Case report

Concurrent typhoid fever and dengue hemorrhage fever

M.Thaufiqurrakhman

Abstract Dengue and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. In Indonesia as well as in many developing countries both typhoid fever and dengue hemorrhagic fever (DHF) are still endemic and prevalent. In Indonesia the incidence of DHF in 1994 was 9.72/100,000 population with CFR of 2.5% and each year about 640,0001,500,000 cases of typhoid fever were reported with mortality of 1.6-3%. The concurrent infection of both diseases may occur in one patient.

Keywords: dengue, typhoid, fever, concurrent

Introduction Typhoid fever is caused by infection of humans with the microorganism Salmonella enterica subspecies enterica serotype Typhi (S. typhi for short). It is a systemic disease characterized by a prolonged fever, malaise and weight loss. On physical examination, characteristic skin lesions, rose spots, usually accompany a hepatosplenomegaly. Without antibiotic treatment the fever may persist for several weeks, and the disease will be fatal in about 15 percent of those affected. The bacterium is transmitted by faecal-oral route, through contaminated water or food.3 S. typhi is highly adapted to its human host; there is no reservoir but man. Therefore, every case of typhoid fever means an infection from a previous one. The immunopathogenesis is characterized by a sustained low-grade bacteremia with microbial invasion of and multiplication within the mononuclear phagocytes lining the sinoids of the liver, spleen, bone marrow, lymph nodes, and Peyers patches. Bacterial multiplication at the latter sites, with necrosis and sloughing of the overlaying mucosal epithelium produces the characteristic ulcerations of Peyers patches in the terminal ileum, a long recognized pathological entity that proved invaluable to distinguish typhoid fever from typhus. Paratyphoid fever is clinically and pathologically a highly similar disease, but caused by Salmonella enterica subspecies enterica serotypes Paratyphi A, B or C (S. paratyphi for short). Enteric fever refers to both typhoid fever and paratyphoid fever.3 Although practically eradicated from the developed Western countries, enteric fever remains a major global health problem due to its high incidence and

signicant morbidity and mortality in developing countries. For the year 2000, it was estimated that 21.650.974 patients contracted typhoid fever, and that 216.510 died due to the disease, whereas paratyphoid fever was responsible for about 25 percent of all enteric fever cases and was estimated to infect 5.412.744 individuals (3). In Indonesia, the annual costs of treatment of typhoid fever cases has been estimated at approximately US$ 60 million, with an additional US$ 65 million loss of income, and typhoid is cause of deaths of about 20.000 individuals (4). In Jakarta, clinicians and public health experts believe that typhoid fever still is one of the ve most common febrile illnesses causing the highest mortality among hospitalized patients.3 Dengue fever (DF) is an acute febrile viral disease frequently presenting with headaches, bone or joint and muscular pains, rash and leukopenia as symptoms. Dengue haemorrhagic fever (DHF) is characterized by four major clinical manifestations: high fever, haemorrhagic phenomena, often with hepatomegaly and, in severe cases, signs of circulatory failure. Such patients may develop hypovolaemic shock resulting from plasma leakage. This is called dengue shock syndrome (DSS) and can be fatal.4 Dengue viruses are transmitted to humans through the bite of infected Aedes mosquitos, principally Aedes aegypti, and are therefore considered to be arboviruses (arthropod-borne viruses). Once infected, a mosquito remains infected for life, transmitting the virus to susceptible individuals during probing and feeding. Infected female mosquitos may also pass the virus to the next generation of mosquitos by transovarian transmission, but this occurs infrequently and probably does not contribute signicantly to human transmission. Humans are the main amplifying host of the virus, although studies have shown that monkeys in some parts of the world may become infected and perhaps serve as a source of virus for feeding mosquitos. The virus circulates in the blood of infected humans at approximately the time that they have fever, and uninfected mosquitos may acquire the virus if they feed on an individual when he or she is viraemic. The virus then develops in the mosquito for a period of 810 days before it can be transmitted to other humans during subsequent probing or feeding. The length of time required for this extrinsic incubation depends in part on environmental conditions, especially ambient temperature.4

Case report A 18-year-old woman was admitted to Ulin Hospital on 10 January 2010. She was sent from Cempaka Local Government Clinic, Banjarbaru with diagnose Typhoid fever and DHF. She complained of fever more than 1 week, headache, nausea and dont want to eat. Trombosit count from Banjarbaru is 90.900. She also has rash over her both hand a few days ago. On admission at the Ulin Hospital, the patients blood pressure was 120/80 mmHg; heart rate 80 beats per minute; body temperature, 36,0 oC; and respiratory rate, 20 breaths per minute. On physical examination, the patient was compos mentis, conjunctiva anemic, pressure pain in epigastrium regio. There is no hematomesis, ginggiva bleeding, melena or other bleeding.

Test HAEMATOLOGY Haemoglobin Leucocyte Erythrocyte Haematocryte Trombocyte RDW-CV MCV.MCH.MCHC MCV MCH MCHC Diff. Count Neutrophil % Lymphocyte % MID % Neutrophil # Lymphocyte # MID#

Result 11,4 3000 4,62 35 72.000 15,5 76 24,7 32,5 22,7 59,1 12,4 0,69 1,79 0,8

Normal Range 12.0 16.0 4,0 10,5 3.90 5.50 35 45 150 450 11.5 14.7 80.0 97.0 27.0 32.0 32.0 38.0 50.0 70.0 25.0 40.0 3.0-9.0 2.50 7.00 1.25 4.00 0.30-1.00

Satuan g/dL thousand/ul billion/ul Vol% billion/ul % fl pg % % % % thousand/ul thousand/ul thousand/ul

Method

Table.1 Laboratory test results on admission (10 January 2010). The conjunctiva was anemic, but from laboratory test show haemoglobin is 11,7 g/dl, transfusion of PRC is not necessary to do. Thrombocyte count is 72.000 thousand/ul but there is no bleeding on the patient. Furthermore there is no reasonable to give her TC transfusion for right now. Her clinical ndings fullled criteria for DHF and typhoid. Fever 1 weeks, myalgia, For control of the disease, on day 1st of admission she was given injection of ranitidine 40mg twice a day, injection metal prednisolon 125mg twice a day, injection antrain twice a day. For oral medication she have cholescor 3 times a day. On day 2th, the oral drug of ciprofloxacin 500mg, 2 times/day added, and metal prednisolon injection was tapered once a day. And for antrain was used when it necessary. On day 3th, all of injection stopped, and the drugs added with imunos tablet once a day. On day 1 until day 3 of admission the patients blood pressure, heart rate, respiratory and body temperature rate were in normal level. Her complained of fever, pain, headache was decrease. The patient was discharged 3 days after admission in stable condition. She had decreased complained. The doctor was planned to give cholescor 3 times a day, imunos once a day and ciprofloxacin twice a day and also regular check-up one week after home. Discussion The definitive diagnosis of typhoid fever requires the isolation of Salmonella enterica serotype Typhi from the patient. Cultures of blood, stool, urine, rose spots, blood mononuclear cell-platelet fraction, bone marrow, and

gastric and intestinal secretions can all be useful for diagnosis. However, this requires laboratory equipment and technical training that are beyond the means of most primary health care facilities in the developing world. Consequently, Widal test is the only specific diagnostic investigation available in most tropical regions. The Widal test which is readily available and inexpensive was introduced as a serologic technique to aid in diagnosis of typhoid fever and has been used for more than a century. The test was based on demonstrating the presence of agglutinin (antibody) in the serum of an infected patient, against the H (flagellar) and O (somatic) antigens of Salmonella typhi. The role of the Widal test had been to increase the index of suspicion for the presence of typhoid fever by demonstrating a positive agglutination during the acute and convalescent period of infection with evidence of a four-fold rise of antibody titre. The Widal test reaction involves the use of bacterial suspensions of S. typhi and S. paratyphi A and B, treated to retain only the O and H antigens. These antigens are employed to detect corresponding antibodies in the serum of a patient suspected of having typhoid fever. The IgM somatic O antibody appears first and represents the initial serologic response in acute typhoid fever, while the IgG flagella H antibody usually develops more slowly butpersists for longer. Two types of agglutination techniques are available: the slide test and the tube test.

Neuropsychiatric (NPSLE) manifestations in the course of SLE occur in about 60% of patients. However, primary neuropsychiatric presentation is seen in 20%, and psychiatric presentation in only 10% of cases of SLE. There are no definite diagnostic criteria for primary presentations of CNS lupus because of its diverse clinical manifestations. Its diagnosis is based on high index of suspicion and on evidence of other American Rheumatological Association (ARA) criteria for the diagnosis of SLE. Commonly recognised presentations are: Organic brain

syndrome (55%), stroke (35%), peripheral neuropathy (29%), seizure (29%), transverse myelitis (19%) and psychiatric 10%. Patient can also present with intractable headache or loss of memory.17 Studies, analyzing cognitive and psychological deficit in SLE without overt central nervous system (CNS) disease, revealed deficits in learning as well as psychological distress without major psychiatric pathology, which may be subtle manifestations of CNS lupus. The commonest associated feature is subsequent thrombocytopenia, which occurs in about 7% cases. Many manifestations can develop because of metabolic abnormality, neuroinfections, or side effects of medications. Thus, in any patient of NPSLE it is crucial to exclude secondary cause of the presenting complaint. It is especially important to exclude neuro-infections, which are the commonest cause of morbidity and mortality.17 On day 1 of admission she was started on methylprednisolone 125 mg IV every 12 hours, metronidazole 500gr IV, ceftriaxone 1gr IV and slow diazepam 5mg IM. Her mental status continued to deteriorate over the next several days. She went from being awake and alert, to being confused, and then pretend that someone want to kill her. On day 12th of admission she got oral methylprednisolone 8 mg 3 times/day, CaCO3 3 times/day, and ranitidine 2 times/day. Methylprednisolone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. It may be used to treat a range of serious inflammatory diseases and tumors, but may have significant side effects. Methylprednisolone can, therefore, be used in autoimmune diseases, inflammatory diseases such as SLE. The usual dose of methylprednisolone is 5 to 10 mg daily. Although methylprednisolone can be started at higher doses (15 to 20mg daily), attempts should be made to taper the dose over a few weeks to less than 10mg daily. Once started, corticosteroid therapy is very difficult to discontinue and even at low doses.18 Calcium carbonate (CaCO3) is widely used medicinally as an inexpensive dietary calcium supplement. It may be used as a phosphate binder for the treatment of hyperphosphatemia (primarily in patients with chronic renal failure) and also to reduce the symptom of gastric acid over production caused prednisone.18 On day 6 of the drugs added with lansoprazole 2 times/day and neurodex 1 times/day. Lansoprazol is a proton pump inhibitor which prevents the stomach from producing acid. Lansoprazole is indicated for treatment of ulcers of the stomach and duodenum, and NSAID-induced ulcers. Neurosanbe 5000 was a vitamin which indicated to neurotropic and deficiency vitamin symptom and also anemia.18 After 7 days on steroids, Yvonne's mental status improved. She responded to voice and became more alert and oriented. Now that she was more cooperative, physical and occupational therapy began for more active range of motion, muscle strengthening, and assistance with activities of daily living. Yvonne was anemic throughout her hospitalization and received a total of 4 units of packed red blood cells.

Biologics/biological response modifiers (BRMs): These are genetically engineered drugs that target specific chemicals in the immune system called cytokines, which are produced by cells that affect other cells during an inflammatory response. Examples of specific cytokines targeted by Biologics include tumour necrosis factor (TNF). Tumor necrosis factor alpha (TNF-) is a pro-inflammatory cytokine produced by macrophages and lymphocytes. It is found in large quantities in the rheumatoid joint and is produced locally in the joint by synovial macrophages and lymphocytes infiltrating the joint synovium. The pro-inflammatory effects of TNF- suggests that inhibition of TNF- would be clinically useful in rheumatoid arthritis. Indeed extensive clinical trial data have confirmed the efficacy of all three currently available TNF inhibitors in relieving the signs and symptoms of RA, and in slowing or halting radiographic damage.18,19 Antimalarials such as hydroxychloroquine and chloroquine are rapidly absorbed, relatively safe, well-tolerated and often effective remittive agents for the treatment of SLE, particularly mild to moderate disease. Mechanism: The mechanism of action of antimalarials in the treatment of patients with SLE is blocking of UV light from skin denaturated, have an anti inflammation effect, decreased the cholesterol amount, prevent blood coagulation, blocking the cytokine and balancing acid-base condition. Dosage: Hydroxychloroquine (Plaquenil, 200 mg tablets) is the drug of choice among antimalarials. Chloroquine is no longer recommended because of its greater ocular toxicity. The usual dose is 400 mg/day (6 mg/kg) but 600 mg/day is sometimes used. Normally it is prescribed as a single nighttime dose to avoid gastrointestinal symptoms. Side Effects: The most important toxicities are ocular: corneal deposits, extraocular muscular weakness, loss of accommodation, and a retinopathy that may progress to irreversible visual loss. Ocular toxicity is only 1 out of 40,000 patients treated at the doses recommended, but a baseline ophthalmologic examination and a follow-up examination every 12 months are recommended during the period of treatment.19 Neuron reactive autoantibodies are considered a much better marker for CNS involvement, with levels significantly higher in SLE patients with cerebritis (Ochola, Hussain, Khamashta, Hughes, & Vergani, 1995). Specifically, lymphocytotoxic antibodies (LCAs) are seen in 80% of patients (Bruyn, 1995). In general, determination of an immunologic marker in the CSF is a better indicator of CNS activity than the similar test in the serum (Barr & Merchut, 1992). Assessment of complement components (C3 and C4), which are part of the coagulation cascade, show low serum and CSF concentrations (Johnson, 1999). Finally, diagnostic indicators for lupus cerebritis may include serial cognitive and neuropsychological testing, which address motor function, dexterity, and verbal and nonverbal abilities. In one study of patients who presented with neuropsychiatric manifestations, 87% had abnormal tests in the Halstead-Reitan Neuropsychological Test Battery and the Luria-Nebraska Battery (Barr & Merchut, 1992). One study illustrated the benefits of using the Beck Depression Inventory in assessing depression in patients with SLE (Iverson, Sawyer, McCracken, & Kozora, 2001).

Conclusion Lupus cerebritis may be the first indication of SLE. No one diagnostic test is conclusive of the CNS involvement in SLE; however, clinical manifestations support diagnosis. Various treatment options are utilized to aid with immunosuppression and the hypercoagulable state. The CNS involvement seen in lupus cerebritis is difficult for the family to deal with not only because of the sudden changes, but also because the waiting period for exact diagnosis may lead the family into a very difficult coping period. The neuroscience nurse has an important role in understanding not only the CNS involvement of SLE but also its diagnostic and treatment modalities, to help the patient and family cope with this sometimes devastating disease.

References 1. Uneke CJ. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications. J Vector Borne Dis 2008;45:133142. Sudjana P, Jusuf H. Concurrent dengue hemorrhagic fever and typhoid fever infection in adult: case report. Southeast Asian J Trop Med Public Health 1998;29:370-372. Ali S. Typhoid fever: aspects of environment, host and pathogen interaction. Hollandse Hoogte, Jakarta 2006. -----. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. WHO Genewa second edition 1997.

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3. 4. 5.