TROPICAL DISEASES - Diagnosis and Management pptx

Evaluation and management of common tropical diseases in intensive care

1. TROPICAL DISEASES

2. Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions . The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by forcing hibernation..

3. Insects such as mosquitoes and flies are by far the most common disease carrier, or vector. These insects may carry a parasite, bacterium or virus that is infectious to humans and animals. Most Often disease is transmitted by an insect "bite", which causes transmission of the infectious agent through subcutaneous blood exchange. Vaccines are not available for most of the diseases, and many do not have cures. Human exploration of tropical rainforests, deforestation. rising immigration and increased international air travel and Other tourism to tropical regions has led to an increased incidence of such diseases to non-tropical countries. Mostly affect people living in remote rural areas or urban slums of tropical countries found in places with low socio-economic progress, where substandard Houses.

4. “syndromic approach” to tropical infections The clinical picture of these diseases is so overlapping that it is almost impossible to achieve differential diagnosis of these diseases in emergency and ICU settings when the time available for intervention is limited. These infections must be suspected in all febrile patients as delay in the institution of specific therapy may lead to increased morbidity and mortality. “syndromic approach” to tropical infections can guide the intensivists regarding the commonest etiologies, investigative modalities and help them to choose early empiric therapy.

5. For ease of diagnosis these infections were divided into five major syndromes: Undifferentiated fever, Fever with rash/thrombocytopenia, Fever with acute respiratory distress syndrome (ARDS), Fever with encephalopathy and Fever with multi organ dysfunction syndrome.

6. Undifferentiated fever :Malaria (P. falciparum), scrub typhus, leptospirosis, typhoid, dengue and other common viral illness. Fever with rash/ thrombocytopenia :Dengue , rickettsial infections, meningococcal infection, malaria (usually falciparum), leptospirosis, measles, rubella and other viral exantem . Fever with ARDS :Scrub typhus, falciparum malaria, influenza including H1N1, leptospirosis, hantavirus infection, meliodosis , severe community acquired pneumonias due to Legionella spp. and Streptococcus pneumoniae and diffuse alveolar hemorrhage due to collagen vascular diseases.

7. Febrile encephalopathy : Encephalitis (Herpes simplex virus encephalitis, Japanese B and other viral encephalitis), meningitis (S. pneumoniae, Neisseria meningitidis, Haemophilus influenzae, enteroviruses), scrub typhus, cerebral malaria and typhoid encephalopathy. Fever with multiorgan dysfunction : Bacterial sepsis, falciparum malaria, leptospirosis, scrub typhus, dengue, hepatitis A or E with fulminant hepatic failure and hepato-renal syndrome, Hanta virus infection, hemophagocytosis and macrophage activation syndrome .

8. Assess and stabilize Airway, Breathing and Circulation Redflag features (Pulse>110/ min,RR >20/min, BP Focus of infection identified? (Pneumonia, pyelonephritis, Biliary source, Cellulitis etc.) Appropriate investigations (including Blood cultures x 2) Empiric Treatment as per the source Assess the clinical syndrome Consider Riskfactors , geography, season and associated symptoms Rash/ thrombocytopenia FEVER with Jaundice ARDS MODS FEVER with ENCEPHALOPATHY (See Flow Chart2)

9. INVESTIGATIONS Essential (to be performed in all) Blood cultures x 2 CBC,Platelets , Electrolytes, CRP,Creatinine , LFT,Urine analysis,CxR Rapid diagnostic tests (to be performed at admission) *Malaria card test (RDT)(kit must use HRP/ LDHantigen )/Malarial smears x 3 #Dengue card tests for NS1antigen, IgM and IgG † Typhidot H1N1 (PCR) Rapid tests suggest diagnosis Malaria Inj.Artesunate 2.4 mg/kg at admission, then at 12 h and 24 hr , then once a day Dengue Isotonic fluids Supportive care for bleeding, electrolyte abnormalities Typhoid Inj. Ceftriaxone 100mg/kg/day Empirical treatment Inj. Ceftriaxone 100mg/kg/day + Tab. Doxycycline 5mg/kg/day + Inj. Azithromycin 10mg/kg/day Further work up (as indicated) Serology for Scrub typhus (Weil felix , IFA) Dengue (IgM, IgG), Leptospira (IgM, Dot ELISA) WIDAL USG abdomen Bone Marrow Examination and Cultures ‡

