Ongoing Transmission Research Articles

Hundred-fold increase in SARS-CoV-2 spike antibody levels over three years in a hospital clinical laboratory.

Natural infection with the SARS-CoV-2 virus and vaccination increase the serum spike antibody levels. These levels, which differ among the various commercial assays, are used by the FDA to qualify individuals as potential COVID-19 convalescent plasma (CCP) donors. Over a 3-year period (April 2020-February 2023), we performed a retrospective analysis of spike IgG antibodies measured by a tertiary hospital clinical immunology laboratory using the Euroimmun SARS-CoV-2 IgG ELISA. The 3-year interval was classified into five periods based on the SARS-CoV-2 strain variant epidemiology. A total of 15,820 sera, derived from 11,022 individuals (6,362 females and 4,660 males) ranging from severe immunocompromised state to routine health visits, were tested. Spike IgG levels rose significantly over time, from a median ELISA 0.13 Arbitrary Units (AU) in the first period to 48.7 in the last period (P < 0.0001). The 80th percentile of the spike IgG distribution was 0.55, 8.1, 9.6, 64.9, and 151 AU in the five periods. Using 3.5 AU, the FDA threshold for qualifying CCP donors with this Euroimmun assay, the percentage of subjects eligible for CCP donation would have been 11%, 44%, 61%, 81%, and 91% in the five time periods. Overall, spike antibody levels have risen more than 100-fold during the pandemic, while SARS-CoV-2 variants have become resistant to monoclonal antibodies. Since CCP containing high titers of spike antibodies is known to be most effective against variants, restricting CCP donors to those with antibody values in the upper two deciles may allow greater therapeutic transfusion protection.IMPORTANCEDespite the evolution of SARS-CoV-2 variants of concern and ongoing transmission, COVID-19 hospitalization and mortality rates continue to decline. Both the percent seropositive and antibody levels have risen over the past 3 years. Here, we observe more than 90% seropositivity as well as more than a hundred-fold increase in spike IgG levels in a tertiary hospital clinical immunology laboratory setting. Antibody effector functions (such as neutralization, opsonization, and complement activation) and cell-mediated immunity all contribute to protection from COVID-19 progression to hospitalization, and all correlate to the total SARS-CoV-2 antibody levels. We recommend therapeutic COVID-19 convalescent plasma be restricted to the top 20% of potential donors to maintain activity against ongoing SARS-CoV-2 variant evolution.

Onchocerciasis-associated epilepsy: an explorative case-control study with viral metagenomic analyses on Onchocerca volvulus

Background A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the O. volvulus virome and identify potential neurotropic viruses linked to OAE. Methods In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared. Ethics and dissemination The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications. Registration ClinicalTrials.gov registration NCT05868551 (https://clinicaltrials.gov/study/NCT05868551). Protocol version 1.1, dated 09/05/2023.

Five years of post-validation surveillance of lymphatic filariasis in Thailand

BackgroundThe World Health Organization (WHO) validated Thailand in 2017 as having eliminated lymphatic filariasis (LF) as a public health problem with recommendations for continued surveillance. This article describes measures and progress made in Thailand with post-validation surveillance (PVS) of LF from 2018 until 2022.MethodsThe implementation unit (IU) is a sub-village in 11 former LF endemic provinces. Human blood surveys are targeted in 10% of IUs each year. In Wuchereria bancrofti areas, filaria antigen test strips (FTS) are used, and in Brugia malayi areas, antibody test kits (Filaria DIAG RAPID) are used. Positive cases are confirmed by thick blood film (TBF) and polymerase chain reaction (PCR). Vector surveys for mosquito species identification and dissection for microfilaria (Mf)/filarial larvae are done in 1% of IUs where human blood surveys are conducted. Human blood surveys using FTS are conducted among migrants in five provinces. Surveillance of cats is done in areas that previously recorded > 1.0% Mf rate among cats. Morbidity management and disability prevention (MMDP) are done every 2 years in LF-endemic areas where chronic disease patients reside.ResultsFrom 2018 to 2022, in a total of 357 IUs in 11 provinces, human blood surveys were conducted in 145 IUs (41%) with an average population coverage of 81%. A total of 22,468 FTS and 27,741 FilariaDIAG RAPID were performed. 27 cases were detected: 3 cases of W. bancrofti in Kanchanaburi province and 24 cases of B. malayi in Narathiwat province. 4 cases of W. bancrofti were detected in two provinces through routine public health surveillance. Vector surveys in 47 IUs detected B. malayi Mf filarial larvae only in Narathiwat province. Chronic LF patients reduced from 114 in 2017 to 76 in 2022. Surveys among 7633 unregistered migrants yielded 12 cases of W. bancrofti. Mf rate among cats in Narathiwat province declined from 1.9% in 2018 to 0.7% in 2022. MMDP assessments revealed gaps in healthcare provider’s management of chronic cases due to staff turnover.ConclusionsIn 2022, after 5 years of PVS, Thailand re-surveyed 41% of its previously endemic IUs and demonstrated ongoing transmission in only one province of Narathiwat, where Mf prevalence is below the WHO provisional transmission threshold of 1%. This study highlights the importance of continued disease surveillance measures and vigilance among health care providers in LF receptive areas.Graphical

Hand dermatitis, Prevalence and Risk Factors among Healthcare Workers during the COVID-19

Background: Healthcare workers (HCWs) need to perform new preventive measures to protect themselves and patients against ongoing COVID-19 transmission, which can increase hand dermatitis (HD) among them. This study aims to investigate the prevalence of HD among HCWs and its possible risk factors in IRAN. Methods: A survey of 159 HCWS working in university hospitals was performed from August to September 2020 in a cross-sectional study. Research data were collected via standardized self-administered questionnaire. The history of HD was determined via standardized Nordic Occupational Skin Questionnaire (NOSQ-2002). Results: The prevalence of HD in the study population was 51.6%. A significant association was found between the prevalence of HD among HCWs and sex, age, working hours per week, and wearing gloves (P&lt;0.05). Females had a 3.84 fold higher risk of HD than males (confidence interval (CI): 1.85-8). HCWs older than 40 and those who aged 30-39 had a 9.6 and 1.72 fold higher risk of HD than those aged 20-29 (CI: 2.6-35.7; CI: 0.87-3.4, respectively). Conclusion: Possible risk factors for developing HD among HCWs are female gender, age, wearing gloves, and fewer working hours per week. Preventive measures for HD are needed for HCWs, especially during the COVID-19 pandemic.

Exploring and Predicting the Drivers of Ongoing HIV-1 Transmission in Guangyuan, Sichuan

Exploring and Predicting the Drivers of Ongoing HIV-1 Transmission in Guangyuan, Sichuan

Long-term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: A modelling study.

Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.

Assessment of geneXpert test for diagnosis of pediatric pulmonary tuberculosis

Introduction: Pediatric tuberculosis is an infectious disease and is a leading cause of death in Nepal. The incidence of pediatric TB is a key tool of ongoing transmission of tuberculosis within the community and vital indicator of disease control. Its diagnosis is very much challenging and delay in diagnosis leads to mortality.&#x0D; Objectives: This study was conducted to assess the utility of the gene Xpert test for diagnosis of pediatric pulmonary tuberculosis.&#x0D; Methodology: A hospital based prospective study done at Pediatric department of a teaching hospital, Nepalgunj, Banke conducted over a period of 1 year from 1 January 2021 to 31 December 2021 with presumptive diagnosis of pediatric pulmonary tuberculosis. Chi-square test was used to determine the association between categorical variables and a receiver operating curve (ROC) analysis was performed to compare the performance of gene Xpert test with other lab parameters like sputum/gastric lavage sample microscopy for acid fast bacilli, erythrocytic sedimentation rate, Tuberculin test (TT) and chest X-ray.&#x0D; &#x0D; Results: We enrolled a total of 294 patients in our study. Out of 294 samples 5.1% samples came out to be positive for gene Xpert for MTB. The sputum/gastric lavage samples for AFB showed both sensitivity and specificity of 100%. The tuberculin test showed a sensitivity of 80% and specificity of 37.3%. Chest X-ray showed a sensitivity of 66.7% and specificity of 43.7%. The area under the curve for acid fast bacilli in microscopy, tuberculin test and ESR was found to be 100% (95% CI: 100%-100%), 58.6% (95% CI: 44.9%-72.4%), and 52.6% (95% CI: 37%-68.3%) respectively. &#x0D; &#x0D; Conclusion: This study highlights the utility of gene Xpert as a good diagnostic tool for rapid diagnosis of pulmonary tuberculosis in pediatric population.

Determining the risk-factors for molecular clustering of drug-resistant tuberculosis in South Africa

BackgroundDrug-resistant tuberculosis (DR-TB) epidemic is driven mainly by the effect of ongoing transmission. In high-burden settings such as South Africa (SA), considerable demographic and geographic heterogeneity in DR-TB transmission exists. Thus, a better understanding of risk-factors for clustering can help to prioritise resources to specifically targeted high-risk groups as well as areas that contribute disproportionately to transmission.MethodsThe study analyzed potential risk-factors for recent transmission in SA, using data collected from a sentinel molecular surveillance of DR-TB, by comparing demographic, clinical and epidemiologic characteristics with clustering and cluster sizes. A genotypic cluster was defined as two or more patients having identical patterns by the two genotyping methods used. Clustering was used as a proxy for recent transmission. Descriptive statistics and multinomial logistic regression were used.ResultThe study identified 277 clusters, with cluster size ranging between 2 and 259 cases. The majority (81.6%) of the clusters were small (2–5 cases) with few large (11–25 cases) and very large (≥ 26 cases) clusters identified mainly in Western Cape (WC), Eastern Cape (EC) and Mpumalanga (MP). In a multivariable model, patients in clusters including 11–25 and ≥ 26 individuals were more likely to be infected by Beijing family, have XDR-TB, living in Nelson Mandela Metro in EC or Umgungunglovo in Kwa-Zulu Natal (KZN) provinces, and having history of imprisonment. Individuals belonging in a small genotypic cluster were more likely to infected with Rifampicin resistant TB (RR-TB) and more likely to reside in Frances Baard in Northern Cape (NC).ConclusionSociodemographic, clinical and bacterial risk-factors influenced rate of Mycobacterium tuberculosis (M. tuberculosis) genotypic clustering. Hence, high-risk groups and hotspot areas for clustering in EC, WC, KZN and MP should be prioritized for targeted intervention to prevent ongoing DR-TB transmission.

Design, Synthesis, and Biological Evaluation of Trisubstituted Piperazine Derivatives as Noncovalent Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease Inhibitors with Improved Antiviral Activity and Favorable Druggability.

The ongoing transmission of SARS-CoV-2 necessitates the development of additional potent antiviral agents capable of combating the current highly infectious variants and future coronaviruses. Here, we present the discovery of potent nonpeptide main protease (Mpro) inhibitors with prominent antiviral activity and improved pharmacokinetic properties. Three series of 1,2,4-trisubstituted piperazine derivatives were designed and synthesized, and the optimal GC-78-HCl demonstrated high enzyme-inhibitory potency (IC50 = 0.19 μM) and exhibited excellent antiviral activity (EC50 = 0.40 μM), reaching the same level as Nirmatrelvir (EC50 = 0.38 μM). Additionally, GC-78-HCl displayed potent antiviral activities against various SARS-CoV-2 variants as well as HCoV-OC43 and HCoV-229E, indicating its potential broad-spectrum anticoronaviral activity. Notably, the pharmacokinetic properties of GC-78-HCl were somewhat enhanced compared to those of the lead compound. Furthermore, the cocrystal and molecular docking elucidated the mechanism of action. In conclusion, we discovered a novel nonpeptidic Mpro inhibitor with promising antiviral activity and a favorable pharmacokinetic profile.

Rapid diagnostic testing for onchocerciasis in Maridi (South Sudan) before and after improving elimination strategies: a repeated cross-sectional survey

Background Maridi County is an onchocerciasis-endemic area in South Sudan. Annual community-directed treatment with ivermectin (CDTi) was instituted in Maridi but interrupted for several years before resuming in 2017. In 2021, the CDTi programme was strengthened to a six-monthly programme. Additionally, the community-based vector control strategy “Slash and Clear” has been implemented since 2019 at the Maridi Dam, the only blackfly breeding site in the area. This study assessed the effect of these reinforced onchocerciasis elimination interventions on the Onchocerca volvulus seroprevalence among young children, an indicator of ongoing transmission. Methods Baseline and follow-up serosurveys were conducted in Maridi in 2019 (prior to strengthening onchocerciasis elimination efforts) and 2023, respectively. During both surveys, children aged three to nine years were recruited from five study sites situated at different distances from the Maridi Dam. Ov16 antibodies were detected via rapid diagnostic tests (RDTs) using whole blood obtained by finger-pricking the participants. Baseline and follow-up Ov16 prevalence rates were calculated and compared. Results In 2019, the Ov16 seroprevalence among children aged three to nine years was 24.5% compared to 30.6% in 2023 (p=0.22). Both surveys found a particularly high Ov16 seroprevalence in the study site closest to the Maridi Dam (35.0% in 2019 and 44.0% in 2023, p=0.52). The Ov16 seroprevalence had a non-significant decreasing trend in the three-year-old children, from 12.5% (3/24) in 2019 to 8.8% (3/34) in 2023 (p=0.65). Conclusion The persistent Ov16 RDT seropositivity among three-year-old children in 2023 indicates ongoing O. volvulus transmission. Therefore, further strengthening of the onchocerciasis elimination programme is required. The study highlights the utility of RDTs in monitoring onchocerciasis transmission in highly endemic settings.

Genome-based tools for onchocerciasis elimination: utility of the mitochondrial genome for delineating Onchocerca volvulus transmission zones

National programs in Africa have expanded their objectives from control of onchocerciasis (river blindness) as a public health problem to elimination of parasite transmission, motivated by the reduction of Onchocerca volvulus infection prevalence in many African meso- and hyperendemic areas due to mass drug administration of ivermectin (MDAi). Given the large, contiguous hypo-, meso-, and hyperendemic areas, sustainable elimination of onchocerciasis in sub-Saharan Africa requires delineation of geographic boundaries for parasite transmission zones, so that programs can consider the risk of parasite re-introduction through vector or human migration from areas with ongoing transmission when making decisions to stop MDAi. We propose that transmission zone boundaries can be delineated by characterising the parasite genetic population structure within and between potential zones. We analysed whole mitochondrial genome sequences of 189 O. volvulus adults to determine the pattern of genetic similarity across three West African countries: Ghana, Mali, and Côte d’Ivoire. Population genetic structure indicates that parasites from villages near the Pru, Daka, and Black Volta rivers in central Ghana belong to one parasite population, indicating that the assumption that river basins constitute individual transmission zones is not supported by the data. Parasites from Mali and Côte d’Ivoire are genetically distinct from those from Ghana. This research provides the basis for developing tools for elimination programs to delineate transmission zones, to estimate the risk of parasite re-introduction via vector or human movement when intervention is stopped in one area while transmission is ongoing in others, to identify the origin of infections detected post-treatment cessation, and to investigate whether persisting prevalence despite ongoing interventions in one area is due to parasites imported from others.

Is there still yaws in Nigeria? Active case search in endemic areas of southern Nigeria.

Yaws is a disease caused by the bacteria Treponema pallidum subspecies pertenue, which is most commonly seen among children below 15 years. In the twentieth century yaws was endemic in Nigeria but eradication strategies markedly reduced the disease burden. Currently there is minimal data on the ongoing transmission of yaws in Nigeria, despite reports of confirmed yaws cases in neighbouring West African countries. We conducted both community and school-based active yaws case search among school-aged children in southeast Nigeria. Children were screened by trained community volunteers. Suspected yaws cases were clinically reviewed and tested using rapid diagnostic serological tests. Between February and May 2021, up to 28 trained community volunteers screened a total of 105,015 school children for yaws. Overall, 7,706 children with various skin lesions were identified. Eight (8) suspected cases of yaws were reported, reviewed and screened, but none was confirmed using rapid diagnostic tests. The four most common skin conditions identified were scabies (39%), papular urticaria (29%), tinea corporis (14%) and tinea capitis (12%). No case of yaws was confirmed in this large population of children in south-east Nigeria. Continuous community awareness and yaws case finding activities have been recommended across Nigeria.

A prospective bacterial whole-genome-sequencing-based surveillance programme for comprehensive early detection of healthcare-associated infection transmission in paediatric oncology patients

Bacterial whole-genome sequencing (WGS) and determination of genetic relatedness is an important tool for investigation of epidemiologically suspected outbreaks. This prospective cohort study evaluated a comprehensive, prospective bacterial WGS-based surveillance programme for early detection of transmission of most bacterial pathogens among patients at a paediatric oncology hospital. Cultured bacterial isolates from clinical diagnostic specimens collected prospectively from both inpatient and outpatient encounters between January 2019 and December 2021 underwent routine WGS and core genome multi-locus sequence typing to determine isolates' relatedness. Previously collected isolates from January to December 2018 were retrospectively analysed for identification of prior or ongoing transmission. Multi-patient clusters were investigated to identify potential transmission events based on temporal and spatial epidemiological links and interventions were introduced. A total of 1497 bacterial isolates from 1025 patients underwent WGS. A total of 259 genetically related clusters were detected, of which 18 (6.9%) multi-patient clusters involving 38 (3.7%) patients were identified. Sixteen clusters involved two patients each, and two clusters involved three patients. Following investigation, epidemiologically plausible transmission links were identified in five (27.8%) multi-patient clusters. None of the multi-patient clusters were suspected by conventional epidemiological surveillance. Bacterial WGS-based surveillance for early detection of hospital transmission detected several limited multi-patient clusters that were unrecognized by conventional epidemiological methods. Genomic surveillance helped efficiently focus interventions while reducing unnecessary investigations.

Mechanism of Arcuate Kisspeptin Neuron Synchronization in Acute Brain Slices From Female Mice.

The mechanism by which arcuate kisspeptin (ARNKISS) neurons co-expressing glutamate, neurokinin B, and dynorphin intermittently synchronize their activity to drive pulsatile hormone secretion remains unclear in females. In order to study spontaneous synchronization within the ARNKISS neuron network, acute brain slices were prepared from adult female Kiss1-GCaMP6 mice. Analysis of both spontaneous synchronizations and those driven by high frequency stimulation of individual ARNKISS neurons revealed that the network exhibits semi-random emergent excitation dependent upon glutamate signaling through AMPA receptors. No role for NMDA receptors was identified. In contrast to male mice, ongoing tachykinin receptor tone within the slice operated to promote spontaneous synchronizations in females. As previously observed in males, we found that ongoing dynorphin transmission in the slice did not contribute to synchronization events. These observations indicate that a very similar AMPA receptor-dependent mechanism underlies ARNKISS neuron synchronizations in the female mouse supporting the "glutamate two-transition" model for kisspeptin neuron synchronization. However, a potentially important sex difference appears to exist with a more prominent facilitatory role for tachykinin transmission in the female.

Validation of public stigma of tuberculosis scale during the COVID-19 pandemic using the Rasch model.

Tuberculosis (TB) is still a major global health problem, and it has been particularly concerning during the COVID-19 pandemic. Non-compliance with anti-TB treatment increases the number of multidrug-resistant cases, causing ongoing transmission and increased morbidity and mortality. The main factors causing TB patients' non-compliance are stigma and lack of financial resources. Stigma harms patients and may cause them to delay seeking and adhering to treatment. Thus, it is important to measure the public stigma surrounding TB. However, few scales are available to measure this stigma as it developed during the COVID-19 pandemic. This study, therefore, aimed to develop and validate such a scale. Mixed methods were employed in this study, consisting of a qualitative phase using in-depth interviews with 26 community leaders and a descriptive quantitative survey of 37 people in the Sumedang District to validate the public stigma of tuberculosis scale during the COVID-19 pandemic. The qualitative data were analyzed using thematic analysis, and the quantitative data were analyzed using the Rasch model. The 21 items yielded by an initial qualitative analysis of the data gathered were validated using the RASCH model, yielding 17 valid items with a Cronbach's Alpha of 0.95, person separation of 3.61, real root mean square deviation (RMSE) of 0.37, infit mean square (INFIT MNSQ) of > +1.25, differential item functioning (DIF) of 1.000, the raw variance of 52.4%, and an unexplained variance ranging from 3.4% to 6.9%. The scale developed to measure the public stigma surrounding TB during the COVID-19 pandemic is valid and reliable to measure stigma surrounding TB in the community, especially the pandemic. Further research is needed to apply the scale to bigger and broader populations to evaluate its measurement consistency.

Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.

The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.

Implication of agricultural practices in the micro-geographic heterogeneity of malaria transmission in Bouna, Côte d’Ivoire

BackgroundWetlands and irrigated agricultural crops create potential breeding sites for Anopheles mosquitoes, leading to a heterogeneity in malaria transmission. In agricultural areas, heterogeneity of malaria transmission is often associated with the presence of hotspots consisting of localized clusters of higher transmission intensity. This study aims to identify micro-geographic hotspots of malaria transmission in an agricultural setting using a multidisciplinary approach.MethodsTwo cross-sectional surveys were conducted at the end of the dry season and at the peak of the rainy season in rural and urban sites in Bouna, northeastern Côte d'Ivoire. A total of 296 individuals from 148 farming households were randomly selected and sociological, geographical, entomological, and clinical data as well as blood samples were collected during each visit. Parasitological data and Anopheles exposure (measured using entomological and immunological methods) were compared with demographic, agricultural, and geographic data to identify drivers of malaria transmission. Heat maps combining these data were used to identify households with ongoing malaria transmission throughout the year.ResultsIn rural areas, Plasmodium prevalence was consistent between the dry and the rainy seasons, with roughly half of the population infected. In urban areas, malaria transmission indicators were lower, with a parasite prevalence of less than 20%, which remained comparable between the dry and the rainy season. The presence of irrigated crops and proximity to wetlands were associated with increased Anopheles exposure. By mapping Plasmodium infection and Anopheles exposure, two different types of hotspots of malaria transmission were identified: micro-geographical scale and local scale hotspots.ConclusionsThe presence of wetlands in urban areas and irrigated agriculture in rural areas resulted in heterogeneity in malaria transmission on a micro-geographical scale. These specific households present particular risk of malaria transmission and could fuel malaria transmission in surrounding households. The identification of micro-geographical areas using heat maps combining several epidemiological parameters can help to identify hotspots of malaria transmission. The implementation of malaria control measures, such as seasonal chemoprophylaxis or vector control, in these areas could help to reduce the incidence of malaria and facilitate its elimination.

