Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

A New Malaria Agent in African Hominids

Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually, mainly among African infants. The origin and evolution of this pathogen within the human lineage is still unresolved. A single species, P. reichenowi, which infects chimpanzees, is known to be a close sister lineage of P. falciparum. Here we report the discovery of a new Plasmodium species infecting Hominids. This new species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa). Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes P. falciparum and P. reichenowi (∼21±9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature). This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification. Investigation of the nuclear genome of this new species will further the understanding of the genetic adaptations of P. falciparum to humans. The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria

Establishment of Fruit Bat Cells (Rousettus aegyptiacus) as a Model System for the Investigation of Filoviral Infection

Marburg virus and several species of Ebola virus are endemic in central Africa and cause sporadic outbreaks in this region with mortality rates of up to 90%. So far, there is no vaccination or therapy available to protect people at risk in these regions. Recently, different fruit bats have been identified as potential reservoirs. One of them is Rousettus aegyptiacus. It seems that within huge bat populations only relatively small numbers are positive for filovirus-specific antibodies or filoviral RNA, a phenomenon that is currently not understood. As a first step towards understanding the biology of filoviruses in bats, we sought to establish a model system to investigate filovirus replication in cells derived from their natural reservoir. Here, we provide the first insights into this topic by monitoring filovirus infection of a Rousettus aegyptiacus derived cell line, R06E. We were able to show that filoviruses propagate well in R06E cells, which can, therefore, be used to investigate replication and transcription of filovirus RNA and to very efficiently perform rescue of recombinant Marburg virus using reverse genetics. These results emphasize the suitability of the newly established bat cell line for filovirus research

Challenges in Diagnosing Paediatric Malaria in Dar es Salaam, Tanzania.

Malaria is a major cause of paediatric morbidity and mortality. As no clinical features clearly differentiate malaria from other febrile illnesses, and malaria diagnosis is challenged by often lacking laboratory equipment and expertise, overdiagnosis and overtreatment is common. Children admitted with fever at the general paediatric wards at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania from January to June 2009 were recruited consecutively and prospectively. Demographic and clinical features were registered. Routine thick blood smear microscopy at MNH was compared to results of subsequent thin blood smear microscopy, and rapid diagnostics tests (RDTs). Genus-specific PCR of Plasmodium mitochondrial DNA was performed on DNA extracted from whole blood and species-specific PCR was done on positive samples. Among 304 included children, 62.6% had received anti-malarials during the last four weeks prior to admission and 65.1% during the hospital stay. Routine thick blood smears, research blood smears, PCR and RDT detected malaria in 13.2%, 6.6%, 25.0% and 13.5%, respectively. Positive routine microscopy was confirmed in only 43% (17/40), 45% (18/40) and 53% (21/40), by research microscopy, RDTs and PCR, respectively. Eighteen percent (56/304) had positive PCR but negative research microscopy. Reported low parasitaemia on routine microscopy was associated with negative research blood slide and PCR. RDT-positive cases were associated with signs of severe malaria. Palmar pallor, low haemoglobin and low platelet count were significantly associated with positive PCR, research microscopy and RDT. The true morbidity attributable to malaria in the study population remains uncertain due to the discrepancies in results among the diagnostic methods. The current routine microscopy appears to result in overdiagnosis of malaria and, consequently, overuse of anti-malarials. Conversely, children with a false positive malaria diagnosis may die because they do not receive treatment for the true cause of their illness. RDTs appear to have the potential to improve routine diagnostics, but the clinical implication of the many RDT-negative, PCR-positive samples needs to be elucidated.\u

Clinical Forms of Chikungunya in Gabon, 2010

Chikungunya fever (CHIK) is a disease caused by a virus transmitted to humans by infected mosquitos. The virus is responsible for multiple outbreaks in tropical and temperate areas worldwide, and is now a global concern. Clinical and biological features of the disease are poorly described, especially in Africa, where the disease is neglected because it is considered benign. During a recent CHIK outbreak that occurred in southeast Gabon, we prospectively studied clinical and biological features of 270 virologically confirmed cases. Fever and arthralgias were the predominant symptoms. Furthermore, variable and distinct clinical pictures including pure febrile, pure arthralgic and unusual forms (neither fever nor arthralgias) were detected. No severe forms or deaths were reported. These findings suggest that, during CHIK epidemics, some patients may not have classical symptoms (fever and arthralgias). Local surveillance is needed to detect any changes in the pathogenicity of this virus

PLoS Negl Trop Dis

BACKGROUND: During the Ebola virus disease (EVD) epidemic in Liberia, contact tracing was implemented to rapidly detect new cases and prevent further transmission. We describe the scope and characteristics of contact tracing in Liberia and assess its performance during the 2014-2015 EVD epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective descriptive analysis of data collection forms for contact tracing conducted in six counties during June 2014-July 2015. EVD case counts from situation reports in the same counties were used to assess contact tracing coverage and sensitivity. Contacts who presented with symptoms and/or died, and monitoring was stopped, were classified as "potential cases". Positive predictive value (PPV) was defined as the proportion of traced contacts who were identified as potential cases. Bivariate and multivariate logistic regression models were used to identify characteristics among potential cases. We analyzed 25,830 contact tracing records for contacts who had monitoring initiated or were last exposed between June 4, 2014 and July 13, 2015. Contact tracing was initiated for 26.7% of total EVD cases and detected 3.6% of all new cases during this period. Eighty-eight percent of contacts completed monitoring, and 334 contacts were identified as potential cases (PPV = 1.4%). Potential cases were more likely to be detected early in the outbreak; hail from rural areas; report multiple exposures and symptoms; have household contact or direct bodily or fluid contact; and report nausea, fever, or weakness compared to contacts who completed monitoring. CONCLUSIONS/SIGNIFICANCE: Contact tracing was a critical intervention in Liberia and represented one of the largest contact tracing efforts during an epidemic in history. While there were notable improvements in implementation over time, these data suggest there were limitations to its performance-particularly in urban districts and during peak transmission. Recommendations for improving performance include integrated surveillance, decentralized management of multidisciplinary teams, comprehensive protocols, and community-led strategies