Voluntary licensing of long-acting HIV prevention and treatment regimens: using a proven collaboration- and competition-based mechanism to rapidly expand at-scale, sustainable, quality-assured and affordable supplies in LMICs.

INTRODUCTION: Emerging long-acting (LA) prevention and treatment medicines, technologies and regimens could be game-changing for the HIV response, helping reach the ambitious goal of halting the epidemic by 2030. To attain this goal, the rapid expansion of at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment products through accelerated and stronger competition, involving both originator and generic companies, will be essential. To do this, global health stakeholders should take advantage of voluntary licensing of intellectual property (IP) rights, such as through the United Nations-backed, not-for-profit Medicines Patent Pool, as a proven mechanism to support broad access to existing HIV medicines across low- and middle-income countries (LMICs). DISCUSSION: While voluntary licensing may unlock the possibility for generic competition to take place ahead of patent expiry, there are additional elements-of amplified importance for more complex LA HIV medicines-that need to be taken into consideration. This paper discusses 10 enablers of voluntary licensing of IP rights as a model to rapidly expand at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment regimens in LMICs: Identifying promising LA technology platforms and drug formulations at an early developmental stage and engaging with patent holders Consolidating a multidisciplinary network and strengthening early-stage coordination and collaboration to foster innovation Embedding public health considerations in product design and delivery Building innovative partnerships for product development and commercialization Raising awareness of and creating demand for emerging LA products Estimating the market size, ensuring sufficient competition and protecting sustainability Using technology transfer and hands-on technical support to reduce product development timelines and costs Exploring de-risking mechanisms and financial incentives to support generic manufacturers Optimizing strategies for generic product development and regulatory filings Aligning and coordinating efforts of stakeholders across the value chain. CONCLUSIONS: Rapid access to emerging LA prevention and treatment regimens and technologies can be facilitated by voluntary licensing-catalyzed and supplemented by enabling collaborative and non-duplicative efforts of various other stakeholders. This can effectively lead to improved-accelerated and cheaper-access to quality-assured medicines for populations in LMICs.

Enhancing Preparedness for Arbovirus Infections with a One Health Approach: The Development and Implementation of Multisectoral Risk Assessment Exercises.

BACKGROUND: One Health is receiving attention for arbovirus infection prevention and control and for defining national "intersectoral" priorities. Increasing awareness of intersectoral priorities through multisectorial risk assessments (MRA) is promising, where data are not systematically shared between sectors. Towards this aim, the MediLabSecure project organized three MRA exercises (hereby called exercises): one on West Nile virus, one on Crimean-Congo haemorrhagic fever, and one on Rift Valley fever, assessing the added value of this approach. METHODS: The exercises relied on RA methodologies of international organisations. Country representatives of the human and animal virology, medical entomology, and public health sectors (hereby called "sectors") involved in the surveillance of vector-borne diseases participated in the exercises. Background documentation was provided before each exercise, and a guide was developed for the facilitators. All three exercises included technical and methodological presentations and a guided RA directed at bringing into play the different sectors involved. To assess the added value of the approach, each participant was asked to rank the level of perceived benefit of the multisectoral collaboration for each "risk question" included in the exercises. RESULTS: In total, 195 participants from 19 non-EU countries in the Mediterranean and Black Sea regions took part in the exercises. The participants assessed the multisectoral approach as valuable in analysing comprehensively the situation by having access to information and knowledge provided by each of the sectors involved. Sharing of information and discussion facilitated reaching a consensus on the level of risk in each country. CONCLUSIONS: Increasing awareness of intersectoral priorities, including cross-border ones, through MRA is relevant to reduce gaps due to unavailability of shared data and information. Given that six out of the ten threats to global health listed by WHO are occurring at the human-animal-environmental interfaces, comprehensive regional RA with a One Health approach made by national authorities can be a relevant added value for the global health security.

Expression of CD300lf by microglia contributes to resistance to cerebral malaria by impeding the neuroinflammation.

Genetic mapping and genome-wide studies provide evidence for the association of several genetic polymorphisms with malaria, a complex pathological disease with multiple severity degrees. We have previously described Berr1and Berr2 as candidate genes identified in the WLA/Pas inbreed mouse strain predisposing to resistance to cerebral malaria (CM) induced by P. berghei ANKA. We report in this study the phenotypic and functional characteristics of a congenic strain we have derived for Berr2WLA allele on the C57BL/6JR (B6) background. B6.WLA-Berr2 was found highly resistant to CM compared to C57BL/6JR susceptible mice. The mechanisms associated with CM resistance were analyzed by combining genotype, transcriptomic and immune response studies. We found that B6.WLA-Berr2 mice showed a reduced parasite sequestration and blood-brain barrier disruption with low CXCR3+ T cell infiltration in the brain along with altered glial cell response upon P. berghei ANKA infection compared to B6. In addition, we have identified the CD300f, belonging to a family of Ig-like encoding genes, as a potential candidate associated with CM resistance. Microglia cells isolated from the brain of infected B6.WLA-Berr2 mice significantly expressed higher level of CD300f compared to CMS mice and were associated with inhibition of inflammatory response.

Strengthening Preparedness for Arbovirus Infections in Mediterranean and Black Sea Countries: A Conceptual Framework to Assess Integrated Surveillance in the Context of the One Health Strategy.

In the context of One Health, there is presently an effort to integrate surveillance of human, animal, entomological, and environmental sectors. This aims to strengthen the prevention of, and preparedness against, arbovirus infections, also in the light of environmental and climate changes that could increase the risk of transmission. However, criteria to define integrated surveillance, and to compare different systems, still need to be identified and tested. We conducted a scoping review to identify and examine surveillance systems for West Nile virus (WNV), chikungunya virus (CHKV), dengue virus (DENV), and Rift Valley fever virus (RVFV), which involve human, animal, entomological, and environmental sectors. We analyzed findings using a conceptual framework we developed for this purpose. The review highlights that the criteria proposed in the conceptual framework to describe integrated surveillance are consistently reported in the context of studies and programs related to integrated surveillance of the selected arboviral diseases. These criteria can facilitate the identification and description of operationalized One Health surveillance.

Surveillance of Arthropod-Borne Viruses and Their Vectors in the Mediterranean and Black Sea Regions Within the MediLabSecure Network.

PURPOSE OF REVIEW: Arboviruses, viruses transmitted by arthropods such as mosquitoes, ticks, sandflies, and fleas are a significant threat to public health because of their epidemic and zoonotic potential. The geographical distribution of mosquito-borne diseases such as West Nile (WN), Rift Valley fever (RVF), Dengue, Chikungunya, and Zika has expanded over the last decades. Countries of the Mediterranean and Black Sea regions are not spared. Outbreaks of WN are repeatedly reported in the Mediterranean basin. Human cases of RVF were reported at the southern borders of the Maghreb region. For this reason, establishing the basis for the research to understand the potential for the future emergence of these and other arboviruses and their expansion into new geographic areas became a public health priority. In this context, the European network "MediLabSecure" gathering laboratories in 19 non-EU countries from the Mediterranean and Black Sea regions seeks to improve the surveillance (of animals, humans, and vectors) by reinforcing capacity building and harmonizing national surveillance systems to address this important human and veterinary health issue. The aim of this review is to give an exhaustive overview of arboviruses and their vectors in the region. RECENT FINDINGS: The data presented underline the importance of surveillance in the implementation of more adapted control strategies to combat vector-borne diseases. Partner laboratories within the MediLabSecure network present a wide range of infrastructures and have benefited from different training programs. SUMMARY: Although reporting of arboviral presence is not carried out in a systematic manner, the expansion of the area where arboviruses are present cannot be disputed. This reinforces the need for increasing surveillance capacity building in this region to prevent future emergences.

Sex-dependent interactions between leptin, wasting and humoral immunity in two ethnic communities of school-aged children differentially exposed to Schistosoma haematobium.

Background: Leptin is a nutritional hormone whose production is generally higher in females. We investigated how leptin is associated with sex dimorphism during urinary schistosomiasis in relation with wasting. Methods: A cross-sectional study was carried out in three villages in northern Senegal. Ninety-eight school-aged children belonging to the Fulani or Wolof villages were enrolled. We performed parasitic diagnosis and anthropometric measurement to evaluate nutritional status. We collected peripheral blood to determine the amount of circulating leptin and immunoglobulin G (IgG), IgG4 and IgE directed to soluble worm antigen preparation (SWAP). Results: The prevalence of Schistosoma haematobium infection was higher among boys regardless of ethnic group, but exposure to parasites did not exacerbate malnutrition. The greater ability of girls to produce leptin was not altered by schistosomiasis and was recovered in both ethnic groups. However, while the usual correlation between leptin and fat storage was preserved in Fulani girls, it was disrupted in Fulani boys, who displayed a remarkable susceptibility for wasting. Finally, we observed that leptin was negatively associated with the level of antibodies in Wolof boys. Conclusions: Leptin can be disconnected from body fat and may exert a sex-dependent influence on host immune response to S. haematobium infection in Senegalese children.

Risk of Zika virus transmission in the Euro-Mediterranean area and the added value of building preparedness to arboviral threats from a One Health perspective.

In the alarming context of risk of Zika virus (ZIKV) transmission in the Euro-Mediterranean area, there is a need to examine whether capacities to detect, diagnose and notify ZIKV infections in the region are in place and whether ongoing capacity-building initiatives are filling existing gaps.The MediLabSecure network, created in 2014, comprises 55 laboratories of virology and medical entomology and 19 public health institutions in 19 countries in the Balkans, North-Africa, the Middle-East and the Black Sea regions. It aims to set up awareness, risk assessment, monitoring and control of emerging and re-emerging vector-borne viruses. We here examine the actions and strategies that MediLabSecure has been implementing and how they will contribute to the prevention and control of the ZIKV threat in the Euro-Mediterranean area.Capacity-building for arbovirus diagnostics is a major objective of the project and follows a methodological rather than disease-driven approach. This enables the implementation of laboratory trainings on techniques that are common to several arboviruses, including ZIKV, and putting into action appropriate diagnostic tools in the target region.Moreover, by its One Health approach and the interaction of its four sub-networks in human virology, animal virology, medical entomology and public health, MediLabSecure is fostering intersectoral collaboration, expertise and sharing of information. The resulting exchanges (methodological, communication and operational) across disciplines and across countries, dedicated research on intersectoral collaboration and increasing diagnostic capacities are providing new paths and tools to public health professionals to face emerging viral threats such as a ZIKV epidemic in the Euro-Mediterranean region.

Immune response to Bordetella pertussis is associated with season and undernutrition in Senegalese children.

BACKGROUND: While vaccines elicit a protective response in most recipients, studies suggest that environmental and nutritional factors can influence the strength of the individual response to immunization and to subsequent natural infectious challenges. METHODS: We conducted a longitudinal survey in Senegal to assess the individual response to B. pertussis, a respiratory disease against which Senegalese children are vaccinated before the age of one (Clinicaltrials.gov ID: NCT01545115). A cohort of 203 children aged 1-9 from four villages of the Senegal River Valley was followed-up for 14 months (October 2008-January 2010). During that period, four visits have been made to the villages to assess the immunological and nutritional status of these children and to determine risk factors involved in the modulation of their humoral immune response to B. pertussis toxin. RESULTS: A multivariate model has demonstrated that birth season and nutritional status appeared to modulate humoral response to pertussis toxin. Moreover, response to B. pertussis was dependent on age, village and time of visit. CONCLUSIONS: These results are consistent with the hypothesis that environmental and nutritional factors modulate children's response to pertussis following natural infection or vaccination.

Children of Senegal River Basin show the highest prevalence of Blastocystis sp. ever observed worldwide.

BACKGROUND: Blastocystis sp. is currently the most common intestinal protist found in human feces and considered an emerging parasite with a worldwide distribution. Because of its potential impact in public health, we reinforced the picture of Blastocystis sp. prevalence and molecular subtype distribution in Africa by performing the first survey of this parasite in Senegal. METHODS: Stool samples from 93 symptomatic presenting with various gastrointestinal disorders or asymptomatic children living in three villages of the Senegal River Basin were tested for the presence of Blastocystis sp. by non-quantitative and quantitative PCR using primer pairs targeting the SSU rDNA gene. Positive samples were subtyped to investigate the frequency of Blastocystis sp. subtypes in our cohort and the distribution of subtypes in the symptomatic and asymptomatic groups of children. RESULTS: By the use of molecular tools, all 93 samples were found to be positive for Blastocystis sp. indicating a striking parasite prevalence of 100%. Mixed infections by two or three subtypes were identified in eight individuals. Among a total of 103 subtyped isolates, subtype 3 was most abundant (49.5%) followed by subtype 1 (28.2%), subtype 2 (20.4%) and subtype 4 (1.9%). Subtype 3 was dominant in the symptomatic group while subtypes 1 and 2 were detected with equal frequency in both symptomatic and asymptomatic groups. The distribution of subtypes was compared with those available in other African countries and worldwide. Comparison confirmed that subtype 4 is much less frequently detected or absent in Africa while it is commonly found in Europe. Potential sources of Blastocystis sp. infection including human-to-human, zoonotic, and waterborne transmissions were also discussed. CONCLUSIONS: The prevalence of Blastocystis sp. in our Senegalese population was the highest prevalence ever recovered worldwide for this parasite by reaching 100%. All cases were caused by subtypes 1, 2, 3 and 4 with a predominance of subtype 3. More than half of the children infected by Blastocystis sp. presented various gastrointestinal disorders. Such high prevalence of blastocystosis in developing countries makes its control a real challenge for public health authorities.

Prevalence and intensity of urinary schistosomiasis among school children in the district of Niakhar, region of Fatick, Senegal.

BACKGROUND: Urinary schistosomiasis is a parasitic disease that exists in all regions of Senegal. It is a major public health issue in this country. This study was carried out to determine the prevalence and intensity of this parasitosis in 12 villages of Niakhar (Fatick, Senegal). METHODS: A total of 210 schoolchildren, aged 7 to 15 years, were enrolled in this study, and urine samples were examined for Schistosoma haematobium eggs using a standard urine filtration technique. RESULTS: Of these children, 121 (57.6%) were found to be infected with a mean geometric count of 185 eggs per 10 ml of urine. The disease was present in all surveyed villages, and the prevalence ranged from 14.3% to 92.8%. The prevalence of infection was significantly correlated with increasing age and was higher in boys. Infection intensity was significantly higher in boys but did not significantly differ with age. Significant relationships between i) water contact or access to running water and ii) the prevalence or intensity of urinary schistosomiasis were also noted. CONCLUSIONS: The district of Niakhar is endemic for urinary schistosomiasis, with a high intensity of infection. A control program to decrease the prevalence and intensity should be implemented in this area to improve community health.

Effects of malnutrition on children's immunity to bacterial antigens in Northern Senegal.

To evaluate immunity to vaccine-preventable diseases according to nutritional status, a longitudinal study was conducted in Senegalese children ages 1-9 years old. A linear regression analysis predicted that weight for age was positively associated with immunoglobulin G (IgG) response to tetanus toxoid in children born during the rainy season or at the beginning of the dry season. A relationship between village, time of visits, and levels of antibodies to tetanus showed that environmental factors played a role in modulating humoral immunity to tetanus vaccine over time. Moreover, a whole-blood stimulation assay highlighted that the production of interferon-γ (IFN-γ) in response to tetanus toxoid was compromised in stunted children. However, the absence of cytokine modulation in response to Mycobacterium tuberculosis-purified protein derivatives and phytohemagglutinin suggests that the overall ability to produce IFN-γ was preserved in stunted children. Therefore, these results show that nutritional status can specifically alter the efficacy of long-lasting immunity to tetanus.

Plasmodium falciparum infection during dry season: IgG responses to Anopheles gambiae salivary gSG6-P1 peptide as sensitive biomarker for malaria risk in Northern Senegal.

BACKGROUND: The Northern part of Senegal is characterized by a low and seasonal transmission of malaria. However, some Plasmodium falciparum infections and malaria clinical cases are reported during the dry season. This study aims to assess the relationship between IgG antibody (Ab) responses to gSG6-P1 mosquito salivary peptide and the prevalence of P. falciparum infection in children during the dry season in the Senegal River Valley. The positive association of the Ab response to gSG6-P1, as biomarker of human exposure to Anopheles vector bite, and P. falciparum infectious status (uninfected, infected-asymptomatic or infected-symptomatic) will allow considering this biomarker as a potential indicator of P. falciparum infection risk during the dry season. METHODS: Microscopic examination of thick blood smears was performed in 371 and 310 children at the start (January) and at the end (June) of the dry season, respectively, in order to assess the prevalence of P. falciparum infection. Collected sera were used to evaluate IgG response to gSG6-P1 by ELISA. Association between parasitological and clinical data (infected-asymptomatic or infected-symptomatic) and the anti-gSG6-P1 IgG levels were evaluated during this period. RESULTS: The prevalence of P. falciparum infection was very low to moderate according to the studied period and was higher in January (23.5%) compared to June (3.5%). Specific IgG response was also different between uninfected children and asymptomatic carriers of the parasite. Children with P. falciparum infection in the dry season showed higher IgG Ab levels to gSG6-P1 than uninfected children. CONCLUSIONS: The results strengthen the hypothesis that malaria transmission is maintained during the dry season in an area of low and seasonal transmission. The measurement of IgG responses to gSG6-P1 salivary peptide could be a pertinent indicator of human malaria reservoir or infection risk in this particular epidemiological context. This promising immunological marker could be useful for the evaluation of the risk of P. falciparum exposure observed during dry season and, by consequences, could be used for the survey of potential pre-elimination situation.