10. DENGUE Dengue Fever, also known as BreakBone Fever, is an infectious tropical diseases caused by the dengue virus. Dengue virus belongs to Flaviviridae Family. The flaviviridae are Positive Sense, Single Stranded RNA viruses. Dengue is transmitted by several species of mosquito within the genus aedes principally Aedes Aegypti An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person during the initial 2-10 days of dengue infection, becomes itself infected with the virus in the cells lining of its Gut About 8—10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. The virus has four different types (DENI, DEN2, DEN3 & DEN4)

11. Risk Factors Virus strain (DENV 2 and 3) Pre-existing anti-dengue antibody : Immune-enhancement Previous infection Maternal antibodies in infants Hyperendemic transmission: Two or more serotypes circulating simultaneously at high levels.Endemic : only one serotype prevalent in the area Age: more severe in children Ethnicity: Africans have less severe illness Chronic diseases (bronchial asthma, sickle cell anaemia and diabetes mellitus)

12. Pathophysiology Two main pathophysiological changes: Increased vascular permeability Hemostatic Disorder: Vascular Changes ,Thrombocytopenia, Coagulopathy Persons exposed to dengue virus serum antibodies neutralize the virus of same type subsequent infection-antibodies form complexes but do not neutralize the new virus. These complexes facilitates the entry of the virus into mononuclear cells by binding with the FC receptors Increased Vascular Permeability is due to infected monocytes which releases Vasoactive mediators and causes Increased vascular permeability. Thrombocytopenia caused by Infection of human haematopoietic cells which inhibits megakaryocytopoieses Increased peripheral destruction of antibody coated platelets and platelet destruction in the liver and spleen. there might be platelet dysfunction( QuaIitative defect) All the above leads to hemorrhagic manifestations DHF, DSS

13. Hemonfiage in Vasculopathy Thrombocytopenia Platelet dysfunction DIC Coagulopathy

14. Febrile phase : This phase is characterized by the sudden rise of body temperature, which is usually highgrade (≥38.5°C) and may be biphasic. This phase may last for 2-7 days and is associated with headache, flushing, vomiting, myalgia, arthralgia, and macular rash. The rash is primarily maculopapular or rubelliform . Bleeding manifestations may be observed in this phase, depending on the severity of the disease. Most of the cases may present with skin and mucosal bleeding (including gastrointestinal or vaginal) and less commonly with hematemesis, melena, heavy menstrual bleeding, epistaxis, or hematuria. Physical examination may reveal facial puffiness, conjunctival congestion, pharyngeal erythema, lymphadenopathy, and hepatomegaly. It is also essential to look for petechiae (on the skin and palate) and bruising (particularly at venipuncture sites) and perform a tourniquet test.

15. • Critical phase (leakage phase) From the febrile phase 5- 10 % of the patients may progress to the critical phase and commonly observed in patients who have a history of previous dengue infection (secondary infection). This may also occur after primary infection in patients with comorbidities and active coinfections. This phase usually begins after 3rd or 4th day of fever and may last about 24 to 48 hours. This phase is characterized by vasculopathy and coagulopathy, leading to plasma leakage, excessive hemoconcentration, bleeding, eventually leading to shock and organ dysfunction. The clinicians need to be carefully in recognizing and observing the warning signs of critical phase at the early stage: Persistent vomiting, abdominal pain and tenderness Lethargy and/or restlessness, sudden behavioral changes ,Bleeding manifestations like epistaxis, melena, hematemesis, excessive menstrual bleeding, and hematuria Syncope or giddiness, Clinical fluid accumulation (ascites and pleural effusion) ,Enlarged Liver(>2cm) Laboratory: Progressive increase in hematocrit with a rapid decrease in platelet count

