescents were tested, 198 testing HIV-positive (0.8%) compared with 77,644 adolescents tested with 534 testing HIV-positive (0.7%) during the postintervention period (both P-values <0.001). The proportion of HIV-positive adolescents linked to care increased from 61.6% to 94.0% (P < 0.001). The increase in linkage to care was observed among both age cohorts and within each facility type (both P-values <0.001). CONCLUSIONS: The adolescent-focused case finding intervention package led to a significant increase in both HIV testing uptake and linkage to care services among adolescents in Western Kenya.