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The evaluation of 1585 typhoid cases published between 1992-2011 in Turkey by pool analysis method

Sebnem Calik1, Bulent Calik2
1 Izmir Urla State Hospital, Department of Infectious Diseases and Clinical Microbiology 2 Izmir Buca Seyfi Demirsoy Large State Hospital Department of General Surgery * Correspondence:

 

calikbulentdr@yahoo.com sebnemozkoren@yahoo.com

Abstract
Purpose: Typhoid is a systemic infection caused by Salmonella enterica serovar
typhi and it is still endemic in our country.

Methods: Three national and two international databases were sought. The key
words were determined as “tifo ve Türkiye” for national databases and “typhoid and Turkey” for international databases.

Results: The data obtained from 1585 cases. Most common symptoms determined in patients were fever (85.1%), abdomen pain (63.7%), vomiting (30.4%), diarrhea (27.9%) and headache (22.8%). Most determined findings in physical examination were hepatomegaly (29.8%), splenomegaly (22.9%), relative bradycardia (17.6%), abdominal tenderness (13.6%) and abdominal distantion (12.3%). In 609 cases (35.3%),the diagnosis was established by isolating S.enterica serovar typhi in cultures performed from various materials. The most common used antibiotics in treatment were ceftriaxone (40.1%), ciprofloxacin (34.3%) and chloramphenicol (15.8%). Most common complications in the examined cases were intestine perforation (29.4%), hepatitis (1.8%) and pneumonia (1.8%).

Conclusion: Typhoid is diagnosed in Turkey mainly by clinical signs and treatment
is carried out empirically. Ceftriaxone and ciprofloxacin are the predominantly used medicines. Though there are no serious problems with these drugs in Turkey, resilient cases are reported in various regions of the world. Protection of people are essential for controlling of typhoid fever in endemic areas.

This article is available from: www.jusurgery.com

Key words: Salmonella enterica serovar typhi, Turkey, case reports

Introduction
Typhoid is an acute systemic infection illness characterized by enteric fever, conscious confusion, nondecreasing fever, headache, abdominal pain, relative bradycardia, splenomegaly, leucopenia and skin rashes named as roseola, human specific, followed by bacteriemia. Typhoid in which salmonella enterica serovar typhi is an agent is seen more frequently than paratyphoid and its clinical evidence is more serious than paratyphoid. The illness infects humans by means of contaminated water and food , through fecal-oral routes. It is endemic in less developed countries including our country, © Copyright iMedPub

Turkey where untreated sewage is mixed up with drinking water, infrastructure and public health services are insufficient and outbreaks are notified in our country at times [1, 2]. Recently, typhoid has drawn attention to itself again with reports regarding multi drug resistance including ciprofloxacin and Salmonella’s origins producing extended spectrum beta-lactamase [3].In this study, the typhoid cases published in Turkey, their clinical and laboratory findings, antimicrobial sensitivity patterns and their systemic management were examined and the contribution of clinical and laboratory findings to diagnosis, the effect of common antibiotic use on typhoid fever, susceptibility patterns and relationships be-

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tween illness’s prognosis, its origins, antibiotic susceptibility pattern and the presence of other underlying illnesses were discussed.

Materials and methods
Three national data bases (Ulakbim Turkish Medicine Literature data base, http:// www.turkishmedline.com, http://medline.pleksus.com.tr) and two international data bases were searched to to find the series of cases published in Turkey. The key words were determined as “typhoid and Turkey” for national data bases and “typhoid fever and Turkey” for international data bases. The single diagnosis analysing typhoidparatyphoid cases together were not included in the study.

(33.8%) and chloramphenicol (28%) were the resistant declared antibiotics. The antibiotics used in the treatment of 530 cases were examined and the most popularly used antibiotics were ceftriaxone (40.1%), ciprofloxacin (34.3%) and chloramphenicol (15.8%). Most common complications seen in the examined cases were intestinal perforation (29.4%), hepatitis (1.8%) and pneumonia (1.8%). Twentytwo cases had underliying diseases. Underlying diseases were chronic obstructive pulmonary disease (ten cases), hematological malignancy (three cases), coronary artery disease (three cases), diabetes mellitus (one case), congenital heart disease (two cases), mental retardation (two cases) and chronic renal insufficiency (one case). Patient with diabetes mellitus had no complication. All of cases with chronic obstructive pulmonary disease (100%), coronary artery disease (100%), chronic renal insufficiency (100%) had intestinal perforation. Prognosis of other cases who had underlying diseases were not reported. Six of them were pregnancy. Altough all babies were born healthy, two mothers had intestinal perforation (33.3%). But pregnancy cases were alive. One case had malaria infection simultanously who did not have any complication. There were reported 105 cases of death due to typhoid fever (6.6%). Causes of death were intestinal perforation in 98 cases (93.3%), massive intestinal bleeding in two cases (1.9%). Causes of death were unknown in five cases (0.3%). The symptoms regarding typhoid were given in Table 1, physical examination findings in Table 2, laboratory findings in Table 3, isolation of bacteria from samples of cases in Table 4, antibiotics utilised in the treatment in Table 5, resistance pattern to antibiotics in Table 6, developed complications in cases were given in charts in Table 7.

Results
As a result of research, 53 case reports and series were identified and the whole text of 50 (94%) cases were attained and 45 of them were included in the study. Since five-series of typhoid-paratyphoid cases were evaluated together, they were not placed in the study. 45 articles were included in the study at issue, 28 of which were national and 17 of which were international. The data obtained from 1585 cases through 21case reports and 24-case series were analysed. Typhoid cases affirmed from 12 cities in Turkey were assessed. Diyarbakır, Van and Ankara are the cities in which the illness is mostly informed. Sex (female/male) and average age were not evaluated as they were not stated in some of the articles. Most common symptoms observed in patients were fever (85.1%), abdomen pain (63.7%), vomiting (30.4%), diarrhea (27.9%) and headache (22.8%). Most determined findings in physical examination were hepatomegaly (29.8%), splenomegaly (22.9%), relative bradycardia (17.6%), abdominal tenderness (13.6%) and abdominal distantion (12.3%). Most frequently determined laboratory findings were AST elevation (23.6%), leucopenia (21.5%), ALT elevation (20.6%), anemia (19.5%) and sedimentation elevation (17.7%). Gruber Widal test was positive in 460 (29%) cases. In 609 cases (35.3%),the diagnosis was established by isolating S.enterica serovar typhi in cultures performed from various materials. S. typhi was isolated in 465 blood culture (76.3%), 111 stools culture (18.2%), 26 bone marrow culture (4.%), abscess (0.6%), urine (0.3%) and empyema (0.1). 16 cases (3.4%) effectively isolated in blood culture were the cases using antibiotic empirically. Bone morrow culture was carried out in 27 cases and agent was produced in 26 of them (96.2%). Ampiciline (36.6%), trimethoprim sulfamethoxazole

Discussion
Typhoid is a systemic infection disease characterized by mental confusion, nondecreasing fever, headache, abdomen pain, relative bradycardia, splenomegaly, leucopenia, bacteriemia and skin rashes called as roseol [1-5]. Infection is transmitted by consumption of contaminated food or water. Shellfish taken from sewage-polluted areas are an important source of infection. Infection occurs also through eating raw fruit and vegetables fertilized by night soil, and through ingestion of contaminated milk and milk products. Flies may cause human infection through transfer of the infectious agents to foods. Pollution of water sources may produce epidemics of typhoid fever, when large numbers of people use the same source of drinking-water [2]. © Copyright iMedPub

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Table 1. Symptoms of typhoid fever cases.
Symptom Fever Abdominal pain Vomiting Diarrhea Headache Nausea Anorexia Weakness Chill Constipation Myalgia Agitation Nonproductive cough Backache/arthralgia Sweeting Sore throat Convulsion walking difficulty Dysuria Aphasia Shortness of breath Swelling of leg productive cough Behavioral disorder difficulty of urination Number 1350 1012 483 443 362 353 351 292 145 140 129 125 118 50 65 25 10 7 7 3 2 1 1 1 1 Ratio (%) 85.1 63.7 30.4 27.9 22,8 22,2 22,1 18,4 9.1 8.8 8.1 7.8 7.4 3.1 4.1 1.5 0.6 0.4 0.4 0.1 0.1 0.06 0.06 0.06 0.06

headache (9-82%), loss af appetite (26-36%),nausea (2336%), vomiting (20-48%), coughing (6-48%) and abdomen pain (11-45%) [7-14]. In the current study, Most common symptoms observed in patients were fever (85.1%), abdomen pain (63.7%), vomiting (30.4%), diarrhea (27.9%) and headache (22.8%) (table 1). Regardless of the classical well-known definition of typhoid, it should be kept in mind that its symptoms are not specific and the illness can proceed in a sneaky way [1]. Although typhoid is most prevalently seen illness by physicians working at primary care institutions, classic symptoms can change via the use of common antibiotics and it should be born in mind that its typical cases are rarely observed in clinic. In addition to that, increasing antibiotic resistance makes its severity and complications raise. Diarrhea (27.9%) was encountered more frequently than constipation (8.8%) in the current study (table 1). Typhoid is notified more prevalent diarrhea (18-75%) than constipation (4-22%) in the literature [7-14]. Leucocytes are typically seen in feces.Complications such as diarrhea, toxicity and common intravenous coagulation disorders are more often witnessed in infants and they progress with higher mortality rate[1]. Most determined physical examination findings in physical examination in the studied cases were hepatomegaly (29.8%), splenomegaly (22.9%), relative bradycardia (17.6%), abdominal tenderness (13.6%) and abdominal distantion (12.3%) (table 2). Most declared findings in typhoid cases in literature Table 2: Signs of typhoid fever cases.
Sign Hepatomegaly Splenomegaly Relative bradicardia Abdominal tenderness Abdominal distantion Confusion/encephalopathy Roseol Cervical LAP Ral Dicrot pulse Jaundice Stiff neck Murmur Number 473 363 279 217 196 118 109 33 14 11 11 3 1 Ratio (%) 29.8 22.9 17.6 13.6 12.3 7.4 6.8 2.0 0.8 0.6 0.6 0.1 0.06

New typhoid case is seen in approximately 16 million in the world and 600000 deaths are observed due to the illness under consideration. The disease is particularly endemic in less developed countries such as India, South East Asia, South and Central America and Africa including our country, Turkey [1, 2]. The morbidity rate of typhoid, potential cases (diagnosed clinically) and definite cases (produced in agent culture) were 33.59 in one hundred thousand in total in Turkey in 2004 [6]. Typhoid cases are more frequently observed in Southern East Anatolia region in our country. The areas in which the illness is endemic have some prevalent features such as rapid population growth, rising urbanization, not processing human waste properly, limited water sources and inadequate health systems. Intubation period in typhoid is typically 7-14 days, however, it can be 5-21 days according to bacteria inoculum amount and immunity response of an individual [1]. Most frequently informed complaints in typhoid events are fever (89-100%), © Copyright iMedPub

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Table 3. Labaratory findings of typhoid fever cases.
Tetkik AST elevation Leukopenia ALT elevation Anemia Sedimentation rate elevation Trombocytopenia Proteinuria CRP elevation Lenfomonocytosis Leucocytosis LDH elevation ALP elevation Bilirubin elevation Hematuria Trombocytosis Sayı 375 342 328 310 282 147 137 125 125 48 45 22 7 5 2 Oran (%) 23.6 21.5 20.6 19.5 17.7 9.2 8.6 7.8 7.8 3.0 2.8 1.3 0.44 0.31 0.1

kaline phosphatase, LDH elevation are more distinct in cases developing hepatitis due to typhoid [1, 2]. Hematuria, proteinuira and pyuria can be detected in typhoid cases that have kidney involvement [1]. Although there are acute kidney failure cases linked with typhoid (0.2%), no irreversible kidney functions loss are reported in this study. Definitive diagnosis of typhoid can be achieved by generation of Salmonella enterica serovar typhi from blood, bone marrow, mononuclear cells, platelet fraction, feces, urine, gastric and intestinal secretions [2]. In the current study, the diagnosis of 609 cases (35.3%) could be attained by isolation of S.typhi in cultures performed by a variety of materials (table 4) The most frequent material by which the agent was isolated was blood (76.3%). The reasons why isolation in blood culture was detected lower than literature points out could be relied on technical equipment insufficiency and absence of automatized blood culture system in many health institutions on account of its expenditure. As susceptibility of blood culture is 50-70% as a diagnosis test and the amount of bacteria is less in patients with typhoid (<15 bacteria /mL), it is reportant that obtaining a precise diagnosis is difficult [1]. If a patient gets antibiotic, it is implied that it can inhibit growth in the blood culture. In the first week of the illness, there can be reproduction in stools and urine cultures, nevertheless, their susceptibility is very low [15]. Bone marrow culture in the most sensitive method in diagnosis (90%), but it is invasive. Futhermore, equipment and trained personnel are required. It is an uncommon applied method. Its susceptibility does not change depending upon patient’s antibiotic use [1, 2]. Gruber-Widal test is positive in 29% of the cases. GruberWidal, the oldest serological test in diagnosis, is an agglutination test measuring antibody titer originating against O

are hepatomegaly (8-52%), splenomegaly (8-46%), susceptibility in the abdomen (10-45%), relative bradycardia (17-27%) and coated tongue (14-20%) [7-14]. Neuropsychiatric manifestations including confusion (10.10%), agitation (10.6%), convulsion (0.8%), behavior disorder )0.8%), aphasia (0.2%) were ascertained. Neuropsychiatric manifestations encountered in typhoid cases at 5-10% can be connected with cytokines released from macrophages infected with pathogen [1].The clinical symptoms and findings of typhoid may have changed depending upon accompanying illnesses and setting an early antibiotic treatment. Most frequently determined laboratory findings were AST elevation (23.6%), leucopenia (21.5%), ALT elevation (20.6%), anemia (19.5%) and sedimentation elevation (17.7%) (table 3). Most common findings stated in literature are anemia (32-54%) and leucopenia (18-26%) [7-14]. The number of leucocytes have reduced in relation to fever and toxicity. On the other hand, leukocytosis is more frequently seen in cases developing intestinal complication [1]. Thrombocytopenia is rarely seen, however, it can principally be an indicator of a serious illness and accompany with a prevalent intravascular coagulopathy pathology [15]. Hematologic findings are not oiginal, they do not help diagnosis process. Though increase is frequently seen in liver function tests, severe liver failure is seldom [15]. Conditions such as bilirubin, transaminase, al-

Table 4. Growth of Salmonella enterica serovar typhi in the cases samples*.
Kültür Blood Stool Bone marrow Abscess Urine Empyema Sayı 465 111 26 4 2 1 Oran (%) 29.3 7 1.5 0.2 0.1 0.06

* S. enterica serovar typhi were yielded both blood and stool culture in 48 cases.

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Table 5. The pattern of antibiotics resistance*
Antibiotic Ampicillin Trimethoprim-sulfamethoxazole Chloramphenicol Tetracycline Ampicillin-sulbactam Gentamicin Ceftriaxone Streptomycin Ciprofloxacin Nalidixic acid Sayı 231 206 171 30 19 16 13 1 0 0 Oran (%) 36.6 33.8 28 4.9 3.1 2.6 2.1 0.1 0 0

as severe illness, excess vomit, serious diarrhea and swelling in abdomen, cases developing complications and cases who had underlying diseases, they must be hospitalized and watched closely. Parenteral antibiotic treatment, proper nutrition and hydration are essential [15]. Most prevalent antibiotics used in the study were identified as ceftriaxone ( 40.1%), ciprofloxacin (34.3%) and chloramphenicol (15.8%) (table 5). Even though ceftriaxone is only used by intravenous administration, its frequent use can be associated with complications documented in literature and cases followed in hospitals. Of Salmonella isolates in most regions of the world, an elevated resistance is documented against ampicillin, chloramphenicol, tetracycline and sulfonamide which have multi-resistant qualities and used to be first option medicines in the treatment [18]. Most frequent resistance determined in S. enterica serovar typhi origin against antibiotics were seen in ampicillin (41.2%), cotrimoxazole (36.7%) and chloramphenicol (30.5%). The medicines used to be first options in S.typhi isolates are resistant to medicines called as chloramphenicol, ampicillin, cotrimoxazole more than 50% [19]. The increase in the resistance of antibiotic has suppressed the immune system, therefore it is vital in terms of having an underlying disease, old patients or leading to systemic prognosis and

* Microorganism were yielded in 609 of typhoid fever cases.

(somatic) and H (flagella) antigens of S. typhi [15, 16]. Although it is an easy viable test and its cost is inexpensive, Gruber-Widal test is not utilised in many of the health care institutions in consequence of having decreased susceptibility and specificity [15]. Modern and swift diagnosis tests have been developed determining IgM antibodies forming against direct pathogen including Typhidot, IgM dipstick and Tubex. However, these tests are not proved to be durable enough in large-scale evaluations in a society. It is not recommended by World Health Organization yet. There are limited data regarding a new developed test determining antigen in urine. “Nested” polymerase chain reaction (PCR) used in H1-d primaries allows amplification of S.typhi specific genes in patients blood [15]. Its susceptibility (100%) and specifity (100%) are high and it is a promising test for a rapid diagnose. Zhou et al, developed blood culture PCR method since the susceptibility of polymerase chain reaction and its specifity were determined low in early research. Salmonella enterica serovar typhi multiplying in blood culture (eniched medium) was determined that it increased the susceptibility by method assigning fliC-d gene of S.typhi and reduced the period for reproduction to 8 hours in blood culture [17]. High cost can restrict the use of these tests in the areas where the typhoid is endemic in the future. Unfortunately despite all these developments, diagnosis is achieved according to clinical criteria in Turkey. It is fundamental to diagnose typhoid early and initiate proper antibiotic treatment in order to prevent the development of complications and decrease mortality rate [15]. 90 % of cases can be observed by peroral antibiotic treatment and regular, out-patient follow-up. If there are conditions in patients such © Copyright iMedPub

Table 6. Antibiotic treatments of cases.
Antibiotic Ceftriaxone Ciprofloxacin Chloramphenicol Tiamphenicol+ofloxacin Tiamphenicol Ofloxacin Ampicillin Ampicillin+chloramphenicol Ciprofloxacin+ornidazole Trimethoprim-sulfamethoxazole Cefoxitin Ampicillin-sulbactam Cefoperazone-sulbactam imipenem-cilastatin Total Sayı 213 182 84 18 12 8 5 2 1 1 1 1 1 1 530 Oran (%) 40.1 34.3 15.8 3.3 2.2 1.5 0.9 0.3 0.1 0.1 0.1 0.1 0.1 0.1 100

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Table 7. Complication of typhoid fever cases.
Complication Intestinal perforation Hepatitis Pneumonia Massive intestinal bleeding Spleen granuloma Sacroiliitis Myocarditis Acute renal failure Empyema Hemolysis due to glucose-6phosphate dehydrogenase deficiency Liver granuloma Bone marow granuloma Acutepakreatitis Pleurisy Ileus Bleeding into the liver cyst Sudden hearing loss Mononeuritis multiplex Guillain-Barre Sayı 467 30 30 8 5 4 3 3 2 2 1 1 1 1 1 1 1 1 1 Oran (%) 29.4 1.89 1.89 0.5 0.3 0.2 0.1 0.1 0.1 0.1 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06

meorpenem, faropenem) can be used [1, 3, 4, 15]. Of cephalosporins, only cefepime and cefpodoksim-proksetil can be taken orally. Intravenous administration of cephalosporins such as cefepim, ceftriaxone, cefotaxime and cefoperazon, high cost treatment and prolonged fever are the disadvantages of the treatment. Recently, there has been resistance forming in Salmonella origins against these drugs, as well. As well as uncommon prevalence, extended spectrum betalactamase (ESBL) producing origins are documented [4, 19]. No Salmonella origin producing ESBL was encountered in the articles examined. Azithromycin has long-term intracellular concentration and half-life. Its advantages are its oral use, having broad spectrum and rapid fever response, limited side effects and drug interactions. Tigecyclin and carbapenems, however, are resistant to ciprofloxacin and it can be an option for treatments against origins generating extended spectrum beta-lactamase [23]. Prognosis in typhoid is dependent on rapid diagnosis and initiation of appropriate antibiotic treatment. Other factors affecting its prognosis are patient’s age, his/her medical condition and nourishment, serotype of Salmonella and developing complications. The death rate of typhoid prior to antibiotic treatment was nearly at 15%, on the other hand, the rate under discussion is at 1-2% in most series today [2]. This rate was 6.6% in this study. In individuals infected with strains having multi drug resistance and facilitating factors such as malnutrition, complication development probability is higher [15]. Complication rates are seen at 10-15% in the third and fourth weeks in untreated patients and can immediately affect the system [1]. A large variety of complications such as intestinal bleeding and perforation, cholecystitis, pancreatitis, liver and spleen abscesses, pericarditis, myocarditis, pyelonephritis, osteomyelitis, orchitis, soft tissue infections, pneumonia, meningitis, encephalomyelitis, Guillain-Barre syndrome, inappropriate ADH syndrome, cranial and peripheral neuritis, psychotic symptoms, common intravascular coagulopathy disorder, hemolytic uremic syndrome are reported to be encountered in patients diagnosed with typhoid in literature [1]. Complications including diarrhea, toxicity and common intravascular coagulopathy disorder are more often seen in infants and they progress with a higher mortality rate [1]. In the current study, most determined complications were intestinal perforation (29.4%), hepatitis (1.8%) and pneumonia (1.8%) (table 7). During the prognosis of typhoid, occult blood in stools of many patients is positive, however, the actual thing mentioned here is gross bleeding. If bleeding is excessive, body temperature falls instantly, pulse accelerates, patient pales, blood pressure decreases and hypovolemic shock follows these. Since more notification of intestinal perforation (0.5%) compared to intestinal bleeding is one of the leading reasons of mortality in typhoid, it can be associ© Copyright iMedPub

severe treatment problems in clinic tables [20]. Quinolon has been the first choice in the treatment of typhoid since the beginning of 1990s. As the administration of quinolon has decreased in the treatment, it has given rise to decreased susceptibility to these kinds of antibiotics and resistance development [4]. In the origins examined in the study, no resistance to ciprofloxacin, ofloxacin or nalidixic acid was documented (table 6). Nonetheless, cases susceptible to ciprofloxacin as of in vitro but unresponsive in clinical atmosphere drew attention [21]. It is reported that if there is a nalidixic acid resistance in strains vulnerable to quinolons as in vitro, treatment failure is likely to occur. Antibiogram disc which is a quinolon comprising nalidixic acid is suggested to be employed in order to determine the quinolon resistance [22]. Gatifloxacin, one of the new generation quinolons, is known to be effective to resistance to nalidixic acid origins [18]. Treatment options are getting narrower in cases resistant to quinolons. In these cases, azithromycin, broad spectrum cephalosporins (cefepim, ceftriaxone, cefotaxime,cefoperazon, cefpodoksim-proksetil, cefiksim) aztreonam, tigecyclin and carbapenems (imipenem,

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ated with emphasizing it further. Patients who had underlying diseases (such as chronic obstructive pulmonary disease, hematological malignancy, coronary artery disease, diabetes mellitus, congenital heart disease, mental retardation, chronic renal insufficiency) had higher intestinal perforation rate and mortality rate compared as other typhoid fever patients. For these reason patients who had underlying diseases should be hospitalized. Perforation is generally seen in terminal ileum; can be single or multiple. There can be severe abdominal pain, sensitivity and hardness in the stomach and vomiting. The general condition of the patient deteriorates and hypovelemic shock develops. Patient’s body temperature decreases quickly, pulse speeds up. Such data appearance on the fever table is called as “death cross”. Bacteriemia and peritonitis develop as secondary, fever increases again and leukocytosis occurs [2]. Late presentation, delay in operation, multi perforation, plenty of pus drainage are the factors that affect mortality in a negative way [1, 2]. Perforation diagnosis relative to typhoid in endemic areas are carried out based on history and physical examination findings. Therefore, not only are early diagnosis and treatment necessary for prevention of perforation development, but also close follow-up of patient is required during treatment. Perforation developed case must be observed in intensive care. It is known that typhoid can lead to abortus [2]. In the current study it did not cause fetus loss but two pregnant women (33.3%) had intestinal perforation. Because of high complication rate, pregnant cases should be hospitalized. Chronic carriers of bacteria in the urine or stool are positive for more than a year. Carrier rate is 1-4% in typhoid fever. Chronic gall bladder carriers are develop 3-4 times higher in women than men. Chronic gall bladder carriers are more commen those with cholelithiazis and gall bladder dysfunction. These people must be performed cholecystectomy as well as long-term antibacterial treatment [2]. Chronic urinary carriers are very rare nowadays. Nephrolithiasis, renal tuberculosis, Schistosomiasis are predisposing underlying condi-

tions in cases which have chronic urinary carriers [2]. Recurrent feces cultures are utilized in the detection of chronic carriers. The disadvantages of this method are its requirement for labour and time. Antibodies forming against Vi antigen can be identified in outbreaks. Nevertheless, the high level of Vi antigen in people living in endemic regions [4]. There are no chronic carriers in the examined cases. It is reported that in contaminated developed countries the control of typhoid fever is totally related to the provision of food hygiene and clean drinking water and infrastructure improvement [4, 24].Treatment of drinking water by its chlorination can be effective where the disease is mostly seen and it is not a high-priced method. Particularly, the determination of chronic carriers related to food production and their treatment are significant steps in the break of transmission cycle [4].

Conclusion
Typhoid fever is an infection disease protecting its importance even today. Salmonella enterica serovar typhi origins developing resistance to antibiotics used in treatment and being responsive are becoming common gradually. As a result of this, typhoid epidemiology has attracted attention to diagnosis methods and treatment options. Its diagnosis is attained through clinical evaluations in Turkey and its treatment is carried out empirically. While there are no troubles in resilience to ciprofloxacin and ESBL producing origins as yet, antibiotics should not be used at random. Knowing the regional antibiotic susceptibility of the origins is important in the management of cases. On the other hand chosing the appropriate antibiotic will aid preventing the development of the origins of resistant Salmonella enterica serovar typhi. Protection of people are essential for controlling of typhoid fever in endemic areas.

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