Gates Open Res Gates Open Research 2572-4754 F1000 Research Limited London, UK 10.12688/gatesopenres.14396.1 Research Article Articles Adult malaria mortality during 2019 at Bo Government Hospital, Sierra Leone

[version 1; peer review: 2 approved with reservations]

 Kpagoi Satta Sylvia T.K. Investigation Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0001-5755-0167 1 Aimone Ashley Conceptualization Investigation Methodology Supervision Writing – Review & Editing 2 Ansumana Rashid Conceptualization Investigation Methodology Resources Supervision Writing – Review & Editing 3 Swaray Ibrahim Conceptualization Writing – Review & Editing 2 3 Gelband Hellen Conceptualization Methodology Writing – Review & Editing https://orcid.org/0000-0002-8002-3135 2 Eikelboom John W. Formal Analysis Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0003-4126-1285 4 Jha Prabhat Conceptualization Funding Acquisition Methodology Resources Supervision Writing – Review & Editing https://orcid.org/0000-0001-7067-8341 2 Bogoch Isaac I. Conceptualization Investigation Methodology Supervision Writing – Original Draft Preparation Writing – Review & Editing a 5 Department of Medicine, Bo Government Hospital, Ministry of Health and Sanitation, Bo, Sierra Leone Centre for Global Health Research, Unity Health Toronto and Dalla Lana School of Public Health, Toronto, Ontario, Canada Health Sciences, Njala University, Bo, Sierra Leone McMaster University, Hamilton, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada isaac.bogoch@uhn.ca

No competing interests were disclosed.

 15 3 2023 2023 7 48 3 3 2023 Copyright: © 2023 Kpagoi SSTK et al. 2023 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We performed a chart review of adults admitted to Bo Government Hospital during 2019. Of 893 admissions, 149 (59% female, mean age 58.5 years) had a laboratory diagnosis of malaria and 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031). Our results suggest that malaria is a common cause of death in hospitalized Sierra Leonian adults.

Malaria Gates Foundation INV-009553 This work was supported by the Gates Foundation [INV-009553]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Introduction

It remains uncertain whether malaria is an important cause of death among adults living in endemic areas 1 . One of the reasons for this uncertainty is that many countries with a high burden of malaria do not have a vital registration system. Malaria statistics for African countries published by the World Health Organization are based on the results of verbal autopsy in children under the age of five and provide little information on malaria mortality in adults 2 .

We further explored the importance of malaria as a cause of death in adults in Sierra Leone by performing a chart review of all patients admitted to one of three adult medical wards at Bo Government Hospital during the 2019 calendar year.

Methods

Ethical permission was granted by the Office of the Sierra Leone Ethics and Scientific Review Committee (dated March 15, 2022). Individual patient consent was not required because the study involved a retrospective chart review. Three investigators (SK, AA, IB) extracted data from the medical charts of unselected consecutive adults admitted with a laboratory diagnosis of malaria to one of three adult medical wards during 2019 as part of the Countrywide Mortality Surveillance for Action (COMSA) Sierra Leone Project 3 . The study included patients admitted over a 12-month period to provide a representative sample in view of the seasonal pattern of malaria. Eligible patients were identified based on review of laboratory results as documented in their medical charts and there were no execution criteria. Data extracted included age, sex, results of diagnostic testing for malaria, information on the severity of malaria as defined by the World Health Organization criteria 4 , and patient outcome.

Data were summarised as counts and mean and standard deviation for continuous variables, and number and percentage for categorical variables. Analyses were performed using SAS version 9.4.

All investigators are listed as authors and had complete access to study data.

Results

Results are summarised in Table 1 5 . Of 893 adult admissions, 149 (59% female, mean age 58.5 years [SD 13.0]) had a laboratory diagnosis of malaria based on positive rapid diagnostic test or parasitemia on blood film. Of these, 20 (13.4%) were categorized as having severe malaria.

