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Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1).

Background With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. Methods We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. Results In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Conclusion Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination. Electronic supplementary material The online version of this article (doi:10.1186/s13071-015-1152-3) contains supplementary material, which is available to authorized users.

Sierra Leone constitutes the western boundary to the West Africa Upper Guinea Rainforest, one of 35 global biodiversity hotspots. The country is home to the third-largest western chimpanzee (Pan troglodytes verus) population, a subspecies upgraded to Critically Endangered on the 2016 IUCN Red List. The main threats facing chimpanzees in Sierra Leone are habitat loss and increasing interactions with humans. The Mobonda Community Conservation Project (MCCP) is a component of Tacugama Chimpanzee Sanctuary's Community Outreach Program and Kids Environmental Education Program. The aim of MCCP is to promote community-based forest management in combination with wildlife conservation through carefully designed programs that benefit communities, wildlife, and ecologically significant habitats. MCCP also aims to promote self-sustained and integrated community landscape conservation, to facilitate policy discussions to strengthen wildlife laws, and to build the capacity of the Government to implement community-based wildlife and forestry protection projects. Since Tacugama began collecting data in Moyamba District in June 2015, the project has evolved into an assembly of components. MCCP currently works with five communities, running programs including environmental education, ecological research, biomonitoring including wildlife law enforcement, habitat rehabilitation through reforestation of identified wildlife corridors, improved sustainable livelihoods, and ecotourism initiatives. These programs contributed to a reduction in the threats facing wildlife in the area; the project has seen stable chimpanzee numbers where decrements to chimpanzee populations continue to be experienced elsewhere. Other MCCP outcomes include boosted sustainable agricultural production and higher oyster yields while decreasing the negative impact on the mangrove ecosystem allowing it to recover and support an array of important fauna and flora.

Background Lymphatic filariasis (LF) is widely endemic in Cote d’Ivoire, and elimination as public health problem (EPHP) is based on annual mass drug administration (MDA) using ivermectin and albendazole. To guide EPHP efforts, we evaluated Wuchereria bancrofti infection indices among humans, and mosquito vectors after four rounds of MDA in four cross-border health districts of Cote d’Ivoire. Methodology We monitored people and mosquitoes for W. bancrofti infections in the cross-border health districts of Aboisso, Blolequin, Odienne and Ouangolodougou, Cote d’Ivoire. W. bancrofti circulating filarial antigen (CFA) was identified using filariasis test strips, and antigen-positive individuals were screened for microfilaremia. Moreover, filarial mosquito vectors were sampled using window exit traps and pyrethrum sprays, and identified morphologically at species level. Anopheles gambiae s.l. and Culex quinquefasciatus females were analyzed for W. bancrofti infection using polymerase chain reaction (PCR) technique. Principal findings Overall, we found a substantial decline in W. bancrofti infection indices after four rounds of MDA compared to pre-MDA baseline data. CFA prevalence fell from 3.38–5.50% during pre-MDA to 0.00–1.53% after MDA interventions. No subjects had detectable levels of CFA in Ouangolodougou. Moreover, post-MDA CFA prevalence was very low, and below the 1% elimination threshold in Aboisso (0.19%) and Odienne (0.49%). Conversely, CFA prevalence remained above 1% in Blolequin (1.53%). W. bancrofti microfilariae (Mf) were not found in Aboisso, Blolequin, and Ouangolodougou, except for Odienne with low prevalence (0.16%; n = 613) and microfilaremia of 32.0 Mf/mL. No An. gambiae s.l. and Cx. quinquefasciatus pools were infected with W. bancrofti in Blolequin and Ouangolodougou, while they exhibited low infection rates in Aboisso (1% and 0.07%), and Odienne (0.08% and 0.08%), respectively. Conclusions In cross-border areas of Cote d’Ivoire, LF infection indices in humans and mosquito vectors substantially declined after four rounds of MDA. CFA prevalence fell under the World Health Organization (WHO)-established threshold (1%) in Aboisso, Ouangolodougou and Odienne. Moreover, W. bancrofti prevalence in mosquitoes was lower than WHO-established threshold (2%) in all areas. This might suggest the interruption of W. bancrofti transmission, and possible MDA cessation. However, a formal transmission assessment survey (TAS) and molecular xenomonitoring in mosquito vectors should be implemented before eventual MDA cessation. However, MDA should pursue in Blolequin where W. bancrofti infection prevalence remained above 1%. Our results provided important ramifications for LF control efforts towards EPHP in Cote d’Ivoire.

Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the human stomach. Infection with this microaerophilic bacterium causes gastric and duodenal ulcer. This study sought to isolate H. pylori, from gastric biopsy samples of dyspeptic patients in Ghana using a 2,3,5-triphenyltetrazolium chloride (TTC) dye incorporated medium method. This TTC dye method was further used in an antimicrobial susceptibility assay involving Dissotis rotundifolia extract (DRE). H. pylori were successfully isolated from gastric biopsy of dyspeptic patients. Pure cultures of H. pylori in 2,3,5-triphenyltetrazolium chloride (TTC) dye incorporated medium were seen as sparkling colonies. Isolates, identified as H. pylori, were gram-negative and urease, catalase, and oxidase positive and showed characteristic morphology as spiral-shaped bacteria under the microscope. The organisms were found to be susceptible to cephalothin and resistant to nalidixic acid. Above all, the observation that H. pylori grew only at 37°C and not 25°C or 42°C affirms that the bacterium is neither Helicobacter cinaedi nor Helicobacter fenneliae. The anti-H. pylori study depicts a statistically lower zone of inhibition for DRE compared to standard drugs [amoxicillin and clarithromycin] (p H. pylori in Ghana using TTC dye. It also shows that DRE possess an in vitro anti-H. pylori activity and that DRE has some therapeutic potential against H. pylori infection.

Data onHelicobacter pylori(H. pylori) infection and virulence factors in countries across West Africa are scattered. This systematic review seeks to present an update on the status ofH. pyloriinfection focusing on prevalence rate, distribution of virulent genes, and their link to clinical outcomes across countries in the western part of Africa. This information is expected to broaden the knowledge base of clinicians and researchers regardingH. pyloriinfection and associated virulence factors in West African countries.Search Method.A comprehensive search of the scientific literature in PubMed and ScienceDirect was conducted using the search terms including “Helicobacter pyloriinfection in West Africa”. Databases were sourced from January 1988 to December 2018.Results.Data on the incidence ofH. pyloriinfection and related pathological factors were found for some countries, whereas others had no information on it. Smoking, alcohol, exposure to high levels of carcinogens and diet were reported to be involved in the pathogenesis of gastroduodenal diseases and gastric cancer. Besides the environmental factors and genetic characteristics, there are important characteristics ofH. pylorisuch as the ability to infect, replicate, and persist in a host that have been associated with the pathogenesis of various gastroduodenal diseases.Concluding Remarks.This systematic search has provided information so far available onH. pylorivirulence factors and clinical outcomes in West Africa. Accordingly, this piece has identified gaps in the body of knowledge highlighting the need for more studies to clarify the role ofH. pylorivirulence factors and associated clinical outcomes in the burden of this bacterial infection in West Africa, as data from these countries do not give the needed direct relation.

Approximately one-third of Lassa virus (LASV)-infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa fever (LF), LASV is a major cause of hearing loss in regions of West Africa where LF is endemic. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent, while the virus isolated from a nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss. IMPORTANCE Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment.

Background Loiasis is a filarial infection endemic in the rainforest zone of west and central Africa particularly in Cameroon, Gabon, Republic of Congo, and Democratic Republic of the Congo. Repeated treatments with ivermectin have been delivered using the annual community directed treatment with ivermectin (CDTI) approach for several years to control onchocerciasis in some Loa loa-Onchocerca volvulus co-endemic areas. The impact of CDTI on loiasis parasitological indicators is not known. We, therefore, designed this cross sectional study to explore the effects of several rounds of CDTI on parasitological indicators of loiasis. Methodology/Principal findings The study was conducted in the East, Northwest and Southwest 2 CDTI projects of Cameroon. Individuals who consented to participate were interviewed for ivermectin treatment history and enrolled for parasitological screening using thick smears. Ivermectin treatment history was correlated with loiasis prevalence/intensity. A total of 3,684 individuals were recruited from 36 communities of the 3 CDTI projects and 900 individuals from 9 villages in a non-CDTI district. In the East, loiasis prevalence was 29.3% (range = 24.2%–34.6%) in the non-CDTI district but 16.0% (3.3%–26.6%) in the CDTI district with 10 ivermectin rounds (there were no baseline data for the latter). In the Northwest and Southwest 2 districts, reductions from 30.5% to 17.9% (after 9 ivermectin rounds) but from 8.1% to 7.8% (not significantly different after 14 rounds) were registered post CDTI, respectively. Similar trends in infection intensity were observed in all sites. There was a negative relationship between adherence to ivermectin treatment and prevalence/intensity of infection in all sites. None of the children (aged 10–14 years) examined in the East CDTI project harboured high (8,000–30,000 mf/ml) or very high (>30,000 mf/ml) microfilarial loads. Individuals who had taken >5 ivermectin treatments were 2.1 times more likely to present with no microfilaraemia than those with less treatments. Conclusion In areas where onchocerciasis and loiasis are co-endemic, CDTI reduces the number of, and microfilaraemia in L. loa-infected individuals, and this, in turn, will help to prevent non-neurological and neurological complications post-ivermectin treatment among CDTI adherents., Author summary Loa loa (the parasite causing loiasis), also known as African eye worm, is endemic in forest areas of west and central Africa. In several of the endemic areas, it co-exists with onchocerciasis and lymphatic filariasis (LF). Because of the benefit individuals suffering from onchocerciasis could have by taking ivermectin where the disease is severe, despite the risk of developing serious side-effects due to being co-infected with L. loa, mass drug administration (MDA) of ivermectin for the control of onchocerciasis has been ongoing in areas where the two diseases overlap. Ivermectin is also effective against loiasis. It is, therefore, hypothesized that several years of ivermectin MDA against onchocerciasis in those areas may have impacted on parasitological indicators for loiasis. In particular, we assess the impact of annual community directed treatment with ivermectin (CDTI) on loiasis with specific reference to the relationship between adherence to treatment and the risk of developing severe (nervous system) complications following ivermectin treatment. We also discuss the feasibility of eliminating onchocerciasis and/or LF in areas endemic for L. loa with ivermectin as the sole intervention tool.

Background Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution. Methods In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages. Results The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1–9 years (11.00%) and the highest in the age group of 40–49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1–9 years and the highest in the age group of 40–49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives. Conclusions A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making. Electronic supplementary material The online version of this article (10.1186/s40249-018-0410-y) contains supplementary material, which is available to authorized users.

Background Control of lymphatic filariasis (LF) in most of the sub-Saharan African countries is based on annual mass drug administration (MDA) using a combination of ivermectin and albendazole. Monitoring the impact of this intervention is crucial for measuring the success of the LF elimination programmes. This study assessed the status of LF infection in Rufiji district, southeastern Tanzania after twelve rounds of MDA. Methods Community members aged between 10 and 79 years were examined for Wuchereria bancrofti circulating filarial antigens (CFA) using immunochromatographic test cards (ICTs) and antigen-positive individuals were screened for microfilaraemia. All study participants were examined for clinical manifestation of LF and interviewed for drug uptake during MDA rounds. Filarial mosquito vectors were collected indoor and outdoor and examined for infection with W. bancrofti using a microscope and quantitative real-time polymerase chain reaction (qPCR) techniques. Results Out of 854 participants tested, nine (1.1%) were positive for CFA and one (0.1%) was found to be microfilaraemic. The prevalence of hydrocele and elephantiasis was 4.8% and 2.9%, respectively. Surveyed drug uptake rates were high, with 70.5% of the respondents reporting having swallowed the drugs in the 2014 MDA round (about seven months before this study). Further, 82.7% of the respondents reported having swallowed the drugs at least once since the inception of MDA programme in 2000. Of the 1054 filarial vectors caught indoors and dissected to detect W. bancrofti infection none was found to be infected. Moreover, analysis by qPCR of 1092 pools of gravid Culex quinquefasciatus collected outdoors resulted in an estimated infection rate of 0.1%. None of the filarial vectors tested with qPCR were found to be infective. Conclusion Analysis of indices of LF infection in the human population and filarial mosquito vectors indicated a substantial decline in the prevalence of LF and other transmission indices, suggesting that local transmission was extremely low if occurring at all in the study areas. We, therefore, recommend a formal transmission assessment survey (TAS) to be conducted in the study areas to make an informed decision on whether Rufiji District satisfied WHO criteria for stopping MDA.

Background: The decision to stop mass drug administration (MDA) and monitor recrudescence has to be made when endpoints for elimination of lymphatic filariasis (LF) have been achieved. Highly sensitive and specific diagnostic tools are required to do this. The main objective of this study was to determine most effective diagnostic tools for assessing interruption of LF transmission. Methods: The presence of filarial infection in blood and mosquito samples was determined using five diagnostic tools: Brugia malayi-14 (BM14) antibody detection ELISA, Onchocerca gibsoni antigen (Og4C3) based ELISA, PCR, immunochromatography (ICT) card test and blood smear. The study was carried out in two communities in the Central Region of Ghana. Results: OG4C3 was found to be the most sensitive test but ICT, the second most sensitive, was the most field applicable. PCR was found to be the most specific. Thirteen out of 30 pools of anopheles mosquitoes tested positive for the DNA of Wuchereria bancrofti. Conclusions: Very low antigen prevalence in primary school children indicates that MDA is working, so children born since the intervention was put in place are not getting infected. Inclusion of xenomonitoring in monitoring the effectiveness of MDA will give a better indication as to when transmission has been interrupted especially in areas where microfilaria prevalence is lower than 1%. Evaluation of human and mosquito based diagnostic tools for defining endpoints for elimination of Anopheles transmitted lymphatic filariasis in Ghana (PDF Download Available). Available from: https://www.researchgate.net/publication/281861241_Evaluation_of_human_and_mosquito_based_diagnostic_tools_for_defining_endpoints_for_elimination_of_Anopheles_transmitted_lymphatic_filariasis_in_Ghana [accessed Jan 25, 2016].

BACKGROUND\ud Lymphatic filariasis (LF) is a mosquito-borne filarial disease targeted for elimination by the year 2020. The Republic of Togo undertook mass treatment of entire endemic communities from 2000 to 2009 to eliminate the transmission of the disease and is currently the first sub-Saharan African country to be validated by WHO for the elimination of LF as a public health problem. However, post-validation surveillance activities are required to ensure the gains achieved are sustained. This survey assessed the mosquito vectors of the disease and determined the presence of infection in these vectors, testing the hypothesis that transmission has already been interrupted in Togo.\ud \ud METHOD\ud \ud Mosquitoes were collected from 37 villages located in three districts in one of four evaluation units in the country. In each district, 30 villages were selected based on probability proportionate to size; eight villages (including one of the 30 villages already selected) where microfilaremia-positive cases had been identified during post-treatment surveillance activities were intentionally sampled. Mosquitoes were collected using pyrethrum spray collections (PSC) in households randomly selected in all villages for five months. In the purposefully selected communities, mosquitoes were also collected using human landing collections (HLC) and exit traps (ET). Collected mosquitoes were identified morphologically, and the identification of Wuchereria bancrofti DNA in the mosquitoes was based on the pool screening method, using the LAMP assay.\ud \ud RESULTS\ud \ud A total of 15,539 mosquitoes were collected during the study. Anopheles gambiae (72.6%) was the predominant LF vector collected using PSC. Pool screen analysis of 9191 An. gambiae in 629 pools revealed no mosquitoes infected with W. bancrofti (0%; CI: 0-0.021).\ud \ud CONCLUSIONS\ud \ud These results confirm the findings of epidemiological transmission assessment surveys conducted in 2012 and 2015, which demonstrated the absence of LF transmission in Togo. The challenges of implementing molecular xenomonitoring are further discussed.

Lymphatic filariasis (LF) is a mosquito-borne disease, broadly endemic in Zambia, and is targeted for elimination by mass drug administration (MDA) of albendazole and diethylcarbamazine citrate (DEC) to at-risk populations. Anopheline mosquitoes are primary vectors of LF in Africa, and it is possible that the significant scale-up of malaria vector control over the past decade may have also impacted LF transmission, and contributed to a decrease in prevalence in Zambia. We therefore aimed to examine the putative association between decreasing LF prevalence and increasing coverage of insecticide-treated mosquito nets (ITNs) for malaria vector control, by comparing LF mapping data collected between 2003-2005 and 2009-2011 to LF sentinel site prevalence data collected between 2012 and 2014, before any anti-LF MDA was started. The coverage of ITNs for malaria was quantified and compared for each site in relation to the dynamics of LF. We found a significant decrease in LF prevalence from the years 2003-2005 (11.5% CI95 6.6; 16.4) to 2012-2014 (0.6% CI95 0.03; 1.1); at the same time, there was a significant scale-up of ITNs across the country from 0.2% (CI95 0.0; 0.3) to 76.1% (CI95 71.4; 80.7) respectively. The creation and comparison of two linear models demonstrated that the geographical and temporal variation in ITN coverage was a better predictor of LF prevalence than year alone. Whilst a causal relationship between LF prevalence and ITN coverage cannot be proved, we propose that the scale-up of ITNs has helped to control Anopheles mosquito populations, which have in turn impacted on LF transmission significantly before the scale-up of MDA. This putative synergy with vector control has helped to put Zambia on track to meet national and global goals of LF elimination by 2020.

Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF), launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA) to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs) there remained eleven ‘urban’ LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs. Methods The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC) in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR). Results The results showed that none of the 981 subjects (constituted of, Author summary Mass drug administration (MDA) for the control of elephantiasis in the state of Kano in Nigeria, started in the year 2010. It was estimated that by 2015, the MDA programme will be extended to 11 remaining urban Local Government Areas (LGAs). However, MDA in urban areas faces specific challenges, the most prominent being the need to achieve coverage rates of 65% and above. As such MDA alone may not be sufficient to achieve the required programme impacts of reducing LF transmission to levels below which transmission cannot be sustained, and additional interventions may be required. This study set out to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs in Kano. Individuals were tested for signs of the disease, and mosquito samples were collected and also tested for the worms that cause the disease. The study revealed that of 981 people tested, none had circulating filarial antigen in the blood. However, the mosquitoes collected revealed the presence of the disease-causing worms, but the level of infection was low. The infection in the mosquitoes was also detected in two different types of mosquitoes. Based on the outcomes of this study, and evidence from other West African cities on the transmission of LF, the Federal Ministry of Health recommended that two rounds of MDA be undertaken in urban areas of Kano. A further reassessment after a couple of years is warranted.

Six species of filariae infect humans in sub-Saharan Africa. We hypothesise that these nematodes are able to polyparasitise human hosts by having successfully, through competitive exclusion, adapted to distinct niches. Despite inhabiting the same host, adult stages reside in different tissue sites. Microfilariae of some species exhibit temporal separation by reaching peak levels in the blood at specific times of day. Spatial and temporal distributions in microfilaria location are exploited by the vector feeding-behaviour whereas adult survival is enhanced by occupying exclusive 'ecological' niches of the body. We present specific examples to demonstrate this concept, which is not only important from the biological aspect but important in the context of elimination programmes.

After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6–7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools. Annual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6–7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8–65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013. Although ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.

The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remain unresolved and only the morphologic species An. farauti, An. koliensis, and An. punctulatus are known as vectors of malaria in Papua New Guinea. Of 1,582 mosquitoes examined morphologically, 737 were identified as An. farauti s.l., 719 as An. koliensis, and 126 as An. punctulatus. All specimens identified morphologically as An. punctulatus were shown to be An. punctulatus by polymerase chain reaction-restriction fragment length polymorphism analysis, but the An. farauti and An. koliensis morphotypes consisted of three or more species including An. farauti s.s., An. farauti No. 2, and An. farauti No. 4. The biting cycles and role in malaria transmission of some of these species are described here for the first time. We also show evidence that An. koliensis could be a sub-complex of two or more species. The epidemiologic implications of our findings are discussed.

Mutations in the chloroquine resistance (CQR) transporter gene of Plasmodium falciparum (Pf crt ; chromosome 7) play a key role in CQR, while mutations in the multidrug resistance gene (Pf mdr1 ; chromosome 5) play a significant role in the parasite's resistance to a variety of antimalarials and also modulate CQR. To compare patterns of genetic variation at Pf crt and Pf mdr1 loci, we investigated 460 blood samples from P. falciparum -infected patients from four Asian, three African, and three South American countries, analyzing microsatellite (MS) loci flanking Pf crt (five loci [∼40 kb]) and Pf mdr1 (either two loci [∼5 kb] or four loci [∼10 kb]). CQR Pf mdr1 allele-associated MS haplotypes showed considerably higher genetic diversity and higher levels of subdivision than CQR Pf crt allele-associated MS haplotypes in both Asian and African parasite populations. However, both Pf crt and Pf mdr1 MS haplotypes showed similar levels of low diversity in South American parasite populations. Median-joining network analyses showed that the Pf crt MS haplotypes correlated well with geography and CQR Pf crt alleles, whereas there was no distinct Pf mdr1 MS haplotype that correlated with geography and/or CQR Pf mdr1 alleles. Furthermore, multiple independent origins of CQR Pf mdr1 alleles in Asia and Africa were inferred. These results suggest that variation at Pf crt and Pf mdr1 loci in both Asian and African parasite populations is generated and/or maintained via substantially different mechanisms. Since Pf mdr1 mutations may be associated with resistance to artemisinin combination therapies that are replacing CQ, particularly in Africa, it is important to determine if, and how, the genetic characteristics of this locus change over time.

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence

Microsatellite markers derived from simple sequence repeats have been useful in studying a number of human pathogens, including the human malaria parasite Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate the genetics and population characteristics of this other important human malaria parasite. We have identified a locus in a P. vivax telomeric clone that contains simple sequence repeats. Primers were designed to amplify this region using a two-step semi-nested polymerase chain reaction protocol. The primers did not amplify template obtained from non-infected individuals, nor DNA from primates infected with the other human malaria parasites (P. ovale, P. malariae, or P. falciparum). The marker was polymorphic in P. vivax-infected field isolates obtained from Papua New Guinea, Indonesia and Guyana. This microsatellite marker may be useful in genetic and epidemiologic studies of P. vivax malaria.

Background The immunochromatographic test (ICT) for lymphatic filariasis is a serological test designed for unequivocal detection of circulating Wuchereria bancrofti antigen. It was validated and promoted by WHO as the primary diagnostic tool for mapping and impact monitoring for disease elimination following interventions. The initial tests for specificity and sensitivity were based on samples collected in areas free of loiasis and the results suggested a near 100 % specificity for W. bancrofti. The possibility of cross-reactivity with non-Wuchereria bancrofti antigens was not investigated until recently, when false positive results were observed in three independent studies carried out in Central Africa. Associations were demonstrated between ICT positivity and Loa loa microfilaraemia, but it was not clearly established if these false positive results were due to L. loa or can be extended to other filarial nematodes. This study brought further evidences of the cross-reactivity of ICT card with L. loa and Onchocerca ochengi (related to O. volvulus parasite) using in vivo and in vitro systems. Methods Two filarial/host experimental systems (L. loa-baboon and O. ochengi-cattle) and the in vitro maintenance of different stages (microfilariae, infective larvae and adult worm) of the two filariae were used in three experiments per filarial species. First, whole blood and sera samples were prepared from venous blood of patent baboons and cattle, and applied on ICT cards to detect circulating filarial antigens. Secondly, larval stages of L. loa and O. ochengi as well as O. ochengi adult males were maintained in vitro. Culture supernatants were collected and applied on ICT cards after 6, 12 and 24 h of in vitro maintenance. Finally, total worm extracts (TWE) were prepared using L. loa microfilariae (Mf) and O. ochengi microfilariae, infective larvae and adult male worms. TWE were also tested on ICT cards. For each experiment, control assays (whole blood and sera from uninfected babon/cattle, culture medium and extraction buffer) were performed. Results Positive ICT results were obtained with whole blood and sera of L. loa microfilaremic baboons, culture supernatants of L. loa Mf and infective larvae as well as with L. loa Mf protein extracts. In contrast, negative ICT results were observed with whole blood and sera from the O. ochengi-cattle system. Surprisingly, culture supernatant of O. ochengi adult males and total worm extracts (Mf, infective larvae and adult worm) were positive to the test. Conclusions This study has provided further evidence of L. loa cross-reactivity for the ICT card. All stages of L. loa seem capable of inducing the cross-reactivity. Onchocerca ochengi. can also induce cross-reactivity in vitro, but this is less likely in vivo due to the location of parasite. The availability of the parasite proteins in the blood stream determines the magnitude of the cross-reactivity. The cross-reactivity of the ICT card to these non-W. bancrofti filariae poses some doubts to the reliability and validity of the current map of LF of Central Africa that was generated using this diagnostic tool. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1556-8) contains supplementary material, which is available to authorized users.

Summary Field studies were carried out to determine the impact of mass human treatment with ivermectin on the survival of anthropophagic mosquitoes of the Anopheles punctulatus complex (Diptera: Culicidae), the vectors of lymphatic filariasis and malaria in Papua New Guinea. In a village where mass treatment had been given, using 400 μg/kg ivermectin plus 6 mg/kg diethylcarbamazine citrate (DEC), we performed pre- and post-treatment collections of freshly blood-engorged mosquitoes from the same nine bedrooms. All blood-fed mosquitoes collected less than 4 days after mass treatment died within 9 days, whereas 67% of those collected before treatment survived for > 9 days. Comparison (using the log-rank test) of the survival curves for mosquitoes collected (i) before treatment, (ii)

The purpose of this study was to develop real-time multiplex quantitative PCR (qPCR) assays for the simultaneous detection of Wuchereria bancrofti (Wb), Plasmodium falciparum (Pf) and P. vivax (Pv) in mosquitoes. We optimized the assays with purified DNA samples and then used these assays to test DNA samples isolated from Anopheles punctulatus mosquitoes collected in villages in Papua New Guinea where these infections are co-endemic. Singleplex assays detected Wb, Pf and Pv DNA in 32%, 19% and 15% of the mosquito pools, respectively, either alone or together with other parasites. Multiplex assay results agreed with singleplex results in most cases. Overall parasite DNA rates in mosquitoes, estimated by PoolScreen 2 software, for Wb, Pf and Pv were 4.9%, 2.7% and 2.1%, respectively. Parasite DNA rates were consistently higher in blood-fed mosquitoes than in host-seeking mosquitoes. Our results show that multiplex qPCR can be used to detect and estimate prevalence rates for multiple parasite species in arthropod vectors. We believe that multiplex molecular xenodiagnosis has great potential as a tool for non-invasively assessing the distribution and prevalence of vector-borne pathogens such as W. bancrofti and Plasmodium spp. in human populations and for assessing the impact of interventions aimed at controlling or eliminating these diseases.

Lymphatic filariasis (LF) is a major cause of acute and chronic morbidity in the tropical and subtropical parts of the world. The availability of safe, single-dose, drug treatment regimens capable of suppressing microfilaremia to very low levels, along with improvements in techniques for diagnosing infection, has resulted in the targeting of this major mosquito-borne disease for global elimination. The Global Program to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the principal objective of breaking the cycles of transmission of Wuchereria bancrofti and Brugia spp. through the application of annual mass drug administrations (MDAs) to entire at-risk populations. Although significant progress in initiating MDA programs in endemic countries has been made, emerging challenges to this approach have raised questions regarding the effectiveness of using MDA alone to eliminate LF without the inclusion of supplementary vector control. Here, we review advances in knowledge of vector ecology, vector-parasite relationships, and both empirical and theoretical evidence regarding vector management to assess the feasibility and strategic value of including vector control in the GPELF initiative to achieve the global elimination of LF.

This study describes the relationship between transmission intensity and infection and disease due to Wuchereria bancrofti in an endemic area of Papua New Guinea. The prevalence of microfilaremia in the entire study population was 66%. Of 1892 persons examined, 6.2% and 12.3% had lymphedema of the legs and hydroceles, respectively. The prevalences of microfilaremia and clinical morbidity were lowest in persons

A popular hypothesis to explain parasite survival in the presence of a pronounced T helper 2 phenotype in helminth-parasitized populations has been FcRI blockade by parasite-induced polyclonal IgE. To begin to test the hypothesis that FcRI-bearing cells would be refractory to activation in parasitized populations, we investigated basophil function in 43 individuals from a hookworm endemic area. Study individuals had high levels of total IgE and eosinophilia and a mean hookworm burden of 2,257 epg. Basophils from all members of this parasitized population were shown to release histamine to a number of agonists, including anti IgE and a hookworm allergen, calreticulin. These data would indicate that FcRI blockade at the level of the basophil did not occur in this parasitized population despite the presence of possible immunologic blocking agents. This would suggest that this effector arm of the T helper 2 phenotype remains operative in infected populations.

The efficacy of diethylcarbamazine alone was compared with diethylcarbamazine plus albendazole in residents of an island in Papua New Guinea endemic for Wuchereria bancrofti. There was no statistically significant difference between the two drug regimens in decreasing the microfilaria positive rate at 12 and 24 months after a single-dose treatment with either regimen, e.g., 50.0% clearance of microfilaria at 24 months for diethylcarbamazine alone versus 65.7% clearance of microfilaria for diethylcarbamazine plus albendazole (P > 0.05). In contrast, diethylcarbamazine plus albendazole resulted in a significant decrease in Og4C3 antigen prevalence (17%; P = 0.003) at 24 months whereas diethylcarbamazine did not (10%; P = 0.564). These data showed no statistically significant difference in the efficacy of the two drug regimens in lowering the microfilaria reservoir, but they support the use of diethylcarbamazine combined with albendazole in mass treatment programs on the basis of greater activity against adult worms.

Background\ud \ud The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 with the goal of interrupting transmission of lymphatic filariasis (LF) through multiple rounds of mass drug administration (MDA). In Guinea, there is evidence of ongoing LF transmission, but little is known about the most densely populated parts of the country, including the capital Conakry. In order to guide the LF control and elimination efforts, serological and entomological surveys were carried out to determine whether or not LF transmission occurs in Conakry.\ud \ud Methods\ud \ud The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in people recruited from all five districts of Conakry. Mosquitoes were collected over a 1-year period, in 195 households in 15 communities. A proportion of mosquitoes were analysed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR).\ud \ud Results\ud \ud CFA test revealed no infection in the 611 individuals examined. A total of 14,334 mosquitoes were collected; 14,135 Culex (98.6 %), 161 Anopheles (1.1 %) and a few other species. Out of 1,312 Culex spp. (9.3 %) and 51 An. gambiae (31.7 %) dissected, none was infected with any stage of the W. bancrofti parasite. However, the LAMP assay revealed that 1.8 % of An. gambiae and 0.31 % of Culex spp. were positive, while PCR determined respective prevalences of 0 % and 0.19 %.\ud \ud Conclusions\ud \ud This study revealed the presence of W. bancrofti DNA in mosquitoes, despite the apparent absence of infection in the human population. Although MDA interventions are not recommended where the prevalence of ICT is below 1 %, the entomological results are suggestive of the circulation of the parasite in the population of Conakry. Therefore, rigorous surveillance is still warranted so that LF transmission in Conakry would be identified rapidly and adequate responses being implemented.

Background\ud \ud Many countries have made significant progress in the implementation of World Health Organization recommended preventive chemotherapy strategy, to eliminate lymphatic filariasis (LF). However, pertinent challenges such as the existence of areas of residual infections in disease endemic districts pose potential threats to the achievements made. Thus, this study was undertaken to assess the importance of these areas in implementation units (districts) where microfilaria (MF) positive individuals could not be found during the mid-term assessment after three rounds of mass drug administration.\ud \ud Methods\ud \ud This study was undertaken in Bo and Pujehun, two LF endemic districts of Sierra Leone, with baseline MF prevalence of 2 % and 0 % respectively in sentinel sites for monitoring impact of the national programme. Study communities in the districts were purposefully selected and an assessment of LF infection prevalence was conducted together with entomological investigations undertaken to determine the existence of areas with residual MF that could enable transmission by local vectors. The transmission Assessment Survey (TAS) protocol described by WHO was applied in the two districts to determine infection of LF in 6–7 year old children who were born before MDA against LF started.\ud \ud Results\ud \ud The results indicated the presence of MF infected children in Pujehun district. An. gambiae collected in the district were also positive for W. bancrofti, even though the prevalence of infection was below the threshold associated with active transmission.\ud \ud Conclusions\ud \ud Residual infection was detected after three rounds of MDA in Pujehun – a district of 0 % Mf prevalence at the sentinel site. Nevertheless, our results showed that the transmission was contained in a small area. With the scale up of vector control in Anopheles transmission zones, some areas of residual infection may not pose a serious threat for the resurgence of LF if the prevalence of infections observed during TAS are below the threshold required for active transmission of the parasite. However, robust surveillance strategies capable of detecting residual infections must be implemented, together with entomological assessments to determine if ongoing vector control activities, biting rates and infection rates of the vectors can support the transmission of the disease. Furthermore, in areas where mid-term assessments reveal MF prevalence below 1 % or 2 % antigen level, in Anopheles transmission areas with active and effective malaria vector control efforts, the minimum 5 rounds of MDA may not be required before implementing TAS. Thus, we propose a modification of the WHO recommendation for the timing of sentinel and spot-check site assessments in national programs.

Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of artemisinin drugs, a novel series of antimalarials. Our aim was to analyze the prevalence of the most commonly observed CYP2B6 alleles in malaria-endemic populations of West Africa (WA) and Papua New Guinea (PNG).Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of CYP2B6*1A, *2, *3, *4, *5, *6, *7, and *9 were determined in WA (n=166) and PNG (n=174). To compare with the results of previous studies, we also determined the allele frequencies in 291 North Americans of various ethnic groups.Significant differences were observed between WA and PNG for the frequencies of alleles CYP2B6*1A (45% vs 33%, P = 0.003), *2 (4% vs. 0%, P0.001), *6 (42% vs 62%, P0.001), and *9 (8% vs 1%, P0.001), and genotypes *1A/*9 (9% vs 0%, P0.001) and *6/*6 (17% vs 43%, P0.001). The frequencies of CYP2B6 genotypes in the populations were in Hardy-Weinberg equilibrium, except for PNG where an overall significant deficit of heterozygosity was observed (H (O)=0.431, H (E)=0.505, P=0.004). The allele frequencies in Asian-Americans and Caucasians-Americans were comparable to those documented for Japanese and Caucasian populations.CYP2B6 variants, previously shown to affect metabolism of a variety of drugs, occur in WA and PNG, and there are significant genetic differences at the CYP2B6 locus in these populations. It may be important to determine if these differences alter the efficacy of artemisinin drugs.

Ethnopharmacological relevance Most adults in West Africa treat acute febrile illnesses with local herbs, but the patterns of herbs used for malaria have not been recently described in Sierra Leone. Materials and methods We used a population-based cross-sectional approach to interview 810 randomly-sampled rural and urban adult residents of Bo, Sierra Leone, in December 2013 and January 2014 about their use of herbal remedies when they suspect they have malaria. Results In total, 55% of the participants reported taking one or more of seven herbs to treat symptoms of malaria. Among herb users, the most commonly used anti-malarial herbs were Moringa oleifera (moringa, 52%) and Sarcocephalus latifolius (yumbuyambay, 50%). The other herbs used included Senna siamea (shekutoure, 18%), Cassia sieberiana (gbangba, 18%), Uvaria afzelii (gone-botai, 14%), Morinda chrysorhiza (njasui, 14%), and Craterispermum laurinum (nyelleh, 7%). Combination herbal therapy was common, with 37% of herb users taking two or more herbs together when ill with suspected malaria. Conclusions Indigenous medical knowledge about herbal remedies and combinations of local herbs remains an integral part of malaria case management in Sierra Leone.

The cytoadherence-linked asexual gene 9 (clag 9) of Plasmodium falciparum has been implicated in the cytoadherence of infected erythrocytes. To determine the immunogenicity of the clag 9 gene product (CLAG 9 protein) in humans, we measured antibody responses to 11 synthetic CLAG 9 peptides in a group of 177 asymptomatic children and adults subject to intense malaria exposure in Madang, Papua New Guinea. The CLAG 9 peptides were immunogenic in adults and children. Antibody responses to peptides 4 and 10 were high across all age groups and detectable in a majority of children less than five years of age. While CLAG 9 peptides are immunogenic in humans, longitudinal studies will be required to determine the longevity of antibody responses to CLAG 9 and their role in protection from disease.

Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTT(n)) 2.5 kilobases upstream from the NOS2 transcription start site and two single nucleotide substitutions: G(r)C at position -954 (G-954C) and C(r)T at position -1173 (C-1173T). Although hypothesized to influence NO production in vivo the functional relevance of (CCTTT) (n) and G-954C is uncertain because disease association studies have yielded inconsistent results. This study found no association between CCTTT repeat number and levels of plasma NO metabolites or peripheral blood mononuclear cell NOS activity in a cohort of asymptomatic malaria-exposed coastal Papua New Guineans 1-60 years old. This suggests that (CCTTT) (n) does not independently influence NOS2 transcription in vivo. Neither the G-954C nor the C-1173T polymorphisms were identified in this population indicating the variability and complexity of selection for NOS2 promoter polymorphisms in different malaria-endemic populations. (authors)

Interleukin-12 (IL-12) has been inversely associated with disease severity in human and murine malaria, and a polymorphism in the IL-12 p40 subunit gene ( IL12B ) has been associated with susceptibility to human cerebral malaria and reduced nitric oxide (NO) production. To better define the relationships between IL-12, NO, malaria parasitemia, and IL12B polymorphisms during malarial tolerance, plasma IL-12 levels and peripheral blood mononuclear cell NO synthase (NOS) activity were measured in asymptomatic Papua New Guineans exposed to intense malaria transmission. The IL-12 level was strongly inversely correlated with the density of Plasmodium falciparum parasitemia (ρ = −0.45; P < 0.001) and was predicted to decrease by 19% (95% confidence interval [CI], 10 to 27%) for each twofold increase in P. falciparum parasitemia. This is consistent with a suppressive effect of parasitemia on IL-12 production, an effect previously shown in vitro and in rodent models of disease. The IL-12 level was inversely correlated with NOS activity ( r = −0.22; P = 0.007), with each twofold increase in NOS activity being predictive of a 25% (95% CI, 7 to 38%) decrease in plasma IL-12 levels. This probably reflects additional down-regulation of IL-12 by the high basal NO production and monocyte NOS expression found in the malaria-tolerant state. Neither the IL-12 level nor NOS activity was associated with either of two IL12B polymorphisms, reflecting the diversity of genetic control over immune responses in different populations.

Plasmodium vivax malaria is widely distributed throughout the world and accounts for over half of all malaria infections outside of Africa and about 10% of malaria infections in Africa (15). The intraerythrocytic stage of the parasite in humans requires specific receptor-ligand interactions for successful invasion of its host (6). P. vivax invasion of erythrocytes is absolutely dependent on binding to the Duffy blood group. As a result, Duffy-negative individuals are completely resistant to P. vivax malaria (19). One member of a large family of erythrocyte binding proteins, referred to as the Duffy binding protein (DBP), mediates binding to the Duffy blood group or Duffy receptor for chemokines (DARC), since this Duffy blood group antigen has been identified to be a chemokine receptor (14). The critical binding motif of P. vivax DBP lies within a cysteine-rich domain referred to as region II between amino acids (aa) 291 and 460 (21). Region II of DBP (DBPII) may be a critical target for host protective immunity, based on several observations. First, certain regions of DBPII are highly polymorphic (24, 25) and appear to be maintained by immune selection (11). Second, antibodies to DBPII from populations in areas endemic for P. vivax inhibit binding of COS-7 cells that express DBPII ligand on their surface to DARC-positive erythrocytes (16, 23). Third, antibodies raised to region II of the Plasmodium knowlesi α protein, a molecule that is 70% homologous to P. vivax DBP and also mediates DARC-dependent infection of human erythrocytes, can inhibit P. knowlesi invasion of human erythrocytes (22). Residents of areas endemic for P. vivax develop progressively stronger humoral and cellular immune responses with increasing age (13, 16, 18, 26), and dominant T-cell epitopes within the critical binding motif of DBPII have been identified (26). The relationship of these antibody responses in the context of concurrent P. vivax infection has not been evaluated in detail, and which regions of DBPII are preferentially recognized by antibodies has not been assessed. The present study aims to relate antibodies to DBP with age and infection in a population in an area of Papua New Guinea (PNG) endemic for P. vivax to identify linear B-cell epitopes within the critical binding motif of DBPII, to determine whether they correspond to polymorphic regions in the molecule, and to determine if variants are differentially recognized by sera from partially immune subjects.

The induction of neutralizing immunity to Plasmodium falciparum toxins by vaccination has been proposed as a preventive strategy to limit the severity of malaria. For this approach to be successful, generation of a sustained immune response would be necessary. This study shows that immunoglobulin G (IgG)-subclass responses elicited by the proposed P. falciparum toxin glycosylphosphatidylinositol (GPI) in Papua New Guinean subjects 5-60 years old predominantly involve IgG(3), with a lesser contribution from IgG(1) and an absence of IgG(2) and IgG(4). IgG(3) levels declined sharply within 6 weeks of pharmacological clearance of parasitemia in all subjects, whereas a significant decrease in IgG(1) levels was seen only in subjectsor =19 years old. Because the natural antibody response to P. falciparum GPIs is skewed toward the short-lived IgG(3) subclass, a vaccination strategy with GPI analogues would likely require augmentation by costimulatory molecules, to induce a more persistent anti-GPI response.

Lymphatic filariasis is a significant public health problem in several Pacific island countries. Papua New Guinea is one of the most populous countries in this region, and 39% of its residents are estimated to be infected with Wuchereria bancrofti. The Ministries of Health of the 22 islands and territories in the Pacific region are committed to taking action against lymphatic filariasis. Accordingly, a regional collaborative effort aimed at the control of filariasis has been organized under the auspices of a program referred to as PacELF. The main objective of PacELF is to eliminate filariasis as public health problem in the Pacific region by the year 2010, 10 years before global elimination of this infectious disease has been targeted. This contribution describes the epidemiology and ecological features of filariasis and prospects for its elimination in Papua New Guinea. The frequencies of microfilaremia, chronic lymphatic disease, and acute filarial morbidity in Papua New Guinea are higher than in many other endemic countries of the Pacific, Africa, and South America. All possible combinations of these three manifestations of filariasis exist. They occur independently of each other, and there is no association between chronic lymphatic disease and microfilarial status. Anopheles punctulatus mosquitoes are the main vectors throughout the country. Transmission intensity is heterogeneous and a major determinant of local patent infection and morbidity rates. Annual transmission potential and annual infective biting rates are positively associated with the village-specific microfilarial rate, mean intensity of microfilaremia, and prevalence of leg edema. Children and adults have similar worm burdens, assessed by circulating filarial antigen levels, in areas of high transmission, whereas worm burdens increase with age in areas of lower transmission. Intensity of exposure to infective third-stage larvae (L3) is significantly correlated with filarial antigen-specific lymphocyte proliferation and cytokine production, possibly by a mechanism that alters APC function. Historical evidence suggests that residual insecticide spraying conducted for malaria control in some parts of the country interrupted transmission of W. bancrofti as it did in the Solomon Islands. Prospects for eliminating lymphatic filariasis in Papua New Guinea are good and may be achieved by the end of the second decade of the twenty-first century if an integrated control approach using mass drug administration with vector control is adopted.

Despite the growing evidence that insecticide-treated mosquito nets reduce malaria morbidity and mortality in a variety of epidemiological conditions, their value against lymphatic filariasis infection and disease is yet to be established. The impact of untreated bednets on the prevalence of Wuchereria bancrofti (Cobbold) (Nematoda: Filarioidea) infection and disease was investigated on Bagabag island in Papua New Guinea, where both malaria and filariasis are transmitted by the same vector mosquitoes of the Anopheles punctulatus Donitz group (Diptera: Culicidae). Community-wide surveys were conducted recording demographic characteristics including bednet usage. Physical examinations for hydrocoele and lymphoedema were performed and blood samples assessed for filarial and malaria parasites. Mosquitoes were sampled using the all-night landing catch method and individually dissected to determine W. bancrofti infection and infective rates. Bednet usage among residents was 61% and the mean age of users (25.6 years) was similar to non-users (22.5 years). Anopheles farauti Laveran was the only species were found to contain filarial larvae: 2.7% infected (all stages), 0.5% infective (L3). The overall W. bancrofti microfilaraemia and antigenaemia rates were 28.5% and 53.1%, respectively. Bednet users had lower prevalence of W. bancrofti microfilaraemia, antigenaemia and hydrocoele rates than non-users. In comparison, untreated bednets had no effect on the prevalence and intensity of Plasmodium falciparum and P. vivax infections. The impact of bednet usage on rates of microfilaraemia and antigenaemia remained significant even when confounding factors such as age, location and sex were taken into account, suggesting that untreated bednets protect against W. bancrofti infection.

Purpose The purpose of this study was to conduct syndromic surveillance for important veterinary diseases in Koinadugu district, Northern Province, Sierra Leone. Methods This study examined all veterinary syndromic surveillance reports submitted to the district veterinary office from January 2011 through December 2012. Results In total, 5679 case reports were submitted, including 2394 fatalities. The most common syndrome reported was consistent with peste de petits ruminants (PPR) in goats (n= 1649). PPR cases were reported from eight of 11 chiefdoms in the district, with a 42 per 1000 reported incidence rate and a 48 % case fatality rate. Other syndromes reported were consistent with trypanosomiasis in cattle (n=1402), Newcastle disease in poultry (n=911), black quarter in cattle (n=691), and haemorrhagic septicaemia in cattle (n=542). Conclusions Expanded use of the PPR virus vaccine may be required to help control the spread of the infection. Improved community-based prevention efforts may be effective for better control of trypanosomiasis and all these conditions.

Background\ud \ud Neglected tropical diseases (NTDs) predominantly occur in resource poor settings where they often present a serious public health burden. Sustained global advocacy has been important in raising awareness of NTDs and the relatively low cost for control of helminthic NTDs using preventive chemotherapy. This enthusiasm was boosted at the London declaration on NTDs in 2012 through commitments by different partners to avail resources required for control of NTDs particularly those that employ preventive chemotherapy as the major intervention strategy. Subsequently, national NTD programmes are responding to these new opportunities by implementing preventive chemotherapy including school-based deworming (SBD). Further, with the availability of increased resources, both financial and pharma, the optimal strategies for implementing preventive chemotherapy in highly endemic settings are under debate and this paper goes some way to addressing this issue in a specific setting in coastal Kenya.\ud \ud Methods\ud \ud We conducted a repeated cross-sectional study in Matuga District, Kwale County, Kenya to evaluate the effect of school-based co-administration of praziquantel and albendazole against urogenital schistosomiasis and soil-transmitted helminth (STH) infections. A total of 1022 school children in 5 study schools were tested for the infections in urine and stool samples during a baseline survey in September 2009. The presence of Schistosoma haematobium infection was determined by the urine filtration method while STH infections were determined by Kato-Katz technique.\ud \ud Results\ud \ud Urogenital schistosomiasis and hookworm infection were the major parasitic infections among the children in the study area. There was significant decrease in both prevalence and intensity of S. haematobium infection after treatment but varying levels of rebound were observed during the period between the treatments. The school-based treatment, however, did not have any significant effect on both the prevalence and intensity of hookworm infection.\ud \ud Conclusions\ud \ud Once per year SBD programmes may not be adequate for controlling hookworm infection and urogenital schistosomiasis in rural areas of Kwale County. There is a need to consider expanded preventive chemotherapy strategies that will allow inclusion of the adult populations. Community-based health education campaigns focusing on increasing household latrine ownership and use, as a complementary measure to control STH and urogenital schistosomiasis in similar settings, may also be useful.

Background\ud \ud Soil-transmitted helminths and schistosomiasis are mostly prevalent in developing countries due to poor sanitation and lack of adequate clean water. School-age children tend to be the target of chemotherapy-based control programmes because they carry the heaviest worm and egg burdens. The present study examines adverse events (AEs) experienced following co-administration of albendazole and praziquantel to school-age children in a rural area in Kwale County, Kenya.\ud \ud Methods\ud \ud Children were treated with single doses of albendazole and praziquantel tablets and then interviewed using a questionnaire for post treatment AEs.\ud \ud Results\ud \ud Overall, 752 children, 47.6% boys, participated in the study. Their median (interquartile range) age was 12.0 (10.0–14.0) years. A total of 190 (25.3%) children reportedly experienced at least one AE. In total, 239 cases of AEs were reported with the most frequent being abdominal pains (46.3%), dizziness (33.2%) and nausea (21.1%). Majority of the reported AEs (80.8%) resolved themselves while 12.1% and 6.3% were countered by, respectively, self-medication and visiting a nearby health facility. More girls (60.5%) than boys (39.5%) reported AEs (P = 0.027).\ud \ud Conclusions\ud \ud The AEs were mild and transient, and were no worse than those expected following monotherapy. The current study adds to the evidence base that dual administration of albendazole and praziquantel in school-based mass drug administration is safe with only mild adverse events noted.

Introduction\ud \ud Lymphatic filariasis is a debilitating disease caused by the filarial worm Wuchereria bancrofti. It is earmarked for elimination by the year 2020 through the Global Program for the Elimination of LF (GPELF). In Ghana, mass treatment has been on-going since the year 2000. Earlier studies have revealed differing epidemiology of LF in the North and South of Ghana. This study was therefore aimed at understanding the possible impacts of W. bancrofti diversity on the epidemiology and control of LF in Ghana.\ud \ud Methods\ud \ud The Mitochondrial, Cytochrome C Oxidase I gene of W. bancrofti samples was sequenced and analyzed. The test sequences were grouped into infrapopulations, and pairwise differences (Π) and mutation rates (θ) were computed. The amount of variance within and among populations was also computed using the AMOVA. The evolutionary history was inferred using the Maximum Parsimony method.\ud \ud Results\ud \ud Seven samples from the South and 15 samples from the North were sequenced, and submitted to GenBank with accession numbers GQ479497- GQ479518. The results revealed higher mutation frequencies in the southern population, compared to the northern population. Haplotype analyses revealed a total of 11 haplotypes (Hap) in all the 22 DNA sequences, with high genetic variation and polymorphisms within the southern samples.\ud \ud Conclusion\ud \ud This study showed that there is considerable genetic variability within W. bancrofti populations in Ghana, differences that might explain the observed epidemiology of LF. Further studies are however required for an in-depth understanding of LF epidemiology and control.

