Intestical polyparasitism in a rural Kenyan community

Background: Polyparasitism seems to be a common feature in human populations in sub-Saharan Africa. However, very little is known about its epidemiological significance, its long term impact on human health or the types of interactions that occur between the different parasite species involved.Objectives: To determine the prevalence and co-occurrence of intestinal parasites in a rural community in the Kibwezi, Makueni district, Kenya.Design: A cross sectional study.Setting: Kiteng’ei village, Kibwezi, Makueni district, between May and September 2006.Subjects: One thousand and forty five who comprised of 263 adult males, 271 adult females> 15 years of age and 232 boys, and 279 girls < 15 years of age.Interventions: All infected members of the community were offered Praziquantel (at dosages of 40 mg/ kg body weight) for Schistosomiasis and Albendazole (600 mg) for soil transmitted helminths.Results: A total of ten intestinal parasite species (five protozoan and five helminth parasite species) were present in this community and polyparasitsm was common in individuals 5- 24 years of age with no gendar related differences. Most of the infections were mild. The protozoan parasites of public health significance present were Entamoeba histolytica and Giardia lamblia with prevalence of 12.6% and 4.2%, respectively. The helminth parasites of public health significance in the locality were Schistosoma mansoni with a prevalence of 28%, and hookworms prevalence of 10%. About 53% of the study population harboured intestinal parasite infections, with 31 % of the infected population carrying single parasite species infections, and 22% harbouring two or more intestinal parasite species per individual. Significant positive associations (p value

Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.&lt;p&gt;&lt;/p&gt; Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (&#8804;13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was &#60;8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.&lt;p&gt;&lt;/p&gt; Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.&lt;p&gt;&lt;/p&gt

A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329) in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (Pmeta = 2.74×10−8, odds ratio = 1.29 [1.18–1.40]). The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients

Type I IFN and TNFα cross-regulation in immune-mediated inflammatory disease: basic concepts and clinical relevance

A cross-regulation between type I IFN and TNFα has been proposed recently, where both cytokines are hypothesized to counteract each other. According to this model, different autoimmune diseases can be viewed as disequilibrium between both cytokines. As this model may have important clinical implications, the present review summarizes and discusses the currently available clinical evidence arguing for or against the proposed cross-regulation between TNFα and type I IFN. In addition, we review how this cross-regulation works at the cellular and molecular levels. Finally, we discuss the clinical relevance of this proposed cross-regulation for biological therapies such as type I IFN or anti-TNFα treatment

Gene Expression Patterns in Larval Schistosoma mansoni Associated with Infection of the Mammalian Host

The schistosome cercaria develops from undifferentiated germ balls within the daughter sporocyst located in the hepatopancreas of its snail intermediate host. This is where the proteins it uses to infect humans are synthesised. After a brief free life in fresh water, if the cercaria locates a host, it infects by direct penetration through the skin. It then transforms into the schistosomulum stage, adapted for life in human tissues. We have designed a large scale array comprising probes representing all known schistosome genes and used it in hybridisation experiments to establish which genes are turned on or off in the parasite during these stages in its life cycle. Genes encoding proteins involved in cell division were prominent in the germ ball along with those for proteases and potential immunomodulators, deployed during skin penetration. The non-feeding cercaria was the least active at synthesising proteins. Conversion to the schistosomulum was accompanied by transcription of genes involved in body remodeling, including production of a new outer surface, and gut activation long before ingestion of red blood cells begins. Our data help us to understand better the proteins deployed to achieve infection, and subsequent adaptations necessary for establishment of the parasite in the human host

The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya

Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5–1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1–1.4, p&lt;0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0–10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5–4.2). Being the slaughterman, the person who cuts the animal’s throat (OR 3.5; 95% CI 1.0–12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV circulation in western Kenya

The HIV-1 transmission bottleneck

It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient