Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration

Abstract Background As The Gambia aims to achieve malaria elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. Methods Within a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis. Results Seasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 years in two transmission settings—the West Coast and Upper River Regions (4.32% and 31.30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1–15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings from the Malaria Transmission Dynamics Study, where individuals infected before the implementation of MDA had two-fold higher odds of re-infection post-MDA. Conclusions Serological markers can serve dual functions as indicators of malaria exposure and incidence. By monitoring age-specific sero-prevalence, the magnitude of age-stratified antibody levels, or identifying groups of individuals with above-average antibody responses, these antigens have the potential to complement conventional malaria surveillance tools. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to reliably measure transmission across endemic settings.

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Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration

10.1101/2020.04.09.20059774 ◽

2020 ◽

Author(s):

Lindsey Wu ◽

Julia Mwesigwa ◽

Muna Affara ◽

Mamadou Bah ◽

Simon Correa ◽

...

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

West Coast ◽

Malaria Infection ◽

Malaria Incidence ◽

The Gambia ◽

Community Based Interventions ◽

The West ◽

Conversion Rates ◽

Antibody Levels

AbstractBackgroundAs The Gambia aims to achieve elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions.MethodsWithin a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis.ResultsSeasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 in two transmission settings – the West Coast and Upper River Regions (4·32% and 31·30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1-15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings where individuals infected pre-MDA had 2-fold higher odds of re-infection post-MDA.ConclusionSerological markers can serve dual functions as indicators of malaria exposure and incidence. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to measure transmission across endemic settings.

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PO 8302 IMPACT OF TWO ANNUAL ROUNDS OF MASS DRUG ADMINISTRATION WITH DIHYDROARTEMISININ-PIPERAQUINE ON MALARIA TRANSMISSION IN A PROSPECTIVE COHORT STUDY

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.72 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A28.2-A28

Author(s):

Julia Mwesigwa ◽

Jane Achan ◽

Miriam Wathuo ◽

Archibald Worwui ◽

Nuredin Mohammed ◽

...

Keyword(s):

Cohort Study ◽

Malaria Transmission ◽

Drug Administration ◽

Prospective Cohort Study ◽

Mass Drug Administration ◽

Prospective Cohort ◽

Malaria Infection ◽

Clinical Malaria ◽

The Gambia ◽

Transmission Season

BackgroundMass drug administration (MDA) may reduce malaria transmission in low-transmission areas and interrupt transmission. The impact of MDA with dihydroartemisinin-piperaquine (DP) on malaria infection and clinical malaria was determined in a prospective cohort study in The Gambia.MethodsSingle annual MDA rounds with DP were done in 2014 and 2015 in a prospective cohort among residents aged >6 months in twelve villages in The Gambia at the start of the transmission season in June. Monthly blood samples for microscopy and PCR were collected during the transmission season from July to December, post MDA and once before MDA during the dry season in April. The incidence of infection and clinical malaria post-MDA were compared to 2013 and mixed effects logistic regression models assessed the efficacy and risk of re-infection post MDA.ResultsCoverage of 3 DP doses was 68.22% in 2014 and 65.60% in 2015. Compliance to 3 doses was high, 83.11% in 2014 and 85.93% in 2015. Incidence of infection in 2014 (2014: IR=0.23 PPY, 2013: IR=1.12 PPY, p<0.01) and clinical malaria in 2014 (2014: IR=0.08 PPY, 2013: IR=0.39: IRR=0.22, p<0.01) and 2015 (2015: IR=0.19, 2013:IR=0.38, IRR=0.50, p<0.01) was significantly lower after MDA compared to 2013. The incidence of clinical malaria remained higher in eastern Gambia compared to the western region. Subjects that took 3 DP doses had lower odds of infection in 2014 at 28 days (OR=0.61, 95% CI: 0.38–0.99) and 42 days (2014: OR=0.52, 95% CI: 0.29–0.89)ConclusionA single annual MDA round with DP temporarily reduced malaria infection and clinical disease during the transmission season and subjects that took 3 doses had lower risk of infection. However, several MDA rounds covering the entire transmission season and some targeting the human reservoir during the dry season, are needed to achieve a more marked sustained reduction of transmission.

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Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Wellcome Open Research ◽

10.12688/wellcomeopenres.15919.1 ◽

2020 ◽

Vol 5 ◽

pp. 136

Author(s):

Tony I. Isebe ◽

Joel L. Bargul ◽

Bonface M. Gichuki ◽

James M. Njunge ◽

James Tuju ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

The Gambia ◽

Antibody Responses ◽

Transmission Intensity ◽

Parasite Development ◽

Natural Immunity ◽

Malaria Transmission Intensity ◽

Transmission Region ◽

Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Wellcome Open Research ◽

10.12688/wellcomeopenres.15919.2 ◽

2021 ◽

Vol 5 ◽

pp. 136

Author(s):

Tony I. Isebe ◽

Joel L. Bargul ◽

Bonface M. Gichuki ◽

James M. Njunge ◽

James Tuju ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Negative Correlation ◽

The Gambia ◽

Antibody Responses ◽

Transmission Intensity ◽

Parasite Development ◽

Malaria Transmission Intensity ◽

Transmission Region ◽

Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in Gambia, compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses indicate negative correlation between antibody levels and malaria transmission intensity for Pf3D7_1102500 and Pf3D7_1401600. We report a correlation in antibody responses between schizont and gametocyte extract, but this is not statistically significant (cor=0.102, p=0.2851, CI=95%) and, Pf3D7_0532400 (cor=0.11, p=0.249, CI=95%) and Pf3D7_1401600 (cor=0.02, p=0.7968, CI=95%). We report a negative correlation in antibody responses between schizont and Pf3D7_1102500 (cor=-0.008, p=0.9348, CI=95%). There is a correlation between gametocyte extract and Pf3D7_1401600 (cor=-0.0402, p=0.6735, CI=95%), Pf3D7_1102500 (cor=0.0758, p=0.4271, CI=95%) and Pf3D7_0532400 (cor=0.155, p=0.1028, CI=95%). Acquisition of anti-PHIST antibodies correlates with exposure to malaria for Pf3D7_0532400 (p=0.009) but not Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels which do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore their potential as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Serological evaluation of a cluster randomised trial on the use of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia

10.1101/2021.04.12.21255334 ◽

2021 ◽

Author(s):

Lindsey Wu ◽

Michelle Hsiang ◽

Lisa M. Prach ◽

Leah Schrubbe ◽

Henry Ntuku ◽

...

Keyword(s):

Vector Control ◽

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

Quantitative Polymerase Chain Reaction ◽

Randomised Trial ◽

Antibody Responses ◽

Cluster Randomised Trial ◽

Serological Markers ◽

Cluster Randomised

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, p<0.001) for rfMDA and 0.79 (95%CI 0.67 - 0.92, p=0.001) for RACD. For combined rfMDA plus RAVC, aPR was 0.58 (95%CI 0.45 - 0.75, p<0.001). 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). The 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.

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The Effectiveness of Reactive Focal Mass Drug Administration (rfMDA) and Reactive Focal Vector Control (RAVC) to Reduce Malaria Transmission: A Cluster-Randomised Controlled Open Label Two-by-Two Factorial Design Trial from the Low-Endemic Setting of Namibia

SSRN Electronic Journal ◽

10.2139/ssrn.3454698 ◽

2019 ◽

Author(s):

Michelle Hsiang ◽

Henry Ntuku ◽

Kathryn W. Roberts ◽

Mi-Suk Kang Dufour ◽

Brooke Whittemore ◽

...

Keyword(s):

Vector Control ◽

Factorial Design ◽

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

Open Label ◽

Endemic Setting ◽

Cluster Randomised ◽

Randomised Controlled

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Prevalence of sexually transmitted infections among pregnant women attending antenatal clinics in West Coast Region of The Gambia

African Health Sciences ◽

10.4314/ahs.v21i2.13 ◽

2021 ◽

Vol 21 (2) ◽

pp. 585-592

Author(s):

Alphonsus Isara ◽

Aru-Kumba Baldeh

Keyword(s):

Pregnant Women ◽

Sexually Transmitted Infections ◽

West Coast ◽

Trichomonas Vaginalis ◽

The Gambia ◽

Age Group ◽

The West ◽

Sexually Transmitted ◽

Neisseria Gonorrhoea ◽

Coast Region

Background: Sexually Transmitted Infections (STI) are the second most common cause of healthy life years lost by women in the 15 – 44 years age group in Africa. Aim/Objective: To determine the prevalence of STIs among pregnant women attending antenatal care (ANC) clinics in the West Coast Region of The Gambia. Materials and Methods: Blood, urine, and high vaginal swabs samples from 280 pregnant women attending ANC in Brika- ma District Hospital, Brikama, and Bandung Maternity and Child Health Hospital, Bandung were examined. Serum samples were tested for HIV using western blot technique and for syphilis using the Venereal Disease Research Laboratory (VDRL) test, and rapid plasma regimen. Candida albicans, Group B Streptococcus and Neisseria gonorrhoea were identified using Analytical Profile Index (API). Direct urine microscopy was used to identify C. albicans and Trichomonas vaginalis while Chlamydia trachomatis was identified using Direct Fluorescent Antibody (DFA) test. Results: The overall prevalence of STIs was 53.6%. The pathogenic agents isolated were Candida albicans (31.8%), Strep- tococcus agalactiae (15.0%), Treponema pallidum (6.8%), HIV (5.7%), Trichomonas vaginalis (3.9%), Neisseria gonorrhoea (1.8%) and Chlamydia trachomatis (0.7%). STIs were more prevalent among women in the younger age group of 15 – 24 years (54.7%), unemployed (54.0%), Primipara (62.3%), and in the third trimester of pregnancy (72.7%). Conclusion: A high prevalence of STIs was found among pregnant women attending ANC in the West Coast region of The Gambia. Public health intervention programmes should be strengthened to promote the sexual and reproductive health of pregnant women in The Gambia. Keywords: Sexually transmitted infections; pregnant women; antenatal clinics; The Gambia.

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Optimising systemic insecticide use to improve malaria control

BMJ Global Health ◽

10.1136/bmjgh-2019-001776 ◽

2019 ◽

Vol 4 (6) ◽

pp. e001776 ◽

Cited By ~ 1

Author(s):

Hannah R Meredith ◽

Luis Furuya-Kanamori ◽

Laith Yakob

Keyword(s):

Vector Control ◽

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

Companion Animals ◽

Malaria Vectors ◽

Systemic Insecticide ◽

Blood Concentrations ◽

Systemic Insecticides ◽

The Impact

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.

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