Need for preventive and control measures for Lassa fever through the One Health strategic approach

Abstract

Lassa virus (LASV) has increasingly been recognised as a significant public-health pathogen transmitted by rodents. LASV infection leads to life-threatening Lassa fever, which has high potential for severe morbidity and mortality. There have been several scientific efforts to understand the genomics and ecological epidemiology of Lassa. However, very limited studies have focused on the short- and long-term impacts of environmental factors, human behaviours and rodent activities on LASV transmission dynamics and control. Recently, a very plausible and ideal way to address the Lassa epidemic has been considered through the One Health approach. The One Health system of intervention is capable of providing better and comprehensive information necessary to address the complex interplay between human, ecological, and environmental determinants of LASV transmission, persistence and re-emergence. Thus, the aim of this article was to review critically the impacts of various environmental factors on rodent infestations, LASV transmission and how human activities contribute to the persistence of Lassa with regard to exploring how they could be harnessed for better understanding of Lassa prevention and control through a concerted One Health approach.

Introduction

It has been speculated that zoonoses will be a major cause (60%) of human suffering in the 21st century. ¹ Indeed, an insight into better preventive and control strategies to mitigate the spread of zoonotic viral pathogens could be achieved through understanding host–pathogen–environment interactions. ¹

Lassa fever is a re-emerging zoonotic viral disease associated with sudden and potentially severe haemorrhage due to infection by Lassa virus (LASV). LASV is a member of the Arenaviridae family. ² Considering the epidemiological pattern of LASV infection, Western African countries such as Benin, Ghana, Mali, Nigeria, Guinea, Sierra Leone and Liberia are considered endemic to Lassa. ³ The multimammate rodent Mastomys natalensis has been the major vector of LASV. In addition, a study has suggested the presence of LASV persistence in species of other Mastomys rodents such as Mastomys huberti and Mastomys erythroleucus. ⁴ In addition, other non-Mastomys small mammals such as Rattus rattus, Hylomyscus pamfi, Praomys daltoni, Mus minutoides and Crocidura spp. have also being identified as harbouring LASV. ⁴

Based on the genomic sequence and phylogenetic analyses of LASV isolates, Lassa has been classified into seven phylogeographic lineages, with each predominant and specific to particular locations or countries. ⁵ Based on these classifications, LASV is highly diverse across various geographical locations and hosts. ⁶ Essentially, LASV infection in humans is typically contracted through the consumption of contaminated food or water, inhalation of aerosolised virus from infected animals and person-to-person transmission through contact with virus-contaminated bodily fluids and secretions. ⁷

Currently, there are no approved LASV vaccines. However, there are a number of candidate vaccines such as the Lister strain vaccinia virus, inactivated LASV, recombinant yellow fever vaccine and Venezuelan equine encephalitis virus replicon platforms in evaluations and trials. ⁸ Chemotherapy for Lassa are largely limited to the use of ribavirin. ⁹ Ribavirin treatments are not cost-effective and are only useful during the early phase (⩽5 days) after the onset of symptoms. ³

The World Health Organization reported that the number of new LASV infections per annum can be as high as 300,000, with approximately 5000 Lassa-associated deaths. ³ The mean case fatality rate (CFR) of LASV infection is estimated as 1%, which can exponentially be as high as 16% for patients admitted in health-care facilities. ³ However, average CFR figures are higher during epidemics and in women in the third trimester of pregnancy.^10,11 This varies disproportionately across countries. For instance, being a major Lassa-affected nation, Nigeria has a very high CFR. Recent national data from Nigeria showed that there were 932 confirmed cases and 176 Lassa-associated deaths from 1 January to 22 March 2020, with a CFR of 18.9%. ¹²

Considering the rising incidence of Lassa in endemic regions, it is necessary to consider the development of alternative and more effective countermeasures against LASV infection through relevant and concerted public-health approaches which will target all possible routes of Lassa transmission and maintenance. Lessons and scientific experiences gained from various Lassa outbreaks and recent advances in throughput genomics and mathematical modelling can be harnessed in tracking future outbreaks and expansion of Lassa to areas with previously no recorded cases. One of the most feasible and successful approaches is an integrated, holistic and proactive measure which can be achieved using the One Health strategic approach.

The One Health system of research takes into consideration the cross-linkages of human health, animals, plants and their shared environment. ¹³ Hence, One Health provides better and comprehensive information necessary to address the complex interplay of ecological, social and environmental determinants of re-emerging viral infections such as Lassa. ¹⁴ This approach will assist researchers and policymakers to tackle public-health threats posed by Lassa accurately and efficiently through concerted coordination across applicable sectors and science disciplines. Understanding the biological, environmental and socio-economic determinants of Lassa spillover and spread is key to its mitigation at community, state and national levels. ¹⁵ Thus, the aim of this article was to review critically the impacts of various environmental factors on rodent infestations, LASV transmission and how human activities contribute to the persistence and transmission of Lassa with regard to exploring how they could be harnessed for better Lassa prevention and control through a concerted One Health approach.

