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An age-stratified serosurvey against purified Salmonella enterica serovar Typhi antigens in the Lao People´s Democratic Republic.

ABSTRACT: The epidemiology of typhoid fever in Lao People`s Democratic Republic is poorly defined. Estimating the burden of typhoid fever in endemic countries is complex due to the cost and limitations of population-based surveillance; serological approaches may be a more cost-effective alternative. ELISAs were performed on 937 serum samples (317 children and 620 adults) from across Lao PDR to measure IgG antibody titers against Vi polysaccharide and the experimental protein antigens, CdtB and HlyE. We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers. The median IgG titres of both anti-HylE and CdtB were significantly higher in children compared to adults (anti-HylE; 351.7 ELISA Units (EU) vs 198.1 EU, respectively; p<0.0001 and anti-CdtB; 52.6 vs 12.9 EU; p<0.0001). Conversely, the median anti-Vi IgG titer was significantly higher in adults than children (11.3 vs 3.0 U/ml; p<0.0001). A non-linear trend line fitted to the anti-CdtB and anti-HlyE IgG data identified a peak in antibody concentration in children <5 years of age. We identified elevated titers of anti-HlyE and anti-CdtB IgG in the serum of children residing in Lao PDR in comparison to adults. These antigens are associated with seroconversion after typhoid fever and may be a superior measure of disease burden than anti-Vi IgG. This approach is scalable and may be developed to assess the burden of typhoid fever in countries where the disease may be endemic, and evidence is required for the introduction of typhoid vaccines.

SUBMITTER: Hefele L

PROVIDER: S-EPMC8700045 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDiphtheria is a vaccine-preventable disease. When vaccination coverage and population immunity are low, outbreaks can occur. We investigated a diphtheria outbreak in Lao People's Democratic Republic that occurred during 2012-2013 and highlighted challenges in immunization services delivery to children in the country.MethodsWe reviewed diphtheria surveillance data from April 1, 2012-May 31, 2013. A diphtheria case was defined as a respiratory illness consisting of pharyngitis, tonsillitis, or laryngitis, and an adherent tonsillar or nasopharyngeal pseudomembrane. To identify potential risk factors for diphtheria, we conducted a retrospective case-control study with two aged-matched neighborhood controls per case-patient in Houaphan Province, using bivariate analysis to calculate matched odds ratio (mOR) with 95% confidence intervals (CI). Reasons for non-vaccination among unvaccinated persons were assessed.ResultsSixty-two clinical cases of diphtheria and 12 diphtheria-related deaths were reported in seven of 17 provinces. Among case-patients, 43 (69%) were <15years old, five (8%) reported receiving three DTP doses (DTP3), 21 (34%) had received no DTP doses, and 35 (56%) had unknown vaccination status. For the case-control study, 42 of 52 diphtheria case-patients from Houaphan province and 79 matched-controls were enrolled. Five (12%) case-patients and 20 (25%) controls had received DTP3 (mOR=0.4, CI=0.1-1.7). No diphtheria toxoid-containing vaccine was received by 20 (48%) case-patients and 38 (46%) controls. Among case-patients and controls with no DTP dose, 43% of case-patients and 40% of controls lacked access to routine immunization services.ConclusionSuboptimal DTP3 coverage likely caused the outbreak. To prevent continued outbreaks, access to routine immunization services should be strengthened, outreach visits need to be increased, and missed opportunities need to be minimized. In the short term, to rapidly increase population immunity, three rounds of DTP immunization campaign should be completed, targeting children aged 0-14years in affected provinces.

Project description:BackgroundTyphoid fever is an acute systemic infection of humans caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). In chronic carriers, the bacteria survive the harsh environment of the gallbladder by producing biofilm. The phenotype of S. Typhi biofilm cells is significantly different from the free-swimming planktonic cells, and studies have shown that they are associated with antibiotic resistance, immune system evasion, and bacterial persistence. However, the mechanism of this transition and the events leading to biofilm formation are unknown. High throughput sequencing was performed to identify the genes involved in biofilm formation and to postulate the mechanism of action.ResultsPlanktonic S. Typhi cells were cultured using standard nutrient broth whereas biofilm cells were cultured in a stressful environment using high shearing-force and bile to mimic the gallbladder. Sequencing libraries were prepared from S. Typhi planktonic cells and mature biofilm cells using the Illumina HiSeq 2500 platform, and the transcriptome data obtained were processed using Cufflinks bioinformatics suite of programs to investigate differential gene expression between the two phenotypes. A total of 35 up-regulated and 29 down-regulated genes were identified. The identities of the differentially expressed genes were confirmed using NCBI BLAST and their functions were analyzed. The results showed that the genes associated with metabolic processes and biofilm regulations were down-regulated while those associated with the membrane matrix and antibiotic resistance were highly up-regulated.ConclusionsIt is proposed that the biofilm phenotype of S. Typhi allows the bacteria to increase production of the membrane matrix in order to serve as a physical shield and to adhere to surfaces, and enter an energy conservation state in response to the stressful environment. Conversely, the planktonic phenotype allows the bacteria to produce flagella and increase metabolic activity to enable the bacteria to migrate and form new colonies of infection. This data provide a basis for further studies to uncover the mechanism of biofilm formation in S. Typhi and to discover novel genes or pathways associated with the development of the typhoid carrier state.

Project description:BACKGROUND: HIV infection is an emerging problem in Laos. We conducted the first prospective study on intestinal parasites, including opportunistic protozoa, in newly diagnosed HIV infected patients, with or without diarrhea. The aims were to describe the spectrum of infections, to determine their prevalence and to assess their associations with diarrhea, CD4 cell count, place of residence and living conditions. METHODOLOGY: One to three stool samples over consecutive days were obtained from 137 patients. The Kato thick smear method, formalin-ethyl concentration and specific stains for coccidia and microsporidia diagnosis were performed on 260 stool samples. Baseline characteristics regarding relevant demographics, place of residence and living conditions, clinical features including diarrhea, were collected using a standardized questionnaire. PRINCIPAL FINDINGS: The 137 patients were young (median age: 36 years) and severely immunocompromised (83.9% at WHO stage 3 or 4, median CD4 cell count: 41/mm3). Diarrhea was present in 43.0% of patients. Parasite infection was found in 78.8% of patients, infection with at least two species in 49.6%. Prevalence rates of protozoan and helminth infections were similar (54.7% and 58.4% respectively). Blastocystis sp. was the most frequent protozoa (26.3%). Cryptosporidium sp., Cytoisospora belli and microsporidia, found at low prevalence rates (6.6%, 4.4%, 2.9%, respectively), were described for the first time in Laos. Cryptosporidium sp. was associated with persistent diarrhea. Strongyloides stercoralis was the most prevalent helminth following Opisthorchis viverrini (20.4% and 47.5% respectively). The most immunocompromised patients, as assessed by a CD4 count ≤ 50 cells/mm3, were more likely to be infected with intestinal parasites. CONCLUSIONS/SIGNIFICANCE: HIV infection was mainly diagnosed at an advanced stage of immunosuppression in Lao patients. Intestinal parasite infections were highly prevalent regardless of their diarrheal status. Opportunistic infections were reported. Improving the laboratory diagnosis of intestinal parasite infections and the knowledge on their local risk factors is warranted.

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An age-stratified serosurvey against purified Salmonella enterica serovar Typhi antigens in the Lao People´s Democratic Republic.

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