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1.  Childhood TB epidemiology and treatment outcomes in Thailand: a TB active surveillance network, 2004 to 2006 
Background
Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand.
Methods
In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006.
Results
Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p < 0.01).
Conclusion
Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality.
doi:10.1186/1471-2334-8-94
PMCID: PMC2483984  PMID: 18637205
2.  Invasive pneumococcal infections among persons with and without underlying medical conditions: Implications for prevention strategies 
Background
The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for persons aged < 65 years with chronic medical conditions. We evaluated the risk and mortality from invasive pneumococcal disease (IPD) among persons with and without the underlying medical conditions which are considered PPV23 indications.
Methods
Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture) reported by Finnish clinical microbiology laboratories during 1995–2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness.
Results
Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000). Patients aged 18–49 and 50–64 years accounted for 1282 (29%) and 934 (21%) of IPD cases, of which 372 (29%) and 427 (46%) had a current PPV23 indication, respectively. Overall, 536 (12%) IPD patients died within one month of first positive culture. Persons aged 18–64 years accounted for 254 (47%) of all deaths (case-fatality proportion, 12%). Of those who died 117 (46%) did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50–64 years were most likely to die.
Conclusion
In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider additional prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects.
doi:10.1186/1471-2334-8-96
PMCID: PMC2507715  PMID: 18647385
3.  Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants 
Background
Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.
Methods
The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).
Results
Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.
Conclusion
This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.
doi:10.1186/1471-2334-8-174
PMCID: PMC2642823  PMID: 19117527
4.  Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: A cohort study 
Background
Single-dose nevirapine (SDNVP) for the prevention of mother-to-child HIV transmission (PMTCT) results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood.
Methods
We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed) and those that had not (unexposed) and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders.
Results
Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0). Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19%) at both the first (unexposed) and second (exposed) delivery. The results were unchanged, if infant death was included as an outcome.
Conclusion
These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.
doi:10.1186/1471-2334-8-172
PMCID: PMC2630918  PMID: 19116004
5.  Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres 
Background
Streptococcus pneumoniae (pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities.
Methods
We followed attendees (N = 59) with their family members (N = 117) and the employees (N = 37) in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods.
Results
Children in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees.
Conclusion
The transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission.
doi:10.1186/1471-2334-8-173
PMCID: PMC2639357  PMID: 19116005
6.  Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan 
Background
The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of Mycobacterium tuberculosis strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of M. tuberculosis isolates from different regions of the country.
Methods
M. tuberculosis strains isolated (2003–2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped.
Results
Of 926 M. tuberculosis strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (M. tuberculosis specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types.
Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family.
Conclusion
Our results show variation of prevalent M. tuberculosis strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the tuberculosis burden in Pakistan.
doi:10.1186/1471-2334-8-171
PMCID: PMC2630917  PMID: 19108722
7.  Molecular epidemiology and evolutionary genetics of Mycobacterium tuberculosis in Taipei 
Background
The control of tuberculosis in densely populated cities is complicated by close human-to-human contacts and potential transmission of pathogens from multiple sources. We conducted a molecular epidemiologic analysis of 356 Mycobacterium tuberculosis (MTB) isolates from patients presenting pulmonary tuberculosis in metropolitan Taipei. Classical antibiogram studies and genetic characterization, using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping, were applied after culture.
Methods
A total of 356 isolates were genotyped by standard spoligotyping and the strains were compared with in the international spoligotyping database (SpolDB4). All isolates were also categorized using the 15 loci MIRU-VNTR typing method and combin with NTF locus and RD deletion analyses.
Results
Of 356 isolates spoligotyped, 290 (81.4%) displayed known spoligotypes and 66 were not identified in the database. Major spoligotypes found were Beijing lineages (52.5%), followed by Haarlem lineages (13.5%) and EAI plus EAI-like lineages (11%). When MIRU-VNTR was employed, 140 patterns were identified, including 36 clusters by 252 isolates and 104 unique patterns, and the largest cluster comprised 95 isolates from the Beijing family. The combination of spoligotyping and MIRU-VNTR revealed that 236 (67%) of the 356 isolates were clustered in 43 genotypes. Strains of the Beijing family was more likely to be of modern strain and a higher percentage of multiple drug resistance than other families combined (P = 0.08). Patients infected with Beijing strains were younger than those with other strains (mean 58.7 vs. 64.2, p = 0.02). Moreover, 85.3% of infected persons younger than 25 years had Beijing modern strain, suggesting a possible recent spread in the young population by this family of TB strain in Taipei.
Conclusion
Our data on MTB genotype in Taipei suggest that MTB infection has not been optimally controlled. Control efforts should be reinforced in view of the high prevalence of the Beijing strain in young population and association with drug resistance.
doi:10.1186/1471-2334-8-170
PMCID: PMC2628671  PMID: 19102768
8.  A discrepancy of Chlamydia trachomatis incidence and prevalence trends in Finland 1983–2003 
Background
Reported rates of Chlamydia trachomatis are on the rise contradicting the declining rates of C. trachomatis associated reproductive sequelae in Western countries. Population based evaluation of the real trend of C. trachomatis infection is important to contemplate prevention efforts. We studied C. trachomatis occurrence during the past 20 years in Finland comparing incidence rate data based on serology and reported C. trachomatis laboratory notifications.
Methods
A random sample of 7999 women with two consecutive pregnancies within five years was selected from the population of the Finnish Maternity Cohort (FMC) serum bank stratified by calendar year and age. C. trachomatis IgG antibodies were determined by a standard peptide-ELISA. The reported incidence rates of C. trachomatis infections based on case notifications were obtained from the National Registry of Infectious Diseases (NIDR).
Results
C. trachomatis seroprevalence rates decreased significantly from 1983 to 2003 both in women under 23 years of age (23.3% to 9.2%) and in women between 23–28-years of age (22.2% to 12.6%). However, seroconversion rates increased from 31 per 10000 person years in 1983–85 to 97 per 10000 person years in 2001–2003 (incidence rate ratio 3.2, 95% CI, 1.1–8.7) among the older age group. Seroconversion rate was highest (264) in 1983–1985 in the younger age-group, then declined and subsequently increased again (188) in 2001–2003. The incidence based on seroconversions was in agreement with the reported incidence rates in both age groups.
Conclusion
C. trachomatis seroprevalence rate decreased during 1983–2003 among fertile-aged women in Finland. During the same time period incidence rates based both on seroconversions and reported laboratory notifications of diagnosed C. trachomatis infections increased. The discrepancy between the C. trachomatis incidence and seroprevalence trends warrants further studies.
doi:10.1186/1471-2334-8-169
PMCID: PMC2615775  PMID: 19094207
9.  Development and evaluation of a real-time one step Reverse-Transcriptase PCR for quantitation of Chandipura Virus 
Background
Chandipura virus (CHPV), a member of family Rhabdoviridae was attributed to an explosive outbreak of acute encephalitis in children in Andhra Pradesh, India in 2003 and a small outbreak among tribal children from Gujarat, Western India in 2004. The case-fatality rate ranged from 55–75%. Considering the rapid progression of the disease and high mortality, a highly sensitive method for quantifying CHPV RNA by real-time one step reverse transcriptase PCR (real-time one step RT-PCR) using TaqMan technology was developed for rapid diagnosis.
Methods
Primers and probe for P gene were designed and used to standardize real-time one step RT-PCR assay for CHPV RNA quantitation. Standard RNA was prepared by PCR amplification, TA cloning and run off transcription. The optimized real-time one step RT-PCR assay was compared with the diagnostic nested RT-PCR and different virus isolation systems [in vivo (mice) in ovo (eggs), in vitro (Vero E6, PS, RD and Sand fly cell line)] for the detection of CHPV. Sensitivity and specificity of real-time one step RT-PCR assay was evaluated with diagnostic nested RT-PCR, which is considered as a gold standard.
Results
Real-time one step RT-PCR was optimized using in vitro transcribed (IVT) RNA. Standard curve showed linear relationship for wide range of 102-1010 (r2 = 0.99) with maximum Coefficient of variation (CV = 5.91%) for IVT RNA. The newly developed real-time RT-PCR was at par with nested RT-PCR in sensitivity and superior to cell lines and other living systems (embryonated eggs and infant mice) used for the isolation of the virus. Detection limit of real-time one step RT-PCR and nested RT-PCR was found to be 1.2 × 100 PFU/ml. RD cells, sand fly cells, infant mice, and embryonated eggs showed almost equal sensitivity (1.2 × 102 PFU/ml). Vero and PS cell-lines (1.2 × 103 PFU/ml) were least sensitive to CHPV infection. Specificity of the assay was found to be 100% when RNA from other viruses or healthy individual was used.
Conclusion
On account of the high sensitivity, reproducibility and specificity, the assay can be used for the rapid detection and quantitation of CHPV RNA from clinical samples during epidemics and from endemic areas. The assay may also find application in screening of antiviral compounds, understanding of pathogenesis as well as evaluation of vaccine.
doi:10.1186/1471-2334-8-168
PMCID: PMC2629476  PMID: 19091082
10.  Sustained high prevalence of sexually transmitted infections among female sex workers in Cambodia: high turnover seriously challenges the 100% condom use programme 
Background
Cambodia's 100% Condom-Use Programme (CUP), implemented nationally in 2001, requires brothel-based female sex workers (FSWs) to use condoms with all clients. In 2005, we conducted a sexually transmitted infection (STI) survey among FSWs. This paper presents the STI prevalence and related risk factors, and discusses prevalence trends in the context of the 100% CUP in Cambodia.
Methods
From March-May, 1079 FSWs from eight provinces consented to participate, provided specimens for syphilis, chlamydia, and gonorrhoea testing, and were interviewed. Univariate and multivariate logistic regression analysis was used to determine factors associated with STIs. STI prevalence was compared with data from the 1996 and 2001 STI surveys.
Results
Most FSWs were young (55% aged 15–24) and new to sex work (60% had worked 12 ≤ months). Consistent condom use with clients was reported by 80% of FSWs, but only 38% of FSWs always used condoms with sweethearts or casual partners. Being new to sex work was the only factor significantly associated with "any STI" (OR = 2.1). Prevalence of syphiliwas 2.3%; chlamydia, 14.4%; gonorrhoea, 13.0%; and any STI, 24.4%. Prevalence of each STI in 2005 was significantly lower than in 1996, but essentially the same as prevalence observed in 2001.
Conclusion
New FSWs were found to have substantially higher prevalence than those with longer experience. The percent of FSWs who used condoms consistently was high with clients but remained low with non-paying sex partners. Because of the high turnover of FSWs, the prevention needs of new FSWs should be ascertained and addressed. Despite 100% CUP implementation, the prevalence of STIs among FSWs was the same in 2005 as it was in 2001. Limited coverage and weak implementation capacity of the programme along with questionable quality of the STI services are likely to have contributed to the sustained high prevalence. The programme should be carefully reviewed in terms of intensity, quality and coverage.
doi:10.1186/1471-2334-8-167
PMCID: PMC2640393  PMID: 19077261
11.  Prevalence of tuberculosis drug resistance in 10 provinces of China 
Background
The emergence of drug-resistant tuberculosis (TB) hampers TB control. Ten provinces in China performed drug resistance surveys among tuberculosis (TB) patients in 1996–2004 to assess levels of drug resistance.
Methods
Provincial drug resistance surveys included all isolates from newly diagnosed, smear-positive TB patients. Drug susceptibility testing (DST) against isoniazid, rifampicin, streptomycin and ethambutol was carried out in the provincial laboratories. For purposes of quality assurance, a random sample (11.6%) was re-tested by the national reference laboratory (NRL).
Results
Of 14,059 patients tested 11,052 (79%) were new TB cases. The weighted mean prevalence of multi-drug resistant tuberculosis (MDR-TB) among all cases was 9.3% (range 2.2%–10.4%); 5.4% (range 2.1% – 10.4%) among new cases and 25.6% (range 11.7%–36.9%) among previously treated cases. Adjusting the drug resistance proportions using the re-testing results did not change the estimated national mean prevalence significantly. However, in some individual provinces the estimated resistance proportions were greatly influenced, especially among re-treatment patients.
Conclusion
MDR-TB levels varied greatly between provinces in China, but on average were high compared to the global estimated average of 4.8%. This study shows the importance of quality-assured laboratory performance. Programmatic management of drug-resistant TB, including high quality DST for patients at high risk of resistance and treatment with second-line drugs, should become the standard, especially in high MDR-TB settings.
doi:10.1186/1471-2334-8-166
PMCID: PMC2630916  PMID: 19077223
12.  Nutritional status and serum zinc and selenium levels in Iranian HIV infected individuals 
Background
Human immunodeficiency virus infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and increased catabolism. Trace elements such as zinc and selenium have major role in maintaining a healthy immune system. This study was designed to evaluate the nutritional status of Iranian subjects who were newly diagnosed with human immunodeficiency virus infection and to compare serum level of zinc and selenium in these patients with those of the sex and aged match healthy subjects.
Methods
After an interview and physical examination, nutritional assessment was done based on clinical and anthropometric parameters. Body mass index (normal range 18.5–27 kg/m2 based on age) of less than 16, 16–16.9 and 17–18.4 kg/m2 were considered as severe, moderate and mild malnutrition respectively. Serum level of zinc and selenium were measured by graphite furnace atomic absorption.
Results
Severe, moderate and mild malnutrition were detected in 15%, 38% and 24% of human immunodeficiency virus infected individuals respectively. Compared with the healthy control group, serum level of zinc and selenium in the human immunodeficiency virus infected subjects were significantly lower (P = 0.01 and P = 0.02 respectively).
Conclusion
Malnutrition found to be prevalent in Iranian human immunodeficiency virus infected individuals and low serum zinc and selenium levels are common in this population.
doi:10.1186/1471-2334-8-165
PMCID: PMC2613901  PMID: 19068104
13.  Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil 
Background
The progression of liver disease in patients with chronic hepatitis C virus (HCV) infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literatute. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics.
Methods
Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms.
Results
A total of 283 patients were included; genotype 1 was idenfied in 163 (57.6%) patients, genotype 3 in 112 (39.6%), genotype 2 in 7 (2.5%), and genotype 4 in 1 (0.35%). Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p < 0.05).
Conclusion
Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.
doi:10.1186/1471-2334-8-164
PMCID: PMC2612665  PMID: 19055835
14.  Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients 
Background
Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.
Methods
review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007.
Results
179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; p < 0.050).
Conclusion
In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.
doi:10.1186/1471-2334-8-163
PMCID: PMC2614426  PMID: 19055740
15.  Knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in Tanzania 
Background
Many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-Sahara African region. These include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. The current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-diagnosis and hence under-reporting.
Methods
The study was designed as a cross-sectional survey. Semi-structured open-ended questionnaire was administered to medical practitioners to establish the knowledge of anthrax, rabies, brucellosis, trypanosomiasis, echinococcosis and bovine tuberculosis in selected health facilities within urban and rural settings in Tanzania between April and May 2005. Frequency data were analyzed using likelihood ratio chi-square in Minitab version 14 to compare practitioners' knowledge of transmission, clinical features and diagnosis of the zoonoses in the two settings. For each analysis, likelihood ratio chi-square p-value of less than 0.05 was considered to be significant. Fisher's exact test was used where expected results were less than five.
Results
Medical practitioners in rural health facilities had poor knowledge of transmission of sleeping sickness and clinical features of anthrax and rabies in humans compared to their urban counterparts. In both areas the practitioners had poor knowledge of how echinococcosis is transmitted to humans, clinical features of echinococcosis in humans, and diagnosis of bovine tuberculosis in humans.
Conclusion
Knowledge of medical practitioners of zoonotic diseases could be a contributing factor to their under-diagnosis and under-reporting in Tanzania. Refresher courses on zoonotic diseases should be conducted particularly to practitioners in rural areas. More emphasis should be put on zoonotic diseases in teaching curricula of medical practitioners' training institutions in Tanzania to improve the diagnosis, reporting and control of zoonotic diseases. Veterinary and medical collaboration should be strengthened to enable more effective control of zoonotic diseases in Tanzania.
doi:10.1186/1471-2334-8-162
PMCID: PMC2611996  PMID: 19046464
16.  A randomized controlled trial of tea tree oil (5%) body wash versus standard body wash to prevent colonization with methicillin-resistant Staphylococcus aureus (MRSA) in critically ill adults: research protocol 
Background
Over the past ten years MRSA has become endemic in hospitals and is associated with increased healthcare costs. Critically ill patients are most at risk, in part because of the number of invasive therapies that they require in the intensive care unit (ICU). Washing with 5% tea tree oil (TTO) has been shown to be effective in removing MRSA on the skin. However, to date, no trials have evaluated the potential of TTO body wash to prevent MRSA colonization or infection. In addition, detecting MRSA by usual culture methods is slow. A faster method using a PCR assay has been developed in the laboratory, but requires evaluation in a large number of patients.
