Identifying the dissemination patterns and impacts of a virus of economic or health importance du... more Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the B.1.1.318 and B.1.525 variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Our results show how regional connectivity in downsampled regions like Africa can often influence virus transmissions between neighbouring countries. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission in the region, generating actionable information for public ...
While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an... more While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and ...
Tuberculosis is a common conditionworld-wide butmore so in developing countrieswhere it accounts ... more Tuberculosis is a common conditionworld-wide butmore so in developing countrieswhere it accounts for95% of all cases. It primarily affects the respiratory system, but other systems including the gastro-intestinal tractcan also be affected. When it does, it has predilection for the ileo-caecal region, where half of the cases occur. Ano-rectal tuberculosis is not very common andwhen it occurs, it could present as amass,making it difficult todifferentiate from malignancy and other granulomatous lesions. We therefore, present a case of a 68-year old man with a huge mass in the ano-rectum with faecal incontinence, which was clinically diagnosed as anadvanced carcinoma of the ano-rectum for which the biopsy was reported as tuberculosis. He improved with anti-tuberculosis treatment.Keywords: Ano-rectum, tuberculosis, cancer
Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massiv... more Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.
Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms in... more Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Fou...
Introduction Sickle cell anemia (SCA) in adults has many clinical manifestations. These manifesta... more Introduction Sickle cell anemia (SCA) in adults has many clinical manifestations. These manifestations are due to effects of recurrent hemolysis, anemia, and ischemia-reperfusion injury on various organs, including the heart. These factors determine the severity of the disease. Objectives The aim of the study was to assess the severity of SCA using a scoring system consisting of clinical and laboratory parameters. In addition, the study aimed to determine the electrocardiographic abnormalities in the adult SCA population. Study design This was a cross-sectional, observational study conducted in the medical outpatient clinic of Irrua Specialist Teaching Hospital, Irrua, Nigeria. Methodology Sixty SCA patients who were older than 18 years old were recruited for this study between February 2017 and January 2018. Sixty healthy individuals matched for age and sex were recruited to serve as controls. Patients who were pregnant or having an acute crises were excluded from the study. Each p...
Crohn’s disease is a chronic idiopathic inflammatory condition of the gastrointestinal tract, whi... more Crohn’s disease is a chronic idiopathic inflammatory condition of the gastrointestinal tract, which rarely affects the oesophagus and stomach together. The usual sites of involvement are the terminal ileum and proximal colon. It is rarer still for gastric Crohn’s disease to present for the first time with haematemesis resulting from acute upper gastrointestinal haemorrhage, especially in an African setting where the disease is thought to be rare. Oesophageal Crohn’s disease is usually asymptomatic for a long period of time, and may come to medical attention when dysphagia or complications such as stricture or fistula occur in the oesophagus, or when extra-oesophageal manifestations occur. We present a 67 year old Nigerian farmer who was brought into our emergency room at the Irrua Specialist Teaching Hospital, Irrua, from his farm with a history of sudden onset haematemesis. The clinical diagnosis was moderate to severe upper gastrointestinal haemorrhage secondary to non-steroidal a...
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that... more Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI’s (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II–IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III ...
Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease... more 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. ...
The high morbidity and mortality associated with clinical cases of Lassa fever, together with the... more The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.
It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of ... more It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV.
Journal of The Egyptian Society of Nephrology and Transplantation, 2019
Background Acute kidney injury (AKI) is a frequent complication of Lassa fever (LF) that is notab... more Background Acute kidney injury (AKI) is a frequent complication of Lassa fever (LF) that is notably associated with poor outcome. The study aimed at evaluating the relationship between the clinical parameters and outcome of hemodialysis-treated patients with AKI complicating LF and to highlight our experience between 2014 and 2018. Materials and methods This was a descriptive, observational, and retrospective study involving patients with LF complicated by AKI who had hemodialysis at the dedicated dialysis suite located in our hospital between January 2014 and September 2018. Information were extracted from the clinical and laboratory records of the patients during the period under review. Results A total of 83 patients had 199 sessions of hemodialysis. Male to female ratio was 2.5 : 1. The mean age was 34.3±13.7 years. The mean number of hemodialysis sessions per patient was 2.4±1.5. The frequency of intradialytic complication was 9.6%, whereas hypotension (62.5%) was the commonest. Occurrence of intradialytic complications was significantly associated with mortality (χ2=5.370, d.f.=1, P=0.020). A high incidence of anemia (65.1%) was observed among the patients. Sixteen (19.3%) of the patients died. There was no significant association between age, sex, number of dialysis session or anemia and outcome of LF. Compared with those who died, patients who recovered had significantly higher mean postdialysis diastolic blood pressure (t=2.382, P=0.020). Conclusion Intradialytic complication is infrequent in dialysis treated LF patients with AKI, but has significant association with mortality.
Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality... more 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.
