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      Household costs associated with zoonotic Plasmodium knowlesi, P. falciparum, P. vivax and P. malariae infections in Sabah, Malaysia

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          Abstract

          Background

          Malaysia has free universal access to malaria care; however, out-of-pocket costs are unknown. This study estimated and compared household costs of illness during a unique time when four species of malaria were present, due to the emergence of zoonotic Plasmodium knowlesi during the elimination phase of non-zoonotic species in Sabah, Malaysia.

          Methodology/principal findings

          Household costs were estimated from patient-level surveys collected from four hospitals between 2013 and 2016. Direct costs including medical and associated travel costs, and indirect costs due to lost productivity were included. One hundred and fifty-two malaria cases were enrolled: P. knowlesi (n=108), P. vivax (n=22), P. falciparum (n=16), and P. malariae (n=6). Costs were inflated to 2023 Malaysian Ringgits and reported in United States dollars (US$). Across all cases, the mean total costs were US$131 (SD=102), with productivity losses accounting for 58% of costs (US$76; SD=70). P. vivax had the highest mean total household cost at US$199 (SD=174), followed by P. knowlesi and P. falciparum at US$119 (SD=81 and SD=83, respectively), and P. malariae (US$99; SD=42). Most patients (80%) experienced direct health costs above 10% of monthly income, with 58 (38%) patients experiencing health spending over 25% of monthly income, consistent with catastrophic health expenditure.

          Conclusions/significance

          Despite Malaysia’s free health-system care for malaria, patients and families face other related medical, travel, and indirect costs. Household out-of-pocket costs were driven by productivity losses; primarily attributed to infections in working-aged males in rural agricultural-based occupations. Costs for P. vivax were higher than those of P. knowlesi and P. falciparum. This may be attributable to a younger age profile and the longer treatment required to clear the liver-stage parasites of P. vivax.

          Author summary

          Malaria patients experience financial barriers when seeking care, despite free access to universal care in Malaysia. In some areas of Southeast Asia, multiple species of malaria can be present within the same setting, including recently emerged knowlesi malaria, which is spread from monkeys to humans via mosquitos. The economic burden of illness due to multiple species of malaria has not previously been estimated in the same setting. We collected data on the cost of illness to households in Sabah, Malaysia, to estimate their related total economic burden during the elimination phase of human-only malaria. Medical costs and time off work and usual activities were substantial in patients with the four species of malaria diagnosed during the time of this study. This research highlights the financial burden which households face when seeking care for malaria in Malaysia, despite the free treatment provided by the government.

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          Most cited references54

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          Severe malaria.

          (2014)
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            Clinical and laboratory features of human Plasmodium knowlesi infection.

            Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections. In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008. Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%). Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.
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              Methodology and Application of the Kruskal-Wallis Test

              This paper describes the methodology and application of the very popular nonparametric test which is a rank based test named as Kruskal-Wallis. This test is useful as a general nonparametric test for comparing more than two independent samples. It can be used to test whether such samples come from the same distribution. This test is powerful alternative to the one-way analysis of variance. Nonparametric ANOVA has no assumption of normality of random error but the independence of random error is required. If the Kruskal-Wallis statistic is significant, the nonparametric multiple comparison tests are useful methods for further analysis. The statistical analysis of the application data in this paper was performed with software MATLAB.

