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1.  Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice 
Background
Acyclovir (ACV) resistant herpes simplex virus (HSV) isolates can be readily selected in animal infection models receiving suboptimal ACV treatment, however no comparative studies of the emergence of resistance following suboptimal treatment with valacyclovir (VCV) or famciclovir (FCV), the prodrugs of acyclovir and penciclovir, respectively, have been reported.
Methods
Mice (n = 30) were infected with HSV type 1 or 2 in the ear pinnae and administered oral prodrugs at one fifth a dose previously shown to be effective. To select and amplify drug-resistant HSV, a total of seven consecutive in vivo passages with suboptimal treatment were performed for each virus sample and progeny virus from each passage was characterized by the plaque reduction (PRA) and plating efficiency assays (PEA).
Results
No drug-resistant HSV-2 and only a single drug-resistant HSV-1 variant were identified. Virus recovered from the first three sequential passages of this HSV-1 sample was susceptible by PRA, although the proportion of resistant virus recovered gradually increased upon passage. The resistant HSV-1 phenotype was confirmed by PRA after four sequential passages in mice. Unexpectedly, this in vivo-selected drug-resistant HSV-1 failed to yield an infection completely refractory to treatment in subsequent passages.
Conclusions
Sub-optimal therapy of immunocompetent mice with either VCV or FCV did not readily select for HSV-mutants resistant to either ACV or PCV, suggesting that selection of resistance with either prodrug remains difficult using this system. Futhermore, this study suggests that the PEA may represent a useful adjunct to the PRA for monitoring alterations in the proportion of drug-resistant virus even when no change in IC50 is apparent.
doi:10.1186/1471-2334-1-24
PMCID: PMC61449  PMID: 11749671
2.  Field trial with oral vaccination of dogs against rabies in the Philippines 
Background
The potential role of oral vaccination of dogs against rabies in the Philippines was investigated in terms of safety and efficacy.
Methods
Prior to the vaccination campaign, a house-to-house survey was carried out to collect data on the dog population in the study area, the coastal village of Mindoro. During the vaccination campaign all households were visited again, and all dogs encountered (>2 months old) were, if possible, vaccinated. Furthermore, 14 dogs vaccinated were bled on different occasions.
Results
During the survey, a total of 216 dogs were counted, and none of these animals had previously been vaccinated against rabies. Only 17 dogs could be restrained and subsequently vaccinated directly by the vaccinators. Another 126 dogs were offered a local-made boiled intestine bait, containing a capsule filled with 3.0 ml SAD B19 (107.9 FFU/ml). The bait acceptance rate of dogs offered a bait was 96.1%. The vaccination coverage of the dog population (> 2 months old) estimated by the number of animals vaccinated directly and the number of dogs that accepted a bait and subsequently punctured the vaccine container was 76%. Fifteen and 29 days after the vaccination campaign 6 and 10 dogs (n = 14) had rabies virus neutralizing antibody titres of ≥ 0.5 IU/ml, respectively. No unintentional contacts of nontarget species, including humans, with the vaccine virus were reported.
Conclusions
The results of the campaign show that oral vaccination of dogs against rabies is a promising supplementary method in dog rabies control in the Philippines.
doi:10.1186/1471-2334-1-23
PMCID: PMC60992  PMID: 11737869
3.  Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report 
Background
Mucormycosis (or zygomycosis) is the term for infection caused by fungi of the order Mucorales. Mucoraceae may produce severe disease in susceptible individuals, notably patients with diabetes and leukemia. Rhinocerebral mucormycosis most commonly manifests itself in the setting of poorly controlled diabetes, especially with ketoacidosis.
Case Presentation
A 31-year-old diabetic man presented to the outpatient clinic with the following signs and symptoms: headache, periorbital pain, swelling and loss of vision in the right eye. On physical examination his right eye was red and swollen. There was periorbital cellulitis and the conjunctiva was edematous. KOH preparation of purulent discharge showed broad, ribbonlike, aseptate hyphae when examined under a fluorescence microscope. Cranial MRI showed involvement of the right orbit, thrombosis in cavernous sinus and infiltrates at ethmoid and maxillary sinuses. Mucormycosis was diagnosed based on these findings. Amphotericin B (AmBisome®; 2 mg/kg.d) was initiated after the test doses. Right orbitectomy and right partial maxillectomy were performed; the lesions in ethmoid and maxillary sinuses were removed. The duration of the liposomal amphotericin B therapy was approximately 6 months and the total dose of liposomal amphotericin B used was 32 grams. Liposomal amphotericin B therapy was stopped six months later and oral fluconazole was started.
Conclusions
Although a total surgical debridement of the lesions could not be performed, it is remarkable that regression of the disease could be achieved with medical therapy alone.
doi:10.1186/1471-2334-1-22
PMCID: PMC60655  PMID: 11737868
4.  Frequency of tuberculous and non-tuberculous mycobacteria in HIV infected patients from Bogota, Colombia 
Background
The prevalence of infections by Mycobacterium tuberculosis and non-tuberculous Mycobacterium species in the HIV-infected patient population in Colombia was uncertain despite some pilot studies. We determined the frequency of isolation of Mycobacterium tuberculosis and of non-tuberculous Mycobacterium species in diverse body fluids of HIV-infected patients in Bogota, Colombia.
Methods
Patients who attended the three major HIV/AIDS healthcare centres in Bogota were prospectively studied over a six month period. A total of 286 patients were enrolled, 20% of them were hospitalized at some point during the study. Sixty four percent (64%) were classified as stage C, 25% as stage B, and 11% as stage A (CDC staging system, 1993). A total of 1,622 clinical samples (mostly paired samples of blood, sputum, stool, and urine) were processed for acid-fast bacilli (AFB) stain and culture.
Results
Overall 43 of 1,622 cultures (2.6%) were positive for mycobacteria. Twenty-two sputum samples were positive. Four patients were diagnosed with M. tuberculosis (1.4%). All isolates of M. tuberculosis were sensitive to common anti-tuberculous drugs. M. avium was isolated in thirteen patients (4.5%), but only in three of them the cultures originated from blood. The other isolates were obtained from stool, urine or sputum samples. In three cases, direct AFB smears of blood were positive. Two patients presented simultaneously with M. tuberculosis and M. avium.
Conclusions
Non-tuberculous Mycobacterium infections are frequent in HIV infected patients in Bogota. The diagnostic sensitivity for infection with tuberculous and non-tuberculous mycobacteria can be increased when diverse body fluids are processed from each patient.
doi:10.1186/1471-2334-1-21
PMCID: PMC60001  PMID: 11722797
5.  Blood borne transit of CJD from brain to gut at early stages of infection 
Background
In Creutzfeldt-Jakob disease (CJD) and other related transmissible spongiform encephalopathies it is critical to understand the various pathways by which the infectious agent spreads to different organs.
Methods
We injected a CJD agent into mice, either intracerebrally (ic) or intraperitoneally (ip) and monitored the progressive appearance of abnormal PrP in peripheral tissues over time.
Results
Abnormal PrP was detected in lymphoreticular tissues of the gastrointestinal tract as early as 28 to 32 days after infection by both routes. This change persisted until the terminal stages of disease. In contrast, abnormal PrP was not detected in brain or spinal cord until 80 to 120 days after ic inoculation, or until 170 days after ip inoculation.
Conclusions
Brain lacks significant lymphatic drainage, and has little infectivity before 40 days, even after ic inoculation. Thus the infectious inoculum must spread to the gut by a vascular route, a direction opposite to that generally assumed. This interpretation is consistent with previous studies demonstrating white blood cell infectivity as well as perivascular PrP accumulations in CJD. Notably, enteric infection at early as well as later stages of disease, and regardless of the route of agent entry, implicates potential environmental spread by fecal matter.
doi:10.1186/1471-2334-1-20
PMCID: PMC59894  PMID: 11716790
6.  Acceptability of local made baits for oral vaccination of dogs against rabies in the Philippines 
Background
In the Philippines, traditional mass dog vaccination campaigns have only achieved limited and transient success in dog rabies control, mainly because a large segment of the dog population is not accessible for traditional parenteral vaccination. Oral vaccination of dogs has been suggested as a supplementary method to increase the overall vaccination coverage of the dog populations involved. For this purpose, it is necessary to identify a suitable bait that is readily accepted by local dogs and that can be prepared without high costs.
Materials and Methods
During a field study, dog bait-acceptance of several baits, made from inexpensive local available material, was examined in the Philippines.
Results
Of three baits tested, chickenneck, intestine, and boiled-intestine, the latter, made from boiled sections of the larger intestine of domestic pigs, had the highest acceptance-rate: none of the dogs that were offered a bait refused it, except for two dogs that ran away when approached.
Other derivatives of the boiled-intestine bait were also accepted by almost all dogs. These baits, using the serosa of the smaller intestine as bait matrix were filled with fish, beef or pork scraps. However, preparation-time was longer and the costs of bait material were higher than those for the boiled-intestine bait (0.01 U$).
Conclusion
The boiled-intestine bait can be produced at very low costs using locally available material and is extremely well accepted by local dogs, hence, providing a realistic opportunity to incorporate oral vaccination of dogs in the national rabies programme of the Philippines.
doi:10.1186/1471-2334-1-19
PMCID: PMC59655  PMID: 11696244
7.  Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance 
Background
Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.
Objectives
To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.
Methods
The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.
Results
Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).
Conclusions
Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.
doi:10.1186/1471-2334-1-18
PMCID: PMC58589  PMID: 11667952
8.  Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120 
Background
Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.
Methods
Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope.
Results
1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus.
Conclusions
These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.
doi:10.1186/1471-2334-1-17
PMCID: PMC57811  PMID: 11602021
9.  The efficacy of chemical agents in cleaning and disinfection programs 
Background
Due to the growing number of outbreaks of infection in hospital nurseries, it becomes essential to set up a sanitation program that indicates that the appropriate chemical agent was chosen for application in the most effective way.
Method
For the purpose of evaluating the efficacy of a chemical agent, the minimum inhibitory concentration (MIC) was reached by the classic method of successive broth dilutions. The reference bacteria utilized were Bacillus subtilis var. globigii ATCC 9372, Bacillus stearothermophilus ATCC 7953, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923. The strains of Enterobacter cloacae IAL 1976 (Adolfo Lutz Institute), Serratia marcescens IAL 1478 and Acinetobactev calcoaceticus IAL 124 (ATCC 19606), were isolated from material collected from babies involved in outbreaks of infection in hospital nurseries.
Results
The MIC intervals, which reduced bacteria populations over 08 log10, were: 59 to 156 mg/L of quaternarium ammonium compounds (QACs); 63 to 10000 mg/L of chlorhexidine digluconate; 1375 to 3250 mg/L of glutaraldehyde; 39 to 246 mg/L of formaldehyde; 43750 to 87500 mg/L of isopropanol or ethanol; 1250 to 6250 mg/L of iodine in polyvinyl-pyrolidone complexes, 150 to 4491 mg/L of chlorine-releasing-agents (CRAs); 469 to 2500 mg/L of hydrogen peroxide; and, 2310 to 18500 mg/L of peracetic acid.
Conclusions
Chlorhexidine showed non inhibitory activity over germinating spores. A. calcoaceticus, was observed to show resistance to the majority of the agents tested, followed by E. cloacae and S. marcescens.
doi:10.1186/1471-2334-1-16
PMCID: PMC57744  PMID: 11591223
10.  Blood and alveolar lymphocyte subsets in pulmonary cytomegalovirus infection after lung transplantation 
Background
Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic alveolitis after lung transplantation. In the present study, we investigated a series of bronchoalveolar (BAL) and blood samples, collected in the absence of rejection or acute infectious episodes. in order -1: to evaluate intra-alveolar cell population changes concomitant with CMV replication and -2: to reappraise the value of cell population analysis in the management of patients after lung transplantation.
