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JMIR Public Health and Surveillance Jun 2021As a consequence of war and the collapse of the health system in Yemen, which prevented many people from accessing health facilities to obtain primary health care,...
BACKGROUND
As a consequence of war and the collapse of the health system in Yemen, which prevented many people from accessing health facilities to obtain primary health care, vaccination coverage was affected, leading to a deadly diphtheria epidemic at the end of 2017.
OBJECTIVE
This study aimed to describe the epidemiology of diphtheria in Yemen and determine its incidence and case fatality rate.
METHODS
Data were obtained from the diphtheria surveillance program 2017-2018, using case definitions of the World Health Organization. A probable case was defined as a case involving a person having laryngitis, pharyngitis, or tonsillitis and an adherent membrane of the tonsils, pharynx, and/or nose. A confirmed case was defined as a probable case that was laboratory confirmed or linked epidemiologically to a laboratory-confirmed case. Data from the Central Statistical Organization was used to calculate the incidence per 100,000 population. A P value <.05 was considered significant.
RESULTS
A total of 2243 cases were reported during the period between July 2017 and August 2018. About 49% (1090/2243, 48.6%) of the cases were males. About 44% (978/2243, 43.6%) of the cases involved children aged 5 to 15 years. Respiratory tract infection was the predominant symptom (2044/2243, 91.1%), followed by pseudomembrane (1822/2243, 81.2%). Based on the vaccination status, the percentages of partially vaccinated, vaccinated, unvaccinated, and unknown status patients were 6.6% (148/2243), 30.8% (690/2243), 48.6% (10902243), and 14.0% (315/2243), respectively. The overall incidence of diphtheria was 8 per 100,000 population. The highest incidence was among the age group <15 years (11 per 100,000 population), and the lowest incidence was among the age group ≥15 years (5 per 100,000 population). The overall case fatality rate among all age groups was 5%, and it was higher (10%) in the age group <5 years. Five governorates that were difficult to access (Raymah, Abyan, Sa'ada, Lahj, and Al Jawf) had a very high case fatality rate (22%).
CONCLUSIONS
Diphtheria affected a large number of people in Yemen in 2017-2018. The majority of patients were partially or not vaccinated. Children aged ≤15 years were more affected, with higher fatality among children aged <5 years. Five governorates that were difficult to access had a case fatality rate twice that of the World Health Organization estimate (5%-10%). To control the diphtheria epidemic in Yemen, it is recommended to increase routine vaccination coverage and booster immunizations, increase public health awareness toward diphtheria, and strengthen the surveillance system for early detection and immediate response.
Topics: Adolescent; Adult; Child; Child, Preschool; Data Analysis; Diphtheria; Disease Outbreaks; Female; Humans; Incidence; Male; Middle Aged; Yemen; Young Adult
PubMed: 34076583
DOI: 10.2196/27590 -
Clinical Infectious Diseases : An... Oct 2021Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment...
BACKGROUND
Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017-2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT.
METHODS
We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017-September 2018. Diphtheria was diagnosed based on the World Health Organization clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons.
RESULTS
We treated 709 patients with DAT; 98% (n = 696) recovered and were discharged. One-fourth (n = 170) had at least 1 adverse reaction. Common reactions included cough (n = 115, 16%), rash (n = 66, 9%), and itching (n = 37, 5%). Three percent (n = 18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT.
CONCLUSIONS
Outcomes for DAT-treated patients were excellent; mortality was <1%. Adverse reactions occurred in one-quarter of all patients, but most reactions were mild and resolved quickly. DAT can be safely administered in a setting with basic critical care, provided there is continuous patient monitoring during the infusion, staff training on management of adverse effects, and attention to safety precautions.
Topics: Bangladesh; Diphtheria; Diphtheria Antitoxin; Disease Outbreaks; Humans; Retrospective Studies
PubMed: 33245364
DOI: 10.1093/cid/ciaa1718 -
Clinical and Experimental Vaccine... Jan 2022In the present study, whole diphtheria toxin (dt) and fragment B (dtb) genes from Park William were cloned into , the purified expressed proteins were evaluated for...
PURPOSE
In the present study, whole diphtheria toxin (dt) and fragment B (dtb) genes from Park William were cloned into , the purified expressed proteins were evaluated for ultimately using as a candidate vaccine.
MATERIALS AND METHODS
The dt and dtb genes were isolated from bacterial strain ATCC (American Type Culture Collection) no. 13812. Plasmid pET29a+ was extracted by DNA-spin TM plasmid purification kit where genes were inserted using BamHI and HindIII-HF. Cloned pET29a+dt and pET29a+dtb plasmids were transformed into BL21(DE3)PlysS as expression host. The identity of the sequences was validated by blasting the sequence (BLASTn) against all the reported nucleotide sequences in the NCBI (National Center for Biotechnology Information) GenBank. Production of proteins in high yield by different types and parameters of fermentation to determine optimal conditions. Lastly, the purified concentrated rdtx and rdtb were injected to BALB/c mice and antibody titers were detected.
RESULTS
The genetic transformation of DH5α and BL21 with the pET-29a(+) carrying the dt and dtb genes was confirmed by colony polymerase chain reaction assay and were positive to grow on Luria-Bertani/kanamycin medium. The open reading frame of dt and dtb sequences consisted of 1,600 bp and 1,000 bp, were found to be 100% identical to dt and dtb sequence of (accession number KX702999.1 and KX702993.1) respectively. The optimal condition for high cell density is fed-batch fermentation production to express the rdtx and rdtb at 280 and 240 Lf/mL, dissolved oxygen was about 24% and 22% and the dry cell weight of bacteria was 2.41 g/L and 2.18 g/L, respectively.
CONCLUSION
This study concluded with success in preparing genetically modified two strains for the production of a diphtheria vaccine, and to reach ideal production conditions to achieve the highest productivity.
PubMed: 35223662
DOI: 10.7774/cevr.2022.11.1.12 -
AIDS (London, England) Dec 2023Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity...
OBJECTIVE
Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity of data on immune responses to Tdap in pregnant women with HIV (PWWH), and its impact on the protection of their infants has not been described.
METHODS
In an open label phase IV clinical trial in South Africa, we evaluated the immunogenicity and safety of Tdap in PWWH compared with HIV-uninfected women. Antigen-specific immunoglobulin G (IgG) to pertussis toxoid, filamentous haemagglutinin, pertactin, fimbriae, diphtheria and tetanus were measured by electrochemiluminescence-based multiplex assay.
RESULTS
Overall, 91 PWWH and 136 HIV-uninfected pregnant women were enrolled. All PWWH were on antiretroviral treatment and 94.5% had HIV viral loads <40 copies per millilitre. Antibody levels prevaccination were lower among PWWH compared with HIV-uninfected women for all antigens. At 1 month postvaccination PWWH compared with HIV-uninfected women had lower fold-increase and antibody concentrations for all epitopes. Also, a lower proportion of PWWH achieved ≥4-fold increase from pre to postvaccination for pertussis toxoid and pertactin, or diphtheria IgG levels ≥0.1 IU/ml and ≥1 IU/ml postvaccination. Adverse events postvaccination were similar in PWWH and HIV-uninfected.
CONCLUSION
Tdap vaccination was safe and immunogenic. PWHW had, however, attenuated humoral immune responses, which could affect the effectiveness of protecting their infants against pertussis compared with those born to women without HIV.ClinicalTrials.gov identifier: NCT05264662.
Topics: Infant; Female; Humans; Pregnancy; Diphtheria; Tetanus; Whooping Cough; Pregnant Women; HIV; HIV Infections; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccination; Immunoglobulin G; Parturition; Antibodies, Bacterial; Immunization, Secondary
PubMed: 37773052
DOI: 10.1097/QAD.0000000000003731 -
International Journal of Infectious... Apr 2022In recent years, outbreaks and a rising incidence of diphtheria, tetanus, and pertussis have occurred in Asia, particularly in older children. (Review)
Review
OBJECTIVES
In recent years, outbreaks and a rising incidence of diphtheria, tetanus, and pertussis have occurred in Asia, particularly in older children.
METHODS
A systematic search of MEDLINE and Embase was conducted from January 2000 to October 2020 to identify the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis in children and adolescents (aged 3-18 years) in Asia. The results were then related to vaccination schedules, booster coverage rates, pertussis source of infection, and booster immunogenicity, as identified by a pragmatic review. The International Prospective Register of Systematic Reviews (PROSPERO) registration: #CRD42020222445.
RESULTS
A total of 35 studies were included in this review. Limited data were reported on the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis. Data from studies reporting the incidence of diphtheria and pertussis exemplify the shift in epidemiology to older children/adolescents. Seroprevalence data suggest that immunity to pertussis and diphtheria is below the level of herd immunity in several Asian countries in this population.
CONCLUSION
The true burden of diphtheria, pertussis, and tetanus in children aged 3-18 years in Asia is unknown because of weak or absent nationwide surveillance systems. The available evidence highlights the inadequacies in immunity, either by gaps in a recommendation or suboptimal booster coverage, supporting the public health need for booster vaccinations in this population.
Topics: Adolescent; Antibodies, Bacterial; Asia; Child; Child, Preschool; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Immunization, Secondary; Poliovirus; Seroepidemiologic Studies; Systematic Reviews as Topic; Tetanus; Vaccines, Combined; Whooping Cough
PubMed: 35077880
DOI: 10.1016/j.ijid.2022.01.045 -
PloS One 2022Haiti has been experiencing a resurgence of diphtheria since December 2014. Little is known about the factors contributing to the spread and persistence of the disease...
BACKGROUND
Haiti has been experiencing a resurgence of diphtheria since December 2014. Little is known about the factors contributing to the spread and persistence of the disease in the country. Geographic information systems (GIS) and spatial analysis were used to characterize the epidemiology of diphtheria in Haiti between December 2014 and June 2021.
METHODS
Data for the study were collected from official and open-source databases. Choropleth maps were developed to understand spatial trends of diphtheria incidence in Haiti at the commune level, the third administrative division of the country. Spatial autocorrelation was assessed using the global Moran's I. Local indicators of spatial association (LISA) were employed to detect areas with spatial dependence. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were built to identify factors associated with diphtheria incidence. The performance and fit of the models were compared using the adjusted r-squared (R2) and the corrected Akaike information criterion (AICc).
RESULTS
From December 2014 to June 2021, the average annual incidence of confirmed diphtheria was 0.39 cases per 100,000 (range of annual incidence = 0.04-0.74 per 100,000). During the study period, diphtheria incidence presented weak but significant spatial autocorrelation (I = 0.18, p<0.001). Although diphtheria cases occurred throughout Haiti, nine communes were classified as disease hotspots. In the regression analyses, diphtheria incidence was positively associated with health facility density (number of facilities per 100,000 population) and degree of urbanization (proportion of urban population). Incidence was negatively associated with female literacy. The GWR model considerably improved model performance and fit compared to the OLS model, as indicated by the higher adjusted R2 value (0.28 v 0.15) and lower AICc score (261.97 v 267.13).
CONCLUSION
This study demonstrates that GIS and spatial analysis can support the investigation of epidemiological patterns. Furthermore, it shows that diphtheria incidence exhibited spatial variability in Haiti. The disease hotspots and potential risk factors identified in this analysis could provide a basis for future public health interventions aimed at preventing and controlling diphtheria transmission.
Topics: Diphtheria; Female; Haiti; Humans; Least-Squares Analysis; Spatial Analysis; Spatial Regression
PubMed: 35994502
DOI: 10.1371/journal.pone.0273398 -
Proceedings of the National Academy of... Jul 2022Bacterial pathogens acquire heme from the host hemoglobin as an iron nutrient for their virulence and proliferation in blood. Concurrently, they encounter cytotoxic-free...
Bacterial pathogens acquire heme from the host hemoglobin as an iron nutrient for their virulence and proliferation in blood. Concurrently, they encounter cytotoxic-free heme that escapes the heme-acquisition process. To overcome this toxicity, many gram-positive bacteria employ an ATP-binding cassette heme-dedicated efflux pump, HrtBA in the cytoplasmic membranes. Although genetic analyses have suggested that HrtBA expels heme from the bacterial membranes, the molecular mechanism of heme efflux remains elusive due to the lack of protein studies. Here, we show the biochemical properties and crystal structures of HrtBA, alone and in complex with heme or an ATP analog, and we reveal how HrtBA extracts heme from the membrane and releases it. HrtBA consists of two cytoplasmic HrtA ATPase subunits and two transmembrane HrtB permease subunits. A heme-binding site is formed in the HrtB dimer and is laterally accessible to heme in the outer leaflet of the membrane. The heme-binding site captures heme from the membrane using a glutamate residue of either subunit as an axial ligand and sequesters the heme within the rearranged transmembrane helix bundle. By ATP-driven HrtA dimerization, the heme-binding site is squeezed to extrude the bound heme. The mechanism sheds light on the detoxification of membrane-bound heme in this bacterium.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Bacterial Proteins; Corynebacterium diphtheriae; Heme; Membrane Transport Proteins; Protein Conformation; Protein Multimerization
PubMed: 35767641
DOI: 10.1073/pnas.2123385119 -
Microbiology Spectrum Jun 2023An increasing number of isolations of Corynebacterium diphtheriae has been observed in recent years in the archipelago of New Caledonia. We aimed to analyze the clinical...
An increasing number of isolations of Corynebacterium diphtheriae has been observed in recent years in the archipelago of New Caledonia. We aimed to analyze the clinical and microbiological features of samples with C. diphtheriae. All C. diphtheriae isolates identified in New Caledonia from May 2015 to May 2019 were included. For each case, a retrospective consultation of the patient files was conducted. Antimicrobial susceptibility phenotypes, gene and diphtheria toxin expression, biovar, and the genomic sequence were determined. Core genome multilocus sequence typing (cgMLST), 7-gene MLST, and search of genes of interest were performed from genomic assemblies. Fifty-eight isolates were included, with a median age of patients of 28 years (range: 9 days to 78 years). Cutaneous origin accounted for 51 of 58 (87.9%) isolates, and C. diphtheriae was associated with Staphylococcus aureus and/or Streptococcus pyogenes in three-quarters of cases. Half of cases came either from the main city Noumea (24%, 14/58) or from the sparsely populated island of Lifou (26%, 15/58). Six -positive isolates were identified, associated with recent travel to Vanuatu; 5 of these cases were linked and cgMLST confirmed recent transmission. Two cases of endocarditis in young female patients with a history of rheumatic fever involved -negative isolates. The 58 isolates were mostly susceptible to commonly used antibiotics. In particular, no isolate was resistant to the first-line molecules amoxicillin or erythromycin. Resistance to tetracycline was found in a genomic cluster of 17 (29%) isolates, 16 of which carried the gene. There were 13 cgMLST sublineages, most of which were also observed in the neighboring country Australia. Cutaneous infections may harbor nontoxigenic C. diphtheriae isolates, which circulate largely silently in nonspecific wounds. The possible introduction of -positive strains from a neighboring island illustrates that diphtheria surveillance should be maintained in New Caledonia, and that immunization in neighboring islands must be improved. Genomic sequencing uncovers how genotypes circulate locally and across neighboring countries. The analysis of C. diphtheriae from the tropical archipelago of New Caledonia revealed a high genetic diversity with sublineages that may be linked to Polynesia, Australia, or metropolitan France. Genomic typing allowed confirming or excluding suspected transmission events among cases and contacts. A highly prevalent tetracycline-resistant sublineage harboring the gene was uncovered. Toxigenic isolates were observed from patients returning from Vanuatu, showing the importance of improving vaccination coverage in settings where it is insufficient. This study also illustrates the importance for diphtheria surveillance of the inclusion of isolates from cutaneous sources in addition to respiratory cases, in order to provide a more complete epidemiological picture of the diversity and transmission of C. diphtheriae.
Topics: Female; Humans; Corynebacterium diphtheriae; Diphtheria; Multilocus Sequence Typing; New Caledonia; Retrospective Studies; Corynebacterium; Genomics; Anti-Bacterial Agents; Tetracycline; Protein Synthesis Inhibitors
PubMed: 37042786
DOI: 10.1128/spectrum.04616-22 -
Iranian Journal of Microbiology Aug 2022Blocking the attachment of diphtheria toxins to host cells through the intact receptor binding site ( B) was the initial mechanism of action of the diphtheria vaccine....
BACKGROUND AND OBJECTIVES
Blocking the attachment of diphtheria toxins to host cells through the intact receptor binding site ( B) was the initial mechanism of action of the diphtheria vaccine. Diphtheria outbreaks in populations with good vaccination coverage can be caused by mutations or changes in the genetic structure of the B protein. The aim of this study was to characterize the Tox B protein produced by isolated from 2018 to 2019 in patients in Jakarta who had already received the diphtheria vaccine.
MATERIALS AND METHODS
Of the 89 throat swab specimens of patients with a clinical diagnosis of diphtheria, 10 were positive for diphtheria and toxin. PCR was used to amplify the B DNA fragment in the 10 positive isolates. DNA sequencing was conducted with overlapping primers and the DNA sequences were analysed by using SeqScape V2.7.
RESULTS
Of the 10 isolates, nine isolate showed a DNA mutation (G30A), but the mutation did not change the amino acid encoding arginin (silent mutation). Our findings indicate that the efficacy of the diphtheria vaccine used in Indonesia has not decreased because of mutations in the B genes not change the amino acid.
CONCLUSION
Overall, there are no amino acid changes in the B protein, indicating that the outbreaks are not affected by mutation in B. Another possible mechanism - overexpression of the toxin - is likely responsible for causing diphtheria in patients who have a complete history of immunization in Indonesia.
PubMed: 36721501
DOI: 10.18502/ijm.v14i4.10248 -
Frontiers in Public Health 2019() is a relatively rare pathogen in most Western countries. While toxin producing strains can cause pharyngeal diphtheria with potentially fatal outcomes, the more... (Review)
Review
() is a relatively rare pathogen in most Western countries. While toxin producing strains can cause pharyngeal diphtheria with potentially fatal outcomes, the more common presentation is wound infections. The diphtheria toxin is encoded on a prophage and can also be carried by and . Currently, across Europe, infections are mainly diagnosed in travelers and refugees from regions where diphtheria is more endemic, patients from urban areas with poor hygiene, and intravenous drug users. About half of the cases are non-toxin producing isolates. Rapid identification of the bacterial pathogen and toxin production is a critical element of patient and outbreak management. Beside the immediate clinical management of the patient, public health agencies should be informed of toxigenic diagnoses as soon as possible. The collection of case-related epidemiological data from the patient is often challenging due to language barriers and social circumstances. However, information on patient contacts, vaccine status and travel/refugee route, where appropriate, is critical, and should be documented. In addition, isolates should be characterized using high resolution typing, in order to identify transmissions and outbreaks. In recent years, whole genome sequencing (WGS) has become the gold standard of high-resolution typing methods, allowing detailed investigations of pathogen transmissions. De-centralized sequencing strategies with redundancy in sequencing capacities, followed by data exchange may be a valuable future option, especially since WGS becomes more available and portable. In this context, the sharing of sequence data, using public available platforms, is essential. A close interaction between microbiology laboratories, treating physicians, refugee centers, social workers, and public health officials is a key element in successful management of suspected outbreaks. Analyzing bacterial isolates at reference centers may further help to provide more specialized microbiological techniques and to standardize information, but this is also more time consuming during an outbreak. Centralized communication strategies between public health agencies and laboratories helps considerably in establishing and coordinating effective surveillance and infection control. We review the current literature on high-resolution typing of and share our own experience with the coordination of a Swiss-German outbreak.
PubMed: 31497588
DOI: 10.3389/fpubh.2019.00235