bims-mosdis Biomed News
on Mosquito distribution and disease
Issue of 2021–09–19
twenty-two papers selected by
Richard Halfpenny, Staffordshire University
  1. Multi-Year Mass-Trapping With Autocidal Gravid Ovitraps has Limited Influence on Insecticide Susceptibility in Aedes aegypti (Diptera: Culicidae) From Puerto Rico.
  2. Identification of Phasi Charoen-Like Phasivirus in Field Collected Aedes aegypti from Karnataka State, India.
  3. On the cost-effectiveness of insecticide-treated wall liner and indoor residual spraying as additions to insecticide treated bed nets to prevent malaria: findings from cluster randomized trials in Tanzania.
  4. Malaria prevalence and associated risk factors in Dembiya district, North-western Ethiopia.
  5. Is malaria elimination a distant dream? Reconsidering malaria elimination strategies in Zimbabwe.
  6. Assessment of Knowledge, Attitude, and Practice towards Prevention and Control of Malaria in Halaba Town, Southern Ethiopia, 2017.
  7. Symbiotic Interactions Between Mosquitoes and Mosquito Viruses.
  8. Early warning systems (EWSs) for chikungunya, dengue, malaria, yellow fever, and Zika outbreaks: What is the evidence? A scoping review.
  9. Assessing the impact of COVID-19 border restrictions on dengue transmission in Yunnan Province, China: an observational epidemiological and phylogenetic analysis.
  10. Cost-effectiveness of malaria elimination in Sampov Loun Operational District, Cambodia.
  11. A Retrospective Study of Malaria Trend in Libokemkem District Over the Last Five Years: North West Ethiopia.
  12. Editorial: The First Monoclonal Antibody Vaccine to Prevent Malaria Heralds a New Era of Malaria Vaccines to the Plasmodium falciparum Circumsporozoite Protein (PfCSP).
  13. Cambodia malaria indicator survey 2020: Implications for malaria elimination.
  14. The central role of Italy in the spatial spread of USUTU virus in Europe.
  15. Prevalence and risk factors associated with asymptomatic malaria among school children: repeated cross-sectional surveys of school children in two ecological zones in Ghana.
  16. Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes.
  17. Risk factors for malaria in high incidence areas of Viet Nam: a case-control study.
  18. Evolution of multidrug resistance in Plasmodium falciparum: a longitudinal study of genetic resistance markers in the Greater Mekong Subregion.
  19. Discrete dynamical models on Wolbachia infection frequency in mosquito populations with biased release ratios.
  20. Dengue and Coronavirus disease (COVID-19) syndemic: Double threat to an overburdened healthcare system in Africa.
  21. Tissue macrophages and interferon-gamma signalling control blood-stage Plasmodium chabaudi infections derived from mosquito-transmitted parasites.
  22. Global burden for dengue and the evolving pattern in the past 30 years.
  1. J Med Entomol. 2021 Sep 17. pii: tjab162. [Epub ahead of print]
    Multi-Year Mass-Trapping With Autocidal Gravid Ovitraps has Limited Influence on Insecticide Susceptibility in Aedes aegypti (Diptera: Culicidae) From Puerto Rico.
    Ryan R Hemme, Eric A Smith, Gilberto Felix, Bradley J White, Marta I Diaz-Garcia, Damaris Rodriguez, Jose Ruiz-Valcarcel, Veronica Acevedo, Manuel Amador, Roberto Barrera.
      Mass-trapping has been used to control outbreaks of Aedes aegypti (Linnaeus) (Diptera: Culicidae) in Puerto Rico since 2011. We investigated the effect of multi-year, insecticide-free mass trapping had on the insecticide susceptibility profile of Ae. aegypti. Eggs collected in southern Puerto Rico were used to generate F1 populations that were tested for susceptibility to permethrin, sumethrin, bifenthrin, deltamethrin, and malathion according to CDC bottle bioassays protocols. All populations of Ae. aegypti were resistant to the synthetic pyrethroids and mosquitoes from two locations were partially resistant to malathion. Population genetic analysis, using a double digest restriction sites associated DNA sequencing (ddRADseq) approach, indicated a large amount of migration between study sites effectively homogenizing the mosquito populations. Mass-trapping using noninsecticidal autocidal gravid ovitraps did not restore susceptibility to five active ingredients that are found in commercial insecticides. Migration between communities was high and would have brought outside alleles, including resistant alleles to the treatment communities. Further investigation suggests that household use of commercially available insecticide products may continue to select for resistance in absence of public health space spraying of insecticides.
    Keywords:   Aedes aegypti ; Puerto Rico; insecticide resistance; population genetics
    DOI:  https://doi.org/10.1093/jme/tjab162
  2. Vector Borne Zoonotic Dis. 2021 Sep 14.
    Identification of Phasi Charoen-Like Phasivirus in Field Collected Aedes aegypti from Karnataka State, India.
    Ashok Munivenkatappa, Dimpal A Nyayanit, Pragya D Yadav, Manjushree Rangappa, Savita Patil, Triparna Majumdar, Sreelekshmy Mohandas, Diamond Prakash Sinha, Manjunath M Jayaswamy, Patil OmPrakash.
      Background: A wide range of insect-specific viruses (ISVs) have been reported worldwide. There are no studies from India that have reported ISVs. The current study describes the identification of Phasi Charoen-like virus (PCLV) from Aedes aegypti mosquito-pools from six districts of Karnataka state, India. Materials and Methods: During the Chikungunya virus (CHIKV) outbreak in the Bangalore Urban district in 2019, using conventional PCR, it was found that both human and mosquito samples were positive for CHIKV. For retrieve the complete genome sequence, mosquito samples were subjected to next generation sequencing (NGS) analysis and PCLV was also found. During 2019, as part of a vector-borne disease surveillance, we received 50 mosquito pool samples from 6 districts of the state, all of them were subjected to NGS to identify PCLV. Results: The A. aegypti mosquito-pools samples were subjected to the NGS platform that led to identification of an ISV, PCLV. PCLV was identified in 26 A. aegypti mosquito-pools collected from 6 districts. We also found mixed infection of PCLV with the Dengue virus (DENV; genotypes 1 and 3) and CHIKV from five pools. The nucleotide identity for the L gene of Indian PCLV sequences ranged between 97.1% and 98.3% in comparison with the Thailand sequences. Conclusions: To the best of our knowledge, this is the first report of PCLV dual infection with DENV and CHIKV in India. The present study confirms the presence of PCLV in A. aegypti mosquitoes from Karnataka state. The study adds India in the global geographical distribution of PCLV.
    Keywords:  Aedes aegypti; entomology; insect specific viruses; vector-borne
    DOI:  https://doi.org/10.1089/vbz.2021.0011
  3. BMC Public Health. 2021 Sep 14. 21(1): 1666
    On the cost-effectiveness of insecticide-treated wall liner and indoor residual spraying as additions to insecticide treated bed nets to prevent malaria: findings from cluster randomized trials in Tanzania.
    Kihomo Robert Mpangala, Yara A Halasa-Rappel, Mohamed Seif Mohamed, Ruth C Mnzava, Kaseem J Mkuza, Peter E Mangesho, William N Kisinza, Joseph P Mugasa, Louisa A Messenger, George Mtove, Aggrey R Kihombo, Donald S Shepard.
       BACKGROUND: Despite widespread use of long-lasting insecticidal nets (LLINs) and other tools, malaria caused 409,000 deaths worldwide in 2019. While indoor residual spraying (IRS) is an effective supplement, IRS is moderately expensive and logistically challenging. In endemic areas, IRS requires yearly application just before the main rainy season and potential interim reapplications. A new technology, insecticide-treated wall liner (ITWL), might overcome these challenges.
    METHODS: We conducted a 44-cluster two-arm randomized controlled trial in Muheza, Tanzania from 2015 to 2016 to evaluate the cost and efficacy of a non-pyrethroid ITWL to supplement LLINs, analyzing operational changes over three installation phases. The estimated efficacy (with 95% confidence intervals) of IRS as a supplement to LLINs came mainly from a published randomized trial in Muleba, Tanzania. We obtained financial costs of IRS from published reports and conducted a household survey of a similar IRS program near Muleba to determine household costs. The costs of ITWL were amortized over its 4-year expected lifetime and converted to 2019 US dollars using Tanzania's GDP deflator and market exchange rates.
    RESULTS: Operational improvements from phases 1 to 3 raised ITWL coverage from 35.1 to 67.1% of initially targeted households while reducing economic cost from $34.18 to $30.56 per person covered. However, 90 days after installing ITWL in 5666 households, the randomized trial was terminated prematurely because cone bioassay tests showed that ITWL no longer killed mosquitoes and therefore could not prevent malaria. The ITWL cost $10.11 per person per year compared to $5.69 for IRS. With an efficacy of 57% (3-81%), IRS averted 1162 (61-1651) disability-adjusted life years (DALYs) per 100,000 population yearly. Its incremental cost-effectiveness ratio (ICER) per DALY averted was $490 (45% of Tanzania's per capita gross national income).
    CONCLUSIONS: These findings provide design specifications for future ITWL development and implementation. It would need to be efficacious and more effective and/or less costly than IRS, so more persons could be protected with a given budget. The durability of a previous ITWL, progress in non-pyrethroid tools, economies of scale and competition (as occurred with LLINs), strengthened community engagement, and more efficient installation and management procedures all offer promise of achieving these goals. Therefore, ITWLs merit ongoing study.
    FIRST POSTED: 2015 ( NCT02533336 ).
    Keywords:  Cost; Cost-effectiveness; Indoor residual spraying; Insecticide-Treated Wall liner; Malaria prevention; Pyrethroid resistance; RCT; Randomized controlled trial; Tanzania; Vector control
    DOI:  https://doi.org/10.1186/s12889-021-11671-2
  4. Malar J. 2021 Sep 17. 20(1): 372
    Malaria prevalence and associated risk factors in Dembiya district, North-western Ethiopia.
    Mihretu Tarekegn, Habte Tekie, Sisay Dugassa, Yitbarek Wolde-Hawariat.
       BACKGROUND: Ethiopia embarked on combating malaria with an aim to eliminate malaria from low transmission districts by 2030. A continuous monitoring of malaria prevalence in areas under elimination settings is important to evaluate the status of malaria transmission and the effectiveness of the currently existing malaria intervention strategies. The aim of this study was to assess the prevalence of malaria and associated risk factors in selected areas of Dembiya district.
    METHODS: A cross-sectional parasitological and retrospective survey was conducted in the two localities of Dembiya District, selected based on their long standing history of implementing malaria prevention and elimination strategies. Thin and thick blood smears collected from 735 randomly selected individuals between October and December, 2018 were microscopically examined for malaria parasites. Six years (2012-2017) retrospective malaria data was collected from the medical records of the health centres. Structured questionnaires were prepared to collect information about the socio-economic data of the population. Logistic regression analysis was used to determine a key risk factor explaining the prevalence of malaria. The data were analysed using SPSS version 20 and p ≤ 0.05 were considered statistically significant.
    RESULTS: The 6-year retrospective malaria prevalence trend indicates an overall malaria prevalence of 22.4%, out of which Plasmodium falciparum was the dominant species. From a total of 735 slides examined for the presence of malaria parasites, 3.5% (n = 26) were positive for malaria parasites, in which P. falciparum was more prevalent (n = 17; 2.3%), Plasmodium vivax (n = 5; 0.7%), and mixed infections (n = 4; 0.5%). Males were 2.6 times more likely to be infected with malaria than females (AOR = 2.6; 95% CI 1.0, 6.4), and individuals with frequent outdoor activity were 16.4 times more vulnerable than individuals with limited outdoor activities (AOR = 16.4, 95% CI 1.8, 147.9). Furthermore, awareness about malaria transmission was significantly associated with the prevalence of malaria.
    CONCLUSIONS: Malaria is still a public health problem in Dembiya district irrespective of the past and existing vector control interventions. Therefore, the authorities should work on designing alternative intervention strategies targeting outdoor malaria transmission and improving community awareness about malaria transmission and control methods in the study area. For this, continuous monitoring of vectors' susceptibility, density, and behaviour is very important in such areas.
    Keywords:  Anopheles; Malaria control; Malaria prevalence; Malaria risk factors; Plasmodium
    DOI:  https://doi.org/10.1186/s12936-021-03906-9
  5. Public Health Pract (Oxf). 2021 Nov;2 100168
    Is malaria elimination a distant dream? Reconsidering malaria elimination strategies in Zimbabwe.
    Elliot Mbunge, Richard Millham, Nokuthula Sibiya, Sam Takavarasha.
      Malaria remains a public health problem decimating vulnerable populace especially in resource-constrained areas in Zimbabwe. Significant progress towards malaria elimination has beenik made in the previous decades through intensified and improved malaria control measures such as indoor residual spraying (IRS), distribution of long-lasting insecticidal nets (LLIN), artemisinin-based combination therapy and administration of intermittent preventive treatment in pregnancy. However, the outbreak of pandemics like coronavirus disease (COVID-19), cyclones and tropical storms, lack of funding, porous political environment, dearth of resources for vector control, changes in vector behaviour, vector resistance to insecticides, community behavioural change and lack of feasible and sustainable digital technologies for managing malaria control interventions retards progress made towards malaria elimination. Also, arbitrary political environment and unstable economic situation often interfere with health programmes which subsequently lead to malaria outbreaks. Most recently, the country recorded a sharp increase in malaria incidences in malaria-endemic areas especially during the pandemic due to some factors such as movement restrictions, temporary cancellation of IRS activities, delayed delivery of IRS chemicals and recursive lockdown. Therefore, we propose ways to mitigate future malaria outbreaks and advocate for reconsidering malaria elimination strategies to addresses emerging challenges in eradicating malaria in Zimbabwe.
    Keywords:  COVID-19; Digital technologies; Elimination; Malaria; Zimbabwe
    DOI:  https://doi.org/10.1016/j.puhip.2021.100168
  6. J Trop Med. 2021 ;2021 5665000
    Assessment of Knowledge, Attitude, and Practice towards Prevention and Control of Malaria in Halaba Town, Southern Ethiopia, 2017.
    Tadesse Menjetta.
       Background: Malaria is one of the primary public health problems in Ethiopia. Therefore, assessment of situation of the disease and communities' knowledge and perceptions about this disease is necessary to introduce appropriate preventive and control measures. Hence, this study was aimed to assess the knowledge, attitude, and practice towards malaria in Halaba town, SNNPR, Ethiopia.
    Methods: A community-based cross-sectional study was conducted in Halaba town from June 2017 to September 2017. A multistage random sampling technique was used to select the study participants. A total of 421 were interviewed to assess their knowledge, attitude, and practice towards malaria.
    Results: About 280 (66.5%) respondents had ever heard of malaria. Most of the respondents (63.4%) attributed the cause of malaria to mosquito bites. However, some of the respondents (36.6%) mentioned contact with malaria patients, lack of personal hygiene, staying together, and transmission via breathing as the causes of malaria. Sleeping under mosquito nets, draining stagnant water, and indoor residual spraying were the most frequently mentioned malaria preventive measures perceived and practiced by the respondents.
    Conclusions: A high level of knowledge about the cause, transmission, and preventive methods of malaria was detected among the community in Halaba town. However, a significant proportion had misconceptions about the cause and transmission of malaria suggesting the necessity of health education to raise the community's awareness about the disease.
    DOI:  https://doi.org/10.1155/2021/5665000
  7. Front Cell Infect Microbiol. 2021 ;11 694020
    Symbiotic Interactions Between Mosquitoes and Mosquito Viruses.
    Mine Altinli, Esther Schnettler, Mathieu Sicard.
      Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.
    Keywords:  Wolbachia; insect symbiosis; insect-specific viruses; interactions; microbiota; mosquitoes
    DOI:  https://doi.org/10.3389/fcimb.2021.694020
  8. PLoS Negl Trop Dis. 2021 Sep;15(9): e0009686
    Early warning systems (EWSs) for chikungunya, dengue, malaria, yellow fever, and Zika outbreaks: What is the evidence? A scoping review.
    Laith Hussain-Alkhateeb, Tatiana Rivera Ramírez, Axel Kroeger, Ernesto Gozzer, Silvia Runge-Ranzinger.
       BACKGROUND: Early warning systems (EWSs) are of increasing importance in the context of outbreak-prone diseases such as chikungunya, dengue, malaria, yellow fever, and Zika. A scoping review has been undertaken for all 5 diseases to summarize existing evidence of EWS tools in terms of their structural and statistical designs, feasibility of integration and implementation into national surveillance programs, and the users' perspective of their applications.
    METHODS: Data were extracted from Cochrane Database of Systematic Reviews (CDSR), Google Scholar, Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, Web of Science, and WHO Library Database (WHOLIS) databases until August 2019. Included were studies reporting on (a) experiences with existing EWS, including implemented tools; and (b) the development or implementation of EWS in a particular setting. No restrictions were applied regarding year of publication, language or geographical area.
    FINDINGS: Through the first screening, 11,710 documents for dengue, 2,757 for Zika, 2,706 for chikungunya, 24,611 for malaria, and 4,963 for yellow fever were identified. After applying the selection criteria, a total of 37 studies were included in this review. Key findings were the following: (1) a large number of studies showed the quality performance of their prediction models but except for dengue outbreaks, only few presented statistical prediction validity of EWS; (2) while entomological, epidemiological, and social media alarm indicators are potentially useful for outbreak warning, almost all studies focus primarily or exclusively on meteorological indicators, which tends to limit the prediction capacity; (3) no assessment of the integration of the EWS into a routine surveillance system could be found, and only few studies addressed the users' perspective of the tool; (4) almost all EWS tools require highly skilled users with advanced statistics; and (5) spatial prediction remains a limitation with no tool currently able to map high transmission areas at small spatial level.
    CONCLUSIONS: In view of the escalating infectious diseases as global threats, gaps and challenges are significantly present within the EWS applications. While some advanced EWS showed high prediction abilities, the scarcity of tool assessments in terms of integration into existing national surveillance systems as well as of the feasibility of transforming model outputs into local vector control or action plans tends to limit in most cases the support of countries in controlling disease outbreaks.
    DOI:  https://doi.org/10.1371/journal.pntd.0009686
  9. Lancet Reg Health West Pac. 2021 Sep;14 100259
    Assessing the impact of COVID-19 border restrictions on dengue transmission in Yunnan Province, China: an observational epidemiological and phylogenetic analysis.
    Naizhe Li, Yun Feng, Bram Vrancken, Yuyang Chen, Lu Dong, Qiqi Yang, Moritz U G Kraemer, Oliver G Pybus, Hailin Zhang, Oliver J Brady, Huaiyu Tian.
       BACKGROUND: In response to the COVID-19 pandemic, China implemented strict restrictions on cross-border travel to prevent disease importation. Yunnan, a Chinese province that borders dengue-endemic countries in Southeast Asia, experienced unprecedented reduction in dengue, from 6840 recorded cases in 2019 to 260 in 2020.
    METHODS: Using a combination of epidemiological and virus genomic data, collected from 2013 to 2020 in Yunnan and neighbouring countries, we conduct a series of analyses to characterise the role of virus importation in driving dengue dynamics in Yunnan and assess the association between recent international travel restrictions and the decline in dengue reported in Yunnan in 2020.
    FINDINGS: We find strong evidence that dengue incidence between 2013-2019 in Yunnan was closely linked with international importation of cases. A 0-2 month lag in incidence not explained by seasonal differences, absence of local transmission in the winter, effective reproductive numbers < 1 (as estimated independently using genetic data) and diverse cosmopolitan dengue virus phylogenies all suggest dengue is non-endemic in Yunnan. Using a multivariate statistical model we show that the substantial decline in dengue incidence observed in Yunnan in 2020 but not in neighbouring countries is closely associated with the timing of international travel restrictions, even after accounting for other environmental drivers of dengue incidence.
    INTERPRETATION: We conclude that Yunnan is a regional sink for DENV lineage movement and that border restrictions may have substantially reduced dengue burden in 2020, potentially averting thousands of cases. Targeted testing and surveillance of travelers returning from high-risk areas could help to inform public health strategies to minimise or even eliminate dengue outbreaks in non-endemic settings like southern China.
    FUNDING: Funding for this study was provided by National Key Research and Development Program of China, Beijing Science and Technology Planning Project (Z201100005420010); Beijing Natural Science Foundation (JQ18025); Beijing Advanced Innovation Program for Land Surface Science; National Natural Science Foundation of China (82073616); Young Elite Scientist Sponsorship Program by CAST (YESS) (2018QNRC001); H.T., O.P.G. and M.U.G.K. acknowledge support from the Oxford Martin School. O.J.B was supported by a Wellcome Trust Sir Henry Wellcome Fellowship (206471/Z/17/Z). Chinese translation of the abstract (Appendix 2).
    Keywords:  COVID-19 border restrictions; dengue expansion; lockdown; mosquito-borne viruses
    DOI:  https://doi.org/10.1016/j.lanwpc.2021.100259
  10. Malariaworld J. 2020 ;11 2
    Cost-effectiveness of malaria elimination in Sampov Loun Operational District, Cambodia.
    Ir Por, Siv Sovannaroth, Alexander Moran, Lek Dysoley, Sokomar Nguon, Om Bunthy, May Sak Meas, Lawrence Barat, Rida Slot, Sharon Thangadurai, Bryan K Kapella, Saad El-Din Hassan, Ly Po, Sen Sam An, John E Gimnig, Mary McDowell, Michael Thigpen, Jennifer Armistead, Hala Jassim AlMossawi, Soy Ty Kheang, Neeraj Kak.
       Background: Over the past decade, Cambodia has seen a significant decline in its malaria burden. The government has established the goal of eliminating malaria in the country by 2025. With PMI/USAID support, Cambodia is implementing a package of interventions as part of its efforts. This assessment aimed to describe the cost of malaria elimination activities in Sampov Loun Operational District (OD) between July 2015 and March 2018, to describe the cost per malaria case detected under PMI programming, and to estimate the incremental cost-effectiveness of the elimination programme per Plasmodium falciparum (Pf) or P. vivax (Pv)/Pf mixed case averted under the Cambodia Malaria Elimination Programme (CMEP) and the U.S. President's Malaria Initiative. Opportunity costs of government workers were also assessed to understand the theoretical cost of sustaining this programme through government efforts alone.
    Materials and methods: We conducted an empirical micro-costing analysis based on elimination activities alone using CMEP internal project implementation data and corresponding epidemiologic data from July 2015 to March 2018 and empirical findings from implementation to date. We then constructed a cost model in Microsoft Excel using empirical data and used a cost-effectiveness decision tree to describe programme effectiveness in the first three years of implementation and to estimate efficacy for the subsequent year.
    Results: The total cost of malaria elimination activities in Sampov Loun OD from July 2015 to March 2018 was $883,096. The cost per case of malaria detected in 2017 was $1,304. Including opportunity costs for government staff from July 2015 to March 2018, the total cost was $926,000. Under continued CMEP implementation, the projected future total cost of the program would be about $110,000 per year, or $0.64 per Sampov Loun resident. The incremental cost-effectiveness of the elimination programme was $28 for every additional Pf or Pv/Pf mix malaria case averted, compared to the no-CMEP proxy.
