Response to some comments in Social Media on our dengue eradication method

We are most grateful to everybody who responded both positively and negatively to these posts. There are some issues that keep appearing and it is felt that they should be addressed promptly. It is also important to understand that the aim of this blog is to stimulate a discussion on the proposed strategy to eradicate dengue from Sri Lanka, and there are no set positions. The aim is to arrive at a solution based on “isolation” of dengue “patients”. I have indicated isolation as well as patient in quotes because in this context they have special meanings. Isolation does not mean keeping a patient under a mosquito net. It means isolation or protection from mosquitoes. Therefore, use of insect repellents and long clothing for full body cover also amount to isolation. Similarly, a patient is someone who is capable of transferring the dengue virus to a mosquito.

The issues that keep being repeated are:

1. Non-symptomatic Patients

2. Period of Infectivity

3. Vertical Transmission of Dengue

4. Resources

1. Non-symptomatic Patients

Asymptomatic patients seem to worry a lot of people. One used the phrase “tip of the iceberg” to suggest that the asymptomatic cases constitute the vast majority of cases and therefore the proposed strategy will not work. The problem is that no one actually knows what number of cases are actually asymptomatic. 

Perhaps the proportion varies from strain to strain, place to place and time to time. In Sri Lanka one study found the ratio of symptomatic to asymptomatic to be 1.4. What is important is whether they would influence attempts at controlling the disease. In other words can they transmit the disease. 

To answer this question we have to know how a asymptomatic case is defined. It is by discovering the household or community members who have been converted from sero-negative to sero-positive after an event or outbreak of dengue infection, without having shown signs of being ill during the event or outbreak. For purposes of preventing the spread of dengue by isolation, what is important is whether these asymptomatic “patients” were infectious to mosquitoes. This is where the question of viraemia (the presence of virus in the blood) comes in. Although the degree of viraemia required for infectivity of the patient may be in dispute, most seem to agree that detectable viraemia in the patient is necessary for the mosquito to acquire the infection. 

It is understood that fever is a good indication of viraemia. The corollary is, if there is no fever there is no viraemia, at least significant viraemia. This raises the issue of whether the viral status of the asymptomatic “patient” is measured before the decision to call a “patient” as being asymptomatic patient? No it is not. So we have no way of knowing whether an asymptomatic “patient” is infectious or not. Nowadays the available tests are positive in the presence of viraemia. And if positive, they would be diagnosed as a case irrespective of symptoms.  The other issue is even if the asymptomatic patient is viraemic, is the degree of viraemia high enough to give rise to transmission. It is not very easy to study the degree of infectivity of asymptomatic “patients”. 

2. Period of Infectivity

The other related issue that people have problems with is the  period of infectivity. Interestingly, one argues against the other. i.e. in actual patients the period of infectivity is short and isolating is not worthwhile  however even asymptomatic patients can transmit the virus. We cannot have it both ways. The people who are concerned about period of infectivity is that the period of infectivity is so short that we would miss them anyway. The argument that the latter group advance is that the peak of infectivity is about the 2nd or 3rd days of illness and most people would be at home and not in hospital or would not have been tested. This is actually a valid point. However, it must be remembered that we are not attempting to isolate EVERY case. We cannot. That does not mean we cannot isolate some or even most cases. The peak time of viraemia maybe the 2nd day. But there is viraemia before as well as AFTER the second day. So it is worth isolating as soon as a patient is found either by testing or symptoms.

My argument is that these issues should be discussed openly and the public educated. Then a point would come when people would “isolate” themselves once they develop fever, whatever the diagnosis arrived at later. The sooner that this point is reached the sooner the outbreak will finish. It can be termed the “Tipping Point”.

3. Vertical Transmission of Dengue

It has been suggested that control of the dengue epidemic in Sri Lanka by isolating dengue patients will not succeed because of vertical transmission. Vertical transmission means the passing of the dengue virus from an infected female mosquito to its offspring through the eggs laid by the infected female. The idea that vertical transmission must be taking place in nature was because of two reasons.

     1. Sometimes dengue cases appear in places after long periods without the disease. (e.g. usually after a drought).

     2. Dengue virus has been found in larvae and male aedes mosquitoes.

There  are  plenty of research article on this subject if anyone is interested enough to find out if vertical transmission actually takes place. The next question is whether the degree to which vertical transmission takes place is sufficient to cause an epidemic or for an epidemic to continue in spite of other control measures.

Aedes eggs persist in the environment even in dry conditions and are also thought to undergo some sort of suspended animation.  But the reason why dengue appears after a long period is thought to be due to the disease being brought to the area by visitors rather than because the virus was found in the aedes mosquito eggs.

Why dengue virus is found in male mosquitoes is thought to be due to cannibalism among larvae.  Of course for that to happen the larvae need to have had dengue virus in them in the first place. In other words, there should have been vertical transmission of the virus.  Another explanation suggested is that male mosquitoes acquire the virus during mating with infected females. To me the second method is more plausible. 

As I say if anyone is interested, they can spend their time perusing the literature. But for our purpose the question is how important is it in the Sri Lankan situation. I think when there is enough horizontal transmission in Sri Lanka with plenty of rainfall why worry about vertical transmission.

There are two articles that I suggest people read if they have any doubts.

     1. J Med Entomol. 2016 Jan;53(1):1-19 How Important is Vertical Transmission of Dengue Viruses by Mosquitoes (Diptera: Culicidae)? Martin Grunnill Michael Boots

The conclusion of the authors was:

“Given the evidence from mathematical models and the number of studies that failed to find evidence of vertical transmission, vertical transmission is unlikely to be important for the persistence of DENVs at a local or regional level. A combination of asymptomatic DENV infection in humans and the movement of viraemic people may well be more important in virus recurrence”
https://academic.oup.com/jme/article/53/1/1/2459705/How-Important-is-Vertical-Transmission-of-Dengue

     2. The abstract of the other study states:

"Transovarial transmission of all four dengue serotypes was demonstrated in Aedes albopictus mosquitoes. The rates of such transmission varied with the serotype and strain of virus. In general, the highest rates were observed with strains of dengue type 1 and the lowest with dengue type 3. Surprisingly, despite the use of viral strains of the four dengue serotypes which gave the highest rates with Aedes albopictus, transovarial transmission was observed in Aedes aegypti only with dengue type 1, and then only at a relatively low rate. Five different strains of Aedes aegypti were employed, including one that was known to be relatively susceptible to oral infection with dengue viruses. The findings support the view that Aedes aegypti, while of major importance from the point of view of transmission of dengue to man, may be relatively unimportant in the overall natural history of dengue viruses."
http://www.ajtmh.org/content/journals/10.4269/ajtmh.1983.32.1108


4. Resources

A few respondents wondered how much all this is going to cost. Ideally all dengue patients in hospital should be cared for in specially designated wards. It is important to screen these wards against mosquito entry. This measure is important not only to keep out the mosquitoes but also to indicate to the general public the importance of preventing mosquito bites. Some wards in the bigger hospitals may be easier to air condition rather than screen with netting. It will achieve the same result if the doors are kept closed.

The other expense is to do with the patients who are not in hospital. They should be cared for under mosquito nets. But this measure alone is not sufficient. In addition, they should also use insect repellent. Now it is the advice of the health ministry that if people suspect that they may be suffering from dengue they should get themselves tested as soon as possible. The best arrangement is if they were issued with a mosquito net and a bottle of insect repellent. It seems a little extravagant, but I believe it is worth the money. Not only will the patient pay attention to the advice to safeguard against mosquito bites, it will be effective immediately as time is of the essence in preventing mosquito bites.

Dr Lal Jayasinghe
laljayasinghe@hotmail.com

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