The relationship between filarial antigenemia and lymphatic pathology was investigated in residents of 11 villages in an area of Papua New Guinea where Wuchereria bancrofti is endemic. Antigenemia was determined in 1322 persons by means of the Og4C3 antibody capture assay. Prevalence of antigenemia by village ranged from 61.7% to 98.2% and did not vary by sex. Antigen level increased with transmission potential among the 4 villages with measured transmission potential (r(2)=.945; P=.028). Antigenemia was associated positively with age in villages with the lowest annual transmission potentials (45 and 404 infective larvae/year; P

Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-119 antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-119–based vaccines.

Lassa fever (LF) is a potentially lethal human disease that is caused by the arenavirus Lassa virus (LASV). Annually, around 300,000 infections with up to 10,000 deaths occur in regions of Lassa fever endemicity in West Africa. Here we demonstrate that mice lacking a functional STAT1 pathway are highly susceptible to infection with LASV and develop lethal disease with pathology similar to that reported in humans.

Background Nigeria has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa. Methodology/Principal findings LF data from the literature and Federal Ministry of Health (FMoH) were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net (LLIN) distributions for malaria were incorporated into overlay maps using geographical information system (GIS) software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n = 162 locations). Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (, Author Summary Nigeria is estimated to have the highest burden of lymphatic filariasis (LF), a disease also known as elephantiasis, which is transmitted by mosquitoes and caused by the parasite Wuchereria bancrofti. The National LF Elimination Programme is planning to scale up the elimination programme through mass drug administration of ivermectin and albendazole. However, a major constraint to this expansion is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa, the causative agent of tropical eye worm (loiasis). To better understand this and other factors that may impact on LF elimination, we collated and mapped all available LF data, and highlighted the overlaps with predicted loiasis prevalence distributions, onchocerciasis ivermectin treatment areas, and bed net distributions for malaria. This study provides a baseline overview for the LF Programme and will help to maximize existing disease interventions, ensuring cost effective use of resources as the programme scales up.

Global efforts to eliminate lymphatic filariasis are based on the annual mass administration of antifilarial drugs to reduce the microfilaria reservoir available to the mosquito vector. Insecticide-treated bed nets are being widely used in areas in which filariasis and malaria are coendemic.We studied five villages in which five annual mass administrations of antifilarial drugs, which were completed in 1998, reduced the transmission of Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anopheles mosquitoes were collected for 26 months before and 11 to 36 months after bed nets treated with long-lasting insecticide were distributed in 2009. We evaluated the status of filarial infection and the presence of W. bancrofti DNA in anopheline mosquitoes before and after the introduction of insecticide-treated bed nets. We then used a model of population dynamics to estimate the probabilities of transmission cessation.Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for 11 months after distribution (P0.001). During the same period, the rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae inoculated per person per year before the bed-net distribution and 0 after the distribution. Among all five villages with a prevalence of microfilariae of 2 to 38%, the probability of transmission cessation increased from less than 1.0% before the bed-net distribution to a range of 4.9 to 95% in the 11 months after distribution.Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and the National Institutes of Health.).

Background Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it is possible to reduce the prevalence of Wb in humans and mosquitoes through mass drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs in the Dreikikir region through 1998 significantly reduced prevalence of Wb infection, parasites continue to be transmitted in the area. Methods We sequenced the Wb mitochondrial Cytochrome Oxidase 1 (CO1) gene from 16 people infected with Wb. Patients were selected from 7 villages encompassing both high and moderate annual transmission potentials (ATP). We collected genetic data with the objectives to (i) document contemporary levels of genetic diversity and (ii) distinguish between populations of parasites and hosts across the study area. Principle Findings We discovered 109 unique haplotypes currently segregating in the Wb parasite population, with one common haplotype present in 15 out of 16 infections. We found that parasite diversity was similar among people residing within the same village and clustered within transmission zones. For example, in the high transmission area, diversity tended to be more similar between neighboring villages, while in the moderate transmission area, diversity tended to be less similar. Conclusions In the Dreikikir region of PNG there are currently high levels of genetic diversity in populations of Wb. High levels of genetic diversity may complicate future MDAs in this region and the presence of dominant haplotypes will require adjustments to current elimination strategies., Author Summary The Global Program to Eliminate Lymphatic Filariasis (LF), initiated by the World Health Organization (WHO), aims to eliminate LF from endemic regions, where 1.34 billion people live at risk of this disease. The causative agent responsible for 90% of LF is the nematode parasite species Wuchereria bancrofti (Wb). The primary approach to LF elimination has been through mass drug administration (MDA), which serves to interrupt transmission by killing the microfilaria required to continue the parasite life cycle through mosquito transmission. Despite success of MDA, evidence indicates that transmission can rebound if drug administration is discontinued. In the void of well-characterized genetic markers, it is difficult to understand how a Wb population will be impacted by or recover from MDA. Here we use recently described mitochondrial DNA polymorphisms to evaluate the diversity of a Wb population that has been previously exposed to MDA in Papua New Guinea. Our data analyses reveal significant genetic diversity and evidence that MDA has not significantly reduced the genetic complexity of the Wb population. This study describes a population genetic approach for assessing the impact of MDA and other transmission control strategies.

It was in Freetown, Sierra Leone, that the malaria mosquito Anopheles coastalis, now known as Anopheles gambiae, was first discovered as the vector of malaria, in 1899. That discovery led to a pioneering vector research in Sierra Leone and neighbouring Liberia, where mosquito species were extensively characterized. Unfortunately, the decade long civil conflicts of the 1990s, in both countries, resulted in a stagnation of the once vibrant research on disease vectors. This paper attempts to fill in some of the gaps on what is now known of the distribution of the sibling species of the An. gambiae complex, and especially the An. coluzzii and An. gambiae s.s, formerly known as the An. gambiae molecular M and S forms respectively, in the cities of Freetown and Monrovia.

Vector control, including the use of bed nets, is recommended as a possible strategy for eliminating lymphatic filariasis (LF) in post-conflict countries such as the Democratic Republic of Congo (DRC). This study examined the geographical factors that influence bed net ownership in DRC in order to identify hard-to-reach communities that need to be better targeted. In particular, urban/rural differences and the influence of population density, proximity to cities and health facilities, plus access to major transport networks were investigated. Demographic and Health Survey geo-referenced cluster level data were used to map bed net coverage (proportion of households with at least one of any type of bed net or at least one insecticide-treated net (ITN)), and ITN density (ITNs per person) for 260 clusters. Bivariate and multiple logistic or Poisson regression analyses were used to determine significant relationships. Overall, bed net (30%) and ITN (9%) coverage were very low with significant differences found between urban and rural clusters. In rural clusters, ITN coverage/density was positively correlated with population density (r = 0.25, 0.27 respectively, p