Methods
We used flow cytometry to investigate modifications of lymphocyte subpopulations related to pulmonary cytomegalovirus infections in blood and BAL samples from a series of 13 lung transplant recipients. After exclusion of samples obtained during pulmonary rejection, bronchiolitis obliterans or acute bacterial infection, 48 blood and BAL samples were retained for analysis: 17 were CMV positive by shell-vial assay and 31 were CMV negative in blood and BAL.
Results
Our results demonstrate that pulmonary CMV infection is associated with a significant increase in the total lymphocyte population in BAL samples, but with minor modifications of the various lymphocyte subpopulations and a significantly higher absolute number of B lymphocytes in blood samples.
Conclusions
Cytomegalovirus pulmonary infection is accompanied by only minor changes in BAL lymphocyte subpopulations. The study of BAL lymphocyte subpopulations therefore appears to be of limited clinical value in the diagnosis of pulmonary CMV infection. However, increased blood B-lymphocytes seems to be a clinical feature associated with CMV infection.
doi:10.1186/1471-2334-1-15
PMCID: PMC57810  PMID: 11602020
Lung Transplantation; Cytomegalovirus; Lymphocytes; Bronchoalveolar lavage; Flow cytometry
11.  Aseptic meningitis in Germany associated with echovirus type 13 
Background
Echoviruses are the commonest cause of aseptic meningitis. Echovirus type 13 which has not been isolated in Germany over a long period of time was the predominant enterovirus serotype associated with different local outbreaks of aseptic meningitis in Germany in 2000.
Methods
Virus isolation was performed from cerebrospinal fluid and stools. In order to study the genetic relationship of echovirus type 13 isolates, sequence analysis of a part of VP1 (~300 nt) was carried out. Isolates from different geographic regions were compared to each other as well as to elder viruses (prototype strain from 1953, four isolates from 1965–1986).
Results
Overall, 55 isolates of echovirus type 13 were obtained from different parts of Germany. It was shown that the new isolated strains have a very high degree of homology on the nucleotide level (> 98%)) but differ significantly from the old strains (76–85%).
Conclusions
a) Rare enterovirus serotypes can cause serious illness.
b) The molecular drift has also been shown for other enterovirus serotypes.
doi:10.1186/1471-2334-1-14
PMCID: PMC57743  PMID: 11591222
12.  Bacteremia in hospitalized patients with human immunodeficiency virus: A prospective, cohort study 
Background
Bacterial infections complicate the course of patients with human immunodeficiency virus infection. The purpose of this study was to describe the bacterial pathogens causing blood stream infection, identify the risk factors for the development of blood stream infection and determine the impact of blood stream infection on the outcome of patients infected with human immunodeficiency virus.
Methods
The incidence, etiology, risk factors and outcome of bacterial blood stream infection were prospectively determined in 1,225 consecutive hospitalizations of adults with human immunodeficiency virus infection.
Results
Blood stream infection occurred in 88 hospitalizations (7%); 73 of 89 infections (82%) were community acquired. The most commonly isolated gram-positive organism was Streptococcus pneumoniae (21); gram-negative, Escherichia coli (14). Blood stream infection was detected in 8% of African Americans and 22% of Hispanics compared with 2% of whites (P = 0.0013). Patients with blood stream infection had higher white blood cell counts (median, 6.5 vs. 4.9 × 109/L; P = 0.0002) and mortality (18% vs. 4%; P < 0.0001) than patients without infection.
Conclusions
In patients with human immunodeficiency virus, blood stream infection is associated with an increased mortality rate. Recognition of the incidence, etiology, and risk factors of blood stream infection in patients with human immunodeficiency virus infection could lead to measures that reduce the increased mortality.
doi:10.1186/1471-2334-1-13
PMCID: PMC57809  PMID: 11602019
13.  Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody 
Background
The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue.
Methods
Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR.
Results
C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG.
Conclusions
We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland.
doi:10.1186/1471-2334-1-12
PMCID: PMC55344  PMID: 11553320
14.  Clinical utility of a nested nucleic acid amplification format in comparison to viral culture for the diagnosis of mucosal herpes simplex infection in a genitourinary medicine setting 
Background
Nested nucleic acid amplification tests are often thought too sensitive or prone to generatingfalse positive results for routine use. The current study investigated the specificity and clinicalutility of a routine multiplex nested assay for mucosal herpetic infections.
Methods
Ninety patients, categorised into those clinically diagnosed to (a) have and (b) not haveherpetic infection, were enrolled. Swabs from oral and ano-genital sites were assayed by thenested assay and culture and the results assessed against clinical evaluation for diagnosingherpetic infections; cell content was also recorded.
Results
Twenty-six and 64 patients were thought to (a) have and (b) not have mucosal herpeticinfection. Taking the clinical evaluation as indicating the presence of herpetic infection, thenested polymerase chain reaction and culture had respective sensitivities of 19/26 (73%) and12/26 (46%) (Χ2 p = 0.02). There was no significant difference in specificities between nPCR62/64 (97%) and culture 63/64 (98%) (Χ2 p = 1.0). Cell content was important for viraldetection by nPCR (Χ2 p = 0.07) but not culture. Nesting was found necessary for sensitivity anddid not reduce specificity. Assay under-performance appeared related to sub-optimal cellcontent (20%) but may have reflected clinical over-diagnosis. The results suggest the need forvalidating specimen cell quality.
Conclusions
This study questions the value of routine laboratory confirmation of mucosal herpetic infection. The adoption of a more discriminatory usage of laboratory diagnostic facilities for genital herpetic infection, taking account of cell content, and restricting it to those cases where it actually affects patient management, may be warranted.
doi:10.1186/1471-2334-1-11
PMCID: PMC57742  PMID: 11591221
15.  An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India 
Background
Plasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures.
Methods
Children aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard.
Results
In all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%.
Conclusions
Determine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas.
doi:10.1186/1471-2334-1-10
PMCID: PMC48149  PMID: 11532200
16.  Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study 
Background
HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments.
Methods
For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia.
Results
Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route.
Conclusions
These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.
doi:10.1186/1471-2334-1-9
PMCID: PMC37356  PMID: 11504564
17.  Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance 
Background
Transmission of hepatitis C vims (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol.
Methods
Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition.
Results
Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients.
Conclusion
One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors.
doi:10.1186/1471-2334-1-8
PMCID: PMC37546  PMID: 11518542
18.  The burden of pediatric HIV/AIDS in Constanta, Romania: a cross-sectional study 
Background
By 1990, 94 percent of the acquired immunodeficiency syndrome (AIDS) cases in Romania were in children less than 13 years of age. The majority of the cases were identified in the city of Constanta. The purpose of this paper was to describe the current burden of pediatric human immunodeficiency virus (HIV) infection in the Constanta county.
Methods
A cross-sectional study was designed to address the primary objective. Between April 1999 and March 2000, all living cases of pediatric HIV infection in the Constanta county were identified from records at the HIV hospital clinic which serves the Constanta county. Standard demographic, social, clinical, treatment and hospitalization data were collected for each study subject. Data were analyzed according to cross-sectional study design methodology.
Results
Of the 762 subjects, the majority were seven to 11 years of age, lived with their parents and attended school. Only 70% of the fathers and 13% of the mothers were employed. Horizontal transmission accounted for 90% of the cases. Most of the children had moderate to severe disease as indicated by their AIDS-defining signs; 40% had AIDS. Less than half of the children were receiving antiretroviral therapy (ART). ART and children of mothers with a high school or greater education were independent predictors of long-term non-progression of HIV disease.
Conclusions
This cross-sectional study demonstrated that ten years after the HIV epidemic was identified in Romania, it remains a health and economic burden. The infected children are very ill, but ART is not available for all. The proportion with vertical transmission has increased from an estimated four % to nine %. Our findings support the need to get HIV therapy to economically challenged countries such as Romania.
doi:10.1186/1471-2334-1-7
PMCID: PMC37311  PMID: 11495632
19.  Clinical features of culture-proven Mycoplasma pneumoniae infections at King Abdulaziz University Hospital, Jeddah, Saudi Arabia 
Objective
This retrospective chart review describes the epidemiology and clinical features of 40 patients with culture-proven Mycoplasma pneumoniae infections at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Methods
Patients with positive M. pneumoniae cultures from respiratory specimens from January 1997 through December 1998 were identified through the Microbiology records. Charts of patients were reviewed.
Results
40 patients were identified, 33 (82.5%) of whom required admission. Most infections (92.5%) were community-acquired. The infection affected all age groups but was most common in infants (32.5%) and pre-school children (22.5%). It occurred year-round but was most common in the fall (35%) and spring (30%). More than three-quarters of patients (77.5%) had comorbidities. Twenty-four isolates (60%) were associated with pneumonia, 14 (35%) with upper respiratory tract infections, and 2 (5%) with bronchiolitis. Cough (82.5%), fever (75%), and malaise (58.8%) were the most common symptoms, and crepitations (60%), and wheezes (40%) were the most common signs. Most patients with pneumonia had crepitations (79.2%) but only 25% had bronchial breathing. Immunocompromised patients were more likely than non-immunocompromised patients to present with pneumonia (8/9 versus 16/31, P = 0.05). Of the 24 patients with pneumonia, 14 (58.3%) had uneventful recovery, 4 (16.7%) recovered following some complications, 3 (12.5%) died because of M pneumoniae infection, and 3 (12.5%) died due to underlying comorbidities. The 3 patients who died of M pneumoniae pneumonia had other comorbidities.
Conclusion
our results were similar to published data except for the finding that infections were more common in infants and preschool children and that the mortality rate of pneumonia in patients with comorbidities was high.
doi:10.1186/1471-2334-1-6
PMCID: PMC35282  PMID: 11472636
20.  The estimated economic burden of genital herpes in the United States. An analysis using two costing approaches 
Background
Only limited data exist on the costs of genital herpes (GH) in the USA. We estimated the economic burden of GH in the USA using two different costing approaches.
Methods
The first approach was a cross-sectional survey of a sample of primary and secondary care physicians, analyzing health care resource utilization. The second approach was based on the analysis of a large administrative claims data set. Both approaches were used to generate the number of patients with symptomatic GH seeking medical treatment, the average medical expenditures and estimated national costs. Costs were valued from a societal and a third party payer's perspective in 1996 US dollars.
Results
In the cross-sectional study, based on an estimated 3.1 million symptomatic episodes per year in the USA, the annual direct medical costs were estimated at a maximum of $984 million. Of these costs, 49.7% were caused by drug expenditures, 47.7% by outpatient medical care and 2.6% by hospital costs. Indirect costs accounted for further $214 million. The analysis of 1,565 GH cases from the claims database yielded a minimum national estimate of $283 million direct medical costs.
Conclusions
GH appears to be an important public health problem from the health economic point of view. The observed difference in direct medical costs may be explained with the influence of compliance to treatment and possible undersampling of subpopulations in the claims data set. The present study demonstrates the validity of using different approaches in estimating the economic burden of a specific disease to the health care system.
doi:10.1186/1471-2334-1-5
PMCID: PMC35281  PMID: 11472635
21.  pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea 
Background
Pyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide.
Results
Of the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns.
Conclusion
These data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes.
doi:10.1186/1471-2334-1-4
PMCID: PMC33507  PMID: 11429043
22.  Imiquimod for the treatment of genital warts: a quantitative systematic review 
Objective
To review published randomised controlled trials to assess the benefit and harm of imiquimod in the treatment of external genital warts.
Data sources
MEDLINE (1966 - December 2000), Cochrane Library (Issue 3, 2000) and PubMed (December 15, 2000), review articles and reference lists.
Review methods
Included studies had to be randomised trials of imiquimod, to be full published papers, and to have a comparison group. Quality of trial reporting was assessed. Relative benefit and number needed to treat were calculated for the main outcomes of wart clearance at the end of therapy, of at least 50% reduction in wart area, and of complete clearance at the end of treatment and no recurrence of warts during a follow-up period, as well as for adverse effect withdrawal or lack of efficacy withdrawal.
Results
There were six trials, all with quality scores of 3 (out of 5) or greater. In five trials with HIV-negative patients complete clearance of warts at the end of treatment occurred in 51% of patients treated with imiquimod 2% or 5% cream and 6% of placebo treated patients. The number needed to treat was 2.2 (95% confidence interval 2.0 to 2.6). In four trials at least 50% wart area reduction occurred with 72% of patients treated with imiquimod 5% cream and 20% of placebo treated patients. The number needed to treat was 1.9 (1.7 to 2.2). In three trials complete clearance of warts at the end of treatment plus no recurrence occurred in 37% of patients treated with imiquimod 5% cream and 4% of those treated with placebo. The number needed to treat was 3.0 (2.5 to 3.8). Adverse event withdrawal was rare and no more likely with imiquimod than with placebo. Imiquimod was not effective in one trial in HIV-positive patients.
Conclusion
The evidence base for imiquimod in treating genital warts is of high quality and the necessary size from which to draw useful conclusions. Imiquimod is effective in home application, though not in patients with HIV infection with the evidence presently available.
doi:10.1186/1471-2334-1-3
PMCID: PMC32301  PMID: 11401728
23.  CMV infection of liver transplant recipients: comparison of antigenemia and molecular biology assays 
Background
CMV is a major clinical problem in transplant recipients. Thus, it is important to use sensitive and specific diagnostic techniques to rapidly and accurately detect CMV infection and identify patients at risk of developing CMV disease. In the present study, CMV infection after liver transplantation was monitored retrospectively by two molecular biology assays - a quantitative PCR assay and a qualitative NASBA assay. The results were compared with those obtained by prospective pp65 antigenemia determinations.
Materials and Methods
87 consecutive samples from 10 liver transplanted patients were tested for CMV by pp65 antigenemia, and CMV monitor and NASBA pp67 mRNA assay.
Results
CMV infection was detected in all patients by antigenemia and CMV monitor, whereas NASBA assay identified only 8/10 patients with viremia. Furthermore, CMV infection was never detected earlier by molecular biology assays than by antigenemia. Only 5/10 patients with CMV infection developed CMV disease. Using a cut off value of 8 cells/50,000, antigenemia was found to be the assay that better identified patients at risk of developing CMV disease. However, the kinetics of the onset of infection detected by NASBA and CMV monitor seemed to have better identified patients at risk of developing CMV disease. Furthermore, before onset of disease, CMV pp67 mRNA was found to have similar or better negative and positive predictive values for the development of CMV disease.
Conclusions
The present data, suggests that the concomitant use of antigenemia and pp67 mRNA assay gives the best identification of patients at risk of developing CMV disease.
doi:10.1186/1471-2334-1-2
PMCID: PMC32208  PMID: 11389774
24.  Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir 
Background
In the last decades, attention to cholera epidemiology increased, as cholera epidemics became a worldwide health problem. Detailed investigation of V. cholerae interactions with its host and with other organisms in the environment suggests that cholera dynamics is much more complex than previously thought. Here, I formulate a mathematical model of cholera epidemiology that incorporates an environmental reservoir of V. cholerae. The objective is to explore the role of the aquatic reservoir on the persistence of endemic cholera as well as to define minimum conditions for the development of epidemic and endemic cholera.
Results
The reproduction rate of cholera in a community is defined by the product of social and environmental factors. The importance of the aquatic reservoir depends on the sanitary conditions of the community. Seasonal variations of contact rates force a cyclical pattern of cholera outbreaks, as observed in some cholera-endemic communities.
Conclusions
Further development on cholera modeling requires a better understanding of V. cholerae ecology and epidemiology. We need estimates of the prevalence of V. cholerae infection in endemic populations as well as a better description of the relationship between dose and virulence.
doi:10.1186/1471-2334-1-1
PMCID: PMC29087  PMID: 11208258

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