Dataset Information

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

ABSTRACT:

Background

Due to challenges in measuring changes in malaria at low transmission, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal studies have shown that serological markers, such as Etramp5.Ag1, can reflect spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials.

Methods

Based on data from 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), this study conducted a secondary analysis comparing antibody responses between intervention arms as trial endpoints. Antibody responses were measured on a multiplex immunoassay, using a panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP1₁₉, PfAMA1, and PfGLURP.R2.

Findings

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 prevalence ratio (aPR) for Etramp5.Ag1 was 0.78 (95%CI 0.65 - 0.91, p = 0.0007) in the rfMDA arms and 0.79 (95%CI 0.67 - 0.92, p = 0.001) in the RAVC arms. For the combined rfMDA plus RAVC intervention, aPR was 0.59 (95%CI 0.46 - 0.76, p < 0.0001). Significant reductions were also observed based on continuous antibody responses. Sero-prevalence as an endpoint was found to achieve higher study power (99.9% power to detect a 50% reduction in prevalence) compared to quantitative polymerase chain reaction (qPCR) prevalence (72.9% power to detect a 50% reduction in prevalence).

Interpretation

While the observed relative reduction in qPCR prevalence in the study was greater than serology, the use of serological endpoints to evaluate trial outcomes measured effect size with improved precision and study power. 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.

Funding

This study was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129), and the Horchow Family Fund (5,300,375,400).

SUBMITTER: Wu L

PROVIDER: S-EPMC8851292 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

Wu Lindsey L Hsiang Michelle S MS Prach Lisa M LM Schrubbe Leah L Ntuku Henry H Dufour Mi-Suk Kang MK Whittemore Brooke B Scott Valerie V Yala Joy J Roberts Kathryn W KW Patterson Catriona C Biggs Joseph J Hall Tom T Tetteh Kevin K A KKA Gueye Cara Smith CS Greenhouse Bryan B Bennett Adam A Smith Jennifer L JL Katokele Stark S Uusiku Petrina P Mumbengegwi Davis D Gosling Roly R Drakeley Chris C Kleinschmidt Immo I

EClinicalMedicine 20220214

<h4>Background</h4>Due to challenges in measuring changes in malaria at low transmission, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal studies have shown that serological markers, such as Etramp5.Ag1, can reflect spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials.<h4>Methods</h4>Based on data from a 2017 cluster randomised trial conducted in Zambezi Region ...[more]

PMID: 35198913

Similar Datasets

Project description:BackgroundIn 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).MethodsWe 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.FindingsBetween 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.InterpretationIn 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.FundingNovartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

Project description:BackgroundThe World Health Organization conditionally recommends reactive drug administration to reduce malaria transmission in settings approaching elimination. However, few studies have evaluated the impact of reactive focal drug administration (rFDA) in sub-Saharan Africa, and none have evaluated it under programmatic conditions. In 2016, Senegal's national malaria control programme introduced rFDA, the presumptive treatment of compound members of a person with confirmed malaria, and reactive mass focal drug administration (rMFDA), an expanded effort including neighbouring compounds during an outbreak, in 10 low transmission districts in the north of the country. This evaluation sought to measure the impact of rFDA and rMFDA on malaria incidence.MethodsAn interrupted time series analysis was conducted with routine surveillance data on health post-level monthly confirmed malaria case counts from the District Health Information Software (DHIS2). The study evaluated the change in incidence following rFDA and rMFDA rollout (level change), which ranged from August 2016 to November 2019, and monthly thereafter (trend change), using an adjusted negative binomial regression model with data from January 2015 through January 2020. The model was used to estimate the number of cases averted via a counterfactual simulation.ResultsNo incidence rate reductions were estimated immediately following rollout (level change: incidence rate ratio (IRR) = 1.00, 95% credible interval (CI) = 0.76, 1.33). However, rFDA and rMFDA were associated with a 4% monthly decline in incidence relative to the baseline trend (trend change: IRR = 0.96, 95% CI = 0.95, 0.98). Over the study period, RFDA and rMFDA were estimated to avert 2,070 (95% CI = 577, 4,367) of 4,108 (95% CI = 2,620, 6,425) malaria cases.ConclusionsRFDA and rMFDA were associated with reduced malaria incidence in northern Senegal, supporting their use in malaria control in very low transmission areas. However, additional strategies are likely needed to achieve elimination in this setting.

Project description:BackgroundSubpatent 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.MethodsUsing 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.ResultsPrevalence 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.ConclusionsThis 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.

Project description:BackgroundReactive focal mass drug administration (rfMDA), or presumptive treatment without malaria testing of household members and neighbours of a passively identified malaria case, is currently being explored as a possible malaria elimination strategy in low transmission settings. One of the primary factors determining the effectiveness of rfMDA on reducing or interrupting transmission is achieving high coverage of the target population with drug administration. This study aims to explore the acceptability of rfMDA and identify facilitators and barriers to its potential implementation, as well as the community's general knowledge, attitudes and beliefs with regard to malaria elimination.MethodsA qualitative study was performed using focus group discussions (FGDs) among villagers that received rfMDA through the National Malaria Control Programme in the low transmission setting of Eswatini as part of a 2-year clinical trial. FGDs were audio-recorded, transcribed and translated into English. All transcripts were managed in Dedoose and underwent qualitative content analysis.ResultsThe majority of participants perceived their community to be at high risk of malaria. Witnessing others in their community suffer from malaria, proximity to Mozambique, various ecological factors, and the presence of mosquitoes contributed to this perception. The greatest motivator of participation in rfMDA was witnessing someone else suffer from malaria, since most participants had not personally experienced malaria themselves. Participants valued the education on rfMDA and on malaria in general, particularly when communicated by nurses and other health workers from the Ministry of Health. Participants were overwhelmingly motivated to participate in rfMDA in order to obtain protection from malaria. Most participants did not understand the concept of sub-clinical infection and, therefore, did not perceive the anti-malarial medication given in rfMDA to be a treatment medication.ConclusionsPerceived risk for malaria was a major driver of acceptability; therefore, future intervention campaigns could aim to better quantify risk to inform interventions and encourage uptake. There were misunderstandings about the asymptomatic reservoir of parasites in humans. Given that this phenomenon is the rationale for rfMDA, this misunderstanding could threaten the uptake of the intervention if it persists in the community. Using local authorities to deliver messaging, additional education on this concept with re-inforcement that risk of malaria is ongoing, even in the absence of frequent cases, may help to maximize and maintain acceptability.

Dataset Information

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

Background

Methods

Findings

Interpretation

Funding

Publications

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets