Dealing with dengue annually

Delhi recorded 763 new cases of dengue in November; a look at why the disease makes a comeback every year


Photo: Hindustan Times
Photo: Hindustan Times

New Delhi: The dengue outbreak in India is far from over—in November alone, as many as 763 fresh cases have were registered in the capital city, while Tamil Nadu sounded alerts for taking preventive measures after heavy rainfall flooded cities.

Delhi is facing the worst outbreak of dengue, transmitted by mosquito bites, in 20 years with more than 15,652 cases and 38 deaths. Across the country, more than 64,000 cases have been reported with 135 deaths, according to the latest data from the National Vector Borne Disease Control Programme (NVBDCP).

But these figures may be misleading—as with most other outbreaks of disease, experts suspect there is under-reporting of deaths and cases. In a high-level meeting last month, Union health minister J.P. Nadda admitted that the data currently generated by the central (vector borne disease control programme) and state governments is highly variable. He called for a mechanism to store patients’ details at the central level in order to reduce discrepancies in data.

Amid growing public unease, fights over data, the medical response, funding and turf war—between the central government, the state government and municipal authorities—have flared up around the latest outbreak of dengue in Delhi.

The fact remains that while there is no cure for dengue, it is a highly preventable disease. Nevertheless, it has become hyper-endemic in India, with the frequency of outbreaks increasing through the decades.

Evolution of a disease

The mosquito is arguably the deadliest insect in the world, as was illustrated by US philanthropist Bill Gates in his blog last year that said mosquitoes kill a massive 700,000 people worldwide every year. Most of these deaths are due to malaria, but dengue—a disease that can cause rapid deterioration of health—affects at least 50-100 million people every year. Although the increase in the frequency of outbreaks is a recent phenomenon in India, dengue itself has been recorded in the country for a long time.

The first epidemic of a dengue-like illness was recorded in Madras city (now Chennai) in 1780 and the first virologically proven epidemic of dengue occurred in Calcutta and the eastern Indian coast in 1963-64. It then spread to the northern parts and reached Delhi in 1967.

Simultaneously, it also spread in the southern regions, gradually enveloping the entire country, which was reported to be endemic and eventually hyper-endemic with the prevalence of all the four serotypes of the dengue virus in Vellore in 1968.

There are four serotypes of the dengue virus with mostly the same clinical manifestations— DEN-1, DEN-2, DEN-3, and DEN-4. The most virulent are DEN-2 and DEN-4, and one reason this outbreak is the worst in Delhi is that this time serotypes Type 2 and Type 4 are the dominant strains detected, according to a report by the All India Institute of Medical Sciences (AIIMS) in Delhi.

The first major epidemic of dengue hemorrhagic fever, a severe form of dengue that can often be fatal, occurred in India in 1996 in areas around Delhi and Lucknow. Since 1996, India has seen periodic dengue outbreaks, with the number of cases increasing with each passing year.

“Nineteen ninety-six was the first major epidemic in Delhi and north India and that was of hemorrhagic fever with dengue 2 and 4 being the strains that were isolated, causing a high rate of death,” said Ekta Gupta, additional professor, department of clinical virology at the Institute of Liver and Biliary Studies in Delhi.

Gupta remembers 2003 as the turning point for Delhi. She was a senior resident at the microbiology department of AIIMS, when the first case was reported in August. Gupta was amazed when the clinician gave a query for dengue. “We were wondering if this is even possible in Delhi since it had not been reported for a while. We didn’t even have tests available because although diagnostics were used in 1996, routinely, these tests were not kept in the lab.”

It did turn out to be dengue— and the cases flooded in. “That year was just the beginning. After that year, dengue cases have been reported every year,” says Gupta.

Continued survival of a deadly mosquito

Experts say the increase in cases can be attributed to increases in long-distance travel, population growth and urbanization, lack of sanitation and ineffective mosquito control—but also better surveillance and reporting of cases. With the high prevalence of the carrier mosquito and dense population, dengue is a huge problem for India.

“This is not just a medical issue—this is a vector-borne diseases, which makes it more of an environment management issue. With increasing urbanization or unplanned urbanization, there is more scope for vectors to grow. The incidence and geographical reach of the disease are bound to expand,” said P.A. Azeez from the division of environmental impact assessment, Sálim Ali Centre for Ornithology and Natural History, Coimbatore.

Dengue, or dengue hemorrhagic fever, is caused by a small black mosquito with white stripes called Aedis aegypti, the primary vector for the disease. The 5mm mosquito takes seven to eight days to develop the virus in its body. It rests in dark corners of houses, on hanging objects such as clothes or under the furniture.

During the outbreak, there is a human cycle, and during the non-outbreak period there is a mosquito cycle. But even during the non-outbreak period—typically when the temperature falls—the virus remains, although just in mosquitoes. And when the mosquito population peaks during the monsoon due to water collection, they start biting humans (only female mosquitoes bite, needing the blood to develop eggs), which is when the mosquito-human cycle starts.

The dengue virus is spread through a human-mosquito-human-mosquito cycle. “If we have to stop these outbreaks, we have to break this cycle,” says Gupta.

When a mosquito bites a person who has the dengue virus in their blood (because of a mosquito bite), the mosquito becomes infected with the dengue virus. The mosquito will remain infected with the dengue virus for its entire life, generally three to four weeks.

It breeds in any containers with small to large quantities of water but its eggs can survive without water for more than a year.

“So now the situation in Delhi is that the frequency of outbreaks has increased and multiplicity of the serotypes detection is there. But there is no large-scale study. Isolated studies which are hospital based are taking place,” says Gupta. She stresses the need for large-scale epidemiological studies along with studies on mosquitoes in the inter-epidemic phase so that experts can find ways to control the next outbreak.

“When the blame game starts, the fingers are always pointed at the doctors, but why? We are doing our best, but we can only treat the symptoms. This is something that can be prevented and we need to understand how to control these infected mosquitoes from growing,” Gupta says.

Fogging operations and larvicidal treatment in hot spots should be conducted before the rainy season rather than after cases start pouring in, Gupta said.

Fever clinics

There are 499 hospitals in India which have been listed as sentinel surveillance hospitals for dengue this year. Of them, 33 are in Delhi. In most places, hospitals have been flooded with people suspecting they have dengue. Many are turned away as doctors are overstretched. The Delhi government increased the bed strength for dengue patients from 945 to around 4,000 beds this year.

In the wake of this year’s outbreak which led to hundreds of panicked people flooding ill-equipped hospitals with dengue-like symptoms, the Delhi government started 55 fever clinics in government dispensaries.

One afternoon last month—it was a weekday—the small government dispensary in south Delhi’s busy Saket area was heaving with 150 people, most complaining of fever and many in a state of fear.

Around 10 patients crowded the small examination room, shouting in panic-stricken voices even as Saurabh Nagpurkar, the harried medical officer on duty, bellowed back, asking everyone to make a queue.

“Out of the 150 patients that have come to the fever clinic since the morning, 20 were suspected of dengue and only one has been confirmed,” says Nagpurkar after finishing his shift. “These clinics definitely help because all these people would be on the waiting list at the hospital and if anyone does have dengue, they would get neglected.”

Delhi has reported the highest number of cases, followed by Haryana with 5,452 cases and Karnataka with 4,158 cases. “We have been working continuously for months—no holidays. It is exhausting, but it definitely helps that quite a few of these patients can come to the fever clinics instead of waiting at the already overflowing government hospitals,” says Nagpurkar.

The search for a vaccine

There is no way out with dengue except for prevention, as a cure does not exist. There are no vaccines against the disease despite worldwide efforts to develop one. The closest to approval is French drug maker Sanofi SA’s experimental dengue vaccine, which showed efficacy for all four strains and against dengue hemorrhagic fever in its Phase III clinical trials.

“It is extremely challenging to develop a vaccine for dengue. A major hurdle which has come to the fore from Sanofi’s efforts on developing live attenuated dengue vaccine, is the phenomenon of viral interference. This results in an imbalance in the immune response elicited against the four serotypes,” says S. Swaminathan, professor, department of biological sciences at the Hyderabad-based Birla Institute of Technology and Science. He is a key member of the team working on the dengue vaccine in India.

Viral interference occurs when an infection by a virus results in resistance in cells to infection by a second unrelated virus.

“Another important hurdle is the lack of an animal model in which experimental dengue vaccines can be tested which can reliably predict efficacy in humans. Thus, when we take an experimental dengue vaccine, (even) after animal experiments, into human trials, we are taking a blind leap. This is a challenge,” Swaminathan adds.

There are efforts being made in India to develop a dengue vaccine that can overcome these challenges. Under a department of biotechnology-funded initiative as part of an Indo-US Vaccine Action Programme, the Delhi-based International Centre for Genetic Engineering and Biotechnology has shown promising preliminary results in experiments with mice.

“Unlike Sanofi’s live attenuated vaccine, this is a non-replicating sub-unit vaccine candidate produced in a yeast host, and bypasses the problem of viral interference. This vaccine is basically a virus-like particle which displays on its surface ‘bits’ of the surface proteins of all four dengue virus serotypes. These ‘bits’ stimulate a potent immune response, that can block the infectivity of the four dengue virus serotypes,” Swaminathan says.

But a vaccine and cure still seem like a distant dream, which puts the onus on civil authorities and state governments to prevent outbreaks from becoming as common as they have become.

“India represents about half of the global population estimated to be at risk of dengue infection by the World Health Organization. Unfortunately, we do not have any systematic surveillance mechanism and consequently no reliable epidemiological data,” says Swaminathan. According to a study published in American Journal for Tropical Medicine and Hygiene in 2014, the National Vector Borne Disease Control Programme captures only 0.35% of the annual number of clinically diagnosed dengue cases in India.