CLINICAL MATTERS

It started with Quezon City, followed by several other municipalities declaring dengue outbreaks. Perhaps it was because of the recent rains that sporadically occur even in the dry season. It doesn’t take much water to get Aedes mosquitoes to breed. Stagnant water in uncovered containers, old tires that can serve as water reservoirs, and flower vases that aren’t properly cleaned but periodically refilled with water are ideal places for mosquitoes to lay their eggs. Sometimes, several family members fall ill simultaneously, and I have had my share of patients who are siblings sharing a hospital room with low platelet counts from dengue.

Dengue is hyperendemic in the Philippines, which means transmission occurs year-round. Cases usually peak near June and July when the rainy season starts, but an outbreak can occur at any time. More than 90 percent of Filipino children by the age of 12 have been infected by at least one dengue serotype and are therefore at the highest risk for severe dengue which is more likely to occur on the second dengue infection. Many hospitals in rural areas are filled to the brim during dengue outbreaks, and this harms not just the people who get dengue, but also patients with other conditions who need hospitalization but cannot get a bed.

Many interventions have been tried in the past to try to solve our dengue problem. There is still no effective anti-viral treatment for dengue, and it is very difficult to predict who will get severe dengue. What works, and what is in the pipeline that could potentially help with our dengue trouble?

Mosquito repellents

This is a common go-to for most people, especially for kids. However, not all mosquito repellants work equally. DEET (N-Diethyl-meta-toluamide) is the product with the most clinical experience and is the active ingredient in the most popular mosquito-repellent formulas. For dengue-carrying Aedes mosquitoes, it is recommended that a product contains at least 25 percent DEET, which will last about four to six hours before needing to be reapplied. However, the American Academy of Pediatrics cautions against the use of more than 30 percent DEET in children and to avoid using it at all in those below two months old. Lower concentrations of DEET, for instance, 10 percent, last only for about two hours and may need to be reapplied. Avoid applying the repellent around the eyes, nose, or mouth as well as the palms of the hands which younger children may bring to their mouths.

Other locally available clinically proven insect repellents include those that contain picaridin, para-menthane-diol (PMD), oil of lemon eucalyptus (OLE), and IR3535. Be sure to check the label to see how long it lasts and if reapplication is needed. Some products such as picaridin should not be used in children three years old and below as well.

Essential oils such as citronella, cedar, fennel, and soybean also have some activity as mosquito repellents but are less standardized in terms of concentration and duration of activity. These may need to be reapplied frequently, and effectivity can be variable between non-standard preparations. 

Other methods that are on the market but are of uncertain efficacy are wristbands or clothing stickers soaked in chemicals, ultrasonic devices, and taking garlic or vitamin supplements like vitamin B1 and vitamin D.

Dengue vaccines

After the Dengvaxia controversy, many Filipinos are understandably wary of dengue vaccines. Dengvaxia itself has remained safe and effective in people with at least one infection, but due to poor sales, Sanofi is closing its remaining production plants. 

A new dengue vaccine made by Takeda that works for both seronegative and seropositive patients has recently received World Health Organization prequalification, which means that it is likely safe and effective for use in areas with high rates of dengue. The WHO currently recommends that it be given to children six to 16 years old in high transmission settings where seroprevalence is at least 60 percent by the age of nine. Since there was no safety signal in seronegative recipients, screening for prior dengue infection is not required. We are still waiting to see if Takeda gets market authorization in the Philippines and whether there will be a good uptake.

A third vaccine (Butantan DV) recently showed good efficacy and safety in a clinical trial with a single dose after up to 3.7 years of follow-up. It will be submitted for regulatory evaluation once five years of follow-up have been completed as long as it continues to show good safety and efficacy.

Mosquito biological warfare

Aside from the usual attempts to eliminate mosquito vectors by fumigation, spraying and removal of breeding sites, scientists have developed innovative methods for controlling the Aedes mosquito population. Three such methods that are currently being used in different parts of the world are irradiated male mosquitoes, Wolbachia-infected mosquitoes, and genetically modified mosquitoes.

Releasing irradiated male mosquitoes which are sterile significantly reduces the mosquito population because these compete with fertile males for mating with the female mosquitoes. Female mosquitoes that mate with sterile males do not produce any offspring, and the continued release of sterile males eventually reduces the overall mosquito populace. However, getting the correct radiation dose for the male mosquitoes can be tricky and sometimes incapacitates the males or makes them less fit to mate than the wild male mosquitoes.

Wolbachia-infected mosquitoes are an innovation that uses the bacteria Wolbachia to make the Aedes mosquitoes resistant to dengue viruses. Wolbachia is a ubiquitous bacteria that lives inside insect cells and plays a role in the reproduction of the species. Aedes mosquitoes are normally not infected with Wolbachia, but when mosquito eggs were experimentally infected with the bacteria, they developed into adults that were resistant to infection with not just dengue but also Zika and Chikungunya viruses. The mosquitoes then began to transmit Wolbachia to their offspring and these naturally perpetuated. When Wolbachia-infected Aedes mosquitoes are released into an area, these mate with the wild Aedes population and within a few months almost all the Aedes in the area are already carrying Wolbachia. This method has already been used successfully in several areas to reduce dengue infection in mosquitoes resulting in decreased human cases of dengue.

Genetically modified mosquitoes carry a gene that prevents the development of wings in female mosquitoes. Male mosquitoes with the gene mate with wild female mosquitoes and any female offspring that carry the gene will not be able to develop wings normally and will die before reproducing. Since only female mosquitoes bite and transmit dengue, eliminating females decreases the prevalence of dengue in an area.

All three innovative mosquito control methods have been shown to be environmentally safe and have not shown any unexpected adverse effects on other insect populations. Locally, our scientists are already looking at these methods to augment our fight against dengue. It will likely take multiple interventions across various sectors of society to eventually solve our dengue problem once and for all. We’ll need a massive effort on the part of the government, the private sector, and each one of us who are willing to put in the time and effort to eliminate the scourge of dengue in our country.