Persons 'never treated' in mass drug administration for lymphatic filariasis: identifying programmatic and research needs from a series of research review meetings 2020-2021.

As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action.

Schoolchildren with asymptomatic malaria are potential hotspot for malaria reservoir in Ethiopia: implications for malaria control and elimination efforts

BackgroundSchoolchildren with asymptomatic malaria infections often go undiagnosed and untreated, serving as reservoirs for infection that hamper malaria control and elimination efforts. In this context, little is known about the magnitude of asymptomatic malaria infections in apparently healthy schoolchildren in Ethiopia. This study was aimed at determining the prevalence of asymptomatic malaria infection and its associated factors in apparently healthy schoolchildren in Ethiopia.MethodsFrom September 2021 to January 2022, a school-based cross-sectional study was conducted on 994 apparently healthy schoolchildren (aged 6–15 years) selected from 21 primary schools in the Gomma district, of Jimma zone, southwestern Oromia, Ethiopia. A multi-stage sampling technique was used to select schools and participants. After allocating the total sample proportionally to each school and then to each grade, participants were selected using the lottery method from a list of student records (rosters). Finger-pricked blood samples were collected for microscopy blood film preparation and malaria rapid diagnostic test (RDT) (SD Bioline Malaria Ag Pf/Pv). Moreover, dry blood spots (DBSs) were prepared onto filter papers for quantitative real time polymerase chain reaction (qPCR) analysis.ResultsAs determined by RDT and microscopy, the prevalence of asymptomatic malaria was 2.20% and 1.51%, respectively. Using qPCR, the overall prevalence was 5.03% (50/994). Of this, Plasmodium falciparum, Plasmodium vivax and mixed infections accounted for 90%, 6% and 4%, respectively. Submicroscopic asymptomatic malaria infection was also accounted for 70% (35/50) of the overall prevalence. Household head age, nighttime outdoor activities of household heads, family history of malaria, absence of insecticide-treated nets (ITN), and presence of stagnant water around the houses are all significantly associated with asymptomatic malaria infections among schoolchildren.ConclusionsThis study found that both RDT and microscopy underestimated the prevalence of asymptomatic malaria in schoolchildren. However, qPCR was able to detect even low levels of parasitaemia and revealed a higher prevalence of asymptomatic submicroscopic malaria infections. The findings imply that schoolchildren with asymptomatic malaria infection are potential hotspot for malaria reservoir that fuels ongoing transmission. Therefore, it is imperative to include schoolchildren and schools in malaria intervention package and equally important is the adoption of more advanced and sensitive diagnostic tools, which would be crucial for successful malaria control and elimination efforts. Targeted interventions for asymptomatic malaria-infected schoolchildren can provide invaluable support to the National Malaria Control Programme in controlling and eventually eliminating the disease.

Community-wide versus school-based targeted deworming for soil-transmitted helminth control in school-aged children in Vietnam: the CoDe-STH cluster-randomised controlled trial

Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC ("school arm") or community-wide MDA ("community arm"). A single dose of albendazole 400mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). The analysis included 4955 children in the school arm and 5093 children in the community arm. N.americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5-36.9) and the community arm (34.6%, 95% CI 19.9-49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N.americanus infection intensity (56.0%, 95% CI 39.9-72.1) compared to the school arm (3.4%, 95% CI-24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N.americanus infections (81.1%; 95% CI 69.7-92.6) compared to the school arm (39.0%, 95% CI 13.7-64.2). Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N.americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. National Health and Medical Research Council, Australia (APP1139561).