Pediatric Acquired Immune Deficiency Syndrome

Introduction to Pediatric Acquired Immunodeficiency Syndrome Acquired immunodeficiency syndrome (AIDS), a childhood AIDS epidemic, is an infectious disease caused by the human immunodeficiency virus (HIV) invading the lymphatic system of children. AIDS is currently one of the most serious infectious diseases in humans. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of transmission: sexual transmission, blood transmission Complications: brain atrophy anemia

Pediatric acquired immunodeficiency syndrome etiology

Cause:

The pathogen of AIDS is HIV, which is a subfamily of lentiviruses in human retroviruses. It is a typical C-type RNA virus containing a single-stranded ribonucleic acid (ssRNA).

Pathogenesis:

The central link of HIV pathogenesis is to selectively consume large amounts of CD4 T lymphocytes, leading to defects in immune function. When HIV invades human body, it first recognizes CD4 T lymphocytes and macrophages, and the envelope protein gp120 of the outer membrane of the virus. Binding to the CD4 receptor and co-receptor on the cell surface, the conformation of gp120 is altered, and the site that binds to the chemokine receptor is exposed and acts to mediate the adsorption of HIV on CD4 cells, causing virus stripping. The shell, the core part of the virus enters the cell. Under the action of reverse transcriptase, the RNA of the virus is transcribed into double-stranded DNA. The double-stranded DNA integrates with the chromosomal DNA of the host cell under the action of integrase and forms proviral DNA, which is copied with the chromosome. Replication, in humans, from mucosal infection to the onset of initial viremia takes 4 to 11 days. After a brief period of high titer viremia, the virus spreads to the lymphoid tissues of the body. Due to the immune response of the body, the virus is replicated. Inhibition, the blood content of the virus rapidly declines. Since then, HIV infection has been divided into two different development trends, one is rapid progress, the infected person is rapidly morbid and dying; the other is slow Slow progress, the infection into the chronic persistent infection stage, the factors affecting the trend of HIV infection development is still unclear, may be related to the virus's virulence, content, host cell co-receptor and immune response ability differences.

Mechanism of CD4 T lymphocyte depletion: HIV can infect CD4 T lymphocytes and monocytes/macrophages and dendritic cells expressing CD4 molecules. The virus replicates, expresses, integrates and forms fused cells in susceptible cells, suggesting HIV It can interfere with or inhibit the normal function of cells, and even cause direct damage to cells. However, the specific immune response against HIV is the direct cause of damage to HIV-infected cells. The infected CD4 T cells can express HIV antigen on their surface. It is recognized and attacked by the body's cytotoxic T lymphocyte (CTL), which destroys the virus while destroying a large number of infected CD4 T lymphocytes, but HIV is highly variable, although a large number of viruses are cleared and mutated. The virus strain can still survive, invade and reproduce the nascent CD4 T lymphocytes; in order to recognize, attack and clear CTL, CD4 T lymphocytes are destroyed in large quantities, so that the CD4 T lymphocytes are finally Excessive consumption, the formation of secondary immunodeficiency, a variety of opportunistic pathogens take advantage of, and breed in the body and cause disease.

Pediatric acquired immunodeficiency syndrome prevention

The key to preventing pediatric AIDS is to prevent HIV-infected women and screen blood donors. Sexual pre-marital examinations should be strictly implemented. If the mother is an AIDS patient or HIV-infected person, strict measures should be taken to prevent transmission to future generations because of pregnancy, childbirth and Children can be infected during lactation. It is strictly forbidden to import and use blood products contaminated with AIDS virus. The most powerful preventive weapon is publicity and education. The prevalence and severity of AIDS should be widely publicized.

Vaccines that prevent HIV infection are called preventive vaccines, and vaccines that prevent the progression to AIDS after infection are called therapeutic vaccines. So far, there are no clear prospects for HIV vaccines to be widely used. The main difficulty in vaccine development lies in HIV. The pathogenic mechanism and the host's immune response to HIV are still not enough. Another important obstacle is the emergence of HIV variants. In HIV-infected patients, the mutation rate of HIV-1 is 0.1% to 1% per year, which means There is not only one virus in each HIV (+) person, but a group of HIV variants. The pathogenicity, growth rate and transmission characteristics of each variant are different. The genetic variation of HIV will affect its pathogenic mechanism. A good prophylactic vaccine should be able to induce long-term stable, systemic and mucosal protective immunity at small doses and protect against the world's most prevalent antigenic HIV strains. It must be effective. Safe, stable, easy to store, easy to use and inexpensive.

Pediatric acquired immunodeficiency syndrome complications Complications, brain atrophy

1. Central nervous system complications: mainly refers to AIDS encephalopathy, the incidence of pediatric AIDS patients is higher, the incidence rate in perinatal HIV-infected children is about 23%, the seizure often accompanied by the deterioration of immunodeficiency, the most serious clinical process For subacute encephalopathy, it often dies weeks to months after the onset of symptoms, and its histopathological changes are mainly brain atrophy.

2. Other complications: Common consumption syndrome of the digestive system. It is reported that about 0.5% of pediatric AIDS has malignant tumors. Common tumor types are non-Hodgkin's lymphoma, Kaposi sarcoma, B lymphocytic leukemia, and hepatocytes. Tumors, etc., cardiovascular complications of pediatric AIDS have attracted attention in recent years, with the reduction of CD4 T lymphocytes, progressive left ventricular dysfunction, opportunistic infections (cryptococcal and aspergillosis) and malignant tumors (Kaposi sarcoma) Cardiac diseases causing AIDS in children and adults, clinically visible congestive heart failure, pericardial tamponade, non-bacterial thrombotic endocarditis, conduction disorders and sudden death, nephritis and nephropathy, and blood system of HIV-infected children Abnormalities, often manifested as leukopenia, anemia and thrombocytopenia.

There are growth retardation, hepatosplenomegaly, lymphadenopathy, diarrhea and chronic skin infections, severe sepsis, opportunistic pneumonia, interstitial pneumonia, meningitis, urinary tract infection, cellulitis, chronic otitis media, chronic sinus Inflammation, amebic disease, tuberculosis infection, EB virus infection, Listeria infection, etc.

Symptoms of Acquired Immune Deficiency Syndrome in Children Common Symptoms Slow Growth Intermittent Heat Liver enlargement Lymph node enlargement Hepatosplenomegaly Large granulocytopenia Diarrhea Cellulitis Urinary tract infection Thrombocytopenia

After HIV infection in children, symptoms appear after about 5 years of incubation. Most of the intrauterine HIV-infected infants have no clinical symptoms at birth, and the physical examination is normal. 15% to 25% of perinatal HIV-infected babies are born. After a few months of onset, the annual increase of about 10%, after the onset of death within 1 to 5 years, a small number of sick children can survive for 9 years or longer, so the clinical experience of AIDS in children is more dangerous than adult AIDS, in the diagnosis Before AIDS, children often have some non-specific clinical manifestations, including mild growth retardation, hepatosplenomegaly, systemic lymphadenopathy, intermittent fever, non-specific intermittent diarrhea and chronic skin infections, which are easily confused with other pediatric diseases. Delayed diagnosis, it should be vigilant, detailed medical history, consider the possibility of HIV infection in the differential diagnosis of the disease.

Clinical staging

In 1994, the US Centers for Disease Control classified HIV infection according to clinical manifestations into the following four phases: no clinical manifestations (N), mild clinical manifestations (A), moderate clinical manifestations (B), and severe clinical manifestations (C).

(1) No clinical presentation period (N): no signs and symptoms of any infection, or only one of the mild clinical manifestations.

(2) Mild clinical presentation period (A): Clinical signs with two or more of the following, but no moderate or severe clinical presentation:

1 lymph node enlargement (>0.5cm, occurred in more than 2 sites, bilaterally symmetric distribution).

2 liver enlargement.

3 splenomegaly.

4 dermatitis.

5 mumps.

6 repeated or persistent upper respiratory infections, sinusitis or otitis media.

(3) Moderate clinical presentation period (B): In addition to the performance of stage A, the following performances are also available:

1 anemia (Hb < 80g / L), neutropenia (<1 × 109 / L), or thrombocytopenia (<100 × 109 / L), for 30 days.

2 bacterial meningitis, pneumonia or sepsis.

Oral candidiasis in which the baby lasts for more than 2 months within 36 months.

4 cardiomyopathy.

5 Cytomegalovirus infection (CMV) occurs within 1 month after birth.

6 repeated and chronic diarrhea.

7 hepatitis.

8 herpes simplex virus stomatitis occurred repeatedly (2 times within 1 year).

9 cases of herpes simplex bronchiolitis, pneumonia or esophagitis occurred 1 month after birth.

10 Herpes zoster occurs at least 2 times or at different sites of skin lesions.

11 leiomyosarcoma with EB virus infection.

12 lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia syndrome.

13 kidney lesions.

14 nocardiosis (nocardiosis).

15 sustained fever for more than 1 month.

16 Toxoplasma infection occurred within 1 month of birth.

17 disseminated varicella (complication of chickenpox).

(4) Severe clinical manifestation period (C): including the following:

1 severe recurrent and multiple bacterial infections, including sepsis, pneumonia, meningitis, bone and joint infections and deep abscesses.

2 Candida infection involves the esophagus, trachea, bronchi and lungs.

3 Deep fungal infections, disseminated (in areas other than the lungs, hilar and cervical lymph nodes).

4 extrapulmonary cryptococcosis.

5 Cryptosporidium infection with persistent diarrhea for more than 1 month.

6 cytomegalovirus infection 1 month after birth, involving the liver, spleen and lymph nodes.

7 encephalopathy: one of the following manifestations, the course of the disease lasts at least 2 months, and cannot be explained by other reasons:

A. Development lags or reverses, and the intelligence reverses.

B. Impaired brain development, head circumference measurement confirmed as acquired microcephaly or CT/MRI examination showed brain atrophy.

C. Acquired systemic motor dysfunction, manifested as the following two or more signs: paralysis, pathological reflex, ataxia gait instability.

8 herpes simplex mucosal ulcer persists for more than 1 month, or a child born after 1 month has herpes simplex bronchitis.

9 histoplasmosis involves the lungs, areas other than the hilar and cervical lymph nodes.

10Kaposi sarcoma.

11 primary intracerebral lymphoma.

12 Burkitt lymphoma, a large cell lymphoma with unknown B-cell or immunological phenotype.

13 disseminated or extrapulmonary tuberculosis.

14 Pneumocystis carinii pneumonia (PCP).

15 progressive multiple leukoencephalopathy.

16 Salmonella (non-typhoid) sepsis, repeated attacks.

17 Toxoplasma infection occurred 1 month after birth.

18 wasting syndrome:

A. The body weight is continuously reduced by more than 10%.

B. The weight-age curve of those older than 1 year old decreased by 25 percentile.

C. The weight-height curve after 1 month of birth decreased by 5 percentage points.

D. Accompanied by chronic diarrhea (at least 2 times a day for more than 1 month) or fever for more than 1 month (continuous or intermittent).

2. Classification of HIV infection in children

Once the class is fixed, even if the condition improves, it cannot be reduced to a lighter class.

3. The main clinical signs of pediatric AIDS

(1) persistent systemic lymphadenopathy: often the first clinical manifestation, systemic lymphadenopathy can last for more than 3 months without any reason, but the immune function has been disordered.

(2) Prolonged pathogenic microbial infections: repeated diarrhea, rash, hepatosplenomegaly, oral thrush, mucocutaneous candidiasis, etc., severe sepsis, bacterial pneumonia, meningitis, urinary system can occur with disease progression Infection, cellulitis, chronic otitis media, chronic sinusitis, Pneumocystis carinii, amebic disease, tuberculosis infection, EB virus infection, Listeria infection, etc., repeated bacteria, viruses, fungi and Other pathogenic microbial infections are one of the main clinical manifestations of pediatric AIDS. The most important pathological findings are chronic pneumonia, mostly lymphocytic interstitial pneumonia, and reticular and nodular infiltrates are seen on X-ray chest radiographs.

1 immune function defects are prone to opportunistic infections: children with HIV infection are identified. If the following opportunistic infections occur, a presumed diagnosis of AIDS should be made:

A. Candida esophagitis.

B. Cytomegalovirus retinitis.

C. Pneumocystis carinii pneumonia.

D. Toxoplasmosis (after 1 month of age).

E. Diffuse chronic atypical mycobacterial infection.

2 Opportunistic infections with the following histological diagnosis can confirm AIDS:

A. Diffuse.

B. Diffuse histoplasmosis.

C. Pneumococcal disease.

D. Extrapulmonary tuberculosis.

E. Recurrent Salmonella sp.

F. Diffuse/sustained herpes simplex.

Pediatric acquired immunodeficiency syndrome

Etiology check

(1) Specific antibody detection: It can be used for epidemiological investigation of HIV infection and diagnosis of current patients. However, due to the late onset of serum antibody, it is usually detected 22 to 27 days after infection, so antibody negative can not be detected. The exclusion of early HIV infection should be reviewed after 2 to 4 weeks. It should be noted that passive antibodies from the mother may be present in infants under 18 months of age.

1 screening test: serum HIV antibody is detected by ELISA or immunofluorescence test, positive test should be done to eliminate false positive reaction.

2 Verification test: Western blotting test for serum anti-gp120, anti-gp41 and anti-gp24, positive can establish the diagnosis of HIV infection.

(2) Antigen examination: The p24 antigen in serum is examined, which appears earlier than serum antibodies, and thus can be used for early diagnosis.

(3) HIV nucleic acid test: PCR technology is used to detect HIV RNA in serum. The positive result is often 3 to 5 days earlier than p24 antigen detection, 1 to 3 weeks earlier than antibody detection, and can be quantitatively detected, so it is early diagnosis and judgment. An ideal indicator of prognosis and antiviral drug efficacy, this method is very sensitive, should pay attention to avoid false positive caused by cross-contamination between specimens, in situ hybridization technology can be used to examine HIV or nucleic acid in tissues or cells, but it is not a routine diagnostic method.

2. Immunological examination

It is important to understand the immune function status of patients, and to the stage, prognosis and treatment of the disease.

(1) Blood cell examination: including white blood cells, reduction of platelet count and red blood cell count, and the like.

(2) Lymphocyte examination: T lymphocyte subset count: normal CD4 T cell/CD8 T cell ratio is 1.5 to 2.0, and AIDS is less than 1.0. In addition, absolute count of CD4 T cells contributes to disease staging and judgment .

(3) Delayed skin allergy test: HIV-infected patients are low or negative.

(4) Immunoglobulins, complements, immune complexes, and autoantibodies.

3. Classification of immune status

There are differences in the normal values of CD4 T lymphocytes in children of all ages. The age characteristics should be noted when discriminating the inhibition of T lymphocytes. The US Centers for Disease Control (CDC) accounts for the absolute value of CD4 T lymphocytes in peripheral blood or CD4 T lymphocytes. The percentage of the total is shown to indicate the patient's immune status and is classified as follows.

Regular X-ray, B-ultrasound, CT, electrocardiogram and other examinations.

Diagnosis and identification of acquired immunodeficiency syndrome in children

Diagnostic principles for HIV infection in infants born to HIV-infected mothers:

1. 18 months of infants with a definitive diagnosis: ELISA test antibody 2 positive and confirmatory test (immunoblot or fluorescence-free detection) 1 positive; or 2 virus test tests in different samples (HIV isolation, HIV gene and P24 antigen assay) positive; or there is a pediatric AIDS definition disease (see clinical classification), 18 months infants with a presumed diagnosis: with a virus test (ibid.) positive (except cord blood).

2. <18 months of babies' definitive diagnosis: with either two virus test tests (ibid.) in different samples; or a pediatric AIDS definition disease.

3. Except for congenital immunodeficiency disease.

Differential diagnosis

Identification with secondary immunodeficiency, epidemiological history and laboratory tests can help diagnose. Secondary immunodeficiency Many diseases can be associated with secondary immunodeficiency diseases, including infections (rubella, measles, leprosy, tuberculosis, cytomegalovirus infection, coccidioid infection, etc.), malignant tumors (Hodgkin's disease, acute and Chronic leukemia, myeloma, etc., autoimmune diseases (SLE, rheumatoid arthritis, etc.), protein loss (nephropathy syndrome, protein loss bowel disease), insufficient immunoglobulin synthesis, lymphocyte loss (due to drugs, systems) Infection, etc.) and certain other diseases (such as diabetes, cirrhosis, subacute sclerosing panencephalitis) and immunosuppressive therapy. Secondary immunodeficiency disease can be temporary, and when the primary disease is treated, the immune defect can return to normal; it can also be persistent. Secondary immunodeficiency is often caused by multiple factors. For example, secondary immunodeficiency disease associated with cancer can be caused by factors such as tumor, anti-cancer treatment and malnutrition.

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