Article Information

Ranjan Ramasamy

ID-FISH Technology Inc., 556 Gibraltar Drive, Milpitas, CA 95035, USA

*Corresponding author: Ranjan Ramasamy, ID-FISH Technology Inc., 556 Gibraltar Drive, Milpitas, CA 95035, USA.

Received: 1 July 2024; Accepted: 18 July 2024; Published: 14 August 2024

Citation: Ranjan Ramasamy. Analysis of Some Societal Factors Constraining COVID-19, Dengue, Malaria and Tick-Borne Borreliosis Control. Archives of Microbiology and Immunology. 8 (2024): 365-375.

Abstract

Keywords

Aedes aegypti; Aedes albopictus; Anopheles culicifacies; Anopheles stephensi; Borreliosis diagnostics; COVID-19; Dengue; Infectious disease control; Malaria; Media misinformation; Salinity adaptation in mosquito vectors; Societal constraints in infectious disease control; Vaccine hesitancy

Article Details

Introduction

The benefits conferred by recent scientific discoveries, e.g. new chemotherapeutics, monoclonal antibodies for diagnosis and treatment, recombinant protein antigens for diagnosis, and vaccines for infectious diseases like COVID-19, dengue and malaria, are widely appreciated. However, some societal factors that limit the application of new scientific advances for improving the control of COVID-19, dengue, malaria and tick-borne borreliosis are less well understood. This article separately analyses specific societal constraints in each of these four diseases with the objective of broadening understanding and promoting the development of appropriate measures to mitigate the constraints.

Dengue

Dengue is the most prevalent arboviral disease in the world with 5.2 million annual cases reported to the WHO in 2019, but with a higher estimated global incidence of 100 - 400 million cases [1,2]. Dengue vaccines have recently become available, while anti-viral drugs to specifically treat dengue have yet to be approved [1,2]. Aedes aegypti mosquitoes are the principal vectors of dengue and other human arboviral diseases, including chikungunya, yellow fever and Zika, in tropical and sub-tropical countries [1,2]. Aedes albopictus is a secondary arboviral vector that has recently expanded its range to several temperate zone countries, partly through developing diapausing eggs able to survive winters [1,2]. Larval source reduction measures are important worldwide for controlling Aedes vectors of dengue, in comparison with the spraying of adulticides indoors and the use of insecticide impregnated bed nets which are effective against Anopheles mosquito vectors of malaria [1-4]. This is because the two Aedes species, in contrast to the Anopheles vectors, tend to blood feed on humans outdoors during the day [1-4]. Most countries follow the World Health Organization (WHO) recommendations on vector control [1,3,4] for dengue and other arboviral diseases.

Development of Aedes mosquito vectors in coastal brackish water and implications for the control of dengue and other arboviral diseases

Both Ae. aegypti and Ae. albopictus are widely regarded to lay eggs and undergo preimaginal development only in fresh water (FW) collections containing <0.5 gL^-1 salt, so that the present WHO[3,4] and US Centres for Disease Control and Prevention (CDC) [2] guidelines for larval source reduction through applying larvicides and eliminating preimaginal habitats are only directed towards their freshwater habitats. The WHO recommends measures to minimize or eliminate freshwater collections where the Aedes vectors oviposit and undergo preimaginal development, the application of the organophosphate larvicide Temephos at concentrations up to 1 mgL^-1 to freshwater storage containers which constitute important Aedes larval habitats in the tropics, and space spraying with adulticides during epidemics to control dengue [1,3,4].

Aedes aegypti and Ae. albopictus, however, have been reported since 2011 to be capable of ovipositing and undergoing preimaginal development to adulthood in brackish water (BW) habitats of up to 15 gL^-1 salt in the northern coastal peninsula of Jaffna in the island of Sri Lanka (Figure 1) with FW, BW and saline water being defined as containing < 0.5, 0.5-30 and > 30 gL^-1 salt, respectively [5-10].

Figure 1: (a) Map showing the location of Sri Lanka in relation to South India; (b) the relative locations of the Jaffna peninsula, Mannar island and Jaffna city within Sri Lanka; (c) sites within Jaffna city where Anopheles stephensi (discussed in section 2) larvae are found. Reproduced with permission under the creative commons licence from [11].

The preimaginal development of Ae. aegypti and Ae. albopictus in BW has since been reported in coastal areas of other countries, including Brunei Darussalam [12], the US [13], Brazil [14], Mexico [15], Indonesia [16], and India [17]. Typical BW habitats of Ae. aegypti are BW accumulations in beach debris, fishing boats, and coastal wells, as well as discarded containers in swamps, drainage canals, urban drains, surface ground water and household containers in coastal areas [5-10,12-17]. The variety of BW habitats where Ae. aegypti larvae can be found in Jaffna city and other sites in the Jaffna peninsula are illustrated in Figure 2.

Figure 2: BW habitats of Ae. aegypti in the Jaffna peninsula, Sri Lanka. Photographs show the brackish water collections containing larvae in: A & B - disused boats; C & E: abandoned wells; D & F: discarded food and beverage containers. Reproduced with permission under the creative commons licence from [5].

BW-derived Ae. aegypti and Ae. albopictus larvae in the Jaffna peninsula were more salinity-tolerant, possessing higher LC₅₀ for salt, than the corresponding FW-derived larvae from the Sri Lankan mainland as shown in Figure 3 [5,10,18]. Aedes albopictus was observed to be more salinity tolerant than Ae. aegypti at both locations (Figure 3).

Figure 3: Effect salinity on Ae. aegypti and Ae. albopictus from (A) coastal Jaffna peninsula and (B) mainland Sri Lanka on the L1 and L3 larvae to adult transformation. L1 and L3 refer to first and third instar larvae respectively. Ppt - parts per thousand or gL^-1. Reproduced with permission under the creative commons licence from [5].

Further investigations on laboratory colonies established from field-collected BW and FW Ae. aegypti demonstrated that, although they remained reproductively compatible, BW-adapted or salinity-tolerant Ae. aegypti significantly differed from FW Ae. aegypti in several important biological features summarized in Table 1. These structural and physiological differences are likely to be important for the greater salinity tolerance in BW Ae. aegypti.

Table 1: Differences between BW and FW Ae. aegypti

L1-L4: first to fourth instar larval stages, AFM: atomic force microscopy, SEM: scanning electron microscopy, TEM: transmission electron microscopy, LC50: concentration producing 50% lethality

It is expected that the salinity-adaptive structural and molecular changes seen in Ae. aegypti will be paralleled in the secondary arboviral vector Ae. albopictus, as well as other FW mosquito vectors that have adapted to develop in coastal BW, e.g., the malaria vector Anopheles culicifacies discussed in section 2. However, further investigations are needed to confirm this hypothesis.

The euryhaline nature of salinity-tolerant Aedes vectors in coastal areas and the neglect of BW habitats in vector control programs, allows them to serve as arboviral reservoirs in coastal areas and function as bridging vectors for adjoining inland areas, thereby enhancing arboviral disease transmission and facilitating epidemics as discussed in more detail elsewhere [21]. As a consequence, it may be predicted that small islands and countries with long coastlines in relation to their total land area, e.g. Indonesia, Sri Lanka and the Caribbean islands, will be particularly prone to the enhanced transmission of arboviral diseases like dengue, chikungunya and Zika [22,23]. Moreover, it is expected that global warming leading to a rise in sea level will increase ground water salinisation in coastal areas, and further exacerbate arboviral disease transmission in this manner [24,25]. Therefore, it is important in coastal zones throughout the world to (i) extend larval source reduction efforts also to the BW habitats of Aedes vectors, and (ii) monitor the efficacy of widely-used larvicides such as Temephos in coastal areas because of the demonstrated diminished susceptibility of BW Aedes to Temephos [10]. Dengue, the most prevalent arboviral disease world, causes >100,000 cases annually in Sri Lanka. Despite overwhelming published evidence beginning with the first demonstration of salinity tolerant Aedes vectors in Sri Lanka in 2011 [5] and subsequently in other countries [12-17], Sri Lanka’s Ministry of Health has been slow to target BW collections in coastal areas in its dengue control program. The WHO and CDC guidelines for controlling dengue however continue to only focus on FW habitats of the Aedes vectors [1-4]. Because the WHO guidelines serve as a model for many countries, their modification to additionally target BW habitats of the two vectors can be an important advance globally for the more effective control of dengue and other arboviral diseases. The documented preimaginal development of both Ae. aegypti and Ae. albopictus in BW habitats in coastal areas of the state of Florida [13], and Ae. aegypti in neighbouring Mexico [15], suggests that modifying the existing CDC guidelines [2] to target coastal BW habitats of the two vectors will likewise benefit the control of dengue and other arboviral diseases in the US.

Understanding the implications of the reduced Aedes vector densities and dengue incidence observed during the COVID-19 lockdown for dengue control measures

Public health measures that severely curtailed the movement of people to reduce COVID-19 transmission during the period from 2020 to 2022, termed lockdown, were initially predicted to adversely affect mosquito control programs and increase the incidence of diseases like malaria and dengue in endemic countries [26]. A significant increase in the incidence and mortality from malaria during the COVID-19 lockdown was indeed reported in Zimbabwe [27]. A small increase in dengue incidence was also reported from Singapore [28] which is a country that employs stringent larval source reduction measures in both public places and residences to control dengue transmission. However, dengue incidence markedly decreased in all districts of Sri Lanka during the COVID-19 lockdown [29-32]. An 89% reduction in the number of predicted dengue cases during the most drastic lockdown period from March 2020 to April 2021 in the northern Jaffna district (Figure 4) was accompanied by an 89% drop in Aedes larvae collected from ovitraps in Jaffna city [29,30].

Figure 4: Numbers of actual and predicted dengue cases in the Jaffna district during COVID-19 movement restrictions. Severe restrictions on movement of people were in place from 1 March 2020 to 30 April 2021 (period A) to lower COVID-19 transmission. These were variably eased and reimposed from 1 May 2021 until 22 November 2021 (period B), but removed altogether with the full opening of all schools from 22 November 2021 onward (period C). Reproduced with permission under the creative commons licence from [30].

