Lassa fever outbreaks in Nigeria

KEYWORDS:

• Case management capacity
• dedicated surveillance and treatment centers
• Lassa fever, Nigeria
• progress in control
• trends of the outbreaks

1. Introduction

First described from Nigeria in 1969 [1], Lassa fever (LF) is not new here but continues to manifest in epidemic proportions and as endemic or sporadic outbreaks. Recent data show both the increasing occurrence of sporadic outbreaks and the continued spread across the country [2,3].

Neither the morbidity nor mortality from LF in Nigeria is insignificant. About 6% of febrile adults [4] and 3.5% of acutely febrile ill children [5] in endemic areas have confirmed infections. Even with improved supportive care and treatment with ribavirin [6], case fatalities were still as high as 24–33% in tertiary hospital settings in recent times [7,8] while about 13.5% of survivors have sensorineural hearing loss [9]. Besides these, LF accounts for about 22% of hospital maternal mortality in endemic areas [10].

Unfortunately, LF control was until quite recently neglected in Nigeria. This failure allowed the outbreaks to gain in frequency and severity with many deaths, including that of health-care workers [11]. Prof. Tomori put the scenario in sharp focus in a remark in 2007 thus, ‘Talking about these last thirty-eight years of Lassa fever in Nigeria, is telling of the tragedy of a nation. The story of Lassa fever in Nigeria is the story of criminal apathy and vicious ignorance’ [12].

Thus there are many questions to which urgent answers are needed in addressing the challenge of LF in Nigeria and the West African sub region. Among them, we shall focus on the two we consider most critical: Why has progress in LF control seemed elusive? And, which issues should be foremost in rising to the challenge?

2. Slow progress in LF control in Nigeria and the West African sub region

A combination of factors could be responsible. Since LF became known, there had been only little decisive effort by national governments and international health agencies and organizations (IHA&O). There had also only been little sub-regional cooperation. Where efforts were made to draw attention to the onslaught of the outbreaks, there was no follow-up action to ensure successful implementation of the programs of action. In this regard, the December 2007 sub-regional conference [12] and the Freetown meeting of 2011 are apt examples.

The National Lassa Fever Stakeholders’ Forum of Nigeria was formed in 2007. The Forum organized the first sub-regional conference in December of the same year and lack of laboratory infrastructure for surveillance, a low clinical index of suspicion, erratic supply of ribavirin, poor clinical case management capacity, and lack of political will were identified as the major challenges bedeviling Nigeria’s response [12]. The program of action drawn up at the end of the conference included the establishment of LF/viral hemorrhagic fever (VHF) diagnosis and treatment centers at strategic locations in the country [12] to address the issues of surveillance and case management challenges but it was not implemented. Similarly, other plans of action drawn up by successive National Lassa Fever Control Committees met with the same fate.

Thus sadly, almost a decade after the conference and in the wake of an increasing number of deaths during the 2016 outbreak [2], the establishment of strategically located diagnostic laboratories for the purpose of surveillance was still the subject of discussion. And 2 years later during the 2018 outbreak, one of the few functional LF diagnostic centers at Irrua Specialist Teaching Hospital (ISTH) was virtually overwhelmed by the pressure of requests from other parts of the country. The erstwhile weak response, non-prioritization, and non-acknowledgment by government of the outbreaks of LF as a significant public health problem partly explains why IHA&O also did not give the outbreaks serious attention over the years.

The Freetown meeting was convened by the World Health Organization (WHO) and involved LF affected and at-risk countries. These jointly developed a five-year strategic plan (2012–2017) for the prevention and control of LF and other severe Emerging Infectious Diseases in the sub region. Although signed subsequently as a declaration of collaboration by Health Ministers during the 61^st session of WHO/Africa Regional Office Regional Committee Meeting at Yamoussoukro, Côte d’Ivoire in September 2011, little or none of the plans were executed.

The lack of significant progress in LF control in Nigeria could be traced to a number of factors. First, laboratory facilities for diagnosis, where they once existed, were allowed to deteriorate [12]. Second, little interest and emphasis were placed on the capacity building required for diagnosis and case management. Third, underlying both factors is poor political will coupled with politicization of the response to LF outbreaks. The scathing editorials and opinion columns in the popular print media [13,14] attest to the impact of poor governance on the trends of the outbreaks.

Accordingly, full commitment to implementation of the several comprehensive plans of action has been lacking perhaps because the control of LF was not high up on the national health agenda unlike some other infectious diseases. In this context, the response to LF outbreaks could also be contrasted with Nigeria’s mobilization against the imported outbreak of Ebola in 2014, which was perceived as a universal threat. Finally, that the reduction of case fatality through appropriate medical response is complementary and essential to the success of the public health response was not sufficiently appreciated.

3. What is the way forward?

Compared to previous outbreaks, the 2018 outbreak witnessed better-coordinated efforts by both the government, acting through the Nigerian Centre for Disease Control (NCDC), and IHA&O than in previous years. The WHO together with Wellcome Trust is drawing up a LF control Research and Development Roadmap for the engagement of stakeholders and partners toward further development of diagnostics, therapeutics, and vaccines. While some of these responses may have been partly precipitated by the scale of the 2018 outbreak, the largest since 1969 [15], the actions are reassuring and give hope of an end to the neglect of LF control.

However, it is important that the lessons of the past are appropriately factored into current and future control efforts. The Nigerian government should revisit and harmonize the strategic plans of action with a view to committed implementation of best practices in the control of LF outbreaks. The public health measures already initiated must be sustained and strengthened. It is also important to scale up the medical response to the outbreaks. Both published [2,3,7,8] and unpublished data [Akpede GO et al., personal communication] from the Institute of Lassa Fever Research and Control (ILFR&C), ISTH, provide a model of success in surveillance and clinical case management that could be replicated in other places to reduce the annual LF death toll.

In addition, the necessary research required to provide the evidence base needed for the formulation of counter measures must be supported. Furthermore, the technical input and logistic support from IHA&O should be sustained through their continued engagement and involvement in the formulation and implementation of strategic plans.

4. Conclusion

There are a number of imperatives for success and sustainability of the control efforts in Nigeria and the sub region. First, national governments must wake up to their constitutional responsibility for the welfare of their peoples. Alongside this, sub-regional cooperation in LF control should be scaled up with expansion of the LF network of the Mano River Union Countries formed in 2004 to include other affected or at-risk countries. Alternatively, Nigeria, Togo, and the Republic of Benin, which are close to each other geographically, could form a complementary network.

Second, aside from sub-regional cooperation, collaboration between national and international organizations and institutions to speed up the implementation of plans to combat LF in Nigeria in particular, and West Africa in general should be strengthened. The impact of such collaborations is already clear from the extant relationship between Nigerian institutions and overseas partners [7]. It was also clearly demonstrated in the synergy between NCDC and the WHO, among others, in the success of the response to the 2018 LF outbreak in Nigeria.

Third, the control programs must be adequately funded. We believe that with adequate prioritization, prompting, and prodding countries in the sub region, Nigeria certainly can and should contribute meaningfully toward this. Costing of the requirements for research and development of the diagnostics, therapeutics, and vaccines needed for LF control is beyond the scope of this editorial. However, with regard to surveillance and case management, there are indications that about 65–68 million USD could suffice for the establishment and initial maintenance of the minimum of six dedicated strategic zonal LF/VHF control centers required for the effective surveillance and case management of LF in Nigeria. We believe that it should be possible to raise this through the combined efforts of the government, the private sector, donor agencies, and philanthropists.

Fourth, indigenous surveillance capacity must be strengthened. We have demonstrated the feasibility of the establishment of modern diagnostic centers in the sub region [7], and there is a clear case for the establishment of more static and mobile diagnostic laboratories. Progress in the development of rapid point-of-care diagnostic tests could also enhance surveillance and case management. In this regard, the development of a rapid diagnostic pan-Lassa virus enzyme-linked immunosorbent assay (pan-LASV-ELIZA) or other related tests which is capable of detecting infection with any of the LASV lineages should be accelerated. Such a screening test should be deployable throughout the different health-care facilities in Nigeria and other countries in the sub region.

Fifth, case management capacity must also be strengthened through the establishment of well-equipped dedicated treatment/referral centers and the training of clinical care teams. There is, for example, a high prevalence and case fatality associated with acute kidney injury from LF [7,8] and thus a role for renal replacement therapy in mitigating outcome. The impact of adequate case management on outcome during the recent Ebola outbreak in West Africa [16] is an added example. Interestingly, with the many similarities in diagnosis and clinical management needs [17], dedicated diagnosis and treatment centers could serve the surveillance and case management needs of multiple VHFs.

Within the context of adequate clinical care, the development of standard case management guidelines at international, national, and institutional levels for the treatment of patients with suspected and confirmed LF should be speeded up. These can be updated periodically as more evidence becomes available from ongoing and subsequent research initiatives. The guidelines should of course be inclusive of protocols for the post-exposure prophylaxis and follow-up of close contacts of infected persons.

Sixth, there should be surveillance of variations in the levels of LASV carriage among reservoir rodents, principally Mastomys natalensis [18]. There should also be surveillance of antigenic variations among LASV lineages in rodents as well as infected persons [19], and surveillance of variations in the populations of carrier rodents [20]. These could help to anticipate outbreaks, areas prone to outbreaks, and clinical case severity during outbreaks, and thereby facilitate outbreak preparedness and response. Finally, the processes for the indigenous production of reagents for diagnosis and consumables for clinical care should be put in place.

In all these, the Nigerian government through NCDC should carry immense responsibility for coordination, resource mobilization, and advocacy. Thankfully the country is no longer in denial of the challenge of LF but the new consciousness requires nurturing and sustenance. The IHA&O have the responsibility to mobilize assistance and provide technical advice, and to urge, nudge and, if necessary, even cajole sub-regional governments into action. And, there should be hope with concerted action.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

The manuscript was not funded.