Researchers have identified blood proteins that could detect at an early stage a lesser-known malarial parasite, Plasmodium vivax, which has become more virulent among the Indian population in the last few years.
The finding is significant since India accounts for more than 50% of global vivax malaria cases.The treatment of the strain is a challenge because the parasite has a longer incubation period and can remain dormant in the liver — a trait absent in falciparum malaria.
A 28-member team led by the Indian Institute of Technology — Bombay (IIT-B) collected 200 blood samples from three endemic cities — Mumbai, Kolkata, and Bikaner (Rajasthan) for one malaria season in 2014. In Mumbai, KEM, Sir JJ and Hinduja hospitals participated in the study.
Malaria caused by falciparum or vivax may lead to kidney failure, seizures, permanent neurological damage, coma and even death. While both strains cause fever and flu like symptoms, doctors cannot detect the development of vivax malaria during the early stages.
“Markers for identification of vivax malaria can shorten the time required for diagnosis, as early diagnosis and treatment lessens the severity,” said Dr Arunansu Talukdar, medicine department, Medical College Hospital, Kolkata, and a co-investigator.
Researchers said falciparum malaria is well studied with a case definition by the World Health Organisation (WHO). At present, doctors follow the diagnostic procedure suggested by the WHO for severe falciparum to determine the debilitating impact of vivax strain, but recently the world health body recognised the latter as a separate entity. Vivax patients are treated with standard anti-malaria drugs, including Chloroquine, which are effective for falciparum. “Inadequate or inappropriate treatment can lead to drug resistance in the long run,” said Dr Sanjay Kochar, professor and clinician at SP Medical College, Bikaner.
“Across the country, including Mumbai and Maharashtra, the increasing number of cases with vivax malaria has not been studied well. Unlike the past, most malaria cases today in regions such as Maharashtra and Rajasthan are transmitted via vivax parasite,” said professor Sanjeeva Srivastava, lead investigator, and head of the proteomics research at the department of biosciences and bioengineering, IIT-B.
Researchers recorded approximately 90% of patients with vivax malaria, with only 10% patients having falciparum in the Mumbai part of the study. Unlike falciparum malaria which is more dangerous, vivax malaria is usually associated with extremely low parasite load but can still be severe, said professor Swati Patankar, a co-investigator.
“Parasite load in such patients is not a good indicator of the acuteness of the infection,” said Dr Jayanthi Shastri, a collaborator from the municipal corporation-run BYL Nair Hospital, Mumbai.
To look for proteins that cause the switch from non-severe to severe malaria, the study compared 200 blood samples across three groups — severe vivax patients, non-severe patients and healthy group.
Through a series of laboratory investigations, the study has listed potential predictive protein biomarkers for vivax malaria severity — superoxide dismutase, vitronectin, titin, apolipoprotein E, serum amyloid A, and haptoglobin — that are likely to indicate changes in the patient during various stages of the disease.
When patients developed complications, the team found changes in five biological pathways — oxidative stress pathways, cytoskeletal regulation, lipid metabolism, acute phase pathway and amino acid biosynthesis — of patients with severe vivax cases.
The team found that one of the protein levels, serum amyloid A, increased in severe disease conditions. But in case of another protein – haptoglobin – the count dropped drastically. This trend was found to be unique in malaria patients as compared to other febrile diseases (dengue and leptospirosis).
It is here, said researchers, that the panel of these protein biomarkers with unique trends, and not individual proteins, in the blood could determine the severity of malaria caused by the vivax parasite. Studies are now underway to expound on the severity between falciparum and vivax.
VICIOUS VIVAX ON THE RISE
A recent study at Medical College Hospital (MCH) Kolkata recorded 22% of 900 vivax cases of severe nature. “There is no separate diagnostic criterion for severe vivax malaria. Anti-malarial drugs, which are commonly used, cannot kill dormant phase of vivax in liver tissue. That’s why relapse is quite common in vivax malaria unless specific drug (Primaquine) is not administered,” said co-investigator Dr Arunansu Talukdar, medicine department, MCH.