RESUMEN
Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection. Our results demonstrate that, because the average age at infection increases as spillover is reduced, programs that reduce spillover can actually increase population-level disease burden if the clinical severity of infection increases sufficiently rapidly with age. If, however, immunity wanes over time and reinfection is possible, our results reveal that negative health impacts of spillover reduction become substantially less likely. When our model is parameterized using published data on Lassa virus in West Africa, it predicts that negative health outcomes are possible, but likely to be restricted to a small subset of populations where spillover is unusually intense. Together, our results suggest that adverse consequences of spillover reduction programs are unlikely but that the public health gains observed immediately after spillover reduction may fade over time as the age structure of immunity gradually re-equilibrates to a reduced force of infection.
RESUMEN
In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.
RESUMEN
The black rat (Rattus rattus) is a globally invasive species that has been widely introduced across Africa. Within its invasive range in West Africa, R. rattus may compete with the native rodent Mastomys natalensis, the primary reservoir host of Lassa virus, a zoonotic pathogen that kills thousands annually. Here, we use rodent trapping data from Sierra Leone and Guinea to show that R. rattus presence reduces M. natalensis density within the human dwellings where Lassa virus exposure is most likely to occur. Further, we integrate infection data from M. natalensis to demonstrate that Lassa virus zoonotic spillover risk is lower at sites with R. rattus. While non-native species can have numerous negative effects on ecosystems, our results suggest that R. rattus invasion has the indirect benefit of decreasing zoonotic spillover of an endemic pathogen, with important implications for invasive species control across West Africa.
Asunto(s)
Reservorios de Enfermedades , Especies Introducidas , Fiebre de Lassa , Virus Lassa , Murinae , Zoonosis , Animales , Virus Lassa/patogenicidad , Virus Lassa/fisiología , Fiebre de Lassa/transmisión , Fiebre de Lassa/epidemiología , Fiebre de Lassa/virología , Fiebre de Lassa/veterinaria , Reservorios de Enfermedades/virología , Humanos , Ratas , Murinae/virología , Zoonosis/virología , Zoonosis/transmisión , Zoonosis/epidemiología , Sierra Leona/epidemiología , Guinea/epidemiología , Ecosistema , Enfermedades de los Roedores/virología , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/transmisiónRESUMEN
The Natal multimammate mouse (Mastomys natalensis) is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and therapeutic drugs are limited, we explored rodent control as an alternative to prevent Lassa virus spillover in Upper Guinea, where the disease is highly endemic in rural areas. In a seven-year experiment, we distributed rodenticides for 10-30 days once a year and, in the last year, added intensive snap trapping for three months in all the houses of one village. We also captured rodents both before and after the intervention period to assess their effectiveness by examining alterations in trapping success and infection rates (Lassa virus RNA and IgG antibodies). We found that both interventions reduced the rodent population by 74-92% but swiftly rebounded to pre-treatment levels, even already six months after the last snap-trapping control. Furthermore, while we observed that chemical control modestly decreased Lassa virus infection rates annually (a reduction of 5% in seroprevalence per year), the intensive trapping unexpectedly led to a significantly higher infection rate (from a seroprevalence of 28% before to 67% after snap trapping control). After seven years, we conclude that annual chemical control, alone or with intensive trapping, is ineffective and sometimes counterproductive in preventing Lassa virus spillover in rural villages. These unexpected findings may result from density-dependent breeding compensation following culling and the survival of a small percentage of chronically infected rodents that may spread the virus to a new susceptible generation of mice.
Asunto(s)
Fiebre de Lassa , Virus Lassa , Ratones , Animales , Virus Lassa/genética , Guinea/epidemiología , Control de Roedores , Estudios Seroepidemiológicos , Reservorios de Enfermedades , Fiebre de Lassa/epidemiología , Fiebre de Lassa/prevención & control , Murinae , África Occidental/epidemiologíaRESUMEN
West African Mastomys rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and considerable mortality in humans. To date, the role of Mastomys immunogenetics in resistance to, and persistence of, LASV infections is largely unknown. Here, we investigated the role of Major Histocompatibility Complex class I (MHC-I) on LASV infection status (i.e., active vs. cleared infection, determined via PCR and an immunofluorescence assay on IgG antibodies, respectively) in Mastomys natalensis and M. erythroleucus sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in M. natalensis and M. erythroleucus, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In M. natalensis, the MHC allele ManaMHC-I*006 was negatively associated with active infections (PCR-positive) and positively associated with cleared infections (IgG-positive) simultaneously, suggesting efficient immune responses that facilitate LASV clearance in animals carrying this allele. Contrarily, alleles ManaMHC-I*008 and ManaMHC-I*021 in M. natalensis, and MaerMHC-I*008 in M. erythroleucus, were positively associated with active infection, implying susceptibility. Alleles associated with susceptibility shared a glutamic acid at the positively selected codon 57, while ManaMHC-I*006 featured an arginine. There was no link between number of MHC alleles per Mastomys individual and LASV prevalence. Thus, specific alleles, but not MHC diversity per se, seem to mediate antibody responses to viremia. We conclude that co-evolution with LASV likely shaped the MHC-I diversity of the main LASV reservoirs in southwestern Nigeria, and that information on reservoir immunogenetics may hold insights into transmission dynamics and zoonotic spillover risks.