    Conclusion: CMEP activities are cost effective compared to the no-CMEP proxy, as shown through an incremental cost-effectiveness of $28 for every additional Pf or Pv/Pf mix malaria case averted. The total cost of the project is 0.93% of the total per capita spending on health in Cambodia and about 5% of all government health expenditure. Continuing investments in malaria will be needed at national level for stewardship and governance and at local level for ensuring programme readiness in case of malaria outbreaks.
  11. Infect Drug Resist. 2021 ;14 3683-3691
    A Retrospective Study of Malaria Trend in Libokemkem District Over the Last Five Years: North West Ethiopia.
    Lemma Workineh, Setegn Mekuria, Teklehaimanot Kiros, Wasihun Hailemichael, Tahir Eyayu.
       Background: Malaria is a vector-borne disease caused by public health important Plasmodium species. Despite the fact that Ethiopia has implemented several malaria prevention and control techniques aimed at reducing its morbidity and death, it continues as major cause of morbidity and mortality in Ethiopia. Transmission dynamics are really critical for guiding the selection of the appropriate intervention in a given area. As a result, the goal of this study was to analyze the trend of malaria prevalence over the last five years in the Addis Zemen health center.
    Methods: An institutional-based retrospective analysis on malaria data from 2015/16 to 2019/20 was undertaken in Addis Zemen health center of Libokemkem district. The data collectors thoroughly and systematically collected the results of 15,452 blood films performed over a five-year period from the malaria registration book in the health center. Any data missing species and stage of the parasite, as well as sociodemographic characteristics, date, month, and year of blood film performed, were omitted from the study. Finally, data were entered and analyzed using SPSS version 25, with P-values of less than or equal to 0.05 deemed statistically significant variables.
    Results: The overall malaria slide positivity rate over the last five years in the study area was 10.9%. From 2015/16 to 2018/19, the positive rate fell, then it spiked in 2019/20. Plasmodium falciparum was the most common parasite found, accounting for 72.6% of the total. The months of October, November, May, June, August, and September showed the largest number of malaria cases. Males, rural residents, and adult population groups were more affected by malaria, according to multivariate logistic regression (P ≤0.05).
    Conclusion: There was high malaria morbidity case in 2019/20 as compared to the remaining years. Therefore, malaria control, prevention, and intervention programs in the district should be strengthened.
    Keywords:  Libokemkem district; malaria slide positivity rate; malaria trend analysis
    DOI:  https://doi.org/10.2147/IDR.S329708
  12. Med Sci Monit. 2021 Sep 13. 27 e934676
    Editorial: The First Monoclonal Antibody Vaccine to Prevent Malaria Heralds a New Era of Malaria Vaccines to the Plasmodium falciparum Circumsporozoite Protein (PfCSP).
    Dinah V Parums.
      Malaria affects more than 3 billion people in 95 countries, with an estimated mortality rate of 400,000 per year. The female Anopheles spp mosquito most commonly transmits malaria, and the main burden of disease is due to Plasmodium falciparum. The most abundant antigen on the sporozoite surface is the Plasmodium falciparum circumsporozoite protein (PfCSP). PfCSP is required for parasite development and attachment to host hepatocytes. The first potential protein vaccine, RTS,S/ASO1, consists of a recombinant fusion antigen based on PfCSP. Initial findings from a phase 3 trial of RTS,S/ASO1 were promising but resulted in recommendations for further evaluation in large-scale trials. R21, a circumsporozoite protein-based vaccine, combined with an adjuvant, Matrix-M (MM), was recently evaluated in a phase 2 investigational study in children between 5-17 months of age in Burkina Faso. The R21/MM candidate vaccine resulted in high titers of malaria-specific antibodies. On August 26, 2021, the findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, showed that a single dose of the CIS43LS monoclonal antibody resulted in protection against malaria. These new findings have implications for the seasonal control of malaria in endemic regions and a possible future role in public health strategies to eliminate malaria. This Editorial aims to provide the background to developing and evaluating the new malaria vaccines that target PfCSP, including the first monoclonal antibody vaccine to malaria.
    DOI:  https://doi.org/10.12659/MSM.934676
  13. Malariaworld J. 2021 ;12 5
    Cambodia malaria indicator survey 2020: Implications for malaria elimination.
    Soy T Kheang, Ir Por, Siv Sovannaroth, Lek Dysoley, Huch Chea, Ly Po, Hala J AlMossawi, Abu Al Imran, Neeraj Kak.
       Background: Cambodia has made significant progress in controlling malaria in the past decade. It now aims to eliminate malaria from the country by 2025. It launched the Malaria Elimination Action Framework (MEAF 2016-2020) in 2015 with strong political commitment targeting appropriate interventions on high-risk populations, particularly mobile and migrant groups.
    Methods: In 2020, the household-level Cambodia Malaria Survey 2020 (CMS 2020) was conducted with the objective to assess the performance of malaria control activities using the indicators outlined in MEAF 2016-2020. The survey used a cross-sectional probability proportional to size approach drawing 4,000 households from 100 villages across the malaria-endemic districts of the country.
    Results: A total of 3,996 households with 17,415 inhabitants were interviewed. Of the surveyed households, 98.4% owned a long-lasting insecticide-treated bednet or hammock (LLIN/LLIHN). However, only 79.5% of these reported sleeping under a net the previous night, with only 45.7% sleeping under an insecticide treated net (ITN). Given that forest visitors are at the highest risk of getting malaria, the survey also targeted this group. Of the forest visitor respondents, 89.3% brought an ITN along and 88.9% reported to have used a net during their forest stay. About 10.8% of forest goers had received a forest kit for malaria prevention from mobile malaria workers the last time they went to the forest. Knowledge about mosquito repellents was high among forest goers (62.5%) but the actual use thereof during the last visit to the forest was low (22%). While awareness about malaria prevention with LLINs remained high among most respondents, knowledge about malaria diagnosis and treatment was not universal. Source of malaria knowledge and its treatment was usually from a household member, followed by a village malaria worker or a primary health care center staff. Of those who had fever during the previous two weeks, 93.6% sought advice or treatment outside the home, and the most commonly reported source for advice or treatment was private providers (39.4%) followed by health center/district hospital (31.3%).
