Blood Group AB Is Associated with Increased Risk for Severe Dengue Disease in Secondary Infections

Why certain individuals progress to severe dengue disease is unknown. In this study, blood groups associated with dengue disease were investigated. ABO phenotypes were identified by use of serum from 399 patients with dengue-virus infection who participated in a cohort study. ABO blood-group frequencies were similar in primary versus secondary dengue-virus infections. However, in secondary infection, individuals with blood group AB were likely to have dengue hemorrhagic fever grade 3 than either grades 1 and 2 combined (corrected P value, <.0001; odds ratio, 0.097 [95% confidence interval, 0.03–0.33]) or dengue fever (corrected P value, <.0001; odds ratio, 0.119 [95% confidence interval, 0.04–0.37]). To our knowledge, this is the first report demonstrating an association between ABO blood group and the severity of dengue disease.

Infection with dengue virus is a serious emerging health threat and has commanded considerable medical and public-health concern worldwide [1]. Today, dengue disease is considered to be, in terms of morbidity and mortality, the most important arthropod-borne human viral disease [1]. Globally, it has been estimated that 50–100 million new dengue-virus infections occur annually. Among these, there are 200,000–500,000 cases of potentially life-threatening dengue hemorrhagic fever (DHF)/dengue-shock syndrome (DSS), characterized by thrombocytopenia and increased vascular permeability [1]. The death rate associated with the more severe form of DHF/DSS (DHF grades 3 [DHF3] or 4 [DHF4]) is ∼5%, mainly in children <15 years of age [1].

The dengue viruses are mosquito-borne viruses of the Flaviviridae family. Four genetically related but distinct serotypes, designated “DENV-1,” “-2,” “-3,” and “-4,” circulate worldwide [1]. Infection with any serotype can be either asymptomatic or lead to 1 of the 4 clinical scenarios of increasing severity: undifferentiated fever, dengue fever (DF), DHF, and DSS [2]. Infection with one serotype leads to lifelong immunity to that serotype but to only partial and temporary immunity to the others; circulation of >1 serotype increases the risk of secondary infections and of DHF and DSS [2].

DF results from the bite of a mosquito carrying infectious dengue virus and is an acute self-limited disease comprising 5–7 days of fever, headache, myalgia, bone/joint pain, and rash, often accompanied by leukopenia. Occasionally variable degrees of thrombocytopenia and cutaneous hemorrhage are observed. Infrequently, DF may be accompanied by unusual bleeding complications that may cause death [1].

The clinical features of DHF are similar to those of DF during the early febrile phase, but, at defervescence, patients develop the pathophysiologic hallmarks of plasma leakage, because of increased vascular permeability and abnormal hemostasis [1]; studies of samples collected during and after the acute disease suggest that immune and inflammatory molecules play a role in increasing the permeability of blood vessels [3]. The risk factors for DHF are complex and poorly understood. Secondary infections, which occur commonly in areas where dengue disease is endemic, have proven to be one of the main risk factors for severe dengue disease [2, 4]; and this has led to the antibodydependent enhancement theory [2]. In addition, other probable risk factors for DHF are the infecting virus’s strain/serotype, the age of the patient, and the genetic background of the patient [2]; however, none of these factors alone accounts for the risk of DHF in patients with dengue-virus infections.

The important role that host genetics plays in determining the susceptibility to infectious pathogens in humans has long been known. Although predisposition to DHF or DSS determined by human leukocyte antigen (HLA) haplotype has been proposed by several researchers, no clear, specific polymorphisms have been unequivocally described for severe forms of dengue disease [5]. The ABO blood-group system is part of the innate immune system [6], and it has been shown that individuals with different ABO blood groups differ in their susceptibility or resistance to viral and bacterial infections and diseases [6, 7]. A relationship between blood groups and disease was first hypothesized by Kaipainen et al. during 1960 [8], and the gene involved in ABO blood groups was discovered in 1990 [6].

Material and methods. Serum samples were collected from children with acute febrile illnesses who were enrolled in a prospective study that has been described elsewhere [9]. The severity of DHF grading and diagnostic criteria followed World Health Organization guidelines. Acute dengue-virus infections were confirmed both virologically (by virus isolation and/or reverse-transcriptase polymerase chain reaction) and serologically (by ELISA for IgM/IgG) [9]. Standard hemagglutination assays were used to type the blood groups [6]. The protocol was approved by the Human Subjects Research Review Board, the Thai Ministry of Public Health, and the Institutional Review Board of the University of Massachusetts Medical School. Written, informed consent was obtained from the parent or guardian of each child.

