Why does Brazil not resume production of the Montenegro test?

The Montenegro test evaluates the delayed response of cellular hypersensitivity and represents the main complementary test for the diagnosis, especially for the mucocutaneous form

Tegumentary Leishmaniasis (TL) is a public health problem, subject to compulsory notification and that can have very serious consequences if not treated. Diagnosis is important to safely treat patients and avoid indiscriminate use of potentially toxic treatments However, diagnosis is a difficult task. The serological tests applied to diagnose leishmaniasis are based on the detection of the specific humoral response in infected mammals, however, they fail to identify asymptomatic cases or when patients have low levels of antibodies against Leishmania. In addition, cured and treated patients generally present specific humoral reactivity for parasitic antigens at similar levels, months or years after treatment, thus making it difficult to differentiate those with active disease. As a consequence, these patients are erroneously classified as false positives in serological assays.

Montenegro Intradermal Coronation (IDRM) or leishmaniasis skin reaction is a simple and straightforward test, of  low cost and easy to perform. However, with the regulation imposed on intradermal products for diagnosis, the Montenegro test was no longer produced in Brazil and abroad, causing an impact on the identification and treatment of cutaneous leishmaniasis, a neglected disease. The Montenegro test consists of an intradermal injection of a solution containing an antigenic substance composed of dead promastigotes. The result is considered positive with the appearance of a hardened papule, equal to or greater than 5 mm after 48 hours of application in the anterior forearm. The IDRM, also known as the leishmanin skin test, evaluates the delayed response of cellular hypersensitivity and represents the main complementary test for the diagnosis of TL. To learn more about the subject, the Communication Advisory of the Brazilian Society of Tropical Medicine (BSTM) interviewed Dr. Mady Barbeitas, a veterinarian with specialization in science, technology and innovation policies and PhD in public health and social sciences.

Check the interview in full:

BSTM: How important is the Montenegro Test?

Dr. Mady Barbeitas: The Montenegro test can make a difference in numerous scenarios conducive to the circulation of Leishmania, mainly because it is simple and cheap. Poor and/or hard-to-reach areas, areas of armed conflict, forest and indigenous areas in Brazil and around the world, are good examples of where it could make a difference. It is noteworthy that these scenarios are not rare and represent a large part of the endemic areas for cutaneous leishmaniasis. Moreover, in a context where there are no other simple and inexpensive option for use, this test becomes essential because it avoids the indiscriminate use of antimonial. The use of antimonial, although unofficial, is a very common practice to establish the differential diagnosis in lesions suggestive of leishmaniasis.

SBMT: What are the advantages and disadvantages of this test?

Dr. Mady Barbeitas: As mentioned, the main advantage of the Montenegro test is that it is simple, inexpensive and can be used in virtually any scenario. It is also an excellent surveillance tool in epidemiological studies and recently one could think of its use as a marker of immunity in clinical trials of vaccines in humans.

The main disadvantage is the lack of accuracy in the diagnosis of cutaneous leishmaniasis given that the test does not distinguish a recent infection (active lesions) from a previous and already cured infection. However, it can be used as a complementary test to other clinical laboratory tests in scenarios where this is possible.

SBMT: We can seek better diagnostic tools for TL, Brazil has the infrastructure and capacity for this. So, in your opinion, why doesn’t the country resume the production of the Montenegro test?

Dr. Mady Barbeitas: I recently discussed this in the article that is in the process of being published in the Journal of the Brazilian Society of Tropical Medicine (RSBMT). At the time of the interruption of the production of the Montenegro test due to the new requirements of the National Health Surveillance Agency (Anvisa), the expert committee on cutaneous leishmaniasis, which participates in numerous meetings in the Ministry of Health and in international organizations, influencing decision-making and prioritization of actions on the disease, pointed mainly to the need for a new and more advanced point of care diagnostic test from a technological point of view. The Montenegro test was considered “archaic”, not worth the investment they supposedly imagined would be high for an “archaic” test. It would be better to invest in something new right away. The problem is that for any innovation to reach patients, especially in the context of a neglected disease, it can take several years or simply never reach the shelves, even with the knowledge and technology at their disposal.

It is important to emphasize that neglected diseases do not form a strong and attractive (or profitable) market, in this context the action of the Government is essential to guarantee the purchase of the new technology. So, in a way, the need to produce the Montenegro test was overshadowed by a promise of a future that may never come.

It is undoubtedly necessary to invest in an innovation in the diagnosis of cutaneous leishmaniasis and some organizations are already taking this demand forward. However, we must not forget the Montenegro test used over a hundred years ago. Brazil was the only world producer of leishmanin; this product simply does not exist in another country, and we have the ability to resume production within the requirements of Anvisa very quickly. If the former supplier, the Center for the Production and Research of Immunobiologicals (CPPI) does not have the necessary infrastructure to produce according to Good Manufacturing Practices, other laboratories, such as Bio-Manguinhos, could resume production without having to restructure their industrial plant.

SBMT: How can the scientific community contribute?

Dr. Mady Barbeitas: The expert committee on cutaneous leishmaniasis and the scientific community in general should also support the resumption of production of the Montenegro test through the publication of manifests, taking this agenda to meetings within the Ministry of Health, Pan American Health Organization (PAHO) and other bodies. This should also be a priority in the meetings of the Brazilian Society of Tropical Medicine and the meeting of MedTrop in Belém would be a good opportunity to address the issue.

The Network of Leishmaniasis Researchers and Collaborators (redeLEISH) launched during WorldLEISH 7, the most important event on leishmaniasis in the world, a Manifesto that addresses the urgent need to develop simple diagnostic techniques for cutaneous leishmaniasis. The document will circulate during the ChagasLeish meetings, a satellite event that will be held simultaneously with the Congress of the Brazilian Society of Tropical Medicine (MEDTROP), that will take place, in Belém (PA) from November 13 to 16.