16. Convalescent phase (Recovery phase) With the timing and optimal management during critical phase patients start recovering and passes through the recovery phase. Majority of the patients from febrile phase also pass through this recovery phase for the complete cure. In this recovery phase the extracellular fluid loss owing to capillary leakage returns to the circulatory system during the recovery phase, and signs and symptoms improve. This phase occurs after the critical phase and lasts2-3 days. The patient develops a convalescent rash characterized by confluent erythematous eruption with sparing areas of normal skin. It is often pruritic. Patients with severe shock, organ involvement or other issues that may require specific therapy can expect a longer recovery time. If fluid replacement is not carefully optimized, the patient may develop pulmonary edema as a result of fluid excess.

17. Severe dengue (Group C) These patients are those who have progressed from mild or moderate dengue to develop symptoms and signs of shock, plasma leakage, and organ dysfunction. Severe dengue involves patients presenting with history of fever with shock, patients with severe bleeding, patients presenting with severe organ involvement, and metabolic disorders (severe acidosis). Manifestations of severe dengue 1. Severe plasma leakage leading to: • Shock • Fluid accumulation with respiratory distress 2. Severe bleeding (as evaluated by the treating team) 3. Severe organ dysfunction 4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1000 units/L 5. Impaired consciousness (GCS < 9)

18. Diagnosis of Dengue virus infection

19. Primary Dengue: negative IgG in the acute phase and a positive IgG in the convalescent phase of the infection Secondary Dengue: positive IgG in the acute phase and a four fold rise in IgG titer in the convalescent phase requires paired sera with at least 7 day interval between the two samples.

20. Treatment principles Management Decisions Depending on the clinical manifestations and other circumstances, Group A : can be sent HomeGroup A(Out patient treatment) Group B : In-hospital management Group C : Require emergency treatment and ICU care

21. Fluid Overload : Causes Excessive and/or too rapid intravenous fluids Incorrect use of hypotonic rather than isotonic crystalloid solutions Inappropriate use of large volumes of intravenous fluids in patients with unrecognized severe bleeding Inappropriate transfusion of FFP, PRP and Cryoprecipitate Continuation of intravenous fluids after plasma leakage has resolved Co-morbid conditions: CHD, IHD, COPD,CKD Recognition Respiratory Distress, Pulmonary oedema Tachypnea Irreversible shock Wheezing Large Pleural Effusion Tense Ascites Increased JVP

22. Issues in Platelet transfusion Platelet rich plasma (PRP) when managing thrombocytopenia Platelets present a strong antigenic stimulus Evoking an exaggerated immune response Further immune mediated platelet destruction In cases of severe bleeding, use of blood is preferable instead of platelets and FFP Criteria for Platelet Transfusion Platelet counts of dengue patients fluctuate in an unpredictable manner despite platelet transfusion Prophylactic platelet transfusions are not necessary Stable patients with Platelet Count Patients with Platelet Count < 20,000/cc with minor bleeding Patients with Platelet Count < 50,000/cc with significant bleeding

23. Criteria for discharging inpatients Absence of fever for at least 24 hours without the use of antipyretic therapy Return of appetite Visible clinical improvement Good urine output Stable haematocrit Passing of at least 2 days after recovery from shock No respiratory distress from pleural effusion or ascites Platelet count >50 000 per mm3.

24. Malaria 4 species of Plasmodium were known to cause malaria in humans: P. Falciparum P. Vivax P malariae P. ovale

25. Clinical Features Symptoms of Malaria Headache, Chills, Sweating, Fever, Fatigue, Dry cough Spleen enlargement, back pain, Nausea, Vomiting Clinical Features Prodromal symptoms Headache, photophobia, muscle ache and pain, anorexia and vomiting Cold stage Sudden shaking chills or rigor, pale and cyanotic lasting 10-15 min Hot stage Flushed, agitated, restless, disoriented, delirious ,Severe frontal headache, pain in limbs and back lasting for 2-4 hrs Sweating Profuse sweating weak and exhausted for Several hrs

26. Severe complicated malaria I. Confusion, drowsiness, severe weakness or continuous high grade fever 2. Hyperparasitemia (P. falciparum > 10% ) 3. Impaired consciousness 4. Hypoglycemia 5. Multiple seizures 6. Respiratory distress 7. Pulmonary edema (HYPOXIA) 8. Jaundice 9. Hemoglobinuria (Red or Black Urine) 10. Abnormal bleeding 11. Severe anemia Circulatory collapse P. VIVAX causes BENIGN TERTIAN MALARIA:Benign because it's rarely fatal ,tertian as it's causes fever every 3rd day (48 hr ). Relapse is a problem P. FALCIPARUM causes MALIGNANT TERTIAN MALARIA:Malignant because it's very fatal ,tertian as it's causes fever every 3rd day (48 hr ) Infected RBCs forms clusters called ROSSETS, Such ROSSETS blocks end organ capillaries causes Renal failure & cerebral malaria

27. Diagnosis of malaria Can take any time (or at the height of fever) 3 consecutive days Giemsa-stained Thick film and Thin film Thick film & Thin film •Thick film for MP positive or not •Thick film facilitates the diagnosis of low level Parasitemia Thin film is essential •to confirm the diagnosis, •to identify the species of parasite, & •to quantify the parasite load by counting the % Of infected RBCs Rapid Diagnosis Tests (RDT) by ICT Rapid diagnosis for falciparum Parasight -F test based upon HRP 2 (Histidine rich protein 2) Rapid diagnosis for falciparum and vivax •LDH coted optimal test kits Test took only 5 min.Sensitivity 100%, specificity 96% Importance of ICT Rapid Dx Can differentiate falciparum and vivax Suitable for microscopists less experienced in examining blood films Can detect up to 14 days

28. Monitoring & follow-up •Blood smear should be repeated daily (twice daily in severe infection). Within 48- 72 hr after start of treatment, patients usually become afebrile and improve clinically except in complicated cases. •All patients should be investigated with repeated blood film of malarial parasite one month upon recovery of malarial infection, to ensure no recrudescence. PREGNANCY & MALARIA •10 times high risk to develop malaria & high tendency to develops complications •First TM — Quinine / Mefloquine + Clindamycin for 7 days •Second & Third TM - Quinine / Mefloquine + Clindamycin for 7 days •Artemether + lumefentrine can be used •Primaquine & tetracycline never to use •Frequent investigations & monitioring required and Severe & complicated malaria is an medical emergency. Patient should be referred to tertiary care & treatment should start urgently and patients needs multiple investigations, fluid & electrolytes correction

29. LEPTOSPIROSIS Zoonotic disease Animals (Especially Rodents) are natural host they shed the organism in urine intermittently or continuously Viable in neutral pH almost for a month Humans are incidental host No human to human transmission Direct contact : Tissue, blood, urine or organs of affected animals. Indirect contact : Through contaminated water Portal of entry Cut or abraded skin, mucous membranes, or conjunctiva and Ingestion of food contaminated with urine (Rare) Can be sporadic or occurs in outbreak or occur as endemic as in tropics

30. Tightly Coiled with hooked ends Highly motile along the longitudinal axis Not seen by light microscopy – Dark field or Phase Contrast Microscope to be used

31. pathogenesis Blood culture, PCR RDT/ELISA/MAT EndotoxinProduction , Capillary vasculitis,MODS Urine culture

