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BACKGROUND: A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d'Ivoire. METHODS: From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region. RESULTS: Overall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222-298], 43.5 [35.8-51.29] and 3.02 [1.96-4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations. CONCLUSION: These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.
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Anopheles , Mordeduras y Picaduras , Malaria , Animales , Adulto , Humanos , Anopheles/parasitología , Malaria/prevención & control , Côte d'Ivoire/epidemiología , Mosquitos Vectores/parasitología , Estaciones del AñoRESUMEN
BACKGROUND: In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. The consequences on pathogen-specific immune responses are not well known. This study evaluated and compared the humoral responses specific to merozoite stage vaccine candidates of Plasmodium falciparum, in children differentially exposed to Anopheles bites in a natural setting. METHODS: The cross-sectional study was carried out in Bouaké (Côte d'Ivoire) where entomological data and blood samples from children (0-14 years) were collected in two sites with similar malaria prevalence. Antibody (IgG, IgG1, IgG3) responses to PfAMA1 and PfMSP1 were evaluated by ELISA. Univariate and multivariate analysis were performed to assess the relationship between the immune responses to P. falciparum antigens and exposure to Anopheles bites in the total cohort and in each site, separately. The individual level of exposure to Anopheles bites was evaluated by quantifying specific IgG response to the Anopheles gSG6-P1 salivary peptide, which represents a proxy of Anopheles exposure. RESULTS: The anti-Plasmodium humoral responses were different according to the level of exposure of children, with those highly exposed to Anopheles presenting significantly lower antibody responses to PfMSP1 in total population (IgG and IgG3) and in Petessou village (IgG, IgG1, IgG3). No significant difference was seen for PfAMA1 antigen between children differently exposed to Anopheles. In Dar-es-Salam, a neighbourhood where a high Culex density was reported, children presented very low antibody levels specific to both antigens, and no difference according to the exposure to Anopheles bites was found. CONCLUSION: These findings may suggest that immunomodulatory components of Anopheles saliva, in addition to other factors, may participate to the modulation of the humoral response specific to Plasmodium merozoite stage antigens. This epidemiological observation may form a starting point for additional work to decipher the role of mosquito saliva on the modulation of the anti-Plasmodium acquired immunity and clinical protection in combining both field and ex vivo immunological studies.
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Anopheles/fisiología , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Mordeduras y Picaduras de Insectos , Plasmodium falciparum/inmunología , Adolescente , Animales , Formación de Anticuerpos , Niño , Preescolar , Côte d'Ivoire , Estudios Transversales , Femenino , Humanos , Lactante , Malaria Falciparum/inmunología , MasculinoRESUMEN
BACKGROUND: In some African cities, urban malaria is a threat to the health and welfare of city dwellers. To improve the control of the disease, it is critical to identify neighbourhoods where the risk of malaria transmission is the highest. This study aims to evaluate the heterogeneity of malaria transmission risk in one city (Bouaké) in a West African country (Côte d'Ivoire) that presents several levels of urbanization. METHODS: Two cross-sectional studies were conducted in three neighbourhoods (Dar-es-Salam, Kennedy and N'gattakro) in Bouaké during both the rainy and dry seasons. Data on insecticide-treated net (ITN) use and blood samples were collected from children aged between 6 months and 15 years to determine the parasite density and the prevalence of Plasmodium falciparum and the level of IgG against the Anopheles gSG6-P1 salivary peptide, used as the biomarker of Anopheles bite exposure. RESULTS: The specific IgG levels to the gSG6-P1 salivary peptide in the rainy season were significantly higher compared to the dry season in all neighbourhoods studied (all p < 0.001). Interestingly, these specific IgG levels did not differ between neighbourhoods during the rainy season, whereas significant differences in IgG level were observed in the dry season (p = 0.034). ITN use could be a major factor of variation in the specific IgG level. Nevertheless, no difference in specific IgG levels to the gSG6-P1 salivary peptide was observed between children who declared "always" versus "never" sleeping under an ITN in each neighbourhood. In addition, the prevalence of P. falciparum in the whole population and immune responders was significantly different between neighbourhoods in each season (p < 0.0001). CONCLUSION: This study highlights the high risk of malaria exposure in African urban settings and the high heterogeneity of child exposure to the Anopheles vector between neighbourhoods in the same city. The Anopheles gSG6-P1 salivary peptide could be a suitable biomarker to accurately and quantitatively assess the risk of malaria transmission in urban areas.
