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Spatial and temporal structure of typhoid outbreaks in Washington, D.C., 1906-1909: evaluating local clustering with the Gi* statistic.

BACKGROUND: To better understand the distribution of typhoid outbreaks in Washington, D.C., the U.S. Public Health Service (PHS) conducted four investigations of typhoid fever. These studies included maps of cases reported between 1 May - 31 October 1906 - 1909. These data were entered into a GIS database and analyzed using Ripley's K-function followed by the Gi* statistic in yearly intervals to evaluate spatial clustering, the scale of clustering, and the temporal stability of these clusters. RESULTS: The Ripley's K-function indicated no global spatial autocorrelation. The Gi* statistic indicated clustering of typhoid at multiple scales across the four year time period, refuting the conclusions drawn in all four PHS reports concerning the distribution of cases. While the PHS reports suggested an even distribution of the disease, this study quantified both areas of localized disease clustering, as well as mobile larger regions of clustering. Thus, indicating both highly localized and periodic generalized sources of infection within the city. CONCLUSION: The methodology applied in this study was useful for evaluating the spatial distribution and annual-level temporal patterns of typhoid outbreaks in Washington, D.C. from 1906 to 1909. While advanced spatial analyses of historical data sets must be interpreted with caution, this study does suggest that there is utility in these types of analyses and that they provide new insights into the urban patterns of typhoid outbreaks during the early part of the twentieth century.

Disease Outbreaks↗

"Winged sponges": houseflies as carriers of typhoid fever in 19th- and early 20th-century military camps.

Typhoid fever was the scourge of 19th- and early 20th-century armies. During the Spanish-American War (1898) and the Anglo-Boer War (1899- 1902), typhoid killed more soldiers than enemy bullets. Walter Reed and his coworkers investigated the cause of the typhoid epidemics in the U.S. Army camps and concluded that, next to human contact, the housefly (Musca domestica) was the most active agent in the spread of the disease. British medical officers in South Africa, facing even worse typhoid epidemics, reached the same conclusion. The experiences of the American and British armies finally convinced the medical profession and public health authorities that these insects conveyed typhoid. The housefly was now seen as a health menace. Military and civilian sanitarians waged fly-eradication campaigns that prevented the housefly's access to breeding places (especially human excrement), and that protected food and drink from contamination. Currently, M. domestica is recognized as the mechanical vector of a wide variety of viral, bacterial, and protozoal pathogens. Fly control is still an important public health measure in the 21st century, especially in developing countries.

Animals↗

Spatial-temporal and phylogenetic analyses of epidemiologic data to help understand the modes of transmission of endemic typhoid fever in Samoa.

Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S. Typhi circulation remain unclear. From April 2018-June 2020, epidemiologic data and GPS coordinates were collected during household investigations of 260 acute cases of typhoid fever, and 27 asymptomatic shedders of S. Typhi were detected among household contacts. Spatial and temporal distributions of cases were examined using Average Nearest Neighbor and space-time hotspot analyses. In rural regions, infections occurred in sporadic, focal clusters contrasting with persistent, less clustered cases in the Apia Urban Area. Restrictions to population movement during nationwide lockdowns in 2019-2020 were associated with marked reductions of cases. Phylogenetic analyses of isolates with whole genome sequences (n = 186) revealed one dominant genotype 3.5.4 (n = 181/186) that contains three Samoa-exclusive sub-lineages: 3.5.4.1, 3.5.4.2, and 3.5.4.3. Variables of patient sex, age, and geographic region were examined by phylogenetic groupings, and significant differences (p<0.05) associated genetically-similar isolates in urban areas with working ages (20-49 year olds), and in rural areas with age groups typically at home (<5, 50+). Isolates from asymptomatic shedders were among all three sub-lineages. Whole genome sequencing provided evidence of bacterial genetic similarity, which corroborated 10/12 putative epidemiologic linkages among cases and asymptomatic shedders, as well as 3/3 repeat positives (presumed relapses), with a median of one single nucleotide polymorphism difference. These findings highlight various patterns of typhoid transmission in Samoa that differ between urban and rural regions as well as genomic subtypes. Asymptomatic shedders, detectable only through household investigations, are likely an important reservoir and mobile agent of infection. This study advances a "Samoan S. Typhi framework" that supports current and future typhoid surveillance and control efforts in Samoa.

Humans↗

Oral administration of fluoroquinolones in the treatment of typhoid fever and paratyphoid fever in Japan.

OBJECTIVE: To study the adverse reactions and therapeutic effects of fluoroquinolones to investigate whether they can be used for the treatment of patients with typhoid fever and paratyphoid fever. METHODS: The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever. PATIENTS: 58 patients (54 Japanese) with typhoid fever, 42 patients (41 Japanese) with paratyphoid fever, and 1 Japanese patient with both typhoid fever and paratyphoid fever, who were admitted in hospitals in Tokyo, Kawasaki, Yokohama, Kyoto, and Osaka from 1995 to 1998 and treated with fluoroquinolones. RESULTS: Almost 80% of the patients were treated with tosufloxacin (TFLX) and the remaining 20 % were treated with norfloxacin, ciprofloxacin, levofloxacin, or sparofloxacin. Side effects (nausea, urticaria, aphthous stomatitis) and elevation of serum amylase were found in 3.6% and 8.3 % of patients treated with TFLX, respectively, but these adverse reactions disappeared in all of these cases either with or without a change in the drug used. No adverse reactions were found in patients treated with the other fluoroquinolones. The clinical and bacteriological effects of these drugs were adequate. CONCLUSION: Though further studies still need to be performed on the fluoroquinolones other than TFLX, we can preliminarily conclude that fluoroquinolones are safe drugs and they can be recommended for the initial therapy of patients with typhoid fever and paratyphoid fever.

Administration, Oral↗

Typhoid fever as a rare cause of hepatic, splenic, and bone marrow granulomas.

During the course of typhoid fever, the usual histologic finding of the liver is "nonspecific reactive hepatitis." Hepatic granuloma (HG) is a rare complication of typhoid fever. We present two cases of typhoid fever with HG and review the relevant literature. Case 1 (a 53-year-old female) was found to have both hepatic and splenic granulomas. This is the first case of typhoid fever with splenic granulomas in the English language literature. Case 2 (a 66-year-old male) developed granulomas in the bone marrow in addition to HG. It should be considered that typhoid fever may lead to granulomas in several organs.

Aged↗

Risk of travel-associated typhoid and paratyphoid fevers in various regions.

BACKGROUND: Although enteric fever (typhoid and paratyphoid fevers) is a major global public health problem, comparable data on the risks of contracting travel-associated enteric fever in various regions of the world are scarce. METHODS: From the Swedish database on notifiable communicable diseases, we retrieved all case records from 1997 to 2003 on typhoid and paratyphoid fevers. The data set was compared with data on travel patterns obtained from a comprehensive travel database with information from interviews with more than 16,000 Swedish residents with recent overnight travel outside Sweden. RESULTS: The overall risk of being notified with enteric fever after travel was 0.42 in 100,000 travelers. The highest risk for typhoid fever was seen in travelers from India and neighboring countries (41.7 in 100,000), the Middle East (5.91 in 100,000), and Central Africa (3.33 in 100,000), whereas the risk was comparatively low in East Asia (0.24 in 100,000). Almost the same risk areas stood out for paratyphoid fever: India and neighbors (37.5 in 100,000), the Middle East (3.64 in 100,000), and East Africa (3.33 in 100,000). The epidemiology of paratyphoid fever was considerably affected by a large outbreak of paratyphoid B in a Turkish tourist resort in 1999. The youngest children were at highest risk for typhoid fever (odds ratio 44.2), whereas youths ages 7 to 18 years were at highest risk for paratyphoid fever (odds ratio 9.7). CONCLUSIONS: Detailed risk data for enteric fever after travel could form the basis for travel advice. Vaccination against typhoid fever should always be considered for travelers to the Indian subcontinent, the Middle East, and Africa but should not routinely be given to travelers to the Malay Peninsula.

Adolescent↗

Diagnostic value of the Widal test in areas endemic for typhoid fever.

The usefulness of a single Widal test to diagnose typhoid fever in endemic areas was investigated. Reciprocal Salmonella typhi O and H titers greater than or equal to 40 and greater than or equal to 80, respectively, occurred in approximately 90% of 42 Mexican patients with bacteriologically-confirmed typhoid fever at the time of presentation to hospital and, by day 4 to 5 of clinical illness, in 70% of U.S. adult volunteers who developed typhoid fever in the course of vaccine efficacy trials but in only 0.7% (O) to 3% (H) of 275 healthy individuals from a non-endemic area. Healthy Peruvians from areas endemic for typhoid fever commonly had antibody which was age-related. Peak prevalence was found in 15- to 19-yr-olds in whom 29% had O titers greater than or equal to 40 and 76% had H titers greater than or equal to 80. A single Widal test in an unvaccinated individual showing elevated O and H titers is strongly suggestive of typhoid fever if the person comes from a non-endemic area or is a child less than 10 yr of age in an endemic area. Because of the high prevalence of antibody amongst healthy invididuals over 10 yr of age in endemic, areas, a single Widal test offers virtually no diagnostic assistance in adolescents and adults.

Adolescent↗

The need for high index of suspicion in early diagnosis of typhoid fever in young children.

BACKGROUND: The diagnosis of typhoid fever in young children is more difficult than in the adult due to the unusual pattern of presentation. This letter aims to sensitize general physicians and paediatricians on the need for a high index of suspicion in the diagnosis of typhoid fever in children. METHOD: The case records of a child diagnosed with typhoid fever and a review of literature on the subject were used. RESULT: A five year old female misdiagnosed as a case of severe malaria and sepsis was found to have typhoid fever on post mortem examination. CONCLUSION: It is important to make an early diagnosis of typhoid fever in young children in order to prevent mortality from this treatable disease.

Age Factors↗

Interference by malaria in the diagnosis of typhoid using Widal test alone.

A total of 270 febrile patients (130 males and 140 females) aged between 15 and 59 were screened using thick and thin blood film stains for malaria, bacteriologic culture and Widal test for enteric fevers. Sixty (22%) were positive for malaria while 38 (14%) were positive for enteric fevers out of which 16 (26.6%) concomitantly had malaria parasite. Cases without malaria parasite (MP) or enteric fever organism were 172 (63.7%) and classified as pyrexia of unknown origin (PUO). Forty-four were strictly malaria cases out of which 36 (82%) were due to Plasmodium falciparum, and all had antibody Widal titres > or = 160 to 0 antigen while 4 (9%) were due to Plasmodium malariae, 3 (6.8%) were due to P. ovale and 1 (2.3%) was due to P. vivax. Twenty (52.6%) of the 38 patients with enteric fever had typhoid, all had Widal titres > or = 160 to 0 antigen. In all, antibody reaction Widal titres to H antigen were < 20. There was no statistical significant difference [chi2 = 327.2, P > 0.05] between Widal titres of malaria and typhoid cases. Hence using Widal test alone, one cannot differentiate typhoid fever from malaria. In another 250 healthy adults, of equal sex distribution, used as controls 12 (4.8%) had malaria parasite and 4 (1.6%) had enteric fever organisms. While only 4 (1.6%) gave Widal titre of 80 to 0 antigen the rest had antibody titres of < 20 to O antigen. Malaria could interfere with serological diagnosis of typhoid and hence lead to over diagnosis of typhoid in Nigeria.

Adolescent↗

Participation of the thymus in the mechanism of bacterial discharge in carriers of typhoid bacteria.

Typhoid carrier state was reproduced in 54 rabbits by the injection of typhoid bacilli into the bone marrow of the femoral bone. The animals were divided into 3 groups. Those in the 1st and 2nd group were hydrocortisone and ATC before the infection, respectively, whereas the 3rd group served as control. The data obtained pointed to the great incidence of prolonged persistence of typhoid bacilli in the bone marrow. A much greater vital disharge of the causative agent with the feces was noted in the animals which before the infection were given hydrocortisone and ATC preparations depressing the functional activity of the thymus. In the second experimental series it was shown that ATC administration to rabbits on the 85th day after their intraosseous infection with typhoid bacilli promoted vital discharge of the causative agent with the feces. Problem of participation of the thymus in the mechanism of bacterial discharge in the carriers of typhoid bacilli are discussed.

Animals↗

Ceftriaxone therapy in ciprofloxacin treatment failure typhoid fever in children.

BACKGROUND & OBJECTIVES: The rapid spread of multidrug resistant (MDR) typhoid fever has posed a great challenge for the treatment of these cases the world over. After the emergence of chloramphenicol resistant Salmonella typhi strains, ciprofloxacin has become the drug of choice for the treatment of typhoid fever even in the paediatric age group. This study evaluated the role of ceftriaxone therapy in bacteriologically confirmed MDR typhoid cases who did not respond to 12-14 days of ciprofloxacin therapy. Attempts have also been made to investigate the in vitro susceptibility of isolated S. typhi strains to chloramphenicol, ciprofloxacin and ceftriaxone. METHODS: A total of 140 children, aged 3-10 yr, clinically diagnosed as having typhoid fever, without any clinical response after 12-14 days of ciprofloxacin therapy were screened for S. typhi by blood culture. In the bacteriologically positive children the treatment was changed to intravenous ceftriaxone for 14 days. The isolated strains of S. typhi were tested for in vitro antimicrobial susceptibility. RESULTS: Clinical and bacteriological cure was observed with intravenous ceftriaxone therapy in all the 32 bacteriologically positive patients. All isolated S. typhi strains were uniformly (100%) susceptible to ciprofloxacin and ceftriaxone but 50 per cent of the strains were resistant to chloramphenicol. The MIC values of chloramphenicol, ciprofloxacin and ceftriaxone ranged between 125-500, 0.0625-0.5 and < 0.0625 microgram/ml respectively. INTERPRETATION & CONCLUSION: The study indicates that although the S. typhi strains were susceptible to ciprofloxacin in vitro, the patients did not respond clinically and bacteriologically to ciprofloxacin therapy. Hence, ciprofloxacin may not represent a reliable and useful option for treating MDR typhoid fever; ceftriaxone may be an effective alternative for the treatment of such cases.

Anti-Infective Agents↗

Diagnostic value of dot-enzyme-immunoassay test to detect outer membrane protein antigen in sera of patients with typhoid fever.

Typhoid fever is still an important public health problem in many developing countries especially in tropical parts of the world, as in Indonesia. This problem opens the way for a further study with the aim of finding an alternative serological test with a high degree of reliability for the detection of typhoid fever. Given the above mentioned purpose, a study on the reliability of a laboratory test, the dot-enzyme-immunoassay outer membrane protein (DOT-EIA-OMP) was conducted comprising sera from 207 subjects (44 adult typhoid patients, 43 adult nontyphoid patients and sera from 120 adult healthy individuals serving as controls. The result of the study revealed that the diagnostic sensitivity of the DOT-EIA-OMP test for the detection of typhoid fever can be classified as high (93.16%), the specificity as moderate (76.74%), the efficiency (accuracy), positive predictive value and negative predictive value as high (85.06%, 80.39% and 91.66% respectively). The within run and between days reproducibility of this test was very high (CV=0%). Analysis of data obtained indicated that the DOT-EIA-OMP test was a reliable screening test for the establishment of the diagnosis of typhoid fever in health centers with simple laboratory facilities. The application of this test has to be more contemplated in countries where the cost of laboratory test is a problem.

Adult↗

Inhibition of virus and T-haemagglutination by typhoid fever Vi-antigen.

This paper reports on tests of the effect of polysaccharide-lipid antigens of enteric bacteria and Rickettisa prowazekii antigen on virus and T-haemagglutination. It is shown that treatment of erythrocytes with typhoid Vi-antigen greatly reduces their agglutinability by myxoviruses or the Stewart-Eddy polyoma virus.Erythrocytes treated with typhoid antigen retained their capacity to adsorb and elute myxoviruses, although to a somewhat lesser degree than normal erythrocytes, and such treatment did not affect adsorption of the SE polyoma virus. The typhoid antigen does not fix or destroy the virus receptor of the erythrocyte.Adsorption of the typhoid antigen prevents T-agglutination of erythrocytes which have first been treated with receptor-destroying enzyme. On the surface of RDE-treated erythrocytes the typhoid antigen is fixed outside the T-antigen loci and does not block unmasked T-antigen. The general conclusion is that, in the systems reviewed, the Vi-antigen is able to increase the resistance of erythrocytes to agglutination.

Antigens, Bacterial↗

An evaluation of the SAT in the diagnosis of typhoid.

Salmonella typhi O and H antibody titres were determined by the Standard Agglutination Test (SAT) in 85 patients with bacteriologically proven typhoid, 102 patients with non-typhoidal febrile illnesses (control group 1), and 170 healthy subjects (control group 2). An O antibody titre of 1/120 occurred in 93% of patients with typhoid fever (7% false negatives), and in 17% and 12% control groups 1 and 2 respectively. An H antibody titre of 1/120 was found only in 64% of patients with typhoid (false negatives in 36%). At titres other than 1/120, the proportion of false negatives or false positives increased ie. the sensitivity and specificity decreased. Although the SAT continues to be used in Sri Lanka as the main diagnostic test in typhoid, the sensitivity and specificity of this test fall below the requirements of a useful diagnostic test.

Agglutination Tests↗

Changing characteristics of typhoid fever in Taiwan.

