Critical Appraisal of Epidemiological Research Studies on Lassa fever

Epidemiology in Public Health

Critical Appraisal of Epidemiological Research Studies on Lassa fever, Strengths and weaknesses of relevant epidemiological study designs, implications of evidences and Progression of the disease (Principle of time, place and person.

Brief: Identification of an infectious disease outbreak in a developing country and how evidence were used and implications of evidence for public health action.

Selected case: Lassa fever outbreak in Nigeria

  1. Introduction and disease frequency

As a science, epidemiology is concerned with the relationship of health or disease with other health- related factors in human populations. According to Denue et al. (2019), such factors include mainly other human pathogens. Essentially, the field of epidemiological have as outcome the generation of information which serves as key inputs in the design, development, implementation and evaluation of intervention programmes that would be aimed at the prevention of disease and the promotion of health (Adewuyi et al., 2009). Based on the above, it is important that a critical appraisal of epidemiological evidence be done in order to ensure that epidemiological data tailored towards the design of health promotion campaigns have a high level of integrity. This importance is reflected in health promotion in the developing countries where an inadequate healthcare system mandates continuous health promotions. Adewuyi et al. (2009) suggested that healthcare systems in Nigeria -which because of its level of GDP per capita is termed a developing country- are not comprehensive in terms of cover and not adequate in meeting the diverse health needs of the population. Over the years, this situation has led to the outbreak of different infectious diseases including malaria, monkey- pox, diarrhoea, meningitis, avian influenza, yellow fever and cholera. Ilori et al. (2019) reported that thee infectious diseases take their toll in terms of lives and significant commitment of resources necessary to combat them.

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One of the diseases requiring constant health promotion campaign in Nigeria is Lassa fever. Frame et al. (1970) described Lassa fever as a febrile infectious disease which is caused by the Lassa virus. As a disease, Lassa fever is spread to humans through food substances which have been contaminated with the faeces or urine of infected rats. Denue et al. (2019) further stated that Lassa fever can also be transmitted from one human to another through bodily fluids. The incubation period for Lassa fever is between 3 and 21 days with clinical manifestations that include fatigue, fever, diarrhoea, dyspnea, seizures and chest- pains among others (McCormick et al, 1986; Isere et al, 2015; Yinka- Ogunleye et al, 2018). Ilori et al. (2019) reported that the observed case- fatality rate (CFR) among hospitalised patients in Nigeria is 15%- 50% while approximately 80% of infections are considered to cause mild or no symptoms in humans and are usually undiagnosed. The causative organism for Lassa fever is the Lassa virus which is a member of the Arenaviridae family; the virus is by nature enzootic inside the Mastomys natalensis– a rodent found in West African countries. Akpede et al. (2018) reported that the rodents become infected at birth and they excrete infections via body fluids such as urine which is then transmitted to humans.

A key aspect of epidemiology is an examination of the frequency of the disease and its impact. While Lassa fever is endemic in other West African countries including Liberia, Guinea, and Liberia, Nigeria as a country bears the most burden of the disease. According to Denue et al. (2019), the reason for this spread is the distribution of the vector Mastomys natalensis throughout the West African region. An important characteristics of the management of Lassa fever in the West African region is the lack of totally reliable and accurate epidemiological evidence about the prevalence of the disease, as such estimates are relatively crude compared to what obtains in the developed countries of Asia, Europe and North America. Tambo et al. (2018) reported that West Africa have an estimated 100, 000- 300, 000 cases of Lassa fever every year with approximately 5,000 fatalities. The authors further asserted that the rate of occurrence of the disease increases during the dry season across West Africa and that the dry season provides a window of opportunity for outbreaks. Akhuemokhan et al. (2017) have linked the increased prevalence of Lassa fever in the dry season to the increased chances of encounters between humans and rodents and because the decreased relative humidity during the dry season increases transmission risks. Also, the increased prevalence of the disease in Nigeria led to the establishment of three Lassa fever treatment centers in Edo, Ondo and Ebonyi States.

While Lassa fever is considered endemic in Nigeria, the last major outbreak occurred from January to May, 2018 (specifically January 1- May 6). According to Ilori et al (2019), while from 2014 till 2016 only around 100 laboratory confirmed cases of Lassa fever were reported in Nigeria, this frequency surged to 423 for January 1- May 18. However Denue et al. (2019) put the number of cases reported at 1, 893 with 423 being the laboratory confirmed cases. For the period of the outbreak, the 423 laboratory confirmed cases are distributed unevenly through 2o states and the Federal Capital Territory; of these cases, 80.6% were reported from the 3 states which have a dedicated Lassa fever treatment center (NCDC, 2018). Ilori et al. (2019) put this distribution at 178, 99 and 64 cases for Edo, Ondo and Ebonyi states respectively. In further statistical breakdown, Ilori et al. (2019) stated that Edo, Ondo and Ebonyi states also have the highest incidence rates for Lassa fever while the positive rate for the disease is also unevenly distributed nationally with Delta State having a rate of 70% and Lagos State having the minimal rate of 3.4%. Shehu et al. (2018) defined positive rate as the proportion or ratio of the number of laboratory confirmed cases among all persons reported as suspected cases and tested for a particular condition. During the period of the outbreak, the national positive rate for Lassa fever was 22.5% (423 laboratory confirmed/1, 893 reported).

Also epidemiological evidences report that the Case Fatality Rate (CFR) which is defined as the number of deaths among confirmed cases for the condition (Shehu et al., 2018) ranged from 20.9% to 29.2% (Tambo et al., 2018; Ilori et al., 2019). The states with the highest level of prevalence also had the highest case fatality rates with Ondo having 24.2% and Ebonyi and Edo States having 23.4%and 14.6% respectively. There are also noticeable trends in terms of the statistical distribution of the disease between age and sex. NCDC (2018) and Ilori et al. (2019) reported that out of the 423 laboratory confirmed cases of Lassa fever, complete information was available for only 97.9% of patients. Complete information in this case was taken to denote availability of full data on demography, onset date, symptoms, history of exposure and ribavirin administration. The median age of the laboratory confirmed cases was 32 years with an interquartile range of 20- 44 years, also 62.1% of cases (257 patients) were male while 37.9% were female (NCDC, 2018; Shehu et al, 2018). Epidemiologically, there are also age- and sex- based variations for case fatality rates. According to Ilori et al. (2019), CFR is highest in patients who are older than 60 years (38.2%) and lowest in children who are less than 11 years (11.1%). The authors also reported that patients who are between 41 and 60 years have a higher rate of CFR than children. The gender differences in CFR between male (26.6%) and female patients (21.8%) was found to be not statistically different.

As with any disease condition and more importantly an infectious disease which often take on the dimensions of an epidemic, Lassa fever has negative impacts on the country. The more obvious impact of Lassa fever is the fatalities associated with the disease. According to Akpede et al. (2019), the outbreaks of Lassa fever have upgraded spatially and temporarily with the potentials for increasing severity. According to the authors, suspected cases of Lassa fever from 2008 to 2018 was 14, 168 with the total number of confirmed cases being 1, 637 and fatalities being 410. This signifies tremendous loss of human potential and resources. Another dimension of the impact of Lassa fever relates to its disruptive role in the economy. According to Adagunodo (2018), Lassa fever outbreaks often necessitate disruption or partial shut- down of the cassava processing industry with the additional implications of revenue loss both to processors and the government. These outbreaks also disrupt general economic activities including transportation and tourism. From another perspective, Shehu et al. (2018) observed that Lassa fever outbreaks increase government expenditure on health necessitated by the acquisition of protective gear, and drugs such as Ribavirin (which is a very expensive drug).

  1. Use of epidemiological evidence

2.1 Risk factors

A crucial part of the processes of gathering and applying epidemiological evidence is an examination of the risk factors that predispose individuals to diseases and also to the fatal outcome of diseases. Adagunodo (2018) and Ilori et al. (2019) asserted that while Lassa fever can affect all age groups and both gender, the individuals at the greatest risk of contracting the disease are those who are living in the rural areas. The propensity of these individuals to contract Lassa fever is predicated on the observation that these rural areas are often communities with poor sanitation and crowded living conditions which favours the breeding of rats and exposure to their faeces and urine which can easily contaminate food substances. Ilori et al. (2019) also expressed that healthcare workers have a higher risk of contracting Lassa fever from infected patients especially in the absence of effective infection prevention and control practices or proper barrier nursing. Denue et al. (2019) also observed that individuals, cultures and communities that favour the consumption of rodents as a delicacy are also at a very high risk of contracting Lassa fever. This is also another factor that explains the relatively higher prevalence rate of Lassa fever in the rural areas of the country.

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2.2 Progression of the disease (Principle of time, place and person)

The progression of the Lassa fever outbreak that occurred from January to May, 2018 can be explained using the principles of time, place and person. As related from Gunther and Lenz (2004), a key component of the use of epidemiological evidence is the use of patterns which refers to the time, place and personal characteristics relating to a particular event. In terms of time, and as usually associated with Lassa fever, the 2018 outbreak was during the dry season in which there was an increased rate of interaction between human and the rodents bearing the virus. This aligns with the period of occurrence of earlier Lassa fever outbreaks in the country. The progression of the disease also followed a geographical pattern. As reported by NCDC (2018) and Ilori et al. (2019), the outbreak affected 20 states in the country showing concentrations in the Southwest, North- Central, South- East, South- South and North- East geopolitical zones. The states affected included the heavily affected ones such as Ondo, Edo and Ebonyi, the moderately affected ones like Taraba, Plateau and Bauchi and states with less than ten reported cases such as Osun, Ekiti, Kaduna and Nassarawa. NCDC (2018) further reported that the condition was more concentrated in the rural areas. The progression of the infection can also be explained in terms of the demographic characteristics of individuals affected. The median age of affected individuals is 32 years, affected individuals are predominantly male (62.1%), and more likely to live in the rural areas than in the urban areas. Among the infected individuals cohort, the most expressed symptoms include fever, fatigue, abdominal pain and haemorrhaging.

    1. Strengths and weaknesses of relevant epidemiological study designs

A number of epidemiological studies reported on the Lassa fever outbreak in Nigeria in 2018. Ilori et al. (2019) examined the epidemiologic and clinical features of Lassa fever outbreak in Nigeria (January 1- May 6, 2018). The study was an observational study of laboratory- confirmed patients during the 2016 outbreak. The authors obtained blood samples and data from four different laboratories. Laboratory confirmation was performed using the RealStar Lassa Virus RT- PCR Kit. A key strength of the study was that it was comprehensive and focused on suspected, probable and confirmed cases and as such signified the most up-to- date report on Lassa fever for the period considered. While the study was comprehensive, a number of limitations can be observed. These include the incompleteness of some field data, lack of case- control, non- investigation of localised clusters as well as the fact that the study did not provide insights on the large number of cases recorded for the 2018 outbreak as against those in earlier years. It is however important to point out that the robustness of this study was also because of the tremendous cooperation of the NCDC which also recognised the need for comprehensive and up-to- date data in the management of Lassa fever outbreaks.

Akpede et al. (2019) studied the caseload and case fatality of Lassa fever in Nigeria from 2001 to 2018. The research was an observational study of Lassa fever caseload and mortality from 2001 to 2018 in terms of the contribution of confirmed cases of Lassa to admissions and death and the case fatalities of reported patients. The study was able to establish that case fatalities have decreased from 94% in 2001 to 15% in 2018, a reflection of advances in treatment while caseload increased from 0.3% to 3.4%. A key strength of this study is the robustness of data from which epidemiological evidences were derived and the longitudinal nature of the study which spanned 2001 till 2018. The major weakness of the study was that it was limited to a designated Lassa fever management facility in Edo State and as such the results are not reflective of national data. Tambo et al. (2018) examined re- emerging Lassa fever outbreaks in Nigeria from the perspective of the One Health community surveillance and emergency response practice. The study was an assessment of the current trends in re-emerging Lassa fever outbreak in understanding spatio- geographical reservoir(s), risk factors pattern and Lassa virus incidence mapping, inherent gaps and raising challenges in health systems. The study covered the incidence, fatality and geographical and seasonal distribution of Lassa fever. The study also emphasized the lack of comprehensive data on different aspects of the management of Lassa fever and the implications of these on public health practice. A key strength of the study was that it provided a link between epidemiology and human- animal interactions and how this linkage can be utilised in strengthening Lassa fever outbreak early detection and surveillance, warning alerts and rapid response implementation in vulnerable settings.

  1. Implications

Epidemiological evidences about Lassa fever in Nigeria and in particular the Lassa fever outbreak of 2018 have had important implications on public health practice in Nigeria. During and after the outbreak, epidemiological findings prompted a number of policy responses which in turn impacted public health practice. Ihekweazu (2018) reported that epidemiological findings after the outbreak prompted the activation of the Emergency Operations Centre (EOC) at NCDC to coordinate response, the establishment of the Case Management Helpdesk, deployment of drugs, PPE, medical supplies and rapid response teams to the states and the distribution of guidelines, SOPs and IEC materials to the affected states. Usifoh et al. (2018) reported that an important implication of the outbreak was the review of the national treatment protocol and the development of a national protocol for the diagnosis of Lassa fever. Ihekweazu (2018) and Usifoh et al (2018) further reported that the 2016 outbreak also led to a revamp of the surveillance and detection architecture. This included an increase in the number of laboratories that can handle Lassa fever from two to four, development and deployment of a national sample transportation protocol, introduction of SORMAS tool (an open- source early warning and management system based on mobile and web applications) to enhance surveillance and development of programs aimed at increasing awareness for clinicians and members of the public. Ilori et al. (2016) asserted that the surge in the rates of incidence of Lassa fever in 2018 played a significant role in the increase in the level of awareness of the disease and its risk factors among the general public.

The outbreak and the various epidemiological studies also have implications on epidemiological research. The outbreak brought to fore the fact that there is a gap in the existence and functionality of comprehensive epidemiological information management systems as regards Lassa fever in Nigeria. In a bid to address this gap, Ihekweazu (2018) stated that Lassa fever research in Nigeria have shifted towards the development of vaccines, treatment protocols, laboratory diagnostic methods, disease vectors and the route of transmission of disease and community practices and behavioural changes. Another important implication of the outbreak on epidemiological research is the potential development of a national guideline for the management of Lassa fever which would be built around the core principles of detection, preparedness and response. This will in the long run create conditions that would help in reducing the incidences of Lassa fever outbreaks and improve coordinated management during outbreaks.

  1. Conclusions

This paper have examined epidemiological evidences relating to the outbreak of Lassa fever in Nigeria in 2018. Review of evidence showed that Lassa fever was contracted from the urine and faeces of rodents carrying the virus. Evidence also suggests that out of the West African countries, Nigeria bears the most burden of the disease with confirmed cases reaching 1, 637 by 2018. The 2018 outbreak had 1, 893 reported cases and 423 laboratory confirmed cases with Edo, Ondo and Ebonyi having the highest number of confirmed cases at 178, 99 and 64 respectively. Evidences have also suggested that there are geographical differentials in the incidence of the diseases. Lassa fever have been shown to have tremendous impact in terms of fatalities, economic disruption and the high level of expenditure necessitated by the acquisition of protective gear, and drugs such as Ribavirin. A number of risk factors were also shown to have tremendous impact on the prevalence of the disease, these include rural properties such as poor sanitation and crowded living conditions and exposure to infected persons. The outbreak have also been demonstrated to have enormous impact on public health practice and epidemiological research; these include the development of treatment protocols and guidelines, improvement of surveillance and detection architecture and increased level of awareness among the general public, clinicians and public health officials. Further research areas that have been prompted by the outbreak include research on vaccines, treatment protocols diagnosis and community practices and behavioural changes.

In conclusion, Lassa fever is a public health threat of topmost priority in Nigeria and its coordinated management is an important step towards reducing its impact. The outbreak of 2018 have brought to fore the fact that there are gaps in information management systems as regards the epidemiological aspects of the disease. This must be addressed in order to provide quality input for the design and implementation of Lassa fever management measures.

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