The Malawi NCD BRITE Consortium: Building Research Capacity, Implementation, and Translation Expertise for Noncommunicable Diseases.

Africa is experiencing an increasing prevalence of noncommunicable diseases (NCD). However, few reliable data are available on their true burden, main risk factors, and economic impact that are needed to inform implementation of evidence-based interventions in the local context. In Malawi, a number of initiatives have begun addressing the NCD challenge, which have often utilized existing infectious disease infrastructure. It will be crucial to carefully leverage these synergies to maximize their impact. NCD-BRITE (Building Research Capacity, Implementation, and Translation Expertise) is a transdisciplinary consortium that brings together key research institutions, the Ministry of Health, and other stakeholders to build long-term, sustainable, NCD-focused implementation research capacity. Led by University of Malawi-College of Medicine, University of North Carolina, and Dignitas International, NCD-BRITE's specific aims are to conduct detailed assessments of the burden and risk factors of common NCD; assess the research infrastructure needed to inform, implement, and evaluate NCD interventions; create a national implementation research agenda for priority NCD; and develop NCD-focused implementation research capacity through short courses, mentored research awards, and an internship placement program. The capacity-building activities are purposely designed around the University of Malawi-College of Medicine and Ministry of Health to ensure sustainability. The NCD BRITE Consortium was launched in February 2018. In year 1, we have developed NCD-focused implementation research capacity. Needs assessments will follow in years 2 and 3. Finally, in year 4, the generated research capacity, together with findings from the needs assessments, will be used to create a national, actionable, implementation research agenda for NCD prioritized in this consortium, namely cardiovascular disease, diabetes mellitus, and asthma and chronic obstructive pulmonary disease.

Early experiences integrating hypertension and diabetes screening and treatment in a human immunodeficiency virus clinic in Malawi.

Background: Human immunodeficiency virus (HIV) programmes can be leveraged to manage the growing burden of non-communicable diseases (NCDs). Methods: In October 2015, a model of integrated HIV-NCD care was developed at a large HIV clinic in southeast Malawi. Blood pressure was measured in adults at every visit and random blood glucose was determined every 2 y. Uncomplicated antiretroviral therapy (ART)-only care was provided by nurses, integrated HIV-NCD management was provided by clinical officers. Waiting times were assessed using the electronic medical record system. The team met monthly to identify bottlenecks. Results: All (n=6036) adult HIV patients were screened and 765 were diagnosed with hypertension (prevalence 12.7% [95% confidence interval {CI} 11.9-13.5). A total of 2979 adult HIV patients were screened and 25 were diagnosed with diabetes mellitus (prevalence 0.8% [95% CI 0.6-1.2]). The mean duration of ART visits by clinical officers increased from 80.5 to 90 min during the first quarter following HIV-NCD integration but returned to 75 min the following quarter. The mean number of patients seen per day by clinical officers increased from 6 to 11 and for nurses decreased from 92 to 82 in that time period. The robust vertical HIV system made the design of integrated tools demanding. Challenges of integrated HIV-NCD care were related to patient flow, waiting times, NCD drug availability, data collection, clinic workload and the timing of diabetes and hypertension screening. Conclusions: Integrated HIV-NCD services provision was feasible in our clinic.

Opportunities and challenges for evidence-informed HIV-noncommunicable disease integrated care policies and programs: lessons from Malawi, South Africa, Swaziland and Kenya.

INTRODUCTION: Countries in sub-Saharan Africa (SSA) are recognizing the growing dual burden of HIV and noncommunicable diseases (NCDs). This article explores the availability, implementation processes, opportunities and challenges for policies and programs for HIV/NCD integration in four SSA countries: Malawi, Kenya, South Africa and Swaziland. METHODS: We conducted a cross-sectional analysis of current policies and programs relating to HIV/NCD care integration from January to April 2017 using document review and expert opinions. The review focussed on availability and content of relevant policy documents and processes towards implementating national HIV/NCD integration policies. RESULTS: All four case study countries had at least one policy document including aspects of HIV/NCD care integration. Apart from South Africa that had a phased nation-wide implementation of a comprehensive integrated chronic disease model, the three other countries - Malawi, Kenya and Swaziland, had either pilot implementations or nation-wide single-disease integration of NCDs and HIV. Opportunities for HIV/NCD integration policies included: presence of overarching health policy documents that recognize the need for integration, and coordinated action by policymakers, researchers and implementers. Evidence gaps for cost-effectiveness, effects of integration on key HIV and NCD outcomes and funding mechanisms for sustained implementation of integrated HIV/NCD care strategies, were among challenges identified. CONCLUSION: Policymakers in Malawi, Kenya, South Africa and Swaziland have considered integration of NCD and HIV care but a lack of robust evidence hampers large-scale implementation of HIV/NCD integration. It is crucial for SSA Ministries of Health and throughout low-and-middle-income countries to utilize existing opportunities and advocate for evidence-informed HIV/NCD integration strategies.

Early experiences in integrating cervical cancer screening and treatment into HIV services in Zomba Central Hospital, Malawi.

