A new twenty-first century science for effective epidemic response.

With rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems, epidemics will become more frequent, more complex and harder to prevent and contain. Here we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world-especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow's leaders in epidemic prevention and response.

Population health outcomes in Nigeria compared with other west African countries, 1998-2019: a systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. METHODS: In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. FINDINGS: Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2-66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0-9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9-6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1-3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7-2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. INTERPRETATION: Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. FUNDING: The Bill & Melinda Gates Foundation.

Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.

Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.

A continent-wide effort and solidarity at curbing COVID-19 pandemic: the Africa task force for novel coronavirus (AFTCOR) infection prevention and control technical working group's experience.

A continent-wide Africa Task Force for Coronavirus with its six technical working groups was formed to prepare adequately and respond to the novel Coronavirus disease (COVID-19) outbreak in Africa. This research in practice article aimed to describe how the infection prevention and control (IPC) technical working group (TWG) supported Africa Centre for Disease Control and Prevention (Africa CDC) in preparedness and response to COVID-19 on the continent. To effectively address the multifaceted IPC TWG mandate of organizing training and implementing rigorous IPC measures at healthcare service delivery points, the working group was sub-divided into four sub-groups-Guidelines, Training, Research, and Logistics. The action framework was used to describe the experiences of each subgroup. The guidelines subgroup developed 14 guidance documents and two advisories; all of which were published in English. In addition, five of these documents were translated and published in Arabic, while three others were translated and published in French and Portuguese. Challenges faced in the guidelines subgroup included the primary development of the Africa CDC website in English, and the need to revise previously issued guidelines. The training subgroup engaged the Infection Control Africa Network as technical experts to carry out in-person training of IPC focal persons and port health personnel across the African continent. Challenges faced included the difficulty in conducting face-to-face IPC training and onsite technical support due to the lockdown. The research subgroup developed an interactive COVID-19 Research Tracker on the Africa CDC website and conducted a context-based operation and implementation research. The lack of understanding of Africa CDC's capacity to lead her own research was the major challenge faced by the research subgroup. The logistics subgroup assisted African Union (AU) member states to identify their IPC supply needs through capacity building for IPC quantification. A notable challenge faced by the logistics subgroup was the initial lack of experts on IPC logistics and quantifications, which was later addressed by the recruitment of professionals. In conclusion, IPC cannot be built overnight nor can it be promoted abruptly during outbreaks of diseases. Thus, the Africa CDC should build strong national IPC programmes and support such programmes with trained and competent professionals.

Exportation of Monkeypox Virus From the African Continent.

BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.

Lessons from Nigeria's Adaptation of Global Health Initiatives during the COVID-19 Pandemic.

Nigeria receives funds from several global health initiatives that are aimed at addressing elevated risks and overall burden of infectious disease outbreaks. These funds include the Global Fund to Fight AIDS, Tuberculosis and Malaria; US President's Emergency Plan for AIDS Relief; US President's Malaria Initiative; and Global Polio Eradication Initiative. These initiatives have contributed to a substantial reduction in illness and death from HIV, tuberculosis, malaria, and polio. However, Nigeria has experienced mixed success with leveraging the capacities built through these donor-funded vertical programs to respond to new health threats. This report describes experiences using resources from vertical disease programs by the Nigeria Centre for Disease Control in response to the 2014-2016 Ebola outbreak in West Africa and the COVID-19 pandemic. Integrating resources from different disease programs with government-led systems and institutions will improve responses to endemic outbreaks and preparedness for future pandemics in Nigeria.

Pathogens that Cause Illness Clinically Indistinguishable from Lassa Fever, Nigeria, 2018.

During the 2018 Lassa fever outbreak in Nigeria, samples from patients with suspected Lassa fever but negative Lassa virus PCR results were processed through custom gene expression array cards and metagenomic sequencing. Results demonstrated no single etiology, but bacterial and viral pathogens (including mixed co-infections) were detected.

Effect of Nigeria Presidential Task Force on COVID-19 Pandemic, Nigeria.

Nigeria had a confirmed case of COVID-19 on February 28, 2020. On March 17, 2020, the Nigerian Government inaugurated the Presidential Task Force (PTF) on COVID-19 to coordinate the country's multisectoral intergovernmental response. The PTF developed the National COVID-19 Multisectoral Pandemic Response Plan as the blueprint for implementing the response plans. The PTF provided funding, coordination, and governance for the public health response and executed resource mobilization and social welfare support, establishing the framework for containment measures and economic reopening. Despite the challenges of a weak healthcare infrastructure, staff shortages, logistic issues, commodity shortages, currency devaluation, and varying state government cooperation, high-level multisectoral PTF coordination contributed to minimizing the effects of the pandemic through early implementation of mitigation efforts, supported by a strong collaborative partnership with bilateral, multilateral, and private-sector organizations. We describe the lessons learned from the PTF COVID-19 for future multisectoral public health response.

The first and second waves of the COVID-19 pandemic in Africa: a cross-sectional study.

BACKGROUND: Although the first wave of the COVID-19 pandemic progressed more slowly in Africa than the rest of the world, by December, 2020, the second wave appeared to be much more aggressive with many more cases. To date, the pandemic situation in all 55 African Union (AU) Member States has not been comprehensively reviewed. We aimed to evaluate reported COVID-19 epidemiology data to better understand the pandemic's progression in Africa. METHODS: We did a cross-sectional analysis between Feb 14 and Dec 31, 2020, using COVID-19 epidemiological, testing, and mitigation strategy data reported by AU Member States to assess trends and identify the response and mitigation efforts at the country, regional, and continent levels. We did descriptive analyses on the variables of interest including cumulative and weekly incidence rates, case fatality ratios (CFRs), tests per case ratios, growth rates, and public health and social measures in place. FINDINGS: As of Dec 31, 2020, African countries had reported 2 763 421 COVID-19 cases and 65 602 deaths, accounting for 3·4% of the 82 312 150 cases and 3·6% of the 1 798 994 deaths reported globally. Nine of the 55 countries accounted for more than 82·6% (2 283 613) of reported cases. 18 countries reported CFRs greater than the global CFR (2·2%). 17 countries reported test per case ratios less than the recommended ten to 30 tests per case ratio range. At the peak of the first wave in Africa in July, 2020, the mean daily number of new cases was 18 273. As of Dec 31, 2020, 40 (73%) countries had experienced or were experiencing their second wave of cases with the continent reporting a mean of 23 790 daily new cases for epidemiological week 53. 48 (96%) of 50 Member States had five or more stringent public health and social measures in place by April 15, 2020, but this number had decreased to 36 (72%) as of Dec 31, 2020, despite an increase in cases in the preceding month. INTERPRETATION: Our analysis showed that the African continent had a more severe second wave of the COVID-19 pandemic than the first, and highlights the importance of examining multiple epidemiological variables down to the regional and country levels over time. These country-specific and regional results informed the implementation of continent-wide initiatives and supported equitable distribution of supplies and technical assistance. Monitoring and analysis of these data over time are essential for continued situational awareness, especially as Member States attempt to balance controlling COVID-19 transmission with ensuring stable economies and livelihoods. FUNDING: None.

Establishing a national reference laboratory for antimicrobial resistance using a whole-genome sequencing framework: Nigeria's experience.

Whole-genome sequencing (WGS) is finding important applications in the surveillance of antimicrobial resistance (AMR), providing the most granular data and broadening the scope of niches and locations that can be surveilled. A common but often overlooked application of WGS is to replace or augment reference laboratory services for AMR surveillance. WGS has supplanted traditional strain subtyping in many comprehensive reference laboratories and is now the gold standard for rapidly ruling isolates into or out of suspected outbreak clusters. These and other properties give WGS the potential to serve in AMR reference functioning where a reference laboratory did not hitherto exist. In this perspective, we describe how we have employed a WGS approach, and an academic-public health system collaboration, to provide AMR reference laboratory services in Nigeria, as a model for leapfrogging to national AMR surveillance.

Epidemiological description of and response to a large yellow fever outbreak in Edo state Nigeria, September 2018 - January 2019.

BACKGROUND: Edo State Surveillance Unit observed the emergence of a disease with "no clear-cut-diagnosis", which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State. METHODS: A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as "Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019". Our response involved active case search in health facilities and communities, retrospective review of patients' records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made. RESULTS: A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented. CONCLUSION: Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.

Clones and Clusters of Antimicrobial-Resistant Klebsiella From Southwestern Nigeria.

BACKGROUND: Klebsiella pneumoniae is a World Health Organization high-priority antibiotic-resistant pathogen. However, little is known about Klebsiella lineages circulating in Nigeria. METHODS: We performed whole-genome sequencing (WGS) of 141 Klebsiella isolated between 2016 and 2018 from clinical specimens at 3 antimicrobial-resistance (AMR) sentinel surveillance tertiary hospitals in southwestern Nigeria. We conducted in silico multilocus sequence typing; AMR gene, virulence gene, plasmid, and K and O loci profiling; as well as phylogenetic analyses, using publicly available tools and Nextflow pipelines. RESULTS: Phylogenetic analysis revealed that the majority of the 134 K. pneumoniae and 5 K. quasipneumoniae isolates from Nigeria characterized are closely related to globally disseminated multidrug-resistant clones. Of the 39 K. pneumoniae sequence types (STs) identified, the most common were ST307 (15%), ST5241 (12%), ST15 (~9%), and ST25 (~6%). ST5241, 1 of 10 novel STs detected, is a single locus variant of ST636 carrying dfrA14, tetD, qnrS, and oqxAB resistance genes. The extended-spectrum ß-lactamase (ESBL) gene blaCTX_M-15 was seen in 72% of K. pneumoniae genomes, while 8% encoded a carbapenemase. No isolate carried a combination of carbapenemase-producing genes. Four likely outbreak clusters from 1 facility, within STs 17, 25, 307, and 5241, were ESBL but not carbapenemase-bearing clones. CONCLUSIONS: This study uncovered known and novel K. pneumoniae lineages circulating in 3 hospitals in Southwest Nigeria that include multidrug-resistant ESBL producers. Carbapenemase-producing isolates remain uncommon. WGS retrospectively identified outbreak clusters, pointing to the value of genomic approaches in AMR surveillance for improving infection prevention and control in Nigerian hospitals.

Evaluation of National Event-Based Surveillance, Nigeria, 2016-2018.

Nigeria Centres for Disease Control and Prevention established an event-based surveillance (EBS) system in 2016 to supplement traditional surveillance structures. The EBS system is comprised of an internet-based data mining tool and a call center. To evaluate the EBS system for usefulness, simplicity, acceptability, timeliness, and data quality, we performed a descriptive analysis of signals received during September 2017-June 2018. We used questionnaires, semistructured interviews, and direct observation to collect information from EBS staff. Amongst 43,631 raw signals detected, 138 (0.3%) were escalated; 63 (46%) of those were verified as events, including 25 Lassa fever outbreaks and 13 cholera outbreaks. Interviewees provided multiple examples of earlier outbreak detections but suggested notifications and logging could be improved to ensure action. EBS proved effective in detecting outbreaks, but we noted clear opportunities for efficiency gains. We recommend improving signal logging, standardizing processes, and revising outputs to ensure appropriate public health action.

Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018.

During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time. We found that the increase in cases was not attributable to a particular Lassa virus strain or sustained by human-to-human transmission. Instead, the data were consistent with ongoing cross-species transmission from local rodent populations. Phylogenetic analysis also revealed extensive viral diversity that was structured according to geography, with major rivers appearing to act as barriers to migration of the rodent reservoir.

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study.

BACKGROUND: Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. METHODS: We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. RESULTS: Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. CONCLUSIONS: Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

The niche of One Health approaches in Lassa fever surveillance and control.

Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa.

Electronic reporting of integrated disease surveillance and response: lessons learned from northeast, Nigeria, 2019.

BACKGROUND: Electronic reporting of integrated disease surveillance and response (eIDSR) was implemented in Adamawa and Yobe states, Northeastern Nigeria, as an innovative strategy to improve disease reporting. Its objectives were to improve the timeliness and completeness of IDSR reporting by health facilities, prompt identification of public health events, timely information sharing, and public health action. We evaluated the project to determine whether it met its set objectives. METHOD: We conducted a cross-sectional study to assess and document the lessons learned from the project. We reviewed the performance of the local government areas (LGAs) on timeliness and completeness of reporting, rumors identification, and reporting on the eIDSR and the traditional paper-based system using a checklist. Respondents were interviewed online on the relevance, efficiency, sustainability, project progress and effectiveness, the effectiveness of management, and potential impact and scalability of the strategy using structured questionnaires. Data were cleaned, analyzed, and presented as proportions using an MS Excel spreadsheet. Responses were also presented as direct quotes. RESULTS: The number of health facilities reporting IDSR increased from 103 to 228 (117%) before and after implementation of the eIDSR respectively. The timeliness of reporting was 43% in the LGA compared to 73% in health facilities implementing eIDSR. The completeness of IDSR reports in the last 6 months before the evaluation was ≥85%. Of the 201 rumors identified and verified, 161 (80%) were from the eIDSR pilot sites. The majority of the stakeholders interviewed believed that eIDSR met its predetermined objectives for public health surveillance. The benefits of eIDSR included timely reporting and response to alerts and disease outbreaks, improved timeliness, and completeness of reporting, and supportive supervision to the operational levels. The strategy helped stakeholders to appreciate their roles in public health surveillance. CONCLUSION: The eIDSR has increased the number of health facilities reporting IDSR, enabled early identification, reporting, and verification of alerts, improved timeliness and completeness of reports, and supportive supervision of staff at the operational levels. It was well accepted by the stakeholder as a system that made reporting easy with the potential to improve the public health surveillance system in Nigeria.

Clinical Course and Outcome of Human Monkeypox in Nigeria.

In a retrospective review of hospital records of 40 human monkeypox cases from Nigeria, the majority developed fever and self-limiting vesiculopustular skin eruptions. Five deaths were reported. Compared to human immunodeficiency virus (HIV)-negative cases, HIV type 1-coinfected cases had more prolonged illness, larger lesions, and higher rates of both secondary bacterial skin infections and genital ulcers.

Use of Surveillance Outbreak Response Management and Analysis System for Human Monkeypox Outbreak, Nigeria, 2017-2019.

In November 2017, the mobile digital Surveillance Outbreak Response Management and Analysis System was deployed in 30 districts in Nigeria in response to an outbreak of monkeypox. Adaptation and activation of the system took 14 days, and its use improved timeliness, completeness, and overall capacity of the response.