Leprosy: researchers find potential markers for disease diagnosis
Early diagnosis and treatment strategy are fundamental to cure, which decreases the chance of sequelae10/09/2022
Leprosy persists as a global public health problem, accounting for approximately 200 thousand new cases diagnosed worldwide annually. In addition, millions of people still live with some type of physical disability or deficiency due to the disease. Brazil ranks second among the countries with the highest number of cases in the world, behind only India. According to data from the “epidemiological bulletin of the Ministry of Health Leprosy 2022“, 155,359 new cases were diagnosed in Brazil between 2016 and 2020. In 2021, 18,318 new notifications were registered in the country, a reduction of 34% compared to 2019 due to the impact of the pandemic on disease control programs. Historically, leprosy presents more occurrences in the North, Northeast and Midwest regions. Diagnosis remains a great challenge, tests are limited and there are currently no kits or techniques that allow the laboratory diagnosis of the disease in all its complexity of clinical manifestations.
With this in mind, researchers from the Healing and Leprosy Laboratory of the National Reference Center for Sanitary Dermatology and Leprosy (CRNDSHansen) of the University of São Paulo at Ribeirão Preto Medical School (FMRP/SP) evaluated the levels of antibodies against a protein of the disease-causing bacterium in samples of newly diagnosed patients with leprosy, cases treated with polychemotherapy (PQT), household contacts of patients and healthy individuals living in the endemic city of Parnaíba (PI). The article “Serological Immunoassay for Hansen’s Disease Diagnosis and Monitoring Treatment: Anti-Mce1A Antibody Response Among Hansen’s Disease Patients and Their Household Contacts in Northeastern Brazil” was published in Frontiers in Medicine.
For the study, the researchers collected blood from 82 volunteers to evaluate antibodies against the Mce1A protein of the disease-causing bacterium Mycobacterium leprae. They were divided into four groups: new cases of leprosy in Parnaíba, patients treated in the former colony of Carpina (PI); people who lived with a person with the disease for at least six months before diagnosis; and another formed by healthy people, without diagnosis or contact with leprosy and who reside in the endemic region of Parnaíba. According to the biomedical clinical pathologist and first author of the study, Dr. Filipe Rocha Lima, the objective was to seek new markers that have the necessary sensitivity to diagnose the largest number of patients and to screen contacts, maintaining satisfactory specificity for a serological test.
“We demonstrated that IgA antibodies against the Mce1A protein are important markers of contact with the bacillus, due to their positivity in patients new cases, treated cases and contacts. Positive results for IgM serology were associated with active disease, as they were negative in treated cases and present in new cases of the disease. On the other hand, a higher frequency of positive tests for IgG serology was identified in patients already treated,” explains Dr. Lima. According to him, the results confirmed the importance of these molecules for the diagnosis of all clinical forms of the disease, therapeutic monitoring and contact tracing, as well as their better performance and accuracy compared to the examination of the antibodies against the PGL-I molecule of the bacterium.
Antibodies undergoing tests in various regions of Brazil with different levels of endemicity for the disease and with larger groups of patients, contacts and controls. The study aims to ensure the quality of the proposed assay and to evaluate the effect of bacillus circulation in the environment on the antibody levels of these individuals and for the evaluation parameters of a serological test, such as the assay’s positivity threshold by region.
Cases light up alert for challenging diagnosis
Brazil ranks second in the number of new cases in the world and about 93% of those registered in the Americas. Early diagnosis and administration of effective treatment are essential for cure, thus reducing the chance of sequelae. The diagnosis is mainly clinical, through dermatological and neurological evaluation. The available laboratory tests are complementary tools, but they have important limitations for identifying all clinical forms of the disease, therapeutic monitoring and especially the identification of only infected individuals, that is, before the appearance of signs and symptoms.
“With the use of antibodies against the Mce1A protein, we had the opportunity to identify cases of the disease even in early stages and with mostly neurological signs, the main difficulties of the other tests studied,” says Dr. Lima. Also according to him, the incorporation of new diagnostic technologies allows to eliminate the main gaps in the laboratory diagnosis of leprosy and contribute to the objectives of the World Health Organization (WHO) for the identification of initial paucibacillary cases, infected contacts and consequently for the interruption of bacillary transmission, effectively reaching zero physical disability and eliminating the stigma of the disease.
The researcher points out that until today there are no commercial kits capable of effectively diagnosing individuals who came into contact with the M. leprae bacillus and were infected, that is, identification of patients before the signs and symptoms of the disease. “Undoubtedly, the lack of technology with this sensitivity does not allow us to control the disease, in view of the continuity of the bacillary circulation provided by the absence of early diagnosis and subsequent prescription of polychemotherapy. Given this scenario, we invested in the evaluation of these anti-Mce1A antibodies to screen the contacts and a pattern of positivity that allows us to predict the onset of the disease and identify priority contacts for the implementation of a dermatoneurological evaluation of greater complexity,” he adds.
Finally, the researcher reveals that the final objective of the research is the implementation of low-cost diagnostic platforms, of easy execution and interpretation. These should be available not only to reference centers, which already have an evaluation apparatus superior to those available in less complex and basic health units, but also for all services of assistance, control and active search for leprosy.
Since the beginning of July, the Unified Health System (SUS) and the National Supplementary Health Agency (ANS) have included a rapid test for the detection of antibodies against the bacteria that causes leprosy in the list of mandatory procedures. It is an unprecedented reinforcement in the detection of antibodies against the bacillus, with Brazil being the first country in the world to offer it. The inclusion of the rapid test will also assist in population monitoring in areas of higher incidence and in the classification of suspected patients, since in some cases the disease may take several years to manifest. The versatility of the test is one of the advantages of use, since the conditions for testing are expanded, it can reach places of difficult access, since leprosy is a neglected disease that affects vulnerable populations.
For the dermatologist Dr. Maurício Lisboa Nobre, leprosy advisor at the World Health Organization (WHO) and researcher at the Institute of Tropical Medicine of UFRN (IMT), in Rio Grande do Norte, the great advantage of the rapid test is to increase the chances of early diagnosis of the disease, which allows the identification of infected individuals, who should be better investigated and monitored. That is, if these cases show signs of leprosy symptoms, they will be alert about this diagnostic possibility and the health team as well. “Another advantage is that communicants with a positive test, for five years, can make a closer follow-up, in the health unit”, he points out. However, the WHO advisor regrets the huge lack of complementary tests that are not yet accessible to the majority of the population, not even in specialized care units, such as electroneuromyography and peripheral nerve ultrasonography. According to Dr. Nobre, this really needs to improve in Brazil, in view of the latest publications of the Clinical Protocol and Therapeutic Guidelines of the Ministry of Health.
Record of cases increase in India
The district of Deoghar, a large city in Jharkhand, India, has seen a sharp increase in the number of leprosy cases recently. According to government data, 250 new patients were identified between April and August of this year, which are operationally classified into two categories based on the findings of skin and nerve lesions: those with fewer spots are kept in the Paucibacillary (PB) category while those with more are classified as Multibacillary (MB). The number of PB patients reaches 145, while MB patients add up to 105. A national program for the identification of leprosy patients is underway in the district and the field team is undertaking hard work to discover the affected patients.
Dr. Nobre recalls that India diagnoses around 115 thousand new cases of leprosy per year, while Brazil’s average is 25 thousand new cases. “However, when we look at the indicator, that is, the detection coefficient (number of cases is divided by population), our indicator reaches higher levels than India, because, although India has four times more cases, the population is much larger than that of Brazil. That is, proportionally, we have an indicator, a coefficient, a higher rate of leprosy than India”, he points out. Asked why our indicators remain so high, the dermatologist is categorical in stating that this is because we still have a very large social inequality, people do not have easy access to the diagnosis and, therefore, the indicators increase. “As leprosy is a disease with very clear social determinants and occurs mainly in disadvantaged populations from the socioeconomic point of view, who live especially in the peripheries of large cities, in population clusters, with little ventilation, with inadequate hygiene conditions, this facilitates the transmission of M.leprae,” he emphasizes.
About the disease
Leprosy is an endemic, infectious, chronic disease, transmitted by droplets of saliva eliminated in speech, cough, sneezing and nasal secretions, in close and frequent contacts with people who have not started treatment and are in an early stage of the disease. Hands, arms, feet, legs and eyes may suffer from alteration, decrease or loss of thermal, painful, tactile sensitivity and reduction of muscle strength. The nerves of the lower limbs, upper limbs and face are slowly compromised, changes that may go unnoticed. Treatment ranges from 6 to 12 months, depending on the clinical form presented. Medicines are provided free of charge at health facilities and should be taken daily. Treatment interrupts transmission and prevents physical disabilities.
Leprosy is considered a silent disease with nonspecific initial symptoms. Advanced symptoms include: spots with loss or alteration of sensitivity to heat, pain or touch; tingling, pins and needles, cramps or numbness in the lower or upper limbs; decreased muscle strength, difficulty in picking up or holding objects, or keeping shoes open on the feet; thickened and sore nerves, wounds that are difficult to heal, especially in the feet and hands; very dry areas of the skin that do not sweat, with hair loss, (especially in the eyebrows), lumps in the body; itching or irritation in the eyes; clogging, bleeding or wound in the nose. The disease can affect any individual and generate permanent disabilities. Early diagnosis prevents transmission, complications and deficiencies.