Adult malaria mortality during 2019 at Bo Government Hospital, Sierra Leone

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.


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
We conducted a retrospective hospital-based chart review of adults (age ≥18) admitted to Bo Government Hospital from 1 st January to 31 st December 2019.Bo Government Hospital is major regional hospital in Southern Province, Sierra Leone and provides adult, maternal and pediatric care services to the city of Bo and surrounding districts.Three investigators (SK, AA, IB) extracted data from the medical charts of unselected consecutive adults admitted with a laboratory diagnosis of malaria 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 exclusion criteria.Data extracted included age, sex (female/male), results of diagnostic testing for malaria (rapid diagnostic test, thick and thin film), information on the severity of malaria as defined by the World Health Organization criteria 4 , and patient outcome (discharged alive or died in hospital).
Data were summarised as counts and mean and standard deviation for continuous variables, and number and percentage for categorical variables.The significance of any differences in proportions was evaluated with a chi square test and a 2-sided p value <0.05 was considered statistically significant.Analyses were performed using SAS version 9.4.
All investigators are listed as authors and had complete access to study data.
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.

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.
Of 149 patients with a malaria diagnosis, 22 (14.8%)died.There were no significant differences in age, sex or proportion of patients with hypertension among those whose chart review included criteria for severe malaria (including prostration, severe anaemia, jaundice, reduced level of consciousness, seizures, shock) compared with those who did not.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).

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.
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 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 and are therefore unable to determine the reasons for the high adult malaria mortality in this study.It is also unclear whether concomitant infections, such as bacteremia, or other conditions may have contributed to malaria mortality seen in our study.Finally, our study was performed in a single regional hospital and the high mortality in hospitalized patients may not be generalizable to other hospitals in Sierra Leone.
In conclusion, our data demonstrate that the burden of adult malaria mortality in Bo Government Hospital, Sierra Leone is high.Further studies are needed to explore the reasons for the high mortality and more effective prevention and treatment strategies should be urgently implemented.
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
Is the study design appropriate and is the work technically sound?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

Are the conclusions drawn adequately supported by the results? Yes
Competing Interests: No competing interests were disclosed.
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.
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?

Table 1 . Baseline characteristics and outcomes of patients admitted to Bo Government Hospital during 2019 with a diagnosis of malaria*. Characteristic and outcome Admissions with malaria (n=149)
4he 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 adults4.
*Number of patients with missing data: age, n=33; sex, n=4 hypertension, n=22.†Comparison between severe and non-severe malaria: p=0.031 significant contributor to adult mortality.

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.

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 Are the conclusions drawn adequately supported by the results? Yes Competing Interests:
No competing interests were disclosed.
Reviewer Expertise: Infectious disease, hepatology, Gastroenterology I confirm that I