All patients with confirmed dengue-virus infections were included in these analyses. We compared ABO blood-group frequencies in primary versus secondary infections, as well as in the analysis of associations with disease severity (DF vs. DHF), according to World Health Organization criteria. Theχ2 test for ABO blood groups (2×2 contingency tables) was used. P < .05 was considered to be significant. We used Bonferroni’s method to correct for multiple comparisons; this included correcting for blood groups (n = 4), primary versus secondary infections (n = 2), and number of groups of patients (DF, DHF1, DHF2, DHF3, all grades of DHF combined, and DF+DHF combined [n = 6]). Corrected P values (Pc) <.05 were considered to be highly significant. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the predisposition risk of disease severity associated with a specific ABO blood group.

Results. The frequencies of each blood group in the sample population are presented in table 1 and were consistent with those in the general Thai population [10]. The distribution of each blood group among patients with DF was similar to that among patients with DHF. Secondary infections are known to be associated with a higher risk of development of severe disease, so each patient was assayed by IgM/IgG ELISA to determine whether he or she was presenting with a primary or secondary infection.Table 2 shows the results of these assays, stratified by ABO blood group. In primary dengue-virus infections, all 4 blood groups had similar susceptibility to severe disease—that is, to DHF3—and no correlation between blood group and disease severity was seen. In contrast, among patients with secondary dengue-virus infection, blood group AB’s association with DHF3 was similar to both its association with DF (Pc < .0001; OR, 0.119 [95% CI, 0.04–0.37]) and its association with DHF1 and DHF2 combined (Pc < .0001; OR, 0.097 [95% CI, 0.03–0.33]). Also notable in secondary dengue-virus infection was that blood group O was associated less with DHF3 than with DF (P = .0304); however, this difference was not statistically significant after correction for multiple comparisons (Pc = 1.5).

Table 1.

Table 2.

Discussion. The results of the present study suggest that, when associated with a secondary infection, blood group AB may be a risk factor predisposing for severe dengue disease. The innate immune system—consisting of NK cells, dendritic and mast cells, macrophages, natural antibody—producing B cells, the complement system, and the host genetic factors—clearly plays a role in elimination of viral infections [11]. Among these innate factors, a predisposition for an individual to be susceptible or resistant to phenotypes of infectious diseases and their clinical manifestations resides in host genetic factors [6]. Two genetic factors—HLA and ABO blood groups—have, to some extent, been demonstrated to play an important role in resistance or susceptibility to infectious diseases [6].

DHF/DSS has been documented in infants during their first dengue-virus infection [1]. Presumably the enhancement of dengue disease in infants is due to preexistent dengue antibody that is passively acquired, via cord blood, from mothers immune to dengue-virus infection [1]. One limitation of the present study is that no infants were included. Whether ABO blood groups will play a similar role in infants remains to be delineated. In the present cohort study, the incidence of DHF in children with primary dengue-virus infection was low (table 2). Factors contributing to DHF in these children are unknown; perhaps individual genetic background may play a critical role in these children [2, 6].

In ABO blood-group antigens, individuals who lack an antigen have natural antibodies with the ability to agglutinate cells carrying that antigen [6]. The antigens are carbohydrate in nature; the immundominant sugar in the case of the A determinant is N-acetyl-D-galactosamine, and that in the case of the B determinant is D-galactose. Galactosyltransferases are involved in the synthesis of these carbohydrates [6]. The antibody that recognizes these carbohydrates is primarily natural IgM. Interestingly, several dengue viral proteins have been shown to be glycosylated [12], and antibodies, particularly IgM, produced in patients with dengue-virus infection have been shown to cross-react with host cells [3]. Two earlier studies found no association between blood group and disease severity in patients with dengue-virus infection [13, 14]; however, either the collected data were incomplete [13] or not all patients in the study had laboratory-confirmed dengue-virus infection and a comparison group with DF was not included [14]. Therefore, whether the combination of ABO blood group and the level of natural IgM antibody circulating in individuals has an effect on dengue disease remains to be seen.

Additionally, a correlation between HLA and dengue disease has been reported; but no specific polymorphisms have been found to be unequivocally associated with disease severity [5]. It therefore is of interest to see whether there is any correlation between a polymorphism in the galactosyltransferase gene and dengue-disease severity.

A previous study of HLA and dengue-virus infection found that the infecting viral serotype influenced the strength of the association between specific HLA alleles and dengue-disease severity [15]. The potential influence of dengue viral serotype in association with disease severity and ABO group was analyzed. All 4 serotypes were circulating during the periods of the study, and the results suggest that, for blood groups O, A, and B, no serotype was associated with disease severity. Interestingly, in the present study we found that, for blood group AB, moresevere dengue disease seemed to be associated more with dengue serotypes 2, 3, and 4 than with dengue serotype 1 (data not shown). Blood group AB’s association with DHF versus its association with DF was not significantly different from that in the other blood groups. Because of the limitations of the sample size in the present study, further studies will be necessary to determine whether dengue serotype, HLA, and ABO are independent variables—and whether some blood subgroups are associated with a particularly high risk of dengue-virus infection.

Acknowledgments

We thank Dr. Henry A. F. Stephens (Institute of Urology and Nephrology, University College London), for his excellent technical support in the statistical analysis and for helpful discussions, and Drs. SuchitraNimmannitya (Queen Sirikit National Institute of Child Health, Bangkok) and Alan Rothman (University of Massachusetts Medical School, Boston), for their knowledgeable comments and suggestions regarding the manuscript.

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Rh negative people more resistant to chikungunya

Rh positive blood groups are more susceptible to chikungunya fever over Rh negative individuals are resistant to it, a new study suggests. Also, people with ‘O’ positive blood group are more susceptible to infection by the virus than people of other blood groups, the research says.

CHIKWorldMap-061714

The researchers studied genetic predisposition to chikungunya fever, based on blood group antigens, on 100 families affected by the disease. They conducted blood group (ABO) tests by focusing on individuals who were likely to have a risk of chikungunya and identified the blood group involved in susceptibility/resistance to chikungunya.

The individuals were screened under four groups — A, B, AB and O. The result obtained showed that all Rh positive blood group individuals were susceptible to chikungunya fever.

Among ABO groups, O +ve individuals were found to bemore susceptible to chikungunya than other blood groups. No blood group with Rh negative was affected with chikungunya, indicating more resistance to chikungunya.

Source: natureINDIA

Chikungunya (pronunciation: \chik-en-gun-ye click to hear pronunciationExternal Web Site Icon) virus is transmitted to people by mosquitoes. The most common symptoms of chikungunya virus infection are fever and joint pain. Other symptoms may include headache, muscle pain, joint swelling, or rash. Outbreaks have occurred in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. In late 2013, chikungunya virus was found for the first time in the Americas on islands in the Caribbean. Chikungunya virus is not currently found in the United States. There is a risk that the virus will be imported to new areas by infected travelers. There is no vaccine to prevent or medicine to treat chikungunya virus infection. Travelers can protect themselves by preventing mosquito bites. When traveling to countries with chikungunya virus, use insect repellent, wear long sleeves and pants, and stay in places with air conditioning or that use window and door screens

By natureINDIA chart showing which blood types is more likely to get the virus

These Bizarre Events are Happening all Over the World! What the Heck is Going On? Are We the Last Generation?

 

“There will be signs in sun and moon and stars, and on the earth dismay among nations, in perplexity at the roaring of the sea and the waves, men fainting from fear and the expectation of the things which are coming upon the world; for the powers of the heavens will be shaken.” Luke 21:25-26

 

“For when they say, “Peace and safety!” then sudden destruction comes upon them, as labor pains upon a pregnant woman. And they shall not escape.” 1 Thess. 5:3

 

Mysterious, bizarre events are happening all across the globe: Pandemics rising (Ebola, TB, cancer, aids, a mysterious respiratory illness), Blood Moons, the Shmita, mass animal death, Earthquakes, Fukushima, Damascus desolation, Georgia Guidestones’ new anomaly, ISIS beheadings, and TONS more…

 

I URGE you with everything in me to watch the video below in its entirety. Considering Biblical prophecies are on the brink of fulfillment and that things can happen at any second, I beg you to ready yourself for what’s ahead and prepare for the coming disaster prophesied in the Bible….

 

 

Signs of the Times??

 

1- False Prophets and False Christ’s

 

“For false christ’s and false prophets will rise and show great signs and wonders to deceive, if possible, even the elect.” Matthew 24:24

 

“These people are false apostles. They have fooled you by disguising themselves as apostles of Christ. But I am not surprised! Even Satan can disguise himself as an angel of light. So it is no wonder his servants can also do it by pretending to be godly ministers.” 2 Corinthians 11:13-15

 

2- Wars and Rumors of Wars (Distress Among Nations)

 

And you will hear of wars and rumors of wars. See that you are not troubled; for all these things must come to pass, but the end is not yet.” Matthew 24:6

 

3- Famines and Pestilences

 

“For nation will rise against nation, and kingdom against kingdom. And there will be famines, pestilences, and earthquakes in various places.” Matthew 24:7

 

4- Signs in the Sun, Moon, and Stars

 

“There will be signs in the sun, moon and stars…” Luke 21:25

 

5- Increase in Natural Disasters— Violent Weather, Earthquakes, Fires

 

“There will be signs in sun and moon and stars, and on the earth dismay among nations, in perplexity at the roaring of the sea and the waves, men fainting from fear and the expectation of the things which are coming upon the world; for the powers of the heavens will be shaken.” Luke 21:25-26

 

6- Gospel Preached Throughout the World

 

“And this gospel of the kingdom will be preached in all the world as a witness to all the nations, and then the end will come.” Matthew 24:14

 

7- Godlessness

 

“But realize this, that in the last days difficult times will come. For men will be lovers of self, lovers of money, boastful, arrogant, revilers, disobedient to parents, ungrateful, unholy, unloving, irreconcilable, malicious gossips, without self-control, brutal, haters of good, treacherous, reckless, conceited, lovers of pleasure rather than lovers of God, holding to a form of godliness, although they have denied its power… always learning and never able to come to the knowledge of the truth.” 2 Timothy 3:1-5,7

 

8- The Revived Roman Empire

 

In the book of Daniel it tells of a dream interpretation given to King Nebuchadnezzar from  Daniel himself. The very interpretation of this dream tells of future events. Daniel 2:32-33, “The head of the statue was made of fine gold [represents Babylon]…its legs of iron [represents the Old Roman Empire], its feet partly of iron and partly of clay [represents the Revived Roman Empire that we see today].” In this dream Nebuchadnezzar was given a vision of things to come and this final empire was to be called the Roman Empire. It existed back in 70 A.D. and exists again.

 

9- One World Government

 

Daniel 7:23-25“The fourth beast shall be a fourth kingdom on earth, which shall be different from all other kingdoms, and shall devour the whole earth…and another shall rise after them…he shall speak pompous words against the Most High…”

 

10- Mark of the Beast

 

“He causes all, both small and great, rich and poor, free and slave, to receive a mark on their right hand or on their foreheads, and that no one may buy or sell except one who has the mark or the name of the beast, or the number of his name.” Revelations 13:16-17

 

11- Increase In Knowledge and Travel

 

“But as for you, Daniel, conceal these words and seal up the book until the end of time; many will go back and forth, and knowledge will increase.” Daniel 12:4

 

12- Existence of an Army with 2 million 

 

“And the number of the armies of the horsemen was two hundred million; I heard the number of them.” Revelations 9:16

 

13- Rise of Russia and its Alliances

 

“‘Son of man, prophesy against Gog of the land of Magog [Russia], the prince who rules over the nations of Meshech and Tubal [places in Russia]. Give him this message from the Sovereign Lord: Gog, I am your enemy! I will turn you around and put hooks into your jaws to lead you out to your destruction. I will mobilize your troops and cavalry and make you a vast and mighty horde, all fully armed. Persia [Iran], Ethiopia, and Put [Libya] will join you, too, with all their weapons. Gomer [Turkey] and all its hordes will also join you, along with the armies of Beth-togarmah [Turkey, Armenia, and the Turkish-speaking people of Asia Minor] from the distant north and many others.’”  Ezekiel 38:1-6 (emphasis mine)

 

14- Attempts for World Peace

 

“For when they say, “Peace and safety!” then sudden destruction comes upon them, as labor pains upon a pregnant woman. And they shall not escape.” 1 Thess. 5:3

 

15- Persecution of Christians and Jews

 

“Then shall they deliver you [believers of Jesus] up to be afflicted, and shall kill you: and ye shall be hated of all nations for my name’s sake.” Matthew 24:9

 

16- Death of Animals

 

“The land mourns, and all who dwell in it languish, and also the beasts of the field and the birds of the heavens, and even the fish of the sea are taken away.” Hosea 4:3

 

17- Jerusalem, a Burdensome Stone  

 

“Behold, I will make Jerusalem a cup of drunkenness to all the surrounding peoples, when they lay siege against Judah and Jerusalem. And it shall happen in that day that I will make Jerusalem a burdensome stone for all peoples; all who would heave it away will surely be cut in pieces, though all nations of the earth are gathered against it.” Zech. 12:2-3

 

18- Dividing Land in Israel  

 

“For behold, in those days, and in that time [last days], when I shall bring again the captivity of Judah and Jerusalem, I will also gather all nations, and will bring them down into the valley of Jehoshaphat, and will plead with them there for my people and for my heritage Israel, whom they have scattered among the nations, and divided my land.” Joel 3:1-2

 

19- The Fall of Damascus  

 

“The burden of Damascus. Behold, Damascus is taken away from being a city, and it shall be a ruinous heap.” Isaiah 17:1