Role of Estimated Glomerular Filtration Rate in Clinical Research: The Never-Ending Matter

Background: Chronic kidney disease (CKD) burden is crucial both on a global scale and at individual patient level, affecting morbidity and mortality directly and through its effect on both cardiovascular damage and CKD progression to end-stage-kidney-disease (ESKD). Unfortunately, the awareness of CKD is poor, with few CKD patients conscious of the severity of their health status. The principal biomarker of kidney function is estimated glomerular filtration rate (eGFR). Methods: We searched the literature and present a review article with the aim of summarizing the role of eGFR in clinical research. In particular, we report the eGFR role as a prognostic, enrichment and endpoint biomarker and its role in the early detection of CKD. Results: eGFR has a major role as a biomarker in clinical research. As a prognostic marker, eGFR reduction is associated with cardiovascular events, ESKD and mortality. As an enrichment biomarker, eGFR values are pivotal for selecting patients to be included in randomized and observational studies; it helps to test a pre-defined drug in early CKD or in more advanced CKD allowing also to avoid screening failures and to shorten the duration of clinical trials. Moreover, eGFR decline (expressed as a percentage of reduction from baseline or continuous slope) can be considered a good endpoint in clinic trials overcoming delays whilst waiting for hard endpoints to develop. Conclusions: eGFR is a strong clinical measure for both observational and intervention studies. It is also helpful in screening the general population for kidney disease and, in particular, to increase awareness of CKD

Seroepidemiologic studies of hantavirus infection among wild rodents in California.

A total of 4,626 mammals were serologically tested for antibodies to Sin Nombre virus. All nonrodent species were antibody negative. Among wild rodents, antibody prevalence was 8.5% in murids, 1.4% in heteromyids, and < 0.1% in sciurids. Of 1,921 Peromyscus maniculatus (deer mice), 226 (11.8%) were antibody positive, including one collected in 1975. The highest antibody prevalence (71.4% of 35) was found among P. maniculatus on Santa Cruz Island, off the southern California coast. Prevalence of antibodies among deer mice trapped near sites of human cases (26.8% of 164) was significantly higher than that of mice from other sites (odds ratio = 4.5; 95% confidence interval = 1.7, 11.6). Antibody prevalence increased with rising elevation (> 1,200 meters) and correlated with a spatial cluster of hantavirus pulmonary syndrome cases in the Sierra Nevada

Marburg Virus Infection Detected in a Common African Bat

Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80–90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus

Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore

We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS

Nipah virus outbreak with person-to-person transmission in a district of Bangladesh, 2007

In February 2007 an outbreak of Nipah virus (NiV) encephalitis in Thakurgaon District of northwest Bangladesh affected seven people, three of whom died. All subsequent cases developed illness 7-14 days after close physical contact with the index case while he was ill. Cases were more likely than controls to have been in the same room (100% vs. 9.5%, OR undefined, P<0.001) and to have touched him (83% vs. 0%, OR undefined, P<0.001). Although the source of infection for the index case was not identified, 50% of Pteropus bats sampled from near the outbreak area 1 month after the outbreak had antibodies to NiV confirming the presence of the virus in the area. The outbreak was spread by person-to-person transmission. Risk of NiV infection in family caregivers highlights the need for infection control practices to limit transmission of potentially infectious body secretions

Detection of SARS Coronavirus in Patients with Suspected SARS

Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens

Genetic Characterization of Nipah Virus, Bangladesh, 2004

Until 2004, identification of Nipah virus (NV)-like outbreaks in Bangladesh was based on serology. We describe the genetic characterization of a new strain of NV isolated during outbreaks in Bangladesh (NV-B) in 2004, which confirms that NV was the etiologic agent responsible for these outbreaks

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

Severe Acute Respiratory Syndrome–associated Coronavirus Infection

Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare

Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection