Clinical characteristics and predictors of human mpox outcome during the 2022 outbreak in Nigeria: a cohort study.

BACKGROUND: Research from sub-Saharan Africa that contributes to our understanding of the 2022 mpox (formerly known as monkeypox) global outbreak is insufficient. Here, we describe the clinical presentation and predictors of severe disease among patients with mpox diagnosed between Feb 1, 2022, and Jan 30, 2023 in Nigeria. METHODS: We did a cohort study among laboratory-confirmed and probable mpox cases seen in 22 mpox-treatment centres and outpatient clinics across Nigeria. All individuals with confirmed and probable mpox were eligible for inclusion. Exclusion criteria were individuals who could not be examined for clinical characterisation and those who had unknown mortality outcomes. Skin lesion swabs or crust samples were collected from each patient for mpox diagnosis by PCR. A structured questionnaire was used to document sociodemographic and clinical data, including HIV status, complications, and treatment outcomes from the time of diagnosis to discharge or death. Severe disease was defined as mpox associated with death or with a life-threatening complication. Two logistic regression models were used to identify clinical characteristics associated with severe disease and potential risk factors for severe disease. The primary outcome was the clinical characteristics of mpox and disease severity. FINDINGS: We enrolled 160 people with mpox from 22 states in Nigeria, including 134 (84%) adults, 114 (71%) males, 46 (29%) females, and 25 (16%) people with HIV. Of the 160 patients, distinct febrile prodrome (n=94, 59%), rash count greater than 250 (90, 56%), concomitant varicella zoster virus infection (n=48, 30%), and hospital admission (n=70, 48%) were observed. Nine (6%) of the 160 patients died, including seven (78%) deaths attributable to sepsis. The clinical features independently associated with severe disease were a rash count greater than 10 000 (adjusted odds ratio 26·1, 95% CI 5·2-135·0, p<0·0001) and confluent or semi-confluent rash (6·7, 95% CI 1·9-23·9). Independent risk factors for severe disease were concomitant varicella zoster virus infection (3·6, 95% CI 1·1-11·5) and advanced HIV disease (35·9, 95% CI 4·1-252·9). INTERPRETATION: During the 2022 global outbreak, mpox in Nigeria was more severe among those with advanced HIV disease and concomitant varicella zoster virus infection. Proactive screening, management of co-infections, the integration and strengthening of mpox and HIV surveillance, and preventive and treatment services should be prioritised in Nigeria and across Africa. FUNDING: None.

Circulation of Lassa virus across the endemic Edo-Ondo axis, Nigeria, with cross-species transmission between multimammate mice.

We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained from Mastomys rodents in seven localities across the highly endemic Edo and Ondo States within Nigeria. Sequencing 1641 nt from the S segment of the virus genome, we resolved clades within lineage II that were either limited to Ebudin and Okhuesan in Edo state (2g-beta) or along Owo-Okeluse-Ifon in Ondo state (2g-gamma). We also found clades within Ekpoma, a relatively large cosmopolitan town in Edo state, that extended into other localities within Edo (2g-alpha) and Ondo (2g-delta). LASV variants from M. natalensis within Ebudin and Ekpoma in Edo State (dated approximately 1961) were more ancient compared to those from Ondo state (approximately 1977), suggesting a broadly east-west virus migration across south-western Nigeria; a pattern not always consistent with LASV sequences derived from humans in the same localities. Additionally, in Ebudin and Ekpoma, LASV sequences between M. natalensis and M. erythroleucus were interspersed on the phylogenetic tree, but those from M. erythroleucus were estimated to emerge more recently (approximately 2005). Overall, our results show that LASV amplification in certain localities (reaching a prevalence as high as 76% in Okeluse), anthropogenically-aided spread of rodent-borne variants amidst the larger towns (involving communal accommodation such as student hostels), and virus-exchange between syntopic M. natalensis and M. erythroleucus rodents (as the latter, a savanna species, encroaches southward into the degraded forest) pose perpetual zoonotic hazard across the Edo-Ondo Lassa fever belt, threatening to accelerate the dissemination of the virus into non endemic areas.

COVID-19 mortality rate and its associated factors during the first and second waves in Nigeria.

COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of COVID-19 mortality was higher in the first wave [54∙25 (95% CI: 50∙98-57∙73)] than in the second wave [19∙19 (17∙60-20∙93)]. Factors independently associated with increased risk of COVID-19 mortality in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35-2∙02) and second wave 1∙52 (1∙11-2∙06)], being symptomatic [aIRR 3∙17 (2∙59-3∙89) and 3∙04 (2∙20-4∙21)], and being hospitalised [aIRR 4∙19 (3∙26-5∙39) and 7∙84 (4∙90-12∙54)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country's surveillance system during the study.

Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021.

BACKGROUND: With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria. METHODS: We conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13. RESULTS: There were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66 121 (18.2%) and 91 644 (20.8%) tested positive in the first and second waves, respectively. There was a 21.3% increase in the number of tests conducted in the second wave with TPR increasing by 14.3%. CI during the first and second waves were 30.3/100 000 and 42.0/100 000 respectively. During the second wave, confirmed COVID-19 cases increased among females and people 30 years old or younger and decreased among urban residents and individuals with travel history within 14 days of sample collection (p value <0.001). Most confirmed cases were asymptomatic at diagnosis during both waves: 74.9% in the first wave; 79.7% in the second wave. CFR decreased during the second wave (0.7%) compared with the first wave (1.8%). CONCLUSION: Nigeria experienced a larger but less severe second wave of COVID-19. Continued implementation of public health and social measures is needed to mitigate the resurgence of another wave.

A national survey of hospital readiness during the COVID-19 pandemic in Nigeria.

INTRODUCTION: The COVID-19 pandemic continues to overwhelm health systems across the globe. We aimed to assess the readiness of hospitals in Nigeria to respond to the COVID-19 outbreak. METHOD: Between April and October 2020, hospital representatives completed a modified World Health Organisation (WHO) COVID-19 hospital readiness checklist consisting of 13 components and 124 indicators. Readiness scores were classified as adequate (score ≥80%), moderate (score 50-79.9%) and not ready (score <50%). RESULTS: Among 20 (17 tertiary and three secondary) hospitals from all six geopolitical zones of Nigeria, readiness score ranged from 28.2% to 88.7% (median 68.4%), and only three (15%) hospitals had adequate readiness. There was a median of 15 isolation beds, four ICU beds and four ventilators per hospital, but over 45% of hospitals established isolation facilities and procured ventilators after the onset of COVID-19. Of the 13 readiness components, the lowest readiness scores were reported for surge capacity (61.1%), human resources (59.1%), staff welfare (50%) and availability of critical items (47.7%). CONCLUSION: Most hospitals in Nigeria were not adequately prepared to respond to the COVID-19 outbreak. Current efforts to strengthen hospital preparedness should prioritize challenges related to surge capacity, critical care for COVID-19 patients, and staff welfare and protection.

Factors associated with progression to death in patients with Lassa fever in Nigeria: an observational study.

BACKGROUND: Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood. We aimed to determine host protein biomarkers capable of determining disease outcome. METHODS: In this observational study, we analysed left-over blood samples from patients who tested positive for Lassa fever at Irrua Specialist Teaching Hospital, Nigeria, between January, 2014, and April, 2017. We measured viral load, concentrations of clinical chemistry parameters, and levels of 62 circulating proteins involved in inflammation, immune response, and haemostasis. Patients with a known outcome (survival or death) and at least 200 µL of good-quality diagnostic sample were included in logistic regression modelling to assess the correlation of parameters with Lassa fever outcome. Individuals who gave consent could further be enrolled into a longitudinal analysis to assess the association of parameters with Lassa fever outcome over time. Participants were divided into two datasets for the statistical analysis: a primary dataset (samples taken between Jan 1, 2014, and April 1, 2016), and a secondary dataset (samples taken between April 1, 2016, and April 1, 2017). Biomarkers were ranked by area under the receiver operating characteristic curve (AUC) from highest (most predictive) to lowest (least predictive). FINDINGS: Of 554 patients who tested positive for Lassa fever during the study period, 201 (131 in the primary dataset and 70 in the secondary dataset) were included in the biomarker analysis, of whom 74 (49 in the primary dataset and 25 in the secondary dataset) had died and 127 (82 in the primary dataset and 45 in the secondary dataset) had survived. Cycle threshold values (indicating viral load) and levels of 18 host proteins at the time of admission to hospital were significantly correlated with fatal outcome. The best predictors of outcome in both datasets were plasminogen activator inhibitor-1 (PAI-1; AUC 0·878 in the primary dataset and 0·876 in the secondary dataset), soluble thrombomodulin (TM; 0·839 in the primary dataset and 0·875 in the secondary dataset), and soluble tumour necrosis factor receptor superfamily member 1A (TNF-R1; 0·807 in the primary dataset and 0·851 in the secondary dataset), all of which had higher prediction accuracy than viral load (0·774 in the primary dataset and 0·837 in the secondary dataset). Longitudinal analysis (150 patients, of whom 36 died) showed that of the biomarkers that were predictive at admission, PAI-1 levels consistently decreased to normal levels in survivors but not in those who died. INTERPRETATION: The identification of PAI-1 and soluble TM as markers of fatal Lassa fever at admission, and of PAI-1 as a marker of fatal Lassa fever over time, suggests that dysregulated coagulation and fibrinolysis and endothelial damage have roles in the pathophysiology of Lassa fever, providing a mechanistic explanation for the association of Lassa fever with oedema and bleeding. These novel markers might aid in clinical risk stratification and disease monitoring. FUNDING: German Research Foundation, Leibniz Association, and US National Institutes of Health.

Acute kidney injury and mortality in pediatric Lassa fever versus question of access to dialysis.

OBJECTIVES: To assess the prevalence of acute kidney injury (AKI), and its impact on outcome in hospitalized pediatric patients with Lassa fever (LF). METHODS: We reviewed the presenting clinical and laboratory features and outcomes of 40 successive hospitalized children with PCR-confirmed LF. The diagnosis and staging of AKI was based on KDIGO criteria. We compared groups of patients using t- or χ2 tests as necessary, and took p-values <0.05 as indicative of the presence of significant differences. RESULTS: Sixteen (40%) children had AKI. Case fatality rate (CFR) was 9/16 (56%) in children with and 1/24 (4%) in those without AKI (OR [95% CI] of CFR associated with AKI = 29.57 [3.17, 275.7]). Presentation with abnormal bleeding (p = 0.008), encephalopathy (p = 0.004), hematuria plus proteinuria (p = 0.013), and elevated serum transaminase levels (p <0.02) were significantly associated with an increased prevalence of AKI. CONCLUSION: AKI prevalence in hospitalized pediatric patients with Lassa fever is high, and correlated with illness severity/CFR. The high prevalence underscores the need for access to hemodialysis, and clinical presentation and/or presence of hematuria plus proteinuria could serve as a ready prompt for referral for such specialized care.

Field evaluation of a Pan-Lassa rapid diagnostic test during the 2018 Nigerian Lassa fever outbreak.

Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease. LF is endemic in Nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid Test (Pan-Lassa RDT) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (II, III and IV). We compared the performance of the Pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDT positive compared to RDT negative.

Mainstreaming the private health sector in the response to COVID-19: facility readinessassessment for screening services in Edo State, Nigeria.

INTRODUCTION: The COVID-19 pandemic presents an opportunity for the Nigerian health system to harness the potentials available in the private sector to augment the capacity within the public health system. This survey was carried out to assess private facility readiness in providing screening services in Edo State. METHODS: This was a descriptive cross-sectional study carried out among private facilities in Edo state. Facilities were selected using stratified sampling technique. Data was collected using adapted questionnaires and an observational checklist. Facility readiness was assessed using the Nigeria Centre for Disease Control recommendations for screening. Parameters were scored and overall scores were converted to proportions. Facilities that scored 70% and above were adjudged to be ready while facilities that scored 69% and below were adjudged to be not ready. RESULTS: A total of 252 health facilities were assessed, comprising 149 (59.1%) hospitals/clinics, 62 (24.6%) pharmacies and 41 (16.3%) laboratories. One hundred and forty-two (95.3%), 60 (96.8%) and 41 (100.0%) hospitals/clinics, pharmacies and laboratories, respectively had hand hygiene facilities. However, overall facility readiness assessment scores for screening services were low with only 51 (34.2%) hospitals/clinics, 2 (3.2%) pharmacies and 2 (4.9%) laboratories achieving high enough scores to be adjudged ready for screening services. CONCLUSION: Overall facility readiness of the private health sector to provide screening services in Edo State was assessed to be low. The government and facility owners will need to ensure that screening services are improved in all facilities to help mitigate community spread of COVID-19.

Corrigendum: Caseload and Case Fatality of Lassa Fever in Nigeria, 2001-2018: A Specialist Center's Experience and Its Implications.

[This corrects the article DOI: 10.3389/fpubh.2019.00170.].

Phylogeography of Lassa Virus in Nigeria.

Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatiotemporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian states. The final data set, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 states. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while a few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi Within lineages II and III, seven and five sublineages, respectively, were distinguishable. Phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal toward the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast toward Taraba and Adamawa and south toward Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sublineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at a higher resolution. In addition, we estimated the direction and time frame of virus dispersal in the country.IMPORTANCE Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sublineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows us to predict into which geographical areas the virus might spread in the future and prioritize areas for Lassa fever surveillance. Our study not only aimed to generate Lassa virus sequences from across Nigeria but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.

Caseload and Case Fatality of Lassa Fever in Nigeria, 2001-2018: A Specialist Center's Experience and Its Implications.

Background: The general lack of comprehensive data on the trends of Lassa fever (LF) outbreaks contrasts with its widespread occurrence in West Africa and is an important constraint in the design of effective control measures. We reviewed the contribution of LF to admissions and mortality among hospitalized patients from 2001 to 2018 in the bid to address this gap. Methods: Observational study of LF caseload and mortality from 2001 to 18 in terms of the contribution of confirmed LF to admissions and deaths, and case fatality (CF) among patients with confirmed LF at a specialist center in Nigeria. The diagnosis of LF was confirmed using reverse transcription polymerase chain reaction (RT-PCR) test, and medians and frequencies were compared using Kruskal-Wallis, Mann-Whitney and χ2 tests, with p-values <0.05 taken as significant. Results: The contribution of confirmed LF to deaths (362/9057, 4.0%) was significantly higher than to admissions (1,298/185,707, 0.7%; OR [95% CI] = 5.9 [5.3, 6.7], p < 0.001). The average CF among patients with confirmed LF declined from 154/355 (43%) in 2001-09 to 183/867 (21.1%) (OR [95% CI] = 2.9 [2.2, 3.7], p < 0.001) in 2011-18. The annual CF declined from 94% in 2001 to 15% in 2018 whereas the caseload increased from 0.3 to 3.4%. The outbreaks were characterized by irregular cycles of high caseload in 2005-2007, 2012-2014, and 2016-2018, and progressive blurring of the seasonality. Conclusion: LF outbreaks in Nigeria have upgraded spatially and temporally, with the potential for cycles of increasing severity. The strategic establishment of LF surveillance and clinical case management centers could be a pragmatic and cost-effective approach to mitigating the outbreaks, particularly in reducing the associated CF. Urgent efforts are needed in reinvigorating extant control measures while the search for sustainable solutions continues.

Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases.

To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.

Lessons learnt from the management of a case of Lassa fever and follow-up of nosocomial primary contacts in Nigeria during Ebola virus disease outbreak in West Africa.

OBJECTIVE: To describe our experiences in the management of a case of Lassa fever (LF) and follow-up of nosocomial primary contacts during the 2014 Ebola outbreak in West Africa. METHODS: Clinical management of the index case and infection control/surveillance activities for primary contacts are described. Laboratory confirmation was by Lassa virus-specific reverse-transcriptase PCR. RESULTS: A 28-year-old man with a 10-day history of febrile illness was referred to a major tertiary hospital in south-east Nigeria from a city that previously experienced a LF outbreak and was recently affected by Ebola. On observation of haemorrhagic features, clinicians were at a crossroads. Diagnosis of LF was confirmed at a National Reference Centre. The patient died despite initiation of ribavirin therapy. Response activities identified 121 primary contacts comprising 78 (64.5%) hospital staff/interns, 19 (15.7%) medical students, 18 (14.9%) inpatients and 6 (5.0%) relatives. Their mean age was 32.8 ± 6.6 years, and 65.3% were women. Twenty (16.5%) had high-risk exposure and were offered ribavirin as post-exposure prophylaxis. No secondary case of LF occurred. Fatigue (43.8%) and dizziness (31.3%) were the commonest side effects of ribavirin. CONCLUSIONS: Response activities contained nosocomial spread of LF, but challenges were experienced including lack of a purpose-built isolation facility, absence of local Lassa virus laboratory capacity, failure to use appropriate protective equipment and stigmatisation of contacts. A key lesson is that the weak health systems of Africa should be comprehensively strengthened; otherwise, we might win the Ebola battle but lose the one against less virulent infections for which effective treatment exists.

Community knowledge and attitude to pulmonary tuberculosis in rural Edo state, Nigeria.

BACKGROUND: A high level of community awareness and positive perception toward pulmonary TB (PTB) and its management is crucial for the success of any control strategy. This study was carried out to assess the knowledge, attitudes, and practice as regard to TB and its treatment. MATERIALS AND METHODS: A descriptive cross sectional study involving 193 persons was carried out in a rural community in Ward 5 of Etsako-West local government area of Edo state, selected through a multi-stage sampling process. RESULTS: About 86% of respondents had heard of PTB, with a greater proportion being females (55.7%). Mean knowledge score (16.26±5.8) showed that a greater proportion (55.1%) had poor knowledge (range 0-35), with males having better (though not significant) knowledge than females (mean score 17.28±5.9 and 16.94±5.0, respectively, P=0.68). Although attitude toward TB did not influence caring for sick relatives or friends, it impeded social interactions and marriage prospects with infected persons within the community. CONCLUSION: Knowledge and attitude toward PTB was generally poor in this rural community. Efforts should be intensified by health authorities in the local government to raise awareness and knowledge of the disease, so as to improve social perception and early recognition of infection.