H5N1

Factors associated with progression to death in patients with Lassa fever in Nigeria

Via The Lancet Infectious Diseases: Factors associated with progression to death in patients with Lassa fever in Nigeria: an observational study. The summary:

Background 

Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood. We aimed to determine host protein biomarkers capable of determining disease outcome. 

Methods 

In this observational study, we analysed left-over blood samples from patients who tested positive for Lassa fever at Irrua Specialist Teaching Hospital, Nigeria, between January, 2014, and April, 2017. We measured viral load, concentrations of clinical chemistry parameters, and levels of 62 circulating proteins involved in inflammation, immune response, and haemostasis. Patients with a known outcome (survival or death) and at least 200 μL of good-quality diagnostic sample were included in logistic regression modelling to assess the correlation of parameters with Lassa fever outcome. Individuals who gave consent could further be enrolled into a longitudinal analysis to assess the association of parameters with Lassa fever outcome over time. Participants were divided into two datasets for the statistical analysis: a primary dataset (samples taken between Jan 1, 2014, and April 1, 2016), and a secondary dataset (samples taken between April 1, 2016, and April 1, 2017). Biomarkers were ranked by area under the receiver operating characteristic curve (AUC) from highest (most predictive) to lowest (least predictive). 

Findings 

Of 554 patients who tested positive for Lassa fever during the study period, 201 (131 in the primary dataset and 70 in the secondary dataset) were included in the biomarker analysis, of whom 74 (49 in the primary dataset and 25 in the secondary dataset) had died and 127 (82 in the primary dataset and 45 in the secondary dataset) had survived. Cycle threshold values (indicating viral load) and levels of 18 host proteins at the time of admission to hospital were significantly correlated with fatal outcome. 

The best predictors of outcome in both datasets were plasminogen activator inhibitor-1 (PAI-1; AUC 0·878 in the primary dataset and 0·876 in the secondary dataset), soluble thrombomodulin (TM; 0·839 in the primary dataset and 0·875 in the secondary dataset), and soluble tumour necrosis factor receptor superfamily member 1A (TNF-R1; 0·807 in the primary dataset and 0·851 in the secondary dataset), all of which had higher prediction accuracy than viral load (0·774 in the primary dataset and 0·837 in the secondary dataset). Longitudinal analysis (150 patients, of whom 36 died) showed that of the biomarkers that were predictive at admission, PAI-1 levels consistently decreased to normal levels in survivors but not in those who died. 

Interpretation 

The identification of PAI-1 and soluble TM as markers of fatal Lassa fever at admission, and of PAI-1 as a marker of fatal Lassa fever over time, suggests that dysregulated coagulation and fibrinolysis and endothelial damage have roles in the pathophysiology of Lassa fever, providing a mechanistic explanation for the association of Lassa fever with oedema and bleeding. These novel markers might aid in clinical risk stratification and disease monitoring.

Three Brits brought back from Sierra Leone over Ebola-like Lassa fever fears

Via The Scotsman: Three Brits brought back from Sierra Leone over Ebola-like Lassa fever fears.

Three British nationals have been brought back to the UK from Sierra Leone for medical assessment after coming into close contact with two people diagnosed with Lassa fever.  

One of the two Dutch nationals who contracted the virus, whose symptoms are similar to Ebola, while working in the West African nation has died. 

Public Health England (PHE) said three British people who had stayed in Sierra Leone and had close contact with them have been repatriated by the UK Government to be medically assessed and treated, if required.  

The agency has also contacted another 15 British nationals who had contact with the Dutch Lassa fever cases to monitor them.

Dr Jake Dunning, head of emerging infections and zoonoses at PHE, said: "It is important to emphasise that Lassa fever does not spread easily between people and the overall risk to the public is very low. "There are no confirmed cases of Lassa fever in the UK. 

"PHE is monitoring those who have had close contact with the foreign national to assess them as necessary and provide advice. 

"PHE and the NHS have well established and robust infection control procedures for dealing with cases of imported infectious disease and these will be strictly followed." 

There is no approved vaccine for Lassa fever, whose symptoms are similar to Ebola. 

After starting as a fever with aches and pains, it can progress to headache, vomiting and diarrhoea. According to the World Health Organisation, severe cases can cause victims to bleed from the mouth and nose. 

Like Ebola, Lassa fever can be spread through contact with the bodily fluids of sick people. 

Humans can also contract it from eating food that has been tainted by the urine or faeces of rodents.  

PHE said most people with Lassa fever make a full recovery, although severe illness can occur.

Lassa virus circulating in Liberia: A retrospective genomic characterisation

Via The Lancet Infectious Diseases: Lassa virus circulating in Liberia: a retrospective genomic characterisation. The summary:

Background 

An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. 

Methods 

Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. 

Findings 

The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300–350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. 

Interpretation 

The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics.

A new vaccine against Lassa fever

Via Pathogens, an encouraging report: A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge. The abstract:

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. 

Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. 

Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. 

This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.

Liberia declares health emergency as Lassa fever deaths rise to 21

Via Xinhua: Liberia declares health emergency as Lassa fever deaths rise to 21.

MONROVIA, Sept. 2 (Xinhua) -- Health authorities in Liberia on Monday declared a health emergency following the outbreak of Lassa fever which has so far claimed 21 lives this year. 

Liberia's chief medical officer Francis Kateh told reporters here that four counties had been so far affected by the disease, a viral hemorrhagic fever caused by the Lassa virus.  

"What is more concerning to us is the fact that when health workers that have the authority and have been trained to identify and take care of others are being infected, then that escalates the process to another level," said Kateh.  

He said a laboratory technician has also been identified among those killed by the outbreak between January 1 and August 25.  

The disease has so far spread across the counties of Nimba, Grand Bassa, Bong, and Grand Kru, the official noted, saying the case fatality rate is 36 percent, and that 56 percent confirmed cases were men.  

The situation is alarming and becoming a major issue of concern because it is growing out of the areas identified as "Lassa Belt" in the country.  

Usually, the Lassa fever escalates during the dry season in the west African country.  

Director-General of the National Public Health Institute Tolbert Nyenswah described the disease as "second Ebola" and called for tougher measures to contain it. 

"The Lassa is second Ebola, no need to hide the information. It's better we put the information out there; the situation we're dealing with and how we can prevent it," said Nyenswah.  

"It's important that we raise this and let the general public know that there are a couple of things they can do," he added.  

Humans usually become infected with the Lassa virus from exposure to urine or feces of infected mastomys rats. 

Other than common preventive measures such as washing hands regularly, the World Health Organization has recommended keeping cats.

An experimental Ebola cure may also protect against Nipah virus

Via The New York Times, news of a veritable panacea: An Experimental Ebola Cure May Also Protect Against Nipah Virus. Excerpt:

An experimental drug has protected monkeys against infection with Nipah virus, a lethal disease and emerging pandemic threat for which there is no approved vaccine or cure, scientists reported on Wednesday.  

The antiviral drug, remdesivir, is also being tested against the Ebola virus in the outbreak now underway in the Democratic Republic of Congo.  

The only current treatment for Nipah virus infection is a monoclonal antibody that is still experimental; it was tested during an outbreak in India last year. 

In the new trial, eight African green monkeys were given lethal doses of Nipah virus. Half of them later got intravenous remdesivir. All four monkeys that got the drug survived; the four that did not died within eight days.

If the drug wins approval for use against Nipah, “it will give us an extra treatment that could be used relatively quickly,” said Emmie de Wit, a virologist at the National Institute of Allergy and Infectious Diseases and one of the study’s lead authors. “The average person who reaches a hospital dies within two days, so it’s hard to protect them once they’re infected.” 

Ebola and Nipah belong to different viral families, but remdesivir — made by Gilead Sciences and also known as GS-5734 — appears effective against both.

In mice or cells cultivated in the laboratory, the drug has also shown some effectiveness against two other pandemic threats: Lassa fever and MERS coronavirus. It is also effective against respiratory syncytial virus, which infects children all over the world.  

Although the outer shells of all these viruses are very different, their polymerases — the genome-copying enzyme that remdesivir targets — are similar, Dr. de Wit explained.  

The new study, done jointly by the N.I.A.I.D. and the Centers for Disease Control and Prevention, was published in Science Translational Medicine.

Measures to control protracted large Lassa fever outbreak in Nigeria, 1 January to 28 April 2019

Via Eurosurveillance: Measures to control protracted large Lassa fever outbreak in Nigeria, 1 January to 28 April 2019. The abstract:

Lassa fever cases have increased in Nigeria since 2016 with the highest number, 633 cases, reported in 2018. From 1 January to 28 April 2019, 554 laboratory-confirmed cases including 124 deaths were reported in 21 states in Nigeria. A public health emergency was declared on 22 January by the Nigeria Centre for Disease Control. 

We describe the various outbreak responses that have been implemented, including establishment of emergency thresholds and guidelines for case management.

Nigeria mulls healthcare fund for Lassa fever patients

Via Xinhua: Nigeria mulls healthcare fund for Lassa fever patients. Excerpt:

Nigerian health authorities have said the country will soon launch a healthcare fund to cater for patients with confirmed cases of Lassa fever and ensure that money does not become a hindrance in accessing treatment.  

The Nigeria Center for Disease Control (NCDC) confirmed this in a statement reaching Xinhua in Abuja on Monday, saying this process is at the heart of discussion at all levels of government in the country at the moment. 

"We are making plans through the Basic Primary Healthcare Provision Fund, the new funding instituted by the federal government, to cover the cost of treatment of confirmed cases of Lassa fever patients," said the statement by Chikwe Ihekweazu, head of the NCDC. 

"The aim is to make sure that ability to pay is not a barrier to accessing the treatment for public health diseases such as Lassa fever," the disease control chief said.  

Pending the take-off of the healthcare fund, the Nigerian government is working to reduce the burden of Lassa fever treatment on patients, he said. 

Experts say the cost of Lassa treatment is very high. Ribavirin, a potent antiviral medication, is known to be a very expensive drug in the country.  

"But we want to ensure that every confirmed case gets the drug free," Ihekweazu said. "No matter how accessible you can make the treatment of Lassa, it is always cheaper to prevent it."

Lassa fever outbreak: NCDC confirms 23 new cases, four deaths

Via Vanguard: Lassa fever outbreak: NCDC confirms 23 new cases, 4 deaths. Excerpt:

The Nigeria Centre for Diseases Control, NCDC, has confirmed 23 new cases of Lassa fever including 4 deaths. 

According to the report released on its website for the week 11th ending 17th March, 2019, the new cases were reported from nine states, namely Edo with eight cases; Ondo with four cases; Ebonyi with three cases; Bauchi recorded three cases; Taraba, Enugu, Benue, and Kebbi state have one case each. 

Edo state recorded two deaths while Benue and Bauchi state recorded one death each. 

From 1st January to 17th March, 2019, a total of 1,801 suspected cases have been reported, out of which 495 were confirmed positive, 15 probable and 1277 negative. 

Since the onset of the 2019 outbreak, there have been 114 deaths in confirmed cases with case fatality ratio in confirmed cases at 23.0 percent.

Nigeria: Containing the Lassa fever spread

Via Punch, an editorial: Containing the Lassa fever spread. Excerpt:

NIGERIA is once again at the receiving end of the yearly offensive of the deadly Lassa fever disease. But, working in close collaboration with the World Health Organisation and other experts already in the country, she is slowly but surely rolling back the spread of the current outbreak, which has already claimed scores of lives. Thereafter, there will be the usual lull before the storm, following which there will be an eruption of yet another round of the viral haemorrhagic fever, when deaths will be reported again in nearly all parts of the country. 

This has been the steady and unaltered pattern over the years. Since the disease was first described in the 1950s and the virus causing it identified in 1969 in Lassa town in Borno State, not much has been achieved in terms of halting its rampant spread. Rather, efforts have been concentrated mainly on the management of the sick, which has made it possible for the disease to continue to spread to new areas of the country. It has not come as a surprise that Lassa fever has become endemic in many parts of the country and beyond.  

This year alone, the outbreak has been reported in more than 33 states of the federation, according to the Nigeria Centre for Disease Control. This is barely short of overwhelming the entire country and it is difficult to say how far it would eventually go before grinding to a halt. States where cases have been reported so far include Ondo, Bauchi, Cross River, Kebbi, Ebonyi, Plateau, Delta Imo, Adamawa, Kwara and Benue. No official reason has been given for the alarming spread, but it may not be unconnected with the high rate of human mobility that occurred across the country as a result of the just-concluded elections. It is possible that some infected people may have taken it to other parts of the country as they travelled. 

An acute viral haemorrhagic fever, just like the deadly Ebola that is currently ravaging the Congo Democratic Republic, Lassa fever is primarily contracted through exposure to the urine or faeces of a species of rat called multimammate or Mastomys rat. It is also possible to be infected by coming in contact with the blood, urine, faeces and body secretions of an infected person. The outbreak is usually common in dry seasons when these rats find their way into people’s homes in search of food after human activities such as bush burning or clearing dislodge them from their natural habitat.   

Over time, the concerted efforts of humanity have led to the eradication of some very deadly diseases, especially smallpox, which used to be a prolific killer across the world, including Europe. Right now, the world is also on the cusp of ending the scourge of poliomyelitis, once a global child killer, whose presence has now been confined to just three countries, Pakistan, Nigeria and Afghanistan. Perhaps the same can be done of Lassa fever, a zoonotic disease that can also be spread from man to man. Even when it is not possible to completely eradicate it, a conscious effort should be made to limit its unbridled spread.  

Beyond Nigeria, Lassa fever is known to be endemic in the West African states of Benin, Ghana, Guinea, Liberia, Mali and Sierra Leone, among others. In fact, more countries are likely to start experiencing outbreaks if efforts are not shifted from mere treatment to possible eradication or rigorous containment. This can be done by focusing on the elimination of rats from homes and making it difficult for them to find their way back.  

When symptoms such as fever, general weakness, headache, sore throat, muscle and chest pains, nausea, diarrhoea, vomiting and abdominal pain are noticed, it is important to visit the hospital promptly, where proper diagnosis can be done. This will avoid its being mistaken for shigellosis, malaria, typhoid fever, Ebola virus disease and yellow fever, which all seem to share symptoms. Experts also recommend contact tracing, a common practice in tracking Ebola, to be able to limit the spread.