Typhoid fever, a systemic disease caused by Salmonella typhi, is classically characterized by fever and abdominal symptoms. Although now considered uncommon, it seems to have re-emerged in Taiwan in recent years. We conducted a retrospective study of the clinical characteristics and microbiologic findings in 24 confirmed cases of typhoid fever treated over a 7-year period at a medical center in northern Taiwan. There were 11 males and 13 females, including 15 adults (over 18 years in age) and 9 children. Their mean age was 24.7 years (range, 9 months to 58 years). Twelve patients had recently returned from abroad, mostly from Southeast Asia. The most common complaints were fever (24/24), diarrhea (18/24), abdominal pain (10/24), and cough (10/24). The average duration of fever before diagnosis was 14.1 days, with a maximum of 30 days. Relative bradycardia was noted in 6 patients. Leukopenia was noted in 2 patients. S. typhi was isolated from blood culture in 20 cases, from stool culture in 3 cases, and from bone marrow culture in 1 case. Widal test was only positive initially in 7/18 cases. Fever of unknown origin was the most common initial diagnosis. Typhoid or enteric fever was impressed initially in only 2 cases. Almost all isolates of S. typhi were susceptible to antibiotics currently used for typhoid fever, with only 1 isolate resistant to chloramphenicol. All patients survived after antibiotic treatment. Only 1 patient developed recurrence after a 10-day course of ceftriaxone. In conclusion, the diagnosis of typhoid fever is often challenging due to non-specific symptoms and lack of an immediate confirmatory test. It is important to include this disease in the differential diagnosis of febrile patients with abdominal symptoms.

Abdominal Pain↗

Study of clinical profile and antibiotic sensitivity pattern in culture positive typhoid fever cases.

OBJECTIVES: The present study was designed to analyze the clinical profile and antibiotic sensitivity pattern in the cases of culture positive typhoid fever. METHOD: The study was conducted over a period of 1 year. Total of 46 culture positive cases of Typhoid fever were included in the study. The sensitivity pattern of isolates from blood culture was recorded. The modes of presentation, clinical course, lab investigation reports were also recorded. RESULTS: Out of 46 cases, 33 (71.7%) were males and 13 (28.3%) were females. Average age of presentation was 26.17 years. Fever was present in all patients. Resistance of S .typhi to amoxycillin, chloramphenicol and co-trimoxazole were significantly high. Ciprofloxacin showed resistance in 2 (4.3%) cases. Sensitivity to ceftriaxone was 100% in our study. CONCLUSION: Typhoid fever is one of the most common health problem in Nepal. Various drugs are being used in the treatment of typhoid fever, in the mean time resistance to many of them are emerging. An appropriate antibiotic has to be initiated only after culture sensitivity in typhoid fever.

Adult↗

Open study on efficacy and safety of levofloxacin in treatment of uncomplicated typhoid fever.

The main objective of this study was to determine the clinical efficacy and safety of levofloxacin in an open setting for typhoid fever cases. Patients with clinical signs and symptoms of typhoid fever without previous antimicrobial treatment admitted to affiliated hospitals of the Faculty of Medicine, University Indonesia were included in this study. Adults, 18 years or above, were screened for any serious underlying conditions, pregnancy or possible complications of typhoid fever before final enrollment. Fifty-three subjects were screened, 48 were enrolled. The final diagnosis of enteric fever was made by positive blood culture, polymerase chain reaction or serology, was obtained in 31 cases, in whom one had a concomitant sinus infection and had to be excluded. Thirty patients (11 males, 19 females) aged between 18-58 years (mean 31.7 years) with a history of fever between 1 and 10 days (mean 6.1 days) showed excellent clinical response, becoming afebrile at an average of 2.43 days (range 1-5 days). Adverse effects noted were nausea in 4 patients, vomiting in one and meteorism in another one, which were all difficult to distinguish from the enteric infection. A pruritic rash occurring in two patients may be related to levofloxacin, and insomnia in another patient may be related. Microbiological clearance was obtained both immediately after treatment and at one month. No carrier states were detected in the cases positive for Salmonella typhi or paratyphi. None of the treated typhoid fever cases experienced a clinical relapse. In this open study of levofloxacin 500 mg/day for one week in treatment of uncomplicated typhoid fever, a 100% clinical efficacy was obtained in 30 patients with minimal adverse reactions warranting more intensive studies for this new indication of an old but well known disease in the developing world.

Adolescent↗

Dot enzyme immunosorbent assay for the serodiagnosis of typhoid fever.

A nitrocellulose membrane strip dotted with a specific 50 kDa outer membrane protein of Salmonella typhi was applied for the serodiagnosis of typhoid fever. Using horseradish peroxidase conjugated IgM and IgG antibodies with 4-chloronaphthol as substrate, antibodies in typhoid patients were clearly visualised as bluish purple dots while sera from patients with non-typhoid fevers gave negative results. The detection of specific IgM and IgG antibodies in typhoid patients suggest either recent or current infection. Combined with the high specificity, reliability and rapidity of the test, the dot EIA technique provides a simple and useful method for the serodiagnosis of typhoid using a single serum specimen.

Enzyme-Linked Immunosorbent Assay↗