Dynamics of disease transmission by vector mosquitoes in a non-immune population is simply described by the Ross-MacDonald equation [33] which can be usefully applied to dengue transmission in the present context. This equation relates the number of secondary infections generated from a single infected person (R₀) to vector parameters as follows:

m= ratio of the number of vector mosquitoes to the number of humans;

a = average number of human blood meals taken by a mosquito in a day;

α = probability of transmission of pathogen from an infected human to a biting mosquito;

β = probability of transmission of a pathogen from an infected mosquito to a non-immune human during feeding;

p = daily probability of survival of the mosquito vector;

n = duration in days from infection of a biting mosquito until the mosquito becomes capable of infecting humans after the pathogen undergoes obligatory development in the mosquito, also termed the extrinsic incubation period;

r = recovery rate in humans (inverse of the average duration of infectiousness in days).

The anthropophagic Ae. aegypti and partially anthropophagic Ae. albopictus vectors are daytime feeders [1-4,9,34]. The two vectors are highly prevalent in premises of schools, hospitals, government offices, transport hubs, and factories in Sri Lanka [9,35]. The closure of schools and offices, as well other forms of restrictions on the movement of people outside of residences, can therefore be expected to reduce blood feeding by the two vectors, particularly Ae. aegypti, leading to a reduction in ‘a’ in the equation. Any reduction in blood meals will result in reduced oviposition and decreased vector densities, manifesting as reductions in ‘m’ and ‘p’. Lower values for ‘a’, ‘m’, and ‘p’ will diminish R₀, which will be particularly impacted by its exponential relationship with ‘a’ and ‘p’. R₀ is directly related to the rate of dengue transmission and therefore the number of dengue cases in the population. Reduced oviposition as a result of decreased blood feeding is consistent with diminished larval collections from ovitraps in Jaffna city [29,30], which was independently also observed in the western Colombo district [32], during the lockdown in Sri Lanka.

In particular, diminished access of Aedes vectors to blood meals in public places like schools, transport hubs, shops, temples and churches during the COVID-19 lockdown have been postulated to reduce vector densities and vector survival and therefore dengue transmission [29,30]. Both infection of uninfected Aedes vectors through feeding on infected persons, and infection of uninfected persons by infected Aedes vectors in new locations are promoted by population mobility, and may have additionally contributed to the reduced dengue incidence observed during the COVID-19 lockdown. Dengue and malaria incidences fell by 75% and 46% respectively during the 2020 lockdown in India [36], a country with similar dengue epidemiology and mosquito vector control programmes to Sri Lanka. Corresponding statistics for malaria are not applicable in Sri Lanka because malaria was eliminated from the island in 2013 [37]. The early expectation of epidemiologists, and the WHO, that the incidence of dengue and malaria will increase due to a collapse of vector control programmes during the COVID-19 pandemic [26], was therefore not borne out in India and Sri Lanka. From the perspective of more effective dengue control in Sri Lanka, India and other countries with similar dengue epidemiology, it would appear that this prevalent view [26] detracts from experimental findings [29,30] which strongly suggest that dengue control measures involving Aedes vector larval source reduction measures need to be more stringently applied than at present in public places where people congregate.

Conclusions

It is suggested that greater awareness of the relevant scientific findings by pertinent national and international organisations and their adoption of appropriate measures can improve the control of dengue and other arboviral diseases. Beneficial measures can include promoting further epidemiological studies to confirm the importance of the reported findings and modifying influential national and international guidelines for the control of Aedes vectors.

Malaria

The WHO in its latest World Malaria Report estimated 249 million cases of malaria occurred worldwide in 2022 (an increase of 5 million over 2021) and 608,000 deaths from malaria worldwide [38]. All known species of Plasmodium parasites that cause human malaria are transmitted by several different species of Anopheles mosquitoes [39].

Understanding the implications of Anopheles vectors adapting to salinity in coastal areas for malaria transmission

Some salinity-tolerant Anopheles that transmit malaria parasites in coastal areas have evolved into distinct species as a result of their reproductive isolation. These include An, farauti in Australasia, An. sundaicus in Asia, An. melas and An. merus in Africa, as well as An. aquasalis and An. albimanus in the Americas [23-25]. It was recently observed for the first time that An. culicifacies, the principal rural FW vector of malaria in South Asia, can also lay eggs and undergo preimaginal development in BW of up to 4 gL^-1 salt in coastal swamps of eastern Sri Lanka [40] and the Jaffna peninsula [7,41]. It remains to be established whether An. culicifacies similarly develops in coastal BW habitats in other South and Southeast Asian countries. Larval source reduction was previously an important component of efforts to control or eradicate malaria but this is no longer the case [38]. However, this position needs to be reconsidered, and anopheline vectors in coastal areas monitored more closely, because global warming leading to a rise in sea levels can expand BW habitats for existing salinity-tolerant anopheline malaria vectors in coastal areas and additionally cause FW anopheline vectors to adapt to develop in coastal BW [23-25].

Appreciating the relevance of salinity adaptation and societal conflicts in the recent rapid range expansion of the malaria vector Anopheles stephensi

Anopheles stephensi, the principal urban vector of malaria in South Asia, was first detected in Mannar island, Sri Lanka (Figure 1) in 2017 [42,43]. This was postulated to be a consequence of its rapid range expansion from northern India to southern India by a predominantly coastal route [44]. Anopheles stephensi has been observed to develop in BW of up to 3.5 gL^-1 in cement water storage tanks and domestic wells in different locations within the coastal city of Jaffna as well as Mannar island (Figure 1) [11,42,43,44]. It seems probable that the pre-adaptation of An. stephensi to similar BW collections in the neighbouring coast of Tamil Nadu state in South India, and the movement of refugees and combatants in boats across the 64 -137 km-wide Palk Strait separating Tamil Nadu from the Jaffna peninsula contributed to the arrival of An. stephensi in northern Sri Lanka [44]. Anopheles stephensi has also recently expanded its range westwards to the Arabian Peninsula and after that to Northeast Africa with coastal zones playing a prominent role in this process [38,44]. Further expansion of the range of An. stephensi to West and East Africa was confirmed in 2023 [38]. It is reasonable to postulate that, as in Sri Lanka [44], adaptation to salinity as well as wars in Yemen, Eritrea, Ethiopia, Sudan and Somalia that caused the collapse of societal infrastructure, governments and malaria vector control programs, and resulted in the large-scale movement of refugees, had a major role in the spread of An. stephensi and a consequent increase in malaria transmission [38].

Conclusions

Scientific findings that demonstrate adaptation of FW malaria vectors to salinity suggest that the extension of control measures to BW preimaginal habitats is important for controlling malaria in coastal areas [23,40]. This can also increase malaria transmission inland because BW-developing vectors can act as bridging vectors in adjoining inland locations [21]. It is suggested that greater awareness of relevant scientific findings, facilitation of epidemiological studies to further evaluate the findings and promotion of malaria control measures in coastal areas by pertinent national and international malaria institutions are needed. However, reducing the impact of wars and movement of refugees on malaria control is a more difficult-to-address societal problem.

Tick-borne borreliosis

The pathogen causing Lyme disease (LD) was first identified in vector ticks in 1982, and then in US patients in 1983, as a spirochete bacterium later named Borrelia burgdorferi. Borrelia burgdorferi sensu stricto (Bbss) is the principal species responsible for LD in the US [45,46]. Other species of the genus Borrelia termed Lyme Disease Borreliae (LDB), or alternatively Borrelia burgdorferi sensu lato, are now known to cause LD in many temperate zone countries [45,46]. Some clinical manifestations of LD are shared with tick-borne relapsing fever (TBRF) caused by a different group of Borrelia species termed relapsing fever Borreliae (RFB) [45,47], and indeed with non-borrelial tick-borne diseases [48]. TBRF is prevalent in both tropical and temperate climates in many parts of the world [45,47].

Importance of serological tests in the diagnosis of LD and TBRF and the implications of recent findings with the tests

In the absence of distinct pathognomonic features, other than erythema migrans at the site of a tick bite which is frequently not noticed, a diagnosis of LD relies heavily on laboratory confirmation of infection. Because LDB are often present at low concentrations in blood, the detection of antibodies in patient sera became the preferred laboratory diagnostic method for LD [45,49]. The recommendation from the US National Conference on Serologic Diagnosis of Lyme Disease meeting in 1994 of a standard two-tier test (STTT) for the serological diagnosis of LD was an important diagnostic advance [49]. The first tier of the STTT is an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) on whole Bbss cell antigens, followed by a second-tier confirmatory western blot (WB) on whole Bbss cell lysates for sera that give positive or equivocal results in the first-tier test [49]. The rationale for the STTT was that the first tier EIA or IFA was highly sensitive but inadequately specific, while the second tier WB was highly specific for detecting serum antibodies to LDB [49]. Drawbacks to STTTs include the need for the cumbersome WB procedure and variable sensitivity for detecting infections with LDB species other than Bbss, both of which can be overcome by using relevant pure proteins as target antigens [45]. As a result, the CDC has been approving modified two-tier tests (MTTTs) amenable to machine reading of results in the US since 2019 [50].

Line immunoblots (IBs), based on pure proteins produced by recombinant DNA technology and applied as lines on blotting media strips, have supported the diagnosis of LD in European laboratories from the beginning of this century [45]. LD IB tests used as potential single tier tests had comparable sensitivity and specificity to STTTs and were also able to detect antibodies against common European LDB species [45,51]. LD IB tests have led to the development of analogous TBRF IB tests that detect RFB-specific antigens [45,52]. The use of TBRF IBs to test patients identified with LD-like symptoms in Ukraine, Australia and the US strongly suggested the many of them had TBRF and not LD [45,52]. Testing of patient sera in parallel in both LD and TBRF IBs, as illustrated in Figure 5, may therefore provide a more definitive diagnosis of tick-borne borreliosis worldwide [45,52].

Figure 5: Representative TBRF and LD IgM and IgG IBs with five sera from patients with LD-like symptoms. Sera of both patients in lanes 1 and 2 were only positive in TBRF IBs. Serum in lane 3 was positive in both TBRF and LD IBs. Serum in lane 4 was negative in both IBs. Serum in lane 5 was only positive in LD IBs. The detection of either IgM or IgG antibodies as shown in Figure 5 provided greater sensitivity than detecting either IgM or IgG alone. The different LDB and RFB antigens used in LD and TBRF IBs are described elsewhere [51,52]. N-negative control. Reproduced with permission under the creative commons licence from [52].

The CDC estimated that approximately 476,000 persons were treated every year for LD in the US during the period 2010-2018 [53]. The number LD cases in western Europe was estimated to be >200,000 per year and increasing every year [54]. The CDC reported 483 cases of TBRF for the entire period of 1990 to 2011 in the US that were confined mainly to the western US states [47], contrasting with other findings that suggest a much greater incidence and broader distribution within the US [52].

Conclusions

Many myths about LD propagated by the print, broadcast and internet media have long compromised its diagnosis and treatment [55]. LD and TBRF in their early stages are readily amenable to antibiotic treatment. However, symptoms and pathology in chronic LD are complex and some cases of chronic LD are difficult to treat [45,46]. Recent findings discussed here suggest a need to re-evaluate the incidence of LD and TBRF in the US and other countries. This would involve promoting further research to verify recent findings and greater coordination between scientific communities working on the diagnosis of LD and TBRF, by relevant national institutions like the CDC in the US.

COVID-19

The WHO estimated 774 million cases of COVID-19 due to infection with the SARS-CoV-2 virus and 7 million deaths worldwide up to the end of 2023 [56]. Vaccines against COVID-19 were rapidly developed after COVID-19 was first identified in 2019. COVID-19 vaccines provided the urgently needed initial immunity in the global population to withstand the severe consequences of the disease. One of the first to complete clinical trials and receive regulatory approval was the University of Oxford-Astra Zeneca ChAdOx1 nCoV-19 vaccine, which utilized a recombinant chimpanzee adenovirus vector expressing the spike protein of SARS-CoV-2 as an immunogen [57]. This vaccine was offered for use on a not-for-profit basis for the duration of the pandemic, and also licensed to be manufactured inexpensively for resource-constrained countries at the Serum Institute of India.

Understanding the impact of vaccination during the COVID-19 pandemic

During the first year of COVID-19 vaccination from December 2020 to December 2021, 55.9% of the global population was estimated to have received one dose of a vaccine, 45.5% two doses, and 4.3% a third booster immunisation [58]. Based on officially reported COVID-19 deaths, 14·4 million (95% confidence interval 13·7-15·9), and alternatively the excess mortality data, 19·8 million (95% interval 19·1-20·4) deaths, were estimated to have been averted by vaccination in 185 countries over this one-year period [58]. Similar findings were reported at the country level from the US [59] and Israel [60]. Vaccination ameliorated the serious effects of SARS-CoV2 infections in persons who had not previously had COVID-19, and served to enhance population immunity that minimized severe disease and mortality. Thus, COVID vaccines had a major beneficial impact on the early course of the pandemic and they continue to be used to boost immunity in elderly and immunocompromised persons at the present time. More lives would have been saved if resource-constrained countries had better early access to vaccines [58], some governments had not delayed beginning vaccinations or been more transparent about the local COVID-19 situation, and more people had not resisted receiving the vaccine due to cultural perceptions and misconceptions spread through the print, broadcast and internet media [61,62].

Understanding the consequences of differential susceptibility of population groups to SARS-CoV-2 infection

Increased susceptibility to SARS-CoV-2 infections and consequent higher mortality during the temperate zone winter in persons with a genetic ancestry in warm tropical countries, was widely attributed to socio-economic factors but not a likely weaker early immune response in the upper respiratory tract for which there is now increasing evidence [63-67]. Timely recognition of this could have led to the implementation of appropriate public health and clinical measures that might have reduced infections, morbidity and mortality during the COVID-19 pandemic among vulnerable immigrant communities living in temperate zone countries.

Conclusions

Media-propagated misinformation on COVID-19 vaccines and delays in administering vaccines in some countries increased morbidity and mortality worldwide. Further investigations into varying SARS-CoV-2 infectivity among different population groups may be useful for minimising morbidity and mortality. It is suggested that these issues need to be addressed at the appropriate national and international levels.

General Conclusions

Some of the societal shortcomings affecting the control of COVID-19, dengue, malaria, and tick-borne borreliosis, highlighted in this article, will have resulted in avoidable morbidity and mortality. Two of the identified societal drawbacks appear to be shared between diseases: (i) the need for greater cognizance of scientific advances and then timely initiation of appropriate responses on the part of pertinent national and international institutions. More extensive investigations and scientific discussion may be needed to fully evaluate the relevant scientific findings cited here but this also need to be facilitated by national and international institutions with the relevant responsibilities; (ii) misleading information in the print, broadcast and internet media, and the potential dangers of advanced computer technology in facilitating such misinformation. The general issue of misinformation in science, its consequences and the steps needed to address it, were recently highlighted in the journal Nature [62]. Misinformation also negatively impacts the control of other infectious diseases. For example, misperceptions and misinformation spread through social internet media have led to reduced vaccine uptake not only in COVID-19 as discussed here [61] but also measles [68]. This has caused widespread resurgence of measles [69].  

Funding:

This research received no external funding.

Institutional Review Board Statement:

Not applicable.

Informed Consent Statement:

Not applicable.

Data Availability Statement:

All data supporting the conclusions of this article are included within the article.

Conflicts of Interest:

The author is affiliated to IDFISH and IGeneX which develop and apply diagnostic techniques for tick-borne and other infectious diseases.

Abbreviations

AFM- atomic force microscopy; CDC - US Centres for Disease Control and Prevention; COVID-19—coronavirus infectious disease 2019; EIA- enzyme immunoassay; IFA- immunofluorescence assay; L1-L4: first to fourth instar larval stages; LC₅₀: concentration producing 50% lethality; LD - Lyme disease; LDB - Lyme disease Borreliae; MTTT- modified two-tier test; RFB - relapsing fever Borreliae; TBRF - tick-borne relapsing fever; SARS-CoV-2—severe acute respiratory syndrome coronavirus 2; SEM: scanning electron microscopy; STTT- standard two-tier test; TEM: transmission electron microscopy; WB - western blot; WHO -World Health Organization.

References

1. World Health Organization. Fact sheet on dengue and severe dengue (2024).
2. Centers for Disease Control and Prevention. Dengue (2024).
3. World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control (2024).
4. World Health Organization. Temephos in drinking-water: use for vector control in drinking-water sources and containers (2024).
5. Ramasamy R, Surendran SN, Jude PJ, Dharshini S, Vinobaba M. Larval development of Aedes aegypti and Aedes albopictus in peri-urban brackish water and its implications for transmission of arboviral diseases. PLoS Negl Trop Dis 5 (2011): e1369.
6. Surendran SN, Jude PJ, Thabothiny V, Raveendran S, Ramasamy R. Preimaginal development of Aedes aegypti in brackish and fresh water urban domestic wells in Sri Lanka. J Vector Ecol 37 (2012): 471-473.
7. Jude PJ, Tharmasegaram T, Sivasubramaniyam G, Senthilnanthanan M, Kannathasan S, Raveendran S, et al. Salinity-tolerant larvae of mosquito vectors in the tropical coast of Jaffna, Sri Lanka and the effect of salinity on the toxicity of Bacillus thuringiensis to Aedes aegypti Parasit Vectors 5 (2012): 269.
8. Surendran SN, Jayadas TTP, Sivabalakrishnan K, Santhirasegaram S, Karvannan K, Weerarathne TC, et al. Development of the major arboviral vector Aedes aegypti in urban drain-water and associated pyrethroid insecticide resistance is a potential global health challenge. Parasit Vectors 12 (2019): 337.
9. Surendran SN, Jayadas TTP, Thiruchenthooran V, Raveendran S, Tharsan A, Santhirasegaram S, et al. Aedes larval bionomics and implications for dengue control in the paradigmatic Jaffna peninsula, northern Sri Lanka. Parasit Vectors 14 (2021): 162.
10. Sivabalakrishnan K, Thanihaichelvan M, Tharsan A, Eswaramohan T, Ravirajan P, Hemphill A, et al. Resistance to the larvicide temephos and altered egg and larval surfaces characterize salinity-tolerant Aedes aegypti. Sci Rep 13 (2023): 8160.
11. Surendran SN, Kesavan L, Jayadas TTP, Sivabalakrishnan K, Tharsan A, Liyanagedara N, et al. Morphological and odorant-binding protein 1 gene intron 1 sequence variations in Anopheles stephensi from Jaffna city in northern Sri Lanka. Med Vet Entomol 36 (2022): 496-502.
12. Idris FH, Usman A, Surendran SN, Ramasamy R. Detection of Aedes albopictus pre-imaginal stages in brackish water habitats in Brunei Darussalam. J Vector Ecol 38 (2013): 197-199.
13. Yee DA, Himel E, Reiskind MH, Vamosi SM. Implications of saline concentrations for the performance and competitive interactions of the mosquitoes Aedes aegypti (Stegomyia aegypti) and Aedes albopictus (Stegomyia albopictus). Med Vet Entomol 28 (2014): 60-69
14. de Brito Arduino M, Mucci LF, Serpa LL, Rodrigues Mde M. Effect of salinity on the behavior of Aedes aegypti populations from the coast and plateau of southeastern Brazil. J Vector Borne Dis 52 (2015): 79-87.
15. Galavíz-Parada JD, Vega-Villasante F, Marquetta M. del C, Guerrero-Galvan SR, Chong O, et al. Effect of temperature and salinity on the eclosion and survival of Aedes aegypti (L) (Diptera: Culicidae) from Western Mexico. Rev Cuba Med Trop 71 (2019): e353.
16. Ratnasari A, Jabal AR, Syahribulan; Idris I, Rahma N, Rustam SNRN, Karmila M, et al. Salinity tolerance of larvae Aedes aegypti inland and coastal habitats in Pasangkayu, West Sulawesi, Indonesia. Biodiversitas 22 (2021): 1203-1210.
17. Shamna AK, Vipinya C, Sumodan PK. Detection of Aedes albopictus (Diptera: Culicidae) breeding in brackish water habitats in coastal Kerala, India and its Implications for dengue scenario in the state. Int J Entomol Res 7 (2022): 214-216.
18. Ramasamy R, Jude PJ, Veluppillai T, Eswaramohan T, Surendran SN. Biological differences between brackish and fresh water-derived Aedes aegypti from two locations in the Jaffna peninsula of Sri Lanka and the implications for arboviral disease transmission. PLoS One 9 (2014): e104977.
19. Surendran SN, Sivabalakrishnan K, Jayadas TTP, Santhirasegaram S, Laheetharan A, Senthilnanthanan M, et al. Adaptation of Aedes aegypti to salinity: Characterized by larger anal papillae in larvae. J Vector Borne Dis 55 (2018): 235-238.
20. Ramasamy R, Thiruchenthooran V, Jayadas TTP, Eswaramohan T, Santhirasegaram S, Sivabalakrishnan K, et al. Transcriptomic, proteomic and ultrastructural studies on salinity-tolerant Aedes aegypti in the context of rising sea levels and arboviral disease epidemiology. BMC Genomics 22 (2021): 253.
21. Ramasamy R, Surendran SN. Mosquito vectors developing in atypical anthropogenic habitats: Global overview of recent observations, mechanisms and impact on disease transmission. J Vector Borne Dis 53 (2016): 91-98.
22. Ramasamy R. Adaptation of freshwater mosquito vectors to salinity increases arboviral disease transmission risk in the context of anthropogenic environmental changes. In: Shapshak P, Sinnott JT, Somboonwit C, Kuhn JH. editors. Global Virology I - Identifying and Investigating Viral Diseases. New York City (NY): Springer (2015): 45-54.
23. Ramasamy R, Surendran SN, Jude PJ, Dharshini S, Vinobaba M. Adaptation of mosquito vectors to salinity and its impact on mosquito-borne disease transmission in the South and Southeast Asian tropics. In: Morand, S, Dujardin, J.P, Lefait, R, Apiwathnasorn, C. editors. Socio-Ecological Dimensions of Infectious Diseases in Southeast Asia. Singapore: Springer (2015): 107-122.
24. Ramasamy R, Surendran SN. Possible impact of rising sea levels on vector-borne infectious diseases. BMC Infect Dis 11 (2011): 18.
25. Ramasamy R, Surendran S. Global climate change and its potential impact on disease transmission by salinity-tolerant mosquito vectors in coastal zones. Front Physiol 3 (2012): 198.
26. Wilder-Smith A, Tissera H, Ooi EE, Coloma J, Scott TW, Gubler DJ. Preventing dengue epidemics during the COVID-19 pandemic. Am J Trop Med Hyg 103 (2020): 570-571.
27. Gavi S, Tapera O, Mberikunashe J, Kanyangarara M. Malaria incidence and mortality in Zimbabwe during the COVID-19 pandemic: analysis of routine surveillance data. Malaria J 20 (2021): 233.
28. Lim JT, Dickens BSL, Chew LZX, Choo ELW, Koo JR, Aik J, et al. Impact of sars-cov-2 interventions on dengue transmission. PLoS Negl Trop Dis 14 (2020): e0008719
29. Surendran SN, Nagulan R, Sivabalakrishnan K, Arthiyan S, Tharsan A, Jayadas TTP, et al. Reduced dengue incidence during the COVID-19 movement restrictions in Sri Lanka from March 2020 to April 2021. BMC Public Health 22 (2022): 388.
30. Surendran SN, Nagulan R, Tharsan A, Sivabalakrishnan K, Ramasamy R. Dengue incidence and Aedes vector collections in relation to COVID-19 population mobility restrictions. Trop Med Infect Dis 7 (2022): 287.
31. Niriella MA, Ediriweera DS, De Silva AP, Premarathna BHR, Jayasinghe S, de Silva HJ Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka. Trans R Soc Trop Med Hyg 115 (2021): 944-946.
32. Ariyaratne D, Gomes L, Jayadas TTP, Kuruppu H, Kodituwakku L, Jeewandara C, et al. Epidemiological and virological factors determining dengue transmission in Sri Lanka during the COVID-19 pandemic. PLoS Glob Public Health 2 (2022): e0000399.
33. MacDonald G. The epidemiology and control of malaria. Oxford University Press: London, UK (1957).
34. Paramasivan R, Philip Samuel P, Pandian RS. Biting rhythm of vector mosquitoes in a rural ecosystem of South India. Int J Mosq Res 2 (2015): 106-113
35. Kusumawathie PHD. Larval infestation of Aedes aegypti and albopictus in six types of institutions in a dengue transmission area in Kandy, Sri Lanka. Dengue Bull 29 (2005): 165-168
36. Mayilsamy M, Vijayakumar A, Veeramanoharan R, Rajaiah P, Balakrishnan V, Kumar A. Impact of COVID-19 lockdown during 2020 on the occurrence of vector-borne diseases in India. J Vector Borne Dis 60 (2023): 207-210.
37. Wijesundere DA, Ramasamy R. Analysis of historical trends and recent elimination of malaria from Sri Lanka and its applicability for malaria control in other countries. Front Public Health 5 (2017): 212.
38. World Health Organization. World Malaria Report (2023).
39. Ramasamy R. Zoonotic malaria - global overview and research and policy needs. Front Public Health 2 (2014): 123.
40. Jude PJ, Dharshini S, Vinobaba M, Surendran SN, Ramasamy R. Anopheles culicifacies breeding in brackish waters in Sri Lanka and implications for malaria control. Malar J 9 (2010): 106.
41. Surendran SN, Jayadas TTP, Tharsan A, Thiruchenthooran V, Santhirasegaram S, Sivabalakrishnan K, et al. Anopheline bionomics, insecticide resistance and transnational dispersion in the context of controlling a possible recurrence of malaria transmission in Jaffna city in northern Sri Lanka. Parasit Vectors 13 (2020): 156.
42. Dharmasiri AG, Perera AY, Harishchandra J, Herath H, Aravindan K, Jayasooriya HTR, et al. First record of Anopheles stephensi in Sri Lanka: a potential challenge for prevention of malaria reintroduction. Malar J 16 (2017): 326.
43. Surendran SN, Sivabalakrishnan K, Gajapathy K, Arthiyan S, Jayadas TTP, Karvannan K, et al. Genotype and biotype of invasive Anopheles stephensi in Mannar Island of Sri Lanka Parasit Vectors 11 (2018): 3.
44. Surendran SN, Sivabalakrishnan K, Sivasingham A, Jayadas TTP, Karvannan K, Santhirasegaram S, et al. Anthropogenic factors driving recent range expansion of the malaria vector Anopheles stephensi. Front Public Health 7 (2019): 53.
45. Shah JS, Burrascano JJ, Ramasamy R. Recombinant protein immunoblots for differential diagnosis of tick-borne relapsing fever and Lyme disease J Vector Borne Dis 60 (2023): 353-364.
46. Centers for Disease Control and Prevention. Lyme Disease (2024).
47. Centers for Disease Control and Prevention. Tick- and Louse-Borne Relapsing Fever (2024).
48. Boulanger N, Boyer P, Talagrand-Reboul, E, Hansmann Y. Ticks and tick-borne diseases. Med Mal Infect 49 (2019): 87-97.
49. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR 44 (1995): 590-591.
50. Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR 68 (2019): 703.
51. Liu S, Cruz ID, Ramos CC, Taleon P, Ramasamy R, Shah J. Pilot study of immunoblots with recombinant Borrelia burgdorferi antigens for laboratory diagnosis of Lyme disease. Healthcare (Basel) 6 (2018): 99.
52. Shah JS, Liu S, Du Cruz I, Poruri A, Maynard R, Shkilna M, et al. Line immunoblot assay for tick-borne relapsing fever and findings in patient sera from Australia, Ukraine and the USA. Healthcare (Basel) 7 (2019): 121.
53. Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018. Emerg Infect Dis 27 (2021): 616-619.
54. Marques AR, Strle F, Wormser GP. Comparison of Lyme disease in the United States and Europe. Emerg Infect Dis 27 (2021): 2017-2024.
55. Glauser W. Combatting Lyme disease myths and the "chronic Lyme industry". CMAJ 2019, 191(40), E1111-E1112. Erratum in: CMAJ 191 (2019): E1389.
56. World Health Organization. Coronavirus (COVID-19) Dashboard (2024).
57. Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet 396 (2021): 1979-1993.
58. Watson OJ, Barnsley G, Toor J, Hogan AB, Winskill P, Ghani AC. Global impact of the first year of COVID-19 vaccination: a mathematical modelling study. Lancet Infect Dis 22 (2022): 1293-1302.
59. Yamana TK, Galanti M, Pei S, Di Fusco M, Angulo FJ, Moran MM, et al. The impact of COVID-19 vaccination in the US: Averted burden of SARS-CoV-2-related cases, hospitalizations and deaths. PLoS ONE 18 (2023): e0275699.
60. Haas EJ, McLaughlin JM, Khan F, Angulo FJ, Anis E, Lipsitch M, et al. Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: A retrospective surveillance study. Lancet Infect Dis 22 (2022): 357-366.
61. Bonnevie E, Goldbarg J, Gallegos-Jeffrey AK, Rosenberg SD, Wartella E, Smyser J. Content themes and influential voices within vaccine opposition on Twitter, 2019. Am J Public Health 110 (2020): S326-S330.
62. Nature Editorial. How online misinformation exploits 'information voids' - and what to do about it. Nature 625 (2024): 215-216.
63. Ramasamy R. Nasal conditioning of inspired air, innate immunity in the respiratory tract and SARS-CoV-2 infectivity (2020). https://doi.org/10.31219/osf.io/4j95b.
64. Ramasamy R. Perspective of the relationship between the susceptibility to initial SARS-CoV-2 infectivity and optimal nasal conditioning of inhaled air Int J Mol Sci 22 (2021): 7919.
65. Ramasamy R. Innate and adaptive immune responses in the upper respiratory tract and the infectivity of SARS-CoV-2 Viruses 14 (2022): 933.
66. Aquino Y, Bisiaux A, Li Z, O'Neill M, Mendoza-Revilla J, Merkling SH, et al. Dissecting human population variation in single-cell responses to SARS-CoV-2. Nature 621 (2023): 120-128.
67. Ramasamy R. COVID-19 vaccines for optimizing immunity in the upper respiratory tract. Viruses 15 (2023): 2203.
68. Ng QX, Teo YQJ, Kiew CY, Lim BP, Lim YL, Liew TM. Examining the prevailing negative sentiments surrounding measles vaccination: unsupervised deep learning of twitter posts from 2017 to 2022. Cyberpsychol Behav Soc Netw 26 (2023): 621-630.
69. De Francesco MA. Measles resurgence in Europe: an open breakthrough in the field of vaccine-preventable diseases. Pathogens 12 (2023): 1192.