    Conclusions: ITN distribution and other malaria prevention interventions have largely benefited the high-risk groups including the forest visitors. Comparing the CMS 2020 results with the 2017 CMS results, it is clear that forest visitors' use of LLIN/LLIHN has improved considerably. However, more needs to be done to ensure forest visitors be protected either through using LLINs or repellents while working and staying in the forest areas. Also, given that sleeping under LLINs has decreased over the past several years among the at-risk populations, the programme will have to develop strategies to ensure that the communities do not lower their guard against malaria as cases further dwindle in malaria prone areas. Heightened awareness amongst the general population will be critical for eliminating malaria in Cambodia without any possibility of malaria re-emergence or re-establishment.
  14. Virus Evol. 2021 Jan;7(1): veab048
    The central role of Italy in the spatial spread of USUTU virus in Europe.
    B Zecchin, A Fusaro, A Milani, A Schivo, S Ravagnan, S Ormelli, C Mavian, A Michelutti, F Toniolo, L Barzon, I Monne, G Capelli.
      USUTU virus (USUV) is an arbovirus maintained in the environment through a bird-mosquito enzootic cycle. Previous surveillance plans highlighted the endemicity of USUV in North-eastern Italy. In this work, we sequenced 138 new USUV full genomes from mosquito pools (Culex pipiens) and wild birds collected in North-eastern Italy and we investigated the evolutionary processes (phylogenetic analysis, selection pressure and evolutionary time-scale analysis) and spatial spread of USUV strains circulating in the European context and in Italy, with a particular focus on North-eastern Italy. Our results confirmed the circulation of viruses belonging to four different lineages in Italy (EU1, EU2, EU3 and EU4), with the newly sequenced viruses from the North-eastern regions, Veneto and Friuli Venezia Giulia, belonging to the EU2 lineage and clustering into two different sub-lineages, EU2-A and EU2-B. Specific mutations characterize each European lineage and geographic location seem to have shaped their phylogenetic structure. By investigating the spatial spread in Europe, we were able to show that Italy acted mainly as donor of USUV to neighbouring countries. At a national level, we identified two geographical clusters mainly circulating in Northern and North-western Italy, spreading both northward and southward. Our analyses provide important information on the spatial and evolutionary dynamics of USUTU virus that can help to improve surveillance plans and control strategies for this virus of increasing concern for human health.
    Keywords:  Italy; North-eastern; USUTU virus; diffusion dynamics; evolutionary analysis
    DOI:  https://doi.org/10.1093/ve/veab048
  15. BMC Public Health. 2021 Sep 17. 21(1): 1697
    Prevalence and risk factors associated with asymptomatic malaria among school children: repeated cross-sectional surveys of school children in two ecological zones in Ghana.
    B A Mensah, J L Myers-Hansen, E Obeng Amoako, M Opoku, B K Abuaku, A Ghansah.
       BACKGROUND: Asymptomatic Plasmodium infections significantly drive malaria transmission and impact control and elimination strategies, but are largely uncharacterized. We investigated the prevalence and risk factors of asymptomatic malaria infections to inform malaria control strategies in Ghana.
    METHOD: Five cross-sectional surveys were conducted at the end of the peak transmission season (August-September) on 4892 school children aged between 6 and 14 years in two distinct ecological settings in Ghana between 2013 and 2017. The study sites were Begoro (forest ecology) and Cape Coast (coastal ecology). The children were screened for malaria parasites by microscopic examination of Giemsa-stained thin and thick blood films. Hemoglobin levels were measured using the Hemocue HB analyzer. In addition, height was measured and the height-for-age z-scores estimated from the reference population defined by WHO to determine children who were stunted. Proportions of categorical and means of continuous variables were compared using Chi-square test and Student's t-test respectively, and multivariable logistic regression was done to assess risk factors associated with asymptomatic infections.
    RESULTS: The overall prevalence of asymptomatic malaria in the school children was higher in Begoro compared to Cape Coast (27% (95% CI: 17, 24%) vs. 24% (95% CI: 17, 24%), p value = 0.04). The study recorded three species of Plasmodium (Plasmodia falciparum, malariae, and ovale) in both sites. Plasmodium falciparum was the predominant species, accounting for about 85% of infections in both study sites. The asymptomatic school children were more likely to be anaemic (OR = 2.01, p value< 0.001) and stunted in growth (OR = 1.46, p value< 0.001). Males carried more asymptomatic infection than females (OR = 1.18, p value = 0.015). School children aged 12-14 years had more asymptomatic infections than those aged 6-8 years (OR = 1.28, p value = 0.005).
    CONCLUSION: There is a considerable burden of asymptomatic malaria in the two regions of Ghana, which is associated with males, older children, anaemia, and stunted growth in children, and may have implications for malaria control and elimination strategies in Ghana.
    Keywords:  Asymptomatic infection; Ghana; Malaria burden; Plasmodium; Risk factors
    DOI:  https://doi.org/10.1186/s12889-021-11714-8
  16. Parasit Vectors. 2021 Sep 16. 14(1): 480
    Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes.
    Adrien Ickowicz, Scott D Foster, Geoffrey R Hosack, Keith R Hayes.
       BACKGROUND: Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains.
    METHODS: In this study, we: (i) describe a diffusion-advection-reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains.
    RESULTS: If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location.
    CONCLUSIONS: Spread and persistence models should form a key component of risk assessments of novel genetic control strategies for malaria vectors. Our predictions, used in an independent risk assessment, suggest that genetically modified sterile male mosquitoes will remain within the locality of the release site, and that they will persist for a very limited amount of time. Data gathered following the release of these mosquitoes will enable us to test the accuracy of these predictions and also provide a means to update parameter distributions for genetic strains in a coherent (Bayesian) framework. We anticipate this will provide additional insights about how to conduct probabilistic risk assessments of stage-released genetically modified mosquitoes.
    Keywords:  Bayesian hierarchical model; Entomological survey data; Expert elicitation; Monitoring; Sterile male
    DOI:  https://doi.org/10.1186/s13071-021-04982-1
  17. Malar J. 2021 Sep 17. 20(1): 373
    Risk factors for malaria in high incidence areas of Viet Nam: a case-control study.
    Richard J Maude, Thang Duc Ngo, Duong Thanh Tran, Binh Thi Huong Nguyen, Dung Viet Dang, Long Khanh Tran, Michael Gregory, Rapeephan R Maude, Ipsita Sinha, Kulchada Pongsoipetch, Nicholas J Martin.
       BACKGROUND: A key step to advancing the goal of malaria elimination in Viet Nam by 2030 is focusing limited resources for treatment and prevention to groups most at risk for malaria transmission.
    METHODS: To better understand risk factors for malaria transmission in central Viet Nam, a survey of 1000 malaria positive cases and 1000 malaria negative controls was conducted. Cases and controls were matched for age and gender and self-presented at commune health stations (CHS) in Binh Phuoc, Dak Nong and Dak Lak Provinces. Diagnoses were confirmed with microscopy, rapid diagnostic test and PCR. Participants were interviewed about 50 potential risk factors for malaria, which included information about occupation, forest visitation, travel, healthcare-seeking behaviour and prior use of anti-malaria interventions. Participants were enrolled by trained government health workers and the samples were analysed in Vietnamese government laboratories. Data were analysed by univariable, block-wise and multivariable logistic regression.
    RESULTS: Among cases, 61.8% had Plasmodium falciparum, 35.2% Plasmodium vivax and 3% mixed species infections. Median (IQR) age was 27 (21-36) years and 91.2% were male. Twenty-five risk factors were associated with being a case and eleven with being a control. Multivariable analysis found that malaria cases correlated with forest workers, recent forest visitation, longer duration of illness, having a recorded fever, number of malaria infections in the past year, having had prior malaria treatment and having previously visited a clinic.
    CONCLUSIONS: This study demonstrates the benefits of increased statistical power from matched controls in malaria surveillance studies, which allows identification of additional independent risk factors. It also illustrates an example of research partnership between academia and government to collect high quality data relevant to planning malaria elimination activities. Modifiable risk factors and implications of the findings for malaria elimination strategy are presented.
    DOI:  https://doi.org/10.1186/s12936-021-03908-7
  18. Antimicrob Agents Chemother. 2021 Sep 13. AAC0112121
    Evolution of multidrug resistance in Plasmodium falciparum: a longitudinal study of genetic resistance markers in the Greater Mekong Subregion.
    Mallika Imwong, Kanokon Suwannasin, Suttipat Srisutham, Ranitha Vongpromek, Cholrawee Promnarate, Aungkana Saejeng, Aung Pyae Phyo, Stephane Proux, Tiengkham Pongvongsa, Chea Nguon, Olivo Miotto, Rupam Tripura, Nguyen Hoang Chau, Dysoley Lek, Ho Dang Trung Nghia, Thomas J Peto, James J Callery, Rob W van der Pluijm, Chanaki Amaratunga, Mavuto Mukaka, Lorenz von Seidlein, Mayfong Mayxay, Nguyen Thanh Thuy-Nhien, Paul N Newton, Nicholas Pj Day, Elizabeth A Ashley, Francois H Nosten, Frank M Smithuis, Mehul Dhorda, Nicholas J White, Arjen M Dondorp.
      Increasing drug resistance in Plasmodium falciparum to artemisinins and their ACT partner drugs jeopardises effective antimalarial treatment. Resistance is worst in the Greater Mekong Subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins (PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1, PfMDR1,), and piperaquine (PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter, PfCRT, mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao PDR, Cambodia, Thailand, Myanmar between 2007 and 2019. Against a high background prevalence of PfKelch mutations, PfMDR1 and PfPlasmepsin2/3 amplification closely followed regional drug pressures over time. PfPlasmepsin2/3 amplification preceded piperaquine-resistance associated PfCRT mutations in Cambodia, and reached a peak prevalence of 23/28 (82%) in 2015. This declined to 57/156 (38%) after changing first-line treatment away from dihydroartemisinin-piperaquine to artesunate-mefloquine (ASMQ) between 2014 and 2017. PfMDR1 amplification increased from 0/293 (0%) between 2012 and 2017 to 12/156 (8%) in 2019. Amplification of PfMDR1 and PfPlasmepsin2/3 in the same parasites was extremely rare (4/6,722; 0.06%) and dispersed over time. Mechanisms conferring mefloquine and piperaquine resistance may be counterbalancing. This supports the development of ASMQ plus piperaquine as a triple artemisinin combination therapy.
    DOI:  https://doi.org/10.1128/AAC.01121-21
  19. J Biol Dyn. 2021 Sep 17. 1-20
    Discrete dynamical models on Wolbachia infection frequency in mosquito populations with biased release ratios.
    Yantao Shi, Bo Zheng.
      We develop two discrete models to study how supplemental releases affect the Wolbachia spreading dynamics in cage mosquito populations. The first model focuses on the case when only infected males are released at each generation. This release strategy has been proved to be capable of speeding up the Wolbachia persistence by suppressing the compatible matings between uninfected individuals. The second model targets the case when only infected females are released at each generation. For both models, detailed model formulation, enumeration of the positive equilibria and their stability analysis are provided. Theoretical results show that the two models can generate bistable dynamics when there are three positive equilibrium points, semi-stable dynamics for the case of two positive equilibrium points. And when the positive equilibrium point is unique, it is globally asymptotically stable. Some numerical simulations are offered to get helpful implications on the design of the release strategy.
