Francine Ntoumi’s research while affiliated with Universitätsklinikum Tübingen and other places

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Publications (336)


Map of the study area
Susceptibility profile of A. gambiae s.s. to permethrin only and after preexposure to PBO. A Proportion of mosquitoes knocked down after exposure to various concentrations. B Mean mortality after exposure to various concentrations. The horizontal green line represents the 98% WHO threshold for susceptibility. Error bars represent standard error of mean mortality after the 24h recovery period following insecticide exposure
Susceptibility profile of A. gambiae s.s. to deltamethrin only and after preexposure to PBO. A Proportion of mosquitoes knocked down after exposure to various concentrations. B Mean mortality after exposure to various concentrations. The horizontal green line represents the 98% WHO threshold for susceptibility. Error bars represent standard error of mean mortality after the 24h recovery period following insecticide exposure. Proportion of mosquitoes knocked down after exposure to various concentrations of deltamethrin
Mean mortality of A. gambiae s.s. after exposure to diagnostic concentrations of malathion and bendiocarb. The horizontal green line represents the 98% WHO threshold for susceptibility. Error bars represent standard error of mean mortality after the 24h recovery period following insecticide exposure
Resistance of Anopheles gambiae s.s. against commonly used insecticides and implication of cytochrome P450 monooxygenase in resistance to pyrethroids in Lambaréné (Gabon)
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October 2024

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68 Reads

BMC Infectious Diseases

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Background Insecticides are a crucial component of vector control. However, resistance constitute a threat on their efficacy and the gains obtained over the years through malaria vector control. In Gabon, little data on phenotypic insecticide resistance in Anopheles vectors are published, compromising the rational implementation of resistance management strategies. We assessed the susceptibility to pyrethroids, carbamates and organophosphates of Anopheles gambiae sensu lato (s.l.) and discuss the mechanisms involved in the pyrethroid resistance-phenotype. Methods A. gambiae s.l. larvae were collected from breeding sites in Lambaréné. Emerging adults were used in WHO tube assays at an insecticide concentration that defines resistance (diagnostic concentration). Subsequently, deltamethrin and permethrin were used at 5x and 10x diagnostic concentrations and after preexposure with the cytochrome p450 (and glutathione S-transferase) inhibitor piperonyl butoxide (PBO). A subset of mosquitoes was typed by molecular methods and screened using Taqman assays for mutations conferring target site resistance at the Voltage-gated sodium channel 1014 (Vgsc-1014) locus and the acetylcholinesterase (Ace-1) gene. Results All mosquitoes were A. gambiae sensu stricto (s.s.) and resistant to permethrin, deltamethrin and alphacypermethrin (mortality less than 98%). However, mosquitoes were susceptible to malathion but resistant to bendiocarb. The level of resistance was high for permethrin and at least moderate for deltamethrin. Pre-exposure to PBO significantly increased the mortality of resistant mosquitoes (P < 0.0001). They became fully susceptible to deltamethrin and permethrin-induced mortality increased 4-fold. The G119S Ace-1 resistance allele, which confers resistance to both organophosphates and carbamates, was not present. All sampled mosquitoes were either homozygous for the Vgsc-L1014F or heterozygous for Vgsc-L1014F/L1014S, a marker for resistance to pyrethroids and organochlorides. Conclusion These findings demonstrate a role of cytochrome P450 monooxygenases in the pyrethroid-resistance of A. gambiae s.s. from Lambaréné. Combining PBO with pyrethroids, as done in second generation bednets, may be used to revert resistance. In addition, malathion could also be used in combination with pyrethroids-based methods for resistance management.

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The 2024 Public Health Emergency of International Concern: A Global Failure to Control Mpox

October 2024

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63 Reads

The American journal of tropical medicine and hygiene

On August 14, 2024, following a regional declaration by the Africa Centres for Disease Control and Prevention, the World Health Organization declared mpox a Public Health Emergency of International Concern, marking the second such declaration in two years. A series of outbreaks involving the more virulent clade I virus (compared to clade II, which caused a global outbreak in 2022), has now spread in 13 African countries, exposing the inadequacies of the public health infrastructure in these settings. There was significant investment during the 2022 global outbreak, but these efforts failed to address vaccine access and treatment in the Global South. Regulatory delays, unequal access to vaccines, and a lack of compassionate use treatments for severe cases have resulted in preventable cases and deaths, especially among vulnerable populations such as pregnant women, children, and the immunocompromised. The current outbreak also underscores critical knowledge gaps in our understanding of mpox, including its transmission, pathogenesis, and viral evolution. We join intensified calls for global solidarity and action to control mpox, emphasizing immediate containment measures and long-term local and international investment in African public health systems, to prevent future epidemics.


Emergence of the B.1.214.2 SARS-CoV-2 lineage with an Omicron-like spike insertion and a unique upper airway immune signature

October 2024

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53 Reads

BMC Infectious Diseases

We investigate the emergence, mutation profile, and dissemination of SARS-CoV-2 lineage B.1.214.2, first identified in Belgium in January 2021. This variant, featuring a 3-amino acid insertion in the spike protein similar to the Omicron variant, was speculated to enhance transmissibility or immune evasion. Initially detected in international travelers, it substantially transmitted in Central Africa, Belgium, Switzerland, and France, peaking in April 2021. Our travel-aware phylogeographic analysis, incorporating travel history, estimated the origin to the Republic of the Congo, with primary European entry through France and Belgium, and multiple smaller introductions during the epidemic. We correlate its spread with human travel patterns and air passenger data. Further, upon reviewing national reports of SARS-CoV-2 outbreaks in Belgian nursing homes, we found this strain caused moderately severe outcomes (8.7% case fatality ratio). A distinct nasopharyngeal immune response was observed in elderly patients, characterized by 80% unique signatures, higher B- and T-cell activation, increased type I IFN signaling, and reduced NK, Th17, and complement system activation, compared to similar outbreaks. This unique immune response may explain the variant's epidemiological behavior and underscores the need for nasal vaccine strategies against emerging variants.


Fig. 1 | Distribution of CONCNVACT network research centers across Africa. This map provides a visual representation of the geographical distribution of the 21 research centers affiliated with the CONCVACT Network across Africa.
Fig. 2 | R&D Centers will regionally consolidate infrastructure, capacity and expertise across a given portion of the R&D value chain supported by a Coordinating Platform.
Strengthening and expanding capacities in clinical trials: advancing pandemic prevention, preparedness and response in Africa

October 2024

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62 Reads

Enhancing the clinical trial capabilities within Africa is essential to augment the continent’s pandemic prevention, preparedness and response efforts. Here, we describe the critical challenges of clinical trials in Africa and draw upon the lessons learnt from the Consortium for COVID-19 Vaccine Clinical Trials (CONCVACT) experience, such as the importance of regional collaboration, capacity building and establishing standardized protocols.






Likely cross-border introductions of MPXV Clade I into the Republic of the Congo from the Democratic Republic of the Congo

August 2024

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88 Reads

Background: Mpox virus (MPXV) Clade I is endemic in several central African countries and characterized by severe disease and high mortality. Since October 2023, a large-scale Mpox outbreak has emerged in the Democratic Republic of the Congo (DRC), with 22,477 cases and 1,038 deaths reported as of May 26, 2024, and World Health organization (WHO) has declared mpox a public health emergency of international concern on august 14 2024. Twenty-three provinces in the DRC have been affected, 15 of which border another country, including the Republic of the Congo (RoC). The RoC is bordered by five of these affected provinces, increasing the risk of cross-border spread. In the RoC, Mpox cases have historically occurred in the endemic areas of the Likouala department in the north. Recently, suspected cases have emerged outside this region, and it is unclear if these cases are recent spillover events from the DRC outbreaks. Therefore, we performed molecular analyses of these cases in the RoC. Methods: Samples were collected from suspected cases between January and April 29, 2024, in Likouala, Cuvette-Centralle, and Pointe-Noire. Blood samples, skin/oropharyngeal swabs or skin crusts were obtained for molecular diagnosis at the Laboratoire National de Sante Publique (LNSP), Brazzaville. MPXV sequences were obtained and analyzed using newly established Nanopore sequencing methodology and bioinformatic pipeline. Findings: Phylogenetic analysis of sequences shows the clustering of MPXV sequences obtained from cases in RoC with sequences from the ongoing Mpox outbreak in the DRC. In addition, sequences from the RoC show multiple phylogenetic positioning suggesting the occurrence of multiple co-circulating strains in the human population. Interpretation: The close genetic relatedness between sequences from RoC and those from DRC indicates a possible cross-border transmission of MPXV from DRC to RoC. These data highlight the need for implementation of expanded surveillance in countries bordering DRC and RoC, in combination with control measures focused at containing the current outbreaks in DRC and RoC to prevent escalation into a larger-scale epidemic.



Citations (62)


... Since 2022, Africa has reported 40,874 cases and 1,512 deaths across 15 member states of the African Union (AU), with a significant increase in cases and deaths noted in 2024 compared to 2023. Notably, in 2024 alone, 17,541 cases and 517 deaths were reported, with the DRC accounting for the majority of these figures [9]. ...

Reference:

Time Series Modelling and Forecasting of Monkeypox Outbreak Trends in Africa's in Most Affected Countries
Mpox outbreaks in Africa constitute a public health emergency of continental security

The Lancet Global Health

... PLHIV exhibited both humoral and cellular immune responses targeted specifically against SARS-CoV-2 after being administered several types of SARS-CoV-2 vaccines, such as inactivated, adenovirus vector, and mRNA vaccines [7][8][9]. The antibody responses in PLHIV increased gradually after mRNA-based vaccination [10]. ...

Neutralizing antibody responses assessment after vaccination in people living with HIV using a surrogate neutralization assay

BMC Immunology

... Efforts to enhance Mpox research and response in Africa have faced challenges due to limited funding, despite the increasing burden of the disease. The establishment of the Mpox Research Consortium (MpoxReC) aims to improve research capacity, surveillance, and public health responses across endemic countries [32,33]. However, African countries continue to struggle with accessing vaccines, diagnostics, and treatments, leading to significant disparities in resource allocation. ...

The surge of mpox in Africa: a call for action

The Lancet Global Health

... The Mpox outbreak in Africa from 2022 to 2024 has demonstrated significant regional disparities, influenced by varying transmission dynamics, public health strategies, and socioeconomic factors. Notably, the DRC has been central to these outbreaks, reporting substantial numbers with 7,851 cases and 384 deaths by early 2024 [27][28][29]. This region has seen shifts in transmission routes, including both heterosexual and homosexual transmissions, complicating control efforts. ...

Implications of the 2023-2024 MPXV Clade I Outbreak in the DRC to Global Public Health
  • Citing Article
  • April 2024

Clinical Microbiology and Infection

... The screening strategies are reported in terms of political commitments, as the Prevention and Systematic Screening Initiative, which is a new approach to technical assistance, focused on prevention and systematic screening, to end TB in the WHO European Region by 2030 [ 10 , 11 ]. Screening procedures and TPT are also discussed, with a focus on persons moving from high-to low-TB endemic countries [12] . This highlights the importance of identifying persons with TB infection and ensuring they receive TPT to prevent the re-activation of latent TB infection (LTBI) toward TB disease, leading to further transmission. ...

Screening for Latent Tuberculosis in Migrants – Status Quo and Future Challenges
  • Citing Article
  • March 2024

International Journal of Infectious Diseases

... Malaria is an infectious disease caused by the bite of infected female mosquitoes belonging to the Anopheles genus when they take a blood meal to mature their eggs (Escobar et al., 2020;Jeyaprakasam et al., 2022;Mbama Ntabi et al., 2024). It results in numerous deaths, particularly among children under five and pregnant women (Onyamboko et al., 2024;Yadouleton et al., 2010). ...

Contribution of Anopheles gambiae sensu lato mosquitoes to malaria transmission during the dry season in Djoumouna and Ntoula villages in the Republic of the Congo

... The average annual rainfall is about 1100 mm, with a rainy season that lasts for 9 months, with two rainfall maxima: one from March to May and the other from September to November (INS, 2020;Samba and Nganga, 2012). Malaria transmission in the area is perennial, with P. falciparum being responsible for about 96% of malaria infections (Mbama et al., 2022) and Anopheles gambiae sensus lato, representing about 91% of Anopheles mosquitoes (Mbama et al., 2024). The entomological inoculation rate in the setting was 47.5 infecting bites/person/year (ib/p/y) in 2022 (Mbama et al., 2024). ...

Entomological indicators of Plasmodium species transmission in Goma Tsé-Tsé and Madibou districts, in the Republic of Congo

Malaria Journal

... Out of the estimated tens of millions of people living with HIV globally, around two-thirds of the projected 38.4 million cases worldwide are concentrated in Africa, highlighting the region's disproportionate burden of the HIV epidemic [32]. The HIV prevalence in the Republic of the Congo is 3.3% making it the 2nd highest rate in Central Africa and the 14th in the world (UNAIDS data 2021) with an estimated COVID-19 vaccine coverage as low as 11.6% in the general population after 2 years of vaccination campaigns [33][34][35]. Of the few studies on vaccine effectiveness conducted in Africa [32,36], one has been conducted in Central Africa precisely in the Republic of the Congo and PLWOH population [37]. ...

Mucosal response of inactivated and recombinant COVID‐19 vaccines in Congolese individuals

... As this callto-action advocates for increased youth involvement in health research, a spotlight on equity is indispensable to ensure balanced representation inclusive of marginalized communities and individuals. This approach transcends bridging health research gaps; it aims at addressing disparities in contributions among different youth groups, thereby promoting a more equitable research landscape [32]. Envisioning the future, this call foresees Africa steering global health research, with African researchers, buoyed by youthful zest, innovation, and resilience, leading transformative research endeavours. ...

Evolution of a strategic, transformative Europe–Africa Global Health partnership—EDCTP3
  • Citing Article
  • December 2023

The Lancet Infectious Diseases

... Ebola hemorrhagic fever is a highly infectious and lethal disease caused by a virus called Ebola virus [5] ( fig. 2). The Ebola virus can be transmitted through a patient's aerosol, respiratory droplets, body fluids, urine, feces, and contact. ...

Preparedness for future outbreaks: strengthening surveillance of survivors of Ebola virus disease
  • Citing Article
  • November 2023

The Lancet Infectious Diseases