gSG6-P1 salivary biomarker discriminates micro-geographical heterogeneity of human exposure to Anopheles bites in low and seasonal malaria areas.

BACKGROUND: Over the past decade, a sharp decline of malaria burden has been observed in several countries. Consequently, the conventional entomological methods have become insufficiently sensitive and probably under-estimate micro-geographical heterogeneity of exposure and subsequent risk of malaria transmission. In this study, we investigated whether the human antibody (Ab) response to Anopheles salivary gSG6-P1 peptide, known as a biomarker of Anopheles exposure, could be a sensitive and reliable tool for discriminating human exposure to Anopheles bites in area of low and seasonal malaria transmission. METHODS: A multi-disciplinary survey was performed in Northern Senegal where An. gambiae s.l. is the main malaria vector. Human IgG Ab response to gSG6-P1 salivary peptide was compared according to the season and villages in children from five villages in the middle Senegal River valley, known as a low malaria transmission area. RESULTS: IgG levels to gSG6-P1 varied considerably according to the villages, discriminating the heterogeneity of Anopheles exposure between villages. Significant increase of IgG levels to gSG6-P1 was observed during the peak of exposure to Anopheles bites, and decreased immediately after the end of the exposure season. In addition, differences in the season-dependent specific IgG levels between villages were observed after the implementation of Long-Lasting Insecticidal Nets by The National Malaria Control Program in this area. CONCLUSION: The gSG6-P1 salivary peptide seems to be a reliable tool to discriminate the micro-geographical heterogeneity of human exposure to Anopheles bites in areas of very low and seasonal malaria transmission. A biomarker such as this could also be used to monitor and evaluate the possible heterogeneous effectiveness of operational vector control programs in low-exposure areas.

Molecular epidemiology of Blastocystis in Lebanon and correlation between subtype 1 and gastrointestinal symptoms.

Blastocystis is the most common eukaryotic parasite in the intestinal tract of humans. Because of its potential impact in public health, we acquired the first data concerning the prevalence of this parasite and the frequency of the Blastocystis subtypes (STs) in the Lebanese population. In this study, fecal samples from 220 Lebanese symptomatic and asymptomatic patients were collected and a total of 42 patients (19%) were identified as positive for this parasite by direct-light microscopy of smears. Among these, 36 Blastocystis isolates were genotyped using partial small subunit ribosomal RNA gene sequencing. The ST distribution in the present Lebanese population was as follows: ST3 (33.3%), ST2 (33.3%), ST1 (30.6%), and ST4 (2.8%). These data were compared with those available in other Middle Eastern and neighboring countries. Finally, ST1 was significantly more prevalent among symptomatic patients of this Lebanese population.

Seroprevalence of pertussis in Senegal: a prospective study.

BACKGROUND: Pertussis, also known as whooping cough, is a vaccine-preventable respiratory disease caused by Bordetella pertussis infection, against which Senegalese children are immunized with the diphtheria-tetanus-whole cell pertussis vaccine (DTwP). Seroepidemiology of pertussis has been widely described in industrialized countries, but rare are the studies referring to it in developing countries. METHODS: We conducted a longitudinal survey in Northern Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG antibody (Ab) response against pertussis toxin (PT). A cohort of 410 children aged 1 to 9 from five villages in the Middle Senegal River Valley were followed-up for 18 months. During that period, five visits were made to assess the immunological status of the children. PRINCIPAL FINDINGS: PT-specific IgG responses were significantly different according to age. Until the age of 3, there was a decrease in the Ab response, which then increased in the older groups. Assessment of IgG antibodies to PT (IgG-PT) suggested evidence of recent exposures to the pathogen. Surprisingly, in one of the five villages the average Ab response to PT was very low at all ages during the first 6 months of the study. At the third visit, IgG-PT concentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed. CONCLUSIONS: Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs.

