Human study supports theory on why dengue can be worse the next time around

Et tu, antibody? In humans, dengue can be more severe the second time around. Now, a study implicates an immune system treachery as the culprit.

The study suggests that the amount of anti-dengue antibodies a person has matters. In a 12-year study of Nicaraguan children, low levels of dengue antibodies left over in the blood from a prior infection increased the risk of getting a life-threatening form of the disease the next time around, researchers report online November 2 in Science.

Four related viruses cause dengue. The theory that antibodies protective against one type of dengue can collude with a different type of the virus to make a second infection worse was proposed in the 1960s. Such antibody-dependent enhancement has been shown in cells and lab animals. But “there’s been this controversy for five decades about, does this antibody-dependent enhancement really happen in dengue” in humans, says coauthor Eva Harris, a viral immunologist at the University of California, Berkeley’s School of Public Health. “And this says, yes, it does.”

About 2.5 billion people live where there is a risk of dengue infection. The virus infects 50 million to 100 million people every year, the World Health Organization estimates, but many cases go unreported. Infection with the mosquito-transmitted virus often leads to no symptoms, but can cause fever, joint and muscle pain and other flulike symptoms. The most severe form, which affects about half a million people annually, can include internal bleeding, respiratory distress or organ failure, and may be fatal.
Getting sick with one of the four virus types can protect against a future infection of the same type. But in some cases, the theory goes, leftover antibodies from the first illness can actually help the second infection invade cells, increasing the risk of severe dengue disease.

“This study provides support for this idea that antibodies under certain conditions can be bad and actually cause severe disease when people are infected with dengue,” says viral immunologist Sujan Shresta of the La Jolla Institute for Allergy and Immunology in California. The next step, she says, is to learn more about the antibodies involved and see whether the findings hold up in other populations.

From 2004 to 2016, Harris and her colleagues studied more than 6,500 children aged 2 to 14 in Managua, Nicaragua. The researchers took blood samples each year, at a time when the kids were healthy, and assessed their antibody levels. The scientists also monitored which kids developed dengue and how severe the disease was.

An analysis showed that kids with a specific low range of anti-dengue antibodies had around a 7½ times higher risk of developing the most severe form of the disease than those who had either no antibodies or a high amount. The team’s test couldn’t tell what kind of dengue antibodies each child had. Harris and colleagues are now working on characterizing the antibodies measured in their test, to learn what makes them protective or harmful.

The new study supports the theory of antibody-dependent enhancement in humans, says Anna Durbin, an infectious diseases physician at Johns Hopkins Bloomberg School of Public Health. But she also argues that the risk of developing severe disease depends on the quality of the antibody — that is, how potent it is — as much as, or more than, the quantity. “A number in and of itself doesn’t tell you a whole lot.”

CONCACAF 2022 World Cup Qualifying: Schedule, standings, TV for soccer Octagonal

We're now into the second half of the qualifying schedule and it's Canada at the top of the CONCACAF 2022 World Cup qualifying standings.

A 2-1 home win over Mexico allowed the Canadians to overtake the USA atop the eight-team table. Canada is the only remaining unbeaten team in qualifying as it continues to push to qualify for its first World Cup since 1986.

The USA (2nd, 15 points) and Mexico (3rd, 14 points), long the powers of the region, are now chasing. Meanwhile, Panama continued its surge with another dramatic come-from-behind victory to go level with Mexico on 14 points. The top three teams earn automatic berths to the World Cup, while fourth-place earns passage to a play-in series for one of the final spots in Qatar 2022.

The other half of the table is in precarious position. A group of three teams — Costa Rica (5th), Jamaica (6th), El Salvador (7th) — is now between 5-8 points behind Panama for fourth place. Meanwhile, it's looking unlikely that Honduras will be able to recover from its last-place point total. 

The first standings tiebreakers are (1) goal difference, (2) goals scored and (3) most points obtained from matches between teams that are tied. The full list of tiebreakers and results for Matchdays 1-7 follow at the bottom of this post.

CONCACAF World Cup Qualifying Standings & Results
Team PTS GP W L D GF GA GD

  1. Canada 16 8 4 0 4 13 5 +8
  2. USA 15 8 4 1 3 12 5 +7
  3. Mexico 14 8 4 2 2 11 7 +4
  4. Panama 14 8 4 2 2 11 9 +2
  5. Costa Rica 9 8 2 3 3 6 7 -1
  6. Jamaica 7 8 1 3 4 6 10 -4
  7. El Salvador 6 8 1 4 3 4 10 -6
  8. Honduras 3 8 0 5 3 5 15 -10
    Matchday 8
    Date Match
    Tues, Nov. 16, 2021 Jamaica 1 , USA 1 Highlights
    Tues, Nov. 16, 2021 Costa Rica 2 , Honduras 1 Highlights
    Tues, Nov. 16, 2021 Panama 2 , El Salvador 1 Highlights
    Tues, Nov. 16, 2021 Canada 2, Mexico 1 Highlights
    Matchday 9
    Date Match Time (ET) Stream
    Thurs, Jan. 27, 2022 Honduras vs. Canada TBD TBD
    Thurs, Jan. 27, 2022 USA vs. El Salvador TBD TBD
    Thurs, Jan. 27, 2022 Costa Rica vs. Panama TBD TBD
    Thurs, Jan. 27, 2022 Jamaica vs. Mexico TBD TBD
    Matchday 10
    Date Match Time (ET) Stream
    Sun, Jan. 30, 2022 Canada vs. USA TBD TBD
    Sun, Jan. 30, 2022 Honduras vs. El Salvador TBD TBD
    Sun, Jan. 30, 2022 Mexico vs. Costa Rica TBD TBD
    Sun, Jan. 30, 2022 Panama vs. Jamaica TBD TBD
    Matchday 11
    Date Match Time (ET) Stream
    Wed, Feb. 2, 2022 El Salvador vs. Canada TBD TBD
    Wed, Feb. 2, 2022 USA vs. Honduras TBD TBD
    Wed, Feb. 2, 2022 Mexico vs. Panama TBD TBD
    Wed, Feb. 2, 2022 Jamaica vs. Costa Rica TBD TBD
    Matchday 12
    Date Match Time (ET) Stream
    Thurs, March 24, 2022 Costa Rica vs. Canada TBD TBD
    Thurs, March 24, 2022 Panama vs. Honduras TBD TBD
    Thurs, March 24, 2022 Jamaica vs. El Salvador TBD TBD
    Thurs, March 24, 2022 Mexico vs. USA TBD TBD
    Matchday 13
    Date Match Time (ET) Stream
    Sun, March 27, 2022 Canada vs. Jamaica TBD TBD
    Sun, March 27, 2022 Honduras vs. Mexico TBD TBD
    Sun, March 27, 2022 El Salvador vs. Costa Rica TBD TBD
    Sun, March 27, 2022 USA vs. Panama TBD TBD
    Matchday 14
    Date Match Time (ET) Stream
    Wed, March 30, 2022 Panama vs. Canada TBD TBD
    Wed, March 30, 2022 Jamaica vs. Honduras TBD TBD
    Wed, March 30, 2022 Mexico vs. El Salvador TBD TBD
    Wed, March 30, 2022 Costa Rica vs. USA TBD TBD
    CONCACAF World Cup Qualifying results & highlights
    Matchday 1
    Date Match
    Thurs, Sept. 2, 2021 Canada 1, Honduras 1 Highlights
    Thurs, Sept. 2, 2021 Panama 0, Costa Rica 0 Highlights
    Thurs, Sept. 2, 2021 Mexico 2, Jamaica 1 Highlights
    Thurs, Sept. 2, 2021 El Salvador 0, USA 0 Highlights
    Matchday 2
    Date Match
    Sun, Sept. 5, 2021 Jamaica 0, Panama 3 Highlights
    Sun, Sept. 5, 2021 Costa Rica 0, Mexico 1 Highlights
    Sun, Sept. 5, 2021 El Salvador 0, Honduras 0 Highlights
    Sun, Sept. 5, 2021 USA 1, Canada 1 Highlights
    Matchday 3
    Date Match
    Wed, Sept. 8, 2021 Canada 3, El Salvador 0 Highlights
    Wed, Sept. 8, 2021 Panama 1, Mexico 1 Highlights
    Wed, Sept. 8, 2021 Costa Rica 1, Jamaica 1 Highlights
    Wed, Sept. 8, 2021 Honduras 1, USA 4 Highlights
    Matchday 4
    Date Match
    Thurs, Oct. 7, 2021 USA 2, Jamaica 0 Highlights
    Thurs, Oct. 7, 2021 Honduras 0, Costa Rica 0 Highlights
    Thurs, Oct. 7, 2021 Mexico 1, Canada 1 Highlights
    Thurs, Oct. 7, 2021 El Salvador 1, Panama 0 Highlights
    Matchday 5
    Date Match
    Sun, Oct. 10, 2021 Panama 1, USA 0 Highlights
    Sun, Oct. 10, 2021 Jamaica 0, Canada 0 Highlights
    Sun, Oct. 10, 2021 Costa Rica 2, El Salvador 1 Highlights
    Sun, Oct. 10, 2021 Mexico 3, Honduras 0 Highlights
    Matchday 6
    Date Match
    Wed, Oct. 13, 2021 USA 2, Costa Rica 1 Highlights
    Wed, Oct. 13, 2021 Canada 4, Panama 1 Highlights
    Wed, Oct. 13, 2021 Honduras 0, Jamaica 2 Highlights
    Wed, Oct. 13, 2021 El Salvador 0, Mexico 2 Highlights
    Matchday 7
    Date Match
    Fri, Nov. 12, 2021 Honduras 2 , Panama 3 Highlights
    Fri, Nov. 12, 2021 USA 2 , Mexico 0 Highlights
    Fri, Nov. 12, 2021 Canada 1 , Costa Rica 0 Highlights
    Fri, Nov. 12, 2021 El Salvador 1 , Jamaica 1 Highlights
    How CONCACAF World Cup Qualifying works
    Eight nations from the CONCACAF region (North America, Central America and the Caribbean) are competing for three automatic berths to the 2022 Qatar World Cup in the final "octagonal" qualifying round.

The eight countries are facing off in a round-robin format with each team playing the other seven opponents once at home and once on the road. The 14 total matches for each national team began in September 2021 and will wrap up in March 2022.

The top three finishers will earn automatic berths to Qatar, while the fourth-place team will head to an intercontinental playoff with a final ticket to Qatar on the line. Here are the standings tiebreakers for teams even on points:

Goal difference in all group matches
Most goals scored in all group matches
Most points obtained from group matches between teams concerned
Goal difference from group matches between teams concerned
Most goals scored in group matches between teams concerned
Goals scored away from home (if two teams tied)
Discipline points (based on yellow/red cards)
Drawing of lots by FIFA
The Qatar World Cup will be played from Nov. 21 to Dec. 18, 2022.