Morbidity due to Loiasis: population-wide evaluation and identification of pathogenic mechanisms

Informazioni relative al progetto

MorLo

ID dell’accordo di sovvenzione: 949963

DOI

10.3030/949963

Progetto chiuso

Data della firma CE 15 Gennaio 2021

Data di avvio 1 Febbraio 2021

Data di completamento 31 Gennaio 2026

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 499 105,00

Contributo UE

€ 1 499 105,00

Coordinato da

INSTITUT DE RECHERCHE POUR LE DEVELOPPEMENT
France

Periodic Reporting for period 3 - MorLo (Morbidity due to Loiasis: population-wide evaluation and identification of pathogenic mechanisms)

Periodo di rendicontazione: 2024-02-01 al 2025-07-31

Sintesi del contesto e degli obiettivi generali del progetto

Loiasis, an infectious disease caused by the parasitic worm Loa loa, affects more than 15 million individuals in central Africa, and more than 100 million people are potentially exposed to infection. Since its first description in 1770, the international scientific community has considered this filarial disease as benign. I recently demonstrated that loiasis significantly reduces the life expectancy of infected people. I aim to definitively shift the prevailing paradigm of “benign loiasis” by showing that it can induce severe complications in various organs. I will conduct the first population-wide evaluation of morbidity in rural areas of Central Africa by performing systematic examinations on 4,900 selected individuals. This sample size will enable accurate estimation of prevalences of cardiovascular and renal diseases and of functional asplenia. Our results may lead to the recognition of loiasis as a significant public health problem. Such recognition could motivate the integration of loiasis into the WHO’s list of Neglected Tropical Diseases. In addition, should loiasis be found to induce functional asplenia, combating this disease could have a huge impact on the incidence and severity of other severe and common infections favored by asplenia, such as malaria and pneumonia. Incidentally, specific recommendations regarding pneumococcal vaccination in loiasis-endemic areas could be made. Another possible consequence of our findings is changed in the management of people identified as having high levels of Loa loa infection during routine surveys or onchocerciasis elimination activities. Presently, these people are excluded from ivermectin treatment (because of the risk of post-treatment encephalopathy), and little is done to lower their level of infection. Confirmation that loiasis can cause serious complications would motivate an ethical obligation to develop strategies to manage these cases in order to lower the burden of the disease.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

From the beginning of the project, all the equipment and consumables were delivered on time both in Cameroon and the Republic of Congo, and administrative and ethical authorizations were obtained. Our pilot biological study has been finalized, focusing on hematological disorders related to loiasis. We were able to launch our cohort study in the Republic of Congo in June 2022 with 990 individuals included in the villages surrounding Sibiti, in the Lekoumou Department. Clinical examinations, as well as parasitological, biological, vascular, urinary, and ultrasound examinations, were successfully performed at our baseline inclusion. From this inclusion, we are following our study population for all infectious complications and general symptoms related to loiasis.

Last, we launched our cross-sectional study in Cameroon but the data obtained in Congo have allowed us to significantly reduce our sample size. Indeed, our analyses from the baseline inclusion in Congo, evidence of an association between proteinuria, altered cognition, and arterial stiffness, with microfilaremia of Loa loa were already reported with higher strength of association than expected.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Our investigation within the Congo cohort has yielded compelling insights, providing valuable findings even at this early stage. While the primary objective of the cohort was to reveal disparities in the incidence of infectious complications between individuals with and without microfilariae, we have already identified noteworthy statistical associations.

Firstly, in the Republic of Congo, our research has affirmed the presence of a significant excess mortality rate linked to microfilaraemia. This underscores the health implications associated with this condition.

Secondly, our observations unveiled a clear relationship between the density of Loa loa microfilariae and the severity of proteinuria. A robust gradient effect and substantial association forces were evident, emphasizing the pivotal role of microfilariae quantity in influencing renal function. Moreover, we estimate that approximately 30% of proteinuria cases can be attributed to the presence of microfilaremic individuals.

Thirdly, while the neurological impact of loiasis following ivermectin treatment is well-documented, our study has, for the first time, indicated a discreet cognitive impairment associated with a high incidence of microfilariae. This intriguing finding warrants further confirmation and understanding.

Additional noteworthy results, pertaining to various organ infections, are currently in the process of submission or publication. The cohort promises to offer valuable insights into the role of loiasis in the development of specific complications. In Cameroon, data collection is on track for completion by June 2024, providing precise estimates of existing complications and comorbidities in rural Central Africa. This will offer a more comprehensive understanding of the impact, whether positive or negative, of loiasis on these communities.

Loa loa microfilariae