(Focus - India)
Dengue, a vector-borne, tropical disease, can sometimes be misinterpreted as a routine viral fever and leads to severe complications in the absence of timely diagnosis and treatment. Approximately 33 million cases of Dengue are reported in India each year, which accounts for a third of the global dengue burden. To counter this and bring awareness about Dengue and the preventive measures, the Ministry of Health and Family Welfare in India observes May 16th as National Dengue Day. In the same spirit of raising awareness, we interviewed Dr. V Ramasubramanian, a renowned infectious disease specialist from India, who enthusiastically highlighted the importance of proper diagnosis to avoid misinterpretation of the disease.
Dr. V. Ramasubramanian (MD, DTM&H (Lon), DGUM (Lon), FRCP (Glas)) is currently serving as a Senior Consultant Infectious Diseases, Apollo Hospitals, Chennai Director, Medical Services, Capstone Multispeciality Clinic, Chennai.
The role of public health is to assess, guide and monitor the situation, and develop policies to ensure access to safe and quality care. I feel it is the responsibility of every individual to ensure that things are properly taken care of, whether by early reporting or by early diagnosis.
Unplanned urbanization is identified as one of the reasons behind spread of Dengue in India (1). What are your thoughts on this?
Dr. Ramasubramanian: In any situation where man defies the rules of nature, problems ensue. Whether converting forest lands for cultivation, whether increasing proximity of wild animals with humans as in the exotic markets of Wuhan or Hong Kong, or whether there is unplanned urbanization, infections like Nipah, Zika, Encephalitis or COVID can occur. Wherever the normal laws of nature are broken, there is bound to be an increased possibility of infections, and it all leads to an occurrence of either an outbreak or novel infections, which can affect mankind. There are probably several more viral infections, which we are not even aware of, waiting to inflict human damage. There was a time in the past where dengue was reasonably well controlled, but now we have increased outbreaks of dengue in certain pockets world over, related to defiance of natural laws. So, it is rather intuitive that this is bound to happen again and probably with far worse impact.
What do you think is the role of public health officials in dengue-endemic region for sustainable prevention?
Dr. Ramasubramanian: The role of public health is to assess, guide and monitor the situation, and develop policies to ensure access to safe and quality care. I feel it is the responsibility of every individual to ensure that things are properly taken care of, whether by early reporting or by early diagnosis. In a country like India, where the contribution of National Health Care delivery is at best about 20% to 30%, it becomes important that private healthcare providers and citizens play a significant role in helping public health departments get over these outbreaks. So, I would not say it should be only a public health initiative, which is optimal in western countries where the National Health Service plays a huge role in health care delivery. In countries like India, it has more to do with individual citizen responsibility and private healthcare providers.
We understand that dengue can be easily neglected, and misinterpreted as a simple viral fever from patients, which later causes several complications. What can be done to educate and create awareness among people for timely diagnosis?
Dr. Ramasubramanian: There is a fundamental principle in infectious diseases, paraphrasing Vince Lombardi, a famous football coach in the United States, we say that ‘diagnosis is not everything, it is the only thing’. For any condition, diagnosis is of paramount importance to identify the problem and its source, because you cannot come up with a solution unless you identify and define a problem. And this message has to be very clearly spelled out to the public and the primary care physicians who are going to take care of these patients because the eye does not see what the mind does not know. It is the duty of both primary care providers and the patients to understand how dengue infects a person, and what it can cause.
As we are in a situation where the diagnostic modalities are sometimes more expensive than the treatment, I do not think people are going to invest in getting a diagnosis. Also, there is no specific treatment for dengue and the necessity for treatment is limited to a very small minority. So, if you are going to ensure that people can get diagnosed early, then we have to understand that treatment modalities have to be aligned accordingly.
Do you think severe dengue mortality rate can be reduced with timely intervention of diagnostic tests like by using point of care tests?
Dr. Ramasubramanian: Absolutely! I am a big fan of obtaining an accurate diagnosis. Unfortunately, a majority of people depend on antibiotics for all conditions. In a situation where a person continues to have fever, the demand of the patient is such that they want instant gratification. So, when the fever does not settle in 48 hours, they start on an antibiotic, and two days later, another one. Hence, I would say, patients are responsible for the self-treatment of symptoms, which can lead to several complications, including antibiotic resistance, especially in situations like dengue. So, point of care testing, which is inexpensive, easily accessible, and gives immediate quantifiable results, would play a big role in controlling the outbreak, improving outcomes and limiting collateral damage.
Accurate diagnosis is the only way forward. We need to have tests that have a high positive predictive, and negative predictive value. So, the hit rate should be good. Genetic tests such as polymerase chain reaction-based assays, are the way forward.
Do you see any innovation in point of care tests for dengue?
Dr. Ramasubramanian: We are resorting to tests either via genetic assays or enzyme-based antigen assays, which will give early reports. Systems for diagnosis are moving rapidly ahead in medical care. So, we should have a cheap and easily accessible test to detect dengue. There is definitely a lot of scope for this, especially when WHO is coming up with the basic essentials for diagnostics, and I think dengue diagnosis will definitely improve with time.
What are the challenges associated with implementing point of care diagnostics for dengue detection in endemic areas of developing countries like India?
Dr. Ramasubramanian: There are a lot of viruses that are very similar to dengue. For example, flaviviruses and arboviruses have cross-reacting antigens. Also, Zika tests may become positive in the case of dengue and in several other situations, where there will be an overlap of test results. So, getting a test that will specifically diagnose the condition is important. I think it is a matter of time, but we should have such tests available soon.
One of the research papers says that, “The irrational pharmacotherapy as a result of a misdiagnosis can be fatal for a dengue patient.” (2) Have you observed any misdiagnosed dengue cases, especially during COVID 19 pandemic?
Dr. Ramasubramanian: When you are having a COVID outbreak, ‘base neglect’ can happen. Everybody is diagnosed to have COVID at that time, and sometimes a case of dengue may be missed. Fortunately, I have not had any personal experience where the consequences have been disastrous. But yes, there is definitely a possibility that incorrect diagnosis can sometimes lead to adverse outcomes.
According to you what would be the reason for such misdiagnosis?
Dr. Ramasubramanian: The presentation will be very similar in a lot of these conditions. For example, sepsis is a severe bacterial infection, which leads to multi-organ failure, due to organ perfusion and immune response. Normally, when you say ‘sepsis’, you only think of bacterial infections which require antibiotics.
A study was done in low and middle-income countries, published in Lancet a few years ago. It said that in low-income countries, almost 60% of cases were because of ‘non-bacterial infections’, viral infections which varied anywhere from influenza to dengue to Hantavirus to several other viruses, which can present in a fulminating manner very similar to sepsis and septic shock. Yes, there is a definite possibility of misdiagnosis; there is a possibility of inappropriate analysis and deduction, leading to adverse consequences
What do you think can be done to avoid such misdiagnosis?
Dr. Ramasubramanian: Accurate diagnosis is the only way forward. We need to have tests that have a high positive predictive, and negative predictive value. So, the hit rate should be good. Genetic tests such as polymerase chain reaction-based assays, are the way forward. We still have to evolve, because the PCR test causes a lot of ‘noise’, in the sense that it picks up a lot of genetic material which may not be relevant. Weeding out the music from the noise is probably what people are doing right now to get more specific diagnostic tests.
In other words, ‘point of care’ diagnostic tests are the only way in order to avoid this type of misdiagnosis, right, Doctor?
Dr. Ramasubramanian: Definitely! It is necessary to come up with some diagnostic algorithms. Nowadays, artificial intelligence is steadily improving, so it would be great to have some innovation such as being able to relate the symptom/symptoms to the specific result. In addition, a prediction of the likely agent causing the problem would be a feather in the cap for diagnosis.
What interesting trends do you foresee in treatment and management pathway of dengue infection?
Dr. Ramasubramanian: About 10 years ago, I still remember that with patients who presented with, and were diagnosed with dengue and had a platelet count of less than one lakh, there was panic. All of them were admitted, all of them were transfused with platelets, and we used to run out of platelets! For patients whose platelet count was less than 50,000, people used to rush to give them platelets, till their platelet level improved.
But now we realize that patients with dengue, who have a low platelet count, what is called ‘thrombocytopenia’, surprisingly do not bleed. The chances of bleeding are less than expected. Unless the platelet count falls below 10,000 or 5,000, there is no need to transfuse platelets. This has been recommended by the National Guidelines as well.
Earlier, drugs like steroids were given to see whether the platelet counts could be improved, but now the trend is changing. Fluid management is probably going to play a very important role, and identifying symptoms which may portend a poor prognosis clinically, is what we are looking at. Yes, there are a lot of developments, at least in India, and we are able to recognize and manage things much better than in the past.
As the saying goes “Prevention is better than cure”. What do you suggest to a people living in a dengue endemic region as a preventive measure?
Dr. Ramasubramanian: In all aspects of medical care, we realize that treating a condition is passé.
You need to ensure that you diagnose patients who are at high risk and then make sure that you prevent them from getting the disease in the first place. To prevent heart attacks, we now use statins or Ecosprin. We are looking at measures that can be instituted much before a person develops a problem.
With regard to all infectious diseases, vaccines are now being looked upon, not just in children, but in adults as well. We have vaccines for shingles, flu, pneumonia, etc. We also have vaccines to prevent cancers, for example, vaccines against the human papilloma virus, and against Hepatitis B. We are looking 10 to 15 years ahead of the person developing a disease to prevent them from getting a human papillomavirus infection or a hepatitis infection; in this manner, we can safeguard and prevent one from probably developing cancers.
Similarly, dengue is a condition where treatment modalities are limited to being primarily supportive in most situations. Like the Western World has got rid of malaria, the only way to get rid of dengue is by administering a vaccine. In fact, the number of people getting dengue is several million times more than malaria! So, as I said, preventing dengue is the best option. We have still not fine-tuned them, because if the dengue vaccine is given to a person who has never been exposed to dengue, it can sometimes lead to adverse consequences when the person has the first attack of dengue. So, the way forward in dengue endemic regions is the introduction of vaccines so that people do not get dengue in the first place or even if they get it, they will be able to recover.
Thank you very much for an insightful discussion.
Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583666/
https://onlinelibrary.wiley.com/doi/10.1002/jmv.26987