Baseline characteristics and outcomes of patients admitted to Bo Government Hospital during 2019 with a diagnosis of malaria <xref ref-type="other" rid="FN1">*</xref>.
Characteristic and outcome Admissions with malaria (n=149)
Age, mean (SD) 58.5 (SD 13.0)
Female, n (%) 84 (59.2%)
Malaria severity, n (%)
   Non-severe 129 (86.6%)
   Severe 20 (13.4%)
Deaths, n (%) † 22 (14.8%)
   Severe 6 (30.0%)
   Non-severe 16 (12.4%)

*Number of patients with missing data: age, n=33; sex, n=7

†Comparison between severe and non-severe malaria: p=0.031

SD=standard deviation.

Of 149 patients with a malaria diagnosis, 22 (14.8%) died. Mortality was significantly higher among patients whose chart review included criteria for severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031).

Discussion

The results of our chart review indicate that 1 in 7 adult patients admitted to Bo Government Hospital with laboratory confirmed malaria died. As expected, the mortality rate was highest in patients admitted with severe malaria but most deaths still occurred in patients who did not have severe disease.

Our data have some limitations. First, rapid diagnostic tests for malaria may be associated with both false positive and false negative results. It is likely that some adults had other underlying acute medical conditions leading to hospitalization but were categorized as having malaria due to an incidental finding of parasitemia on rapid testing or blood film examination. Second, classification of the severity of malaria was limited by lack of complete medical information, and it is possible that misclassification of the severity of disease explains the higher-than-expected mortality rate in those with non-severe malaria. Third, we did not have access to treatment information or the possible presence of drug resistance. Finally, it is unclear whether concomitant infections, such as bacteremia, or other conditions may have contributed to malaria mortality seen in our study.

The large number of malaria admissions and high malaria mortality among adults observed during 2019 at Bo Government Hospital is consistent with emerging data that malaria is a significant contributor to adult mortality. The Indian Million Death Study (MDS) suggested a higher adult mortality rate than expected, especially in persons aged over 45 years 6 . Similar results were reported by the International Network for Demographic Evaluation of Populations and their Health (INDEPTH) Network 7 . The Sierra Leone Sample Registration System (SL-SRS) of births and deaths performed between September 1, 2019 and December 15, 2020 found that malaria accounted for 22% of deaths under the age of 70 years and was a leading cause of death in adults 4 .

Our data from Bo Government Hospital further highlight the substantial burden of adult malaria mortality in Africa and underscore the urgent need for implementation of more effective prevention and treatment strategies.

 Data availability

DRYAD: Health records from hospitalized adults with malaria during 2019 at Bo Government Hospital, Sierra Leone. https://doi.org/10.5061/dryad.5hqbzkh9s 5 .

This project contains the following underlying data:

Data file 1: data extracted from retrospective medical chart review

Data file 2: data dictionary

README file: description of dataset

Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

 Gelband H Bogoch II Rodriguez PS : Is Malaria an Important Cause of Death among Adults? Am J Trop Med Hyg. 2020;103(1):41–47. 32314692 10.4269/ajtmh.20-0036 7356479 World Health Organization: World Malaria Report 2021. Accessed February 7, 2022. Reference Source Carshon-Marsh R Aimone A Ansumana R : Child, maternal, and adult mortality in Sierra Leone: nationally representative mortality survey 2018-20. Lancet Glob Health. 2022;10(1):e114–e123. 34838202 10.1016/S2214-109X(21)00459-9 8672062 World Health Organization: Severe Malaria. Trop Med Int Health. 2014;19 Suppl 1:7–131. 25214480 10.1111/tmi.12313_2 Aimone A : Health records from hospitalized adults with malaria during 2019 at Bo Government Hospital, Sierra Leone. Dryad. [Dataset],2023. http://www.doi.org/10.5061/dryad.5hqbzkh9s Dhingra N Jha P Sharma VP : Adult and child malaria mortality in India: a nationally representative mortality survey. Lancet. 2010;376(9754):1768–1774. 20970179 10.1016/S0140-6736(10)60831-8 3021416 Streatfield PK Khan WA Bhuiya A : Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites. Glob Health Action. 2014;7(1):25369. 25377329 10.3402/gha.v7.25369 4220130 10.21956/gatesopenres.15708.r33141 Reviewer response for version 1 Amede Peter Okpeh 1 Referee Nigeria Field Epidemiology and Laboratory Training Programme, Abuja, Nigeria

Competing interests: No competing interests were disclosed.

 3 5 2023 Copyright: © 2023 Amede PO 2023 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve-with-reservations

Congratulations to the authors for their manuscript. The study is about the burden of malaria among adults hospitalized in General Hospital Bo, Sierra Leone from 1 st January to 31 st December 2019. The study is part of the Countrywide Mortality Surveillance for Action (COMSA) Sierra Leone project.

Listed below are points that require the authors’ attention to qualify the study.

Abstract: Suggested reconstruction for consideration by the authors.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We conducted a chart review of adults admitted to Bo General Hospital during 2019. Of the 893 adult admissions, 149 had laboratory diagnosis of malaria with mean (SD) age of 58.5 ±13.0 years, and most being female (59.0%). Among the laboratory confirmed malaria, 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [60%] versus (16/129 [12.4%], p=0.031). The finding suggests that malaria is a common cause of death among adults hospitalized in Bo General Hospital, Sierra Leone.

Keywords: Just one?

Methods: The authors should start the method section with the study design (We conducted a hospital-based retrospective chart review of malaria patients from 1 st January to 31 st December 2019. Three trained investigators ……..). A brief background of Bo General Hospital, Sierra Leone is required to bring readers up to speed on the study setting. The authors should define both the dependent and independent variables and how they were measured. The ethical permission should come just before data summary. The authors should explain clearly how one out of three medical wards was selected or there are three medical wards and all were included in the study? If so, the authors should please clarify. What level of significance was used for the study?

Results: The result section is quite scanty as in all the sections. The dataset has much information that were not analysed. For instance, is mortality higher among those with severe hypertension/elevated blood pressure? Or higher among the aged say 60 years and above? Among severe malaria cases how many are males/females? What about age distribution for severe malaria? Were there cases of malaria in pregnancy or they were excluded?

Authors need to do more analysis from the available data, rather than clump everything as limitations. The data available is enough to provide solution/answers to most of what was put as limitations. Risk factor analysis could inform readers if age, sex, comorbidity are responsible for the severity or deaths. Also sensitivity analysis by excluding those with severe hypertension and sickle cell disease could have been helpful.

Discussion: The discussion is not robust. The authors should discuss possible reasons for the high morbidity and mortality in the study, though it is a secondary data analysis, available data could provide reasons for the finding. And compare and contrast their findings with that of previous studies and discuss reasons for the similarity or otherwise between the studies.

Limitations should be moved to the last paragraph of the discussion before the concluding paragraph.

Conclusion from this study may not be generalizable; the authors need to limit the conclusion to the study setting, extending the findings of this study from a single hospital in one country to the entire Africa continent is superfluous.

My suggestion for the authors’ consideration. The study demonstrated that the burden of adult malaria mortality among malaria patients in Bo General Hospital, Sierra Leone was high. We therefore recommended that more effective prevention and treatment strategies be urgently implemented and there should be training and retraining of the healthcare workers by the health facility authority on proper documentation of medical records to improve data quality.

Is the work clearly and accurately presented and does it cite the current literature?

Partly

If applicable, is the statistical analysis and its interpretation appropriate?

No

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

No

Reviewer Expertise:

NA

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Eikelboom John McMaster University, Canada

Competing interests: No competing interests were disclosed.

 29 7 2023

Congratulations to the authors for their manuscript. The study is about the burden of malaria among adults hospitalized in General Hospital Bo, Sierra Leone from 1 st January to 31 st December 2019. The study is part of the Countrywide Mortality Surveillance for Action (COMSA) Sierra Leone project.

Response: Thank you for these positive comments.

Listed below are points that require the authors’ attention to qualify the study.

Abstract: Suggested reconstruction for consideration by the authors.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We conducted a chart review of adults admitted to Bo General Hospital during 2019. Of the 893 adult admissions, 149 had laboratory diagnosis of malaria with mean (SD) age of 58.5 ±13.0 years, and most being female (59.0%). Among the laboratory confirmed malaria, 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [60%] versus (16/129 [12.4%], p=0.031). The finding suggests that malaria is a common cause of death among adults hospitalized in Bo General Hospital, Sierra Leone.

Response: In the revised manuscript the abstract has been modified according to the suggestions of the Reviewer.

Keywords: Just one?

Response: In the revised manuscript additional key words have been provided.

Methods: The  authors should start the method section with the study design (We conducted a hospital-based retrospective chart review of malaria patients from 1 st January to 31 st December 2019. Three trained investigators ……..). A brief background of Bo General Hospital, Sierra Leone is required to bring readers up to speed on the study setting. The authors should define both the dependent and independent variables and how they were measured. The ethical permission should come just before data summary. The authors should explain clearly how one out of three medical wards was selected or there are three medical wards and all were included in the study? If so, the authors should please clarify. What level of significance was used for the study?

Response: The methods section has been revised according to the suggestions of the reviewer. The statistical analyses are largely descriptive and test the significance of any differences between groups without any analyses that involve independent and dependent variables. We clarify that all adult general medical admissions were included.

Results: The result section is quite scanty as in all the sections. The dataset has much information that were not analysed. For instance, is mortality higher among those with severe hypertension/elevated blood pressure? Or higher among the aged say 60 years and above? Among severe malaria cases how many are males/females? What about age distribution for severe malaria? Were there cases of malaria in pregnancy or they were excluded?

Authors need to do more analysis from the available data, rather than clump everything as limitations. The data available is enough to provide solution/answers to most of what was put as limitations. Risk factor analysis could inform readers if age, sex, comorbidity are responsible for the severity or deaths. Also sensitivity analysis by excluding those with severe hypertension and sickle cell disease could have been helpful.

Response: In the revised manuscript additional analyses have been provided in relation to age, sex and hypertension. Unfortunately, data on comorbidities and on sickle cell disease are extremely limited which precludes further analysis.  

Discussion: The discussion is not robust. The authors should discuss possible reasons for the high morbidity and mortality in the study, though it is a secondary data analysis, available data could provide reasons for the finding. And compare and contrast their findings with that of previous studies and discuss reasons for the similarity or otherwise between the studies.

Limitations should be moved to the last paragraph of the discussion before the concluding paragraph.

Response: The discussion has been elaborated along the lines suggested.

Conclusion from this study may not be generalizable; the authors need to limit the conclusion to the study setting, extending the findings of this study from a single hospital in one country to the entire Africa continent is superfluous.

Response: We agree and have modified the revised manuscript accordingly.  

My suggestion for the authors’ consideration. The study demonstrated that the burden of adult malaria mortality among malaria patients in Bo General Hospital, Sierra Leone was high. We therefore recommended that more effective prevention and treatment strategies be urgently implemented and there should be training and retraining of the healthcare workers by the health facility authority on proper documentation of medical records to improve data quality.

Response: The conclusion of the revised manuscript has been modified along the lines suggested although we have stopped short of making recommendations regarding training / retraining of health care workers and regarding quality of health care records since we did not explicitly examine the possible contribution of these factors in the present study. We are currently in the process of further exploring these issues.

 10.21956/gatesopenres.15708.r32984 Reviewer response for version 1 Bittaye Sheikh Omar 1 2 Referee https://orcid.org/0000-0001-8162-7363 Department of Internal Medicine, Edward Francis Small Teaching Hospital, Banjul, The Gambia Internal medicine, University of the Gambia, Serrekunda, Banjul, The Gambia

Competing interests: No competing interests were disclosed.

 3 4 2023 Copyright: © 2023 Bittaye SO 2023 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve-with-reservations

The authors provide some useful information about adult malaria mortality in Sierra Leone, specifically Bo Government hospital. However, the study has some inherent weaknesses. I have some comments and suggestions as to how the paper might be improved.

1) It remains uncertain whether malaria is an important cause of death among adults living in endemic areas.

Comment: I doubt if this reflects the current situation. A lot of studies in endemic countries like Mauritania, Gambia, Uganda, Benin etc. have found malaria to have caused a significant burden in the adult age group.

The statement could be true for Sierra Leone and thus could be stated as such and use the other studies already done to reference what they found.

2) A chart review of all patients admitted to one of three adult medical wards at Bo Government Hospital.

Comment: The study used only one ward out of the three adult wards in Bo government hospital. It would have been better to look at all three wards to have a better representative of all adult admissions with malaria in Bo. 

3. Execution in methodology

Comment: Change to Exclusion

4. Adult definition

Comment: What's the definition for adult? 15 years and above?

5.This number of severe malaria cases could have been underestimated due to limitations in availability of laboratory investigations in the diagnosis of severe malaria in Bo Hospital. The limitations in investigations should be highlighted and those diagnosed we should know the criteria used e.g how many were AKI, impaired conciousness etc.

Is the work clearly and accurately presented and does it cite the current literature?

Partly

If applicable, is the statistical analysis and its interpretation appropriate?

Yes

Are all the source data underlying the results available to ensure full reproducibility?

Partly

Is the study design appropriate and is the work technically sound?

Yes

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Infectious disease, hepatology, Gastroenterology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

References : Clinical manifestations and outcomes of severe malaria in adult patients admitted to a tertiary hospital in the Gambia. Malar J .2022;21(1) : 10.1186/s12936-022-04294-4 270 36131306 10.1186/s12936-022-04294-4 Eikelboom John McMaster University, Canada

Competing interests: Nil

 4 4 2023

The authors provide some useful information about adult malaria mortality in Sierra Leone, specifically Bo Government hospital. However, the study has some inherent weaknesses. I have some comments and suggestions as to how the paper might be improved.

Author Response: Thank you for these thoughtful comments.

1) It remains uncertain whether malaria is an important cause of death among adults living in endemic areas.

Comment: I doubt if this reflects the current situation. A lot of studies in endemic countries like Mauritania, Gambia, Uganda, Benin etc. have found malaria to have caused a significant burden in the adult age group.

The statement could be true for Sierra Leone and thus could be stated as such and use the other studies already done to reference what they found.

Author Response: We agree with the reviewer that at a local level there is an appreciation of the burden of adult malaria mortality in many countries. However, this is less well appreciated by many others including the WHO, and accordingly we report that also in Sierra Leone adult malaria in higher than expected.  

2) A chart review of all patients admitted to one of three adult medical wards at Bo Government Hospital.

Comment: The study used only one ward out of the three adult wards in Bo government hospital. It would have been better to look at all three wards to have a better representative of all adult admissions with malaria in Bo. 

Author Response: We apologize for the lack of clarity on this point. We did not restrict inclusion to patients admitted to one ward; rather we included patients admitted to any one of the three wards (i.e., all three wards were included). 

3. Execution in methodology

Comment: Change to Exclusion

Author Response: We will correct this typographical error.

4. Adult definition

Comment: What's the definition for adult? 15 years and above?

Author Response: Adults were defined as 18 years and above. 

5.This number of severe malaria cases could have been underestimated due to limitations in availability of laboratory investigations in the diagnosis of severe malaria in Bo Hospital. The limitations in investigations should be highlighted and those diagnosed we should know the criteria used e.g. how many were AKI, impaired consciousness etc.

Response: We acknowledge that there are limitation sin testing protocols. The data on which these results are based are feely available on-line (see link in paper) and we would be pleased to provide additional details in the paper if required. 

Is the work clearly and accurately presented and does it cite the current literature?

Partly

Author response: We agree that not all current literature is cited reflecting our focus on the Sierra Leone results. We suggest that it would be timely to prepare a review article on adult malaria mortality that cites all of the recent literature and addresses potential strategies to address this (including adult immunization).      

Is the study design appropriate and is the work technically sound?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Yes

Are all the source data underlying the results available to ensure full reproducibility?

Partly

 Author response: All available data are freely available on line

Are the conclusions drawn adequately supported by the results?

Yes

References

1. Bittaye SO, Jagne A, Jaiteh LE, Nadjm B, et al.: Clinical manifestations and outcomes of severe malaria in adult patients admitted to a tertiary hospital in the Gambia. Malar J. 2022;  21 (1): 270  PubMed Abstract |  Publisher Full Text