RESUMO
BACKGROUND: It has been proposed that childhood vaccines in high-mortality populations may have substantial impacts on mortality rates that are not explained by the prevention of targeted diseases, nor conversely by typical expected adverse reactions to the vaccines, and that these non-specific effects (NSEs) are generally more pronounced in females. The existence of these effects, and any implications for the development of vaccines and the design of vaccination programs to enhance safety, remain controversial. One area of controversy is the reported association of non-live vaccines with increased female mortality. In a previous randomized controlled trial (RCT), we observed that non-live alum-adjuvanted animal rabies vaccine (ARV) was associated with increased female but not male mortality in young, free-roaming dogs. Conversely, non-live non-adjuvanted human rabies vaccine (NRV) has been associated with beneficial non-specific effects in children. Alum adjuvant has been shown to suppress Th1 responses to pathogens, leading us to hypothesize that alum-adjuvanted rabies vaccine in young dogs has a detrimental effect on female survival by modulating the immune response to infectious and/or parasitic diseases. In this paper, we present the protocol of a 3-arm RCT comparing the effect of alum-adjuvanted rabies vaccine, non-adjuvanted rabies vaccine and placebo on all-cause mortality in an owned, free-roaming dog population, with causal mediation analysis of the RCT and a nested case-control study to test this hypothesis. METHODS: Randomised controlled trial with a nested case-control study. DISCUSSION: We expect that, among the placebo group, males will have higher mortality caused by higher pathogen loads and more severe disease, as determined by haematological parameters and inflammatory biomarkers. Among females, we expect that there will be no difference in mortality between the NRV and placebo groups, but that the ARV group will have higher mortality, again mediated by higher pathogen loads and more severe disease. We anticipate that these changes are preceded by shifts in key serum cytokine concentrations towards an anti-inflammatory immune response in females. If confirmed, these results will provide a rational basis for mitigation of detrimental NSEs of non-live vaccines in high-mortality populations.
Assuntos
Doenças do Cão , Vacina Antirrábica , Raiva , Adjuvantes Imunológicos/farmacologia , Compostos de Alúmen , Animais , Anti-Inflamatórios , Biomarcadores , Estudos de Casos e Controles , Ensaios Clínicos Veterinários como Assunto , Citocinas , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Cães , Feminino , Humanos , Masculino , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária , Vacinação/veterináriaRESUMO
A novel rickettsial agent, 'Candidatus Rickettsia asembonensis' strain NMRCiiT, was isolated from cat fleas, Ctenocephalides felis, from Kenya. Genotypic characterization of the new isolate based on sequence analysis of five rickettsial genes, rrs, gltA, ompA, ompB and sca4, indicated that this isolate clustered with Rickettsia felis URRWXCal2. The degree of nucleotide similarity demonstrated that isolate NMRCiiT belongs within the genus Rickettsia and fulfils the criteria for classification as a representative of a novel species. The name Rickettsia asembonensis sp. nov. is proposed, with NMRCiiT (=DSM 100172T=CDC CRIRC RAS001T=ATCC VR-1827T) as the type strain.
Assuntos
Ctenocephalides/microbiologia , Filogenia , Rickettsia/classificação , Animais , Técnicas de Tipagem Bacteriana , Gatos , DNA Bacteriano/genética , Genes Bacterianos , Quênia , RNA Ribossômico 16S/genética , Rickettsia/genética , Rickettsia/isolamento & purificação , Análise de Sequência de DNARESUMO
Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone-resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.
Assuntos
Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Resistência às Cefalosporinas , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Animais , Farmacorresistência Bacteriana Múltipla , Monitoramento Epidemiológico , Feminino , Humanos , Quênia/epidemiologia , Masculino , Prevalência , Fatores de Risco , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Infecções por Salmonella/epidemiologiaRESUMO
BACKGROUND: Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. METHODOLOGY/PRINCIPAL FINDINGS: We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children's homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08-0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02-0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0-1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5-37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2-12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. CONCLUSIONS AND SIGNIFICANCE: Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents.
