To guide the timely and effective diagnosis and treatment of human granulocytic anaplasmosis around the world, reduce critical and fatal cases, and prevent nosocomial infections, this program has been developed.
I. Clinical manifestations
The incubation period is generally 7-14 days (average 9 days). Acute onset, the main symptoms are fever (mostly persistent high fever, which can be more than 40℃), general malaise, malaise, headache, muscle pain, as well as nausea, vomiting, anorexia, diarrhea, etc.. Some patients are accompanied by cough and sore throat. Physical examination may show indifferent expression, relatively slow pulse, and a few patients may have superficial lymph node enlargement and skin rash. It may be accompanied by multiple organ function damage such as heart, liver and kidney with corresponding clinical manifestations.
Severely ill patients may have interstitial pneumonia, pulmonary edema, acute respiratory distress syndrome, and secondary bacterial, viral, and fungal infections. A small number of patients may have severe thrombocytopenia and coagulation abnormalities, with bleeding manifestations in the skin, lungs, and gastrointestinal tract. If not treated promptly, death may occur due to respiratory failure, acute renal failure and other multi-organ failure, as well as diffuse intravascular coagulation.
Elderly patients, immunodeficient patients and those on hormone therapy are more critical when infected with this disease.
Laboratory tests
The peripheral blood picture has decreased leukocytes and platelets, and increased heterogeneous lymphocytes. In patients with combined organ damage, heart, liver and kidney function tests are abnormal. Pathogenic and serological tests are positive. Among them.
Routine blood tests: leukocytosis and thrombocytopenia can be an important clue for early diagnosis. Patients show leukopenia in the first week of illness, mostly 1.0-3.0×10/L;
Heterogeneous lymphocytes can be seen.
Urine routine: proteinuria, hematuria, tubular urine.
Blood biochemistry: abnormal liver and kidney function; elevated cardiac enzyme profile; elevated blood amylase, urinary amylase and blood glucose in a few patients.
Some patients have prolonged prothrombin time and elevated fibrinogen degradation products. There may be blood electrolyte disturbances, such as low sodium, low chloride, and low calcium. In a few patients, bilirubin and serum protein are also decreased.
Complications
If treatment is delayed, patients may develop opportunistic infections, sepsis, toxic shock, toxic myocarditis, acute renal failure, respiratory distress syndrome, diffuse intravascular coagulation and multi-organ failure, which directly affect the condition and prognosis.
IV. Case diagnosis
Diagnosis is based on epidemiological history, clinical manifestations and laboratory test results.
(A) Epidemiological history.
1. History of tick bite within 2 weeks before the onset of the disease;
2. History of working or living in hilly, mountainous (forested) areas where ticks are active;
3. direct contact with blood and other body fluids of critically ill patients.
(ii) Clinical manifestations.
Acute onset, the main symptoms are fever (mostly persistent high fever, can be as high as 40 ℃ or more), general malaise, malaise, headache, muscle aches, and nausea, vomiting, anorexia, diarrhea, etc.. Individual severe cases may show skin petechiae and hemorrhage with multiple organ damage and diffuse intravascular coagulation.
(C) Laboratory tests.
1. routine blood and biochemical tests
(1) Early peripheral blood picture: decreased white blood cells and platelets, progressive decrease in severe cases, increased heterogeneous lymphocytes.
(2) Mulberry-shaped inclusion bodies can be seen in neutrophils on microscopic examination of terminal blood smear.
(3) Elevated glutamic (alanine aminotransferase, ALT) and/or glutamic (aspartate aminotransferase, AST) aminotransferases.
2. Serum and pathogenic tests
(1) Positive serum indirect immunofluorescence antibody (IFA) for phagocytic apheresis IgM in the acute phase.
(2) Acute phase serum IFA was positive for phagocytic aphagocytic IgG antibody.
(3) A 4-fold or higher increase in the titer of phagocytophagocytic IgG antibodies in serum IFA during the recovery period compared to the acute period.
(4) PCR of whole blood or blood cell specimens was positive for phagocytic apheresis-specific nucleic acids, and sequence analysis confirmed homology with phagocytic apheresis of 99% or more.
(5) Pathogens were isolated.
(D) Diagnostic criteria.
Suspected cases: with (1) and (3) of (i), (ii) and (iii) 1 above. A clear epidemiological history may not be available for some cases.
Clinically diagnosed cases: suspected cases with both (2) of (iii) 1, or (1) or (2) of (iii) 2.
Confirmed cases: suspected cases or clinically diagnosed cases with either (3), (4), (5) in (3) item 2.
V. Differential diagnosis
(A) Differentiation from other tick-borne diseases and rickettsial diseases: human monocytic ehrlichiosis (HME), typhus, scrub typhus, spotted fever, and Lyme disease, etc.
(ii) Differentiation from infectious diseases with fever, hemorrhage and elevated enzymatic parameters: mainly viral hemorrhagic diseases, such as epidemic hemorrhagic fever and dengue fever.
(iii) Differentiation from gastrointestinal diseases with fever, decreased blood leukocytes and platelets: typhoid fever, acute gastroenteritis, viral hepatitis.
(iv) Differentiation from internal diseases with fever and decreased blood leukocytes and platelets or bleeding tendency: mainly hematologic diseases such as thrombocytopenic purpura, granulocytopenia, and myelodysplastic syndrome. Identification can be made by bone marrow aspiration and corresponding pathogen testing.
(v) Differentiation from medical diseases with fever with several elevated enzymatic indices: mainly immune system diseases, such as dermatomyositis, systemic lupus erythematosus, rheumatic fever. It can be differentiated by autoantibodies and other immunological indexes.
(vi) Other: such as mycoplasma infection, leptospirosis, rat bite fever, drug reactions, etc.
VI. Treatment
Use antibiotics early to avoid complications. Empirical treatment can be given to suspected cases. Generally use hormonal drugs with caution to avoid aggravating the disease.
(A) Pathogenic treatment.
1. Tetracycline antibiotics
(1) Doxycycline. It is the drug of choice and should be used early and in sufficient quantity. Adult oral: 0.1g/time, 2 times a day,
If necessary, the first dose can be doubled, and the usual dose for children over 8 years old: 4mg/kg for the first dose; after that, 2mg/kg for each dose, twice a day. Oral administration is sufficient in general cases, but intravenous administration can be considered in severe cases.
(2) Tetracycline. Oral: The usual dose for adults is 0.25-0.5g/dose, once every 6 hours; the usual dose for children over 8 years old is 25-50 mg/kg a day.
mg/kg, divided into 4 doses. Intravenous drip: adults 1-1.5g a day, divided into 2-3 doses; children over 8 years old is 10-20
Inpatients are recommended to be given intravenously. Tetracycline has more toxic side effects and should be used with caution in pregnant women and children.
The course of treatment with either Doxycycline or Tetracycline should not be less than 7 days. It is usually used until at least 3 days after the fever has subsided, or the white blood cell and platelet counts have rebounded, various enzymatic indicators are basically normal, and the symptoms have completely improved. Early use of drugs such as doxycycline or tetracycline can generally reduce the fever within 24-48 hours. Because of the non-specific clinical manifestations of human granulocytic anaplasmosis and the lack of rapid laboratory diagnostic methods, empirical treatment can be given to suspected cases, and the diagnosis of human granulocytic anaplasmosis can be considered to be ruled out for those who are still ineffective with medication for 3-4 days.
2. Rifampicin: For children, those who are allergic to doxycycline or those who should not use tetracycline antibiotics, use rifampicin. Adults 450-600 mg, children 10 mg/kg, once daily orally.
3. Quinolones: such as levofloxacin, etc.
Sulfonamides have the effect of promoting the reproduction of pathogens and should be prohibited.
(B) General treatment.
Patients should rest in bed, high-calorie, moderate amount of vitamins, liquid or semi-liquid food, drink more water, pay attention to oral hygiene, and keep the skin clean.
For patients with severe disease, adequate fluids and electrolytes should be supplemented to maintain water, electrolytes and acid-base balance; weak or malnourished, hypoproteinemia can be given gastrointestinal nutrition, fresh plasma, albumin, gammaglobulin and other treatments to improve the systemic functional status and increase the body resistance.
(C) symptomatic support treatment.
1.Physical cooling for hyperthermia, if necessary, use drugs to reduce fever.
2. For those with obvious bleeding, platelets and plasma can be transfused.
3.For those who have diffuse intravascular coagulation, heparin can be used early.
4.For patients with severe low granulocytes, granulocyte colony-stimulating factor can be used.
5.For patients with oliguria, alkalinize urine and monitor blood pressure and blood volume changes. For patients with oliguria even after adequate rehydration, diuretics can be used. If acute renal failure occurs, treat accordingly.
6. In case of cardiac insufficiency, absolute bed rest should be given, and cardiac drugs and diuretics should be used to control heart failure.
7. Hormones should be used with caution. Foreign literature reports that the use of glucocorticoids in patients with human granulocytic anaplasmosis may aggravate the disease and enhance the infectiousness of the disease, so it should be used with caution. For patients with severe symptoms of poisoning, glucocorticoids can be used appropriately under the condition of using effective antibiotics for treatment.
(iv) Isolation and protection.
For general cases, routine protection is carried out according to insect-borne infectious diseases. When treating or caring for critically ill patients, especially when the patient is bleeding, medical staff and accompanying personnel should strengthen personal protection. Disinfect the patient’s blood, secretions, excreta and their contaminated environment and objects.
(E) Discharge criteria.
Discharge after normal body temperature, disappearance of symptoms, and basic normalization or significant improvement of clinical laboratory test indicators.
(F) Prognosis.
According to foreign reports, the morbidity and mortality rate is less than 1%. If timely management, the majority of patients have a good prognosis. Patients with serious complications such as sepsis, toxic shock, toxic myocarditis, acute renal failure, respiratory distress syndrome, diffuse intravascular coagulation and multi-organ failure are prone to death.