scholarly journals Resurgence of malaria infection after mass treatment: a simulation study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Thomas A. Smith ◽  
Peter Pemberton-Ross ◽  
Melissa A. Penny ◽  
Nakul Chitnis

Abstract Background Field studies are evaluating if mass drug administration (MDA) might shorten the time to elimination of Plasmodium falciparum malaria, when vector control measures and reactive surveillance strategies are scaled-up. A concern with this strategy is that there may be resurgence of transmission following MDA. Methods A conceptual model was developed to classify possible outcomes of an initial period of MDA, followed by continuously implementing other interventions. The classification considered whether elimination or a new endemic stable state is achieved, and whether changes are rapid, transient, or gradual. These categories were informed by stability analyses of simple models of vector control, case management, and test-and-treat interventions. Individual-based stochastic models of malaria transmission (OpenMalaria) were then used to estimate the probability and likely rates of resurgence in realistic settings. Effects of concurrent interventions, including routine case management and test-and-treat strategies were investigated. Results Analysis of the conceptual models suggest resurgence will occur after MDA unless transmission potential is very low, or the post-MDA prevalence falls below a threshold, which depends on both transmission potential and on the induction of bistability. Importation rates are important only when this threshold is very low. In most OpenMalaria simulations the approximately stable state achieved at the end of the simulations was independent of inclusion of MDA and the final state was unaffected by importation of infections at plausible rates. Elimination occurred only with high effective coverage of case management, low initial prevalence, and high intensity test-and-treat. High coverage of case management but not by test-and-treat induced bistability. Where resurgence occurred, its rate depended mainly on transmission potential (not treatment rates). Conclusions A short burst of high impact MDA is likely to be followed by resurgence. To avert resurgence, concomitant interventions need either to substantially reduce average transmission potential or to be differentially effective in averting or clearing infections at low prevalence. Case management at high effective coverage has this differential effect, and should suffice to avert resurgence caused by imported cases at plausible rates of importation. Once resurgence occurs, its rate depends mainly on transmission potential, not on treatment strategies.

2020 ◽  
Author(s):  
Emma L Davis ◽  
T Déirdre Hollingsworth ◽  
Matt J Keeling

Abstract Background: Vector control is a vital tool utilised by malaria control and elimination programmes worldwide, and as such it is important that we can accurately quantify the expected public health impact of a range of vector control methods. There are very few previous models that consider vector control induced changes in the age-structure of the vector population and the resulting impact this will have on transmission.Methods: The steady-state solution of a novel age-structured deterministic compartmental model describing the mosquito gonotrophic cycle is analytically derived, with the age of each mosquito measured in the number of gonotrophic cycles (or successful blood meals) completed. From this model we derive analytical expressions for key transmission measures, such as the effective reproductive ratio under control, Rc, and investigate the impact of commonly used vector control methods on the age-structure of the vector population.Results: We derive and analyse a novel model with an explicit solution that can be used to directly quantify key transmission statistics and investigate the age-structured impact of vector control. Application of this model confirms current knowledge that adult-acting interventions, such as IRS or LLINs, are highly effective at reducing transmission, particularly in comparison to larvicide usage at the same coverage. We also find that scaling up coverage results in a wider gap in transmission reduction between adult-active and larval-based interventions. For LLINs and IRS the effective reproductive ratio under control, Rc, decreases exponentially with coverage, whereas for larvicides the relationship is linear. We also find that mid-ranges of LLIN coverage see the largest effect of reduced net integrity on transmission.Conclusions: Well-maintained, adult-acting vector control measures are substantially more effective than larval-based action at reducing the transmission potential of the mosquito population, particularly at medium to high coverage levels.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Arthur Mpimbaza ◽  
Asadu Sserwanga ◽  
Damian Rutazaana ◽  
James Kapisi ◽  
Richard Walemwa ◽  
...  

