H5N1

A hat-tip to the World Mosquito Program

While the pandemic has taken up most of our time, we really need to pay some attention to other global health problems as well. Mosquito-borne diseases are as urgent as ever.From the website of the World Mosquito Program:

The World Mosquito Program uses safe and natural bacteria called Wolbachia to prevent the transmission of mosquito-borne viral diseases such as dengue, Zika, chikungunya and yellow fever.  

Since releasing the first Wolbachia mosquitoes in 2011, evidence from international pilot studies shows that we can use Wolbachia more broadly to decrease the risk of Aedes aegypti mosquitoes transmitting viruses. Multiple trials in various locations demonstrate that our method is a safe and effective way to help prevent the spread of diseases across entire cities and regions.  

We continue to rapidly expand our operations by building partnerships with local governments and communities around the world who are embracing our Wolbachia method.  

 The World Mosquito Program currently has two regional hubs – our Asia hub in Ho Chi Minh City, Vietnam and our Oceania hub, based at Monash University in Melbourne, Australia. We are in the process of establishing our third Americas hub in Panama. These hubs support projects in their respective regions and contribute to core global operations. 

We have projects operating in 12 countries and our Wolbachia-carrying mosquitoes have reached 5 million people as at December 2019. 

In areas where Wolbachia is self-sustaining at a high level, monitoring shows that virus transmission is greatly reduced. Our measured impact is consistent with local elimination of disease. We are committed to improving health conditions and strengthening the capacity of local communities around the world to help reduce the threat of mosquito-borne diseases.  

Through collaboration and innovation, we can make a difference to millions of lives.

The Program has asked me to get the word out about a Twitter event on October 12 at which Professor Scott O'Neill, director of the Program, will answer questions. I'm happy to oblige. You can post your questions ahead of time at #Releasing Hope.

WHO: Yellow fever – Bolivarian Republic of Venezuela

WHO has published Yellow fever – Bolivarian Republic of Venezuela. Excerpt:

On 13 November 2019, the Venezuela International Health Regulations (IHR) National Focal Point (NFP) and the Venezuela PAHO/WHO Country Office shared information about a confirmed case of yellow fever in Bolivar State. 

The case-patient is a 46-year-old male resident of the municipality of Gran Sabana, Bolivar State. He was in the locality of Uriman municipality of Gran Sabana within the 19 days prior to the onset of symptoms. Symptom onset was on 14 September 2019, and included fever, chills, nausea, vomiting, epistaxis, petechiae, and diarrhoea. On 26 September 2019, he visited a public hospital in the municipality of Heres where his condition deteriorated, with moderate dehydration, bleeding from the gums, jaundice, choluria, abdominal pain, and hepatomegaly. As of 13 November 2019, the patient remains hospitalized with chronic renal failure and moderate anaemia.  

On 26 September 2019, the first serum sample was sent to the National Reference Laboratory, the National Institute of Hygiene “Rafael Rangel” per its acronym in Spanish, IHRR1 , in Caracas. On 13 November 2019, the sample tested positive for yellow fever by reverse-transcriptase polymerase chain reaction (RT-PCR), and negative for dengue on 14 November 2019 by RT-PCR. On 10 October 2019, a second serum sample was taken and sent to the IHRR; for which the results are still pending. 

Most of the territory of Venezuela is considered as at risk for sylvatic yellow fever and this case marks the first confirmed autochthonous case of yellow fever diagnosed in Venezuela since 2005.  

Public health response 

A joint investigation team (WHO Country Office and the Venezuela Ministry of Health) was deployed on 12 November to characterize the risk and develop the response plan. PAHO Immunizations (IM) Unit along with the Revolving Fund have secured a donation of 571,000 doses of yellow fever vaccine from UNICEF that arrived in the country at the end of October (for more information, please see here).  

The local public health authorities have strengthened the active and passive epidemiological surveillance activities in humans and non-human primates. Additionally, strategic vaccination activities have been planned.

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.

WHO: Yellow fever – Nigeria

WHO has published Yellow fever – Nigeria. Excerpt:

On 16 July 2019, the Ebonyi State Ministry of Health received information about suspected yellow fever cases in Ndingele ward, Izzi Local Government Area (LGA), Nigeria. The cases had symptoms of fever and jaundice, reported with onset since May 2019. As of 30 August 2019, a total of 84 suspected yellow fever cases, including 26 deaths (case fatality ratio: 31 %), have been reported across nine LGAs within Ebonyi State. 

Of the suspected yellow fever cases, fifty-five per cent (46/84) are male. The most affected age group is 0-9 years (28 cases, 33%), followed by age groups 20-29 years and above 30 years each with 20 cases (24%). The 10-19 year age group has the least number of cases (16 cases, 19%). Seventy-nine per cent of suspected cases (66/84), including seven confirmed cases positive by real-time polymerase chain reaction (RT-PCR) are reported from Izzi LGA which is located in the north-eastern part of the State, bordered with Cross River State in the east, and Benue State in the north. One case has been confirmed in an international worker involved in the extractive industry in Izzi LGA, and residing in adjacent Abakiliki LGA (an urban centre in the State). 

The assessment conducted by the LGA rapid response team (RRT) and national agencies found low vaccination coverage and poor routine immunization documentation. Community surveys were conducted and yellow fever vaccination coverage was estimated to be 56% (64% for children aged less than 5 years and 48% for those older than 5 years of age). Though Nigeria introduced routine vaccination for yellow fever into the immunization schedule in 2004, most adults remain susceptible and overall population immunity is low. Although no entomological studies were conducted at the time, the geography and vegetation of the affected state is compatible with the presence of the Aedes mosquitoes, as illustrated by the transmission patterns.  

Since September 2017, when the Nigeria Centre for Disease Control (NCDC) informed WHO of a confirmed case of yellow fever in Kwara State, Nigeria has been responding to successive yellow fever outbreaks over a wide geographic area. Following the country’s official notification to WHO (via the International Health Regulations, 2005) on 15 September 2017 of the resurgence in yellow fever outbreaks, suspect cases have been reported from all States and the Federal Capital Territory (FCT), and outbreak responses to protect over 10 million people have occurred in select areas in 13 States. Efforts to strengthen surveillance are ongoing.  

From 1 January through 31 July 2019, over 2,000 suspected yellow fever cases have been reported in 506 LGAs from all 36 States including the Federal Capital Territory (FCT) of Nigeria. 

Public health response 

The response to the ongoing outbreak is being coordinated by the Nigerian Centre for Disease Control (NCDC) at the national level through a multi-agency, multi-partner Incident Management System (IMS). The public health emergency operations centre (PHEOC) located at the Ebonyi State Ministry of Health has been activated to monitor the outbreak. Active case finding, case management, risk communication and community engagement have been implemented in affected LGAs. 

An International Coordination Group (ICG) request for reactive vaccination in the affected area has been approved covering three LGAs in Ebonyi, two LGAs in Benue State and one LGA in Cross River State targeting a population of about 1.64 million people aged 9 months to 44 years in Ebonyi and Benue States, and aged 1-6 years in Yala LGA of Cross River State.  

Routine yellow fever vaccination was introduced to Nigeria’s Expanded Programme on Immunization (EPI) in 2004, but the overall population immunity in areas affected by the current outbreak remains below recognized herd immunity thresholds. 

A four-year (2018-2021) national yellow fever Preventive Mass Vaccination Campaign (PMVC) plan supported by GAVI and partners is currently being implemented. By 2024, it is anticipated that all the States in Nigeria will have undergone campaign activities to protect at-risk populations against yellow fever.

Genomic surveillance of yellow fever virus epidemic waves in São Paulo, Brazil, 2017 – 2018

Via bioRxiv: Genomic Surveillance of Yellow Fever Virus Epidemic Waves in São Paulo, Brazil, 2017 – 2018. The abstract:

São Paulo (SP), a densely populated state in southeast Brazil that contains one of the world's largest urban regions, has experienced its largest yellow fever virus (YFV) outbreak in decades. Surveillance in non-human primates (NHP) is important in order to detect YFV early during an epidemic or epizootic, to quantify the magnitude of the outbreak in NHP, and to evaluate the risk of YFV spillover infection in human populations. 

To better understand the genetic diversity and spatial distribution of YFV during the current outbreak in southeast Brazil, we generated 46 new virus genomes from YFV positive cases identified in 18 different municipalities in SP, mostly sampled from non-human primates between April 2017 and February 2018. 

Our data show that most NHP cases in São Paulo state were likely caused by the introduction of a single YFV lineage from Minas Gerais to São Paulo. Phylogenetic and phylogeographic analyses of these data indicate that YFV spread southwards from Minas Gerais into São Paulo state at a typical rate of <1km per day. 

These results shed light in the sylvatic transmission of yellow fever in highly fragmented forested regions in São Paulo state and highlight the importance of continued operational research and surveillance of zoonotic pathogens in sentinel populations.

WHO: Yellow fever – Brazil

WHO has published Yellow fever – Brazil. Excerpt:

In Brazil, seasonal increases of yellow fever have historically occurred between December and May. During the 2016-2017 and 2017-2018 seasons, the number of yellow fever cases was much larger than in previous years (Figures 1 & 2). The increase in cases was partly due to a geographical expansion of the areas affected by yellow fever to include areas previously considered risk-free (Figure 3).  

In the current 2018- 2019 season (July 2018 to March 2019), a total of 75 confirmed human cases, including 17 deaths (case fatality rate = 23%), have been reported in Brazil in the states of São Paulo (62), Paraná (12), and Santa Catarina (1). Of these cases, 88% (66/75) are males, the median age is 43 years, and 71% (53/75) are rural workers.  

In the state of São Paulo, the municipalities that reported confirmed cases are: Eldorado (16), Iporanga (15), Barra do Turbo (6), Cajati (5), Cananeia (4), Jacupiranga (4), Pariquera-açu (4), Juquia (1), Registro (1), Serra Negra (1), Sete Barras (1), Ribeira (1), Vargem (1) and for 2 cases, the municipalities were unknown. In the state of Paraná, the municipalities with confirmed cases are: Guaraqueçaba (2), Antonina (2), São José dos Pinhais (2), Morretes (1), Andrinópolis (3), Paranaguá (1) and in 1 case, the municipality is unknown. The state of Santa Catarina reported one fatal confirmed human case of yellow fever. The case is a 36-year-old male, without vaccination, whose municipality is unknown. 

Likewise, in the same reporting period of July 2018 to March 2019, 33 confirmed epizootics were reported in five federal states: São Paulo (20), Rio de Janeiro (8), Minas Gerais (1), Mato Grosso (2), and Paraná (2). In the four weeks preceding this report, epizootics have been confirmed in São Paulo and Paraná states.

PAHO epidemiological update - yellow fever - 6 March 2019 - Brazil

Via ReliefWeb, a PAHO report: Epidemiological Update - Yellow Fever - 6 March 2019 - Brazil. Click or tap through for information on Bolivia and Peru as well. Excerpt:

Brazil is currently in the period historically recognized as having the highest transmission (seasonal period), which occurs between December and May. The expansion of the historical area of yellow fever transmission to areas previously considered risk-free led to two waves of transmission (Figure 1), one during the 2016-2017 seasonal period, with 778 confirmed human cases, including 262 deaths, and another during the 2017-2018 seasonal period, with 1,376 confirmed human cases, including 483 deaths.  

In the current seasonal period (2018-2019), 50 confirmed human cases, including 12 deaths, have been reported in the states of São Paulo (46 cases) and Paraná (4 cases). In São Paulo, the municipalities considered as probable sites of infection are: Eldorado (15 cases), Iporanga (12 cases), Cananeia (4 cases), Cajati (3 cases), Barra do Turbo (2 cases), Jacupiranga (2 cases), Caraguatatuba (1 case), Registro (1 case), Pariquera-açu (1 case), Serra Negra (1 case), Sete Barras (1 case), Juquiá (1 case), Vargem (1 case), and the probable site of infection for 1 case remains under investigation. With the exception of Serra Negra, Vargem (bordering the state of Minas Gerais), and Caraguatatuba, the rest of the municipalities are in the southern part of the state of São Paulo. 

The probable sites of infection for the 4 confirmed cases in the state of Paraná are Guaraqueçaba (2 cases) and Adrianópolis (2 cases) municipalities. 

Among confirmed cases, 90% (45/50) are male and the median age is 43 years (range 18 to 87 years). All of the deaths occurred among confirmed cases in the state of São Paulo. 

To date, the number of human cases reported during the current 2018-2019 seasonal period is substantially lower than observed during the two previous seasonal periods, when the number of cases surpassed that which was reported in several decades. Nonetheless, the occurrence of cases and epizootics in the southern part of the state of São Paulo and in the state of Paraná indicates the progression of transmission towards the Southeast and South regions of the country (Figure 2), with the possibility of reaching bordering countries such as Argentina and Paraguay.  

In the 2018-2019 seasonal period, most of the confirmed epizootics (90%) were reported in the Southeast Region of the country (27/30). In epidemiological week (EW) 4 of 2019, a confirmed epizootic was also reported in the South Region in the state of Paraná, in areas where yellow fever virus circulation was not detected since the re-emergence of the virus in 2014.

WHO: Yellow fever – Brazil

WHO has published Yellow fever – Brazil. Excerpt:

Brazil is currently in the seasonal period for yellow fever, which occurs from December through May. The expansion of the historical area of yellow fever transmission to areas in the south-east of the country in areas along the Atlantic coast previously considered risk-free led to two waves of transmission (Figure 1). One during the 2016–2017 seasonal period, with 778 human cases, including 262 deaths, and another during the 2017–2018 seasonal period, with 1376 human cases, including 483 deaths.  

From December 2018 through January 2019, 361 confirmed human cases, including eight deaths, have been reported in 11 municipalities of two states of Brazil. In the southern part of São Paulo state, seven municipalities:El dorado (16 cases), Jacupiranga (1 case), Iporanga (7 cases), Cananeia (3 cases), Cajati (2), Pariquera-Açu (1), and Sete Barras (1) reported confirmed cases. In the same state, additional cases in Vargem (1) and Serra Negra (1) municipalities were confirmed on the border with Minas Gerais State. Additionally, two cases have been confirmed in the municipalities of Antonina and Adrianópolis, located in the eastern part of Paraná State. These are the first confirmed yellow fever cases reported since 2015 from Paraná, a populous state with an international border. Among these confirmed cases, 89% (32/36) are male, the median age is 43 years, and at least 64% (23/36) are rural workers. 

Human cases reported so far during the current 2018–2019 period (July 2018 to Jan 2019) in nine municipalities in São Paulo State, as well as the confirmation of human cases and epizootic due to yellow fever in the state of Paraná, mark the beginning of what could be a third wave and a progression of the outbreak towards the Southeast and South regions of the country (Figure 2). 

While too early to determine if this year will show the high numbers of human cases observed in the last two large seasonal peaks, there is indication that the virus transmission is continuing to spread in a southerly direction and in areas with low population immunity.

Nigeria: Kwara confirms cases of Lassa fever, yellow fever, polio

Via Punch: Kwara confirms cases of Lassa Fever, Yellow fever, Polio. Excerpt:

The Kwara State Government has confirmed two cases of Lassa Fever infecting a husband and wife in the state. 

The government also confirmed an outbreak of circulating Vaccine Derived Polio Virus which claimed the life of a two-year-old girl and a case of Yellow Fever infecting a farmer. 

Speaking with newsmen on Tuesday during at a news briefing, the Kwara Commissioner for Health, Alhaji Usman Rifun-Kolo said the outbreak of Lassa Fever was identified in a farm settlement in Taberu, Baruten Local Government Area. 

 He, however, explained that the two cases of the disease affected a husband and wife, who were natives of Benin Republic, which shares a border with the state. He added that the husband and wife are farming in Baruten. 

“These cases of Lassa Fever originated from Benin Republic, whose citizen have inter-relations with people in Baruten area,” he said. 

According to him, the husband and wife were diagnosed in a health facility, and that the state government had already deployed disease surveillance team to identify those who have been in contact with the patients.  

Rifun-Kolo further explained that the surveillance team identified four people with history of fever in the area.  

He said that the four cases raised suspicion of Lassa fever, which prompted them to take samples from the individuals for further investigation.

Scientists say 'mosquito birth control' drug could be ready in five years

Via Thomson Reuters: Scientists say "mosquito birth control" drug could be ready in five years. Excerpt:

LONDON, Jan 8 (Thomson Reuters Foundation) - Scientists in the United States said on Tuesday they had taken a major step toward developing a "mosquito birth control" drug to curb the spread of malaria and other killer diseases blamed for hundreds of thousands of deaths a year.  

Researchers at the University of Arizona said they had discovered a protein unique to female mosquitoes which is critical for their young to hatch. 

When the scientists blocked the protein, the females laid eggs with defective shells causing the embryos inside to die.  

The team said developing drugs which targetted the protein could provide a way to reduce mosquito populations without harming beneficial insects such as bees. 

"It's an important discovery," Roger Miesfeld, head of the university's department of chemistry and biochemistry, told the Thomson Reuters Foundation by phone. 

"We're certainly excited about it ... This gets around mosquito resistance and also has a much better chance of being bio-safe (than other methods)." 

Mosquitoes are one of the world's deadliest animals, according to the World Health Organization (WHO) which has warned that global progress against malaria is stalling.  

The disease infected around 216 million people in 2016, killing 445,000 of them, predominantly babies and young children in sub-Saharan Africa. 

Other diseases spread by mosquitoes include Zika, Chikungunya, yellow fever, West Nile virus and dengue, which has risen 30-fold in recent decades, according to the WHO. 

Miesfeld said current methods of controlling mosquitoes had been used for so long that the insects were becoming resistant. 

He said the research team was surprised to find that treated females could no longer reproduce for the rest of their two- to three-week life span. 

"Once we knock down this protein she (the mosquito) no longer makes viable eggs even after multiple blood feedings so ... birth control is a great way to describe it."  

He said he hoped the discovery could lead to the development of a new generation of insecticides in five years. 

These could be applied to bed nets and other areas in the same way as current sprays and would be absorbed by the mosquito through her legs and body.