Systematic Review of Hypertension and Diabetes Burden, Risk Factors, and Interventions for Prevention and Control in Malawi

screening and 0.80 for the full text screening. Detailed search results are summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart (Fig. 1). Descriptive overview of included studies Of the 23 included studies, 6 reported on point prevalence estimates of hypertension or diabetes, 5 reported on the status of diabetes care (primary care approach, patient experience, peer support program, diabetes control and complications, and quality of life), 1 reported uptake of care and retention of hypertension and diabetes care, 3 reported an integrated hypertension or diabetes and human immunodeficiency virus (HIV) model of care, 2 reported implementation of policies and strategies for NCD care, and 8 provided information on risk factors associated with hypertension and diabetes. Studies spanned both urban and rural settings and included 17 cross-sectional studies (78%), 4 case studies or lesson learned (17%), 1 case-control study (4%), and 1 policy brief (4%). A detailed overview of all included studies is shown in Table 1. Prevalence of hypertension and diabetes Prevalence of hypertension was reported in 6 studies. Estimated rates of hypertension varied widely, ranging from 15.8% to 32.9%; the majority were undiagnosed and therefore untreated (Table 2) [5,6]. One isolated study using routinely collected facility-based electronic medical records data reported a 53% prevalence of hypertension [10]. The only large and rigorous population-based study in Malawi [5] reported a crude prevalence of hypertension of 14.7% in urban areas and 13.6% in rural areas, with a weighted age-standardized national prevalence of 15.8%. Although one study took place solely in an urban setting and one took place solely in a rural setting, the majority contained data from both, with only one nationallyrepresentative survey. Mean participant age ranged from 36.6 to 51.5 years and sample size ranged from 356 to 28,871 persons (Table 2). There was no clear trend in the prevalence estimates over the past 10 years. Prevalence of diabetes was reported in 5 independent studies, with estimates ranging from 1.7% to 5.6% (Table 2) [5,11], with an isolated facility based study reported an 18% prevalence of diabetes [10]. Urban settings presented a higher prevalence compared with rural areas. In a nationwide WHO STEPwise approach to Surveillance (STEPS) survey, the prevalence of diabetes was reported to be 5.4% in urban areas and 4.4% in rural settings [11]. The only large and rigorous population-based study in Malawi [5] reported a crude diabetes prevalence of 2.4% overall (3.0% in urban areas and 1.7% in rural areas), representing a national prevalence of 2.6% (weighted for urban vs. rural population distribution). Sample size ranged considerably between studies, from 356 in a rural study in Chiradzulu GLOBAL HEART, VOL. 14, NO. 2, 2019 June 2019: 109-118 district [12] to 28,871 in a 2-site population-based survey by Price et al. [5]. Of the included studies, only one was a nationally covered survey whereas most others took place in both rural and urban settings. Mean participant age ranged from 36.6 to 51.5 years, with the majority of studies presenting a greater proportion of female participants (Table 2). No studies specifically reported the prevalence of type 1 diabetes. Risk factors for hypertension and diabetes Risk factors for diabetes and hypertension in Malawi were reported in 8 independent studies (Table 3). Reported risk factors for hypertension included old age, obesity, high body mass index (BMI), high waist-to-hip ratio (WHR), tobacco smoking, excessive alcohol consumption, physical inactivity, low fruit and vegetable intake, and in 1 isolated study, television ownership [6,13,14] (Table 3). For HIVinfected individuals, a current antiretroviral therapy (ART) regimen of zidovudine/lamivudine/nevirapine was shown to be a risk factor for hypertension [15]. Among the most commonly cited risk factors for diabetes mellitus were old age, tobacco smoking, excessive alcohol consumption, obesity, physical inactivity, low fruit and vegetable intake, high BMI, and high WHR [10,14,15]. For HIV-infected individuals, a current ART regimen other than tenofovir/lamivudine/efavirenz and zidovudine/lamivudine/nevirapine was shown to be a risk factor for diabetes in 1 study [15]. HIV-infected patients had a 2-fold higher prevalence of diabetes than negative control participants [12] (Table 3). Clinical care of patients with hypertension and diabetes Clinical care of diabetes and hypertension were thematically synthesized based on intervention strategies. The 3 types of clinical studies included in this review examined the quality of clinical care of diabetes and hypertension at a primary health care facility, the components of innovative models of care, and the efficacy of self-management and peer-support programs which aim to support formal care in Malawi. A summary of the barriers and facilitators to implementing hypertension and diabetes interventions and clinical care in Malawi is shown in Table 4. Clinical care Clinical care takes place in specialized diabetes clinics, general hypertension or NCD clinics in district hospitals, central hospitals, or health centers [16]. Uptake of clinical care among patients referred for care was 61%; higher in rural areas (72%) than in urban areas (51%) [17]. The quality of clinical management was generally reported as low, with poorly trained personnel, a persistent shortage of supplies and medication, poor patient record-keeping, low

As in other countries in Africa, Malawi lacks reliable data to accurately quantify the burden of NCDs and their risk factors to design context specific interventions. However, a number of research initiatives have been set up recently to respond to these emerging concerns. Among these is the NCD BRITE (Building Research capacity, Implementation, and Translation Expertise)-a transdisciplinary consortium consisting of key institutions in Malawi aimed at building research capacity, implementation, and translation expertise. In this systematic and narrative review, we critically synthesize available literature from Malawi on the burden, risk factors, and interventions that have been implemented for their prevention and control. The review has focused on hypertension and diabetes, as they are important in the local setting. Here, we draw together available data from Malawi to identify implementation research strategies to tackle these NCDs.

Search strategy and selection criteria
This systematic review follows the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses The NCD BRITE consortium is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under grant number 5U24HL136791-01. The content in this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors report no relationships that could be construed as a conflict of interest. Supplementary data associated with this article can be found, in the online version, at https://doi. org/10.1016/j.gheart.2019. 05.001. From *Dignitas International, Zomba, Malawi; yDalla Lana School of Public Health, University of [8]. PubMed, Medline, EMBASE, and the World Health Organization Global Health Library databases were searched in June 2018 using Medical Subject Headings and free text terms to identify eligible studies (Online Appendix). Studies from January 2008 to June 2018 were retrieved without language restriction. The search strategy was tailored to each database to allow for variations in structure and terminology. Detailed search parameters are available in the Online Appendix.
Two authors (S.H.L. and D.J.) independently reviewed each title and abstract for inclusion, followed by a comprehensive full-text screening. Any disagreement was resolved by joint review of the article with a third reviewer (A.A.). All studies conducted in Malawi that reported on the prevalence of hypertension, diabetes, or their associated risk factors and interventions for prevention and control were included. No restrictions were placed on population, age, or language. Owing to the paucity of research in this setting, all study designs were made eligible for inclusion, with the exception of commentaries and editorials.

Data extraction
Study data were extracted from all included studies in a pre-formulated table. Extracted data included the first author's name, condition studied, study location, study setting (population based or hospital-based), study design (cross-sectional, case-control, cohort, or case study), year of study, study population, methods used to diagnose diabetes and hypertension, point prevalence estimates, mean or median age of the population, proportion of male and female individuals, and study results. Risk factors relating to hypertension and diabetes were collated using a narrative synthesis approach. Two investigators (S.H.L. and D.J.) independently extracted data from individual studies, and extracted data were re-evaluated by a third investigator (A.A.), with disagreements being resolved through consensus.

Quality assessment
The methodological quality of included studies was evaluated independently by 2 authors (S.H.L. and D.J.) using an adapted version of the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies [9]. The detailed quality assessment tool and results are available in the Online Appendix. Inter-rater agreement between investigators for study inclusion and methodological quality assessment were assessed using Cohen's kappa coefficient.

Review process and study characteristics
A total of 237 publications met the inclusion criteria. After elimination of 112 duplicates, 125 articles were screened based on title and abstract, 23 of which were included in the systematic review after careful screening of search results. Among the included studies, 12 (52.2%) were rated as high quality, 6 (26.1%) were rated as medium quality, and 5 (21.7%) were rated as low quality. Inter-rater agreement (Cohen's kappa) was 0.78 for the title and   jg REVIEW abstract screening and 0.80 for the full text screening. Detailed search results are summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart (Fig. 1).

Descriptive overview of included studies
Of the 23 included studies, 6 reported on point prevalence estimates of hypertension or diabetes, 5 reported on the status of diabetes care (primary care approach, patient experience, peer support program, diabetes control and complications, and quality of life), 1 reported uptake of care and retention of hypertension and diabetes care, 3 reported an integrated hypertension or diabetes and human immunodeficiency virus (HIV) model of care, 2 reported implementation of policies and strategies for NCD care, and 8 provided information on risk factors associated with hypertension and diabetes. Studies spanned both urban and rural settings and included 17 cross-sectional studies (78%), 4 case studies or lesson learned (17%), 1 case-control study (4%), and 1 policy brief (4%). A detailed overview of all included studies is shown in Table 1.

Prevalence of hypertension and diabetes
Prevalence of hypertension was reported in 6 studies. Estimated rates of hypertension varied widely, ranging from 15.8% to 32.9%; the majority were undiagnosed and therefore untreated (Table 2) [5,6]. One isolated study using routinely collected facility-based electronic medical records data reported a 53% prevalence of hypertension [10]. The only large and rigorous population-based study in Malawi [5] reported a crude prevalence of hypertension of 14.7% in urban areas and 13.6% in rural areas, with a weighted age-standardized national prevalence of 15.8%. Although one study took place solely in an urban setting and one took place solely in a rural setting, the majority contained data from both, with only one nationallyrepresentative survey. Mean participant age ranged from 36.6 to 51.5 years and sample size ranged from 356 to 28,871 persons ( Table 2). There was no clear trend in the prevalence estimates over the past 10 years.
Prevalence of diabetes was reported in 5 independent studies, with estimates ranging from 1.7% to 5.6% (Table 2) [5,11], with an isolated facility based study reported an 18% prevalence of diabetes [10]. Urban settings presented a higher prevalence compared with rural areas. In a nationwide WHO STEPwise approach to Surveillance (STEPS) survey, the prevalence of diabetes was reported to be 5.4% in urban areas and 4.4% in rural settings [11]. The only large and rigorous population-based study in Malawi [5] reported a crude diabetes prevalence of 2.4% overall (3.0% in urban areas and 1.7% in rural areas), representing a national prevalence of 2.6% (weighted for urban vs. rural population distribution). Sample size ranged considerably between studies, from 356 in a rural study in Chiradzulu district [12] to 28,871 in a 2-site population-based survey by Price et al. [5]. Of the included studies, only one was a nationally covered survey whereas most others took place in both rural and urban settings. Mean participant age ranged from 36.6 to 51.5 years, with the majority of studies presenting a greater proportion of female participants (Table 2). No studies specifically reported the prevalence of type 1 diabetes.

Risk factors for hypertension and diabetes
Risk factors for diabetes and hypertension in Malawi were reported in 8 independent studies (Table 3). Reported risk factors for hypertension included old age, obesity, high body mass index (BMI), high waist-to-hip ratio (WHR), tobacco smoking, excessive alcohol consumption, physical inactivity, low fruit and vegetable intake, and in 1 isolated study, television ownership [6,13,14] (Table 3). For HIVinfected individuals, a current antiretroviral therapy (ART) regimen of zidovudine/lamivudine/nevirapine was shown to be a risk factor for hypertension [15]. Among the most commonly cited risk factors for diabetes mellitus were old age, tobacco smoking, excessive alcohol consumption, obesity, physical inactivity, low fruit and vegetable intake, high BMI, and high WHR [10,14,15]. For HIV-infected individuals, a current ART regimen other than tenofovir/lamivudine/efavirenz and zidovudine/lamivudine/nevirapine was shown to be a risk factor for diabetes in 1 study [15]. HIV-infected patients had a 2-fold higher prevalence of diabetes than negative control participants [12] (Table 3).