    Keywords:  65Q10; 92B05; 92D30; Wolbachia; cytoplasmic incompatibility; maternal transmission leakage rate; release ratio; the infection frequency
    DOI:  https://doi.org/10.1080/17513758.2021.1977400
  20. Int J Health Plann Manage. 2021 Sep 14.
    Dengue and Coronavirus disease (COVID-19) syndemic: Double threat to an overburdened healthcare system in Africa.
    Abdullahi Tunde Aborode, Anna Chiara Corriero, Emmanuel Adebowale Fajemisin, Mohammad Mehedi Hasan, Syeda Kanza Kazmi, Olayinka Olajiga.
      Dengue fever (DF) is a significant public health problem in the African continent. The primary prevention strategy against the disease is vaccination and entomological control of vectors; however, implementing such a strategy in several countries in the continent is far below what is necessary to control the disease. The Coronavirus disease (COVID-19) pandemic further aggravated this situation and negatively impacted these measures, mainly the coverage of vaccination campaigns, due to restrictive measures to control the disease. Therefore, the most significant risk is that the incidence of DF in the continent will increase even more in the coming years, as a reflection of the negative impact of the pandemic on the control of the disease. To prevent another public health crisis, immediate and multidisciplinary approaches are required to address the epidemiological control of DF in African countries.
    Keywords:  COVID-19; dengue fever; dengue transmission; syndemic; vector control
    DOI:  https://doi.org/10.1002/hpm.3334
  21. Curr Res Immunol. 2021 ;2 104-119
    Tissue macrophages and interferon-gamma signalling control blood-stage Plasmodium chabaudi infections derived from mosquito-transmitted parasites.
    Katrien Deroost, Christopher Alder, Caroline Hosking, Sarah McLaughlin, Jing-Wen Lin, Matthew D Lewis, Yolanda Saavedra-Torres, John W G Addy, Prisca Levy, Maria Giorgalli, Jean Langhorne.
      Natural infection with Plasmodium parasites, the causative agents of malaria, occurs via mosquito vectors. However, most of our knowledge of the immune response to the blood stages of Plasmodium is from infections initiated by injection of serially blood-passaged infected red blood cells, resulting in an incomplete life cycle in the mammalian host. Vector transmission of the rodent malaria parasite, Plasmodium chabaudi chabaudi AS has been shown to give rise to a more attenuated blood-stage infection in C57Bl/6J mice, when compared to infections initiated with serially blood-passaged P. chabaudi-infected red blood cells. In mouse models, the host immune response induced by parasites derived from natural mosquito transmission is likely to more closely resemble the immune responses to Plasmodium infections in humans. It is therefore important to determine how the host response differs between the two types of infections. As the spleen is considered to be a major contributor to the protective host response to P. chabaudi, we carried out a comparative transcriptomic analysis of the splenic response to recently mosquito-transmitted and serially blood-passaged parasites in C57Bl/6J mice. The attenuated infection arising from recently mosquito-transmitted parasites is characterised by an earlier and stronger myeloid- and IFNγ-related response. Analyses of spleen lysates from the two infections similarly showed stronger or earlier inflammatory cytokine and chemokine production in the recently mosquito-transmitted blood-stage infections. Furthermore, tissue macrophages, including red pulp macrophages, and IFNγ-signalling in myeloid cells, are required for the early control of P. chabaudi recently mosquito-transmitted parasites, thus contributing to the attenuation of mosquito-transmitted infections. The molecules responsible for this early activation response to recently-transmitted blood-stage parasites in mice would be important to identify, as they may help to elucidate the nature of the initial interactions between blood-stage parasites and the host immune system in naturally transmitted malaria.
    Keywords:  IFNγ; Macrophages; Plasmodium chabaudi; Red pulp macrophages; Spleen; Transcriptomics
    DOI:  https://doi.org/10.1016/j.crimmu.2021.07.002
  22. J Travel Med. 2021 Sep 11. pii: taab146. [Epub ahead of print]
    Global burden for dengue and the evolving pattern in the past 30 years.
    Xiaorong Yang, Mikkel B M Quam, Tongchao Zhang, Shaowei Sang.
       BACKGROUND: Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. We present the global, regional, and national burden of dengue from 1990 to 2019 based on the findings from the Global Burden of Diseases, Injures, and Risk Factors Study 2019 (GBD 2019).
    METHODS: Based upon GBD 2019 dengue data on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate, this study estimates and presents annual percentage change (EAPC) to quantify trends over time to assess potential correlates of increased dengue activity such as global travel, and warming.
    RESULTS: Globally from 1990 to 2019, dengue incident cases, deaths and DALYs gradually increased. Those under 5, once accounting for the largest portion of deaths and DALYs in 1990, were eclipsed by those 15-49 years old in 2019. Age standardized incidence (ASIR: EAPC 3.16, 95%CI: 2.90-3.43), death (ASDR: EAPC 5.42, 95%CI: 2.64-8.28), and DALY rates (EAPC 2.31, 95%CI: 2.00-2.62) accelerated most among high-middle and high socio-demographic index (SDI) regions. Southeast Asia and South Asia had most of the dengue incident cases, deaths and DALYs, but East Asia had the fastest rise in ASIR (EAPC 4.57, 95%CI: 4.31, 4.82), while Tropical Latin America led in ASDR (EAPC 11.32, 95%CI: 9.11, 13.58) and age-standardized DALYs rate (EAPC 4.13, 95%CI: 2.98, 5.29). SDI showed consistent bell shape relationship with ASIR, ASDR and age-standardized DALYs rate. Global Land-Ocean Temperature Index and air passenger travel metrics were found to be remarkably positively correlated with dengue burden.
    CONCLUSIONS: The burden of dengue has become heavier from 1990 to 2019, amidst the three decades of urbanization, warming climates and increased human mobility in much of the world. Southeast Asia and South Asia remain regions of concern, especially in conjunction with the Americas swift rise in dengue burden.
    Keywords:  Age-standardized DALYs rate; Age-standardized death rate; Age-standardized incidence rate; Dengue; Global Burden of Disease
    DOI:  https://doi.org/10.1093/jtm/taab146
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