Abstract Background The World Health Organization (WHO) promotes long-lasting insecticidal nets (LLIN) and indoor residual house-spraying (IRS) for malaria control in endemic countries. However, long-term impact data of vector control interventions is rarely measured empirically. Methods Surveillance data was collected from paediatric admissions at Tororo district hospital for the period January 2012 to December 2019, during which LLIN and IRS campaigns were implemented in the district. Malaria test positivity rate (TPR) among febrile admissions aged 1 month to 14 years was aggregated at baseline and three intervention periods (first LLIN campaign; Bendiocarb IRS; and Actellic IRS + second LLIN campaign) and compared using before-and-after analysis. Interrupted time-series analysis (ITSA) was used to determine the effect of IRS (Bendiocarb + Actellic) with the second LLIN campaign on monthly TPR compared to the combined baseline and first LLIN campaign periods controlling for age, rainfall, type of malaria test performed. The mean and median ages were examined between intervention intervals and as trend since January 2012. Results Among 28,049 febrile admissions between January 2012 and December 2019, TPR decreased from 60% at baseline (January 2012–October 2013) to 31% during the final period of Actellic IRS and LLIN (June 2016–December 2019). Comparing intervention intervals to the baseline TPR (60.3%), TPR was higher during the first LLIN period (67.3%, difference 7.0%; 95% CI 5.2%, 8.8%, p < 0.001), and lower during the Bendiocarb IRS (43.5%, difference − 16.8%; 95% CI − 18.7%, − 14.9%) and Actellic IRS (31.3%, difference − 29.0%; 95% CI − 30.3%, − 27.6%, p < 0.001) periods. ITSA confirmed a significant decrease in the level and trend of TPR during the IRS (Bendicarb + Actellic) with the second LLIN period compared to the pre-IRS (baseline + first LLIN) period. The age of children with positive test results significantly increased with time from a mean of 24 months at baseline to 39 months during the final IRS and LLIN period. Conclusion IRS can have a dramatic impact on hospital paediatric admissions harbouring malaria infection. The sustained expansion of effective vector control leads to an increase in the age of malaria positive febrile paediatric admissions. However, despite large reductions, malaria test-positive admissions continued to be concentrated in children aged under five years. Despite high coverage of IRS and LLIN, these vector control measures failed to interrupt transmission in Tororo district. Using simple, cost-effective hospital surveillance, it is possible to monitor the public health impacts of IRS in combination with LLIN.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Praveen K. Bharti ◽  
Harsh Rajvanshi ◽  
Sekh Nisar ◽  
Himanshu Jayswar ◽  
Kalyan B. Saha ◽  
...  

Abstract Background Many malaria endemic countries are heading towards malaria elimination through the use of case management and vector control strategies, which employ surveillance, improving access to early diagnosis, prompt treatment., and integrated vector control measures. There is a consensus that elimination of malaria is feasible when rapid detection and prompt treatment is combined with mosquito-human contact interruption in an efficient and sustainable manner at community levels. This paper describes results of an integrated case management and vector control strategy for reducing malaria cases in 1233 villages over 3 years in district Mandla, Madhya Pradesh, India. Methods The project enrolled the entire population (1,143,126) of Mandla district for fever surveillance followed by testing of febrile cases and treatment of positive subjects using T4 strategy, which is Track (by fever), Test (by RDTs), Treat (by ACT) and Track (for completion of treatment). In addition to the active and passive surveillance for detection and treatment of febrile cases, the project conducted mass screening and treatment to clear the asymptomatic reservoirs of infection. Febrile cases were also tested in the out-patient department of the District Hospital from June 2018 to September, 2018 and in a community-based medical camp from November 7 to 14, 2019. The project also used vector control measures for interrupting human-mosquito contact, and information, education and communication (IEC) campaigns to increase demand for malaria services at community level. Results This project has revealed about 91% reduction of indigenous cases of malaria during the period from June 2017 to May 2020, through case management and vector control strategies. A total 357,143 febrile cases were screened, out of which 0.19% were found positive for the presence of malaria parasites, with Plasmodium falciparum and Plasmodium vivax ratio of 62:38. The prevalence of malaria was higher in individuals > 15 years of age (69% cases). The positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. In all of the 3 years of the project, the peak transmission correlated with rains. Mass screening revealed 0.18% positivity in Sep-Oct 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. Imported cases into the district were mostly contributed by the distant state of Telangana (51.13%). Fever patients tested for malaria parasites in the District Hospital and medical camp revealed zero cases. Conclusion Using the current intervention and prevention tools along with optimum utilization of human resources, a 91% reduction in indigenous cases of malaria was seen in the district in 3 years. The reduction was similar in the three high prevalence blocks of the district. These results reveal that malaria elimination is achievable in India within a stipulated time frame. The reduction of malaria at the community level was further validated when zero malaria cases were diagnosed during hospital and community-based studies in Mandla. Prompt detection and treatment of imported/migratory cases may have prevented outbreaks in the district. This project has demonstrated that field programmes backed by adequate technical, management, operational, and financial controls with robust monitoring are needed for achieving malaria elimination.


2017 ◽  
Author(s):  
Sandra M Goldlust ◽  
Phung Duc Thuan ◽  
Dang Duy Hoang Giang ◽  
Ngo Duc Thang ◽  
Guy E Thwaites ◽  
...  

AbstractA central component of malaria control initiatives throughout the world is the use of artemisinin-based combination therapies (ACTs) for treatment of uncomplicated P. falciparium malaria. Despite the well-documented clinical efficacy of ACTs, the population-level effects of ACT case management on malaria transmission have not been studied thoroughly until recently. An ideal case study for the population-level effects of artemisinin use can be found in Vietnam, where a major increase of malaria cases in the 1980s was followed by the gradual adoption of artemisinin-based clinical case management. We assembled annual data from Vietnam’s National Institutes for Malariology, Parasitology, and Entomology showing the degree to which artemisinin therapies were adopted in different provinces, the effort placed on vector control, and the funding available to provincial malaria control programs, from 1991 to 2014. Data on urbanization were also collected for this period. We found that a 10% increase in the artemisinin proportion of treatments procured by a provincial control program corresponded to a 32.8% (95% CI: 27.7 – 37.5%) decline in estimated malaria cases; the association persisted and the effect size was nearly unchanged if confirmed cases or suspected cases were used. There was no consistent effect of vector control on malaria cases in Vietnam as a whole, nor was any effect found when the data were broken up regionally. The association between urbanization and malaria was generally negative and sometimes statistically significant. This was most pronounced in the central region of Vietnam, where a 10% increase in urbanization corresponded to a 43.3% (95% CI: 21.6 – 58.9%) decrease in suspected malaria incidence; this association was not statistically significant if confirmed cases or estimated cases were used. The decline of malaria in Vietnam from 1991 to 2014 can largely be attributed to the rapid adoption of artemisinin-based drugs. Recent analyses of aggregated data from Africa have shown that insecticide-treated nets have had the greatest effect on lowering malaria prevalence over the past fifteen years, suggesting that the success of different types of malaria interventions is region specific. Continuing global efforts on malaria elimination should focus on both vector control measures and increased access to artemisinin-combination therapies.


2019 ◽  
Author(s):  
Jaline Gerardin ◽  
Caitlin A. Bever ◽  
Daniel Bridenbecker ◽  
Thomas P. Eisele ◽  
Busiku Hamainza ◽  
...  

AbstractMaintaining zero transmission after malaria elimination will be a challenging task for many countries where malaria is still endemic. When local transmission potential is high, and importation of malaria infections continues from neighboring areas with ongoing transmission, malaria programs must develop robust surveillance and outbreak response systems. However, the requirements for such systems remain unclear. Using an agent-based, spatial microsimulation model of two areas in southern Zambia, where elimination efforts are currently underway, we compare the ability of various routine and reactive intervention packages to maintain near-zero prevalence in the face of continued importation. We find that in formerly moderate-transmission areas, high treatment rate of symptomatic malaria is sufficient to prevent reestablishment of malaria. Routine redistributions of insecticide-treated nets and reactive case detection with antimalarial drugs cannot completely compensate for inadequate case management. In formerly high-transmission areas, excellent case management and maintenance of good bednet coverage are both required to prevent resurgence, and outbreak response with antimalarial drugs or additional vector control is also necessary. These results begin to describe the essential criteria for operations that successfully prevent reestablishment of malaria post-elimination and highlight the need for both long-term, sustainable excellence in primary care and comprehensive surveillance that feeds into rapid and flexible outbreak response.Author SummaryThe global community is working toward malaria elimination, but some areas will eliminate before others. Eliminated areas will need to develop intervention programs capable of preventing imported infections from leading to reestablishment, a particular challenge when transmission was previously very high. Past experience has shown that stopping elimination interventions leads to massive resurgence, but it is unclear which interventions must be continued, which can be stopped to conserve resources, and what new interventions should be deployed. Using a simulation model built to capture malaria transmission and intervention history of two areas that recently made enormous progress toward elimination, we tested how well different intervention programs were able to prevent reestablishment of malaria. We found that treating as many symptomatic cases as possible was the single most important intervention to implement. In some contexts, this intervention alone was sufficient to prevent reestablishment. Other areas with historically higher transmission required maintaining vector control to contain mosquito populations. Localized outbreak response with antimalarial drugs or additional vector control was also necessary and predicted to be a highly efficient use of resources. These findings provide quantitative guidance for policy-makers considering how to stratify eliminated areas and plan new operational modes for the post-elimination era.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Harsh Rajvanshi ◽  
Praveen K. Bharti ◽  
Sekh Nisar ◽  
Himanshu Jayswar ◽  
Ashok K. Mishra ◽  
...  

Abstract Background Malaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited. The project’s goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project. Methods The project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training.  The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP. Results The MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC. Conclusions Malaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030. In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India. This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Harsh Rajvanshi ◽  
Sekh Nisar ◽  
Praveen K. Bharti ◽  
Himanshu Jayswar ◽  
Ashok K. Mishra ◽  
...  

Abstract Background The Malaria Elimination Demonstration Project (MEDP) maintained a workforce of 235 Village Malaria Workers (VMWs) and 25 Malaria Field Coordinators (MFCs) to conduct disease surveillance, case management, IEC/BCC activities, capacity building, and monitoring of vector control activities in 1233 villages of Mandla, a high malaria endemic district of Madhya Pradesh in central India. Methods The induction training was conducted for 3 days on malaria diagnosis, treatment, prevention, and ethics. All trainings were assessed using a pre and post-training assessment questionnaire, with 70% marks as qualifying threshold. The questionnaire was divided into three thematic areas viz. general knowledge related to malaria (KAP), diagnosis and treatment (DXRX), and vector control (PVC). Results In 2017, the project trained 330 candidates, followed by 243 and 247 candidates in 2018 and 2019, respectively. 94.3% candidates passed after a single training session. Almost all (95%) candidates showed improvement in knowledge after the training with 4% showing no effect and 1% showing deterioration. Progressive improvement in scores of 2017 cohort was seen along with significant improvement in performance of candidates in 2019 after the introduction of systematic monitoring and ‘shadowing’ training exercises. Conclusion The project has successfully demonstrated the value of recruitment of workers from the study area, outcome of training, and performance evaluation of field staff in malaria elimination programme. This careful strategy of recruitment and training resulted in a work-force that was capable of independently conducting surveillance, case management, vector control, and Information Education Communication/Behaviour Change Communication (IEC/BCC). The learnings of this study, including the training modules and monitoring processes, can be used to train the health delivery staff for achieving national goal for malaria elimination by 2030. Similar training and monitoring programmes could also be used for other public health delivery programmes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ellen Brooks-Pollock ◽  
Hannah Christensen ◽  
Adam Trickey ◽  
Gibran Hemani ◽  
Emily Nixon ◽  
...  

AbstractControlling COVID-19 transmission in universities poses challenges due to the complex social networks and potential for asymptomatic spread. We developed a stochastic transmission model based on realistic mixing patterns and evaluated alternative mitigation strategies. We predict, for plausible model parameters, that if asymptomatic cases are half as infectious as symptomatic cases, then 15% (98% Prediction Interval: 6–35%) of students could be infected during the first term without additional control measures. First year students are the main drivers of transmission with the highest infection rates, largely due to communal residences. In isolation, reducing face-to-face teaching is the most effective intervention considered, however layering multiple interventions could reduce infection rates by 75%. Fortnightly or more frequent mass testing is required to impact transmission and was not the most effective option considered. Our findings suggest that additional outbreak control measures should be considered for university settings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdou Talipouo ◽  
Konstantinos Mavridis ◽  
Elysée Nchoutpouen ◽  
Borel Djiappi-Tchamen ◽  
Emmanouil Alexandros Fotakis ◽  
...  

AbstractCulex mosquitoes particularly Culex quinquefasciatus are important arboviral and filariasis vectors, however despite this important epidemiological role, there is still a paucity of data on their bionomics. The present study was undertaken to assess the insecticide resistance status of Cx. quinquefasciatus populations from four districts of Yaoundé (Cameroon). All Culex quinquefasciatus populations except one displayed high resistance to bendiocarb and malathion with mortalities ranging from 0 to 89% while high resistance intensity against both permethrin and deltamethrin was recorded. Molecular analyses revealed high frequencies of the ACE-1 G119S mutation (ranging from 0 to 33%) and kdr L1014F allele (ranging from 55 to 74%) in all Cx. quinquefasciatus populations. Significant overexpression was detected for cytochrome P450s genes CYP6AA7 and CYP6Z10, as well as for Esterase A and Esterase B genes. The total cuticular hydrocarbon content, a proxy of cuticular resistance, was significantly increased (compared to the S-lab strain) in one population. The study confirms strong insecticide resistance mediated by different mechanisms in Cx. quinquefasciatus populations from the city of Yaoundé. The expansion of insecticide resistance in Culex populations could affect the effectiveness of current vector control measures and stress the need for the implementation of integrated vector control strategies in urban settings.


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