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Transmisión de Enfermedad Infecciosa , Exposición a Riesgos Ambientales , Malaria Falciparum/epidemiología , Malaria Falciparum/transmisión , Mosquitos Vectores/crecimiento & desarrollo , Población Urbana , Adolescente , Animales , Anticuerpos Antiprotozoarios/sangre , Niño , Preescolar , Ciudades/epidemiología , Côte d'Ivoire/epidemiología , Estudios Transversales , Utilización de Equipos y Suministros , Femenino , Humanos , Inmunoglobulina G/sangre , Lactante , Proteínas de Insectos/inmunología , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Masculino , Plasmodium falciparum/inmunología , Plasmodium falciparum/aislamiento & purificación , Medición de Riesgo , Proteínas y Péptidos Salivales/inmunología , Estaciones del Año , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Emergence of artemisinin resistance has raised concerns that the most potent anti-malarial drug may be under threat. Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are, respectively, the first- and second-line treatments for uncomplicated falciparum malaria in Côte d'Ivoire. Constant monitoring by National Malaria Control Programme (NMCP) of drug efficacy is an important tool in establishing rational anti-malarial drug policies in Côte d'Ivoire. METHODS: In an open label, randomized controlled clinical trial, children and adults were randomized to receive AS-AQ or AL. Both drug regimens were given for three days, and follow-up was for 42 days. The primary endpoint was the 42-day cure rate and was defined as proportion of patients with PCR-corrected cure rate after 42 days of follow-up. RESULTS: A total of 383 patients who were attending the Anonkoua-koute (Abidjan), Petit Paris (Korhogo) and Libreville (Man) hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive AS-AQ (188) and AL (195). The intention-to-treat analysis showed effectiveness rates of 94.7% and 96.4% for AS-AQ and AL, respectively on day 42. After adjustment for PCR, these rates were 96.8% and 99%, respectively. At day 42, in per-protocol analysis, Adequate clinical and parasitological response (ACPR) PCR uncorrected was 97.8% and 97.4% for AS-AQ and AL, respectively. The PCR adjusted ACPR was 100% for each combination and both regimens were well tolerated. CONCLUSIONS: This study has shown the high efficacy of AS-AQ in patients of all ages with acute uncomplicated falciparum malaria and AS-AQ was non-inferior to AL. Continuous efficacy monitoring is recommended.
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Amodiaquina/administración & dosificación , Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Etanolaminas/administración & dosificación , Fluorenos/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Combinación Arteméter y Lumefantrina , Niño , Preescolar , Côte d'Ivoire , Combinación de Medicamentos , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The massive scale-up of long-lasting insecticidal nets (LLIN) has led to a major reduction in malaria burden in many sub-Saharan African (SSA) countries. The World Health Organization (WHO) has recently issued a strong recommendation for the use of chlorfenapyr-pyrethroid LLINs compared to standard pyrethroid-only LLINs in areas of high insecticide resistance intensity. However, there is still a lack of conclusive evidence on the efficacy of piperonyl butoxide-pyrethroid (PBO-py) LLINs, especially in West Africa, where vector composition and resistance mechanisms may be different from vectors in East Africa. METHODS: This is a three-arm, superiority, triple-blinded, cluster randomised trial, with village as the unit of randomisation. This study conducted in Côte d'Ivoire will evaluate the efficacy on epidemiological and entomological outcomes of (1) the control arm: MAGNet® LN, which contains the pyrethroid, alpha-cypermethrin, (2) VEERALIN® LN, a net combining the synergist PBO and alpha-cypermethrin, and (3) Interceptor® G2 LN, which incorporates chlorfenapyr and alpha-cypermethrin, two adulticides with different mechanisms of action. A total of 33 villages with an average of 200 households per village will be identified, mapped, and randomised in a ratio of 1:1:1. Nets will be distributed at a central point following national guidelines with 1 net for every 2 people. The primary outcome of the trial will be incidence of malaria cases (confirmed by rapid diagnostic test (RDT)) in a cohort of 50 children aged 6 months to 10 years in each cluster, followed for 12 months (active case detection). Secondary outcomes are cross-sectional community prevalence of malaria infection (confirmed by RDT) in the study population at 6 and 12 months post-intervention (50 randomly selected persons per cluster), vector density, entomological inoculation rate (EIR), and phenotypic and genotypic insecticide resistance at baseline and 12 months post-intervention in 3 sentinel villages in each treatment arm. DISCUSSION: In addition to generating further evidence for next-generation LLINs, this study will also provide the first evidence for pyrethroid-PBO nets in a West African setting. This could further inform WHO recommendations on the pragmatic use of pyrethroid-PBO nets. TRIAL REGISTRATION: ClinicalTrials.gov NCT05796193. Registered on April 3, 2023.
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Anopheles , Mosquiteros Tratados con Insecticida , Insecticidas , Malaria , Piretrinas , Niño , Animales , Humanos , Butóxido de Piperonilo/farmacología , Côte d'Ivoire/epidemiología , Estudios Transversales , Control de Mosquitos , Mosquitos Vectores , Piretrinas/farmacología , Insecticidas/efectos adversos , Resistencia a los Insecticidas , Malaria/epidemiología , Malaria/prevención & controlRESUMEN
BACKGROUND: Culex mosquitoes are vectors for a variety of pathogens of public health concern. New indicators of exposure to Culex bites are needed to evaluate the risk of transmission of associated pathogens and to assess the efficacy of vector control strategies. An alternative to entomological indices is the serological measure of antibodies specific to mosquito salivary antigens. This study investigated whether the human IgG response to both the salivary gland extract and the 30 kDa salivary protein of Culex quinquefasciatus may represent a proxy of human exposure to Culex bites. METHODOLOGY/PRINCIPAL FINDINGS: A multidisciplinary survey was conducted with children aged 1 to 14 years living in neighborhoods with varying exposure to Culex quinquefasciatus in the city of Bouaké, Côte d'Ivoire. Children living in sites with high exposure to Cx quinquefasciatus had a significantly higher IgG response to both salivary antigens compared with children living in the control site where only very few Culex were recorded. Moreover, children from any Culex-high exposed sites had significantly higher IgG responses only to the salivary gland extract compared with children from the control village, whereas no difference was noted in the anti-30 kDa IgG response. No significant differences were noted in the specific IgG responses between age and gender. Sites and the use of a bed net were associated with the level of IgG response to the salivary gland extract and to the 30 kDa antigen, respectively. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the IgG response to Culex salivary gland extracts is suitable as proxy of exposure; however, the specificity to the Culex genus needs further investigation. The lower antigenicity of the 30 kDa recombinant protein represents a limitation to its use. The high specificity of this protein to the Culex genus makes it an attractive candidate and other specific antibody responses might be more relevant as a biomarker of exposure. These epidemiological observations may form a starting point for additional work on developing serological biomarkers of Culex exposure.
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Biomarcadores/sangre , Culex/inmunología , Inmunoglobulina G/sangre , Mordeduras y Picaduras de Insectos/sangre , Proteínas y Péptidos Salivales/inmunología , Adolescente , Animales , Niño , Preescolar , Côte d'Ivoire , Culex/fisiología , Femenino , Humanos , Lactante , Mordeduras y Picaduras de Insectos/parasitología , Masculino , Proyectos Piloto , Glándulas Salivales/inmunologíaRESUMEN
Humoral immunity to Plasmodium falciparum is acquired after repeated infections, and can lead to clinical protection. This study aimed to evaluate how human-, parasite-, and environment-related determinants can modulate the dynamics of IgG responses to Plasmodium falciparum after an infection. Individuals (n = 68, average age = 8.2 years) with uncomplicated malaria were treated with ACT and followed up for 42 days. IgG responses to P. falciparum merozoite antigens (PfMSP1, PfMSP3, PfAMA1, PfGLURP-R0), to whole schizont extract (PfSchz), and to Anopheles gSG6-P1 and Aedes Nterm-34 kDa salivary peptides were measured. Regression analyses were used to identify factors that influence the dynamics of IgG response to P. falciparum antigen between D0 and D42, including demographic and biological factors and the level of exposure to mosquito bites. The dynamics of IgG response to P. falciparum differed according to the antigen. According to multivariate analysis, IgG responses to PfSchz and to PfGLURP-R0 appear to be affected by exposure to Aedes saliva and are associated with age, parasite density, and anti-Plasmodium pre-existing immune response at study inclusion. The present work shows that human exposure to Aedes saliva may contribute, in addition to other factors, to the regulation of anti-Plasmodium immune responses during a natural infection.
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BACKGROUND: Malaria is still a major public health concern in Côte d'Ivoire despite mass distribution of long-lasting insecticidal nets (LLINs) as a key preventive strategy. This study intended to evaluate the operational effectiveness of LLINs on the level of human-vector contact using 1 antibody-based biomarker of exposure to Anopheles in urban areas. METHODS: This cross-sectional study collected socio-demographic data and use of LLINs from 9 neighborhoods in the city of Bouaké (Côte d'Ivoire). Dry blood spots performed in children aged >6 months and adults were used to evaluate immunoglobulin G (IgG) responses to the Anopheles gSG6-P1 salivary peptide. RESULTS: IgG response levels to the salivary peptide were significantly lower in individuals who declared having "always" (nâ =â 270) slept under an LLIN compared with those who had "often" (nâ =â 2087) and "never" (nâ =â 88) slept under an LLIN (Pâ <â .0001). IgG response levels to gSG6-P1 between those who declared having "always" and "not always" slept under an LLIN varied according to neighborhood, socio-professional category, and age group. CONCLUSIONS: The human IgG level to this gSG6-P1 salivary peptide could be a useful tool to evaluate the actual effectiveness of LLINs and help design behavioral change interventions that are crucial for sustaining universal coverage.
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Urban malaria is an underestimated serious health concern in African countries. This study aimed to evaluate the risk of malaria transmission in an urban area by evaluating the level of human exposure to Anopheles bites using an Anopheles salivary biomarker (gambiae Salivary Gland Protein-6 peptide 1 [gSG6-P1] peptide). Two multidisciplinary cross-sectional studies were undertaken in five sites of Bouaké city (three urban districts and two surrounding villages, used as control; Côte d'Ivoire) during the rainy season and the dry season. Blood samples were obtained from children 6 months to 14 years of age for immunological tests. The level of anti-gSG6-P1 immunoglobulin G (IgG) antibodies was significantly higher in the rainy season than the dry season in both urban and rural sites (P < 0.0001). Interestingly, children with the highest anti-gSG6-P1 IgG responses in the rainy season were infected by Plasmodium falciparum. Surprisingly, no difference of anti-gSG6-P1 IgG level was observed between urban and rural areas, for either season. The current data suggest that children in the urban city of Bouaké could be as highly exposed to Anopheles bites as children living in surrounding villages. The immunological biomarker of human exposure to Anopheles bites may be used to accurately assess the potential risk of malaria transmission in African urban settings.
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Anopheles , Mordeduras y Picaduras de Insectos/epidemiología , Proteínas de Insectos/inmunología , Malaria/prevención & control , Proteínas y Péptidos Salivales/inmunología , Población Urbana , Animales , Biomarcadores/sangre , Preescolar , Côte d'Ivoire/epidemiología , Estudios Transversales , Humanos , Inmunoglobulina G/sangre , Mordeduras y Picaduras de Insectos/prevención & control , Mosquitos Vectores , Factores de Riesgo , Población Rural , Estaciones del AñoRESUMEN
Background: In Africa, malaria care is mostly based on clinical presumption and the general application of antimalarial treatment to all febrile episodes over several years. Treatment limited to confirmed cases might curb the practice of equating fever with malaria, antimalarial drug abuse and the extension of Plasmodium resistance, provided that powerful and reliable rapid diagnostic tests are used. This study aimed at determining the performances of the Optimal-IT® test in the strategy for the exclusive treatment of uncomplicated malaria in rural areas. Materials and Methods: A prospective study conducted in the forest region of San Pedro, Côte d'Ivoire, included patients exhibiting clinical signs of uncomplicated malaria who gave their consent and benefited from thick blood film (TBF), blood smear (BS) and Optimal-IT® (pLDH-based) test. Rapid diagnostic test (RDT) results were taken into consideration to decide on malaria treatment and then compared with TBF/BS results (reference) to assess the performances and clinical usefulness of the RDT. Results: The mean age of the 384 patients included (209 men, 175 women) was 28 years and the mean temperature was 38.1°C. TBF/BS and Optimal-IT® were concordant in 92% of patients but discordant in 10 false negative (3%) and 19 false-positive patients (5%). The average parasite density of P. falciparum was 25,600 trophozoites/µl. The performances calculated were: sensitivity=95%, specificity=91%, positive predictive value=90%, negative predictive value=95%, positive likelihood ratio=10, negative likelihood ratio=0.06 and diagnostic odds ratio=166, indicating that Optimal-IT® is a powerful and credible diagnostic tool. The 193 RDT-positive patients treated were healed, despite three recurrence cases at day (D) D17, D25 and D27, respectively. RDT-negative patients received various treatments (antibiotics, paracetamol), but two patients among them presented with a bout of malaria on D7. None of the previously untreated patients returned with severe malaria. Conclusions: The Optimal-IT® test, which is already used in the field, showed good performances to effectively detect patients with and without malaria. It is therefore adapted to the malaria treatment strategy limited to confirmed cases.
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BACKGROUND: The growing development of pyrethroid resistance constitutes a serious threat to malaria control programmes and if measures are not taken in time, resistance may compromise control efforts in the foreseeable future. Prior to Long Lasting Insecticidal Nets (LLINs) distribution in Eastern Cote d'Ivoire, we conducted bioassays to inform the National Malaria Control Programme of the resistance status of the main malaria vector, Anopheles gambiae s. s. and the need for close surveillance of resistance. METHODS: Larvae of An. gambiae s. s. were collected in two areas of Adzopé (Port-Bouët and Tsassodji) and reared to adults. WHO susceptibility tests with impregnated filter papers were carried out to detect resistance to three pyrethroids commonly used to develop LLINs: permethrin 1%, deltamethrin 0.05% and lambda-cyhalothrin 0.05%. Molecular assays were conducted to detect M and S forms and the L1014F kdr allele in individual mosquitoes. RESULTS: Resistance, at various degrees was detected in both areas of Adzopé. Overall, populations of An. gambiae at both sites surveyed showed equivalent frequency of the L1014F kdr allele (0.67) but for all tested pyrethroids, there were significantly higher survival rates for mosquitoes from Tsassodji (32-58%) than those from Port-Bouët (3-32%) (p < 0.001), indicating the implication of resistance mechanisms other than kdr alone. During the survey period (May-June) in this forested area of Côte d'Ivoire, An. gambiae s. s. found were exclusively of the M form and were apparently selected for pyrethroid resistance through agricultural and household usage of insecticides. CONCLUSION: Prior to LLINs scaling up in Eastern Côte d'Ivoire, resistance was largely present at various levels in An. gambiae. Underlying mechanisms included the high frequency of the L1014F kdr mutation and other unidentified components, probably metabolic detoxifiers. Their impact on the efficacy of the planned strategy (LLINs) in the area should be investigated alongside careful monitoring of the trend in that resistance over time. The need for alternative insecticides to supplement or replace pyrethroids on nets must be stressed.