Dynamics of transmission of Plasmodium falciparum by Anopheles arabiensis and the molecular forms M and S of Anopheles gambiae in Dielmo, Senegal

<p>Abstract</p> <p>Background</p> <p>The adaptation of <it>Anopheles gambiae </it>to humans and its environment involves an ongoing speciation process that can be best demonstrated by the existence of various chromosomal forms adapted to different environments and of two molecular forms known as incipient taxonomic units.</p> <p>Methods</p> <p>The aim of this study was to compare the epidemiologic role of <it>Anopheles arabiens </it>is and the molecular forms M and S of <it>Anopheles gambiae </it>in the transmission of Plasmodium in a rural areas of southern Senegal, Dielmo. The sampling of mosquitoes was carried out monthly between July and December 2004, during the rainy season, by human volunteers and pyrethrum spray catches.</p> <p>Results</p> <p><it>Anopheles arabiensis</it>, <it>An. gambiae </it>M and S forms coexisted during the rainy season with a predominance of the M form in September and the peak of density being observed in August for the S form. Similar parity rates were observed in <it>An. arabiensis </it>[70.9%] (n = 86), <it>An</it>. <it>gambiae </it>M form [68.7%] (n = 64) and <it>An</it>. <it>gambiae </it>S form [81.1%] (n = 156). The circumsporozoite protein (CSP) rates were 2.82% (n = 177), 3.17% (n = 315) and 3.45% (n = 405), with the mean anthropophilic rates being 71.4% (n = 14), 86.3% (n = 22) and 91.6% (n = 24) respectively for <it>An</it>. <it>arabiensis </it>and <it>An</it>. <it>gambiae </it>M and S forms. No significant difference was observed either in host preference or in <it>Plasmodium falciparum </it>infection rates between sympatric M and S populations.</p> <p>Conclusion</p> <p>No difference was observed either in host preference or in <it>Plasmodium falciparum </it>infection rates between sympatric M and S populations, but they present different dynamics of population. These variations are probably attributable to different breeding conditions.</p

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>A cross-sectional entomological study was performed in September 2008 in 20 villages of the middle Senegal River valley to evaluate the variations of <it>Anopheles </it>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.</p> <p>Results</p> <p>Among malaria vectors, 72.34% of specimens collected were <it>An. arabiensis</it>, 5.28% <it>An. gambiae </it>of the S molecular form, 3.26% M form, 12.90% <it>An. pharoensis</it>, 4.70% <it>An. ziemanni</it>, 1.48% <it>An. funestus </it>and 0.04% <it>An. wellcomei</it>. <it>Anopheles </it>density varied according to village location. It ranged from 0 to 21.4 <it>Anopheles</it>/room/day and was significantly correlated with the distance to the nearest ditch water but not to the river.</p> <p>Seasonal variations of <it>Anopheles </it>density and variety were observed with higher human biting rates during the rainy season (8.28 and 7.55 <it>Anopheles </it>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.</p> <p>Conclusions</p> <p>Malaria vectors are present at low-moderate density in the middle Senegal River basin with <it>An. arabiensis </it>as the predominant species. Other potential vectors are <it>An. gambiae </it>M and S form and <it>An. funestus</it>. Nonetheless, malaria transmission was extremely low and seasonal.</p

Hepatitis C Virus Infection May Lead to Slower Emergence of P. falciparum in Blood

International audienceBACKGROUND: Areas endemic for Plasmodium falciparum, hepatitis B virus (HBV) and hepatitis C virus (HCV) overlap in many parts of sub-Saharan Africa. HBV and HCV infections develop in the liver, where takes place the first development stage of P. falciparum before its further spread in blood. The complex mechanisms involved in the development of hepatitis may potentially influence the development of the liver stage of malaria parasites. Understanding the molecular mechanisms of these interactions could provide new pathophysiological insights for treatment strategies in Malaria. METHODOLOGY: We studied a cohort of 319 individuals living in a village where the three infections are prevalent. The patients were initially given a curative antimalarial treatment and were then monitored for the emergence of asexual P. falciparum forms in blood, fortnightly for one year, by microscopy and polymerase chain reaction. PRINCIPAL FINDINGS: At inclusion, 65 (20.4%) subjects had detectable malaria parasites in blood, 36 (11.3%) were HBV chronic carriers, and 61 (18.9%) were HCV chronic carriers. During follow-up, asexual P. falciparum forms were detected in the blood of 203 patients. The median time to P. falciparum emergence in blood was respectively 140 and 120 days in HBV- and HBV+ individuals, and 135 and 224 days in HCV- and HCV+ individuals. HCV carriage was associated with delayed emergence of asexual P. falciparum forms in blood relative to patients without HCV infection. CONCLUSIONS: This pilot study represents first tentative evidence of a potential epidemiological interaction between HBV, HCV and P. falciparum infections. Age is an important confounding factor in this setting however multivariate analysis points to an interaction between P. falciparum and HCV at the hepatic level with a slower emergence of P. falciparum in HCV chronic carriers. More in depth analysis are necessary to unravel the basis of hepatic interactions between these two pathogens, which could help in identifying new therapeutic approaches against malaria

Artemisinin-naphthoquine combination (ARCO™) therapy for uncomplicated falciparum malaria in adults of Papua New Guinea: A preliminary report on safety and efficacy

<p>Abstract</p> <p>Background</p> <p>The use of anti-malarial drug combinations with artemisinin or with one of its derivatives is now widely recommended to overcome drug resistance in falciparum as well as vivax malaria. The fixed oral dose artemisinin-naphthoquine combination (ANQ, ARCO™) is a newer artemisinin-based combination (ACT) therapy undergoing clinical assessment. A study was undertaken to assess the safety, efficacy and tolerability of ANQ combination in areas of multi-drug resistance to generate preliminary baseline data in adult population of Papua New Guinea.</p> <p>Methods</p> <p>The clinical assessment was an open-labeled, two-arm, randomized study comparing ANQ combination as a single dose regimen and three days regimen (10 mg/kg/day) of chloroquine plus single dose sulphadoxine-pyrimethamine (CQ+SP) for the treatment of uncomplicated falciparum malaria with 28 days follow-up in an adult population. The primary outcome measures for efficacy were day 1, 2, 3 7, 14 and 28-day cure rates. Secondary outcomes included parasite clearance time, fever clearance time, and gametocyte carriage. The main outcome measures for safety were incidences of post-treatment clinical and laboratory adverse events.</p> <p>Results</p> <p>Between June 2005 and July 2006, 130 patients with confirmed uncomplicated <it>P. falciparum </it>were randomly assigned to receive ANQ and CQ+SP, only 100 patients (51 in ANQ group and 49 in CQ+SP group) were evaluated for clinical and parasitological outcomes. All the patients treated with ANQ and CQ+SP showed adequate clinical and parasitological response with 28 days follow-up. The cure rate for ANQ on day 1, 2, 3, 7, 14, and 28 was 47%, 86%, 92%, 94%, 94% and 94%, respectively. Recrudescence account for 6%; all were cleared on day 21. For CQ+SP treated group the cure rates were 24%, 67%, 82%, 82%, 84% and 88%, respectively. Recrudescence accounted for 10%; all were cleared on day 28 except for one patient. Both regimens were well tolerated with no serious adverse events. The proportion of gametocyte carriers was higher in CQ+SP treated group than ANQ treatment (41% versus 12%; p < 0.05).</p> <p>Conclusion</p> <p>While these data are not themselves sufficient, it strongly suggests that the ANQ combination as a single dose administration is safe and effective for the treatment of uncomplicated <it>P. falciparum </it>malaria in the adult population of Papua New Guinea and deserves further clinical evaluation.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Association of antibodies to Plasmodium falciparum merozoite surface protein-4 with protection against clinical malaria

Identification of parasite antigens targeted by immune effector mechanisms that confer protection against malaria is important for the design of a multi-component malaria vaccine. Here, the association of antibodies reacting with the Plasmodium falciparum merozoite surface protein-4 (MSP4) with protection against clinical malaria was investigated in a Senegalese community living in an area of moderate, seasonal malaria transmission. Blood samples were collected at the end of an 8-month long dry season without any recorded parasite transmission from 206 residents enrolled in a prospective follow-up study. Active daily clinical monitoring was implemented during the subsequent five months. Entomologic monitoring documented parasite transmission during the first three months of follow-up. Serum IgG levels were determined by ELISA against three MSP4 baculovirus-encoded recombinant protein constructs, namely the full-length MSP4p40, MSP4p30 devoid of a highly polymorphic sequence stretch and the conserved C-terminal EGF-containing MSP4p20, as well as against a merozoite crude extract. Community seroprevalence against all three constructs was quite high, the lowest being against MSP4p30. Seroprevalence and antibody levels against the three MSP4 constructs were age-dependent. IgG1 dominated the anti-MSP4p20 responses, while both IgG1 and IgG3 were observed against MSP4p40. Anti-MSP4 antibodies were associated with the antibody-dependent respiratory burst (ADRB) activity in a functional assay of merozoite phagocytosis by polymorphonuclear cells. Importantly, high antibody levels against each of the three MSP4 constructs at the end of the dry season were associated with reduced morbidity during the subsequent transmission season in an age-adjusted Poisson regression model (IRR = 0.65 [0.50-0.83], P < 0.001 for responses over the median values). These data are consistent with a protective role for the naturally acquired anti-MSP4 antibodies and support further development of MSP4 as a candidate component of malaria vaccine

Antibodies to Plasmodium falciparum merozoite surface protein-1p19 malaria vaccine candidate induce antibody-dependent respiratory burst in human neutrophils

Background: Identification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development. Among functional assays, the neutrophil antibody-dependent respiratory burst (ADRB) induced by opsonized Plasmodium falciparum merozoites has been correlated with acquired immunity to clinical malaria in endemic areas, but the target merozoite antigens are unknown. Here, the contribution of antibodies to the conserved C-terminal domain of the P. falciparum merozoite surface protein-1 (PfMSP1p19) in mediating ADRB was investigated in sera from individuals living in two Senegalese villages with differing malaria endemicity. Methods: Anti-PfMSP1p19 antibody levels in sera from 233 villagers were investigated and the involvement of anti-PfMSP1p19 antibodies in ADRB was explored in a subset of samples using (1) isogenic P. falciparum parasite clones expressing P. falciparum or Plasmodium chabaudi MSP1p19; (2) PfMSP1p19-coated plaque ADRB; and, (3) ADRB triggering using sera depleted from PfMSP1p19 antibodies by absorption onto the baculovirus recombinant antigen. Results: ADRB activity correlated with anti-PfMSP1p19 IgG levels (P < 10(-3)). A substantial contribution of PfMSP1p19 antibody responses to ADRB was confirmed (P < 10(-4)) in an age-adjusted linear regression model. PfMSP1p19 antibodies accounted for 33.1 % (range 7-54 %) and 33.2 % (range 0-70 %) of ADRB activity evaluated using isogenic merozoites (P < 10(-3)) and depleted sera (P = 0.0017), respectively. Coating of PfMSP1p19 on plates induced strong ADRB in anti-PfMSP1p19-positive sera. Conclusion: These data show that naturally acquired P. falciparum MSP1p19 antibodies are potent inducers of neutrophil ADRB and support the development of PfMSP1p19-based malaria vaccine using ADRB assay as a functional surrogate for protection

The implication of long-lasting insecticide-treated net use in the resurgence of malaria morbidity in a Senegal malaria endemic village in 2010-2011

Background: Although the burden of malaria has significantly declined in recent years in sub-Saharan Africa through the widespread use of long-lasting insecticide treated bed-nets (LLINs) and artemisinin-based combination therapy, resurgence of malaria is observed in some settings after several years of LLINs use. This study aimed to assess if LLINs use remains protective against malaria during a period of resurgence of malaria morbidity in Dielmo, a rural village of Senegal. Methods: In July 2008, LLINs were offered to all villagers and lately in July 2011, LLINs were renewed. A longitudinal study was conducted between July, 2010 and December, 2011 among inhabitants of the village of Dielmo to identify all episodes of fever. Thick smears stained with Giemsa were done for every febrile villager and malaria attacks were treated with combination of Artesunate plus Amodiaquine. Cross-sectional surveys were also conducted at the end of the rainy season (October 2010 and November 2011) to assess asymptomatic carriage. A survey on LLINs use was done every quarter of the year. A random-effect logistic regression was used to assess the effect of LLINs use on the risk of having a malaria attack after adjusting for the main risk factors. Results: The study population included 449 individuals corresponding to a total of 2140 observations. One hundred and fifteen (115) clinical malaria attacks attributed to P. falciparum (cases) have been recorded over the study period. Most of the malaria cases occurred in October-December 2010 (49/115 i.e. 43%) and among adults aged 15 years and over (50/115, i.e. 43%). During the study period, the use of LLINs was 61% among non-malaria cases and only 42% among malaria clinical cases but differenced according to age group. After adjusting on gender, age, rainfall and LLINs replacement, we found that LLINs use (AOR [95%CI] = 0.40 [0.25; 0.62], p < 0.001) remained a protective factor against malaria attacks during the study period. Conclusion: LLINs use remains effective to reduce malaria burden. These results highlight the need to pursue LLINs implementation in the current context of malaria elimination and to provide positive incentives to increase its use in the population

Temporal analysis of IgG antibody responses to Plasmodium falciparum antigens in relation to changing malaria epidemiology in a West African setting

Background: Coordinated scaled-up malaria control interventions have substantially contributed to the dramatic decrease of malaria-related morbidity and mortality in several endemic countries, including Senegal. However, the impacts of a given malaria control intervention on vector and parasite populations, acquired immunity, and disease burden remain very poorly documented largely due to the lack of continuous surveys. This study took advantage of the sera bank established as part of the Dielmo longitudinal project to investigate the dynamics of IgG antibody responses that accompanied the epidemiological changes resulting from malaria control interventions. Schizonts crude extract of a local strain of Plasmodium falciparum (Pfsch07/03) was used in ELISA to measure and compare seroprevalence and magnitude of IgG antibody responses from 2000 to 2012. Results: The prevalence of Pfsch07/03 IgG antibody responses progressively decreased from 97.25% in 2000 to 57.3% in 2012. The prevalence of Pfsch07/03 antibodies categorized between three different age groups ( 15 years) revealed increased seroprevalence with age ranging from 47.19 to 62.67 and 89.45%, respectively in ( 15 years) old age groups. A marked drop in seroprevalence was observed after 2008 and was significant in the younger ( 15 years (p = 1.00). Conclusions: The study revealed a substantial contribution of all malaria control interventions to the decrease of IgG antibodies responses to Pfsch07/03 throughout prevention of human-mosquitos contacts, or reduction of parasite biomass. The present study demonstrates the wider potential of sero-epidemiological analysis in monitoring changes in malaria transmission resulting from a given malaria control intervention

Substantial asymptomatic submicroscopic Plasmodium carriage during dry season in low transmission areas in Senegal : implications for malaria control and elimination

Background In the progress towards malaria elimination, the accurate diagnosis of low-density asymptomatic infections is critical. Low-density asymptomatic submicroscopic malaria infections may act as silent reservoirs that maintain low-level residual malaria transmission in the community. Light microscopy, the gold standard in malaria diagnosis lacks the sensitivity to detect low-level parasitaemia. In this study, the presence and prevalence of submicroscopic Plasmodium carriage were investigated to estimate the parasites reservoir among asymptomatic individuals living in low transmission areas in Dielmo and Ndiop, Senegal during the dry season. Methods A total of 2,037 blood samples were collected during cross-sectional surveys prior the malaria transmission season in July 2013 (N = 612), June 2014 (N = 723) and June 2015 (N = 702) from asymptomatic individuals living in Dielmo and Ndiop, Senegal. Samples were used to determine the prevalence of submicroscopic Plasmodium carriage by real time PCR (qPCR) in comparison to microscopy considered as gold standard. Results The prevalence of submicroscopic Plasmodium carriage was 3.75% (23/612), 12.44% (90/723) and 6.41% (45/702) in 2013, 2014 and 2015, respectively. No Plasmodium carriage was detected by microscopy in 2013 while microscopy-based prevalence of Plasmodium carriage accounted for only 0.27% (2/723) and 0.14% (1/702) in 2014 and 2015, respectively. Plasmodium falciparum accounted for the majority of submicroscopic infections and represented 86.95% (20/23), 81.11% (73/90) and 95.55 (43/45) of infections in 2013, 2014 and 2015 respectively. Conclusion Low-density submicroscopic asymptomatic Plasmodium carriage is common in the study areas during the dry season indicating that traditional measures are insufficient to assess the scale of parasite reservoir when transmission reaches very low level. Control and elimination strategies may wish to consider using molecular methods to identify parasites carriers to guide Mass screening and Treatment strategies