Background: Malawi has the highest rate of cervical cancer globally and cervical cancer is six to eight times more common in women with HIV. HIV programmes provide an ideal setting to integrate cervical cancer screening. Methods: Tisungane HIV clinic at Zomba Central Hospital has around 3,700 adult women receiving treatment. In October 2015, a model of integrated cervical cancer screening using visual inspection with acetic acid (VIA) was adopted. All women aged 20 and above in the HIV clinic were asked if they had cervical cancer screening in the past three years and, if not, were referred for screening. Screening was done daily by nurses in a room adjacent to the HIV clinic. Cold coagulation was used to treat pre-cancerous lesions. From October 2016, a modification to the HIV programme's electronic medical record was developed that assisted in matching numbers of women sent for screening with daily screening capacity and alerted providers to women with pre-cancerous lesions who missed referrals or treatment. Results: Between May 2016 and March 2017, cervical cancer screening was performed in 957 women from the HIV clinic. Of the 686 (71%) women who underwent first ever screening, 23 (3.4%) were found to have VIA positive lesions suggestive of pre-cancer, of whom 8 (35%) had a same-day cold coagulation procedure, seven (30%) deferred cold coagulation to a later date (of whom 4 came for treatment), and 8 (35%) were referred to surgery due to size of lesion; 5/686 (0.7%) women had lesions suspicious of cancer. Conclusion: Incorporating cervical cancer screening into services at HIV clinics is feasible. A structured approach to screening in the HIV clinic was important.

Reframing noncommunicable diseases and injuries for the poorest Malawians: the Malawi National NCDI Poverty Commission.

Noncommunicable diseases and injuries (NCDIs) account for nearly 70% of deaths worldwide, with an estimated 75% of these deaths occurring in low- and middle-income countries. Globally, the burden of disease from noncommunicable diseases (NCDs) is most often caused by the "big 4," namely: diabetes, cardiovascular diseases, cancer, and chronic lung diseases. However, in Malawi, these 4 conditions account for only 29% of the NCDI disease burden. The Malawi National NCDI Poverty Commission was launched in November 2016 and will describe and evaluate the current NCDI situation in Malawi, with a focus on the poorest populations. The National Commission will investigate which NCDIs cause the biggest burden, which are more present in the young, and which interventions are available to avert death and disability from NCDIs in Malawi, particularly among the poorest segments of the population. The evidence gained through the work of this Commission will help inform research, policy, and programme interventions, all through an advocacy lens, as we strive to address the impact of NCDIs among all populations in Malawi.

The burden of hypertension, diabetes mellitus, and cardiovascular risk factors among adult Malawians in HIV care: consequences for integrated services.

BACKGROUND: Hypertension and diabetes prevalence is high in Africans. Data from HIV infected populations are limited, especially from Malawi. Integrating care for chronic non-communicable co-morbidities in well-established HIV services may provide benefit for patients by preventing multiple hospital visits but will increase the burden of care for busy HIV clinics. METHODS: Cross-sectional study of adults (≥18 years) at an urban and a rural HIV clinic in Zomba district, Malawi, during 2014. Hypertension and diabetes were diagnosed according to stringent criteria. Proteinuria, non-fasting lipids and cardio/cerebro-vascular disease (CVD) risk scores (Framingham and World Health Organization/International Society for Hypertension) were determined. The association of patient characteristics with diagnoses of hypertension and diabetes was studied using multivariable analyses. We explored the additional burden of care for integrated drug treatment of hypertension and diabetes in HIV clinics. We defined that burden as patients with diabetes and/or stage II and III hypertension, but not with stage I hypertension unless they had proteinuria, previous stroke or high Framingham CVD risk. RESULTS: Nine hundred fifty-two patients were enrolled, 71.7% female, median age 43.0 years, 95.9% on antiretroviral therapy (ART), median duration 47.7 months. Rural and urban patients' characteristics differed substantially. Hypertension prevalence was 23.7% (95%-confidence interval 21.1-26.6; rural 21.0% vs. urban 26.5%; p = 0.047), of whom 59.9% had stage I (mild) hypertension. Diabetes prevalence was 4.1% (95%-confidence interval 3.0-5.6) without significant difference between rural and urban settings. Prevalence of proteinuria, elevated total/high-density lipoprotein-cholesterol ratio and high CVD risk score was low. Hypertension diagnosis was associated with increasing age, higher body mass index, presence of proteinuria, being on regimen zidovudine/lamivudine/nevirapine and inversely with World Health Organization clinical stage at ART initiation. Diabetes diagnosis was associated with higher age and being on non-standard first-line or second-line ART regimens. CONCLUSION: Among patients in HIV care 26.6% had hypertension and/or diabetes. Close to two-thirds of hypertension diagnoses was stage I and of those few had an indication for antihypertensive pharmacotherapy. According to our criteria, 13.0% of HIV patients in care required drug treatment for hypertension and/or diabetes.

Clinical development of dietary supplements: the perils of starting at phase III.

Dietary supplements are in worldwide use particularly for diseases for which conventional agents are ineffective. Many of the diseases have subjective endpoints and variable natural histories which lead to large placebo effects. Phase III studies with their large resource requirements should not be undertaken until the commonly used dose of the dietary supplement has been evaluated vs placebo, and if necessary raised until specific efficacy is demonstrated, in phase II testing. If phase II tests precede phase III evaluation, a product destined to fail will not consume important resources, and the optimum dose of products destined to succeed can be identified.

Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C.

Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferon-based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady-state exposures for silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5-fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.

Tolerability of azithromycin as malaria prophylaxis in adults in northeast papua, indonesia.

Drug tolerability affects compliance. We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day; n = 148 subjects), doxycycline (100 mg/day; n = 75), and placebo (n = 77) as prophylaxis against malaria in Indonesian adults over 20 weeks. Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed. The loading dose was well tolerated. The frequencies (number per person-years [p-yr]) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo. Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 [95% confidence interval, 2.8 to 88.1]), paresthesia (2.03 [1.08 to 4.24]), and mild (1.55 [1.01 to 2.48]) and severe (11.2 [1.34 to infinity ]) itching but less often of fever (0.21 [0.09 to 0.49]) and tinnitus (0.09 [0.04 to 0.21]). Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity. One azithromycin recipient developed an erythematous rash. Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment.