Is it dangerous to Rabies Vaccine for Immunodeficiency patients


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What is Immunodeficiency?

Immunodeficiency is a general term agreed upon in conditions where the immune system’s requirements to fight disease and infection can overcome difficulties or deficiencies.

Therefore, immunodeficiency patients will experience various infections or arise from malignant body cells. In general, immunodeficiency syndromes can be categorized based on components of the immune system that repair the disorder.

Abnormalities in B cells will cause humoral immunity failure. This type of immunodeficiency will cause hypogammaglobulinemia (reduced number of antibodies) or agammaglobulinemia (no antibodies).

Meanwhile, abnormalities in T cells will cause immunity damage that is mediated by cells, which will leave patients vulnerable to viral infections. This type of immunodeficiency usually improves with the risk of secondary immunodeficiency. Severe combined immunodeficiency (SCID) is the most severe and fatal type of immunodeficiency.

In the case of SCID, B cells and T cells cannot work normally, so the patient will be vulnerable to all types of infections. Although less common, other components of the immune system, such as granulocytes and the body’s complement system, can also overcome problems due to immunodeficiency safety.

Causes of Immunodeficiency

Immunodeficiency can be primary or secondary. Primary immunodeficiency is a congenital disease; this means that the disease has been suffered by the patient from birth and may be obtained from his parents.

In primary immunodeficiency, genetic factors have an important role. Patients with this type of immunodeficiency are born with abnormalities in certain components of their immune system. At present, there are 80 types of primary immunodeficiency that have been identified. Meanwhile, secondary immunodeficiency is an acquired disease.

There are various external factors that can cause this condition, including old age and malnutrition. Diseases that can cause immunodeficiency are chronic infections, disseminated tuberculosis, acquired immune deficiency syndrome (AIDS) and cancer, especially malignant cells that are in blood cells and bone marrow. Splenectomy, which is an operation to remove the spleen for some reason, can also cause immunodeficiency syndromes.

In addition to these factors, there are certain drugs that can interfere with the immune system, thus causing a weakening of the immune system. These drugs include chemotherapy drugs, drugs for graft, steroids, and others. Secondary immunodeficiency is more common than primary immunodeficiency.

The main problem is immunodeficiency

The main effect of immunodeficiency syndrome is that patients are increasingly susceptible to infection. Patients with humoral immunity will be susceptible to bacterial infections.

Patients with this type of immunodeficiency will experience recurrent respiratory infections, including pneumonia, infections of the digestive tract, and meningitis. Chronic infections, such as otitis media, can also occur.

Patients with agammaglobulinemia tend to cause severe infections and tend to cause fatal conditions. Meanwhile, patients with immunity-mediated cell immunity will be vulnerable to infections due to viruses and fungi. In patients with this disease, infectious viruses that are not yet active, such as Varicella zoster and Herpes simplex, can spread. Fungal infections will also affect all bodily functions. Candidiasis or yeast infections also often occur, usually in the mucous membrane.

The immune response is a response that occurs with interactions between B cells and T cells; So, usually patients will discuss different problems at the same time. Therefore, patients who use humoral immunodeficiency can also use recurrent and chronic viral infections, while patients who use cell-mediated immunodeficiency are also susceptible to pyogenic bacterial infections. Patients with severe combined immunodeficiency will have multiple infections at the same time.

Rabies is a rapidly progressive viral encephalitis caused by RNA viruses of the family Rhabdoviridae, genus Lyssavirus. Dogs are the major reservoir for these viruses worldwide and usually transmit the virus by conveying their infected saliva through the penetrated skin of bitten humans or animals.

The usual incubation period in humans ranges from 10 days to 1 year (average 20–60 days). Rabies causes 30,000–70,000 human deaths throughout the world each year. The rabies-related death rate is ≈100% in unvaccinated patients.

Thus, preexposure prophylaxis and postexposure prophylaxis (PEP) are the main effective approaches for treating the disease . I describe a case in which an acceptable antibody response to rabies vaccine did not develop in an immunocompromised patient. I also searched the literature for similar cases and summarize the demographic, clinical, and epidemiologic characteristics of such case-patients to date.

A 74-year-old woman was admitted to the Sanglah hospital in August 2018; he reported progressive general weaknesses that had begun several months before his acceptance. The blood count upon entry shows severe lymphopenia (250 lymphocytes / μL). In addition, his recent medical history shows that he has been exposed to category II or III (4) exposure to monkey bites, as classified by the World Health Organization (WHO), 10 days before entering, when he traveled in a country where rabies is endemic.

The patient was treated with a standard PEP regimen for immunocompromised patients according to Ministry of Health guidelines at the time he was treated. This guideline is also in accordance with the latest guidelines from WHO and the American Advisory Committee on Immunization Practices (ACIP) regarding PEP for patients with immune disorders (4,6). In short, 5 doses of cell culture rabies vaccine, of which pure Vero cell (PVRV) vaccine and pure chicken embryo cell vaccine are available, are given intramuscularly on day 0 (along with 20 IU / kg of human rabies immune globulin) .

The PEP regimen for patients starts 12 days after the potential exposure to the rabies virus through monkey bites by administering the vaccine. On the 15th day of the PEP regimen, 2 bottles of serum and 1 bottle of cerebrospinal fluid (CSF), each containing> 2 mL of fluid from a routine sample, were tested for rabies for neutralizing antibody (VNA) by the National Rabies Laboratory at the Kimron Veterinary Institute. These samples were adequately cooled until the time of analysis. VNA titers are measured using a neon rapid focus inhibition test.

Before the fifth PVRV could be administered, the patient died of sepsis, most likely of nosocomial origin, induced by her rapidly progressive immunodeficient condition. The pathologic and histologic findings from a lymph node biopsy specimen were concordant with the diagnosis of advanced B-cell lymphoma. reported a patient who had an inadequate rabies antibody response to a standard PEP regimen possibly because of an underlying immune deficiency condition.

In addition to these case patients, from a literature survey, we found reports of 7 additional immunocompromised patients who also showed a lack of acceptable response rates. These patients have followed various rabid PEP regimens with various types of vaccines, methods of administration, number of injection sites, and doses. However, apart from these steps, an adequate immune response did not develop in these 7 patients during the entire follow-up period of each study.

WHO cut-off titer level is 0.5 IU / mL (4), equivalent to complete virus neutralization in serum dilution: 1: 50 by rapid fluorescent focus inhibition test, and lower titers recommended by ACIP (serum dilution 1: 5) (6) is an arbitrary laboratory value that does not correlate directly with seroprotection. In addition, the WHO cut-off titer is initially based on an adequate level of immune response that is needed when repeatedly monitoring healthy patients who need prophylactic pre-exposure regimens regularly, for example, veterinarians.

The response of a VNA titer should ideally be determined 2-4 weeks (WHO) or 1-2 weeks (ACIP) after the last dose of the vaccine to assess whether additional doses are needed (4,6). This points to the limitations of the current study, which has 1 measurement point on day 15; thus, the measurement time in our study might only reflect the immune response to the first 3 doses (days 0, 3, and 7).

The same limitations also apply to previously published studies (8-12), all of which have the last VNA measurements on the same day or only a few days after the end of the vaccination regimen. However, not even a slight increase in VNA titer was observed on day 15 in either CSF or serum samples, which might imply a lack of further immune response. A low or undetectable VNA level on day 90, the last day of the PEP regimen, was also observed in several previous studies (8-10). As such, we cannot expect antibody titers to increase even further, even if additional measurements will be taken 1-4 weeks after the last vaccine dose as indicated by the guidelines.

In conclusion, current epidemiological knowledge and existing PEP regimens may not provide sufficient guarantees for public health experts and consult doctors when advising and treating immunocompromised patients. Therefore, establishing a collaborative international rabies registry with special emphasis on patients with immune disorders can provide evidence that will contribute to decisions regarding appropriate vaccination protocols.