Clinical care of patients with hypertension and diabetes
Clinical care of diabetes and hypertension were thematically synthesized based on intervention strategies. The 3 types of clinical studies included in this review examined the quality of clinical care of diabetes and hypertension at a primary health care facility, the components of innovative models of care, and the efficacy of self-management and peer-support programs which aim to support formal care in Malawi. A summary of the barriers and facilitators to implementing hypertension and diabetes interventions and clinical care in Malawi is shown in Table 4.

Clinical care
Clinical care takes place in specialized diabetes clinics, general hypertension or NCD clinics in district hospitals, central hospitals, or health centers [16]. Uptake of clinical care among patients referred for care was 61%; higher in rural areas (72%) than in urban areas (51%) [17]. The quality of clinical management was generally reported as low, with poorly trained personnel, a persistent shortage of supplies and medication, poor patient record-keeping, low gREVIEW j  patient education, and poorly defined protocol for care delivery [16,18,19].

Innovative models of care
Innovative models of care involved leveraging HIV clinical service delivery facilities to provide a platform for NCDs screening and treatment [20,21]. The studies documented that integration of hypertension and diabetes screening and care into an HIV clinic is feasible despite various challenges including frequent stock out and dispensing of NCD drugs, workload, and issues related to data monitoring and evaluation. Applying an electronic monitoring and evaluation system to routinely monitor and report these patients for efficient rational drug forecasting and planning of logistics and staffing has been recommended [22].