32. CLINICAL FEATURES: Variable spectrum. Mild self limited to potentially fatal Incubation period 2-26 days. Average around 10 days Has following clinical features Presents with abrupt onset of fever, rigor, myalgia and headache in 75-100% Conjunctival suffusion - Occurs in 55% patients Even SCH can happen Frequently overlooked Not a common finding in other causes of febrile illness

33. GI symptoms - Nausea, diarrhea and vomiting can happen in 50% of patients Non productive cough can happen in 25-35 % of patients Muscle tenderness along with myalgia, arthralgia, bone pain can be an important diagnostic clue Others : Splenomegaly, hepatomegaly, lymphadenopathy Pharyngitis, sore throat are other rare presentations Icteric leptospirosis (Weil's disease) occurs in 5-15% – Jaundice, proteinuria, haematuria , oliguria and/or anuria, pulmonary haemorrhage , ARDS, myocarditis

34. Biphasic illness Two phases may be separated by apparent afebrile period or phases may overlap in the setting of severe disease Phase 1 Acute febrile bacteremia characterized by high fever, chills, GI symptoms, myalgia more pronounced in the calf region which lasts for around 2-9 days Leptospira can be isolated from the blood during this phase Phase 2 Immunological phase. May last even up to 30 days Recurrence of fever, worsening of symptoms and onset of complications Leptospira are absent in blood but may appear from urine IgM antibodies are commonly found during this phase

35. Complications Acute Kidney injury Liver involvement (Jaundice, Transaminitis) Pulmonary haemorrhage Myocarditis Aseptic meningitis Uveitis Cholecystitis Pancreatitis MODS DIC

36. ICMR Doxycycline 100mg bd for 7days Amoxycilin 500 mg qid for 7 days Azithromycin 500mg for 5 days Pencillin 1.5mu iv qid for 7 days Ceftriaxone 1g iv od for 7 days

37. Scrub thypus C aused by Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). Gram negative coccobacillus it has the following unique characteristics Obligate intracellular parasites Has trilaminar outer membrane that is unique Doesn't have vacuolar membrane – Antigenically distinct from other typhus group Rickettsiae Exhibit extensive genomic and antigenic heterogeneity -  Has five major serotypes ( Boryon , Karp, Gilliam, Kato, Kawazaki ) . Distinct No cross immunity Highly virulent.

38. LIFE CYCLE & PATHOGENESIS The reservoir and vector of scrub typhus are larval trombiculid mites of the genus Leptotrombidium - Chigger Spreads by bite of larva. The larva (chigger) is the only stage that can transmit the disease

39. pathogenesis

40. Clinical feature Fever ,myalgia ,headache ,vomiting ,abdominal pain ,diarrhea, altered sensorium and eschar Eschars are painless, punched out ulcers up to 1 cm width with a black necrotic centre surrounded by an erythematous margin. Occurs at the site of chigger bite - Common sites being neck,axillae , groin and can be multiple Biopsy of Eschar:The pathological hallmark of scrub typhus is a lymphohistiocytic vasculitis

41. Complications : Respiratory: ARDS Cardiac: SHOCK Neurology: MENINGOENCEPHALITIS Liver: HEPATITIS(Transaminitis) Renal: ACUTE RENAL FAILURE Hamatology : MODS AKI

42. EEG: Bilateral diffuse cerebral dysfunction with epileptiform discharges with no specific lateralization CT: Diffuse cerebral edema MRI: Diffuse cerebral edema Hyperintense lesions in the putamen and thalamus in T2-weighted and fluid-attenuated inversion recovery (FLAIR) image

43. Treatment Start empirical therapy on clinical suspicion – Do not wait for laboratory confirmation In adults: (a) Doxycycline 200 mg/day in two divided doses for individuals above 45 kg for a duration of seven days. Or (b) Azithromycin 500 mg in a single dose for five days. In pregnant women: Azithromycin 500 mg in a single dose for five days. Doxycycline is contraindicated. Management of the individual complications should be done as per the existing practices.