Wednesday, March 26, 2008

Fungi vs insects 1:0

In a recent paper in Heredity, Alex Kraaijeveld and Charles Godfray show that Drosophila melanogaster has little chance in developing resistance to fungal pathogens such as Beauveria bassiana. This is significant as the same fungi and the related Metarhizium anisopliae are targeted to be used as biopesticides against disease vectoring mosquitoes (such as Anopheles) and other insect pests. In this paper, in a long-term artificial selection experiment for 15 generations, selected flies did not have higher overall fitness after infection compared with control lines. However, late-life fecundity increased in the selected lines, which may indicate evolved tolerance of the fungal pathogen. Nonetheless, this increase was balanced by decreased early-life fecundity in the selected lines. More importantly, in the absence of fungal infection, selected lines had lower overall fitness than control flies. In general, the paper demonstrated that Drosophila have a weak selection response to the fungal infection. If this is true to insects in general and to mosquitoes in particular, this might suggest that resistance to such fungal pesticides will not evolve easily and rapidly. This might give  us just another novel tool for vector control, which is badly needed to reduce vector-borne diseases globally.

Tuesday, March 25, 2008

More on the dengue outbreak in Rio de Janeiro

News of a large dengue outbreak are starting to circulate on the Internet. PromedMail reported today that in addition to the 47 confirmed mortalities due to dengue in Rio de Janeiro since the start of the year, an additional 49 cases of death are suspected to be due to the disease. Bloomberg.com also reports that 2053 dengue cases have been reported on a single day (March 20, 2008), which is much higher (cc. 84) cases per hour than was previously reported (51 cases of dengue per hour). This outbreak is very alarming, and surely overwhelms the public health infrastructure of the city. In the same report, Edmilson Migovski, a professor of infectious diseases at the Federal University of Rio de Janeiro is quoted saying that part of the reason of this large outbreak is that  the 'virus is becoming more virulent'. Although I haven't seen any report of any dengue serotypes evolving higher virulence, Prof. Migovski might have meant that DHF/DSS is occuring due to pre-existing herd immunity to heterologous serotypes in the population. It would be interesting to know what is the dominant serotype of this outbreak. The Asian variant of DEN-2 is known to cause more serious disease as well as DHF/DSS.


Monday, March 24, 2008

Dengue outbreak in Brazil

CNN reports that there is a dengue outbreak in Rio de Janeiro, that has already affected 32,000 people [possibly reported dengue fever cases] and claimed at least 47 lives [probably since the start of this year]. The number of deaths is already higher than it was in 2002, the last officially recognized epidemic year. According to the Federal Health Minister, Jose Gomes Temporao, 51 new cases are reported every hour [I can only imagine how much this can overburned the health system]. A crisis center will open today  in Rio state to coordinate response from federal, state government and the armed forces to combat the disease.

Although ProMedMail doesn't have a corresponding report, PAHO has a similar news item with more information. It seems that while the number of dengue cases nationally is 40% less than last year [probably due to a lack of a huge outbreak like last year in Paraguay], the dengue prevalence has more than doubled this year compared to last year in Rio de Janeiro.


Thursday, March 20, 2008

ICEID 2008

On March 18th, I visited the International Conference of Emerging Infectious Diseases (ICEID 2008) in the Hyatts Regency Hotel, in Atlanta, GA. Even though I was only able to attend half a day of this conference, I felt that it was incredibly useful and highly worth the trip from Athens to Atlanta. In general, the meeting was very well organized, with several concurrent sessions in the morning. I was able to attend 3 sessions on arboviral disease.

At first, Thomas Monath from the Kleiner Perkins Caufield and Byers Pandemic and Biodefense Fund talked about the challenges and possible solutions of dengue control. Tom Monath has been a major force behind the development of dengue vaccines, personally working on the ChimeriVax dengue vaccine at Acambis. He gave a thorough introduction to dengue and then summarized the status of the dengue vaccines under development. He mentioned that there is a lot of genetic plasticity within dengue serotypes, which was unknown to me. Also, he acknowledged that there is a prolonged convalescence period even for dengue fever, characterized by weakness and fatigue, which is usually not included in the burden of disease studies. He featured a highly useful and intuitive diagram showing the variety of societal, economic, ecological and evolutionary components that lead to the increasing incidence and geographic range of dengue. In terms of the US, he acknowledged that dengue is present in south Texas, and has the potential to spread further north. On one of his maps, northern Argentina was shown to have Aedes aegypti, which I wasn't aware of either (although not surprising given the proximity of Paraguay and Brazil). He also warned about the widespread distribution of Aedes albopictus in the US, which is although less capable vector of dengue as Aedes aegypti is, could nonetheless drive an epidemic in Hawaii in 2001. He mentioned that Aedes albopictus might be present on the west coast of the US, however, this is not mentioned in the recent paper on the distribution of Aedes albopictus (although I might have misunderstood).

Friday, March 14, 2008

Chikungunya outbreak in Sri Lanka rages on

ProMedMail reports that the chikungunya outbreak in Sri Lanka is ongoing. The number of cases mentioned is the same as in an earlier report.  The importance raising of public awareness and insanitary conditions [ample breeding sites] are cited in the current report. While these are undoubtedly important, I hope that the response to the epidemic is not left solely to the affected public. Isolation of infectious patients from bites of susceptible mosquitoes and immediate and major reduction of the adult and larval mosquito population by all available means is the only solution, unless the authorities want to let the epidemic run its course.


Thursday, March 13, 2008

African Horse Sickness outbreak reported in South Africa

ProMedMail reports that there is an outbreak of African Horse Sickness in Gauteng, KwaZulu-Natal and the Eastern Cape of South Africa.
Mod AS. adds that African Horse Sickness is endemic and seasonal in these areas. Authorities have imposed an embargo on the movement of horses into the province. African Horse Sickness is caused by an orbivirus, which is phylogenetically similar to bluetongue virus, and is vectored by the same Culicoides biting midges (e.g. C. imicola) that spread bluetongue. This is a life-threatening disease with fever, internal bleeding, attacking the internal organs, and causes high rates of mortality. It is therefore understandable that the EU placed a ban on importing horses from the affected area a few years ago. I suppose the European horse industry does not want to have it's own bluetongue.

West Nile virus detected in birds in San Diego

According to ProMedMail, West Nile virus was found in 6 birds in San Diego County, California. This is unusual as evidence of viral infection in birds usually doesn't show up until the summer or fall. Fifteen cases have been reported in humans in 2007, 14 of them in people aged over 50. [Actually, ArboNET reports 16 total human cases in San Diego County, California in 2007 up to March 4, 2008]. The report mentions that mosquitoes usually die off in the winter, but a wet winter and a warm spring may have helped them survive in recent months. While this might be true, it is also possible that WNV is maintained by direct transmission between birds during the winter period. Interestingly, looking at reports of WNV-positive birds in 2007 in California, a few cases occured as early as January and February. Undoubtedly, human cases were only reported starting in June. Interestingly, WNV-positive mosquitoes appeared in earnest in July as well, while a few were reported in January [a warm spell?] and May. This could support the idea that cases of West Nile in birds are due to direct transmission between birds, and not vector-borne. Agreeing with Mod TY in the ProMedMail report, it would be very interesting (and important) to know whether there are any WNV-positive mosquito pools in San Diego County at the moment.

Wednesday, March 12, 2008

Malaria model predicts successful malaria eradication in regions of mesoendemic transmission

Bob Snow and his colleagues, Ricardo Augas, Lisa White and M. Gabriela M. Gomes published a very interesting study in PLOS One predicting that malaria could be successfully eradicated in regions of mesoendemic transmission (areas with infection prevalence between 11% and 50%, see here) if prevalence of the disease could be brought below a certain threshold. The authors used a classical SIRI-type epidemiological model, where recovered hosts can become infected but not infectious for the second time, and recovered hosts can lose their immunity over time. The authors parameterized this model using clinical data from eight endemic regions in Sub-Saharan Africa. The model predicts a regime of bistability of endemic and malaria-free states, induced by a shorter estimated infectious period for clinical infections, in regions of mesoendemic transmission. These two states are separated by a threshold of prevalence (total number of cases), predicting that malaria can be eradicated in these areas if the number of cases can be kept below a certain level by a combination of interventions. This result is definitely encouraging as both e.g. India, South-America as well as some parts of sub-Saharan Africa belong to the hypo- and mesoendemic region (see this figure). I haven't read the paper thoroughly yet, but it's definitely in my pile. However, just by glimpsing at it, I see that the epidemiological model only follows hosts and not vectors (vectors are implicitly assumed as part of the force of infection). My opinion is that the inclusion of vectors might make the disease dynamics more complex, as well as more realistic. Since the predictions of this paper are so important for public health programmes that aim to control malaria, I would suggest to look at the effect of vectors on the dynamics as well.

Interesting videos about selfish genetic elements on YouTube

Enthusiastic master students of Tom van Dooren and Ken Kraaijeveld at the Institute of Biology in Leiden, the Netherlands produced interesting ideo materials on selfish genetic elements, which they made available on YouTube. The 14 videos feature such selfish genetic elements as B-chromosomes, transposable element, selfish sex chromosomes and meiotic drive (although I didn't see this one). The videos are all below 10 minutes in length, and make a good effort in introducing these elements. Since selfish genetic elements have been proposed to drive genes that make mosquitoes (e.g. Aedes aegypti) refractory to pathogens (e.g. dengue), these videos could be of interest to researchers working on vector-borne diseases. There is also a movie included more generally on Mendelian inheritance and selfish genetic elements, as well as on how to turn Powerpoint presentations into such movies. I think this a very nice project. My only criticism is that the graphical resolution of some of the movies is inadequate (see e.g. the movie on how to make movies from presentations), which is possibly due to the difficulty in capturing high-resolution movies with limited infrastructure.




Monday, March 10, 2008

Immunohistochemistry suggested to differentiate between yellow fever and dengue

The recent yellow fever epidemic in Paraguay with a number of urban cases highlighted the importance of differentiating between dengue and yellow fever in areas where these two Flaviviruses cocirculate. Dr. C.J. Peters at the University of Texas Medical Branch suggested on ProMedMail to use immunohistochemistry for this purpose. Immunohistochemistry localizes the antigens (virus) of the specific disease by presenting labeled antibodies. This method works in fixed tissues which are much easier to obtain from outbreaks in remote locations than fresh tissue or blood samples. He also lists a number of examples when such a method was shown to be effective for yellow fever.
This method seems to be low-tech and efficient, probably cheap method, which I, coming from Hungary, can appreciate.

Uric acid produced by Plasmodium kicks the immune system into lethal overdrive in malaria

PLOS Pathogens just published a very interesting paper by Orengo and others at the Department of Medical Parasitology of the New York University School of Medicine and the Department of Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School on how Plasmodium-infested red blood cells accumulate high concentrations of hypoxanthine. This is degraded into uric acid upon the rupture of these red blood cells, which is a danger signal for the immune system, inducing the production of inflammatory cytokine TNF (tumor necrosis factor) from dendritic cells in a mouse model. Possibly because of my limited knowledge of malaria pathology, it was a surprise to me that the real danger seems to be the malaria-induced inflammatory response. This is quite similar to dengue haemmorrhagic fever or shock syndrome, which I wasn't aware before.

Two people died of DHF on Tonga; Dengue spreading in NE Queensland

Dengue haemorrhagic fever has claimed the lives of a 23-year old man and an infant during the last week, reports ProMedMail. According to local sources, the number of dengue fever cases tripled relative to last year, with more than 200 cases [over an uncertain period]. Interestingly, the report states that the epidemic occurred between June and December. Recommendations to the public in the report include using mosquito nets, which might not have much effect as Aedes aegypti is a day-biting mosquito.

The same report announces that the number of dengue cases in Port Douglas, North Queensland, Australia reached 14, despite control efforts by mosquito trapping and spraying. As usual, residents are urged to remove potential breeding sites. The report includes interesting notes of previous outbreaks with 30 cases in Cairns in 2003 and a large outbreak of 500 cases in 1997-98 in the same area. I noticed that the link at the end of the report is erroneous. The proper link is <http://www.health.qld.gov.au/dengue>. Interestingly, this local health authority website seems to be out-of-date, showing only 6 cases in total for the current outbreak.

Friday, March 7, 2008

African Swine Fever kills hundreds of pigs in Tanzania

ProMEDMail reports that African Swine Fever, a febrile disease transmitted by ticks in Africa, has killed hundreds of pigs at two locations in Tanzania. The case fatality rate of this disease is close to 100%. In this case, 20% of susceptible animals died so far at these locations. The ProMEDMail commentary adds that these two locations are in different provinces which raises the question about their connection epidemiologically.



Chikungunya spreading in Sri Lanka

It seems that Chikungunya is spreading fast in Sri Lanka, according to ProMEDMail and the Daily News. So far 150 patients have been reported, of which some have been confirmed (presumably by ELISA). Authorities are giving the usual advice to the public to eliminate breeding site, which will not help them in the short run as adult infectious mosquitoes are flying around. According to the knowledgeable comment of Mod TY on ProMEDMail, this is the first report of local transmission of chikungunya in Sri Lanka in 2008. However, in January 2008 an imported case of chikungunya to Hong Kong was originated in Sri Lanka, indicating that transmission has occured in Sri Lanka prior to this report. Hopefully India will be spared from chikungunya this year, unlike in 2006 and 2007. If not, imported cases during the Northern Hemisphere summer will have the potential to start another local epidemic such as the one that occurred in Italy in 2007 in regions of Europe and the US where Aedes albopictus is prevalent.


Yellow fever vaccination campaign nearing its end in Paraguay

ProMEDMail reports, based on this WHO update that more than 1.27 million people have been vaccinated in 18 states of Paraguay. This means 83% of the population in Ascunsion and 75% of the people at the Central Department have been vaccinated against yellow fever.
This is great news, which basically means an end to the threat of a potentially disastrous yellow fever epidemic in Paraguay.
However, at the same time they report that the number of confirmed cases has risen by 5, leading to a total number of cases of 21, and a total of 5 fatalities during the outbreak. 12 suspected cases are still under evaluation. The WHO update also reports that officials from Brazil, Paraguay, Uruguay, Venezuela, Bolivia and Peru agreed to coordinate and monitor yellow fever immunization for the populations of border areas, with the support of PAHO. While this is very promising, I hope that this program will be extended to other populations not living in the border areas. Also, the officials reiterated breeding site reductions as the preferred method to combat Aedes mosquitoes and yellow fever (and dengue). While I don't doubt that breeding site reductions can be very effective, I hope that integration with other forms of vector control will be considered, or at least breeding site reduction will target rare, but highly productive breeding sites.



Wednesday, March 5, 2008

Indirect evidence for excess deaths due to chikungunya infection

The current issue of Emerging Infectious Diseases carries an article by Dileep Mavalankar and coauthors at the Indian Institute of Management, Ahmedabad, India. The article, reported by PromedMail as well claims that 3056 more deaths than expected that occured in 2006 in Ahmedabad, India are due to the chikungunya epidemic. The authors arrived at this conclusion by estimating the expected number of deaths in 2006 based on the number of deaths reported in 2002-2005, and comparing it with the actual number of cases reported. About 2944 additional deaths occured in the period August-November when the chikungunya epidemic was at its height in 2006 in the city.  Statistically significant difference was shown between the observed number of deaths and the expected number of deaths for July, August and September of 2006. Overall, 60,777 suspected chikungunya cases were reported in 2006 in Ahmedabad. The authors generalize this case-fatality-ratio of around 5% to the chikungunya epidemic in the whole of India in 2006 with 1.39 million suspected cases, estimating around 50,000 [see the ProMedMail report] deaths due to chikungunya infection in the whole of India in 2006. [According to my calculation, 70,000 deaths would be more appropriate estimate for a CFR of 5% with 1.39 million cases] It seems reasonable to assume some mortality with any infection in the elderly or immuno-compromised patients, as the article claims. However, no mechanism has been found so far by which chikungunya infection would lead to mortality in itself. Another recent article in the Virology Journal shows that the chikungunya virus produces acute arthritis by large area of necrosis and collagenosis or fibrosis, damaging the cartilage and connective metabolism and releasing the degraded products from the tissue, increasing levels of proline, hydroxyproline and mucopolysaccharides in affected patients. Whether this mechanism in itself is life-threatening in elderly or immunocompromised patients, or other opportunistic infections cause the mortality, seems to be an open question.

Additional 4 cases of yellow fever confirmed in Paraguay

An additional 4 cases of yellow fever deaths have been confirmed in Paraguay by health authorities, according to a report on ProMedMail. All four cases occured in a jungle area in the department of San Pedro, 220 km from the capital Ascuncion and 400 km from Mato Grosso in Brazil. The total number of yellow fever cases confirmed in Paraguay during 2008 stands at 20, of which 10 people died. Of these 10 deaths, only 4 has been confirmed by autopsy, however the other 6 cases show similar clinical signs. The report claims that residents of San Pedro generally refuse the yellow fever vaccination in fear of its side-effects. In Paraguay, approximately 2 million people have been already immunized for free, and a vaccination campaign is continuing using an additional 1 million dose of vaccines that arrived to Paraguay during the last two month.