Search

The global SARS-CoV-2 immune landscape and population protection against emerging variants is largely unknown. We assessed SARS-CoV-2 antibody changes in the Dominican Republic and implications for immunological protection against variants of concern. Between March 2021 and August 2022, 2,300 patients with undifferentiated febrile illnesses were prospectively enrolled. Sera was tested for total anti-spike antibodies and simultaneously collected nasopharyngeal samples for acute SARS-CoV-2 infection with RT-PCR. Geometric mean anti-spike titers increased from 6.6 BAU/ml (95% CI 5.1–8.7) to 1,332 BAU/ml (1055–1,682). Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40–0.74), 0.38 (0.27–0.55), and 0.27 (0.18–0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening can leverage existing acute fever surveillance platforms to monitor population-level immunological markers and concurrently characterize implications for emergent variant transmission in near real-time.

Background Identifying efficient and effective strategies to reach and monitor populations at greatest risk of malaria in low-transmission settings is a key challenge for malaria elimination. In Namibia’s Zambezi Region, transmission is ongoing yet its drivers remain poorly understood. A growing literature suggests that night-time social activities may lead to malaria exposure that is beyond the reach of conventional preventive interventions, such as insecticide treated bed nets and indoor residual spraying. Methods Formative research was conducted with community members in March, 2015 in the catchment areas of six randomly selected health facilities in the western Zambezi Region to identify night-time locations where large numbers of individuals regularly congregate. Using time-location sampling, a survey was conducted between March and May, 2015 at community-identified venues (bars and evening church services) to develop representative estimates of the prevalence of parasite infection and risk factors among venue-goers. Results When compared to a contemporaneous household survey of the general population aged 15 and older (N = 1160), venue-goers (N = 480) were more likely to have spent the night away from their home recently (17.3% vs. 8.9%, P = 0.008), report recent fever (65.2% vs. 36.9%, P

In areas of low and unstable transmission, malaria cases occur in populations with lower access to malaria services and interventions, and in groups with specific malaria risk exposures often away from the household. In support of the Namibian National Vector Borne Disease Program’s drive to better target interventions based upon risk, we implemented a health facility-based case control study aimed to identify risk factors for symptomatic malaria in Zambezi Region, northern Namibia. A total of 770 febrile individuals reporting to 6 health facilities and testing positive by rapid diagnostic test (RDT) between February 2015 and April 2016 were recruited as cases; 641 febrile individuals testing negative by RDT at the same health facilities through June 2016 were recruited as controls. Data on socio-demographics, housing construction, overnight travel, use of malaria prevention and outdoor behaviors at night were collected through interview and recorded on a tablet-based questionnaire. Remotely-sensed environmental data were extracted for geo-located village residence locations. Multivariable logistic regression was conducted to identify risk factors and latent class analyses (LCA) used to identify and characterize high-risk subgroups. The majority of participants (87% of cases and 69% of controls) were recruited during the 2016 transmission season, an outbreak year in Southern Africa. After adjustment, cases were more likely to be cattle herders (Adjusted Odds Ratio (aOR): 4.46 95%CI 1.05–18.96), members of the police or other security personnel (aOR: 4.60 95%CI: 1.16–18.16), and pensioners/unemployed persons (aOR: 2.25 95%CI 1.24–4.08), compared to agricultural workers (most common category). Children (aOR 2.28 95%CI 1.13–4.59) and self-identified students were at higher risk of malaria (aOR: 4.32 95%CI 2.31–8.10). Other actionable risk factors for malaria included housing and behavioral characteristics, including traditional home construction and sleeping in an open structure (versus modern structure: aOR: 2.01 95%CI 1.45–2.79 and aOR: 4.76 95%CI: 2.14–10.57); cross border travel in the prior 30 days (aOR: 10.55 95%CI 2.94–37.84); and outdoor agricultural work at night (aOR: 2.09 95%CI 1.12–3.87). Malaria preventive activities were all protective and included personal use of an insecticide treated net (ITN) (aOR: 0.61 95%CI 0.42–0.87), adequate household ITN coverage (aOR: 0.63 95%CI 0.42–0.94), and household indoor residual spraying (IRS) in the past year (versus never sprayed: (aOR: 0.63 95%CI 0.44–0.90). A number of environmental factors were associated with increased risk of malaria, including lower temperatures, higher rainfall and increased vegetation for the 30 days prior to diagnosis and residing more than 5 minutes from a health facility. LCA identified six classes of cases, with class membership strongly correlated with occupation, age and select behavioral risk factors. Use of ITNs and IRS coverage was similarly low across classes. For malaria elimination these high-risk groups will need targeted and tailored intervention strategies, for example, by implementing alternative delivery methods of interventions through schools and worksites, as well as the use of specific interventions that address outdoor transmission.

Due to challenges in measuring changes in malaria in low transmission settings, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal cohort studies have shown serological markers, such as Etramp5.Ag1, to be particularly discriminatory of spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials. This study is an extended analysis of a 2017 cluster randomised trial conducted in Zambezi Region, Namibia, evaluating the effectiveness of reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC). A panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP119, PfAMA1, and PfGLURP.R2 - was used on a multiplex immunoassay to measure population antibody responses as trial endpoints.Reductions in sero-prevalence to antigens Etramp.Ag1, PfMSP119, Rh2.2030, and PfAMA1 were observed in study arms combining rfMDA and RAVC, but only effects for Etramp5.Ag1 were statistically significant. Etramp5.Ag1 sero-prevalence was significantly lower in all intervention arms. Compared to the reference arms, adjusted Etramp5.Ag1 prevalence ratio (aPR) was 0.77 (95%CI 0.65 – 0.90, pThe use of serological endpoints to evaluate trial outcomes was comparable to qPCR and measured effect size with improved precision. Serology has clear application in cluster randomised trials, particularly in settings where measuring clinical incidence or infection is less reliable due to seasonal fluctuations, limitations in health care seeking, or incomplete testing and reporting.Key questionsWhat is already known?▪Numerous serological studies across sub-Saharan Africa have found that malaria-specific antibody responses are highly correlated with malaria transmission.▪Serology is increasingly being used to complement traditional malaria surveillance data in settings where clinical or parasitological measures of incidence or infection may be less reliable due to fluctuations in parasite densities, limitations in health care seeking, or incomplete testing and reporting.▪The identification of new serological markers associated with recent malaria exposure hold promise as measures of malaria incidence. In previous longitudinal cohort studies, Etramp5.Ag1 has been shown to be a discriminatory serological marker capable of detecting spatio-temporal differences in malaria transmission. However, these markers have never been formally used as endpoints in a malaria cluster randomised trial.What are the new findings?▪This study is the first application of serological endpoints in a malaria cluster randomised trial. Using a multiplexed immunoassay, a panel of sero-incidence markers of recent malaria exposure were used to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) compared to reactive case detection (standard of care) to reduce malaria transmission.▪Cluster-level antibody responses were significantly lower in all intervention arms compared to control, and effect sizes were measured with greater study power than other trial endpoints such as quantitative polymerase chain reaction (qPCR) parasite prevalence.What do the new findings imply?▪The findings from this study, together with ongoing innovations in assay design and multi-disease platforms, illustrate the potential application of serological markers as endpoints in cluster randomised trials. The use of serological endpoints can help achieve trial efficiencies, such as reduced sample size, particularly in low transmission settings or multi-intervention trials where measuring differences between study arms may be challenging with clinical or parasitological endpoints alone.

Background In Namibia, as in many malaria elimination settings, reactive case detection (RACD), or malaria testing and treatment around index cases, is a standard intervention. Reactive focal mass drug administration (rfMDA), or treatment without testing, and reactive focal vector control (RAVC) in the form of indoor residual spraying, are alternative or adjunctive interventions, but there are limited data regarding their community acceptability. Methods A parent trial aimed to compare the effectiveness of rfMDA versus RACD, RAVC versus no RAVC, and rfMDA + RAVC versus RACD only. To assess acceptability of these interventions, a mixed-methods study was conducted using key informant interviews (KIIs) and focus group discussions (FGDs) in three rounds (pre-trial and in years 1 and 2 of the trial), and an endline survey. Results In total, 17 KIIs, 49 FGDs were conducted with 449 people over three annual rounds of qualitative data collection. Pre-trial, community members more accurately predicted the level of community acceptability than key stakeholders. Throughout the trial, key participant motivators included: malaria risk perception, access to free community-based healthcare and IRS, and community education by respectful study teams. RACD or rfMDA were offered to 1372 and 8948 individuals in years 1 and 2, respectively, and refusal rates were low ( Conclusions Communities found both reactive focal interventions and their combination highly acceptable. Engaging communities and centering and incorporating their perspectives and experiences during design, implementation, and evaluation of this community-based intervention was critical for optimizing study engagement.

Summary Background In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). Methods We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov , number NCT02610400 . Findings Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8–48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0–53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0–45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7–57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2–44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5–61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16–0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16–0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10–0·68], p=0·006). No serious adverse events were reported. Interpretation In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. Funding Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

Background Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized. Methods Using a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed. Results Prevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77–14.23, and 11.82, 95% CI 1.06–131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not. Conclusions This study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups. Electronic supplementary material The online version of this article (10.1186/s12936-018-2626-5) contains supplementary material, which is available to authorized users.

Background: In low-endemic malaria settings, screening and treatment near index cases (reactive case detection, RACD) is practiced for surveillance and response; however, other approaches may be more effective. Methods: We conducted a cluster-randomised controlled two-by-two factorial design trial to evaluate the impact of reactive focal mass drug administration, rfMDA, and reactive focal vector control, RAVC, in the low-endemic setting of Zambezi, Namibia. Fifty-six clusters were randomised to: RACD or rfMDA, and RAVC or no RAVC (RACD: rapid diagnostic testing and treatment with artemether-lumefantrine (AL); rfMDA: presumptive treatment with AL; RAVC: indoor residual spraying using pirimiphos-methyl), with interventions administered within 500 meters of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitos (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA+RAVC vs RACD only), a modified intention-to-treat analysis was used to compare cumulative incidence of locally acquired malaria cases and cross-sectional prevalence of infection with parasites. Trial registration: ClinicalTrials.gov NCT02610400. Findings: From Jan-Nov 2017, 55 clusters had index cases triggering 342 interventions that covered 8 948 individuals. Incidence per 1 000 person-years for rfMDA, RAVC, and rfMDA+RAVC clusters vs control was: 30·8 vs 38·3 (adjusted incidence rate ratio (aIRR) 0·54 [95% CI 0·14-0·94, p=0·03]), 30·2 vs 38·9 (aIRR 0·51 [0·12-0·90, p=0·01]), and 25·0 vs 41·4 (aIRR 0·28 [0·10-0·84, p=0·02]), respectively. Compared to control, prevalence of infection (%) for rfMDA, RAVC, and rfMDA+RAVC vs control was 3·2 vs 3·8 (adjusted prevalence ratio (aPR) 0·58 [95% CI 0·18-0·98, p=0·04]), 2·9 vs 4·1 (aPR 0·34 [0·11-0·57, p

As countries move toward malaria elimination, imported infections become increasingly significant as they often represent the majority of cases, can sustain transmission, cause resurgences, and lead to mortality. Here we review and critique current methods to prevent malaria importation in countries pursuing elimination and explore methods applied in other transmission settings and to other diseases that could be transferred to support malaria elimination. To improve intervention targeting we need a better understanding of the characteristics of populations importing infections and their patterns of migration, improved methods to reliably classify infections as imported or acquired locally, and ensure early and accurate diagnosis. The potential for onward transmission in the most receptive and vulnerable locations can be predicted through high-resolution risk mapping that can help malaria elimination or prevention of reintroduction programs target resources. Cross border and regional initiatives can be highly effective when based on an understanding of human and parasite movement. Ultimately, determining the optimal combinations of approaches to address malaria importation will require an evaluation of their impact, cost effectiveness, and operational feasibility.

Setting: A comparison of routine Namibia National Malaria Programme data (reported) vs. household survey data (administrative) on indoor residual spraying (IRS) in western Zambezi region, Namibia, for the 2014-2015 malaria season. Objectives: To determine 1) IRS coverage (administrative and reported), 2) its effect on malaria incidence, and 3) reasons for non-uptake of IRS in western Zambezi region, Namibia, for the 2014-2015 malaria season. Design: This was a descriptive study. Results: IRS coverage in western Zambezi region was low, ranging from 42.3% to 52.2% for administrative coverage vs. 45.9-66.7% for reported coverage. There was no significant correlation between IRS coverage and malaria incidence for this region (r = -0.45, P = 0.22). The main reasons for households not being sprayed were that residents were not at home during spraying times or that spray operators did not visit the households. Conclusions: IRS coverage in western Zambezi region, Namibia, was low during the 2014-2015 malaria season because of poor community engagement and awareness of times for spray operations within communities. Higher IRS coverage could be achieved through improved community engagement. Better targeting of the highest risk areas by the use of malaria surveillance will be required to mitigate malaria transmission. Contexte : Une comparaison des donnees de routine du programme national de lutte centre le paludisme de Namibie (rapportees) et des donnees d'enquete dans les foyers (administratives) relatives a la pulverisation d'insecticide a effet remanent (IRS) dans la region ouest du Zambeze, en Namibie, pour la saison 2014–2015 du paludisme.Objectifs : Determiner 1) la couverture de l'IRS (administrative et rapportee), 2) son effet sur l'incidence du paludisme, et 3) les raisons de la non couverture de l'IRS dans la region ouest du Zambeze, Namibie, pendant la saison 2014–2015 du paludisme.Schema : Une etude descriptive.Resultats : La couverture de l'IRS dans la region ouest du Zambeze a ete faible, allant de 42,3% a 52,2% pour la couverture administrative contre 45,9% a 66,7% pour la couverture rapportee. Il n'y a pas eu de correlation significative entre couverture de l'IRS et incidence du paludisme dans cette region (r = −0,45 ; P = 0,22). Les raisons majeures pour lesquelles les foyers n'ont pas beneficie de pulverisations ont ete l'absence des residents a leur domicile lors de la pulverisation ou, inversement, la non-venue des operateurs de pulverisation dans les foyers.Conclusions : La couverture de l'IRS dans la region ouest du Zambeze, Namibie, a ete faible pendant la saison 2014–2015 du paludisme en raison de l'engagement mediocre de la communaute et de la meconnaissance des dates d'operations de pulverisation dans les communautes. Une couverture plus elevee de l'IRS pourrait etre obtenue avec une meilleur engagement de la communaute. Un meilleur ciblage des zones a risque les plus eleves en utilisant la surveillance du paludisme sera requis pour attenuer la transmission du paludisme. Marco de referencia: Una comparacion de los datos corrientes del Programa Nacional contra el Paludismo de Namibia (notificados), con los datos de una encuesta domiciliaria (administrativos) sobre la fumigacion de interiores con insecticidas de efecto residual (IRS) en la region occidental de Zambezi en Namibia, durante la temporada de paludismo del 2014–2015.Objetivos: Determinar 1) la cobertura de la IRS (administrativa y notificada), 2) su efecto sobre la incidencia de paludismo, y 3) las razones de la falta de IRS en la region occidental de Zambezi, en Namibia, durante la temporada de paludismo del 2014–2015.Metodo: Un estudio descriptivo.Resultados: La cobertura de la IRS en la region occidental de Zambezi fue baja, del 42,3% al 52,2% segun la cobertura administrativa, en comparacion con el 45,9% al 66,7% segun la cobertura notificada. paludismo en la region (r = −0,45; P = 0,22). Las principales razones por las cuales no se fumigaron los domicilios fueron que los residentes no se encontraban presentes en el momento de la fumigacion o que los operadores de fumigacion no visitaron los hogares.Conclusiones: La cobertura de la fumigacion de interiores con insecticidas de efecto residual en la region occidental de Zambezi, en Namibia, fue baja durante la temporada de paludismo del 2014–2015 por falta de participacion comunitaria y de conocimiento de los horarios de fumigacion en las comunidades. La cobertura se puede ampliar si se fomenta el compromiso comunitario y es necesario dirigir mejor las campanas a las zonas de mayor riesgo, segun lo indiquen los datos de la vigilancia del paludismo, con el proposito de disminuir la transmision de la enfermedad.