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. 2021 Mar 19;16(3):e0248966. doi: 10.1371/journal.pone.0248966

An assessment of non-communicable disease mortality among adults in Eastern Uganda, 2010–2016

Davis Natukwatsa 1,2,*, Adaeze C Wosu 3, Donald Bruce Ndyomugyenyi 1,2, Musa Waibi 1,2, Dan Kajungu 1,2
Editor: Amir Radfar4
PMCID: PMC7978282  PMID: 33739993

Abstract

Background

There is a dearth of studies assessing non-communicable disease (NCD) mortality within population-based settings in Uganda. We assessed mortality due to major NCDs among persons ≥ 30 years in Eastern Uganda from 2010 to 2016.

Methods

The study was carried out at the Iganga-Mayuge health and demographic surveillance site in the Iganga and Mayuge districts of Eastern Uganda. Information on cause of death was obtained through verbal autopsies using a structured questionnaire to conduct face-face interviews with carers or close relatives of the deceased. Physicians assigned likely cause of death using ICD-10 codes. Age-adjusted mortality rates were calculated using direct method, with the average population across the seven years of the study (2010 to 2016) as the standard. Age categories of 30–40, 41–50, 51–60, 61–70, and ≥ 71 years were used for standardization.

Results

A total of 1,210 deaths among persons ≥ 30 years old were reported from 2010 to 2016 (50.7% among women). Approximately 53% of all deaths were due to non-communicable diseases, 31.8% due to communicable diseases, 8.2% due to injuries, and 7% due to maternal-related deaths or undetermined causes. Cardiovascular diseases accounted for the largest proportion of NCD deaths in each year, and women had substantially higher cardiovascular disease mortality rates compared to men. Conversely, women had lower diabetes mortality rates than men for five of the seven years examined.

Conclusions

Non-communicable diseases are major causes of death among adults in Iganga and Mayuge; and cardiovascular diseases and diabetes are leading causes of NCD deaths. Efforts are needed to tackle NCD risk factors and provide NCD care to reduce associated burden and premature mortality.

Introduction

Non-communicable diseases (NCDs) are serious global health challenges, particularly in low and middle income countries (LMICs) where rates of these conditions are rising due to significant and rapid changes in social and behavioural risk factors, and health systems are often overstretched [1]. Global efforts to curb the rise of NCDs include the WHO global action plan for prevention and control of NCDs which was established in 2013 [2], and the current United Nations agenda of 17 Sustainable Development Goals (SDGs) includes the goal of “ensuring healthy lives and promoting well-being for all at all ages”, as well as reducing premature deaths due to non-communicable diseases by a third through prevention and treatment by 2030 [3]. Monitoring NCD morbidity and mortality is necessary to ascertain progress on national and global efforts. However, timely and accurate population-level health data remains limited in many LMICs due to lack of unbiased data collection systems [4].

Many LMICs lack civil registration and vital statistics systems and depend on mortality estimates from hospitals. However, hospital-based estimates do not give a complete picture on mortality as these facilities do not collect information on deaths occurring outside the healthcare system [5–7]. Given the challenges around civil registration and vital statistics in LMICs, health and demographic surveillance systems (HDSS) present an important source of information about the health of communities. A health and demographic surveillance system is a platform that collects longitudinal data, and monitors demographic transitions and health indicators among individuals within a well-defined geographic area [1].

A typical health and demographic surveillance system conducts verbal autopsies (VA) to generate cause-of-death data where standardized interviews are held with carers or close relatives of deceased persons to understand the circumstances surrounding the deaths [8,9]. The tool used to carry out these interviews is detailed and provides the interviewer an opportunity to get more in-depth information about the deceased. Questions are focused on the deceased’s history, tracing from birth, to any illness that led to death, care-seeking patterns, challenges involved in getting treatment, and place of death. Interviews are then analysed to ascertain the most probable cause of death [10,11]. Leveraging on the capacity of HDSS to capture deaths, these systems present useful platforms for understanding mortality through longitudinal surveillance.

The present analysis is based on cause-of-death data generated through verbal autopsies conducted in Iganga-Mayuge Health and Demographic Surveillance Site (IMHDSS) in Eastern Uganda. We assessed mortality rates due to NCDs among persons ≥ 30 years old for the period 2010 to 2016. We were particularly interested in understanding mortality patterns due to cardiovascular diseases (CVD), cancers, and diabetes, conditions which are leading contributors to NCD mortality globally and within sub-Saharan Africa [1].

Materials and methods

Study area and population

The Iganga-Mayuge HDSS is located in the Iganga and Mayuge districts in Eastern Uganda and was established in 2005. The demographic surveillance area consists of 65 villages spread over a 155km2 area with a population of 94,568 at the end of 2017. The average household size is five individuals, and the area is predominantly rural, with some peri-urban areas. Subsistence agriculture is the main occupation and sex distribution is roughly equal, with 51% female. Approximately 40% of the population is less than 15 years old. The Iganga-Mayuge HDSS collects longitudinal data on births, deaths (and causes of deaths), and migrations; and monitors key interventions at a community-level [12].

Verbal autopsy

Verbal autopsy is an epidemiological tool used to assess cause of death in settings where reliable civil registration and vital statistics systems are lacking [13,14]. Iganga-Mayuge HDSS conducts verbal autopsies to ascertain causes of death in the population. Data collectors report deaths that occur in the surveillance communities to the HDSS offices during routine data collection rounds conducted every six months. As of 2017, the overall response rate in the HDSS survey rounds was over 75%, after accounting for vacant homes (10.4%), demolished homes (5.8%), changed status of premises (5.5%), those not found at home (0.2%) and refusals (0.04%) [12]. The Verbal Autopsy Structured Questionnaire (developed by World Health Organisation in 2014 and standardized by the HDSS) is used to conduct face-to-face interviews with relatives or carers of the deceased [15]. The questionnaire requests information about the circumstances surrounding the death as well as healthcare sought.

Classification of causes of death

Two physicians independently review verbal autopsies and assign cause of death using the International Statistical Classification of Diseases and Related Health Problems (ICD-10). In case of disagreements, both physicians hold a consensus meeting to compare results and establish the most probable cause of death. In case of further disagreement on cause of death, a third physician breaks the tie [16,17]. For the present analysis, information on deaths among persons aged ≥ 30 years old was extracted from the Iganga-Mayuge HDSS database.

Statistical analyses

Age-adjusted mortality rates (AAMR) were calculated using direct method, with the average population across the seven years of the study (2010 to 2016) as the standard. We used age categories of 30–40, 41–50, 51–60, 61–70, and ≥ 71 years for the standardization. For these calculations, the numerator was the number of deaths among persons ≥ 30 years old while the denominator was total number of people ≥ 30 years old in the population at midyear. Stata version 14 was used for analyses [18].

Outcome definitions

First, causes of death were broadly classified as communicable diseases, non-communicable diseases and injuries. Communicable diseases included those diseases that can be transmitted including: HIV/AIDS, pulmonary tuberculosis, malaria, acute febrile illnesses, diarrhoeal diseases, pneumonia and acute respiratory infections. Non-communicable diseases included those conditions that are non-infectious and typically of a chronic duration including: heart disease, diabetes, cardiovascular diseases, renal disorders, cancers, abdominal conditions and central nervous system disorders. Injuries consisted of accidental and intentional deaths including: accidental poisoning, animal bite/attack, drowning, falls, homicidal injuries, road traffic accidents, and suicidal injuries. As our focus is on major non-communicable diseases (NCDs), we further classified this category into cardiovascular diseases, cancers, diabetes, acute abdominal conditions, and other NCDs.

Ethical considerations

Ethical approval was received from the Makerere University School of Public Health Research and Ethics Committee (MakSPH IRB 042) and the Uganda National Council of Science and Technology (UNCST SS2002). Informed consent was received from relatives or carers of the deceased who were ≥ 18 years of age, and data was anonymized before analysis. All respondents were told about the content and purpose of the data collection.

Results

All NCD mortality

A total of 1,210 deaths among persons ≥ 30 years old were reported from 2010 to 2016. Of the total number of deaths under consideration, 50.7% were among women. The mean age of the deceased was 49.3 years, with a standard deviation of 14.4 years. Approximately 53% of all deaths among persons ≥ 30 years were due to non-communicable diseases, 31.8% due to communicable diseases, 8.2% due to injuries, and 7% due to maternal-related deaths or undetermined causes. Fig 1 shows the age-adjusted mortality rates from NCDs, communicable diseases and injuries for each of the seven years under consideration.

Fig 1. Age-adjusted mortality rates of three major disease categories (communicable diseases, NCDs, and injuries) in IM-HDSS, expresses per 10,000 persons, 2010–2016.

Fig 1

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As shown in Table 1, cardiovascular diseases accounted for the largest proportion of reported NCD deaths in each year. There were substantial fluctuations in the rates of cardiovascular disease deaths between 2010 and 2016. Specifically, between 2010 and 2011, cardiovascular disease mortality rates (per 10,000 persons) increased by 71.2% (15.52 vs. 26.57), and decreased by over half between 2011 and 2012. Cardiovascular disease mortality rates also increased over two-fold between 2012 and 2013, from 12.55 to 30.33 (per 10,000 persons). Similar jumps were observed in diabetes mortality rates—between 2010 and 2011, the diabetes mortality rate increased 67.6% (4.47 vs. 7.49 per 10,000 persons). For the other years, mortality rates from cardiovascular disease remained relatively stable within the range of 12.55 to 16.78 deaths per 10,000 persons. No discernible trends were seen in overall mortality rates from cancers and acute abdominal conditions between 2010 and 2016. Age-adjusted mortality rates (per 10,000 persons) from other NCDs was highest in 2010 (11.89), then 2011 (8.61), and 2012 (7.91), and was in the range of 3.53 to 5.25 per 10,000 persons for the years 2013 to 2016.

Table 1. Age-adjusted mortality rates from major non-communicable diseases in Iganga-Mayuge health and demographic surveillance site, expressed per 10,000 persons, 2010–2016.

All Cardiovascular diseases Diabetes Cancers Acute abdominal conditions Other NCDs
Year Population, number Deaths No. of deaths AAMR No. of deaths AAMR No. of deaths AAMR No. of deaths AAMR No. of deaths AAMR
2010 16,982 180 28 15.52 8 4.47 13 7.32 13 7.40 21 11.89
2011 17,850 208 50 26.57 14 7.49 9 4.80 7 3.84 16 8.61
2012 18,634 149 24 12.55 10 5.26 7 3.68 18 9.48 15 7.91
2013 19,650 196 60 30.33 18 9.08 15 7.58 16 8.06 7 3.53
2014 20,619 152 30 15.02 13 6.46 10 5.01 10 4.93 10 4.96
2015 21,375 165 31 14.91 22 10.59 9 4.21 12 5.81 11 5.25
2016 22,749 160 37 16.78 17 7.78 9 4.13 12 5.35 10 4.50
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AAMR: Age-adjusted mortality rates; NCDs: Non-Communicable Diseases.

Age-adjusted mortality rates are expressed per 10,000 persons.

Gender differences in NCDs

Table 2 shows gender and disease specific NCD mortality rates in 2010 and 2016. As shown in Table 2, women had higher mortality rates from cardiovascular diseases compared to men—in 2010 and 2016, mortality rates per 10,000 persons were 21.38 and 21.86 among women; and 9.49 and 11.28 among men (Fig 2). Across all the years, women had substantially higher cardiovascular disease mortality rates compared to men. Conversely, women had lower diabetes mortality rates than men for all years, except in 2011 and 2015. Women had higher mortality rates from cancers compared to men in 2010 (8.71 vs. 5.84 per 10,000 persons); however, cancer mortality rates were lower for both genders for the subsequent years (with the exception of the jump seen in women in 2013). Overall, men had higher rates of mortality from acute abdominal conditions compared to women. The rate of mortality from other NCDs was higher for men than for women in 2010, and lower for both genders in 2016 (Table 2).

Table 2. Age-adjusted mortality rates by gender, and expressed per 10,000 persons, 2010–2016.
  2010 2011 2012 2013 2014 2015 2016
Cardiovascular disease              
Total 15.52 26.57 12.55 30.33 15.02 14.91 16.78
Men 9.49 21.11 6.54 15.73 10.15 7.90 11.28
Women 21.38 31.59 18.15 43.91 19.68 21.48 21.86
Diabetes              
Total 4.47 7.49 5.26 9.08 6.46 10.59 7.78
Men 4.71 6.58 6.56 11.46 9.13 10.00 11.44
Women 4.22 8.30 4.06 6.86 3.91 11.14 4.39
Cancers              
Total 7.32 4.80 3.68 7.58 5.01 4.21 4.13
Men 5.84 5.47 2.20 4.17 5.18 3.05 4.85
Women 8.71 4.17 5.08 10.75 4.90 5.30 3.48
Acute abdominal conditions              
Total 7.40 3.84 9.48 8.06 4.93 5.81 5.35
Men 11.73 5.69 11.87 9.39 4.05 7.08 5.46
Women 3.33 2.06 7.19 6.81 5.76 4.65 5.26
Other NCDs              
Total 11.89 8.61 7.91 3.53 4.96 5.25 4.50
Men 18.70 14.44 10.96 6.28 6.12 10.95 8.49
Women 5.52 3.13 5.07 0.98 3.83 0.00 0.80
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Fig 2. Age-adjusted, gender-specific mortality rates in IM_HDSS (expressed per 10,000 persons), 2010 and 2016.

Fig 2

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Discussion

We report on NCD mortality rates among persons ≥ 30 years obtained from verbal autopsy reports collected by the Iganga-Mayuge Health and Demographic Surveillance Site (IMHDSS) in Eastern Uganda from 2010 to 2016. Cause of death was determined by verbal autopsies (i.e., physicians studied the history and circumstances surrounding each death to assign most probable cause of death based on ICD-10 codes), a method used to assign cause of death in the absence of well-established vital statistics systems [8,9]. In total, 1,210 deaths were reported between 2010 and 2016. Among broad categories of causes of death, NCDs were the leading cause, accounting for 53% of all deaths. Approximately 31.8% of all deaths were due to communicable diseases, 8.2% due to injuries, and 7% due to maternal-related deaths or of undetermined causes. Furthermore, cardiovascular diseases accounted for the largest proportion of NCD deaths, with substantially higher rates of cardiovascular disease deaths observed for women than for men.

Population-representative studies conducted within the Iganga-Mayuge health and demographic surveillance site show appreciable rates of major NCDs and NCD risk factors in the community. For example, in a study of men and women aged 35 to 60 years old conducted between March and April 2012, Mayega and colleagues observed a 7.4% prevalence of diabetes and 8.6% prevalence of pre-diabetes [19]. Moreover, 6.5% and 9.3% of men had diabetes and pre-diabetes respectively, while the percentages were 8.1% and 8.0% among women. In the same study, the authors noted a 20.5% prevalence of hypertension, 5.8% prevalence of current tobacco use, 4.8% prevalence of harmful use of alcohol, 12.6% prevalence of overweight, and 5.3% prevalence of obesity [19]. In another study examining overweight and obesity among persons aged ≥ 18 years and over, Kirunda and colleagues observed substantial prevalence of overweight and obesity, and significant gender differences. Using standard definitions of overweight (BMI between 25.0–29.99 kg/m2), and obesity (BMI ≥ 30 kg/m2), the authors estimated a 17.8% overweight prevalence (12.4% in men, 23.1% in women); and 7% obesity prevalence (2.0% in men, and 12.7% in women) [20]. Differences in the distribution of NCD risk factors across gender in this geographic area may play a role in observed differences in NCD mortality rates. Qualitative studies conducted within the Iganga-Mayuge area also show that myths and misconceptions about NCDs and their metabolic risk factors are commonplace [21]. Estimates of NCDs and NCD risk factors from studies conducted in Iganga-Mayuge HDSS are congruent with findings from the national non-communicable diseases risk factor survey published in 2015 which found a high prevalence of hypertension in the Eastern region of Uganda (26.4%) among persons 18 to 64 years old [22] Likewise, other studies conducted in rural and urban areas of Uganda showed substantial prevalence of NCDs and NCD risk factors [23–26]. In the national non-communicable diseases risk factor survey, prevalence of hypertension in the Northern, Central and Western regions of Uganda were 23.3%, 28.5%, and 26.3% respectively [22].

While peer-reviewed literature on rates of NCD morbidity and risk factors in Uganda have become more available over the last decade, there is much less information on NCD mortality rates in the country. However, emerging data indicate NCDs as major causes of hospitalization and in-hospital deaths. Investigators of a retrospective study published in 2019 examined medical records on admissions and mortality among in-patients at Mulago Hospital, Kampala, the largest public hospital in Uganda. They observed that an NCD was the primary reason for admission in 72% of patients between January 2011 and December 2014. Of 8,637 deaths that occurred during hospitalization, the following conditions had the highest case-fatality rates: non-tuberculosis pneumonia (28.8%), tuberculosis (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%) [27].

Findings from neighbouring countries also show substantial prevalence of NCD risk factors and conditions, though much less information is available on NCD mortality. A study examining households in Nandi district, rural Kenya, and Dar es Salaam, urban Tanzania found age-standardized hypertension prevalence of 21.4% in the Kenyan sample and 23.7% on the Tanzanian sample [28]. Nationally representative data show a 15.4% prevalence of hypertension in Rwanda among persons aged 15–64 years [29]; and a prevalence of 24–25% among adults aged 25–64 years in Tanzania [30]. A study published in 2019 reported increasing disability-adjusted life years attributable to NCDs between 1990 and 2016 in Kenya [31].

While we are not able to validate the verbal autopsy reports within our study population, findings from some validation studies conducted within sub-Saharan Africa provide support for the utility of physician review of verbal autopsies for determination of NCD deaths. In a study of adult deaths at Kilifi District hospital in Kenya, the authors observed that hospital cause of death (HCOD) based on clinical and laboratory data (gold standard), a computer-based probabilistic model, and physician-certified verbal autopsy (PCVA) obtained the same underlying top five causes of deaths, and the kappa statistic for HCOD compared to PCVA was 0.52 (95% CI: 0.48–0.54). Furthermore, sensitivity for cardiovascular diseases was 70% and 100% for diabetes, while the specificities were both 96% [32]. In another study from Agincourt, South Africa, investigators observed sensitivity, specificity, and positive predictive values of 75%, 98% and 60% for NCDs among adults when comparing physician reviewed verbal autopsies to hospital records [33]. The Addis Ababa Mortality Surveillance Program observed sensitivity, specificity, and positive predictive values of 69%, 78% and 79% for NCDs when comparing physician reviewed verbal autopsies to hospital reports [34]. Physician-certified verbal autopsy has been more widely used for assessments of child mortality within sub-Saharan Africa, and investigators have noted that accuracy and reliability of verbal autopsies may be dependent on respondent factors (e.g., the level of healthcare they have access to), as well as physician knowledge about the epidemiology of disease in the geographic area [35]. These and other factors may influence accuracy and reliability of verbal autopsies in which NCDs are determined to be causes of death.

We cannot completely rule out or determine the extent of potential cause of death misclassification in our study, especially among individuals with multiple morbidities—this is a limitation. Relatedly, we only examined data for seven years within a relatively modest population, thus we were unable to establish clear patterns or trends due to lack of statistical power. Despite these limitations, our study provides much needed assessment of sub-national NCD mortality in Uganda, and at least two physicians reviewed each verbal autopsy report to adjudicate causes of deaths.

Conclusions

From these analyses, it emerges that NCDs are leading causes of death in the Iganga and Mayuge communities in Eastern Uganda, with cardiovascular diseases and diabetes being two predominant causes. Furthermore, there appear to be differences in NCD mortality rates between men and women. In the absence of well-established vital statistics systems, verbal autopsies serve an important role in enabling monitoring of trends and mortality levels in low-resource settings; the utility of these platforms can be further enhanced through assessments of their validity and reliability to identify opportunities for improvements. Our findings contribute to understanding of leading causes of death to inform investments in health systems financing, support for burden of disease research, disease prevention strategies, as well as policy and health systems improvement initiatives in Uganda. Efforts are needed to tackle NCD risk factors and NCD care to reduce the burden and premature mortality due to these conditions.

Acknowledgments

We thank the people of Iganga and Mayuge districts for supporting the activities of Makerere University Center for Health and Population Research (MUCHAP). Special thanks go to MUCHAP staff for their efforts in this study. Finally, we acknowledge the INDEPTH Network for providing technical support towards improving cause-of-death analysis and reporting.

Data Availability

Data is confidential and cannot be shared publicly. Anonymized data can only be shared upon request, as per the data sharing agreement from Makerere University Center for Health and Population Research (MUCHAP). The Iganga Mayuge Health and Demographic Surveillance Site (IMHDSS) is bound to a data sharing agreement with the larger INDEPTH network health and demographic surveillance sites. There is a formal data sharing process guided by data sharing standard operating procedures. Data can be requested formally from the IMHDSS leader (info@muchap.mak.ac.ug) who is the point of contact for all data requests. There are more details on the website (www.muchap.mak.ac.ug)."

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Amir Radfar

1 Dec 2020

PONE-D-20-31885

An analysis of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016

PLOS ONE

Dear Dr. NATUKWATSA,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise the manuscript and address all peer review comments (especially the quality of written English).

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We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. The authors have included adults above 30 years in the study. Adults above 60 years are considered Elderly population. Elderly population usually have many NCDs.

2. Abstract : Keywords : NCD has been repeated.

3. Introduction : Sex may be replaced by Gender in the text and Tables.

4. References - Although relevant references have been cited but they are not uniform.

5. Ref.Nos.7, Name of the journal is missing.

6. Some references are quite old. If possible, cite recent ones.

7. The authors have cited references from Uganda and Nairobi. Is NCD not a problem of other countries ? Try to include relevant references from studies in other countries.

Reviewer #2: Dear Authors,

Thank you for Very interesting and important work on NCD mortality among the among adults in Eastern Uganda.

Abstract, title and references

Yes; the aim of the study is clear. It is very clear what the study found and how they did it.; Yes; the title of the study is relevant, self-explanatory and informative but I would like to suggest to omit an analysis of from the title and the title might be "Non-communicable disease mortality among adults in Eastern Uganda, 2010-2016". References are relevant and recent. Authors used the references very correctly and they included all the appropriate key studies.

Introduction/background

Introduction is explained nicely and justify the importance of the study. It is also explaining the topic in different dimension.; Yes; research question is outlined clearly and aligned with the research problem.

Methods

Yes; the process of subject selection is clear’.; Yes; this study can be replicated easily with the existing methodology written by the authors.

Results

Yes; data is presented in an appropriate way and tables are relevant and clearly presented but it will be better if the trends can be presented through 2 to 3 graphs. Titles, columns, and rows labelled correctly and clearly.; Yes; categories grouped appropriately in the tables.; Yes; the text in the results add to the data and is not repetitive and critically discussed in to the text.; Yes; I am clear about what is a statistically significant result.; Yes; I am also clear enough about what is a practically meaningful result.

Discussion and Conclusions

Yes; the results discussed from multiple angles and placed into context without being overinterpreted.; Yes; the conclusions answered the aims of the study.; Yes; the conclusions supported by results.; No; the limitations of the study are not fatal; and Yes; they are opportunities to inform future research

Major Comments

-----------------

1. Yes, the study design appropriate to answer the aim

2. Yes, this study adds something new that is not known on this topic.

3. Yes, the article is consistent within itself

Minor Comments

-----------------

Need to trend analysis to understand the NCD mortality pattern. Now it is just distribution of NCDs deaths.

Reviewer #3: PLOS REVIEW REPORT

SUMMARY

Use of verbal autopsy to assess premature NCD mortality in resource-poor settings such as rural Eastern Uganda appears appropriate in the absence of country wide civil registration and vital statistics.This study adds to the growing premature NCD mortality data in Africa, even in rural areas.

MAJOR ISSUES

Lack of comparison of these results with the INDEPTH Network data from multiple sites in Africa.

Lack of comparison with epidemiology studies in rural and urban Uganda and and rest of the East Africa region

Wide unexplained disparity and fluctuations in mortality rates in different years especially in CVD and diabetes as well as between males and females. Raises questions about the reliability and accuracy of the data.

Lack of explanation with the unexpectedly high NCD mortality rates in a rural area in the presence of low NCD risk factors such as obesity rates (5.3%) and other risk factors.

In other studies in sub-Saharan Africa, some of the sites reporting the highest rates of NCD mortality were also those with the greatest burden of HIV/AIDS-related mortality. It has been suggested that in such settings, around half of the mortality attributed to NCDs may well be associated with HIV. It is not clear how the authors dealt with this.

MINOR ISSUES

1. The use of a probabilistic model to assign cause of death would have been preferable to

the use of doctors.

OTHER COMMENTS

Very useful source of information in the absence of inadequate data in the rest of the country.

Similar longitudinal studies would be useful in monitoring NCD mortality trends in other areas of the country to determine more reliable national trends.

Despite the HIV, Ebola and the COVID-19 epidemics, for the present as well as the foreseeable future, NCDs will be responsible for the highest morbidity and mortality in sub-Saharan Africa.The findings of studies like this, should spur policy makers to take action to reduce premature adult mortality due to NCDs.

Reviewer #4: Title: An analysis of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016

1. Do the title and abstract accurately convey what has been found?

Yes, title is ok, but I would use the word “assessment” instead of analysis – this is usually reserved for a novel way of analysis e.g., new statistical analysis method

2. Is the writing acceptable?

Yes, writing is acceptable.

3. Are the data sound?

Yes, steps followed look sound and well documented

4. Do the figures appear to be genuine, i.e., without evidence of manipulation?

Yes, figures appear genuine

5. Does the manuscript adhere to the relevant standards for reporting and data deposition?

Yes, standards are adhered to

6. Are the discussion and conclusions well balanced and adequately supported by the data?

Yes, but discussion is quite light might need some beefing up.

7. Are limitations of the work clearly stated?

Yes, study limitations are clearly stated.

8. Do the authors clearly acknowledge any work upon which they are building, both published and unpublished?

Yes, this is done well in the discussion perhaps a little more in the introduction.

9. General Observation

Overall, it is a well described and interesting paper that adds to the current body of evidence and speaks to the current NCD burden especially NCD mortality within sub-Saharan Africa generally and Uganda specifically.

10. Minor Essential Revisions

• Classification of outcomes - indicate how multiple causes of death or multiple conditions present at time of death were handled and death classified in that case e.g., if at death someone had both Cancer and DM or had both DM and accidental death

• Need to reformat the tables to highlight points of interest e.g., bolding or re-aligning or smaller font size for some figures e.g. Table 2 can be better displayed as below

2016 2015 2014

Men Women Overall Men Women Overall Men Women Overall

11.29 19.68 16.78 7.9 21.48 14.91 10.15 21.86 15.02

• Indicate the AAMR units e.g. is it deaths per 10,000 or per 100,000?

• Built up the discussion nicely to indicate the burden and CV risk factor profile in Iganga-Mayuge - but do but not tie it up to show how this would lead to a high CVD mortality e.g.

o What are the known mortality trends in the region if any e.g. Eastern Uganda, in Uganda or E. Africa?

o How do these trends compare with what was found?

o How do they compare with regional hospital mortality trends, any surprises there??

o What might account for the anomalies e.g., fewer deaths in females, fewer deaths to DM in 2016 etc..

o How might these data on mortality be useful going forward, perhaps operationally??

11. Level of interest

I think this is a worthwhile study and a timely addition of valuable information to the current body of evidence with regard to NCD mortality in sub-Saharan Africa.

12. Quality of written English

Acceptable

13. Declaration of competing interests

I declare that I have no competing interests

Reviewer #5: The manuscript is technically sound as a verbal autopsy, a well-established method for such study, was utilized. The data also support the major conclusion of the manuscript that NCD is a major cause of death among the study population. However, the recommendation “…….a unified approach towards disease prevention and treatment that focuses on strengthening health systems” seems far fetching as the finding did not allude to any health system issues.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: TAHZIBA HUSSAIN

Reviewer #2: Yes: Palash Chandra Banik

Reviewer #3: Yes: Prof. Peter Lamptey

Reviewer #4: No

Reviewer #5: Yes: DR. FEKADU ADUGNA DADI, PUBLIC HEALTH SPECIALIST

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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Attachment

Submitted filename: Review for PloS - Natukwatsa et al, 2020.docx

Click here for additional data file. (18.6KB, docx)
PLoS One. 2021 Mar 19;16(3):e0248966. doi: 10.1371/journal.pone.0248966.r002

Author response to Decision Letter 0

18 Feb 2021

Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:

1. The authors have included adults above 30 years in the study. Adults above 60 years are considered Elderly population. Elderly population usually have many NCDs.

Thank you for this comment. Given our modest population, and observations that individuals in low- and middle-income country settings tend to develop and die from NCDs at an earlier age than individuals in high income country settings, we decided to examine NCD mortality in persons aged 30 years and above within our setting. Additionally, we performed age-adjustment to account for confounding by age.

2. Abstract: Keywords: NCD has been repeated.

We have deleted the repeated word.

3. Introduction: Sex may be replaced by Gender in the text and Tables.

The tables and text have been updated as suggested.

4. References - Although relevant references have been cited but they are not uniform.

Thank you for this comment. We have adjusted the references so that they are uniform.

5. Ref.Nos.7, Name of the journal is missing.

Name of journal has now been added to Reference No. 7.

6. Some references are quite old. If possible, cite recent ones.

Thank you for this comment. We have included more recent citations where possible.

For example: Kajungu D, Hirose A, Rutebemberwa E, Pariyo GW, et al. Cohort Profile: The Iganga-Mayuge Health and Demographic Surveillance Site, Uganda (IMHDSS, Uganda). International Journal of Epidemiology 2020 has been referenced in the materials and methods sections. Similarly, Nahimana MR, Nyandwi A, Muhimpundu MA, Olu O, et al. A population-based national estimate of the prevalence and risk factors associated with hypertension in Rwanda: implications for prevention and control. BMC Public Health 2018 has been cited under the discussion section.

7. The authors have cited references from Uganda and Nairobi. Is NCD not a problem of other countries? Try to include relevant references from studies in other countries.

Thank you for this comment. More references from sub-Saharan Africa reporting findings from neighboring countries (Kenya, Rwanda, and Tanzania) have now been added to the discussion section.

Reviewer #2:

We thank the reviewer for recognizing the merits of our study. Below, we have provided point-by-point responses to the reviewer comments

Major Comments

-----------------

1. Yes, the study design appropriate to answer the aim

2. Yes, this study adds something new that is not known on this topic.

3. Yes, the article is consistent within itself

We thank the reviewer for recognizing the merits of our study

Minor Comments

-----------------

Need to trend analysis to understand the NCD mortality pattern. Now it is just distribution of NCDs deaths.

We agree that a trend analysis would be helpful. However, due to few years of data under consideration (only seven years’ worth of data), the modest size of our population, and the few deaths observed in each year, we decided to focus on NCDs assessment with a possibility of doing trend analyses in subsequent publications when there is enough data.

Reviewer #3: PLOS REVIEW REPORT

SUMMARY

Use of verbal autopsy to assess premature NCD mortality in resource-poor settings such as rural Eastern Uganda appears appropriate in the absence of country wide civil registration and vital statistics. This study adds to the growing premature NCD mortality data in Africa, even in rural areas.

We thank the reviewer for recognizing the merits of our study

MAJOR ISSUES

Lack of comparison of these results with the INDEPTH Network data from multiple sites in Africa.

We have now described findings from available peer-reviewed data from verbal autopsy validations and population-based NCD surveys in Africa within the discussion section.

Lack of comparison with epidemiology studies in rural and urban Uganda and rest of the East Africa region

We have now described findings from other epidemiological studies on the prevalence of NCD risk factors and morbidity within Uganda within the discussion section. Unfortunately, what is lacking are studies about NCD mortality, where much work still remains to be done. This is one of the gaps we aim to help bridge with the current study.

Wide unexplained disparity and fluctuations in mortality rates in different years especially in CVD and diabetes as well as between males and females. Raises questions about the reliability and accuracy of the data.

We agree with the reviewer that these disparities and fluctuations raise concerns. However, this is to be expected as our study was conducted in a very modest population over a relatively short period of time. Thus, even a few deaths can greatly influence the estimates in a given year. What we hope readers take away is that the findings show that NCDs contribute to a large proportion of deaths among adults, and there appear to be differences in some NCD mortality patterns between men and women. These differences warrant further exploration. In addition, interventions are needed to reduce NCD risk factors, morbidity, and mortality.

Lack of explanation with the unexpectedly high NCD mortality rates in a rural area in the presence of low NCD risk factors such as obesity rates (5.3%) and other risk factors.

Thank you for this comment. We note that other studies have shown substantial prevalence of various NCD risk factors in the Iganga and Mayuge communities. However, the mechanisms underlying the NCD mortality rates observed in our setting are not fully understood. We hope to study the potential social and metabolic mechanisms behind NCD mortality rates in this population in greater detail in future.

In other studies in sub-Saharan Africa, some of the sites reporting the highest rates of NCD mortality were also those with the greatest burden of HIV/AIDS-related mortality. It has been suggested that in such settings, around half of the mortality attributed to NCDs may well be associated with HIV. It is not clear how the authors dealt with this.

Thank you for this comment. However, we were unable to comprehensively examine the influence of HIV; this is a limitation of our study.

MINOR ISSUES

1. The use of a probabilistic model to assign cause of death would have been preferable to

the use of doctors.

We would like to thank the reviewer for this comment. The use of physician review to assign cause of death is the method used by the Iganga-Mayuge Health and Demographic Surveillance Site, and thus what our analysis was based upon.

OTHER COMMENTS

Very useful source of information in the absence of inadequate data in the rest of the country.

Similar longitudinal studies would be useful in monitoring NCD mortality trends in other areas of the country to determine more reliable national trends.

Despite the HIV, Ebola and the COVID-19 epidemics, for the present as well as the foreseeable future, NCDs will be responsible for the highest morbidity and mortality in sub-Saharan Africa. The findings of studies like this, should spur policy makers to take action to reduce premature adult mortality due to NCDs.

We thank the reviewer for recognizing the merits of our study.

Reviewer #4: Title: An analysis of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016

1. Do the title and abstract accurately convey what has been found?

Yes, title is ok, but I would use the word “assessment” instead of analysis – this is usually reserved for a novel way of analysis e.g., new statistical analysis method

Thank you for this comment. We have now modified the title and used the word assessment instead of analysis

2. Is the writing acceptable?

Yes, writing is acceptable.

3. Are the data sound?

Yes, steps followed look sound and well documented

4. Do the figures appear to be genuine, i.e., without evidence of manipulation?

Yes, figures appear genuine

5. Does the manuscript adhere to the relevant standards for reporting and data deposition?

Yes, standards are adhered to

6. Are the discussion and conclusions well balanced and adequately supported by the data?

Yes, but discussion is quite light might need some beefing up.

We have added additional information within the discussion.

7. Are limitations of the work clearly stated?

Yes, study limitations are clearly stated.

8. Do the authors clearly acknowledge any work upon which they are building, both published and unpublished?

Yes, this is done well in the discussion perhaps a little more in the introduction.

Thank you for this comment and for acknowledging the work that has been put together.

9. General Observation

Overall, it is a well described and interesting paper that adds to the current body of evidence and speaks to the current NCD burden especially NCD mortality within sub-Saharan Africa generally and Uganda specifically.

10. Minor Essential Revisions

• Classification of outcomes - indicate how multiple causes of death or multiple conditions present at time of death were handled and death classified in that case e.g., if at death someone had both Cancer and DM or had both DM and accidental death

This is a good point! In scenarios where there were multiple causes of deaths, we relied on information from physicians who would compare results and establish the most probable cause of death. We have noted the inability to account for multiple causes of death as a limitation in our discussion section.

• Need to reformat the tables to highlight points of interest e.g., bolding or re-aligning or smaller font size for some figures e.g. Table 2 can be better displayed as below

2016 2015 2014

Men Women Overall Men Women Overall Men Women Overall

11.29 19.68 16.78 7.9 21.48 14.91 10.15 21.86 15.02

We appreciate the advice. After trying a number of different reformats, we made the decision to leave Table 2 as it was, in order to allow the reader easily have information to compare across the years and across genders. The table is to enable the reader to reference/confirm the results we report in the text, e.g., cardiovascular disease death rates are higher for women than for men.

• Indicate the AAMR units e.g. is it deaths per 10,000 or per 100,000?

We have indicated the units in the title for the table due to limited space within the table. We also included a note in the last row of the table to state that the age-adjusted mortality rates are expressed per 10,000 persons.

• Built up the discussion nicely to indicate the burden and CV risk factor profile in Iganga-Mayuge - but do but not tie it up to show how this would lead to a high CVD mortality e.g.

o What are the known mortality trends in the region if any e.g. Eastern Uganda, in Uganda or E. Africa?

Thank you for the comment and advice. We have made amendments to the discussion section. Unfortunately, studies are still limited about NCD mortality in Uganda and neighboring countries, especially within population-based settings. This is one of the gaps we aim to help bridge with the current study.

o How do these trends compare with what was found?

The trends are congruent with findings of a substantial prevalence of NCD risk factors and disease burden in the region. Although there is a dearth of hospital or community-based studies on NCD mortality in the East Africa region, we identified a study reporting on disability adjusted life years (DALYs) due to NCDs in Kenya for the period of 1990-2016; this study found increasing DALYs over the time period. We have referenced the study within the discussion section. In addition, we have referenced the NCD mortality trends study we identified which was based on four-year retrospective data from Mulago Hospital.

o How do they compare with regional hospital mortality trends, any surprises there??

Please see comment above

o What might account for the anomalies e.g., fewer deaths in females, fewer deaths to DM in 2016 etc..

Fluctuations and anomalies may be partly explained by our small sample size. Thus, after stratification by year, even a few deaths can have great influence on estimated mortality rates. We are careful about our speculations about the observed anomalies, as they require further study to provide explanations.

o How might these data on mortality be useful going forward, perhaps operationally??

Thank you for this comment. The findings provide a useful baseline from which to track future trends in NCD mortality and to add knowledge to the existing literature on NCD mortality in Uganda and sub-Saharan Africa more generally, where there is currently limited data on NCD mortality.

11. Level of interest

I think this is a worthwhile study and a timely addition of valuable information to the current body of evidence with regard to NCD mortality in sub-Saharan Africa.

12. Quality of written English

Acceptable

13. Declaration of competing interests

I declare that I have no competing interests

Reviewer #5: The manuscript is technically sound as a verbal autopsy, a well-established method for such study, was utilized. The data also support the major conclusion of the manuscript that NCD is a major cause of death among the study population. However, the recommendation “…….a unified approach towards disease prevention and treatment that focuses on strengthening health systems” seems far fetching as the finding did not allude to any health system issues.

Thank you for this comment. The statement has been revised accordingly.

Attachment

Submitted filename: Response to reviewers.docx

Click here for additional data file. (29.4KB, docx)

Decision Letter 1

Amir Radfar

9 Mar 2021

An assessment of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016

PONE-D-20-31885R1

Dear Dr. NATUKWATSA,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I have gone through the revised manuscript entitled, “An analysis of non-communicable disease mortality among adults in Eastern Uganda,2010-2016” carefully.

The authors have incorporated the changes as suggested in the last review.

With all good wishes,

Reviewer #2: Now the manuscript is more improved and can be published in the journal in the present form. It is a very interesting and important study from Uganda. We know that we have very limited data from African region particularly in younger age group people. Best wishes.

Reviewer #4: I am satisfied with the changes made and responses to my original review. With the exception of the table alignments (which they have justified somewhat). I think the authors have done good job at addressing the issues I raised.

Reviewer #5: The manuscript is presented well and written in standard English. However, it needs proofreading (edits) as there are some grammatical errors. Eg. on page 12, fourth line from bottom, the phrase "........aged ≥ 18 years and over......." is redundant (the symbol is not required).

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: TAHZIBA HUSSAIN

Reviewer #2: Yes: Palash Chandra Banik

Reviewer #4: No

Reviewer #5: No

Acceptance letter

Amir Radfar

12 Mar 2021

PONE-D-20-31885R1

An assessment of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016

Dear Dr. Natukwatsa:

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Amir Radfar

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Review for PloS - Natukwatsa et al, 2020.docx

    Click here for additional data file. (18.6KB, docx)
    Attachment

    Submitted filename: Response to reviewers.docx

    Click here for additional data file. (29.4KB, docx)

    Data Availability Statement

    Data is confidential and cannot be shared publicly. Anonymized data can only be shared upon request, as per the data sharing agreement from Makerere University Center for Health and Population Research (MUCHAP). The Iganga Mayuge Health and Demographic Surveillance Site (IMHDSS) is bound to a data sharing agreement with the larger INDEPTH network health and demographic surveillance sites. There is a formal data sharing process guided by data sharing standard operating procedures. Data can be requested formally from the IMHDSS leader (info@muchap.mak.ac.ug) who is the point of contact for all data requests. There are more details on the website (www.muchap.mak.ac.ug)."

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