Treatment of Uncomplicated Falciparum Malaria with Artesunate-Amodiaquine Combination Therapy (ACT) in a Rural Fishing Community in Sierra Leone

Until recently, Chloroquine was the mainstay for malaria chemotherapy in Africa because it is cheap, safe and practicable for out-patient use. Resistance to this drug has however over the past decade, presented a major public health problem with therapeutic and prophylactic implications. As a response to the emergence of resistance to the commonly used antimalarial drugs, the World Health Organisation (WHO) now recommends the use of artemisinin-based combination therapies (ACTs). We assessed the therapeutic efficacy of oral Artesunate-Amodiaquine hydrochloride combination therapy in the treatment of uncomplicated falciparum malaria in a rural fishing community in Sierra Leone. One hundred and fourteen (114) participants aged 0 – 5 years attending the Outpatient Department of Gbondapi Health Centre were screened for recruitment into the study of which 70 fulfilled the inclusion criteria. Artesunate-Amodiaquine hydrochloride combined drug which passed the general counterfeit test of the Ministry of Health and Sanitation was used in the study. Adequate Clinical and parasitological Response (ACPR) was observed in 97% of the study population. Mean parasite clearance time in the participants with ACPR was found to be 24 hours (range 24 –72 hours). All 3% of the treatment failures were observed to be Early Treatment Failures (ETF). Results from the study indicate that Artesunate-Amodiaquine hydrochloride combination therapy is an effective antimalarial drug in a high transmission zone like Sierra Leone, and in the event that the drug is not effective, the results will be evident within one day of commencement of treatment

Depletion of gaseous polycyclic aromatic hydrocarbons by a forest canopy

Rapid uptake of gaseous polycyclic aromatic hydrocarbons (PAHs) by a forest canopy was observed at Borden in Southern Ontario, Canada during bud break in early spring 2003. High volume air samples were taken on 12 individual days at three different heights (44.4, 29.1, and 16.7 m) on a scaffolding tower and on the forest floor below the canopy (1.5 m). Concentrations of PAHs were positively correlated to ambient temperature, resulting from relatively warm and polluted air masses passing over the Eastern United States and Toronto prior to arriving at the sampling site. An analysis of vertical profiles and gas/particle partitioning of the PAHs showed that gaseous PAHs established a concentration gradient with height, whereas levels of particulate PAHs were relatively uniform, implying that only the uptake of gaseous PAHs by the forest canopy was sufficiently rapid to be observed. Specifically, the gaseous concentrations of intermediate PAHs, such as phenanthrene, anthracene, and pyrene, during budburst and leaf emergence were reduced within and above the canopy. When a gradient was observed, the percentage of PAHs on particles increased at the elevations experiencing a decrease in gas phase concentrations. The uptake of intermediate PAHs by the canopy also led to significant differences in gaseous PAH composition with height. These results are the most direct evidence yet of the filter effect of forest canopies for gaseous PAHs in early spring. PAH deposition fluxes and dry gaseous deposition velocities to the forest canopy were estimated from the concentration gradients

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

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.Organismic and Evolutionary Biolog

Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone

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.

Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

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

Ebola virus antibody decay-stimulation in a high proportion of survivors

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1,2,3. 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

Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

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