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Rodents are known reservoirs for a diverse group of zoonotic pathogens that can pose a threat to human health. Therefore, it is crucial to investigate these pathogens to institute prevention and control measures. To achieve this, the current study was conducted to investigate the frequency of different parasites in commensal rodents in Qatar. A total of 148 rodents, including Rattus norvegicus, Rattus rattus, and Mus musculus were captured using traps placed in different habitats such as agricultural and livestock farms, residential areas, and other localities. Blood, feces, ectoparasite, and visceral organs were collected for gross, microscopic, immunological, and molecular analysis. The study identified 10 different parasites, including Capillaria annulosa, Eimeria spp., Giardia spp., Hymenolepis diminuta, Mastophorus muris, Ornithonyssus bacoti, Taenia taeniaeformis, Toxoplasma gondii, Trypanosoma lewisi, and Xenopsylla astia. Overall, 62.2% of the rodents tested positive for at least one parasite species. Helminths were found to be the most prevalent parasites (46.0%), followed by ectoparasites (31.8%), and protozoa (10.1%). However, individually, X. astia was the most prevalent (31.8%), whereas C. annulosa was the least common (0.7%). The prevalence of X. astia and H. diminuta significantly differed between habitats (p

ABSTRACTMonkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus, including ecology and evolution, possible drivers of transmission, clinical features and management, knowledge gaps, and research priorities to reduce the disease transmission. The origin, reservoir(s) and the sylvatic cycle of the virus in the natural ecosystem are yet to be confirmed. Humans acquire the infection through contact with infected animals, humans, and natural hosts. The major drivers of disease transmission include trapping, hunting, bushmeat consumption, animal trade, and travel to endemic countries. However, in the 2022 epidemic, the majority of the infected humans in non-endemic countries had a history of direct contact with clinical or asymptomatic persons through sexual activity. The prevention and control strategies should include deterring misinformation and stigma, promoting appropriate social and behavioural changes, including healthy life practices, instituting contact tracing and management, and using the smallpox vaccine for high-risk people. Additionally, longer-term preparedness should be emphasized using the One Health approach, such as systems strengthening, surveillance and detection of the virus across regions, early case detection, and integrating measures to mitigate the socio-economic effects of outbreaks.

This study assessed the association between multimorbidity and mortality from COVID-19 in the Middle East and North Africa region, where such data are scarce. We conducted a cross-sectional study using data of all cases with COVID-19 reported to the Ministry of Public Health of Qatar from March to September 2020. Data on pre-existing comorbidities were collected using a questionnaire and multimorbidity was defined as having at least two comorbidities. Proportions of deaths were compared by comorbidity and multimorbidity status and multivariable logistic regression analyses were carried out. A total of 92,426 participants with a mean age of 37.0 years (SD 11.0) were included. Mortality due to COVID-19 was associated with gastrointestinal diseases (aOR 3.1, 95% CI 1.16–8.30), respiratory diseases (aOR 2.9, 95% CI 1.57–5.26), neurological diseases (aOR 2.6, 95% CI 1.19–5.54), diabetes (aOR 1.8, 95% CI 1.24–2.61), and CVD (aOR 1.5, 95% CI 1.03–2.22). COVID-19 mortality was strongly associated with increasing multimorbidity; one comorbidity (aOR 2.0, 95% CI 1.28–3.12), two comorbidities (aOR 2.8, 95% CI 1.79–4.38), three comorbidities (aOR 6.0, 95% 3.34–10.86) and four or more comorbidities (aOR 4.15, 95% 1.3–12.88). This study demonstrates a strong association between COVID-19 mortality and multimorbidity in Qatar.

The increasing frequency of spillover of zoonotic pathogens from animals to humans in recent years highlights a need to develop a more comprehensive framework to investigate and prevent pathogens of animal origin, including rodents. Despite the presence of several species of rodents, there is a certain knowledge gap regarding rodent-borne zoonoses in Qatar. The current review provides an update on rodent-borne zoonoses in Qatar, its possible drivers and transmission dynamics, and proposed a One Health framework for intervention. Following an extensive literature review, we conducted a field investigation. Then the qualitative information and knowledge gaps were addressed with a virtual discussion with national, regional, and international experts in the relevant field. Overall, Rattus norvegicus population was found to be more prevalent, followed by Rattus rattus, and M. musculus, which are mainly found in animal farms, followed by agricultural farms, residential areas, and other facilities. Over 50% of rodents carry at least one pathogen of public health importance. Several pathogens were identified at the human, animal, and ecosystem interface, which can be mediated in transmission by rodents. E. coli, Salmonella spp., and Campylobacter spp. are the frequently reported bacteria. Hymenolepis spp., Cryptosporidium spp., Giardia spp., Entamoeba spp., and Toxoplasma spp. are the major parasites. In addition, many vectors, including Ornithonyssus bacoti and Xenopsylla astia were reported in this country. Based on the changes over the past 70 years in Qatar, seven drivers have been identified, which could be important in rodent-borne disease emergences, such as the Oil and gas revolution, fast population growth, rapid urbanization, importation of food and agricultural products, agricultural and livestock development, farm biosecurity, and stray animals. The experts emphasized that mixed-species animal farming with poor biosecurity and management can be associated to increase the risk of zoonoses. Moreover, rapid urbanization and global climate change together can alter the ecosystem of the country and impact on vectors and vector-borne diseases. Finally, the One Health framework has been proposed for the surveillance, and mitigation of any future spillover or epidemic of rodent-borne zoonoses.

One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022–2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface.

Rodents serve as an important reservoir or carrier of zoonotic pathogens on a global scale [...]

Abstract Background Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen. Methods Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique. Results Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation. Conclusions Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.

There is inconclusive evidence whether pregnancy exacerbates COVID-19 symptoms or not, and scarce data from the Middle East and North Africa region. The aim of this study was to investigate the association between pregnancy and COVID-19 symptoms in Qatar. This cross-sectional study was carried out using data of all women with confirmed COVID-19, comparing women of child-bearing age (18-49 years). Data of all COVID-19 cases were collected by the Ministry of Public Health (MoPH) in Qatar, between March and September 2020. Symptoms were compared by pregnancy status and classified into moderate and severe. Multivariable logistic and Poisson regression was carried out to investigate the association between pregnancy and severity of COVID-19 symptoms. During the study period, 105 744 individuals were diagnosed with COVID-19, of which 16 908 were women of childbearing age. From that sample, 799 women were pregnant (mean age 29.9 years (SD 5.2)) and 16109 women were not pregnant (mean age 33.1 years (SD 7.8)). After multivariable logistic regression, pregnancy was associated with 1.4-fold higher odds of reporting any symptoms of COVID-19 (OR 1.41, 95% CI 1.18-1.68), and 1.3-fold higher odds of reporting shortness of breath (OR 1.29, 95% CI 1.02-1.63). In a multivariable Poisson regression, pregnancy was also associated with a higher count of symptoms (IRR 1.03, 95%CI 0.98-1.08), although with weak evidence against the null hypothesis. Our findings suggest that, in this setting, pregnant women are more likely to have symptomatic COVID-19, and shortness of breath, compared to women with no pregnancy.

Qatar is a peninsular country with predominantly hot and humid weather, with 88% of the total population being immigrants. As such, it leaves the country liable to the introduction and dissemination of vector-borne diseases, in part due to the presence of native arthropod vectors. Qatar's weather is expected to become warmer with the changing climatic conditions across the globe. Environmental factors such as humidity and temperature contribute to the breeding and distribution of different types of mosquito species in a given region. If proper and timely precautions are not taken, a high rate of particular mosquito species can result in the transmission of various vector-borne diseases. In this study, we analyzed the environmental impact on the probability of occurrence of different mosquito species collected from several different sites in Qatar. The Naive Bayes model was used to calculate the posterior probability for various mosquito species. Further, the resulting Naive Bayes predictions were used to define the favorable environmental circumstances for identified mosquito species. The findings of this study will help in the planning and implementation of an active surveillance system and preventive measures to curb the spread of mosquitoes in Qatar.

Abstract The overarching objective of this study was to provide the descriptive epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar by addressing specific research questions through a series of national epidemiologic studies. Sources of data were the centralized and standardized national databases for SARS-CoV-2 infection. By July 10, 2020, 397,577 individuals had been tested for SARS-CoV-2 using polymerase-chain-reaction (PCR), of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI 27.8–28.1%). As of July 5, case severity rate, based on World Health Organization (WHO) severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Age was by far the strongest predictor of severe, critical, or fatal infection. PCR positivity of nasopharyngeal/oropharyngeal swabs in a national community survey (May 6–7) including 1,307 participants was 14.9% (95% CI 11.5–19.0%); 58.5% of those testing positive were asymptomatic. Across 448 ad-hoc testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI 13.7–17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI 23.3–24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI 46.2–48.5%) in those who had at least one PCR positive result, but 91.3% (95% CI 89.5–92.9%) among those who were PCR positive > 3 weeks before serology testing. Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to growing immunity levels in the population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR

Abstract Background The increasing antimalarial drug resistance is a significant hindrance to malaria control and elimination programs. For the last six decades, chloroquine (CQ) plus pyrimethamine remains the first-line treatment for P. vivax malaria. Regions where both P. falciparum and P. vivax co-exist, P. vivax is exposed to antifolate drugs due to either misdiagnosis or improper treatment that causes selective drug pressure to evolve. Therefore, the present study aims to estimate antimalarial drug resistance among the complicated and uncomplicated P. vivax patients. Methods A total of 143 P. vivax malaria positive patients were enrolled in this study, and DNA was isolated from their blood samples. Pvcrt-o, Pvmdr-1, Pvdhps, and Pvdhfr genes were PCRs amplified, and drug resistance-associated gene mutations were analyzed. Statistical analysis of the drug resistance genes and population diversity was performed using MEGA vs. 7.0.21 and DnaSP v software. Results Among the CQ resistance marker gene Pvcrt-o, the prevalence of K10 insertion was 17.5% (7/40) and 9.5% (7/73) of complicated and uncomplicated P vivax group isolates respectively. In Pvmdr-1, double mutant haplotype (M 958 /L 1076 ) was found in 99% of the clinical isolates. Among the pyrimethamine resistance-associated gene Pvdhfr, the double mutant haplotype I13P33F57 R 58 T61 N 117 I173 was detected in 23% (11/48) in complicated and 20% (17/85) in uncomplicated group isolates. In the sulphadoxine resistance-associated Pvdhps gene, limited polymorphism was observed with the presence of a single mutant (D459A) among 16 and 5% of the clinical isolates in the complicated and uncomplicated group respectively. Conclusion The study presents the situations of polymorphism in the antimalarial drug resistance-associated genes and emphasizes the need for regular surveillance. It is imperative for the development of suitable antimalarial drug policy in India.

Abstract Background In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. Methods We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. Results Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P = 0.002) and women with LGSIL (44%; P = 0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (P = 0.002 and P = 0.001, respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection. Conclusion Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

There is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibody titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. A total of 300 male participants who received any of the following vaccines BNT162b2/Comirnaty, mRNA-1273, ChAdOx1-S/Covishield, COVID-19 Vaccine Janssen/Johnson, or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan–Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibody titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. Participants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13,720.9 AU/mL (IQR 6426.5 to 30,185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/mL; IQR, 3757.9 to 16,577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7–5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2–4.5 months) and 7.63 months (IQR, 6.3–8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. This evidence on anti-S IgG antibody titers should be considered for informing decisions on the durability of the neutralizing activity and thus protection against infection after the full course of primary vaccination in individuals receiving different type (mRNA verus non-mRNA) vaccines and those with natural infection.

Since its emergence in China in December 2019, COVID-19 remains the recent leading disease of concern drawing the public health attention globally. The disease is known of viral origin and zoonotic nature originating from animals. However, to date neither the source of the spillover nor the intermediate hosts are identified. Moreover, the public health situation is intermittently aggravated by identification of new animals susceptible to the SARS-CoV-2 infection, potentially replicating the virus and maintaining intra and interspecies spread of the disease. Although the role of a given animal and/or its produce is important to map the disease pattern, continuous efforts should be undertaken to further understand the epidemiology of SARS-CoV-2, a vital step to establish effective disease prevention and control strategy. This manuscript attempted to review updates regarding SARS-CoV-2 infection at the human-animal interface with consideration to postulations on the genetic relatedness and origin of the different SARS-CoV-2 variants isolated from different animal species. Also, the review addresses the possible role of different animal species and their produce in transmission of the disease. Also, the manuscript discussed the contamination potentiality of the virus and its environmental stability. Finally, we reviewed the currently instituted measures to prevent and manage the spread of SARS-CoV-2 infection. The manuscript suggested the One Health based control measures that could prove of value for the near future.

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.

Abstract Background Malaria is one of the important vector-borne diseases with high fatality rates in tropical countries. The pattern of emergence and spread of novel antigenic variants, leading to escape of vaccine-induced immunity might be factors responsible for severe malaria. A high level of polymorphism has been reported among malarial antigens which are under selection pressure imposed by host immunity. There are limited reports available on comparative stage-specific genetic diversity among Plasmodium vivax candidate genes in complicated vivax malaria. The present study was planned to study genetic diversity (Pvcsp and Pvs25) among complicated and uncomplicated P. vivax isolates. Methods Pvcsp and Pvs2-specific PCRs and DNA sequencing were performed on P. vivax PCR positive samples. Genetic diversity was analysed using appropriate software. Results The present study was carried out on 143 P. vivax clinical isolates, collected from Postgraduate Institute of Medical Education and Research, Chandigarh. Among the classic and variant types of Pvcsp, the VK210 (99%; 115/116) was found to be predominant in both complicated and uncomplicated group isolates. Out of the various peptide repeat motifs (PRMs) observed, GDRADGQPA (PRM1) and GDRAAGQPA (PRM2) was the most widely distributed among the P. vivax isolates. Whereas among the Pvs25 isolates, 100% of double mutants (E97Q/I130T) in both the complicated (45/45) as well as in the uncomplicated (81/81) group was observed. Conclusion An analysis of genetic variability enables an understanding of the role of genetic variants in severe vivax malaria.

Abstract Background The present study aimed to evaluate the management of severe malaria at Gezira State hospitals in Sudan by assessing hospital readiness, health care provider knowledge and the care received by severe malaria patients. Methods A cross-sectional descriptive study was performed to assess the severe malaria management practices at hospitals level in Gezira State. The study population included hospitals, health care providers and patients. Data was collected using checklists and structured questionnaires. Results A total of 20 hospitals, 158 health care providers and 370 patients were included in the study. Out of the total hospitals, 95% (19/20) were providing 24 h outpatient services, 65% (13/20) had ICU units, while triage system was found in only 35% (7/20) of hospitals. From all hospitals evaluated, 90% (18/20) were suffering from shortage of staff, especially doctors. About half of the health care providers (46.7%) did not receive severe malaria management training. The average knowledge score among health care providers was 55.4%. Microscopy was available in all hospitals (100%), while rapid diagnostic test, complete blood count and renal function test were available in 15 hospitals (75%). Fever was the most presenting symptom (97.8%) followed by repeated vomiting (51.4%), convulsion in children (24.3%) and prostration in adult (57.9%). Correctly diagnosed patients were 68.9%. Essential tests were done for only 11.1% of patients. Majority of patients (91.7%) were treated with quinine, 5.9% received artemether, while 2.4% were treated with artemether–lumefantrine. Those who received both the correct dose and dosing regimen were 53.8%. The overall compliance to guidelines was 2.2%. Conclusion This study highlights the fact that management of severe malaria at hospital level was suboptimal with serious shortcomings in the different aspects of care particularly in specialized hospitals. Technical staff was inadequate, hospitals were anguish from defective emergency services, and most patients were not treated according to the national guidelines.

(1) Background: Qatar does not have any indigenous cases of dengue; however, the influx of immigrants from dengue endemic countries, the environment, and climate suitability for Aedes vector mosquitoes suggest a potential risk for local transmission. In this study, we investigated various demographic factors to determine the epidemiological features of dengue in Qatar. (2) Methods: In the present retrospective study, we reviewed dengue notification data received at the national surveillance system, Ministry of Public Health, Qatar, between January 2013, and December 2021, and we analyzed the incidence of the dengue disease burden to identify factors that could contribute to the dissemination of the disease in Qatar. (3) Results: A total of 166 dengue fever seropositive cases were recorded during the study period in Qatar. The mean incidence was estimated to be 0.7/100,000 population, which increased from 0.7/100,000 in 2013 to 1.5/100,000 in 2019. The majority of the cases were male, between 20–50 years of age and notified during the hot months (June-September). Most of the patients had fever without hemorrhagic manifestations. There were no dengue related deaths during 2013–2021. (4) Conclusion: Dengue fever occurred more frequently among men than women, and its incidence is low among Qatari nationals. The presence of the most efficient vector, Aedes aegypti, in Qatar, if confirmed, poses a risk of local outbreaks. Therefore, regular vector surveillance is needed to assess the distribution, biting habits and abundance of vector mosquito species and the risk for mosquito-borne diseases.

COVID-19 emerged from China in December 2019 and during 2020 spread to every continent including Antarctica. The coronavirus, SARS-CoV-2, has been identified as the causative pathogen, and its spread has stretched the capacities of healthcare systems and negatively affected the global economy. This review provides an update on the virus, including the genome, the risks associated with the emergence of variants, mode of transmission, immune response, COVID-19 in children and the elderly, and advances made to contain, prevent and manage the disease. Although our knowledge of the mechanics of virus transmission and the immune response has been substantially demystified, concerns over reinfection, susceptibility of the elderly and whether asymptomatic children promote transmission remain unanswered. There are also uncertainties about the pathophysiology of COVID-19 and why there are variations in clinical presentations and why some patients suffer from long lasting symptoms—“the long haulers.” To date, there are no significantly effective curative drugs for COVID-19, especially after failure of hydroxychloroquine trials to produce positive results. The RNA polymerase inhibitor, remdesivir, facilitates recovery of severely infected cases but, unlike the anti-inflammatory drug, dexamethasone, does not reduce mortality. However, vaccine development witnessed substantial progress with several being approved in countries around the globe.

Waning immunity following administration of mRNA-based COVID-19 vaccines remains a concern for many health systems. We undertook a study to determine if recent reports of waning for severe disease could have been attributed to design-related bias by conducting a study only among those detected with a first SARS-CoV-2 infection. We used a matched case-control study design with the study base being all individuals with first infection with SARS-CoV-2 reported in the State of Qatar between 1 January 2021 and 20 February 2022. Cases were those detected with first SARS-CoV-2 infection requiring intensive care (hard outcome), while controls were those detected with first SARS-CoV-2 infection who recovered without the need for intensive care. Cases and controls were matched in a 1:30 ratio for the calendar month of infection and the comorbidity category. Duration and magnitude of conditional vaccine effectiveness against requiring intensive care and the number needed to vaccinate (NNV) to prevent one more case of COVID-19 requiring intensive care was estimated for the mRNA (BNT162b2/mRNA-1273) vaccines. Conditional vaccine effectiveness against requiring intensive care was 59% (95% confidence interval (CI), 50 to 76) between the first and second dose, and strengthened to 89% (95% CI, 85 to 92) between the second dose and 4 months post the second dose in persons who received a primary course of the vaccine. There was no waning of vaccine effectiveness in the period from 4 to 6, 6 to 9, and 9 to 12 months after the second dose. This study demonstrates that, contrary to mainstream reports using hierarchical measures of effectiveness, conditional vaccine effectiveness against requiring intensive care remains robust till at least 12 months after the second dose of mRNA-based vaccines.

ABSTRACT Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.

Abstract Background In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19–24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level. Methods We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein–protein and mRNA–miRNA networks to identify highly regulated miRNA. Results In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60–71% and 69–81% respectively and area under curve (AUC) of 0.7 (p

Introduction: Malaria is among the most significant travel-related infections encountered by travelers to endemic countries in terms of morbidity and mortality. In Qatar, imported malaria has increased over the last 5 years; 493 travel-related cases were confirmed in 2016. In the current study, the knowledge of malaria chemoprophylaxis among physicians in the State of Qatar was assessed. Methods: This was a cross-sectional study conducted during a national travel health workshop at the Ministry of Public Health, Qatar. Physicians participating in the workshop from different national healthcare institutions providing travel medicine services were invited to voluntarily complete a self-administered, structured questionnaire. Results: Forty-two medical doctors participated in the study (92 response rate). Based on their specialty, almost two-thirds (64.3%) of the participants were family medicine physicians, and one-fifth (21.43%) were general practitioners. Furthermore, most of the doctors were untrained in travel medicine. The majority of participants demonstrated a good knowledge of the malaria parasite (100%), Plasmodium species (64.3%), incidence (83.3%), transmission (66.7%), and drug-resistance (95.2%) of malaria. Additionally, most physicians (>90) were knowledgeable about the major features of severe or complicated malaria as well as malaria prevention and chemoprophylaxis. Conclusion: This study highlights several areas of good knowledge on travel-related malaria prophylaxis and prevention among the study participants; however, there are still a few knowledge gaps that require mitigation. Continuing training programs on malaria prevention in travelers will sustain this good level of knowledge among physicians and improve the quality of pre-travel advice provided by travel medicine practitioners in Qatar.

Abstract Background Cervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16INK4a in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia. Methods A total of 90 samples, diagnosed for cervical cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies using automated immunohistochemistry platform (ASLink 48-DAKO). Results Immunohistochemical protein expression of p16INK4a positivity was found to be highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The majority of cases (97.4%) were p16INK4a positive in the age group 41–60 years. In addition, a statistically significant difference between p16INK4a and HPV was observed among total cervical tumor cases and SCC cases. Conclusions As expected staining of invasive cervical cancer with anti-HPV showed rare positivity because HPV heralds active infection in dysplastic lesions and not of frank cervical carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in SCC and other cervical tumors.

Background Malaria is a global public health problem across Africa, Asia and Americas. In the recent past, a dramatic increase in global air travel networks and connectivity contributed to increased risk of contracting malaria. Airline cabin crew travelling to malaria high-risk countries are at increased risk of contracting the disease. Awareness plays an important role in prevention of malaria among the crew by having high degree of knowledge of disease and adhering to the protective measures advised. In this study we aimed to evaluate the knowledge about malaria, risk assessment, prevention and prophylaxis of malaria among a major commercial airline crew member. Methods This was qualitative cross-sectional study based on structured questionnaire conducted among crew members in a major commercial airline. We have deployed purposive sampling to pick 40 crew members who frequently travel to malaria endemic areas as part of their duty. The questionnaire contained both close and open-ended questions, which was given to the participants via the receptionists at the medical centre of the airline. Results Most of the cabin crew members were aware about malaria and its causes, symptoms, prevention and effective treatment. Many of the participants have been taking necessary precautions to ensure that they are safe but not all possible measures. Conclusions The baseline data should be further confirmed to assist in giving the appropriate recommendations to help combat the issue of protecting cabin crews from the risks of Malaria.

The current study was undertaken to estimate the morphometric pattern of three commensal rodents, i.e., Mus musculus, Rattus norvegicus, and Rattus rattus in Qatar. One hundred forty-eight rodents were captured from different facilities throughout Qatar. The captured rodents were used to identify the external body and cranio-mandibular morphometry. The study found that R. norvregicus was the most prevalent (n = 120, 81%, 95% CI: 73.83–87.05). Most of the rodents were collected from Al Rayan municipality (n = 92, 62%), were adults (n = 138, 93.2%, 95% CI: 87.92–96.71), and were from livestock farms (n = 79, 49%, 95% CI: 41.02–57.65). The rodents’ average body weights were 18.8 ± 2.2 gm, 264.3 ± 87.5 gm, and 130 ± 71.3 gm for M. musculus, R. norvegicus, and R. rattus, respectively. The research found that the studied rodents are smaller than those of other countries such as Turkey, Tunisia, and Iran. The study of morphometry is a useful tool for the traditional identification of small mammal species, including rodents. The average morphometric measurements of the external body and skull were normally distributed and can be used as a reference of R. norvegicus and R. rattus for Qatar. A further comprehensive study is required to investigate the rodent population index, eco-friendly control program, and public health importance in Qatar.

Abstract Background The emergence of extended-spectrum beta-lactamase (ESBL)-producing isolates has important clinical and therapeutic implications. High prevalence of ESBL-producing Enterobacteriaceae has been reported in the literature for clinical samples from a variety of infection sites. The present study was undertaken to evaluate the prevalence of ESBL-producing Enterobacteriaceae, and to perform molecular characterization and antimicrobial susceptibility testing of clinical isolates from patients admitted to the intensive care units at Hamad Medical Corporation, Doha, Qatar, from November 2012 to October 2013. Methods A total of 629 Enterobacteriaceae isolates were included in the study. Identification and susceptibility testing was performed using Phoenix (Becton Dickinson) and the ESBL producers were confirmed by double-disk potentiation as recommended by the Clinical and Laboratory Standards Institute. Molecular analysis of the ESBL producers was performed by polymerase chain reaction. Results In total, 109 isolates (17.3 %) were confirmed as ESBL producers and all were sensitive to meropenem in routine susceptibility assays. Most of the ESBL producers (99.1 %) were resistant to amoxicillin/clavulanic acid and ceftriaxone and 93.6 % were resistant to cefepime. Among the ESBL-producing genes, bla CTX-M (66.1 %) was the most prevalent, followed by bla SHV (53.2 %) and bla TEM (40.4 %). Conclusions These findings show the high prevalence of ESBL-producing Enterobacteriaceae within the intensive care units at Hamad Medical Corporation, Qatar, and emphasize the need for judicious use of antibiotics and the implementation of strict infection control measures.

Rodents carry many ectoparasites, such as ticks, lice, fleas, and mites, which have potential public health importance. Middle Eastern countries are hotspots for many emerging and re-emerging infectious diseases, such as plague, leishmaniasis, Crimean Congo hemorrhagic fever, and Q fever, due to their ecological, socioeconomic, and political diversity. Rodent ectoparasites can act as vectors for many of these pathogens. Knowledge of rodent ectoparasites is of prime importance in controlling rodent ectoparasite-borne zoonotic diseases in this region. The current systematic review and meta-analysis performs a comprehensive synthesis of the available knowledge, providing an evidence-based overview of the ectoparasites detected on rodents in Middle Eastern countries. Following a systematic search in Pubmed, Scopus, and Web of Science, a total of 113 published articles on rodent ectoparasites were studied and analyzed. A total of 87 rodent species were documented, from which Mus musculus, Rattus norvegicus, and Rattus rattus were found to be the most common. Fleas were the most reported ectoparasites (87 articles), followed by mites (53), ticks (44), and lice (25). Xenopsylla cheopis, Polyplax spinulosa, Ornithonyssus bacoti, and Hyalomma rhipicephaloides were the most commonly described fleas, lice, mites, and ticks, respectively. Based on the reviewed articles, the median flea, louse, mite, and tick indices were highest in Israel (4.15), Egypt (1.39), Egypt (1.27), and Saudi Arabia (1.17), respectively. Quantitative meta-analysis, using a random-effects model, determined the overall pooled flea prevalence in the Middle East as 40% (95% CI: 25–55, I2 = 100%, p < 0.00001), ranging between 13% (95% CI: 0–30, I2 = 95%, p < 0.00001) in Iran and 59% (95% CI: 42–77, I2 = 75%, p < 0.00001) in Israel. The overall pooled louse prevalence was found to be 30% (95% CI: 13–47, I2 = 100%, p < 0.00001), ranging between 25% in Iran (95% CI: 1–50, I2 = 99%) and 38% in Egypt (95% CI: 7–68, I2 = 100%). In the case of mites, the pooled prevalence in this region was 33% (95% CI: 11–55, I2 = 100%, p < 0.00001), where the country-specific prevalence estimates were 30% in Iran (95% CI: 4–56, I2 = 99%) and 32% in Egypt (95% CI: 0–76, I2 = 100%). For ticks, the overall prevalence was found to be 25% (95% CI: 2–47, I2 = 100%, p < 0.00001), ranging from 16% in Iran (95% CI: 7–25, I2 = 74%) to 42% in Egypt (95% CI: 1–85, I2 = 100%). The control of rodent ectoparasites should be considered to reduce their adverse effects. Using the One Health strategy, rodent control, and precisely control of the most common rodent species, i.e., Mus musculus, Rattus norvegicus, and Rattus rattus, should be considered to control the rodent-borne ectoparasites in this region.

Rodents can be a source of zoonotic helminths in the Middle East and also in other parts of the world. The current systematic review aimed to provide baseline data on rodent helminths to recognize the threats of helminth parasites on public health in the Middle East region. Following a systematic search on PubMed, Scopus, and Web of Science, a total of 65 research studies on rodent cestodes, nematodes, and trematodes, which were conducted in the countries of the Middle East, were analyzed. The study identified 44 rodent species from which Mus musculus, Rattus norvegicus, and Rattus rattus were most common (63%) and recognized as the primary rodent hosts for helminth infestation in this region. Cestodes were the most frequently reported (n = 50), followed by nematodes (49), and trematodes (14). The random effect meta-analysis showed that the pooled prevalence of cestode (57.66%, 95%CI: 34.63–80.70, l2% = 85.6, p < 0.001) was higher in Saudi Arabia, followed by nematode (56.24%, 95%CI: 11.40–101.1, l2% = 96.7, p < 0.001) in Turkey, and trematode (15.83%, 95%CI: 6.25–25.1, l2% = 98.5, p < 0.001) in Egypt. According to the overall prevalence estimates of individual studies, nematodes were higher (32.71%, 95%CI: 24.89–40.54, l2% = 98.6, p < 0.001) followed by cestodes (24.88%, 95%CI: 19.99–29.77, l2% = 94.9, p < 0.001) and trematodes (10.17%, 95%CI: 6.7–13.65, l2% = 98.3, p < 0.001) in the rodents of the Middle East countries. The review detected 22 species of helminths, which have zoonotic importance. The most frequent helminths were Capillaria hepatica, Hymenolepis diminuta, Hymenolepis nana, and Cysticercus fasciolaris. There was no report of rodent-helminths from Bahrain, Jordan, Lebanon, Oman, United Arab Emirates, and Yemen. Furthermore, there is an information gap on rodent helminths at the humans-animal interface level in Middle East countries. Through the One Health approach and countrywide detailed studies on rodent-related helminths along with their impact on public health, the rodent control program should be conducted in this region.

Background and Objectives Imported malaria poses a serious public health problem in Qatar because its population is “naïve” to such infection; where local transmission might lead to serious life-threatening infection and might even trigger epidemics. Methods This study is a retrospective review of the imported malaria cases in Qatar reported by the malaria surveillance program at the Ministry of Public Health (MoPH), during the period between January 2008 and December 2015. All cases were imported and underwent parasitological confirmation through microscopy. Results A total of 4092 malaria cases were reported during 2008-2015 in Qatar. The demographic features of the imported cases show that the majority of cases were males (93%), non-Qatari(99.6%), and aged 15 to 44 years(82.1%). Moreover, P. vivax was found to be the main etiologic agent accounting for more than three-quarters (78.7%) of the imported cases. In addition, almost a third (33.1%) of the cases were reported during the months of July, August, and September. Conclusions Imported malaria in Qatar has witnessed an increase during the past 7 years, despite a long period of constant reduction; where the people most affected were adult male migrants from endemic countries. Many challenges need to be overcome to prevent the reintroduction of malaria into the country.

Human Papillomavirus (HPV) infections are known to cause cervical cancer worldwide, however, limited information is currently available on prevalence, types distribution and risk factors for HPV infection in the Arab countries. We conducted a cross-sectional observational study exclusively of women of Arabic origin residing in Qatar (n = 406) who were selected from the Women's Hospital at Hamad Medical Corporation (HMC) and Health Centers of the Primary Health Care Corporation in Doha, Qatar over the period March 2013 to August 2014. Socio-demographic, behavioral and clinical data were collected. Four hundred and six cervical smears and 292 blood samples were included in the study. HPV typing was done using HPV type-specific primers-based real-time PCR, and Sanger sequencing. HPV-IgG and IgM were quantified using ELISA assays. The prevalence of HPV infection amongst Qatari and non-Qatari Arab women were 9.8% and 6.1%, respectively and 7.6% and 16.7% in women with normal and abnormal cytology, respectively. HPV 81 was the most commonly found genotype in women with normal cytology (34.5%), whereas HPV 81, 16 and 59 in women with abnormal cytology (25.0% each). All the HPV DNA positive women were seronegative and HPV-IgG prevalence was higher in Qatari women than in non-Qatari Arab women. None of the studied factors had any significant association with HPV-DNA positivity or HPV-IgG seropositivity. The overall identified HPV DNA prevalence and HPV seroprevalence among Arab women in Qatar were on the low side compared to global levels.

The genetic diversity in Plasmodium falciparum antigens is a major hurdle in developing an effective malaria vaccine. Protective efficacy of the vaccine is dependent on the polymorphic alleles of the vaccine candidate antigens. Therefore, we investigated the genetic diversity of the potential vaccine candidate antigens i.e. msp-1, msp-2, glurp, csp and pfs25 from field isolates of P.falciparum and determined the natural immune response against the synthetic peptide of these antigens. Genotyping was performed using Sanger method and size of alleles, multiplicity of infection, heterogeneity and recombination rate were analyzed. Asexual stage antigens were highly polymorphic with 55 and 50 unique alleles in msp-1 and msp-2 genes, respectively. The MOI for msp-1 and msp-2 were 1.67 and 1.28 respectively. A total 59 genotype was found in glurp gene with 8 types of amino acid repeats in the conserved part of RII repeat region. The number of NANP repeats from 40 to 44 was found among 55% samples in csp gene while pfs25 was found almost conserved with only two amino acid substitution site. The level of genetic diversity in the present study population was very similar to that from Asian countries. A higher IgG response was found in the B-cell epitopes of msp-1 and csp antigens and higher level of antibodies against csp B-cell epitope and glurp antigen were recorded with increasing age groups. Significantly, higher positive responses were observed in the csp antigen among the samples with ≥42 NANP repeats. The present finding showed extensive diversity in the asexual stage antigens.

BACKGROUND:The main processes in the pathogenesis of cerebral malaria caused by Plasmodium falciparum involved sequestration of parasitized red blood cells and immunopathological responses. Among immune factors, IgG autoantibodies to brain antigens are increased in P. falciparum infected patients and correlate with disease severity in African children. Nevertheless, their role in the pathophysiology of cerebral malaria (CM) is not fully defined. We extended our analysis to an Indian population with genetic backgrounds and endemic and environmental status different from Africa to determine if these autoantibodies could be either a biomarker or a risk factor of developing CM. METHODS/PRINCIPAL FINDINGS:We investigated the significance of these self-reactive antibodies in clinically well-defined groups of P. falciparum infected patients manifesting mild malaria (MM), severe non-cerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria epidemic site in central India using quantitative immunoprinting and multivariate statistical analyses. A two-fold complete-linkage hierarchical clustering allows classifying the different patient groups and to distinguish the CM from the others on the basis of their profile of IgG reactivity to brain proteins defined by PANAMA Blot. We identified beta tubulin III (TBB3) as a novel discriminant brain antigen in the prevalence of CM. In addition, circulating IgG from CM patients highly react with recombinant TBB3. Overall, correspondence analyses based on singular value decomposition show a strong correlation between IgG anti-TBB3 and elevated concentration of cluster-II cytokine (IFNgamma, IL1beta, TNFalpha, TGFbeta) previously demonstrated to be a predictor of CM in the same population. CONCLUSIONS/SIGNIFICANCE:Collectively, these findings validate the relationship between antibody response to brain induced by P. falciparum infection and plasma cytokine patterns with clinical outcome of malaria. They also provide significant insight into the immune mechanisms associated to CM by the identification of TBB3 as a new disease-specific marker and potential therapeutic target.

Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.