Methods/Design
This study protocol describes the design of a multicentre, phase II/III prospective open-label randomized controlled clinical trial to evaluate whether a concentration of 5% TTO is effective in preventing MRSA colonization in comparison with a standard body wash (Johnsons Baby Softwash) in the ICU. In addition we will evaluate the cost-effectiveness of TTO body wash and assess the effectiveness of the PCR assay in detecting MRSA in critically ill patients. On admission to intensive care, swabs from the nose and groin will be taken to screen for MRSA as per current practice. Patients will be randomly assigned to be washed with the standard body wash or TTO body wash. On discharge from the unit, swabs will be taken again to identify whether there is a difference in MRSA colonization between the two groups.
Discussion
If TTO body wash is found to be effective, widespread implementation of such a simple colonization prevention tool has the potential to impact on patient outcomes, healthcare resource use and patient confidence both nationally and internationally.
Trial Registration
[ISRCTN65190967]
doi:10.1186/1471-2334-8-161
PMCID: PMC2611995  PMID: 19040726
17.  Frequency and predictors of miliary tuberculosis in patients with miliary pulmonary nodules in South Korea: A retrospective cohort study 
Background
Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules.
Methods
We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea.
Results
We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB.
Conclusion
Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.
doi:10.1186/1471-2334-8-160
PMCID: PMC2613900  PMID: 19036129
18.  Risky sexual practices among youth attending a sexually transmitted infection clinic in Dar es Salaam, Tanzania 
Background
Youth have been reported to be at a higher risk of acquiring STIs with significant adverse health and social consequences. Knowledge on the prevailing risky practices is an essential tool to guide preventive strategies.
Methods
Youth aged between 18 and 25 years attending an STI clinic were recruited. Social, sexual and demographic characteristics were elicited using a structured standard questionnaire. Blood samples were tested for syphilis and HIV infections. Urethral, high vaginal and cervical swabs were screened for common STI agents.
Results
A total of 304 youth were studied with mean age of 21.5 and 20.3 years for males and females respectively. 63.5% of youth were seeking STI care. The mean age of coitache was 16.4 and 16.2 years for males and females respectively. The first sexual partner was significantly older in females compared to male youth (23.0 vs 16.8 years) (p < 0.01). 93.2% of male youth reported more than one sexual lifetime partner compared to 63.0% of the females. Only 50% of males compared to 43% of females had ever used a condom and fewer than 8.3% of female youth used other contraceptive methods. 27.1% of pregnancies were unplanned and 60% of abortions were induced. 42.0% of female youth had received gifts/money for sexual favours. The HIV prevalence was 15.3% and 7.5% for females and males respectively. The prevalence of other STIs was relatively low. Among male youth, use of alcohol or illicit drugs was associated with increased risk of HIV infection. However, the age of sexual initiation, number of sexual partners or the age of the first sexual partner were not associated with increased risk of being HIV infected.
Conclusion
Most female youth seen at the STI clinic had their first sexual intercourse with older males. Youth were engaging in high risk unprotected sexual practices which were predisposing them to STIs and unplanned pregnancies. There is a great need to establish more youth-friendly reproductive health clinics, encourage consistent and correct use of condoms, delay in sexual debut and avoid older sexual partners in females.
doi:10.1186/1471-2334-8-159
PMCID: PMC2596153  PMID: 19019224
19.  Re-emergence of tularemia in Germany: Presence of Francisella tularensis in different rodent species in endemic areas 
Background
Tularemia re-emerged in Germany starting in 2004 (with 39 human cases from 2004 to 2007) after over 40 years of only sporadic human infections. The reasons for this rise in case numbers are unknown as is the possible reservoir of the etiologic agent Francisella (F.) tularensis. No systematic study on the reservoir situation of F. tularensis has been published for Germany so far.
Methods
We investigated three areas six to ten months after the initial tularemia outbreaks for the presence of F. tularensis among small mammals, ticks/fleas and water. The investigations consisted of animal live-trapping, serologic testing, screening by real-time-PCR and cultivation.
Results
A total of 386 small mammals were trapped. F. tularensis was detected in five different rodent species with carrier rates of 2.04, 6.94 and 10.87% per trapping area. None of the ticks or fleas (n = 432) tested positive for F. tularensis. We were able to demonstrate F. tularensis-specific DNA in one of 28 water samples taken in one of the outbreak areas.
Conclusion
The findings of our study stress the need for long-term surveillance of natural foci in order to get a better understanding of the reasons for the temporal and spatial patterns of tularemia in Germany.
doi:10.1186/1471-2334-8-157
PMCID: PMC2629769  PMID: 19014635
20.  Effect of treating Schistosoma haematobium infection on Plasmodium falciparum-specific antibody responses 
Background
The overlapping geographical and socio-economic distribution of malaria and helminth infection has led to several studies investigating the immunological and pathological interactions of these parasites. This study focuses on the effect of treating schistosome infections on natural human immune responses directed against plasmodia merozoite surface proteins MSP-1 (DPKMWR, MSP119), and MSP-2 (CH150 and Dd2) which are potential vaccine candidates as well as crude malaria (schizont) and schistosome (whole worm homogenate) proteins.
Methods
IgG1 and IgG3 antibody responses directed against Schistosoma haematobium crude adult worm antigen (WWH) and Plasmodium falciparum antigens (merozoite surface proteins 1/2 and schizont extract), were measured by enzyme linked immunosorbent assay (ELISA) in 117 Zimbabweans (6–18 years old) exposed to S. haematobium and P. falciparum infection. These responses were measured before and after anti-helminth treatment with praziquantel to determine the effects of treatment on anti-plasmodial/schistosome responses.
Results
There were no significant associations between antibody responses (IgG1/IgG3) directed against P. falciparum and schistosomes before treatment. Six weeks after schistosome treatment there were significant changes in levels of IgG1 directed against schistosome crude antigens, plasmodia crude antigens, MSP-119, MSP-2 (Dd2), and in IgG3 directed against MSP-119. However, only changes in anti-schistosome IgG1 were attributable to the anti-helminth treatment.
Conclusion
There was no association between anti-P. falciparum and S. haematobium antibody responses in this population and anti-helminth treatment affected only anti-schistosome responses and not responses against plasmodia crude antigens or MSP-1 and -2 vaccine candidates.
doi:10.1186/1471-2334-8-158
PMCID: PMC2654038  PMID: 19014683
21.  Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea 
Background
Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality.
Methods
Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-γ and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up.
Results
Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-γ, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis.
Conclusion
High serum concentrations of TNFR p55, IFN-γ, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-γ and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.
doi:10.1186/1471-2334-8-156
PMCID: PMC2605754  PMID: 19014537
22.  Acquisition of methicillin-resistant Staphylococcus aureus after living donor liver transplantation: a retrospective cohort study 
Background
The incidence and risk factors of methicillin-resistant Staphylococcus aureus (MRSA) acquisition after living donor liver transplantation (LDLT) are unclear. The aim of the present study was to assess the incidence and to analyze the risk factors for the acquisition of MRSA after LDLT in adults by multivariate analysis.
Methods
We retrospectively reviewed the data from 158 adult patients that underwent LDLT at the Tokyo University Hospital. The microbiologic and medical records of the patients from admission to 3 months after LDLT were reviewed. Uni- and multivariate analyses were performed to identify the risk factors for postoperative acquisition of MRSA.
Results
Postoperative MRSA acquisition was detected in 35 of 158 patients by median postoperative day 18. Age (>= 60 y) and perioperative dialysis and/or apheresis predicted postoperative MRSA acquisition by multivariate analysis. In contrast, postoperative use of fluoroquinolone was negatively associated with acquisition of MRSA.
Conclusion
MRSA arose early after LDLT in adults with a high incidence (35 of 158 patients). Surveillance culture should be checked periodically after LDLT to identify and prevent the transmission of MRSA.
doi:10.1186/1471-2334-8-155
PMCID: PMC2625350  PMID: 19014465
23.  Streptococcus intermedius causing infective endocarditis and abscesses: a report of three cases and review of the literature 
Background
Streptococcus intermedius is a member of the Streptococcus anginosus group. Clinical disease with S. intermedius is characterized by abscess formation and rarely endocarditis. Identification of Streptococcus intermedius is difficult, leading to the development of molecular methods to more accurately identify and characterize this organism.
Case presentation
Over a period of 6 months we encountered three cases of invasive Streptococcus intermedius infection presenting as hepatic abscesses, brain abscess, and endocarditis. We confirmed our microbiologic diagnosis through 16S sequencing and found a common virulence gene in each case.
Conclusion
Our report illustrates three different clinical manifestations due to Streptococcus intermedius infection that can be encountered in healthy individuals in a community hospital setting. To our knowledge, this is the first case of Streptococcus intermedius endocarditis confirmed by 16S sequencing analysis. The use of molecular methods may allow a better understanding of the epidemiology and pathogenesis of this organism.
doi:10.1186/1471-2334-8-154
PMCID: PMC2600825  PMID: 18992173
24.  Ability of online drug databases to assist in clinical decision-making with infectious disease therapies 
Background
Infectious disease (ID) is a dynamic field with new guidelines being adopted at a rapid rate. Clinical decision support tools (CDSTs) have proven beneficial in selecting treatment options to improve outcomes. However, there is a dearth of information on the abilities of CDSTs, such as drug information databases. This study evaluated online drug information databases when answering infectious disease-specific queries.
Methods
Eight subscription drug information databases: American Hospital Formulary Service Drug Information (AHFS), Clinical Pharmacology (CP), Epocrates Online Premium (EOP), Facts & Comparisons 4.0 Online (FC), Lexi-Comp (LC), Lexi-Comp with AHFS (LC-AHFS), Micromedex (MM), and PEPID PDC (PPDC) and six freely accessible: DailyMed (DM), DIOne (DIO), Epocrates Online Free (EOF), Internet Drug Index (IDI), Johns Hopkins ABX Guide (JHAG), and Medscape Drug Reference (MDR) were evaluated for their scope (presence of an answer) and completeness (on a 3-point scale) in answering 147 infectious disease-specific questions. Questions were divided among five classifications: antibacterial, antiviral, antifungal, antiparasitic, and vaccination/immunization. Classifications were further divided into categories (e.g., dosage, administration, emerging resistance, synergy, and spectrum of activity). Databases were ranked based on scope and completeness scores. ANOVA and Chi-square were used to determine differences between individual databases and between subscription and free databases.
Results
Scope scores revealed three discrete tiers of database performance: Tier 1 (82-77%), Tier 2 (73-65%) and Tier 3 (56-41%) which were significantly different from each other (p < 0.05). The top tier performers: MM (82%), MDR (81%), LC-AHFS (81%), AHFS (78%), and CP (77%) answered significantly more questions compared to other databases (p < 0.05). Top databases for completeness were: MM (97%), DM (96%), IDI (95%), and MDR (95%). Subscription databases performed better than free databases in all categories (p = 0.03). Databases suffered from 37 erroneous answers for an overall error rate of 1.8%.
Conclusion
Drug information databases used in ID practice as CDSTs can be valuable resources. MM, MDR, LC-AHFS, AHFS, and CP were shown to be superior in their scope and completeness of information, and MM, AHFS, and MDR provided no erroneous answers. There is room for improvement in all evaluated databases.
doi:10.1186/1471-2334-8-153
PMCID: PMC2613899  PMID: 18990224
25.  Investigation of Swedish cases reveals an outbreak of cryptosporidiosis at a Norwegian hotel with possible links to in-house water systems 
Background
In March 2007, the Norwegian Institute of Public Health was notified of Swedish individuals diagnosed with cryptosporidiosis after staying at a Norwegian hotel. In Norway, cryptosporidiosis is not reportable, and human infections are rarely diagnosed.
Methods
A questionnaire on illness and exposure history was e-mailed to seven organised groups who had visited the hotel in March. Cases were defined as persons with diarrhoea for more than two days or laboratory-confirmed cryptosporidiosis during or within two weeks of the hotel visit. The risk factor analysis was restricted to two groups with the highest attack rates (AR) and same hotel stay period. Local food safety authorities conducted environmental investigations.
Results
In total, 25 diarrhoeal cases (10 laboratory-confirmed) were identified among 89 respondents. Although environmental samples were negative, epidemiological data suggest an association with in-house water consumption. In one group, the AR was higher amongst consumers of water from hotel dispenser (relative risk [RR] = 3.0; 95% confidence interval [CI]: 0.9–9.8), tap water (RR = 2.3; CI: 0.9–5.8), and lower amongst commercial bottled water drinkers (RR = 0.6; CI: 0.4–1.0). Consumption of ice cubes was a risk-factor (RR = 7.1; CI: 1.1–45.7) in the two groups combined.
Conclusion
This outbreak would probably have remained undetected without the alert from Swedish health authorities, illustrating the difficulties in outbreak detection due to low health care seeking behaviour for diarrhoea and limited parasite diagnostics in Norway. Awareness of cryptosporidiosis should be raised amongst Norwegian medical personnel to improve case and outbreak detection, and possible risks related to in-house water systems should be assessed.
doi:10.1186/1471-2334-8-152
PMCID: PMC2606681  PMID: 18976495

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