Differential acquisition of human antibody responses to Plasmodium falciparum according to intensity of exposure to Anopheles bites.

Malaria immunity is modulated by many environmental and epidemiological factors. This study evaluates the influence of a hitherto unstudied environmental-epidemiological factor, namely the impact of human exposure to Anopheles bites on the isotype profile of acquired antibody responses to Plasmodium falciparum. In two Senegalese villages where the intensity of exposure to Anopheles bites was markedly different (high and low exposure), specific IgG1 and IgG3 responses to P. falciparum whole schizont extract (WSE) and circumsporozoite protein (CSP) were evaluated at the peak of Anopheles exposure (September) and later (December) in a cohort of 120 children aged 3-8 years. Multivariate analysis showed a significantly lower IgG1 response against P. falciparum WSE and CSP in children highly exposed to Anopheles bites (Gankette) compared to those who were weakly exposed (Mboula). In contrast, in both villages, parasitemia and increasing age were strongly associated with higher IgG1 and IgG3 levels. We hypothesize that high exposure to Anopheles bites could inhibit IgG1-dependent responsiveness to P. falciparum known to induce protective immune responses against malaria. The impact of mosquito saliva on the regulation of specific protective immunity may need to be taken into account in epidemiological studies and trials for malaria vaccines.

Low and seasonal malaria transmission in the middle Senegal River basin: identification and characteristics of Anopheles vectors.

BACKGROUND: During the last decades two dams were constructed along the Senegal River. These intensified the practice of agriculture along the river valley basin. We conducted a study to assess malaria vector diversity, dynamics and malaria transmission in the area. METHODS: A cross-sectional entomological study was performed in September 2008 in 20 villages of the middle Senegal River valley to evaluate the variations of Anopheles density according to local environment. A longitudinal study was performed, from October 2008 to January 2010, in 5 selected villages, to study seasonal variations of malaria transmission. RESULTS: Among malaria vectors, 72.34% of specimens collected were An. arabiensis, 5.28% An. gambiae of the S molecular form, 3.26% M form, 12.90% An. pharoensis, 4.70% An. ziemanni, 1.48% An. funestus and 0.04% An. wellcomei. Anopheles density varied according to village location. It ranged from 0 to 21.4 Anopheles/room/day and was significantly correlated with the distance to the nearest ditch water but not to the river.Seasonal variations of Anopheles density and variety were observed with higher human biting rates during the rainy season (8.28 and 7.55 Anopheles bite/man/night in October 2008 and 2009 respectively). Transmission was low and limited to the rainy season (0.05 and 0.06 infected bite/man/night in October 2008 and 2009 respectively). During the rainy season, the endophagous rate was lower, the anthropophagic rate higher and L1014F kdr frequency higher. CONCLUSIONS: Malaria vectors are present at low-moderate density in the middle Senegal River basin with An. arabiensis as the predominant species. Other potential vectors are An. gambiae M and S form and An. funestus. Nonetheless, malaria transmission was extremely low and seasonal.

Schistosomiasis coinfection in children influences acquired immune response against Plasmodium falciparum malaria antigens.

BACKGROUND: Malaria and schistosomiasis coinfection frequently occurs in tropical countries. This study evaluates the influence of Schistosoma haematobium infection on specific antibody responses and cytokine production to recombinant merozoite surface protein-1-19 (MSP1-(19)) and schizont extract of Plasmodium falciparum in malaria-infected children. METHODOLOGY: Specific IgG1 to MSP1-(19), as well as IgG1 and IgG3 to schizont extract were significantly increased in coinfected children compared to P. falciparum mono-infected children. Stimulation with MSP1-(19) lead to a specific production of both interleukin-10 (IL-10) and interferon-γ (IFN-γ), whereas the stimulation with schizont extract produced an IL-10 response only in the coinfected group. CONCLUSIONS: Our study suggests that schistosomiasis coinfection favours anti-malarial protective antibody responses, which could be associated with the regulation of IL-10 and IFN-γ production and seems to be antigen-dependent. This study demonstrates the importance of infectious status of the population in the evaluation of acquired immunity against malaria and highlights the consequences of a multiple infection environment during clinical trials of anti-malaria vaccine candidates.