Presentation on theme: "Tropical Infection Diseases"— Presentation transcript:
1 Tropical Infection Diseases Gatot Sugiharto, MD, InternistInternal Medicine DepartmentFaculty of Medicine, Wijaya Kusuma University SurabayaGSH - Tropmed
2 DENGUE FEVER/DENGUE HEMORHAGIC FEVER Gatot Sugiharto, MD, InternistInternal Medicine DepartmentFaculty of Medicine, Wijaya Kusuma University SurabayaGSH - Tropmed
3 Introduction(1)Dengue fever is a clinical illness with symptoms ranging from a nonspecific viral syndrome such as fever, severe headache, sore throat, rash, and muscle pain, and joint pain, to severe and fatal hemorrhagicPrimarily a disease of the tropics, and the viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans
4 Introduction(2)Dengue is one of the most important mosquito-born viral diseases affecting humans.Viral life cycle involves humans and the mosquito vector Aedes aegypti, some others by Aedes albopictusThe disease is caused by 4 serotypes of the Dengue virus, a member of the genus RNA- Flavivirus: DEN-1, DEN-2, DEN-3, DEN-4.Infection with the DEN virus can result in Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS).It has one of the largest geographic spread of any known virus (exception is HIV).A. aegypti: domestic, day-biting mosquitoes that primarily feed on humans and the DEN virus is transmitted during the feeding process. They also transmit Yellow Fever Virus (In the 1950s the World Pan Health Organization tried to eradicate A. aegypti in order to combat urban Yellow Fever (using DDT). They pulled out in 1970s and by 1997 the geographic spread of the mosquito was larger than before the eradication began).Infection with one serotype does not provide cross-protective immunity, in fact, it is thought that exposure to one serotype can make you more susceptible to infection by the other three (multiple serotype infection leads to DHF- time constraints associated with this).There is a 5% mortality rate associated with DHF in third world countries.
5 HistoryThe first suspected epidemics of dengue fever being reported during 1779 to 1780 in Asia, Africa, and North America.The dengue virus was first isolated in Japan in 1943, but this work was not immediately published.At the same time, Dr. Albert Sabin, working with the U. S. Army Commission on dengue and sandfly Fever, identified the dengue virus.
6 Global Spread of Dengue It has been estimated that in recent years as many as 10 million cases of dengue fever and 500,000 cases of DHF/DSS occur annually. Case fatality rates in some countries reach 5%million infections/yearCountries with active dengue +Aedes aegypti
7 FOUR VIRUSES Life time immunity follows infection to one type. Second, third and possibly four infections are possible.CHILDREN – first infections are mild, largely inapparent.ADULTS - first infections may produce DF, some viruses more overt than others.The four dengue viruses, members of the flavivirus genus, evolved from a common ancestor in subhuman primates and separately were introduced into the urban transmission cycle.
8 Characteristics of the Aedes Mosquito One distinct physical feature – black and white stripes on its body and legs.Bites during the day.Lays its eggs in clean, stagnant water.Close-up of an Aedes mosquitoNow I’ll tell you about the Aedes mosquito which spreads dengue.1) You can identify an Aedes mosquitoe from other mosquitoes by the black & white stripes on its body and legs. Because of this, it is also known as the ‘tiger mosquito.2) It usually bites during the day.3) The Aedes mosquito lays its eggs in clean, stagnant water. A pool of water as small as a twenty cent coin is all that is needed for it to breed.
10 1.The virus is inoculated into humans with the mosquito saliva. 2.The virus localizes and replicates in various target organs, for example, local lymph nodes and the liver.3.The virus is then released from these tissues and spreads through the blood to infect white blood cells and other lymphatic tissues.4.The virus is then released from these tissues and circulates in the blood.5.The mosquito ingests blood containing the virus6.The virus replicates in the mosquito midgut, the ovaries, nerve tissue and fat body. It then escapes into the body cavity, and later infects the salivary glands.7.The virus replicates in the salivary glands and when the mosquito bites another human, the cycle continues.
14 SymptomsA sudden onset of fever 3 – 5 days after bitten by a dengue- infected mosquito, usually continues for 2 to 7 days and can be as high as 104 to 106 °Severe headache, muscle pain, joint pain, conjunctivitis, severe orbital pain, backache, anorexia, and nausea and vomitingOther symptoms : rash, minute reddish/purplish spots, nose bleeds, or bleeding gums.Hemorrhagic manifestations usually occur about the time that the body temperature falls back to or below normalDuring the hemorrhagic, signs of circulatory failure may appear.Evidence of a capillary leak syndrome : reduced blood volume (hypovolemia), shock, and death can follow.Prolonged fatigue and depression continue through the recovery stage.
16 Dengue Disease Course Summary in Untreated Individuals 24 April 2017Dengue Disease Course Summary in Untreated IndividualsDay 1Day 2Day 3Day 4Day 5Day 6Day 7Day 8Day 9Day 10Day 11Day 12Day 13Day 14EXPOSUREIncubation 3-5 DaysHigh fever, headache, etc. lasting 2 to 7 daysMortality rate for untreated DHF can be as high as 20%Dengue is caused by one of four closely related, but antigenically distinct, viral serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus Flavivirus, family Flaviviridae. The severe hemorrhagic forms are called dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Severe cases of the disease appear to be associated with DEN-2 and DEN-3. Infection by one of these serotypes does not provide cross-protective immunity; persons living in a dengue-endemic area can contract all four dengue infections during their lifetimes. Epidemics of mass proportions occur, but fatalities are rare. Each year, tens of millions of cases of dengue fever occur and, depending on the year, up to hundreds of thousands of cases of DHF. The fatality rate of untreated DHF in most countries can be as high as 20 percent; however, with proper care, less than 1 to 2 percent of patients with dengue or DHF will die. Most fatal cases are among children and young adults.A sudden onset of fever appears within 3 to 5 days of being bitten by a dengue-infected mosquito. Other symptoms include severe headache, muscle pain, joint pain, conjunctivitis, severe orbital pain, backache, anorexia, and gastrointestinal disturbances (nausea and vomiting in more severe cases). Other symptoms may include a rash, minute reddish/purplish spots, nose bleeds, or bleeding gums. The illness commonly begins with a sudden rise in temperature accompanied by facial flush. The fever usually continues for 2 to 7 days and can be as high as 104 to 106 °F. Hemorrhagic manifestations usually occur about the time that the body temperature falls back to or below normal. During the hemorrhagic manifestation, signs of circulatory failure may appear. Platelet counts of less than 100,000/cubic millimeter (thrombocytopenia) and evidence of a capillary leak syndrome appears in clinical laboratory tests. Reduced blood volume (hypovolemia), shock, and death can follow. Prolonged fatigue and depression continue through the recovery stage.The references for the text are the Biological and Chemical Warfare Online Repository and Technical Holding System (BACWORTH), Version Battelle Memorial Institute, 1997 and the CDC website (18 June 2001
17 Diagnosis Clinical picture 24 April 2017DiagnosisClinical pictureDetection of anti-dengue immunoglobulin (Ig) M or IgG antibody in a patient's blood serumIsolated from human blood after mosquito inoculation, or from mosquito cell cultures, by immunofluorescence using serotype-specific monoclonal antibodies (MAbs).Detection of dengue virus by culture is the definitive diagnostic test, but practical limitation its useThe two basic methods for establishing a laboratory diagnosis of dengue infection are detection of the virus by culture and detection of anti-dengue antibodies (serology). Dengue virus can be isolated from human blood after mosquito inoculation, or from mosquito cell cultures. The virus is detected and identified by immunofluorescence using serotype-specific monoclonal antibodies (MAbs). Detection of dengue virus by culture is the definitive diagnostic test, but practical considerations limit its use. More commonly, a dengue infection is diagnosed by detection of anti-dengue immunoglobulin (Ig) M or IgG antibody in a patient's blood serum.A polymerase chain reaction (PCR) technique, studied by researchers from Japan and Thailand, provides a rapid, sensitive, and specific method to detect dengue virus. PCR allows simultaneous detection and serotyping of the virus in one procedure, using a pool of type-specific primer pairs for all four dengue virus serotypes.The references for the text are the Biological and Chemical Warfare Online Repository and Technical Holding System (BACWORTH), Version Battelle Memorial Institute, 1997, and Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva : World Health OrganizationThe reference for the images is18 June 2001
18 Clinical spectrum There are actually four dengue clinical syndromes: Undifferentiated fever;Classic dengue fever;Dengue hemorrhagic fever, or DHF; andDengue shock syndrome, or DSS.Dengue shock syndrome is actually a severe form of DHF.
20 Diagnostic criteria Clinical Definition for Dengue Fever : Acute febrile viral disease frequently presenting with headaches, bone or joint pain, muscular pains, rash, and leucopeniaClinical Definition for Dengue Hemorrhagic Fever :Fever, or recent history of acute feverHemorrhagic manifestationsLow platelet count (100,000/mm3 or less)Objective evidence of “leaky capillaries” elevated hematocrit (20% or more over baseline)low albuminpleural or other effusions
21 Diagnostic criteria Clinical Definition for Dengue Shock Syndrome : 4 criteria for DHF + evidence of circulatory failure manifested indirectly by all of the following:Rapid and weak pulseNarrow pulse pressure (< 20 mm Hg) OR hypotension for ageCold, clammy skin and altered mental statusFrank shock is direct evidence of circulatory failure
22 Grades of DHF Grade 1 Fever and nonspecific constitutional symptoms Positive tourniquet test is only hemorrhagic manifestationGrade 2Grade 1 manifestations + spontaneous bleedingGrade 3Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)Grade 4Profound shock (undetectable pulse and BP)
26 Red flag in DHF Danger Signs in Dengue Hemorrhagic Fever ; Abdominal pain - intense and sustainedPersistent vomitingAbrupt change from fever to hypothermia, with sweating and prostrationRestlessness or somnolenceSigns of impending shock and should alert clinicians that the patient needs close observation and fluids.
27 Treatment Supportive care Keep patient hydrated to prevent shock 24 April 2017TreatmentSupportive careKeep patient hydrated to prevent shockHospitalization of patients with advanced symptomsSymptomatic treatment : antipyreticFor complete treatment protocol refer to the following reference:Dengue hemorrhagic fever: diagnosis, treatment, prevention and control. World Health Organization. 2006Treatment for classic dengue fever is supportive. Lost plasma should be replaced early with an electrolyte solution, plasma, or plasma expanders to prevent or treat reduced blood volume (hypovolemic) shock. Patients with mild dengue hemorrhagic fever can usually be rehydrated orally. In addition, an antipyretic drug can be used. Salicylates should be avoided. Patients with advanced symptoms should be hospitalized and treated with intravenous fluid therapy. Blood transfusions are contraindicated in persons with severe plasma leakage.The references for the text are the Biological and Chemical Warfare Online Repository and Technical Holding System (BACWORTH), Version Battelle Memorial Institute, 1997, and Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva : World Health Organization18 June 2001
30 HIV / AIDS Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University SurabayaGSH - Tropmed
31 INTRODUCTION(1) Human Immunodeficiency Virus H = Infects only Human beingsI = Immunodeficiency virus weakens the immune system and increases the risk of infectionV = Virus that attacks the bodyAcquired Immune Deficiency SyndromeA = Acquired, not inheritedI = Weakens the Immune systemD = Creates a Deficiency of CD4+ cells in theimmune systemS = Syndrome, or a group of illnesses takingplace at the same timeDR. S.K CHATURVEDI
32 INTRODUCTION(2) The HIV : virus that causes AIDS. HIV attacks the immune system by destroying CD4 positive (CD4+) T cells, a type of white blood cell that is vital to fighting off infection vulnerable to other infections, diseases and other complications.AIDS is the final stage of HIV infection.AIDS is diagnosed when someone has one or more opportunistic infections, such as pneumonia or tuberculosis, and has a dangerously low number of CD4+ T cells (less than 200 cells/cmm blood).
33 HIV Class of viruses : retroviruses, RNA virus HIV uses an enzyme called reverse transcriptase to convert its RNA into DNA (deoxyribonucleic acid) and then proceeds to replicate itself using the cell's machinery.HIV belongs to a subgroup lentiviruses, or "slow" viruses having a long time period between initial infection and beginning of serious symptoms unaware of HIV infection, can spread the virus to others.Similar versions of HIV : feline immunodeficiency virus (FIV) in cats and simian immunodeficiency virus (SIV) in monkeys and other nonhuman primates.
34 PMTCT Policy for Barbados - Dr. Anton Best, MOH
35 PMTCT Policy for Barbados - Dr. Anton Best, MOH
37 HIV/AIDS transmission Sexual transmissionHeterosexualHomosexualBlood and blood productsIV drug useTransfusionsHaemophiliaOther (knives, needle)Vertical transmissionDuring pregnancyDuring birthBreastfeeding
38 HIV is not transmitted by Coughing, sneezingInsect bitesTouching, huggingWater, foodKissingPublic bathsHandshakesWork or school contactUsing telephonesSharing cups, glasses, plates, or other utensilsDR. S.K CHATURVEDI
39 PathogenesisHIV destroys CD4 positive (CD4+) T cells, which are crucial for the human immune system. less equipped to fight off infection and disease resulting in the development of AIDS.Most people who are infected can carry the virus for years before developing any serious symptoms until the number of CD4+ T cells declineAntiretroviral help reduce the amount of virus in the body, preserve CD4+ T cells and dramatically slow the destruction of the immune system.
40 Generally people in good health have roughly 800 to 1,200 CD4+ T cells per cmm of blood. Some people who have been diagnosed with AIDS have fewer than 50 CD4+ T cells in their entire body.
42 Steps in the HIV Replication Cycle Fusion of the HIV cell to the host cell surface.HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell.Viral DNA is formed by reverse transcription.Viral DNA is transported across the nucleus and integrates into the host DNA.New viral RNA is used as genomic RNA and to make viral proteins.New viral RNA and proteins move to cell surface and a new, immature, HIV virus forms.The virus matures by protease releasing individual HIV proteins.
43 Progression of HIV Infection Progression of HIV disease is measured by:CD4+ countDegree of immune suppressionLower CD4+ count means decreasing immunityViral loadAmount of virus in the bloodHigher viral load means more immune suppressionDR. S.K CHATURVEDI
44 Clinical Progression of HIV Acute Primary InfectionOnce HIV enters the body, the virus infects a large number of CD4+ T cells and replicates rapidly. During this acute phase of infection, the blood has a high number of HIV copies (viral load) that spread throughout the body, seeding in various organs, particularly the lymphoid organs such as the thymus, spleen, and lymph nodes.During this phase, the virus may integrate and hide in the cell’s genetic material. Shielded from the immune system, the virus lies dormant for an extended period of timeIn the acute phase of infection, up to 70 percent of HIV-infected people suffer flu-like symptoms.
45 The Immune System Strikes Back Two to four weeks after exposure to the virus, the immune system fights back with killer T cells (CD8+ T cells) and B-cell- produced antibodies.HIV levels in the blood are dramatically reduced. At the same time, CD4+ T cell counts rebound and for some individuals, the number rises to its original level.Clinical LatencyDuring this phase, a person infected with HIV may remain free of HIV-related symptoms for several years despite the fact that HIV continues to replicate in the lymphoid organs where it initially seeded
46 Progression to AIDSThe immune system eventually deteriorates to the point that the human body is unable to fight off other infections.The HIV viral load in the blood dramatically increases while the number of CD4+ T cells drops to dangerously low levelsHIV-infected person is diagnosed with AIDS when he or she has one or more opportunistic infections, such as pneumonia or tuberculosis, and has fewer than 200 CD4+ T cells per cubic millimeter of blood.
48 Natural History of HIV Infection DR. S.K CHATURVEDI
49 Early symptomsIn the initial stages of HIV infection, most people will have very few, if any, symptoms. Within a month or two after infection, individuals may experience a flu-like illness, including:Fever, headache , tirednessEnlarged lymph nodes in the neck and groin areaThese symptoms usually disappear within a week to a month and are often mistaken for another viral infection, such as influenza (flu).However, during this period people are highly infectious because HIV is present in large quantities in genital fluids and blood.Some people infected with HIV may experience more severe symptoms initially or a longer duration of clinical symptom , while others may remain symptom-free for 10 years or more.
50 Later Symptoms Rapid weight loss Recurring fever or profuse night sweatsExtreme and unexplained fatigueProlonged swelling of the lymph glands in the armpits, groin or neckDiarrhea that lasts for more than a weekSores of the mouth, anus or genitalsPneumoniaRed, brown, pink or purplish blotches on or under the skin or inside the mouth, nose or eyelidsMemory loss, depression and other neurological disorders.Each of these symptoms can be related to other illnesses. The only way to determine if you are infected with HIV is to get tested.
51 Virus can be transmitted during each stage HIV spectrumVirus can be transmitted during each stageSeroconversion : Infection with HIV, antibodies developAsymptomatic : No signs of HIV, immune system controls virus productionSymptomatic : Physical signs of HIV infection, some immune suppressionAIDS : Opportunistic infections, end-stage diseaseDR. S.K CHATURVEDI
52 ABC Approach The ABC Approach to prevent sexual transmission of HIV AbstainBe faithfulUse a CondomLimits of the ABC-ApproachLack of resourcesGender inequalityFaithfulness of partners
53 Types of HIV TestsHealthcare providers can test a sample of blood to see if it contains human antibodies (disease-fighting proteins) specific to HIV. The two key types of HIV antibody tests are the enzyme-linked immunosorbent assay (ELISA) and the Western blot.However, these antibody tests may not detect HIV antibodies in someone who has been recently infected with HIV (within one to three months of infection). In these situations, healthcare providers can test the blood for the presence of HIV genetic material. This test is extremely critical for identifying recently infected individuals who are at risk for unknowingly infecting others with HIV.
54 Voluntary Counselling and Testing (VCT) Why should I get tested?How does the test work?Where to get tested?Voluntary testing vs. Mandatory testingConfidential testing and Anonymous testingHome sampling and testing
55 Treatment Antiretroviral drugs (ARVs) Are not a cure Slow down the process of replication of HIV in the human bodyPrevent and treat Opportunistic InfectionsPrevent mother-to-child-transmission• During pregnancy and delivery• Safer infant feedingAccess to services / availability of drugsAvailability, Coverage, Impact
56 TreatmentImportant role of institutions (hospitals, clinics, VCT centres)Conditions to support treatmentMedication adherence planLiving positively• Adopt a healthy diet• Exercise regularly• Avoid alcohol and tobacco, or certainly minimize their consumption• Reduce stress• Avoid all forms of infection (when possible) because they may compromise your health and further weaken one’s immune system• Don’t use drugs other than those prescribed by your doctor• Visit the doctor regularly
57 Treatment of HIV Infection Today, there are 31 antiretroviral drugs (ARVs) approved by the U.S. Food and Drug Administration (FDA) to treat HIV infection.These treatments do not cure people of HIV or AIDS. Rather, they suppress the virus, even to undetectable levels, but they do not completely eliminate HIV from the bodyBy suppressing the amount of virus in the body, people infected with HIV can now lead longer and healthier lives.However, they can still transmit the virus and must continuously take antiretroviral drugs in order to maintain their health quality.
58 Post Exposure Prophylaxis (PEP) for Healthcare Workers Intact skin, mouth or nose: immediately wash with soap and water and rinse thoroughly to remove all potentially infectious particles.Cut or punctured skin: allow to bleed fully.Eye: flush immediately with water, then irrigate with normal saline for 30 minutes.Consider post exposure prophylaxis (PEP) if high risk of transmission:4 week course of zidovudine (ZDV)preferable to start within 1-2 hoursThe US Centers for Disease Control considers exposure to be high risk if the injury to the healthcare worker is deep, there is visible blood on the device causing injury, the injury was caused by a device previously placed in the client’s vein or artery, or the source patient died as a result of AIDS within 60 days of exposure.Before initiating treatment with antiviral agents, the individual should know that knowledge about the efficacy and toxicity of treatment and potential side effects of treatment is limited.Source: CDC 1996.
59 Post Exposure Treatment of Healthcare Workers, continued HIV testing immediately, 6 weeks, 6 months and 12 monthsTreatment, if started, should continue for 4 weeks. Any or all drugs may be declined by exposed worker.For lesser exposures, prophylaxis is not recommended.
60 PreventionCurrently, there is no vaccine to prevent HIV infection nor is there a cure for HIV/AIDS. To reduce risk of becoming infected with HIV or transmitting the virus to others:Consistent use of male latex condoms can help protect against HIV infection.Get tested regularly for HIVPractice abstinenceRemain faithful to your spouse or partnerConsistently use male latex or female polyurethane condomsDo not share needles