DISCUSSION
This systematic review of the literature revealed a high burden of hypertension and diabetes in Malawi, with estimates ranging from 15.8% to 32.9% and 1.7% to 5.6%, respectively. Most cases of hypertension and diabetes remain undiagnosed, untreated, or inadequately controlled. Risk factors associated with these NCDs include increasing age (older age), tobacco smoking, excessive alcohol consumption, obesity, physical inactivity, low fruit and vegetable intake, high BMI, and high WHR. Selected ART regimens were also associated with increased diabetes and hypertension risk in HIV patient populations. Among the included studies, discrepancies exist in the prevalence and distribution of hypertension between urban and rural settings. While the nationwide STEPS survey reported a higher rural prevalence of 32.0% compared with an urban prevalence of 27.9% [6], studies by Price et al. [5] and Divala et al. [15] report lower estimates, with rural prevalence estimates of 13.6% and 21.0% compared with urban estimates of 14.7% and 26.5%, respectively. For diabetes, higher burden has consistently been reported in urban compared to rural settings, specifically in studies by Price et al. [5], Divala et al [15], and Msyamboza et al [23]. Studies with older population samples generally reported higher prevalence of diabetes and hypertension when compared with younger populations [5,11], which is consistent with previous studies reporting older age as a risk factor for diabetes and hypertension [7].
Our review also found a wide variability in prevalence estimates of both hypertension and diabetes across Malawi with no clear time trend, and is more pronounced for hypertension than diabetes estimates. The substantial heterogeneity found between studies was mainly explained by issues related to study methodology, including variation in the diagnosis criterion, the use of different cutoff measures, study settings, data source (primary vs. routinely collected facility-based data), relatively smaller sample sizes, unclear participant selection, and larger proportion of missing outcome data. Our review demonstrated that there is an increased risk of hypertension and diabetes at a younger age and often in individuals with relatively low or normal BMI [5]. The mechanism is not understood but may be related to early life risk factors including low birth weight and undernutrition. Traditional risk factors including tobacco, alcohol, and physical inactivity in Malawi appear to be increasing [5,6], with at least 1 in 4 men smoking tobacco, 1 in 5 men drinking alcohol excessively, and at least 1 in 4 women were overweight or obese [5,6]. More than one-half of the individuals in urban and rural Malawi reported a consumption of salt exceeding the 5 g/day recommended limit set by the World Health Organization [5]. The use of more than an equivalent of 6 teaspoons of sugar per day in sweetened drinks was also common [5]. The higher burden of hypertension and diabetes in younger age groups and the relative increase in traditional risk factors emphasizes that context-based interventions should start early in the life course.
In this systematic review, clinical care of hypertension and diabetes in Malawi were examined based on 3 categories: typical clinical care, innovative models of care, and external patient support strategies. Given limited human and financial resources, innovative models of care are required to mitigate the growing burden of NCDs in Malawi. More broadly, we identified 2 innovative models of care integration across Malawi [20,21]. The first model of care in southern Malawi is an integrated chronic care clinic that utilizes an HIV program as a platform for various chronic care screening and treatment (hypertension, diabetes, asthma, and epilepsy, regardless of HIV status) [21]. This model of care allows patients with chronic conditions or HIV to be screened and treated at a single facility during a single visit. The second model of care from central Malawi reported leveraging an HIV service platform for the screening and treatment of hypertension [20]. These studies documented that the integration of hypertension and diabetes screening into an HIV clinic is feasible despite various challenges including frequent stock out and dispensing of NCD drugs, patient flow, workload, and issues related to data monitoring and evaluation [20,21]. A recent NCD model of care review in sub-Saharan Africa also revealed that leveraging existing human resources, decentralization of NCD care to primary health facilities, task redistribution including to lay health cadres, designing patient-centered quality of care, and continued training and mentorship are key to successes of NCD treatment and control [24]. Although community screening and sensitization on the need for NCD care is critical, strategies are needed to ensure better linkage and retention into care [17].
In our review, patient-centered diabetes care has been explored in 2 studies [25,26]. Management strategies external to formalized clinical settings include selfmanagement and peer-support programs [25,26]. Selfmanagement centers around patient education regarding their condition to better manage their own care [25]. Peersupport programs leverage the geographic proximity of jg REVIEW patient groups to develop a supportive care network outside of the clinic setting [26].
Malawi's 2011 to 2016 Health Sector Strategic Plan [27] included NCDs, and an NCD Control Program was established with the development of the 2013 National Action Plan for prevention and management of NCDs [28]. Currently, a new Strategic Plan is under development. Although Malawi has begun to address the emerging burden of NCDs, our review of policy implementations for NCD prevention and control showed gaps in terms of provision of quality clinical care and lack of comprehensive active screening, prevention, community awareness, and outreach activities [29]. In terms of financial support, although NCDs are included in district implementation plans, most of the planned activities are unfunded and therefore unexecuted [29].
Although a nationwide STEPS survey was conducted in 2009 [6] and a subsequent large-scale populationbased study was conducted in urban and rural Malawi in 2016 [5] to assess the prevalence and risk factors of hypertension and diabetes in Malawi, there remains a dearth of high-quality literature to support those research findings. To provide reliable data, standardized survey and measurement protocols must be developed and employed. Robust data are needed regarding the burden and risk factors for NCDs, particularly with attention to relative contributions of subtypes of conditions (e.g., causes of cardiovascular disease) and risk factors related to living in poverty. Moreover, this systematic review uncovers a need for a greater amount of high-quality research related to NCDs, particularly among children and adolescents in Malawi as well as among the poor, which may permit a better estimate of the national trends of chronic disease conditions. Phase 4 Translation research is also warranted to assess the implementation of the different innovative models of NCD care, including the cost effectiveness of various approaches to provide information for scaling up. The contribution of nontraditional risk factors for NCDs, including infections and undernutrition, were not explored in Malawi and requires future study.
This systematic review should be interpreted in the context of its limitations. We have only considered literature published in the last 10 years, which precludes data from earlier reports. We included 23 studies, among which 12 (52.2%) were rated as high quality, 6 (26.1%) were rated as medium quality, and 5 (21.7%) were rated as low quality. Prevalence data reported in this review span quite a wide range. The heterogeneity of reported data may be attributed to low sample sizes, differing population demographics, insufficient control for confounders, and the usage of variable diagnostic criteria and measurement techniques between studies. Despite these limitations, this study is the first systematic review of hypertension and diabetes disease burden and risk factors in Malawi providing a clear summary of the existing knowledge on these conditions. Moreover, the review summarized the various models of clinical care currently underway in Malawi.

CONCLUSIONS
The prevalence of and risk factors for hypertension and diabetes is high in Malawi, which is consistent with findings from other settings in sub-Saharan Africa. As treatment of priority conditions such as HIV continues to improve in these settings, NCDs are increasingly being recognized as the next frontier in health. This preliminary review puts the currently available literature into context and elucidates critical gaps of research in the field.