Human factors and Lassa transmission

The exponential growth of the human population, household size, deforestation, bush burning and urbanisation increase the chances of human interaction with wild animals, resulting in a high risk of contracting zoonotic pathogens. ¹⁶ Although several research articles have assessed risk factors for viral spillovers from jungles to urban settlements, very few have studied the quantitative estimation of the impact of the human population and factors such as deforestation and global warming on the frequency and links between human health and zoonotic viral infections.

The transmission routes of LASV zoonotic spillovers have not been adequately understood. Human LASV infections are thought to be mostly due to contact with LASV, probably occurring in houses, farms and gardens where high vector densities exist. ¹⁷

One study reported that hunters who catch and butcher rodents for food and delicacies had a high risk of contracting LASV infection. ¹⁸ However, these findings are not in agreement with another Guinean study which reported no significant association between hunting and butchering rats and the seroprevalence of anti-LASV immunoglobulin G (IgG) in humans. ¹⁹ In 2019, Ogunro et al. reported LASV-specific IgG in 8.1% of monkeys from Southern Nigeria. ²⁰ In Southern Mali, a 6.3% seroconversion rate for LASV IgG antibodies was reported in humans. ²¹ In addition, Sogoba et al. demonstrated a seroprevalence of 14.5–44% of human LASV infection in each of the three villages investigated in Southern Mali. ²² Hence, there is need for more elaborate evidence to elucidate these variations.

There is also a need to ascertain the modes of contact that facilitate contraction of LASV infection. It necessary to determine which mode has the higher risk of acquisition of LASV: direct contact with rodent fluids or inhalation of urine, faeces-contaminated particles or aerosolised virus. The quality of housing, household rodent burrows and high household densities are factors that increase the risk of LASV infection and transmission. ²³

Land-use practices and certain demographic variables such as age-, occupation-, education- and sex-related exposure risk are also determinants of LASV infections.^24,25 These complex sociodemographic factors present challenges for forecasting and planning health interventional measures, since local sociocultural and economic dynamics vary widely across Lassa endemic areas.

A very common communal practice that has been established to encourage food contamination and thus transmission of LASV is the drying of agricultural products in the open sun along roadsides. ²⁶ This practice is very common among rural farmers in West African communities. Other risk factors and practices associated with LASV infection include poor community enlightenment and education, inconsistent farming practices and unsafe food handling and storage. ²⁷ Therefore, the prevention and control of Lassa at the grass-roots level depend largely on encouraging and implementing good personal and environmental hygienic measures. These will prevent people and foodstuff from coming into contact with rodents and their secretions (faecal droppings and urine).

Deforestation for whatever purpose is a major man-made activity that has encouraged the migration of dangerous small rodents from the jungle to human settlements in villages and towns. In addition, bush burning is another practice, especially by some rural farmers particularly during the period of preparation for farms harrowing and ridging after the dry season. ²⁸ These practices significantly encourage the movement of rodents from bushes to human households in search of shelter and food. These practices could have increased the risk of Lassa transmission and expansion to other territories. There should be adequate legislation and enforcement that discourage these practices.

Control measures against reservoir hosts of Lassa

In West Africa, M. natalensis rodents are largely abundant in villages, farms and gardens. However, they occur at much lower densities in forests, cities and urban areas. ²⁹ Essentially, Lassa is a rural disease, with very few cases originating from large urban settlements. ³⁰ This could be due to the low abundance of M. natalensis in adequately built households, possibly because of competitive interactions with other rodent communities (especially Rattus rattus and Mus musculus) and increased use of solid concrete for buildings in urban settlements. ³¹ Recently, several studies into M. natalensis population ecology revealed seasonal population dynamics linked to trends in rainfall in many West African communities. Although these vectors are capable of breeding all year round, the rainy season has been associated with higher frequencies and peaks in activities of M. natelensis, which may be linked to increased food availability. ³²

Understanding these dynamics is not solely for ecological purposes, since the trends in rodent’s LASV prevalence may determine the spatio-temporal differences in the threat of zoonotic infection to humans. The pattern of LASV ecology has also been complicated by the recent discovery of other alternative LASV reservoir hosts: Hylomyscus pamfi and Mastomy erythroleucus. ⁴ This highlights the need for further work to understand fully the spectrum of reservoir and occasional hosts, and to identify whether species other than M. natalensis may be involved in the persistence of LASV in the community.

Since there is no licensed LASV vaccine, rodent control and human behavioural changes are currently the major available options to prevent and control LASV infection in highly endemic settlements.

One interesting rat-control strategy is the use of rat poison. Of note, some studies on the use anticoagulants and acute poisons in Sierra Leone and South Africa show their effectiveness in the control of the rodent population for brief periods. ³³ These studies also indicate that people mainly use these products because they are easily accessible, cost-effective and require less skill in application than rat traps.

In order to achieve effective and sustainable rodent-control measures, it is necessary to consider a number of approaches: rodent traps, rodent-proof walls and roofs, stocking and storage of food and water, natural rodent predators, closing windows and doors and community engagement.

Use of rodent traps

A first approach to rodent control should combine the use of rat poison with regular trapping. ³⁴ Poisons is most appropriate during the dry season, and trapping should be used for the remainder of the year.

Building rodent-proof walls and roofs

Human habitations should not be porous for rodent infestations. One of the major challenges against rodent-control measures is the ability of people to build rodent-proof houses. ³⁵

Appropriate stocking and storage of food and water

Even if people kill rodents, some will certainly find their way to our households in search of food. This could be due to the fact that rats and humans share the same foods, and as such, this relationship cannot be separated. ³⁶ It is thus encouraged to reduce the attractiveness of foodstuff by storing food in bags with odour-proof barrier layers. This form of storage has been successfully tested in other countries, where little rodent damage was recorded, probably because the rodents could not smell the presence of grains stored in these bags. ³⁶

Use of natural predators of rodents

In another study, the use of natural predators, such as the combined application of dogs and cats, effectively scares away rodents. ³⁷ However, there is a need for further studies on the cost implications and the effects of cats on the rodents with this approach. There is also a need to determine better the extent to which cats scare off rats, the relationship between people and these rodent predators and associated public-health consequences (cost–benefit) of cat and dog ownership.

Frequent window and door closure

Adequate and effective rodent-control measures in rural communities require a high level of commitment from the local population. It is crucial that rural residents and, by extension, urban settlers shut their doors and/or windows whenever they are indoors or outdoors, as the need may be. ³⁸ This practice will reduce the chances of rodents sneaking into households and thus decrease the risk of Lassa transmission.

Local community engagement

In a study in an area where Lassa is very endemic, only 36% of the community knew about the disease, and out of these people, only 51% could identify rodents as the source of LASV infection. ³⁹ This reveals the need to start exploring ways to address rodent control with the local population and authorities. ⁴⁰ However, for this to be efficient, information needs to be gathered on the availability and affordability of anticoagulants and rat traps at the community level as well as the budget and cost for individuals to invest and expend yearly on rat poison. The outcome of this will direct the steps needed to address the involvement of community members and authorities in rodent control. There is certainly a need for a concerted programme between the Ministries of Health, Agriculture and Environment for such a programme to be feasible on a large scale and over a prolonged period.

Impacts of environmental factors on Lassa control

The complete routes of LASV transmission have not been definitively established. For instance, there is a paucity of LASV studies on environmental samples to identify the interface with the highest risk of rodent to human to environment transmission. This would help us to understand the conditions that facilitate the persistence and transmission of LASV through the external environment.

The interaction between humans and the environment is a critical aspect for consideration in understanding the epidemiology of zoonotic viral diseases. Even though so many studies have been carried out on the epidemiology and genetics of Lassa, few have focused on the roles of the environment and the ecosystem in the transmission of Lassa. Indeed, the transmission, maintenance and persistence of LASV is strongly related to environmental factors that are closely related to the rodent vector. ³⁰ These rodents usually find their way into comfortable habitats that have dirty and unkept surroundings such as bushy compounds, open solid-waste dump sites and disorganised domestic items.

Waste dump sites are particularly very attractive to rodents because they provide leftover food and thus enhance their breeding and reproduction. ⁴¹ Other environmental factors such as overcrowding in households and poor sanitation have been implicated in the transmission of LASV. ⁴² In urban settlements and cities, the high cost of accommodation, house rents and student hostel overcrowding due to inadequate accommodation, especially in most low- and middle-income countries, make people more vulnerable and at a higher risk of harbouring vectors of LASV infection. Poor solid-waste management and personal and environmental hygiene encourage rat infestations, with a high potential for subsequent transmission and maintenance of LASV.

In addition, identifying other environmental drivers of LASV transmission such as temperature, rainfall, humidity and other climatic indices such as seasonality should not be overlooked. For instance, the dynamics of the dry and wet seasons with regard to human behaviour and the vector have been shown to influence the transmission of LASV. ⁴³ Lassa cases are known to peak during the dry season in endemic regions such as Nigeria. These are strongly predictive of future Lassa outbreaks, and could help to identify high-risk human–vector interactions in locations that are suitable for Lassa-targeted public-health interventions. Considering these myriads of factors that encourage Lassa transmission and persistence, there a need for policymakers to legislate and enforce measures that will address these problems.

Conclusion

Lassa is re-emerging in West Africa, affecting and many people, with a significant morbidity and high CFR. Based on the inadequacies reported from various studies on preventive and control measures, there is a need to diversify from the current state of public-health practices if more meaningful and long-lasting results are going to be achieved against Lassa transmission. A very plausible and arguably best way to address the Lassa epidemic is through the One Health approach. This will provide better and comprehensive information necessary to address the complex interplay of human, ecological, sociocultural and environmental determinants of LASV transmission, persistence and re-emergence.