BACKGROUND Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.)

BackgroundIn November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country.MethodsWe conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models.ResultsThe survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥1∶2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN.ConclusionsThe mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.

The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failure across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere. Using gene editing, we show that R561H, along with C580Y and M579I, confer elevated in vitro ART resistance in some African strains, contrasting with minimal changes in ART susceptibility in others. C580Y and M579I cause substantial fitness costs, which may slow their dissemination in high-transmission settings, in contrast with R561H that in African 3D7 parasites is fitness neutral. In Cambodia, K13 genotyping highlights the increasing spatio-temporal dominance of C580Y. Editing multiple K13 mutations into a panel of Southeast Asian strains reveals that only the R561H variant yields ART resistance comparable to C580Y. In Asian Dd2 parasites C580Y shows no fitness cost, in contrast with most other K13 mutations tested, including R561H. Editing point mutations in ferredoxin or mdr2, earlier associated with resistance, has no impact on ART susceptibility or parasite fitness. These data underline the complex interplay between K13 mutations, parasite survival, growth and genetic background in contributing to the spread of ART resistance.

BackgroundLymphatic filariasis elimination programs are based upon preventative chemotherapy annually in populations with prevalence more than or equal to 1%. The goal is to treat 80% of the eligible, at risk population yearly, for at least 5 years, in order to interrupt transmission and prevent children from becoming infected. This level of coverage has been a challenge in urban settings. Assessing the coverage in a rapidly growing urban/non-rural setting with inadequate population data is also problematic. In Sierra Leone, a 5-day preventative chemotherapy campaign was carried out in the Western Area including the capital: Freetown. An intensive, social mobilization strategy combined traditional and modern communication channels. To aid dissemination of appropriate information Frequently Asked Questions were developed and widely circulated. The population of the Western Area has grown faster than projected by the 2004 National Census due to the post-war settlement of internally displaced persons. As a reliable denominator was not available, independent monitoring was adapted and performed "in process" to aid program performance and "end process" to assess final coverage.ResultsIn 5 days 1,104,407 eligible persons were treated. Using the projected population from the 2004 census this figure represented coverage of 116% in the Urban Western Area and 129% in the Rural Western Area. Independent monitors interviewed a total of 9,253 persons during the 2 End Process days representing 1% of the projected population. Of these, 85.8% recalled taking both ivermectin and albendazole (Urban: 85.2%, Rural: 87.1%). No serious adverse drug reactions were reported.ConclusionThe paper presents the key elements of success of the social mobilization and implementation strategy and describes the independent monitoring used to estimate final coverage in this urban/non-rural setting where the current population size is uncertain. This implementation strategy and Independent Monitoring tool could be useful in similar, rapidly growing cities implementing lymphatic filariasis elimination programs.

A pilot clinical trial using dendritomas, purified hybrids from the fusion of dendritic/tumor cells combined with a low dose of IL-2, in metastatic melanoma patients was conducted in order to determine its safety and potential immunological and clinical responses. Ten metastatic melanoma patients were enrolled into this study. Dendritoma vaccines were created by fusing dendritic cells stained with green fluorescent dye with irradiated autologous tumor cells stained with red fluorescent dye and purifying the hybrids using immediate fluorescent-activated cell sorting. Initial vaccine was given subcutaneously and followed by IL-2 in serially elevated doses from 3-9 million units/m 2 for 5 days. Repeated vaccinations were administered without IL-2, at 3-month intervals for a maximum of 5 times. Immune reactions were measured by the increase of interferon-Á (IFN-Á) expressing T cells. Vaccine doses ranged from 250,000 to 1,000,000 dendritomas. There was no grade 2 or higher toxicity directly attributable to the vaccine. All patients experienced toxicity due to IL-2 administration (9-grade 2, 3-grade 3, 1-grade 4). Eight of nine evaluable patients demonstrated immunologic reactions by increased IFN-Á expressing T cells. One patient developed partial response at 12 weeks after the first vaccine. Nine months later, this patient achieved a complete response. In addition, two patients had stable disease for 9 and 4 months, respectively; one patient had a mixed response. Our findings demonstrated that dendritoma vaccines with a low dose of IL-2 can be safely administered to patients with metastatic melanoma and induce immunological and clinical responses.

BackgroundAs emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate–amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014–January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres.MethodsThe coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms.ResultsAfter two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38–48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41–52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32–38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39–52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29–38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13–46 %) at week 1 post-first MDA and much lower during all the weeks post–second MDA.ConclusionsThe MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1493-1) contains supplementary material, which is available to authorized users.

HighlightsThe evaluated artemisinin combination therapies were highly efficacious for the treatment of uncomplicated malaria.Pfk13 mutations and Pfplasmepsin2 multiple copies, associated with artemisinin and piperaquine resistance, respectively, were absent.The very low prevalence of the quintuple mutant detected supports the introduction of intermittent preventive treatment for infants with SP.The efficacy and molecular markers of the recommended artemisinins and partners drugs should be monitored continuously.

BackgroundPrompt, effective treatment of confirmed malaria cases with artemisinin-based combination therapy (ACT) is a cornerstone of malaria control. Maximizing adherence to ACT medicines is key to ensuring treatment effectiveness.MethodsThis open-label, randomized trial evaluated caregiver adherence to co-formulated artemether–lumefantrine (AL) and fixed-dose amodiaquine–artesunate (AQAS) in Sierra Leone. Children aged 6–59 months diagnosed with malaria were recruited from two public clinics, randomized to receive AL or AQAS, and visited at home the day after completing treatment. Analyses were stratified by site, due to differences in participant characteristics and outcomes.ResultsOf the 784 randomized children, 680 (85.6%) were included in the final per-protocol analysis (340 AL, 340 AQAS). Definite adherence (self-reported adherence plus empty package) was higher for AL than AQAS at both sites (Site 1: 79.4% AL vs 63.4% AQAS, odds ratio [OR] 2.16, compared to probable adherence plus probable or definite non-adherence, 95% confidence interval [CI] 1.34–3.49; p = 0.001; Site 2: 52.1% AL vs 37.5% AQAS, OR 1.53, 95% CI 1.00–2.33, p = 0.049). However, self-reported adherence (ignoring drug package inspection) was higher for both regimens at both sites and there was no strong evidence of variation by treatment (Site 1: 96.6% AL vs 95.9% AQAS, OR 1.19, 95% CI 0.39–3.63, p = 0.753; Site 2: 91.5% AL vs 96.4% AQAS, OR 0.40, 95% CI 0.15–1.07, p = 0.067). In Site 2, correct treatment (correct dose + timing + duration) was lower for AL than AQAS (75.8% vs 88.1%, OR 0.42, 95% CI 0.23–0.76, p = 0.004). In both sites, more caregivers in the AQAS arm reported adverse events (Site 1: 3.4% AL vs 15.7% AQAS, p < 0.001; Site 2: 15.2% AL vs 24.4% AQAS, p = 0.039).ConclusionsSelf-reported adherence was high for both AL and AQAS, but varied by site. These results suggest that each regimen has potential disadvantages that might affect adherence; AL was less likely to be taken correctly at one site, but was better tolerated than AQAS at both sites. Measuring adherence to anti-malarials remains challenging, but important. Future research should focus on comparative studies of new drug regimens, and improving the methodology of measuring adherence.Trial registration: Clinicaltrials.gov, NCT01967472. Retrospectively registered 18 October 2013, https://clinicaltrials.gov/ct2/show/NCT01967472Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2370-x) contains supplementary material, which is available to authorized users.