Clinical and Epidemiological Features of Typhoid Fever in Pemba,Zanzibar: Assessment of the Performance of the WHO Case Definitions

Background

The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever.

Methodology/Principal Findings

Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1∶80.

Conclusions/Significance

Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.     

Shifts in Geographic Distribution and Antimicrobial Resistance during a Prolonged Typhoid Fever Outbreak — Bundibugyo and Kasese Districts,Uganda, 2009–2011

Background

Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo.

Methodology/Principal Findings

A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009–December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1–December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates.

Conclusions/Significance

Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future.     

Typhoid Outbreak in Songkhla,Thailand 2009–2011: Clinical Outcomes,Susceptibility Patterns,and Reliability of Serology Tests

Objective

To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009–2011 typhoid outbreak in Songkhla province in Thailand.

Method

The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated.

Results

S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7–14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively.

Conclusion

Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.     

A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam

Background

Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing.

Objectives

We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.

Methods

An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi).

Principal Findings

We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94–118 hours for gatifloxacin versus 88–112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80–1.26]).Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43–2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant.

Conclusions

Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam.

Trial Registration

Controlled-Trials.com ISRCTN67946944     

The Application of the Grey Disaster Model to Forecast Epidemic Peaks of Typhoid and Paratyphoid Fever in China

Objective

The objectives of this study were to forecast epidemic peaks of typhoid and paratyphoid fever in China using the grey disaster model, to evaluate its feasibility of predicting the epidemic tendency of notifiable diseases.

Methods

According to epidemiological features, the GM(1,1) model and DGM model were used to build the grey disaster model based on the incidence data of typhoid and paratyphoid fever collected from the China Health Statistical Yearbook. Model fitting accuracy test was used to evaluate the performance of these two models. Then, the next catastrophe date was predicted by the better model.

Results

The simulation results showed that DGM model was better than GM(1,1) model in our data set. Using the DGM model, we predicted the next epidemic peak time will occur between 2023 to 2025.

Conclusion

The grey disaster model can predict the typhoid and paratyphoid fever epidemic time precisely, which may provide valuable information for disease prevention and control.     

A Systematic Review and Meta-Analysis of the Performance of Two Point of Care Typhoid Fever Tests,Tubex TF and Typhidot,in Endemic Countries

Background

In the absence of well-equipped laboratory infrastructure in many developing countries the accurate diagnosis of typhoid fever is challenging. Rapid diagnostic tests (RDT) with good performance indicators would be helpful to improve clinical management of suspected cases. We performed a systematic literature review and meta- analysis to determine the performance of TUBEX TF and Typhidot for the diagnosis of typhoid fever using PRISMA guidelines.

Methods

Titles and abstracts were reviewed for relevance. Articles were screened for language, reference method and completeness. Studies were categorized according to control groups used. Meta-analysis was performed only for categories where enough data was available to combine sensitivity and specificity estimates. Sub-analysis was performed for the Typhidot test to determine the influence of indeterminate results on test performance.

Results

A total of seven studies per test were included. The sensitivity of TUBEX TF ranged between 56% and 95%, Specificity between 72% and 95%. Meta-analysis showed an average sensitivity of 69% (95%CI: 45–85) and an average specificity of 88% (CI95%:83–91). A formal meta-analysis for Typhidot was not possible due to limited data available. Across the extracted studies, sensitivity and specificity estimates ranged from 56% to 84% and 31% to 97% respectively.

Conclusion

The observed performance does not support the use of either rapid diagnostic test exclusively as the basis for diagnosis and treatment. There is a need to develop an RDT for typhoid fever that has a performance level comparable to malaria RDTs.     

Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam

Background

Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005.

Principal Findings

The population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene.

Significance

The H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam.     

High-resolution genotyping of the endemic Salmonella Typhi population during a Vi (typhoid) vaccination trial in Kolkata

Background

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas.

Methodology

We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003–December 2006, vaccinations given December 2004).

Principal Findings

A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes.

Conclusions

Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.     

Evaluation of a Typhoid/Paratyphoid Diagnostic Assay (TPTest) Detecting Anti-Salmonella IgA in Secretions of Peripheral Blood Lymphocytes in Patients in Dhaka,Bangladesh

Background

Rapid and reliable diagnostic assays for enteric (typhoid and paratyphoid) fever are urgently needed. We report the characterization of novel approach utilizing lymphocyte secretions, for diagnosing patients with enteric fever by the TPTest procedure.

Methodology

TPTest detects Salmonella-specific IgA responses in lymphocyte culture supernatant. We utilized TPTest in patients with suspected enteric fever, patients with other illnesses, and healthy controls. We also evaluated simplified modifications of TPTest for adaptation in laboratories with limited facilities and equipment.

Principal Findings

TPTest was positive in 39 (27 typhoid and 12 paratyphoid A) patients confirmed by blood culture and was negative in 74 healthy individuals. Among 32 individuals with other illnesses, 29 were negative by TPTest. Of 204 individuals with suspected enteric fever who were negative by blood culture, 44 were positive by TPTest and the patients were clinically indistinguishable from patients with confirmed bacteremia, except they were more likely to be under 5 years of age. We evaluated simplifications in TPTest, including showing that lymphocytes could be recovered using lysis buffer or buffy coat method as opposed to centrifugation, that incubation of cells at 37°C did not require supplemental CO₂, and that results were available for majority of samples within 24 hours. Positive results by TPTest are transient and revert to negative during convalescence, supporting use of the test in endemic areas. The results can also be read using immunodot blot approach as opposed to ELISA. Since no true gold standard currently exists, we used a number of definitions of true positives and negatives. TPTest had sensitivity of 100% compared to blood culture, and specificity that ranged from 78–97% (73–100, 95% CI), depending on definition of true negative.

Conclusion

The TPTest is useful for identification of patients with enteric fever in an endemic area, and additional development of simplified TPTest is warranted.     

Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study

Background

Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed.

Methodology/Principal Findings

We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000–2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R ₀) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5–15 years following a one-time campaign.

Conclusions/Significance

We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.     

Maiden outbreak of chikungunya in dongguan city, guangdong province, china: epidemiological characteristics

Background

This study was conducted to identify epidemiological characteristics of the first documented CHIK fever outbreak in China and evaluate the effect of the preventive measures taken.

Methodology/Principal Findings

From September 1 to October 29, 2010, China''s first documented outbreak of CHIK fever occurred in the Xincun community of Wanjiang District of Dongguan city, Guangdong province; 253 case-patients were recorded, of which 129 were laboratory confirmed, with an attack rate of 1%. Before September 18^th the number of CHIK fever cases remained relatively low in the Xincun community; from September 19^th onwards, the number of cases increased drastically, with an outbreak peak on October 4^th. Cases were distributed across nine small village groups in the Xincun community, with an attack rate of 0–12% at the village level. The household attack rates ranged between 20% and 100%. No significant difference was found in the attack rate between males and females. There was a significant difference in the attack rate in different age groups (chi-square = 18.35, p = 0.005); highest in patients aged 60 years or older and the lowest in patients aged under 10. The major clinical characteristics of patients are fever (100%), joint pain (79%) and rash (54%). Phylogenetic analysis of the E1 gene on the five earliest confirmed cases showed that the strains of CHIKV isolated from their sera were highly homologous (up to 99%) with isogeneic strains isolated in Thailand in 2009. After control measures were taken, including killing adult mosquitoes and cleaning breeding habitats of Aedes mosquitoes, the Breteau index and Mosq-ovitrap index decreased rapidly, and the outbreak ended on October 29.

Conclusion/Significance

The infection source of the outbreak was imported. Cases showed obvious temporal, spatial, and population aggregation during the outbreak. Comprehensive control measures based on reducing the density of Aedes mosquitoes were effective in controlling the epidemic.     

Sarcocystis nesbitti Causes Acute,Relapsing Febrile Myositis with a High Attack Rate: Description of a Large Outbreak of Muscular Sarcocystosis in Pangkor Island,Malaysia, 2012

Background

From the 17^th to 19^th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak.

Methodology/Principal Findings

All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9–11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p = 0.002).

Conclusions/Significance

The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics.     

Dynamic Modularity of Host Protein Interaction Networks in Salmonella Typhi Infection

Background

Salmonella Typhi is a human-restricted pathogen, which causes typhoid fever and remains a global health problem in the developing countries. Although previously reported host expression datasets had identified putative biomarkers and therapeutic targets of typhoid fever, the underlying molecular mechanism of pathogenesis remains incompletely understood.

Methods

We used five gene expression datasets of human peripheral blood from patients suffering from S. Typhi or other bacteremic infections or non-infectious disease like leukemia. The expression datasets were merged into human protein interaction network (PIN) and the expression correlation between the hubs and their interacting proteins was measured by calculating Pearson Correlation Coefficient (PCC) values. The differences in the average PCC for each hub between the disease states and their respective controls were calculated for studied datasets. The individual hubs and their interactors with expression, PCC and average PCC values were treated as dynamic subnetworks. The hubs that showed unique trends of alterations specific to S. Typhi infection were identified.

Results

We identified S. Typhi infection-specific dynamic subnetworks of the host, which involve 81 hubs and 1343 interactions. The major enriched GO biological process terms in the identified subnetworks were regulation of apoptosis and biological adhesions, while the enriched pathways include cytokine signalling in the immune system and downstream TCR signalling. The dynamic nature of the hubs CCR1, IRS2 and PRKCA with their interactors was studied in detail. The difference in the dynamics of the subnetworks specific to S. Typhi infection suggests a potential molecular model of typhoid fever.

Conclusions

Hubs and their interactors of the S. Typhi infection-specific dynamic subnetworks carrying distinct PCC values compared with the non-typhoid and other disease conditions reveal new insight into the pathogenesis of S. Typhi.     

Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: implications for typhoid vaccine use in Africa

Background

High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene.

Methods

During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated.

Results

In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant.

Conclusions

This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.     

Comparison of the Performance of the TPTest,Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh,Including Using a Bayesian Latent Class Modeling Approach

Background

There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot.

Methodology

For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ≥1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis.

Principle findings

Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot.

Conclusion

These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives.     

Seroprevalence of Alphavirus Antibodies in a Cross-Sectional Study in Southwestern Tanzania Suggests Endemic Circulation of Chikungunya

Background

To date, Alphavirus infections and their most prominent member, chikungunya fever, a viral disease which first became apparent in Tanzania in 1953, have been very little investigated in regions without epidemic occurrence. Few data exist on burden of disease and socio-economic and environmental covariates disposing to infection.

Methods

A cross-sectional seroprevalence study was undertaken in 1,215 persons from Mbeya region, South-Western Tanzania, to determine the seroprevalence of anti-Alphavirus IgG antibodies, and to investigate associated risk factors.

Results

18% of 1,215 samples were positive for Alphavirus IgG. Seropositivity was associated with participant age, low to intermediate elevation, flat terrain and with IgG positivity for Rift Valley fever, Flaviviridae, and rickettsiae of the spotted fever group. When comparing the geographical distribution of Alphavirus seropositivity to that of Rift Valley fever, it was obvious that Alphaviruses had spread more widely throughout the study area, while Rift Valley fever was concentrated along the shore of Lake Malawi.

Conclusion

Alphavirus infections may contribute significantly to the febrile disease burden in the study area, and are associated with several arthropod-borne infections. Their spread seems only limited by factors affecting mosquitoes, and seems less restricted than that of Rift Valley fever.     

Seroprevalence of Antibodies to Avian Influenza A (H5) and A (H9) Viruses among Market Poultry Workers, Hanoi, Vietnam, 2001

Background

The frequency of avian influenza A virus infections among poultry workers is not well understood.

Methods

A seroprevalence study of market poultry workers and persons without occupational poultry exposure was conducted during 2001 in Hanoi, Vietnam. Sera were tested for avian influenza H5 and H9 antibodies by microneutralization and Western blot assays.

Results

Seroprevalence of H5 and H9 antibodies was 4% and 3% in poultry workers and 1% and 3.5% in non-poultry workers, respectively.

Conclusions

Seroprevalence of H5 and H9 antibodies was low among Hanoi market poultry workers in 2001, but can serve as a baseline for additional studies.     

Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare,Zimbabwe, 2012

Background

Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare.

Methods

A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff''s spatial scan statistic.

Principal Findings

We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff''s spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic.

Conclusions

This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.     

Identification of Immunogenic Salmonella enterica Serotype Typhi Antigens Expressed in Chronic Biliary Carriers of S. Typhi in Kathmandu,Nepal

Background

Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.

Methodology/Principal Findings

To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.

Conclusions/Significance

Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers.