TROPICAL MEDICINE SYSTEM

INTERNATIONAL CLASSUNIVERSITAS HASANUDDIN

PBL REPORTMODULE 1: FEVER

GROUP: 12

MEDICAL FACULTYHASANUDDIN UNIVERSITY

MAKASSAR2012

Scenario 1 (Fever) :

Case

A man aged 22 years came to the clinic with complaints of fever for a week, less appetite, and accompanied by headache. Ten days ago a new patient comes from Papua.

Keywords

- Man aged 22 years old- Fever for a week- Less appetite- Headache- Ten days ago a new patient comes from Papua

Questions

1- What is the endemic disease that related to Papua?2- What is Different Diagnosis of this case?3- What is the etiology of the diseases based on Question 2?4- What are the signs and symptoms based on Question 2?5- What is the patomechanism of the diseases?6- What is the treatment of the diseases?

Answer

1- Papua comprises most of the western half of the island of New Guinea and nearby islands. Its capital is Jayapura. It's the largest and easternmost province of Indonesia. The province originally covered the entire western half of New Guinea. In 2003, the Indonesian government declared the westernmost part of the island, around Bird's Head Peninsula, a separate province; its name was first West Irian Jaya and is now West Papua. This most place in Papua is Jungle, so, the endemic disease that mostly in Papua is Malaria.

2- Different Diagnosis :

Malaria Dengue High fever Typhoid feverMan, 22 y/o Yes Yes YesFever for a one week

Yes Yes Yes

Less appetite Yes No NoHeadache Yes No YesTen days ago a new patient comes from Papua

Yes No No

3- Malaria Disease

Malaria, which predominantly occurs in tropical areas, is a potentially life-threatening disease caused by infection with Plasmodium protozoa transmitted by an infective female Anopheles mosquito vector. Individuals with malaria may present with fever and a wide range of symptoms. The 5 Plasmodium species known to cause malaria in humans are P falciparum,P vivax, P ovale, P malariae, and P knowlesi. Timely identification of the infecting species is extremely important, as P falciparum infection can be fatal and is often resistant to standard chloroquine treatment. P falciparum and P vivax are responsible for most new infections.

The Plasmodium species can usually be distinguished by morphology on a blood smear. P falciparum is distinguished from the rest of the plasmodia by its high level of parasitemia and the banana shape of its gametocytes.

Among patients with malaria, 5-7% are infected with more than a singlePlasmodium species. Co-infection with different Plasmodium species has also been described in the parasites’ mosquito vectors.

Each Plasmodium species has a defined area of endemicity, although geographic overlap is common. At risk for contraction of malaria are persons living in or traveling to areas of Central America, South America, Hispaniola, sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania. Among these regions, sub-Saharan Africa has the highest occurrence of P falciparum transmission to travelers from the United States.

Etiology

Individuals with malaria typically acquired the infection in an endemic area following a mosquito bite. Cases of infection secondary to transfusion of infected blood are extremely rare. The risk of infection depends on the intensity of malaria transmission and the use of precautions, such as bed nets, diethyl-meta-toluamide (DEET), and malaria prophylaxis.

The outcome of infection depends on host immunity. Individuals with immunity can spontaneously clear the parasites. In those without immunity, the parasites continue to expand the infection. P falciparum infection can result in death. A small percentage of parasites become gametocytes, which undergo sexual reproduction when taken up by the mosquito. These can develop into infective sporozoites, which continue the transmission cycle after a blood meal in a new host.

The mechanisms that underlie immunity remain poorly defined. Additionally, individuals who develop immunity to malaria who then leave the endemic area may lose protection. Travelers who return to an endemic area should be warned that waning of immunity may increase their risk of developing several malaria if reinfected. These travelers returning to endemic areas are a special population, sometimes termed visiting friends and relatives (VFRs).

Incubation

Each Plasmodium species has a specific incubation period. Reviews of travelers returning from endemic areas have reported that P falciparum infection typically develops within one month of exposure, thereby establishing the basis for continuing antimalarial prophylaxis for 4 weeks upon return from an endemic area. This should be emphasized to the patient to enhance posttravel compliance.

Rarely, P falciparum causes initial infection up to a year later. P vivax and P ovalemay emerge weeks to months after the initial infection. In addition, P vivax and P ovale have a hypnozoite form, during which the parasite can linger in the liver for months before emerging and inducing recurrence after the initial infection. In addition to treating the organism in infected blood, treating the hypnozoite form with a second agent (primaquine) is critical to prevent relapse from this latent liver stage.

When P vivax and P ovale are transmitted via blood rather than by mosquito, no latent hypnozoite phase occurs and treatment with primaquine is not necessary, as it is the sporozoites that form hypnozoites in infected hepatocytes.

Life cycle

The vector, the Anopheles species mosquito, transmits plasmodia, which are contained in its saliva, into its host while obtaining a blood meal. Plasmodia enter circulating erythrocytes (red blood cells, or RBCs) and feed on the hemoglobin and other proteins within the cells. One brood of parasites becomes dominant and is responsible for the synchronous nature of the clinical symptoms of malaria. Malaria-carrying female Anopheles species mosquitoes tend to bite only between dusk and dawn.

The protozoan brood replicates inside the cell and induces RBC cytolysis, causing the release of toxic metabolic byproducts into the bloodstream that the host experiences as flulike symptoms. These symptoms include chills, headache, myalgias, and malaise, and they occur in a cyclic pattern. The parasite may also cause jaundice and anemia due to the lysis of the RBCs. P falciparum, the most malignant of the 5 species of Plasmodium discussed here, may induce renal failure, coma, and death. Malaria-induced death is preventable if the proper treatment is sought and implemented.

P vivax and P ovale may produce a dormant form that persists in the liver of infected individuals and emerges at a later time. Therefore, infection by these species requires treatment to kill any dormant protozoan as well as the actively infecting organisms. This dormant infection is caused by the hypnozoite phase of the life cycle, which involves a quiescent liver phase. (During this phase, the infection is not typically eradicated by normal courses of antimalarials and requires treatment with primaquine to prevent further episodes of disease.)

Malaria-causing Plasmodium species metabolize hemoglobin and other RBC proteins to create a toxic pigment called hemozoin.

Sign and Symptoms

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), jaundice, hemoglobinuria, retinal damage,and convulsions. The classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours, occurring every two days in P. vivax and P. ovale infections, and every three days for P. malariae.. P. falciparum can have recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. For reasons that are poorly understood, but that may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage. Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage. This neurologic damage results from cerebral malaria to which children are more vulnerable. Cerebral malaria is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.

Severe malaria is almost exclusively caused by Plasmodium falciparum infection, and usually arises 6–14 days after infection.Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable.Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria withrenal failure may occur. Renal failure is a feature of blackwater fever, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria can progress extremely rapidly and cause death within hours or days.In the most severe cases of the disease, fatality rates can exceed 20%, even with intensive care and treatment. In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten. Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.

Treatment

Several drugs, most of which are used for treatment of malaria, can be taken preventively. Chloroquine may be used where the parasite is still sensitive. However, due to resistance one of three medications, mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone) is frequently needed.Doxycycline and the atovaquone and proguanil combination are the best tolerated; mefloquine is associated with higher rates of neurological and psychiatric symptoms.

The prophylactic effect does not begin immediately upon starting the drugs, so people temporarily visiting malaria-endemic areas usually begin taking the drugs one to two weeks before arriving and must continue taking them for four weeks after leaving (with the exception of atovaquone proguanil that only needs to be started two days prior and continued for 7 days afterwards). Generally, these drugs are taken daily or weekly, at a lower dose than is used for treatment of a person who had contracted the

disease. Use of prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is usually restricted to short-term visitors and travelers to malarial regions. This is due to the cost of purchasing the drugs, negative side effects from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.

Quinine was used historically; however, the development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th century reduced its use. Today, quinine is not generally used for prophylaxis. The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.

Dengue Fever

Etiology

Dengue infection is caused by dengue virus (DENV), which is a single-stranded RNA virus (approximately 11 kilobases long) with an icosahedral nucleocapsid and covered by a lipid envelope. The virus is in the family Flaviviridae, genus Flavivirus, and the type-specific virus is yellow fever.

The dengue virus has 4 related but antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Genetic studies of sylvatic strains suggest that the 4 serotypes evolved from a common ancestor in primate populations approximately 1000 years ago and that all 4 separately emerged into a human urban transmission cycle 500 years ago in either Asia or Africa. Albert Sabin speciated these viruses in 1944. Each serotype is known to have several different genotypes.

Living in endemic areas of the tropics (or warm, moist climates such as the southern United States) where the vector mosquito thrives is an important risk factor for infection. Poorly planned urbanization combined with explosive global population growth brings the mosquito and the human host into close proximity. Increased air travel easily transports infectious diseases between populations.

Sign and Symptoms

Typically, people infected with dengue virus are asymptomatic (80%) or only have mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days, but most often it is 4–7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home.Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea), and generally have less severe symptoms than adults, but are more susceptible to the severe complications.

Clinical course

The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "break-bone fever", comes from the associated muscle and joint pains.The course of infection is divided into three phases: febrile, critical, and recovery.

The febrile phase involves high fever, often over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days. At this stage, a rash occurs in approximately 50–80% of those with symptoms. It occurs in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by brokencapillaries) can appear at this point,as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic in nature, breaking and then returning for one or two days, although there is wide variation in how often this pattern actually happens.

In some people, the disease proceeds to a critical phase, which follows the resolution of the high fever and typically lasts one to two days.During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs. During this phase, organ dysfunction and severe bleeding, typically from the gastrointestinal tract, may occur. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk.

The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, but there may be severe itching and a slow heart rate. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures.

Treatment

There are no specific treatments for dengue fever.Treatment depends on the symptoms, varying from oral rehydration therapy at home with close follow-up, to hospital admission with administration of intravenous fluids and/or blood transfusion. A decision for hospital admission is typically based on the presence of the "warning signs" listed in the table above, especially in those with preexisting health conditions.

Intravenous hydration is usually only needed for one or two days. The rate of fluid administration is titrated to a urinary output of 0.5–1 mL/kg/hr, stable vital signs and normalization ofhematocrit Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk. Paracetamol(acetaminophen) is used for fever and discomfort

while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding. Blood transfusion is initiated early in patients presenting with unstable vital signs in the face of a decreasing hematocrit, rather than waiting for the hemoglobin concentration to decrease to some predetermined "transfusion trigger" level. Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not.

During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.

Typhoid fever

Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness caused primarily by Salmonella typhi. The protean manifestations of typhoid fever make this disease a true diagnostic challenge. The classic presentation includes fever, malaise, diffuse abdominal pain, and constipation. Untreated, typhoid fever is a grueling illness that may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within one month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications.

S typhi has been a major human pathogen for thousands of years, thriving in conditions of poor sanitation, crowding, and social chaos. It may have responsible for the Great Plague of Athens at the end of the Pelopennesian War.  The nameS typhi is derived from the ancient Greek typhos, an ethereal smoke or cloud that was believed to cause disease and madness. In the advanced stages of typhoid fever, the patient's level of consciousness is truly clouded. Although antibiotics have markedly reduced the frequency of typhoid fever in the developed world, it remains endemic in developing countries.

Pathopyhsiology

All pathogenic Salmonella species are engulfed by phagocytic cells, which then pass them through the mucosa and present them to the macrophages in the lamina propria. Nontyphoidal salmonellae are phagocytized throughout the distal ileum and colon. With toll-like receptor (TLR)–5 and TLR-4/MD2/CD-14 complex, macrophages recognize pathogen-associated molecular patterns (PAMPs) such as flagella and lipopolysaccharides. Macrophages and intestinal epithelial cells then attract T cells and neutrophils with interleukin 8 (IL-8), causing inflammation and suppressing the infection.

In contrast to the nontyphoidal salmonellae, S typhi enters the host's system primarily through the distal ileum. S typhi has specialized fimbriae that adhere to the epithelium over clusters of lymphoid tissue in the ileum (Peyer patches), the main relay point for macrophages traveling from the gut into the lymphatic system.S typhi has a Vi

capsular antigen that masks PAMPs, avoiding neutrophil-based inflammation. The bacteria then induce their host macrophages to attract more macrophages.

It co-opts the macrophages' cellular machinery for their own reproduction  as it is carried through the mesenteric lymph nodes to the thoracic duct and the lymphatics and then through to the reticuloendothelial tissues of the liver, spleen, bone marrow, and lymph nodes. Once there, the S typhi bacteria pause and continue to multiply until some critical density is reached. Afterward, the bacteria induce macrophage apoptosis, breaking out into the bloodstream to invade the rest of the body

The gallbladder is then infected via either bacteremia or direct extension of S typhi–infected bile. The result is that the organism re-enters the gastrointestinal tract in the bile and reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the stool and are then available to infect other hosts.

Sign and Symptoms

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, there is a slowly rising temperature with relative bradycardia, malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia, a decrease in the number of circulating white blood cells, with eosinopenia and relative lymphocytosis, a positive reaction and blood cultures are positive for Salmonella typhi or paratyphi. The classic Widal test is negative in the first week.

In the second week of the infection, the patient lies prostrate with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation), classically with a dicrotic pulse wave. Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. There are rhonchi in lung bases. The abdomen is distended and painful in the right lower quadrant where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea soup. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal reaction is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage. (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second week.)

In the third week of typhoid fever, a number of complications can occur:

Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually not fatal.

Intestinal perforation in the distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.

Encephalitis

Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.

Metastatic abscesses, cholecystitis, endocarditis and osteitis

The fever is still very high and oscillates very little over 24 hours. Dehydration ensues and the patient is delirious (typhoid state). By the end of third week the fever has started reducing this (defervescence). This carries on into the fourth and final week.

Treatment

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.

Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin andciprofloxacin, have been commonly used to treat typhoid fever in dicrobiology (Baron S et al.'tment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.

When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases. In some communities, however, case-fatality rates may reach as high as 47%.

Surgical Treatment

Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer simple closure of the perforation with drainage of theperitoneum. Small-bowel resection is indicated for patients with multiple perforations.

If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is not always successful in eradicating the carrier state because of persisting hepatic infection.

References

a) Word web 5.00b) Legacy Owens Boro c) Medscape, Marty, AM. Dermatologic Manifestation of Filariasis.2009 ,By Aillen M.,

MD

d) WHO. Malaria. 2011. http://www.who.int/topics/malaria/en/ e) Fauce et al. Harrison's Internal Medicine. 2008. Chapter 203. Malariaf) Jorge, EVP. Malaria. 2011. http://emedicine.medscape.com/article/221134-

overview#a0199g) http://www.searo.who.int/LinkFiles/Malaria_in_the_SEAR_ende_indo05.pdf h) Mcphee, SJ ; Papadakis, MA. Current Medical Diagnosis and Treatment. 2009.

Chapter 35. Protozoal & Helminthic Infections > Protozoal Infectionsi) Jorge, EVP. Malaria. http://emedicine.medscape.com/article/221134-workupj) Bahan kuliah, Mubin, R. Malaria. 2011k) UNHAS Medical Faculty Tropical Medicine System lecture notesl) Atlas of Medical Helminthology and Protozoology (2001), Chiodini, Moody, Manser,

Elsevier Saundersm) Ahmed, Shadab Hussain. Schistosomiasis. 2010.

http://emedicine.medscape.com/article/228392-overview#showalln) Anonymous, Schistosomiasis.

http://www.medicinenet.com/schistosomiasis/article.htmo) Ahmed, Shadab Hussain. Schistosomiasis Clinical Presentation. 2010.

http://emedicine.medscape.com/article/228392-clinical#showallp) Ahmed, Shadab Hussain. Schistosomiasis Workup. 2010.

http://emedicine.medscape.com/article/228392-workupq) MicrobiologyBytes. Schistosomiasis. 2007.

http://www.microbiologybytes.com/introduction/Schisto.htmlr) Anonymous. Complication of Schistosomiasis. 2011.

http://www.wrongdiagnosis.com/s/schistosomiasis/complic.htms) http://www.emedicine.com/ t) http://www.cdc.gov u) Communicable Disease, USMv) Bahan kuliah, Helminth usus & jaringan. 2011w) Harrison's Internal Medicine, Chapter 210. Intestinal Nematodes