                Author and article information

                Contributors
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Writing – original draft
                Role: ConceptualizationRole: ResourcesRole: Supervision
                Role: ResourcesRole: Supervision
                Role: Formal analysisRole: InvestigationRole: Project administration
                Role: Data curationRole: Formal analysisRole: Project administration
                Role: Data curationRole: Formal analysisRole: Project administration
                Role: Formal analysisRole: Project administration
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLOS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                4 April 2025
                April 2025
                : 19
                : 4
                : e0012180
                Affiliations
                [1 ] Melbourne Health Economics, Centre for Health Policy, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
                [2 ] Infectious Disease Society-Menzies School of Health Research, Kota Kinabalu, Sabah, Malaysia
                [3 ] Queen Elizabeth Hospital II, Ministry of Health Malaysia, Kota Kinabalu, Sabah, Malaysia
                [4 ] School of Medicine and Health Sciences, Monash University Malaysia, Kuala Lumpur, Malaysia
                [5 ] Vector Borne Disease Sector, Ministry of Health Malaysia, Putrajaya, Malaysia
                [6 ] Public Health Research Section, Sabah State Department of Health, Ministry of Health Malaysia, Kota Kinabalu, Sabah, Malaysia
                [7 ] London School of Hygiene & Tropical Medicine, London, United Kingdom
                [8 ] Vector Borne Unit, Sabah State Department of Health, Ministry of Health Malaysia, Kota Kinabalu, Sabah, Malaysia
                [9 ] Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
                Swiss Tropical and Public Health Institute: Schweizerisches Tropen- und Public Health-Institut, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-1239-1363
                Article
                PNTD-D-24-00626
                10.1371/journal.pntd.0012180
                11970689
                40184425
                4a4dd2d1-df7f-431e-96d2-9ef14301a083
                © 2025 Abraham et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 May 2024
                : 25 February 2025
                Page count
                Figures: 1, Tables: 6, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1037304, 1045156, 1042072
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 2017436
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 2025362
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100020687, Australian Centre of Research Excellence in Malaria Elimination;
                Award ID: 1134989
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100020687, Australian Centre of Research Excellence in Malaria Elimination;
                Award ID: 2024622
                Award Recipient :
                Funded by: UK Environmental & Social Ecology of Human Infectious Diseases Initiative
                Award ID: G1100796
                Award Recipient :
                Funded by: National Institutes of Health, USA
                Award ID: R01AI160457-01
                Award Recipient :
                Funded by: Malaysian Ministry of Health
                Award ID: BP00500/117/1002
                Award Recipient :
                Funded by: Australian Centre for International Agricultural Research, and Indo-Pacific Centre for Health Security, DFAT, Australian Government
                Award ID: LS-2019-116
                Award Recipient :
                This work was supported by the National Health and Medical Research Council, Australia (Grant Numbers 1037304 and 1045156 to NMA; 1042072 fellowship to NMA; investigator grants 2017436 to MJG and 2025362 to AD; the Australian Centre of Research Excellence in Malaria Elimination grant 1134989 to NMA and MJG and grant 2024622 to MJG and AD); The MONKEYBAR project (UK Environmental & Social Ecology of Human Infectious Diseases Initiative, Grant #G1100796 to CD); the National Institutes of Health, USA (R01AI160457-01 to TW and GSR); Malaysian Ministry of Health (Grant Number BP00500/117/1002 to GSR), the Australian Centre for International Agricultural Research, and Indo-Pacific Centre for Health Security, DFAT, Australian Government (LS-2019-116 to MJG and AD). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Malaria
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Malaria
                Biology and Life Sciences
                Parasitology
                Parasite Groups
                Apicomplexa
                Plasmodium
                Social Sciences
                Economics
                Health Economics
                Medicine and Health Sciences
                Health Care
                Health Economics
                Social Sciences
                Economics
                Labor Economics
                Salaries
                Medicine and Health Sciences
                Health Care
                Socioeconomic Aspects of Health
                Medicine and Health Sciences
                Public and Occupational Health
                Socioeconomic Aspects of Health
                Social Sciences
                Economics
                Finance
                Financial Management
                Indirect Costs
                People and Places
                Geographical Locations
                Asia
                Malaysia
                Medicine and Health Sciences
                Health Care
                Caregivers
                Custom metadata
                All relevant data used for analysis of the manuscript and supporting information are available via attached online repository ( https://github.com/PatrickAbraham1/Sabah-Knowlesi-COI). This includes the minimum data set and coding for all means, standard deviations, and values used to create figures.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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