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      Optimal control and cost-effective analysis of malaria/visceral leishmaniasis co-infection

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      Author(s): 1 , * , 2
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      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          In this paper, a deterministic model involving the transmission dynamics of malaria/visceral leishmaniasis co-infection is presented and studied. Optimal control theory is then applied to investigate the optimal strategies for curtailing the spread of the diseases using the use of personal protection, indoor residual spraying and culling of infected reservoirs as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And we investigated the most cost-effective strategy of all the control strategies using three approaches, the infection averted ratio (IAR), the average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER). Our results show that the implementation of the strategy combining all the time dependent control variables is the most cost-effective control strategy. This result is further emphasized by using the results obtained from the cost objective functional, the ACER, and the ICER.

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          Post-kala-azar dermal leishmaniasis.

          E Zijlstra, A. M. Musa, E A G Khalil … (2003)
          Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.
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            Optimal control of the chemotherapy of HIV.

            S Serbin, Suzanne Lenhart, Ralf Kirschner (1997)
            Using an existing ordinary differential equation model which describes the interaction of the immune system with the human immunodeficiency virus (HIV), we introduce chemotherapy in an early treatment setting through a dynamic treatment and then solve for an optimal chemotherapy strategy. The control represents the percentage of effect the chemotherapy has on the viral production. Using an objective function based on a combination of maximizing benefits based on T cell counts and minimizing the systemic cost of chemotherapy (based on high drug dose/strength), we solve for the optimal control in the optimality system composed of four ordinary differential equations and four adjoint ordinary differential equations.
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              Self-medication with antibiotics and antimalarials in the community of Khartoum State, Sudan.

              Lloyd Matowe, Idris Eltayeb, Abdelmoneim Awad … (2004)
              To estimate the prevalence of self medication with antibiotics and antimalarials in Khartoum State, Sudan and evaluate factors associated with self medication. A pre-tested questionnaire was used to collect data from a sample of 600 households, (1750 adult persons), selected from three cities in Khartoum State, Sudan, using a multistage stratified clustered sampling. One thousand two hundred and ninety three (73.9%) of the study population had used antibiotics or antimalarials without a prescription within one month prior to the study. Eight hundred and forty one (48.1%) of the respondents agreed that they have used antibiotics, 43.4% used antimalarials, while 17.5% used both. Self medication with either antibiotics/ antimalarials was found to be significantly associated with age, income, gender and level of education. Overall, self medication with any antibiotics or antimalarials was least common among the > or = 60 years compared to youngest age group (OR: 0.07; 0.04 -0.11) and most common among the female gender (OR: 1.8; 1.4 -2.4), the middle income group (OR: 3.7; 2.6-5.3) and the university graduates. Self medication with antibiotic was found to be significantly higher among females (OR: 1.5; 1.16-1.87), middle aged respondents aged 40-59 (OR: 2.1; 1.5-3.0) compared to younger respondents. Lower income and higher level of education was also found to be significantly associated with the increase risk of self medicating with antibiotic. Increase risk for self medication with antimalarials were, however, found to be significantly associated with male gender and younger age group of < 40 years and middle income earners and less educated respondents. The main reason that was indicated for the self-medication was financial constraints. The main source of medicines was the private pharmacies, which were regarded as a cheaper alternative to other primary healthcare sources. The prevalence of self-medication with antibiotics/antimalarials in Khartoum State, Sudan is alarmingly high. Self medication behaviour varies significantly with a number of socio-economic characteristics. Given the growing global resistance for antibiotic and documented health issues related to inappropriate use of such drugs, our findings has major public health policy implications for countries like Sudan.
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                Author and article information

                Contributors
                Henk D. F. H. Schallig: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2017
                Publication date (Electronic): 6 February 2017
                Volume: 12
                Issue: 2
                Electronic Location Identifier: e0171102
                Affiliations
                [1 ]Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, 66045, Kansas, United States of America
                [2 ]Department of Mathematics and Statistics, College of Sciences, Sultan Qaboos University, P.O.Box 36, Al Khodh, Oman
                Academic Medical Centre, NETHERLANDS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: FBA IME.

                • Data curation: FBA.

                • Formal analysis: FBA IME.

                • Funding acquisition: IME.

                • Methodology: FBA IME.

                • Resources: FBA.

                • Software: FBA.

                • Validation: FBA IME.

                • Visualization: FBA IME.

                • Writing – original draft: FBA IME.

                • Writing – review & editing: FBA IME.

                Article
                Publisher ID: PONE-D-16-34400
                DOI: 10.1371/journal.pone.0171102
                PMC ID: 5293207
                PubMed ID: 28166308
                SO-VID: c3cd3fcc-0ef4-4a91-91b6-7fdb94d6847d
                Copyright © © 2017 Agusto, ELmojtaba
                License:

                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
                Date received : 5 September 2016
                Date accepted : 16 January 2017
                Page count
                Figures: 12, Tables: 8, Pages: 31
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004351, Sultan Qaboos University;
                Award ID: IG\DOMS\16\16
                Award Recipient :
                ELmojtaba was supported by grant No: IG\DOMS\16\16, from Sultan Qaboos University.
                Categories
                Subject: Research Article
                Subject: People and Places
                Subject: Demography
                Subject: Death Rates
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Infectious Disease Control
                Subject: Medicine and Health Sciences
                Subject: Tropical Diseases
                Subject: Neglected Tropical Diseases
                Subject: Leishmaniasis
                Subject: Medicine and Health Sciences
                Subject: Parasitic Diseases
                Subject: Protozoan Infections
                Subject: Leishmaniasis
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Zoonoses
                Subject: Leishmaniasis
                Subject: Medicine and Health Sciences
                Subject: Parasitic Diseases
                Subject: Malaria
                Subject: Medicine and Health Sciences
                Subject: Tropical Diseases
                Subject: Malaria
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Co-Infections
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Disease Vectors
                Subject: Insect Vectors
                Subject: Sand Flies
                Subject: Social Sciences
                Subject: Economics
                Subject: Economic Analysis
                Subject: Cost-Effectiveness Analysis
                Subject: Medicine and Health Sciences
                Subject: Tropical Diseases
                Subject: Neglected Tropical Diseases
                Subject: Leishmaniasis
                Subject: Kala-Azar
                Subject: Medicine and Health Sciences
                Subject: Parasitic Diseases
                Subject: Protozoan Infections
                Subject: Leishmaniasis
                Subject: Kala-Azar
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Zoonoses
                Subject: Leishmaniasis
                Subject: Kala-Azar
                Custom metadata
                Data Availability All relevant data are within the paper.

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