H5N1

Covert COVID-19 and false-positive dengue serology in Singapore

Via The Lancet Infectious Diseases: Covert COVID-19 and false-positive dengue serology in Singapore.

Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features. We describe two patients in Singapore with false-positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19. 

The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 109/mL) and a normal chest radiograph. He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary health-care clinic with persistent fever, worsening thrombocytopenia (89 × 109/mL), and new onset lymphopenia (0·43 × 109/mL). A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive. The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR, and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive.  

The second case is a 57-year-old woman with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 13, 2020, with fever, myalgia, a mild cough of 4 days, and 2 days of diarrhoea. She had thrombocytopenia (92 × 109/mL) and tested positive for dengue IgM (SD Bioline). She was discharged with outpatient follow up for dengue fever. She returned 2 days later with a persistent fever, worsening thrombocytopenia (65 × 109/mL), and new onset lymphopenia (0·94 × 109/mL). Liver function tests were abnormal (aspartate aminotransferase 69 U/L [reference range 10–30 U/L], alanine aminotransferase 67 U/L [reference range <55 U/L], total bilirubin 35·8 μmol/L [reference range 4·7–23·2 μmol/L]). Chest radiography was normal and she was admitted for dengue fever. She remained febrile despite normalisation of her blood counts and developed dyspnoea 3 days after admission. She was found to be positive for SARS-CoV-2 by RT-PCR from a nasopharyngeal swab. A repeat dengue test (SD Bioline) was negative and an earlier blood sample also tested negative for dengue by RT-PCR. The initial dengue IgM result was deemed to be a false positive. 

Failing to consider COVID-19 because of a positive dengue rapid test result has serious implications not only for the patient but also for public health. Our cases highlight the importance of recognising false-positive dengue serology results (with different commercially available assays) in patients with COVID-19. We emphasise the urgent need for rapid, sensitive, and accessible diagnostic tests for SARS-CoV-2, which need to be highly accurate to protect public health.

ECDC: Communicable disease threats report, 16-22 February 2020, week 8

ECDC has published Communicable disease threats report, 16-22 February 2020, week 8. The summary:

The ECDC Communicable Disease Threats Report (CDTR) is a weekly bulletin for epidemiologists and health professionals on active public health threats. This issue covers the period 16-22 February 2020 and includes updates on chikungunya, dengue, Ebola virus disease, COVID-19, polio, and seasonal influenza.

At least 78 children died of dengue related illness in Yemen

Via ReliefWeb, a report from Save the Children: At least 78 children died of dengue related illness in Yemen. Excerpt:

Save the Children warns of an epidemic, as 52,000 suspected cases are recorded in the country.  

Seventy-eight children under 16 have already died in the outbreak of Dengue related illness in Yemen[i], with more than 52,000 suspected cases being recorded across the country. Save the Children warned this could signal the start of an epidemic. 

Heavy rainfall, coupled with the ongoing conflict, is disrupting clean water supplies. Because of the disruptions, people use water basins to collect rainwater and these uncovered water sources combined with the rain have contributed to the spread of mosquitoes in the affected areas, resulting in an upsurge in suspected dengue cases. 

If measures are not urgently put in place to strengthen the health care system so that cases can be detected early, the death total which reached 192 people by the end of 2019, could increase sharply. Cases have been recorded in almost all governorates in Yemen with the most affected being Hodeidah and Aden which recorded more than 60% of the deaths in the country.  

Save the Children Hodeidah Field Manager Mariam Aldogani, herself recovering from dengue fever, said: 

“Hodeidah has the second highest death rate in the country with 62 adult and children deaths in 2019. We have never seen anything like this before. More than 40 of our staff including their families have been affected by the fever. We are getting reports of deaths on a daily basis in remote areas of the governorate. Some of our health facilities are working 24 hours a day and last week one of our facilities recorded 30 cases in one day, most of which were children. 

“The economic situation in the country has not made it any better for people. Parents cannot afford to bring their children to the hospital or to buy the medication. Hospitals are full, and some patients are kept in hospitals having to lay on the floor because of a bed shortage. It’s really bad. Children as young as eight months have not been spared by the dengue fever. In some of the hospitals all you can hear are children crying in pain. We are currently supporting 48 health facilities in Hodeidah which recorded more than 6000 dengue fever suspected cases in 2019.”  

Save the Children's health centres have been receiving many cases of children suffering from dengue, and its teams on the ground are diagnosing and treating patients whilst referring the most severe cases.

Climate change, crime and political chaos: A deadly mix in Honduras dengue epidemic

Via The New York Times: Climate Change, Crime and Political Chaos: A Deadly Mix in Honduras Dengue Epidemic. Excerpt:

CHOLOMA, Honduras — More than 400 people died this year as one of the worst dengue epidemics on record swept through Central America — a type of outbreak that some scientists and public health officials are warning is likely to become more frequent and more widespread because of climate change.  

But while climate change is threatening to increase the spread of dengue worldwide by expanding the range of the mosquitoes that carry the virus, the disease has already found an especially fertile breeding ground in Honduras, for reasons that go beyond the environment.  

In Honduras, which accounted for more than 40 percent of the dengue deaths in Central America this year, according to the Pan American Health Organization, the effects of climate change have been compounded by government dysfunction, political tumult and public apathy. 

Dengue has hit the country hard. This year, it had more than 107,000 cases of the viral disease — more than 13 times the number recorded last year — and at least 175 deaths. In 2018, only three people in Honduras died from the disease, according to the Pan American Health Organization.

Honduras’s notorious criminality has worsened matters, too, as public health teams, already stretched thin by budget cuts and a lack of trained personnel, have been blocked by gangs from entering some of the most severely afflicted neighborhoods to educate residents and fumigate against mosquito infestations.  

Dengue is transmitted to humans by a type of mosquito called Aedes, which thrives in urban areas of the world’s tropical and subtropical regions. Tens of millions of cases occur each year in more than 100 countries, and symptoms may include fever, internal bleeding and shock. Inadequately treated, the illness can quickly kill. 

In Honduras, health officials trace the start of the current epidemic to the fall of 2018. The number of incidents then rose sharply during the first half of 2019, hitting a peak this summer before falling off as the year ended. A nationwide health emergency declared in July by the administration of President Juan Orlando Hernández remains in effect.  

The outbreak struck during a time of political turbulence in Honduras, with violent street protests against Mr. Hernández and calls for his ouster. Some of the protests have been driven by fears the government planned to privatize the health and education sectors. 

The nation also suffers from high murder rates and widespread poverty, which have combined to drive tens of thousands of Hondurans in recent years to emigrate, with many trying to make it to the United States.  

The dengue outbreak has met little resistance from a public health system gutted by budget cuts and pervasive corruption, analysts and officials said.  

“It’s a collapsed system, an inefficient system,” said Ismael Zepeda, an economist with Fosdeh, a research group in Tegucigalpa, the capital.

Mosquito sterilization offers new opportunity to control chikungunya, dengue, and Zika

WHO has published Mosquito sterilization offers new opportunity to control chikungunya, dengue, and Zika. Excerpt:

A technique that sterilizes male mosquitoes using radiation will soon be tested as part of global health efforts to control diseases such as chikungunya, dengue, and Zika.  

The Sterile Insect Technique (SIT) is a form of insect birth control.  The process involves rearing large quantities of sterilized male mosquitoes in dedicated facilities, and then releasing them to mate with females in the wild. As they do not produce any offspring, the insect population declines over time. 

The Special Programme for Research and Training in Tropical Diseases (TDR) and the International Atomic Energy Agency (IAEA), in partnership with the Food and Agriculture Organization of the United Nations (FAO), and WHO have developed a guidance document for countries that have expressed interest in testing the Sterile Insect Technique (SIT) for Aedes mosquitoes.  

Half the world at risk of dengue 

“Half the world’s population is now at risk of dengue,” said Dr Soumya Swaminathan, WHO Chief Scientist. “And despite our best efforts, current efforts to control it are falling short. We desperately need new approaches and this initiative is both promising and exciting.”  

In recent decades, the incidence of dengue has increased dramatically due to environmental changes, unregulated urbanization, transport and travel, and insufficient sustainable vector control tools and their application.   

Dengue outbreaks are currently occurring in several countries, notably on the Indian sub-continent. Bangladesh is facing the worst outbreak of dengue since its first recorded epidemic in 2000. The South Asian nation has seen the number of cases rise to over 92,000 since January 2019, with daily admissions peaking at more than 1,500 new dengue patients in hospitals in recent weeks and is one of the countries to express interest in the Sterile Insect Technique. 

Diseases transmitted by mosquitoes such as malaria, dengue, Zika, chikungunya, and yellow fever account for about 17% of all infectious diseases globally, claiming more than 700,000 lives each year, and inflicting suffering on many more. The 2015 outbreak of Zika in Brazil was linked to an increase in the number of babies being born with microcephaly. 

Experiment with genetically modified mosquitos backfires in Brazil

Via brazzil.com, a September 21 report: Experiment with Genetically-Modified Mosquitoes Backfires in Brazil. Excerpt:

An attempt to contain the populations of the yellow fever mosquito Aedes aegypti in Brazil may have failed. It appears that gene mutations have been transferred to the local population. 

The British company Oxitec had released about 450,000 male mosquitoes every week in the city of Jacobina in the Bahia region with official permission over a period of 27 weeks. The experiment was designed to control the infectious diseases dengue, Zika and yellow fever. 

The gene modification called OX513A in the mosquitoes was designed in such a way that the first descendant generation of the mosquitoes, known as F1, would not reach the adult stage and thus not be able to reproduce. 

The hope of the Ministry of Health was to reduce mosquito populations by 90 percent. And this worked well during the field trial. About 18 months after the end of the experiment, the mosquito population returned to what it had been before. 

The gene modification of the released mosquitoes also produced a fluorescent protein that made it possible to distinguish the first F1 generation from other mosquitoes.  

Researchers at Yale University have examined the mosquitoes found in the region for their genetic alterations one year after the release, as well as 27 to 30 months after the release.  

They came to the conclusion that parts of the gene alteration had unexpectedly migrated into the target population of local mosquitoes. 

Gene Modification Passed On 

In the different samples, between 10 and 60 percent of the mosquitoes carried corresponding changes in the genome. The study was published in Nature: Scientific Reports on September 10.  

If the field trial had taken place as originally predicted, the gene modification would not have been allowed to migrate into the mosquito populations because the offspring of the mosquitoes originally released would not have been able to reproduce. 

However, it was already known from previous laboratory experiments that a small proportion of about three to four percent of OX513A descendants can reach adulthood; the scientists had assumed that those would be too weak to reproduce.  

The authors of the study found that the GM mosquitoes were equally suitable as carriers of infectious diseases as the mosquitos were before the experiment. 

Critics Take the Floor  

The Yale research team around Jeffrey Powell warns that the newly formed mosquito population could possibly be more robust than the mosquitoes were before.  

The authors conclude: “These results demonstrate the importance of having in place a genetic monitoring program during releases of transgenic organisms to detect unanticipated consequences”. 

Biologists critical of genetic engineering go one step further with their criticism, among them the Brazilian biologist José Maria Gusman Ferraz: “The release of the mosquitos was carried out hastily without any points having been clarified,” Ferraz told the newspaper Folha de S. Paulo.

ECDC rapid risk assessment: Autochthonous cases of dengue in Spain and France

ECDC has published Rapid risk assessment: Autochthonous cases of dengue in Spain and France. Excerpt from the executive summary:

On 16 September 2019, the Catalonian Public Health Agency confirmed an autochthonous case of dengue in a resident of Barcelonès county in Catalonia, Spain. The case had onset of symptoms on 6 September 2019, with no recent travel history outside of Spain. Dengue infection was confirmed by the Catalan reference laboratory for arboviruses and the Spanish national reference laboratory for arboviruses. Epidemiological investigations in Catalonia are ongoing, and further cases may be detected. According to national authorities, control measures are being implemented.  

On 20 September 2019, the regional public health agency of Provence-Alpes-Côte d’Azur region reported a locally acquired confirmed case of dengue in a resident of the city of Vallauris in the department of Alpes-Maritimes. The case had onset of symptoms on 30 August and did not report any recent travel history outside of mainland France. This case was laboratory-confirmed by the French National Reference Centre for Arboviruses (NRC, Marseille). Door-to-door active case finding was implemented around the home of the autochthonous case on 19 September. Four additional cases in the direct vicinity were identified. 

In addition, the regional public health agency of Auvergne-Rhône-Alpes reported a locally acquired probable dengue case in a resident of Caluire-et-Cuire − a suburban area of the city of Lyon − in the Rhône department. The case had onset of symptoms on 14 July 2019. For this case, NRC laboratory confirmation is still pending. The case did not report any recent travel outside of mainland France. 

To date, these three events should be considered as independent because epidemiological investigations could not identify any epidemiological links between them.

How mosquitos shaped humanity

The Tyee has published my review of Timothy C. Winegard's new book The Mosquito: A Human History of Our Deadliest Predator: How Mosquitos Shaped Humanity. Excerpt:

The mosquito, Timothy Winegard argues, has killed half of all humans who ever lived — 52 billion of us.  

Add all the other mammals and birds it preys upon, and it is clearly the planet’s apex predator. After millions of years in that role, however, the mosquito could be overthrown by its human victims’ ingenuity. 

Winegard’s research makes this an important book for anyone concerned with mosquito-borne diseases. As his subtitle suggests, he focuses on how mosquitos have shaped human history. And they have even shaped us genetically. Humans evolved in an Africa where mosquitos had prospered for millions of years. They preyed on our ancestral species, and by the time modern humans emerged we had even evolved sickle-cell anemia as a defensive measure against malaria.  

Modern humans who left Africa took malaria and other mosquito-borne diseases with them, infecting the mosquito populations they encountered. Migration and settlement must have come at a terrible price in deaths and sickness. The survivors, after repeated infections, might become “seasoned” — able to recover from malaria relatively easily. But if they moved into a new region, an unfamiliar strain of malaria might still finish them off.

Cross-protection of dengue virus infection against congenital Zika syndrome, northeastern Brazil

Via Emerging Infectious Diseases: Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil. The abstract:

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)–mediated immune enhancement may promote CZS development. 

In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case–control framework in northeastern Brazil among 29 Zika virus–seropositive mothers of neonates with CZS and 108 Zika virus–seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. 

Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

ECDC: CDTR, 11-17 August, week 33

ECDC has published Communicable disease threats report, 11-17 August 2019, week 33. The summary:

This issue covers the period from 11 to 17 August 2019 and includes updates on Ebola virus disease in the Democratic Republic of the Congo, chikungunya virus disease and dengue, monitoring environmental sustainability of Vibrio growth in the Baltic Sea, the mass gathering of the Hajj in Saudi Arabia, tularaemia in Sweden and West Nile virus infection.