Identifying the dissemination patterns and impacts of a virus of economic or health importance du... more Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the B.1.1.318 and B.1.525 variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Our results show how regional connectivity in downsampled regions like Africa can often influence virus transmissions between neighbouring countries. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission in the region, generating actionable information for public ...
While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an... more While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and ...
Tuberculosis is a common conditionworld-wide butmore so in developing countrieswhere it accounts ... more Tuberculosis is a common conditionworld-wide butmore so in developing countrieswhere it accounts for95% of all cases. It primarily affects the respiratory system, but other systems including the gastro-intestinal tractcan also be affected. When it does, it has predilection for the ileo-caecal region, where half of the cases occur. Ano-rectal tuberculosis is not very common andwhen it occurs, it could present as amass,making it difficult todifferentiate from malignancy and other granulomatous lesions. We therefore, present a case of a 68-year old man with a huge mass in the ano-rectum with faecal incontinence, which was clinically diagnosed as anadvanced carcinoma of the ano-rectum for which the biopsy was reported as tuberculosis. He improved with anti-tuberculosis treatment.Keywords: Ano-rectum, tuberculosis, cancer
Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massiv... more Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.
Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms in... more Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Fou...
Introduction Sickle cell anemia (SCA) in adults has many clinical manifestations. These manifesta... more Introduction Sickle cell anemia (SCA) in adults has many clinical manifestations. These manifestations are due to effects of recurrent hemolysis, anemia, and ischemia-reperfusion injury on various organs, including the heart. These factors determine the severity of the disease. Objectives The aim of the study was to assess the severity of SCA using a scoring system consisting of clinical and laboratory parameters. In addition, the study aimed to determine the electrocardiographic abnormalities in the adult SCA population. Study design This was a cross-sectional, observational study conducted in the medical outpatient clinic of Irrua Specialist Teaching Hospital, Irrua, Nigeria. Methodology Sixty SCA patients who were older than 18 years old were recruited for this study between February 2017 and January 2018. Sixty healthy individuals matched for age and sex were recruited to serve as controls. Patients who were pregnant or having an acute crises were excluded from the study. Each p...
Crohn’s disease is a chronic idiopathic inflammatory condition of the gastrointestinal tract, whi... more Crohn’s disease is a chronic idiopathic inflammatory condition of the gastrointestinal tract, which rarely affects the oesophagus and stomach together. The usual sites of involvement are the terminal ileum and proximal colon. It is rarer still for gastric Crohn’s disease to present for the first time with haematemesis resulting from acute upper gastrointestinal haemorrhage, especially in an African setting where the disease is thought to be rare. Oesophageal Crohn’s disease is usually asymptomatic for a long period of time, and may come to medical attention when dysphagia or complications such as stricture or fistula occur in the oesophagus, or when extra-oesophageal manifestations occur. We present a 67 year old Nigerian farmer who was brought into our emergency room at the Irrua Specialist Teaching Hospital, Irrua, from his farm with a history of sudden onset haematemesis. The clinical diagnosis was moderate to severe upper gastrointestinal haemorrhage secondary to non-steroidal a...
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that... more Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI’s (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II–IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III ...
Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease... more 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. ...
The high morbidity and mortality associated with clinical cases of Lassa fever, together with the... more The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.
It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of ... more It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV.
Journal of The Egyptian Society of Nephrology and Transplantation, 2019
Background Acute kidney injury (AKI) is a frequent complication of Lassa fever (LF) that is notab... more Background Acute kidney injury (AKI) is a frequent complication of Lassa fever (LF) that is notably associated with poor outcome. The study aimed at evaluating the relationship between the clinical parameters and outcome of hemodialysis-treated patients with AKI complicating LF and to highlight our experience between 2014 and 2018. Materials and methods This was a descriptive, observational, and retrospective study involving patients with LF complicated by AKI who had hemodialysis at the dedicated dialysis suite located in our hospital between January 2014 and September 2018. Information were extracted from the clinical and laboratory records of the patients during the period under review. Results A total of 83 patients had 199 sessions of hemodialysis. Male to female ratio was 2.5 : 1. The mean age was 34.3±13.7 years. The mean number of hemodialysis sessions per patient was 2.4±1.5. The frequency of intradialytic complication was 9.6%, whereas hypotension (62.5%) was the commonest. Occurrence of intradialytic complications was significantly associated with mortality (χ2=5.370, d.f.=1, P=0.020). A high incidence of anemia (65.1%) was observed among the patients. Sixteen (19.3%) of the patients died. There was no significant association between age, sex, number of dialysis session or anemia and outcome of LF. Compared with those who died, patients who recovered had significantly higher mean postdialysis diastolic blood pressure (t=2.382, P=0.020). Conclusion Intradialytic complication is infrequent in dialysis treated LF patients with AKI, but has significant association with mortality.
Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality... more 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.
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