Xenosurveillance reflects traditional sampling techniques for the identification of human pathogens: A comparative study in West Africa

BACKGROUND: Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood. METHODOLOGY/PRINCIPAL FINDINGS: We sought to take advantage of this phenomenon by systematically collecting blood-fed mosquitoes during a field trail in Northern Liberia to determine whether pathogen sequences from blood engorged mosquitoes accurately mirror those obtained directly from humans. Specifically, blood was collected from humans via finger-stick and by aspirating bloodfed mosquitoes from the inside of houses. Shotgun metagenomic sequencing of RNA and DNA derived from these specimens was performed to detect pathogen sequences. Samples obtained from xenosurveillance and from finger-stick blood collection produced a similar number and quality of reads aligning to two human viruses, GB virus C and hepatitis B virus. CONCLUSIONS/SIGNIFICANCE: This study represents the first systematic comparison between xenosurveillance and more traditional sampling methodologies, while also demonstrating the viability of xenosurveillance as a tool to sample human blood for circulating pathogens

Impact of annual versus semiannual mass drug administration with ivermectin and albendazole on helminth infections in southeastern Liberia

We compared the impact of three rounds of annual and five rounds of semiannual mass drug administration (MDA) with albendazole plus ivermectin on helminthic infections in Liberia. Repeated annual cross-sectional community surveys were conducted between 2013 and 2019 in individuals of 5 years and older. Primary outcome was the change of infection prevalence estimates from baseline to month 36 (12 months after the last treatment). After three rounds of annual MDA, Wuchereria bancrofti circulating filarial antigen (CFA) and microfilaria (Mf) prevalence estimates decreased from 19.7% to 4.3% and from 8.6% to 0%, respectively; after semiannual MDA, CFA and Mf prevalences decreased from 37.8% to 16.8% and 17.9% to 1%, respectively. Mixed effects logistic regression models indicated that the odds of having Mf decreased by 97% (P \u3c 0.001) at month 36 (similar odds for annual and semiannual MDA zones). A parallel analysis showed that the odds of CFA were reduced by 83% and 69% at 36 months in the annual and semiannual treatment zones, respectively (P \u3c 0.001). Onchocerca volvulus Mf prevalence decreased slightly after multiple MDA rounds in both treatment zones. Reductions in hookworm and Trichuris trichiura prevalences and intensities were slightly greater in the annual treatment zone. Ascaris lumbricoides prevalence rates were relatively unchanged, although infection intensities decreased sharply throughout. Results show that annual and semiannual MDA were equally effective for reducing LF and soil-transmitted helminth infection parameters over a 3-year period, and reductions recorded at month 36 were sustained by routine annual MDA through month 72

Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia.

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD

Laboratory and field evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human blood

Global Program to Eliminate Lymphatic Filariasis (GPELF) guidelines call for using filarial antigen testing to identify endemic areas that require mass drug administration (MDA) and for post-MDA surveillance. We compared a new filarial antigen test (the Alere Filariasis Test Strip) with the reference BinaxNOW Filariasis card test that has been used by the GPELF for more than 10 years. Laboratory testing of 227 archived serum or plasma samples showed that the two tests had similar high rates of sensitivity and specificity and > 99% agreement. However, the test strip detected 26.5% more people with filarial antigenemia (124/503 versus 98/503) and had better test result stability than the card test in a field study conducted in a filariasis-endemic area in Liberia. Based on its increased sensitivity and other practical advantages, we believe that the test strip represents a major step forward that will be welcomed by the GPELF and the filariasis research community

Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia.

BACKGROUND: The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood. RESULTS: A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state. The microbiomes of individuals able to self-clear the infection had more alike microbiome assemblages compared to individuals who remained infected. One bacterial taxon (Lachnospiracae) was negatively associated with infection in both countries, and 12 bacterial taxa were significantly associated with STH infection in both countries, including Olsenella (associated with reduced gut inflammation), which also significantly reduced in abundance following clearance of infection. Microbial community gene abundances were also affected by deworming. Functional categories identified as associated with STH infection included arachidonic acid metabolism; arachidonic acid is the precursor for pro-inflammatory leukotrienes that threaten helminth survival, and our findings suggest that some modulation of arachidonic acid activity in the STH-infected gut may occur through the increase of arachidonic acid metabolizing bacteria. CONCLUSIONS: For the first time, we identify specific members of the gut microbiome that discriminate between moderately/heavily STH-infected and non-infected states across very diverse geographical regions using two different statistical methods. We also identify microbiome-encoded biological functions associated with the STH infections, which are associated potentially with STH survival strategies, and changes in the host environment. These results provide a novel insight of the cross-kingdom interactions in the human gut ecosystem by unlocking the microbiome assemblages at taxonomic, genetic, and functional levels so that advances towards key mechanistic studies can be made. Microbiome 2018 Feb 28; 6(1):33

West African Anopheles Gambiae Mosquitoes Harbor a Taxonomically Diverse Virome Including New Insect-Specific Flaviviruses, Mononegaviruses, and Totiviruses

Anopheles gambiae are a major vector of malaria in sub-Saharan Africa. Viruses that naturally infect these mosquitoes may impact their physiology and ability to transmit pathogens. We therefore used metagenomics sequencing to search for viruses in adult Anopheles mosquitoes collected from Liberia, Senegal, and Burkina Faso. We identified a number of virus and virus-like sequences from mosquito midgut contents, including 14 coding-complete genome segments and 26 partial sequences. The coding-complete sequences define new viruses in the order Mononegavirales, and the families Flaviviridae, and Totiviridae. The identification of a flavivirus infecting Anopheles mosquitoes broadens our understanding of the evolution and host range of this virus family. This study increases our understanding of virus diversity in general, begins to define the virome of a medically important vector in its natural setting, and lays groundwork for future studies examining the potential impact of these viruses on anopheles biology and disease transmission

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires \u3c2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (\u3e95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV \u3c95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. CONCLUSIONS/SIGNIFICANCE: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission

Evolution and Spread of Ebola Virus in Liberia, 2014–2015

The 2013–present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host.Organismic and Evolutionary Biolog

Virus genomes reveal factors that spread and sustained the Ebola epidemic.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics