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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 characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies 1-3 . Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.

Background: Convalescent blood therapy has been a promising form of treatment for Ebola Virus Disease (EVD), but less attention has been focused on it for treatment., Method: We assessed the effectiveness of convalescent whole blood (CWB) in the treatment of consented EVD patients. We recruited 69 subjects in December 2014 up to April 2015, at the 34 Military Hospital in Wilberforce and the PTS 1 Ebola Treatment Unit in Hastings, Freetown. Forty-four were given CWB, and 25 who consented but preferred to be exempted from the CWB treatment were used to compare clinical outcomes. All were given routine treatment used at the Ebola Treatment Unit., Results: One of 44 subjects treated with CWB dropped out of the study and 31 recovered while 12 succumbed to the disease with a case fatality rate of 27.9%. For the group that was given routine treatment without CWB, 11 died with a case fatality rate of 44%. There was a significant difference between admission viral load and viral load after the first 24 h of treatment with convalescent whole blood (P < 0.01). The odds ratio for survival with CWB was 2.3 (95% CI, 0.8-6.5)., Conclusion: CWB is promising for treating EVD in resource-poor settings, especially in the early phases of outbreaks when resource-mobilization is done. Even though our sample size was small and the evaluation was not randomised, our results contribute to existing evidence that convalescent whole blood could be considered as a useful candidate for treating EVD. Further studies that are randomised will be required to further assess the efficacy of CWB as treatment option during any EVD outbreak., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs., Methods: Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities., Results: Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case., Conclusions: Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases., Methods: Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance., Results: The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 10 5 -9.0 × 10 8 genomes/mL., Conclusions: The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD., Methods: Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014. Banked residual clinical samples were tested in November 2014 and January 2015 in a blinded field trial to estimate the clinical effectiveness of the ReEBOV RDT, compared with EBOV-specific qRT-PCR., Results: Preliminary ReEBOV RDT performance demonstrated a positive percentage agreement (PPA) of 91.1% (195 of 214 results; 95% confidence interval [CI], 86.5%-94.6%) and a negative percentage agreement (NPA) of 90.2% (175 of 194; 95% CI, 85.1%-94.0%). The final estimates used by the Food and Drug Administration to determine whether to grant emergency use authorization for the test, which excluded a qRT-PCR reference method threshold cutoff, were a PPA of 62.1% (72 of 116 results; 95% CI, 52.6%-70.9%) and a NPA of 96.7% (58 of 60; 95% CI, 88.5%-99.6%), with a diagnostic likelihood of 18.6. A subsequent, independent evaluation by the World Health Organization generated results consistent with the preliminary performance estimates., Conclusions: The ReEBOV RDT demonstrated the potential to provide clinically effective rapid and accurate point-of-care test results and, thus, to be a powerful tool for increasing triage efficiency., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design.

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014., Methods: We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase-polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients., Results: Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient., Conclusions: The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.).

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response., (Copyright © 2014, American Association for the Advancement of Science.)

A study was undertaken to evaluate the human energy consumption of various field operations involved in lowland rice cultivation in Malaysia. Based on recorded average heart rates, fertilizing was found to be the most strenuous operation, with an average heart rate of 138 beats min(-1). There were no significant differences in the average heart rates of the subjects among the individual tasks within the first plowing, second plowing, and harvesting operations, with the average heart rates for these three tasks being 116, 106, and 106 beats min(-1), respectively. The corresponding energy expenditures were 3.90, 3.43, and 3.35 kcal min(-1). Loading the seed into the blower tank and broadcasting the seed were the most critical tasks for the seed broadcasting operation, with average heart rates of 124 and 136 beats min(-1), respectively. The highest energy expenditure of 418.38 kcal ha(-1) was observed for seed broadcasting, and the lowest energy expenditure of 127.96 kcal ha(-1) was for second plowing. The total seasonal human energy expenditure for rice cultivation was estimated to be 5810.71 kcal ha(-1), 55.7% of which was spent on pesticide spraying. Although the sample size in this study was relatively small, the results indicated that human energy expenditure per unit area (kcal ha(-1)) was positively linked to the average heart rate of the subjects and negatively linked to the field capacity. Thus, mechanization of certain tasks could decrease worker physical effort and fatigue and increase production.

In this study, we determined normal values for some haematological parameters in male Sierra Leoneans--Haemaglobin concentration (HB), Packed Cell Volume (PCV), White Blood Cell Count (WBC), Red Blood Cell Count (RCC) and Erythrocyte Sedimentation rate (ESR). The result obtained differ significantly from those found in European text books as normal values for these parameters. We recommend that results obtained from this study replace European reference values for male Sierra Leoneans.

Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.

Three thousand five hundred and twenty four (1527 male and 1997 female) samples were screened for the presence of the abnormal haemoglobin--Sickle Cell (HbS) between 1990-1993. 780 (22%) of these show sickle erythrocytes in a reduced oxygen environment. Electrophoretic differentiation of 344 samples positive from the metabisulphite screening test, revealed that 76 are of the homozygous form with 3 being HbSC. Noting the adverse consequences on the health status of those affected and the expense involved in the management of such patients, there is an urgent need for intervention.

The platelet counts of 100 healthy Sierra Leoneans were determined. Fifty six (56) Males and Forty four (44) Females were included in the study. The mean platelet count was 197 x 10(9)/L(SD = 25 x 10(9)/L Range = 115-335 x 10(9)/L The results of this study compare favourably with those obtained from previous studies in other African Countries and confirms that the normal platelet count in the African is lower than in Caucasians.

The prevalence of chronic leg ulcers was investigated in 872 adults with sickle cell disease (SCD) (630 HbSS and 242 HbSC) at Ibadan, Nigeria. The incidence was 7.5% in HbSS and 1.7% in HbSC patients. The sex ratio in HbSS was 2:1 in favour of males, and three of the four HbSC were females. Ulcers were sited around the ankles in more than 70% of the patients. The duration of the ulcers varied from less than 1 year to more than 20 years. There was no bias for social class. Response to therapy, including autologous skin graft, was poor.

An increase in the number of Nigerian patients with acute lymphoblastic leukaemia (ALL), relative to those having acute myelogenous leukaemia, was predicted some years ago. This was expected to result from an enhanced socio-economic status of most members of the general population and improved nutrition. A review of the features of ALL patients seen in University College Hospital, Ibadan, during different periods over the past three decades revealed not only the predicted changes but also an increasing proportion of pediatric and female patients. Except for an unusual number of patients with the rare L3 morphological variant seen within the last 2 years, little else changed in the clinical and laboratory features of the disease. Atrophy of the thymus resulting from malnutrition is thought to inhibit the occurrence of common-ALL in the first decade of life. This inhibition is removed by improved nutrition, thus allowing more cases of common-ALL to develop in children. The trend in Nigeria has been observed earlier among Arabs in the Gaza Strip in the Sinai Peninsula. If the hypothesis is correct, undernutrition occurring for a long enough time in a previously well-nourished population should lead to changes opposite to those observed. The increasing percentage of patients who are either young, female or of high socio-economic class imply better prognosis for more Nigerian ALL patients.