Uncomplicated #malaria as a #risk factor for #COVID19 duration and severity in western #Kenya and #Burkina Faso (MALCOV): a prospective cohort study

 

Summary

Background

The relationship between malaria and COVID-19 varies across different clinical scenarios; historical malaria exposure might protect against severe COVID-19, whereas co-infection in hospitalised patients with severe disease might increase mortality. Interactions between non-severe malaria and COVID-19 remain poorly understood. We conducted a cohort study among COVID-19 patients of all ages in western Kenya and Burkina Faso to assess the effects of acute, uncomplicated Plasmodium falciparum malaria co-infection on COVID-19 outcomes in ambulatory patients.

Methods

Participants with laboratory-confirmed SARS-CoV-2 infection (positive rapid antigen test or reverse transcription quantitative real-time PCR [RT-qPCR]) were tested for malaria by rapid antigen tests with confirmatory microscopy. Patients with COVID-19 and malaria co-infection received artemether–lumefantrine or pyronaridine–artesunate. COVID-19 symptom course was assessed daily using FLU-PRO Plus (a validated patient-reported outcome instrument) until day 14. Viral load was measured by RT-qPCR on days 0, 3, 7, 14, and 28. The primary endpoint was time to symptom resolution on the FLU-PRO Plus. Analyses were adjusted for country, age, disease severity, and viral load.

Findings

Between Jan 8, 2021 and Jan 24, 2022, we screened 5161 participants and recruited 756 with COVID-19. 742 participants with valid malaria tests were enrolled, of which 151 (20%) had malaria co-infection and the remaining 591 (80%) did not have malaria. Patients with malaria were younger (49 [32%] aged <15 years) than those without malaria (35 [6%]; p<0·0001). Time to symptom resolution was similar between those with malaria (median 9 days [IQR 5–13]) and those without (10 days [IQR 6–13]; adjusted hazard ratio [aHR] 1·14 [95% CI 0·91–1·42]; p=0·26). Three (2%) patients with malaria and nine (2%) without malaria were hospitalised; two (1%) with malaria and three (1%) without malaria died, four from acute respiratory distress syndrome and one (in the no malaria group) from perforated peptic ulcer complicated by anaemia. Participants with malaria more frequently reported moderate-to-severe symptoms at enrolment (68% vs 60%; p=0·074), but overall symptom duration was similar (adjusted incidence rate ratio 0·95 [95% CI 0·86–1·05]; p=0·31). Previous malaria exposure significantly modified outcomes, with patients with malaria co-infection and previous exposure having faster symptom clearance than those without previous exposure (pinteraction=0·042). SARS-CoV-2 clearance was slower in the malaria group by day 7 (aHR 0·69 [95% CI 0·51–0·94]; p=0·017) but was similar between groups by day 28 (adjusted risk ratio 0·99 [95% CI 0·79–1·24]; p=0·95).

Interpretation

This study shows that acute uncomplicated malaria co-infection does not adversely affect COVID-19 progression when appropriately treated. Moreover, serological evidence confirms that previous lifelong malaria exposure might provide some protection, with exposed individuals having faster symptom resolution.

Funding

Gates Foundation.

Translation

For the French translation of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(25)00541-8/fulltext

____

Efficacy of ProC6C-AlOH/Matrix-M against #Plasmodium falciparum #infection and #mosquito #transmission: a phase 2, randomised, controlled human malaria infection study

 

Summary

Background

An investigational multistage malaria vaccine, ProC6C, based on distinct Plasmodium falciparum epitopes from the sporozoite stage (P falciparum circumsporozoite protein [PfCSP]) and the transmission stages (Pfs230 and Pfs48/45), adsorbed to aluminium hydroxide (AlOH) and adjuvanted with Matrix-M adjuvant (ProC6C-AlOH/MM), has previously shown safety and immunogenicity in phase 1 studies. We aimed to study vaccine efficacy, safety, and immunogenicity in African adults with lifelong malaria exposure.

Methods

This randomised controlled double-blind vaccination and controlled human malaria infection (CHMI) study was conducted in Sotuba, a peri-urban setting in Mali. Healthy adults (aged 18–50 years), who were malaria experienced and met eligibility criteria, were randomly assigned (1:1) to receive three intramuscular injections of ProC6C-AlOH/MM (100 μg ProC6C and 50 μg Matrix-M adjuvant) or Verorab rabies vaccine (control) 4 weeks apart. Randomisation was done in randomly permuted blocks (random varying block size of two and four) using R Statistical Software (randomizr and blockrand). The content of syringes was masked to ensure blinding and only those responsible for vaccine preparation were unblinded. 94 days after the last vaccination, all participants still in the study underwent CHMI by intradermal inoculation of 22 500 P falciparum sporozoites (Sanaria PfSPZ Challenge [NF54]). Primary outcomes were time to blood-stage infection (quantitative PCR detection of P falciparum, with vaccine efficacy defined as 1 – Cox hazard ratio in the per-protocol population) and vaccine safety and tolerability (in those who were randomly assigned and received at least one vaccination). The trial was registered in the Pan African Clinical Trial Registry (PACTR202404598604620).

Findings

On March 20, April 15, and May 9, 2024, 34 participants (15 males, 19 females) received their vaccinations (n=17 ProC6C-AlOH/MM and n=17 control vaccine). The vaccinations were well tolerated, with 13 (76%) of 17 ProC6C-AlOH/MM recipients experiencing at least one adverse event, almost all of which were mild, compared with three (18%) of 17 control vaccine recipients. On Aug 11, 2024, 94 days after the last dose of vaccine, 32 of 34 participants underwent CHMI, of whom 19 (59%) developed P falciparum parasitaemia by day 28 post-CHMI initiation (13 of 16 in the control group and six of 16 in the ProC6C-AlOH/MM group). In those that became parasitaemic, the median time to positivity was delayed in ProC6C-AlOH/MM recipients by 2 days (14 days ProC6C-AlOH/MM, 12 days control; p=0·049). In the per-protocol time-to-event analysis, vaccine efficacy was 76% (95% CI 36–91, p=0·0022). By proportional analysis (1 – risk ratio) the vaccine efficacy was 54% (95% CI 9–77, p=0·029).

Interpretation

This is the first clinical trial of an anti-PfCSP subunit vaccine that has shown greater than 50% vaccine efficacy against CHMI at 12 weeks after the last vaccine dose, associated with a novel, strong, and mechanistically plausible correlate of protection. Following age de-escalation, future phase 2 studies with ProC6C should therefore assess vaccine efficacy against naturally acquired clinical malaria and onward transmission in the target population, preschool-aged and primary-school-aged children.

Funding

European & Developing Countries Clinical Trials Partnership (EDCTP2 programme) and Gates Foundation.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00664-4/abstract?rss=yes

____

#Vectors on the Move: How #Climate Change Fuels the Spread of #Arboviruses in #Europe

 

Abstract

Climate change is increasingly recognized as a major driver of emerging infectious diseases, particularly vector-borne diseases (VBDs), which are expanding in range and intensity worldwide. Europe, traditionally considered low-risk for many arboviral infections, is now experiencing autochthonous transmission of pathogens such as dengue, chikungunya, Zika virus, West Nile virus, malaria, and leishmaniasis. Rising temperatures, altered precipitation patterns, and milder winters have facilitated the establishment and spread of competent vectors, including Aedes, Anopheles, Phlebotomus, and Culex species, in previously non-endemic areas. These climatic shifts not only impact vector survival and distribution but also influence vector competence and pathogen development, ultimately increasing transmission potential. This narrative review explores the complex relationship between climate change and VBDs, with a particular focus on pediatric populations. It highlights how children may experience distinct clinical manifestations and complications, and how current data on pediatric burden remain limited for several emerging infections. Through an analysis of existing literature and reported outbreaks in Europe, this review underscores the urgent need for enhanced surveillance, integrated vector control strategies, and climate-adapted public health policies. Finally, it outlines research priorities to better anticipate and mitigate future disease emergence in the context of global warming. Understanding and addressing this evolving risk is essential to safeguard public health and to protect vulnerable populations, particularly children, in a rapidly changing climate.

Source: Microorganisms, https://www.mdpi.com/2076-2607/13/9/2034

____

#Cluster of #community #deaths in Basankusu, Equateur- #DRC

Situation at a glance

On 9 February 2025, officials in the Democratic Republic of the Congo reported to regional health authorities a cluster of 24 unexplained community deaths in a single village in Ekoto health area, Basankusu health zone, Equateur province. 

As of 25 February, a total of 53 deaths have been reported, with the last death occurring on 22 February. 

Deaths have occurred in all age groups, but adolescents and young adults, particularly males, appeared to be disproportionately affected in the initial cluster reported. 

Disease progression appeared to be fast, with a median time from onset of symptoms to death of one day. 

Given the rapid decline in the incidence of reported deaths, their geographic clustering, the age profile of deaths and the rapid disease progression in the initial cluster, working hypotheses include chemical poisoning or a rapid onset bacterial meningitis cluster, on a background of malaria and other infectious illnesses endemic in the region. 

The definitive cause of illness remains undetermined, with initial samples testing negative for Ebola and Marburg viruses. 

Field investigations and additional laboratory testing are ongoing including but not limited to the cerebrospinal fluid testing and the toxicological analysis of environmental samples, including water and other samples to explore chemical causes. 

Local authorities began surveillance with a broad case definition including any individual with fever and at least one other symptom, to better understand disease patterns. 

A total of 1318 patients had symptoms meeting the working suspected case definition as of 25 February 2025. Approximately 50% of malaria tests performed on these cases tested positive for malaria, the cases identified through this enhanced surveillance therefore likely reflect the various febrile illnesses in the area. 

With the available information, WHO assesses the local public health risk as moderate, and the national and global public health risk as low.

Description of the situation

On 9 February 2025, an initial cluster of 24 community deaths of unknown origin were reported from a single village in Ekoto Health Area, Basankusu Health Zone, Equateur province, in the Democratic Republic of Congo. This triggered an investigation by the Ministry of Health, supported by WHO.

Enhanced surveillance was implemented shortly after, using a broad working case definition given the limited details on the clinical presentation, disease progression, demographic and other characteristics of the initial cluster. 

As of 25 February, a total of 53 deaths were reported. Deaths occurred across all age groups, but compared to the age and sex distribution of the population, appeared to disproportionately affect adolescents and young adult males, particularly in the initial cluster. This further pointed to an unusual event, as mortality from common causes in the area is usually highest among the elderly, and among young children (under five years) in a context of a high burden from infectious diseases, including malaria. The majority of deaths (50) occurred in the same village. Furthermore, the incidence of death rapidly declined following the initial cluster, suggesting this is not an event spreading in time or place.

The preliminary findings of the in-depth analysis revealed that the median time from symptom onset to death in the initial cluster was one day, with a mean time of two days. Symptoms reported include fever, chills, headaches, muscle aches, abdominal pains, diarrhea, sweating, dizziness, shortness of breath, agitation, and others.

(...)

Since the initiation of enhanced surveillance,1318 people reported symptoms meeting the working suspected case definition. However, given the broad nature of the case definition (fever and one other symptom from a range of general respiratory, gastrointestinal, or neurological symptoms), the trends in cases are difficult to interpret, and most likely reflect the prevalence of a range of febrile illnesses in the community. This is further suggested by the age distribution broadly mirroring that of the population, and the high malaria positivity among cases that were tested (approximately 50% positive on rapid diagnostic tests), which is not deemed unusual in an area where malaria is hyperendemic.

(...)

Although the cases were initially identified using a broad (i.e. non-specific) case definition, given the localized nature of the cluster of deaths, the steady decline in incidence of deaths, the demographic profile of deaths, and the rapid disease progression in the initial cluster, working hypotheses are that of a contamination by a chemical poisoning–be it accidental or deliberate—or possibly a rapid onset bacterial meningitis cluster.

Initial laboratory test results released on 13 February 2025 were negative for both Marburg and Ebola. Additional samples (blood, urine, oral, nasal) have been collected for further testing and investigations are ongoing. In addition, environmental samples–including water and other samples–are being collected to explore chemical causes, such as contamination by organophosphates.

The definitive cause of illness remains undetermined. Further testing and field investigations are ongoing to better characterize the cases and deaths.

Of note, this event in Basankusu follows a recent cluster of community deaths in the Bolomba Health Zone, which occurred from 10 to 27 January 2025. The epidemiological investigation documented 12 cases with eight deaths. Laboratory testing excluded Ebola and Marburg virus diseases and suggested that severe malaria could be the cause. While both Bolomba and Basankusu are located within Equateur Province, these health zones are separated by approximately 175 kilometers of difficult terrain including dense forests and poor road infrastructure; epidemiological investigation has found no evidence linking these distinct events.

Public health response

-- Coordination: A provincial rapid response team deployed to Basankusu and arrived on 16 February. The team was further supported by a WHO-MoH team from Kinshasa which arrived on 23 February.

-- Surveillance: WHO is supporting the MoH teams with field investigations, including the development of a structured epidemiological investigation protocol and the collection of additional samples for testing. As surveillance is being scaled up, the focus is on better understanding the characteristics of deaths. WHO is supporting health teams in their case investigations and active case search in the affected areas, including in communities, churches, and health facilities.

-- Laboratory: WHO is providing laboratory support to guide proper collection, storage, and transport of collected specimens to the National Institute of Biomedical Research (INRB) in Kinshasa, the biggest and most equipped laboratory in the country.

-- Logistics: WHO has provided essential medical supplies for management of usual infectious diseases and their symptoms, laboratory testing and infection prevention and control (IPC).

-- Risk communication and community engagement: Community engagement efforts are ongoing. Training sessions for community health workers are being conducted on how to identify people who meet the case definition and perform disease surveillance reporting. Awareness activities include community briefings and local radio broadcasts, as well as targeted discussion in villages on care-seeking behavior. 

-- Infection prevention and control: Systematic decontamination of isolation rooms at the General Hospital in Basankusu and Ekoto Health Center have been performed. On-site training of IPC supervisors and hygienists on chlorine solution preparation for decontamination have been conducted.

WHO risk assessment

Since the initial cluster of deaths was reported on 9 February 2025, there has been an overall downward trend in deaths. The most recent death was reported on 22 February 2025. Current epidemiological information suggests a localized event with a steady decline in incidence, not expanding in time and place. Given the clinical presentation of deaths and the speed from symptom onset to death in this unusual cluster, current differentials include a rapid onset bacterial meningitis cluster or a contamination by a chemical poisoning as key hypotheses in a context of high incidence of other common infectious diseases in the areas, particularly malaria.

Operational challenges related to this event involve the isolation of Basankusu and resulting logistical barriers, as it is located in a forested region, approximately 450 kilometers from the nearest major city of Mbandaka and has poor infrastructure. The remoteness of Basankusu has hindered the timeliness of the initial investigation and response activities and poses challenges to laboratory testing. Samples must be collected, stored, and shipped long distances to a larger city with laboratory testing capacity (either Mbandaka or Kinshasa), introducing delays in diagnosis. Access to care is another key challenge, as the region lacks robust healthcare services, and the region’s poor infrastructure makes travel to neighboring health zones difficult, leading to delays in treatment.  

The province faces a severe urban water crisis with only 5% of its urban population having access to drinking water. The water network suffers frequent leaks and has never been rehabilitated. Many households rely on unregulated private water sources such as wells, springs and streams which pose contamination risks.

With ongoing investigations and given that the causative agent of the cluster is not yet determined, there remains a level of risk attributed to the event. As such, the overall public health risk level to the affected communities is assessed as moderate.

At the national level, however, the risk is considered low due to the localized nature of the event and apparent decreasing incidence. Similarly, at the regional and global levels, the risk is low at this time. 

WHO advice

To reduce the impact of the event in the Basankusu health zone, WHO advises the following measures:  

-- Careful characterization of the clinical syndrome and outcomes as well as an improved case definition based on collected information to better understand the outbreak.

-- Enhanced surveillance focusing specifically on deaths, and severe febrile cases or severe cases of unexplained illness, with better clinical characterization to reinforce early case detection and reporting.

-- Continued laboratory testing and environmental assessments (including water sources) to evaluate the current hypotheses of meningitis and/or a toxin/poisoning event, particularly among severe cases and deaths.

-- Risk communication and community engagement to increase public awareness about the event, explaining symptoms and the importance of seeking immediate care. It is also critical to address any potential misinformation about the outbreak circulating in the community.

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON557

____

#DRC deepens #investigation on #cluster of #illness and #community #deaths in #Equateur province

Kinshasa – Health authorities in the Democratic Republic of the Congo and experts from World Health Organization (WHO) are carrying out further investigations to determine the cause of another cluster of illness and community deaths in Equateur province. 

In recent months, disease surveillance has identified increases in illness and deaths three times in different areas of the country, and triggered follow-up investigations to confirm the cause and provide needed support.  

Since the beginning of 2025, a series of illnesses and community deaths have affected Equateur province. The most recent cluster occurred in the Basankusu health zone, where last week 141 additional people fell ill, with no deaths reported. In the same health zone, 158 cases and 58 deaths were reported in the same health zone earlier in February. In January, Bolamba health zone reported 12 people who fell ill including 8 deaths. 

Increased disease surveillance has identified in total of 1096 sick people and 60 deaths in Basankusu and Bolomba fitting a broad case definition that includes fever, headache, chills, sweating, stiff neck, muscle aches, multiple joint pain and body aches, a runny or bleeding from nose, cough, vomiting and diarrhoea.  

The Democratic Republic of the Congo is facing many concurrent crises and outbreaks, putting a further strain on the health sector and the population. 

In response to the latest cluster of illness, a national rapid response team from Kinshasa and Equateur including WHO health emergency experts was deployed to Basankusu and Bolomba health zones to investigate the situation and determine if there is an unusual pattern. The experts are stepping up disease surveillance, conducting interviews with community members to understand the background, and providing treatment for diseases such as malaria, typhoid fever and meningitis.  

WHO has delivered emergency medical supplies, including testing kits, and developed detailed protocols to enhance disease investigation. 

Initial laboratory analysis has turned out negative for Ebola virus disease and Marburg virus disease. 

Around half of the samples tested positive for malaria, which is common in the region. Further tests are to be carried out for meningitis. Food, water and environmental samples will also be analysed, to determine if there might be contamination. The various samples will be sent for further testing at the national reference laboratory in Kinshasa. Earlier samples turned out not to be viable and re-testing was undertaken.  

Basankusu and Bolomba are about 180 kilometres apart and more than 300 kilometres from the provincial capital Mbandaka. The two localities are reachable by road or via the Congo River from Mbandaka. This remoteness limits access to health care, including testing and treatment. Poor road and telecommunication infrastructure are also major challenges. 

WHO is supporting the local health authorities reinforce investigation and response measures, with more than 80 community health workers trained to detect and report cases and deaths.   

Further efforts are needed to reinforce testing, early case detection and reporting, for the current event but also for future incidents. WHO remains on the ground supporting health worker, collaborating closely with zonal, provincial and national health authorities to provide lifesaving medical supplies and to coordinate response to curb the spread of the illness and other outbreaks in the region. 

Source: World Health Organization, Regional Office for Africa, https://www.afro.who.int/countries/democratic-republic-of-congo/news/democratic-republic-congo-deepens-investigation-cluster-illness-and-community-deaths-equateur

____