How Kerala reduced mortality from amoebic meningoencephalitis

Pro-active case detection and aggressive treatment led to the saving of 14 lives of the 19 infected with the brain-eating amoeba, bringing down the mortality rate to 26% from the global rate of 97%

Children frolicking in neighbourhood ponds in the summer months is a common sight in Kerala, a State that has an abundance of water bodies. The summer this year, however, took all the pleasure out of the water games for children when many young children fell prey to a rare but lethal infection of the central nervous system, amoebic meningoencephalitis, caused by free-living amoebae (FLA) found in freshwater, lakes, and rivers.

Reassurances from public health experts that the infections were sporadic did nothing to ease public anxiety because of the frequency with which amoebic meningoencephalitis was being reported in the State from various districts. Most of the affected were young children from 5–15. This picture changed dramatically in the month of August when, quite unusually, an all-adult case cluster of amoebic meningoencephalitis — eight cases in all — was reported from Thiruvananthapuram.

But despite reporting an unusually high number of 19 cases of amoebic meningoencephalitis in five months, Kerala also managed to create medical history of sorts because it managed to save 14 out of the 19 cases, bringing down the mortality rate of amoebic encephalitis, from the global rate of 97% to 26%. On September 12, all 10 persons who were undergoing treatment for amoebic encephalitis at Thiruvananthapuram Government Medical College hospital were discharged, having completed the 28-day treatment course of the State-adapted U.S. Centers for Disease Control and Prevention treatment protocol .

“This is a unique feat for Kerala, which is sure to enter global literature on the disease. It was a huge learning experience in itself because we could show that if identified and treated early, we have a fighting chance to save patients with amoebic meningoencephalitis. The infection usually deteriorates so fast that there is no therapeutic window for clinicians to intervene, “ says R. Aravind, head of Infectious Diseases at Government Medical College Hospital, Thiruvananthapuram.

When sporadic cases of amoebic meningoencephalitis began to be reported from North Kerala in May-June, all clinical features were suggestive of primary amoebic meningoencephalitis (PAM), a disease caused usually by infection with Naegleria fowleri, a microscopic amoeba commonly called the “brain-eating amoeba.” The State then set up an experts’ group to bring out technical guidelines on the prevention, diagnosis and treatment of amoebic meningoencephalitis.

What is PAM?

There are two types of amoebic encephalitis, namely primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE). Primary amoebic meningoencephalitis (PAM) is a disease caused usually by infection with Naegleria fowleri, a microscopic amoeba commonly called a “brain-eating amoeba”. This infection destroys brain tissue, causing severe brain swelling and death in most cases. PAM is rare and usually occurs in otherwise healthy children, teens, and young adults, and has a high fatality rate because of rapid onset and delayed diagnosis. The initial symptoms of PAM are indistinguishable from bacterial meningitis, while the symptoms of GAE can mimic a brain abscess, encephalitis, or meningitis. Both PAM and GAE are almost uniformly fatal with only few reported survivors, because of its rapid onset and delayed diagnosis.

“Only 11 survivors of confirmed N fowleri PAM have been reported in medical literature until now. There is not much in the literature on amoebic encephalitis caused by FLA other than N. fowleri. Kerala has reported amoebic infections caused by N. fowleri, Vermamoeba vermiforis as well as Acanthamoeba. Though we do not have the complete genomic sequencing information on all cases, and we yet to confirm if all were cases of PAM were caused by N. fowleri, we just added 14 more persons to the list of survivors,” Dr. Aravind says.

Amoebic meningoencephalitis occurs more often during the warmer months of the year and in warmer climates. There is no seasonal variation with GAE. The risk for infection has been estimated at 1 case per 2.6 million exposures to N fowleri. Patients typically have a history of swimming, diving, bathing, or playing in warm, generally stagnant, freshwater during the previous one to 9 days and this feature was common for all cases reported in Kerala .

In addition to swimming or diving in water bodies contaminated with N fowleri, the use of neti pots for the treatment of sinusitis (using unsterilised tap water) has been implicated in N fowleri infection.

The deadly Naegleria species are ubiquitous in soil and fresh or brackish water (lakes, rivers, ponds). In general, they are sensitive to environmental conditions such as aridity and pH extremes and cannot survive in seawater. As it grows best at elevated temperatures, N fowleri has been isolated from warm-water bodies, including man-made lakes and ponds, hot springs, and thermally polluted streams and rivers.

According to literature, the free-living amoeba with the most evidence of the effects of climate change is N. fowleri. Climate change raising the water temperature and the heat driving more people to recreational water use is likely to increase the encounters with this pathogen.

PAM develops after several days of exposure to contaminated water sources. The clinical presentation of PAM is often indistinguishable from bacterial meningitis. Headache, fever, nausea, rigidity of the neck, and vomiting are the most common symptoms and usually appear 5–7 days after the initial exposure but may also develop after only 24 hours.

By the time other more common causes of meningitis are ruled out and the diagnosis of PAM is considered, it is often too late to save the patient from the cerebral edema that quickly develops and causes death. The disease phase lasts for an average of 6 days and death occurs 4–11 days after onset

Pathophysiology

The amoeba enters through the mucosa of the nasal cavity and the cribriform plate (the cribriform plate is located at the base of the skull and acts as a barrier between the nasal cavity and the brain). The amoeba which enters the nasal cavity, crosses the cribriform plate to reach the brain, where they cause extensive inflammation, necrosis, and hemorrhage

The oral consumption of water contaminated with N. fowleri is not associated with symptomatic disease.

The pathophysiology is thought to be due to an amplified host immune response -- it is thought that N. fowleri causes an acute inflammatory cytokine response (as in the case of Covid-19), leading to neuronal damage and subsequent irreversible brain damage.

Unusual cases and case clusters

Kerala also reported an unusual case cluster of amoebic meningoencephalitis from Athiyannoor grama panchayat in Neyyattinkara taluk in Thiruvananthapuram. A detailed outbreak investigation, however revealed that it was not mere exposure to a mossy, green algae-ridden pond in the neighbourhood, but risky behaviour on the part of a group of youth that landed them all in the medical college hospital with the life-threatening amoebic encephalitis infection.

Two weeks after the death of a youth from the locality following encephalitis, with a history of exposure to a stagnant water body, when a second case turned up from the same area, the health department was alerted to the unusual possibility that there could be a clustering of PAM cases. Health officials reported that youngsters in the locality were grouping by the pond, mixing tobacco, snuff, or other addictive substances with the water from the pond and then inhaling it using handmade contraption — almost akin to vaping. This was a particularly risky behaviour as they gave a direct entry for amoeba into the brain.

With the help of the local body members, health officials managed to track all the youth in the locality who were known to be using snuff in this way. They were all asked to get admitted to the MCH as soon as they developed symptoms. Seven youths were thus picked up early and their CSF samples tested positive for amoebic encephalitis.

Clinicians also got to deal with a lone case wherein the patient was an urban dweller, with no contact with ponds of water bodies. The patient’s history revealed that in his house, water from the well was pumped into the overhead tank and then redirected to the pipe system. The overhead tank had not been cleaned in ages, and thus it was possible that the water harboured amoeba. The patient also had a past history of a head injury, which meant that the cribriform plate may not have been intact, aiding the quick entry of amoeba into the brain during nasal ablution.

Aggressive treatment

The State set up a special medical board, and the patients were treated as per the protocol with a cocktail of antibiotics. What turned the tide in favour of the patients was the introduction of the drug Miltefosin into the antibiotic cocktail. Miltefosine is an anti-parasitic agent, but its use is rare now, and supply is also limited. Amphotericin B has been the mainstay of PAM treatment, but Miltefosine was one of the cocktail of drugs that seemed to give good results, and all of the well-documented PAM survivors across the globe have received it as part of their treatment regimen.

It was pro-active case-finding by clinicians — checking for the presence of amoeba in CSF samples whenever acute encephalitis syndrome (AES) cases were encountered — which threw up more cases. This high degree of clinical suspicion on encountering unusual cases of AES is being maintained by all clinicians in the State since its first Nipah encounter in 2018. Early case finding and aggressive management saved lives.

New learnings and precautions

With several amoebic encephalitis cases reported from multiple locations, one should assume that amoeba is present in most water bodies except in chlorinated water and that the increased environmental heat and other aquatic factors may be aiding the increase in its concentration. The focus of the State health department is now on creating IEC campaigns for the public, to narrow down possible risks and incorporating the new learnings that emerged from this intense encounter with amoebic encephalitis.

The precautions now specify that no one should dive headlong into water bodies and that it is safer to use nasal plugs while swimming. Persons who have had head injuries or nasal surgery in the past should absolutely stay away from entering stagnant water bodies. Under no circumstances should one snort water into the nose while washing one’s face or when swimming in ponds. Those in the habit of sinus irrigation (rinsing the sinus) should use sterilised water and not tap water.

The current directive to all clinicians is to take a close look at the CSF for the presence of amoeba in all cases of meningoencephalitis, irrespective of whether the patient has had direct or indirect contact with water bodies. This is because early diagnosis and treatment might be life-saving in an infection which is almost always fatal, a learning experience that has been unique to Kerala.

Research on PAM

Kerala has also taken the lead to invest in research on the One Health platform to study amoebic meningoencephalitis. A technical workshop organised last month had experts from the Indian Council of Medical Research (ICMR), Institute of Advanced Virology, AV Medical College, Puducherry, Indian Institute of Science, Bengaluru, and the State Pollution Control Board discussing the environmental biotic and abiotic factors encouraging the abundant growth of amoeba in water bodies in the State, public awareness creation, scaling up diagnostic aspects, particularly molecular diagnostic techniques to aid early detection of PAM.

The National Institute of Epidemiology and the ICMR have also proposed to do a case control study to determine why only a few among the scores of people entering the same waterbody contracted PAM.

(maya.c@thehindu.co.in)

Published - September 20, 2024 05:00 am IST