Assuntos
Animais Domésticos , Diarreia/epidemiologia , Fezes/microbiologia , Desinfecção das Mãos , Criação de Animais Domésticos , Animais , Animais Domésticos/microbiologia , Animais Domésticos/parasitologia , Animais Domésticos/virologia , Estudos de Casos e Controles , Galinhas , Pré-Escolar , Diarreia/microbiologia , Diarreia/parasitologia , Diarreia/virologia , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Roedores , População Rural , Índice de Gravidade de Doença , Carneiro Doméstico , Zoonoses/epidemiologiaRESUMO
Candidatus Rickettsia asemboensis was identified molecularly in fleas collected in 2009 from Asembo, Kenya. Multilocus sequence typing using the 17-kD antigen gene, rrs, gltA, ompA, ompB, and sca4 demonstrated that Candidatus R. asemboensis is closely related to Rickettsia felis but distinct enough to be considered for separate species classification. Following this molecular characterization of Candidatus R. asemboensis, the in vitro cultivation of this bacterium was then performed. We used Ctenocephalides canis and Ctenocephalides felis fleas removed from dogs in Kenya to initiate the in vitro isolation of Candidatus R. asemboensis. Successful cultures were obtained using Drosophila melanogaster S2 and Aedes albopictus C6/36 cell lines. Cytological staining and quantitative real-time PCR (qPCR) assays were used to visualize/confirm the culture of the bacteria in both cell lines. Sequencing of fragments of the 17-kD antigen gene, gltA, and ompB genes confirmed the identity of our Candidatus R. asemboensis isolates. To date, we have passaged Candidatus R. asemboensis 12 times through S2 and C6/36 cells, and active and frozen cultures are currently being maintained. This is the first time that a R. felis-like organism has been grown and maintained in culture and is therefore the first time that one of them, Candidatus R. asemboensis, has been characterized beyond molecular typing.
Assuntos
Ctenocephalides/microbiologia , Doenças do Cão/microbiologia , Infestações por Pulgas/veterinária , Infecções por Rickettsia/veterinária , Rickettsia/isolamento & purificação , Aedes , Animais , Linhagem Celular , DNA Bacteriano/química , DNA Bacteriano/genética , Doenças do Cão/parasitologia , Cães , Drosophila melanogaster , Feminino , Infestações por Pulgas/parasitologia , Masculino , Tipagem de Sequências Multilocus/veterinária , Infecções por Rickettsia/microbiologiaRESUMO
Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households was conducted. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8-4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5-3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5-2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3-0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level.
Assuntos
Brucella/isolamento & purificação , Brucelose/epidemiologia , Brucelose/transmissão , Brucelose/veterinária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antibacterianos/sangue , Camelus/microbiologia , Bovinos/microbiologia , Criança , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Feminino , Cabras/microbiologia , Humanos , Imunoglobulina G/sangue , Quênia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Ovinos/microbiologia , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: For most rural households in sub-Saharan Africa, healthy livestock play a key role in averting the burden associated with zoonotic diseases, and in meeting household nutritional and socio-economic needs. However, there is limited understanding of the complex nutritional, socio-economic, and zoonotic pathways that link livestock health to human health and welfare. Here we describe a platform for integrated human health, animal health and economic welfare analysis designed to address this challenge. We provide baseline epidemiological data on disease syndromes in humans and the animals they keep, and provide examples of relationships between human health, animal health and household socio-economic status. METHOD: We designed a study to obtain syndromic disease data in animals along with economic and behavioral information for 1500 rural households in Western Kenya already participating in a human syndromic disease surveillance study. Data collection started in February 2013, and each household is visited bi-weekly and data on four human syndromes (fever, jaundice, diarrhea and respiratory illness) and nine animal syndromes (death, respiratory, reproductive, musculoskeletal, nervous, urogenital, digestive, udder disorders, and skin disorders in cattle, sheep, goats and chickens) are collected. Additionally, data from a comprehensive socio-economic survey is collected every 3 months in each of the study households. FINDINGS: Data from the first year of study showed 93% of the households owned at least one form of livestock (55%, 19%, 41% and 88% own cattle, sheep, goats and chickens respectively). Digestive disorders, mainly diarrhea episodes, were the most common syndromes observed in cattle, goats and sheep, accounting for 56% of all livestock syndromes, followed by respiratory illnesses (18%). In humans, respiratory illnesses accounted for 54% of all illnesses reported, followed by acute febrile illnesses (40%) and diarrhea illnesses (5%). While controlling for household size, the incidence of human illness increased 1.31-fold for every 10 cases of animal illness or death observed (95% CI 1.16-1.49). Access and utilization of animal source foods such as milk and eggs were positively associated with the number of cattle and chickens owned by the household. Additionally, health care seeking was correlated with household incomes and wealth, which were in turn correlated with livestock herd size. CONCLUSION: This study platform provides a unique longitudinal dataset that allows for the determination and quantification of linkages between human and animal health, including the impact of healthy animals on human disease averted, malnutrition, household educational attainment, and income levels.
Assuntos
Gado , Vigilância em Saúde Pública , Saúde Pública , Características de Residência , Animais , Características da Família , Geografia , Inquéritos Epidemiológicos , Humanos , QuêniaRESUMO
Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae-genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya.
Assuntos
Anticorpos Antibacterianos/sangue , Vetores Aracnídeos/microbiologia , Ixodidae/microbiologia , Infecções por Rickettsia/veterinária , Rickettsia/imunologia , Doenças Transmitidas por Carrapatos/veterinária , Animais , Animais Domésticos , Proteínas da Membrana Bacteriana Externa/genética , Sequência de Bases , Bovinos , Primers do DNA/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Cães , Feminino , Cabras , Humanos , Quênia/epidemiologia , Masculino , Dados de Sequência Molecular , Rickettsia/genética , Rickettsia/isolamento & purificação , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Saúde da População Rural , Análise de Sequência de DNA/veterinária , Estudos Soroepidemiológicos , Ovinos , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , ZoonosesRESUMO
The flea-borne rickettsioses murine typhus (Rickettsia typhi) and flea-borne spotted fever (FBSF) (Rickettsia felis) are febrile diseases distributed among humans worldwide. Murine typhus has been known to be endemic to Kenya since the 1950s, but FBSF was only recently documented in northeastern (2010) and western (2012) Kenya. To characterize the potential exposure of humans in Kenya to flea-borne rickettsioses, a total of 330 fleas (134 pools) including 5 species (Xenopsylla cheopis, Ctenocephalides felis, Ctenocephalides canis, Pulex irritans, and Echidnophaga gallinacea) were collected from domestic and peridomestic animals and from human dwellings within Asembo, western Kenya. DNA was extracted from the 134 pooled flea samples and 89 (66.4%) pools tested positively for rickettsial DNA by 2 genus-specific quantitative real-time PCR (qPCR) assays based upon the citrate synthase (gltA) and 17-kD antigen genes and the Rfelis qPCR assay. Sequences from the 17-kD antigen gene, the outer membrane protein (omp)B, and 2 R. felis plasmid genes (pRF and pRFd) of 12 selected rickettsia-positive samples revealed a unique Rickettsia sp. (n=11) and R. felis (n=1). Depiction of the new rickettsia by multilocus sequence typing (MLST) targeting the 16S rRNA (rrs), 17-kD antigen gene, gltA, ompA, ompB, and surface cell antigen 4 (sca4), shows that it is most closely related to R. felis but genetically dissimilar enough to be considered a separate species provisionally named Candidatus Rickettsia asemboensis. Subsequently, 81 of the 134 (60.4%) flea pools tested positively for Candidatus Rickettsia asemboensis by a newly developed agent-specific qPCR assay, Rasemb. R. felis was identified in 9 of the 134 (6.7%) flea pools, and R. typhi the causative agent of murine typhus was not detected in any of 78 rickettsia-positive pools assessed using a species-specific qPCR assay, Rtyph. Two pools were found to contain both R. felis and Candidatus Rickettsia asemboensis DNA and 1 pool contained an agent, which is potentially new.
Assuntos
Infestações por Pulgas/veterinária , Insetos Vetores/microbiologia , Infecções por Rickettsia/transmissão , Rickettsia/isolamento & purificação , Sifonápteros/microbiologia , Animais , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Sequência de Bases , Gatos , Bovinos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Cães , Feminino , Infestações por Pulgas/epidemiologia , Infestações por Pulgas/parasitologia , Humanos , Insetos Vetores/classificação , Quênia/epidemiologia , Gado , Masculino , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Rickettsia/genética , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Rickettsia felis/genética , Rickettsia felis/isolamento & purificação , Sifonápteros/classificação , Especificidade da EspécieRESUMO
We conducted serological surveys for Coxiella burnetii in archived sera from patients that visited a rural clinic in western Kenya from 2007 to 2008 and in cattle, sheep, and goats from the same area in 2009. We also conducted serological and polymerase chain reaction-based surveillance for the pathogen in 2009-2010, in human patients with acute lower respiratory illness, in ruminants following parturition, and in ticks collected from ruminants and domestic dogs. Antibodies against C. burnetii were detected in 30.9% (N = 246) of archived patient sera and in 28.3% (N = 463) of cattle, 32.0% (N = 378) of goats, and 18.2% (N = 159) of sheep surveyed. Four of 135 (3%) patients with acute lower respiratory illness showed seroconversion to C. burnetii. The pathogen was detected by polymerase chain reaction in specimens collected from three of six small ruminants that gave birth within the preceding 24 hours, and in five of 10 pools (50%) of Haemaphysalis leachi ticks collected from domestic dogs.