Yellow fever control in Cameroon: Where are we now and where are we going?

<p>Abstract</p> <p>Background</p> <p>Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan.</p> <p>Methods</p> <p>In January 2003, case-based surveillance of suspected yellow fever cases was instituted in the whole country. A year later, yellow fever immunisation at nine months of age (the same age as routine measles immunisation) was introduced. Supplementary immunisation activities (SIAs), both preventive and in response to outbreaks, also formed an integral part of the yellow fever control plan. Each level of the national health system makes a synthesis of its activities and sends this to the next higher level at defined regular intervals; monthly for routine data and daily for SIAs.</p> <p>Results</p> <p>From 2004 to 2006 the national routine yellow fever vaccination coverage rose from 58.7% to 72.2%. In addition, the country achieved parity between yellow fever and measles vaccination coverage in 2005 and has since maintained this performance level. The number of suspected yellow fever cases in the country increased from 156 in 2003 to 859 in 2006, and the proportion of districts that reported at least one suspected yellow fever case per year increased from 31.4% to 68.2%, respectively. Blood specimens were collected from all suspected cases (within 14 days of onset of symptoms) and tested at a central laboratory for yellow fever IgM antibodies; leading to confirmation of yellow fever outbreaks in the health districts of Bafia, Méri and Ntui in 2003, Ngaoundéré Rural in 2004, Yoko in 2005 and Messamena in 2006. Owing to constraints in rapidly mobilising the necessary resources, reactive SIAs were only conducted in Bafia and Méri several months after confirmation of the outbreak. In both districts, a total of 60,083 people (representing 88.2% of the 68,103 targeted) were vaccinated. Owing to the same constraints, SIAs were not conducted promptly in response to the outbreaks in Ntui, Ngaoundéré Rural, Yoko and Messamena. However, these four and two other health districts at high risk of yellow fever outbreaks (i.e. Maroua Urban and Ngaoundéré Urban) conducted preventive SIAs in November 2006, vaccinating a total of 752,195 people (92.8% of target population). In both the reactive and preventive SIAs, the mean wastage rates for vaccines and injection material were less than 5% and there was no report of a serious adverse event following immunisation.</p> <p>Conclusion</p> <p>Amidst other competing health priorities, over the past four years Cameroon has successfully planned and implemented evidence-based strategies for preventing yellow fever outbreaks and for detecting and responding to the outbreaks when they occur. In order to sustain these initial successes, the country will have to attain and sustain high routine vaccination coverage in each successive birth cohort in every district. This would require fostering and sustaining high-level political commitment, improving the planning and monitoring of immunisation services at all levels, adequate community mobilisation, and efficient coordination of current and future immunisation partners.</p

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis

Life on Arginine for Mycoplasma hominis: Clues from Its Minimal Genome and Comparison with Other Human Urogenital Mycoplasmas

Mycoplasma hominis is an opportunistic human mycoplasma. Two other pathogenic human species, M. genitalium and Ureaplasma parvum, reside within the same natural niche as M. hominis: the urogenital tract. These three species have overlapping, but distinct, pathogenic roles. They have minimal genomes and, thus, reduced metabolic capabilities characterized by distinct energy-generating pathways. Analysis of the M. hominis PG21 genome sequence revealed that it is the second smallest genome among self-replicating free living organisms (665,445 bp, 537 coding sequences (CDSs)). Five clusters of genes were predicted to have undergone horizontal gene transfer (HGT) between M. hominis and the phylogenetically distant U. parvum species. We reconstructed M. hominis metabolic pathways from the predicted genes, with particular emphasis on energy-generating pathways. The Embden–Meyerhoff–Parnas pathway was incomplete, with a single enzyme absent. We identified the three proteins constituting the arginine dihydrolase pathway. This pathway was found essential to promote growth in vivo. The predicted presence of dimethylarginine dimethylaminohydrolase suggested that arginine catabolism is more complex than initially described. This enzyme may have been acquired by HGT from non-mollicute bacteria. Comparison of the three minimal mollicute genomes showed that 247 CDSs were common to all three genomes, whereas 220 CDSs were specific to M. hominis, 172 CDSs were specific to M. genitalium, and 280 CDSs were specific to U. parvum. Within these species-specific genes, two major sets of genes could be identified: one including genes involved in various energy-generating pathways, depending on the energy source used (glucose, urea, or arginine) and another involved in cytadherence and virulence. Therefore, a minimal mycoplasma cell, not including cytadherence and virulence-related genes, could be envisaged containing a core genome (247 genes), plus a set of genes required for providing energy. For M. hominis, this set would include 247+9 genes, resulting in a theoretical minimal genome of 256 genes

Early and Late Pathogenic Events of Newborn Mice Encephalitis Experimentally Induced by Itacaiunas and Curionópolis Bracorhabdoviruses Infection

In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share many pathological and clinical features present in other rhabdoviruses but distinct virulence and glial targets in newborn albino Swiss mice brain

Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in São Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of ∼10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1–4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in São José do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000–2001. Sixty DENV-3 from São José do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R0 = 1.53 and values for lineage 2 of R0 = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area

The great melting pot. Common sole population connectivity assessed by otolith and water fingerprints

Quantifying the scale and importance of individual dispersion between populations and life stages is a key challenge in marine ecology. The common sole (Solea solea), an important commercial flatfish in the North Sea, Atlantic Ocean and the Mediterranean Sea, has a marine pelagic larval stage, a benthic juvenile stage in coastal nurseries (lagoons, estuaries or shallow marine areas) and a benthic adult stage in deeper marine waters on the continental shelf. To date, the ecological connectivity among these life stages has been little assessed in the Mediterranean. Here, such an assessment is provided for the first time for the Gulf of Lions, NW Mediterranean, based on a dataset on otolith microchemistry and stable isotopic composition as indicators of the water masses inhabited by individual fish. Specifically, otolith Ba/Ca and Sr/Ca profiles, and delta C-13 and delta O-18 values of adults collected in four areas of the Gulf of Lions were compared with those of young-of-the-year collected in different coastal nurseries. Results showed that a high proportion of adults (>46%) were influenced by river inputs during their larval stage. Furthermore Sr/Ca ratios and the otolith length at one year of age revealed that most adults (similar to 70%) spent their juvenile stage in nurseries with high salinity, whereas the remainder used brackish environments. In total, data were consistent with the use of six nursery types, three with high salinity (marine areas and two types of highly saline lagoons) and three brackish (coastal areas near river mouths, and two types of brackish environments), all of which contributed to the replenishment of adult populations. These finding implicated panmixia in sole population in the Gulf of Lions and claimed for a habitat integrated management of fisherie