The impact of residual infections on Anopheles-transmitted Wuchereria bancrofti after multiple rounds of mass drug administration

Background 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. Methods 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. Results 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. Conclusions 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

The Use of Mobile Electronic Devices for Public Health Data Collection and Syndromic Surveillance at the Republic Of Sierra Leone Armed Forces

Public health data collection methods in Sierra Leone were compared. First, a household health census was conducted with some interviewers using paper-based forms requiring later data entry and others using tablet computers for immediate electronic data inputting. Electronic data-entry surveys were more time-efficient and accurate than paper-based surveys. In a second evaluation, military Medical Inspection rooms (MIRs) sent syndromic surveillance reports to a central communications hub via cell phone or paper-based forms. The report compliance rate was 89% for daily SMS and 100% for weekly SMS versus 76% for weekly paper reports. Electronic data collection and reporting is feasible and cost-efficient in low-resource settings.Keywords: mobile phones, text messaging, database management systems, census methods, sentinelsurveillanc

Improved mapping strategy to better inform policy on the control of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic in Sierra Leone confirmed by national mapping in 2008. To better inform planning of preventive chemotherapy strategy, another survey was conducted before mass drug administration (MDA) in seven districts according to the mapping results or local knowledge. Fifty-nine chiefdoms and one school in every chiefdom were selected. Thirty school children aged 9-14 years from each school (total: 1760) were examined by parasitological methods for infection with <it>Schistosoma mansoni </it>and STHs.</p> <p>Results</p> <p>The overall prevalence of <it>S. mansoni </it>was 40.2% (95% confidence interval (CI): 37.9-42.5%), particularly in Kailahun (63.3%), Kenema (46.7%), Koinadugu (41.9%) and Kono (71.7%). The results demonstrated the focal distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts with prevalence ranging from 0.0-63.3%, 3.3-90.0% and 0.0-67.9% respectively. The arithmetic mean intensity of <it>S. mansoni </it>infection was 95.4 epg (95% CI: 61.4-129.5 epg), Heavy mean intensity of infection was found in Kailahun (120.2 epg), Kenema (104.5 epg), Koinadugu (112.3 epg) and Kono (250.3 epg). Heavy or moderate infection with <it>S. mansoni </it>occurred in 20.7% of children examined. Hookworm prevalence was moderate: 31.2% (95% CI: 29.1-33.4%), but high in Bo (50.0%) and Tonkolili (56.7%). Hookworm intensity of infection was light with a mean epg of 53.0 (95% CI: 38.4-67.7 epg). Prevalence and intensity of <it>Ascaris lumbricoides </it>(1.5%, 17.8 epg) and <it>Trichuris trichiura </it>(2.5%, 20.3 epg) was low.</p> <p>Conclusions</p> <p>The prediction by previous spatial analysis that <it>S. mansoni </it>was highly endemic across north-eastern Sierra Leone was confirmed with a significant proportion of children heavily or moderately infected. The distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts ranged widely, highlighting the importance of considering the nature of focal transmission in national mapping exercises. These results were used to refine the MDA for schistosomiasis control to chiefdom implementation units rather than the entire district in these 3 districts. The survey demonstrated that sufficient number of survey sites for schistosomiasis mapping in each district should be used to provide a better national planning of MDA activities, and that it is affordable with the contributions from all parties involved and national resources mobilized.</p

Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial.

BACKGROUND: Children account for a substantial proportion of cases and deaths during Ebola virus disease outbreaks. We aimed to evaluate the safety and immunogenicity of a booster dose of the Ad26.ZEBOV vaccine in children who had been vaccinated with a two-dose regimen comprising Ad26.ZEBOV as dose one and MVA-BN-Filo as dose two. METHODS: We conducted an open-label, non-randomised, phase 2 trial at one clinic in Kambia Town, Sierra Leone. Healthy children, excluding pregnant or breastfeeding girls, who had received the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in a previous study, and were aged 1-11 years at the time of their first vaccine dose, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) and were followed up for 28 days. Primary outcomes were safety (measured by adverse events) and immunogenicity (measured by Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration) of the booster vaccine dose. Safety was assessed in all participants who received the booster vaccination; immunogenicity was assessed in all participants who received the booster vaccination, had at least one evaluable sample after the booster, and had no major protocol deviations that could have influenced the immune response. This trial is registered with ClinicalTrials.gov, NCT04711356. FINDINGS: Between July 8 and Aug 18, 2021, 58 children were assessed for eligibility and 50 (27 aged 4-7 years and 23 aged 9-15 years) were enrolled and received an Ad26.ZEBOV booster vaccination, more than 3 years after receiving dose one of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. The booster was well tolerated. The most common solicited local adverse event during the 7 days after vaccination was injection site pain, reported in 18 (36%, 95% CI 23-51) of 50 participants. The most common solicited systemic adverse event during the 7 days after vaccination was headache, reported in 11 (22%, 12-36) of 50 participants. Malaria was the most common unsolicited adverse event during the 28 days after vaccination, reported in 25 (50%, 36-64) of 50 participants. No serious adverse events were observed during the study period. 7 days after vaccination, the Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration was 28 561 ELISA units per mL (95% CI 20 255-40 272), which was 44 times higher than the geometric mean concentration before the booster dose. 21 days after vaccination, the geometric mean concentration reached 64 690 ELISA units per mL (95% CI 48 356-86 541), which was 101 times higher than the geometric mean concentration before the booster dose. INTERPRETATION: A booster dose of Ad26.ZEBOV in children who had received the two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen more than 3 years earlier was well tolerated and induced a rapid and robust increase in binding antibodies against Ebola virus. These findings could inform Ebola vaccination strategies in paediatric populations. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial

Background The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. Methods The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5×1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1×108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant’s last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. Findings Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736–6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312–4383]) at 21 days after the second vaccination. Interpretation The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Impact of three rounds of mass drug administration on lymphatic filariasis in areas previously treated for onchocerciasis in Sierra Leone.

BACKGROUND 1974-2005 studies across Sierra Leone showed onchocerciasis endemicity in 12 of 14 health districts (HDs) and baseline studies 2005-2008 showed lymphatic filariasis (LF) endemicity in all 14 HDs. Three integrated annual mass drug administration (MDA) were conducted in the 12 co-endemic districts 2008-2010 with good geographic, programme and drug coverage. Midterm assessment was conducted 2011 to determine impact of these MDAs on LF in these districts. METHODOLOGY/PRINCIPAL FINDINGS The mf prevalence and intensity in the 12 districts were determined using the thick blood film method and results compared with baseline data from 2007-2008. Overall mf prevalence fell from 2.6% (95% CI: 2.3%-3.0%) to 0.3% (95% CI: 0.19%-0.47%), a decrease of 88.5% (p = 0.000); prevalence was 0.0% (100.0% decrease) in four districts: Bo, Moyamba, Kenema and Kono (p = 0.001, 0.025, 0.085 and 0.000 respectively); and seven districts had reductions in mf prevalence of between 70.0% and 95.0% (p = 0.000, 0.060, 0.001, 0.014, 0.000, 0.000 and 0.002 for Bombali, Bonthe, Kailahun, Kambia, Koinadugu, Port Loko and Tonkolili districts respectively). Pujehun had baseline mf prevalence of 0.0%, which was maintained. Only Bombali still had an mf prevalence ≥1.0% (1.58%, 95% CI: 0.80%-3.09%)), and this is the district that had the highest baseline mf prevalence: 6.9% (95% CI: 5.3%-8.8%). Overall arithmetic mean mf density after three MDAs was 17.59 mf/ml (95% CI: 15.64 mf/ml-19.55 mf/ml) among mf positive individuals (65.4% decrease from baseline of 50.9 mf/ml (95% CI: 40.25 mf/ml-61.62 mf/ml; p = 0.001) and 0.05 mf/ml (95% CI: 0.03 mf/ml-0.08 mf/ml) for the entire population examined (96.2% decrease from baseline of 1.32 mf/ml (95% CI: 1.00 mf/ml-1.65 mf/ml; p = 0.000)). CONCLUSIONS/SIGNIFICANCE The results show that mf prevalence decreased to <1.0% in all but one of the 12 districts after three MDAs. Overall mf density reduced by 65.0% among mf-positive individuals, and 95.8% for the entire population

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.

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. 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. 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. 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