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1.
Emerg Infect Dis ; 29(4): 831-833, 2023 04.
Article in English | MEDLINE | ID: covidwho-2314119

ABSTRACT

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.


Subject(s)
Antimalarials , Blackwater Fever , Malaria, Falciparum , Malaria , Female , Humans , Child , Blackwater Fever/complications , Blackwater Fever/drug therapy , Antimalarials/therapeutic use , Malaria/drug therapy , Italy , Steroids/therapeutic use , Malaria, Falciparum/drug therapy
2.
PLoS Negl Trop Dis ; 17(3): e0011156, 2023 03.
Article in English | MEDLINE | ID: covidwho-2292293

ABSTRACT

BACKGROUND: Prompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death. METHODOLOGY: Health itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - <5 years) admitted with suspected bloodstream infection to Kisantu district hospital, DR Congo. The cohort was followed until discharge to assess in-hospital death. PRINCIPAL FINDINGS: From 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector. CONCLUSIONS: Long health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality. TRIAL REGISTRATION: NCT04289688.


Subject(s)
Bacterial Infections , Malaria, Falciparum , Malaria , Sepsis , Humans , Child , Infant , Democratic Republic of the Congo/epidemiology , Cohort Studies , Hospital Mortality , Malaria/drug therapy , Malaria/epidemiology , Salmonella , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology
3.
EMBO Mol Med ; 15(6): e17556, 2023 06 07.
Article in English | MEDLINE | ID: covidwho-2300566

ABSTRACT

Malaria remains a huge burden on global public health. Annually there are more than 200 million cases with > 600,000 deaths worldwide, the vast majority of which occur within Sub-Saharan Africa (WHO; World Malaria Report, 2021). Malaria disease is the consequence of infection by a protozoan parasite from the genus Plasmodium with most morbidity and mortality caused by P. falciparum. With rates of infection plateauing and rebounding in some areas (in particular, as a result of the disruption caused by the COVID-19 pandemic), there have been increasing calls for new initiatives that can reduce malaria incidence towards local elimination or the hoped for goal of global eradication. In 2021, the World Health Organisation approved the first malaria vaccine RTS,S/AS01 (also called Mosquirix™), indicating it to be safe for use in young children and advocating its integration into routine immunisation programmes. Approval of this vaccine clearly represents a major landmark in global efforts towards malaria control and eradication aspirations. RTS,S modest efficacy, however, points at the need to better understand immune responses to the parasite if we hope to design next generation malaria vaccines with increased potency.


Subject(s)
COVID-19 , Malaria Vaccines , Malaria, Falciparum , Malaria , Child , Humans , Child, Preschool , Plasmodium falciparum , Pandemics , COVID-19/epidemiology , Malaria, Falciparum/prevention & control , Antibodies , Malaria/epidemiology , Protozoan Proteins/genetics
4.
Lancet Infect Dis ; 23(5): 578-588, 2023 05.
Article in English | MEDLINE | ID: covidwho-2299258

ABSTRACT

BACKGROUND: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two parts of a three-part clinical trial, the antimalarial monoclonal antibody CIS43LS conferred high protection against parasitaemia at doses of 20 mg/kg or 40 mg/kg administered intravenously followed by controlled human malaria infection. The ability of CIS43LS to confer protection at lower doses or by the subcutaneous route is unknown. We aimed to provide data on the safety and optimisation of dose and route for the human antimalaria monoclonal antibody CIS43LS. METHODS: VRC 612 Part C was the third part of a three-part, first-in-human, phase 1, adaptive trial, conducted at the University of Maryland, Baltimore Center for Vaccine Development and Global Health, Baltimore, MD, USA. We enrolled adults aged 18-50 years with no previous malaria vaccinations or infections, in a sequential, dose-escalating manner. Eligible participants received the monoclonal antibody CIS43LS in a single, open-label dose of 1 mg/kg, 5 mg/kg, or 10 mg/kg intravenously, or 5 mg/kg or 10 mg/kg subcutaneously. Participants underwent controlled human malaria infection by the bites of five mosquitoes infected with Plasmodium falciparum 3D7 strain approximately 8 weeks after their monoclonal antibody inoculation. Six additional control participants who did not receive CIS43LS underwent controlled human malaria infection simultaneously. Participants were followed-up daily on days 7-18 and day 21, with qualitative PCR used for P falciparum detection. Participants who tested positive for P falciparum were treated with atovaquone-proguanil and those who remained negative were treated at day 21. Participants were followed-up until 24 weeks after dosing. The primary outcome was safety and tolerability of CIS43LS at each dose level, assessed in the as-treated population. Secondary outcomes included protective efficacy of CIS43LS after controlled human malaria infection. This trial is now complete and is registered with ClinicalTrials.gov, NCT04206332. FINDINGS: Between Sept 1, 2021, and Oct 29, 2021, 47 people were assessed for eligibility and 31 were enrolled (one subsequently withdrew and was replaced) and assigned to receive doses of 1 mg/kg (n=7), 5 mg/kg (n=4), and 10 mg/kg (n=3) intravenously and 5 mg/kg (n=4) and 10 mg/kg (n=4) subcutaneously, or to the control group (n=8). CIS43LS administration was safe and well tolerated; no serious adverse events occurred. CIS43LS protected 18 (82%) of 22 participants who received a dose. No participants developed parasitaemia following dosing at 5 mg/kg intravenously or subcutaneously, or at 10 mg/kg intravenously or subcutaneously. All six control participants and four of seven participants dosed at 1 mg/kg intravenously developed parasitaemia after controlled human malaria infection. INTERPRETATION: CIS43LS was safe and well tolerated, and conferred protection against P falciparum at low doses and by the subcutaneous route, providing evidence that this approach might be useful to prevent malaria across several clinical use cases. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health.


Subject(s)
Antimalarials , Malaria Vaccines , Malaria, Falciparum , Adult , Animals , Humans , Antibodies, Monoclonal/therapeutic use , Malaria, Falciparum/drug therapy , Malaria, Falciparum/prevention & control , Plasmodium falciparum , Malaria Vaccines/therapeutic use
5.
Front Cell Infect Microbiol ; 13: 955134, 2023.
Article in English | MEDLINE | ID: covidwho-2255628

ABSTRACT

Malaria, which infected more than 240 million people and killed around six hundred thousand only in 2021, has reclaimed territory after the SARS-CoV-2 pandemic. Together with parasite resistance and a not-yet-optimal vaccine, the need for new approaches has become critical. While earlier, limited, studies have suggested that malaria parasites are affected by electromagnetic energy, the outcomes of this affectation vary and there has not been a study that looks into the mechanism of action behind these responses. In this study, through development and implementation of custom applicators for in vitro experimentation, conditions were generated in which microwave energy (MW) killed more than 90% of the parasites, not by a thermal effect but via a MW energy-induced programmed cell death that does not seem to affect mammalian cell lines. Transmission electron microscopy points to the involvement of the haemozoin-containing food vacuole, which becomes destroyed; while several other experimental approaches demonstrate the involvement of calcium signaling pathways in the resulting effects of exposure to MW. Furthermore, parasites were protected from the effects of MW by calcium channel blockers calmodulin and phosphoinositol. The findings presented here offer a molecular insight into the elusive interactions of oscillating electromagnetic fields with P. falciparum, prove that they are not related to temperature, and present an alternative technology to combat this devastating disease.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria , Parasites , Animals , Humans , Microwaves , SARS-CoV-2 , Malaria, Falciparum/parasitology , Plasmodium falciparum , Mammals
6.
J Travel Med ; 30(3)2023 05 18.
Article in English | MEDLINE | ID: covidwho-2259304

ABSTRACT

BACKGROUND: Delayed treatment is associated with a higher risk of severe malaria. In malaria-endemic areas, the main factors associated with delay in seeking healthcare are low educational level and traditional beliefs. In imported malaria, determinants of delay in seeking healthcare are currently unknown. METHODS: We studied all patients presenting with malaria, from 1 January 2017 to 14 February 2022, in the hospital of Melun, France. Demographic and medical data were recorded for all patients, and socio-professional data were recorded for a subgroup of hospitalized adults. Relative-risks and 95% confidence intervals were determined using univariate analysis by cross-tabulation. RESULTS: There were 234 patients included, all travelling from Africa. Among them, 218 (93%) were infected with P. falciparum, 77 (33%) had severe malaria, 26 (11%) were <18 years old and 81 were included during the SARS-CoV-2 pandemic. There were 135 hospitalized adults (58% of all patients). The median time to hospital admission (THA) , defined by the period from onset of symptoms to arrival at hospital, was 3 days (IQR = 2-5). A THA ≥3 days tended to be more frequent in travellers visiting friends and relatives (VFR; RR = 1.44, 95% CI = [1.0-2.05], P = 0.06), while it was less frequent in children and teenagers (RR = 0.58, 95% CI = [0.39-0.84], P = 0.01). Gender, African background, unemployment, living alone and absence of referring physician were not associated with delay in seeking healthcare. Consulting during the SARS-CoV-2 pandemic was neither associated with a longer THA nor with a higher rate of severe malaria. CONCLUSION: In contrast to an endemic area, socio-economic factors did not impact on delay in seeking healthcare in imported malaria. Prevention should focus on VFR subjects, who tend to consult later than other travellers.


Subject(s)
Antimalarials , COVID-19 , Malaria, Falciparum , Malaria , Adult , Child , Adolescent , Humans , Retrospective Studies , Antimalarials/therapeutic use , COVID-19/epidemiology , SARS-CoV-2 , Malaria/prevention & control , Malaria, Falciparum/drug therapy , Travel , Hospitals , Delivery of Health Care
7.
Front Immunol ; 14: 1120298, 2023.
Article in English | MEDLINE | ID: covidwho-2269662

ABSTRACT

The co-occurrence and the similarities between malaria and COVID-19 diseases raise the question of whether SARS-CoV-2 is capable of infecting red blood cells and, if so, whether these cells represent a competent niche for the virus. In this study, we first tested whether CD147 functions as an alternative receptor of SARS-CoV-2 to infect host cells. Our results show that transient expression of ACE2 but not CD147 in HEK293T allows SARS-CoV-2 pseudoviruses entry and infection. Secondly, using a SARS-CoV-2 wild type virus isolate we tested whether the new coronavirus could bind and enter erythrocytes. Here, we report that 10,94% of red blood cells had SARS-CoV-2 bound to the membrane or inside the cell. Finally, we hypothesized that the presence of the malaria parasite, Plasmodium falciparum, could make erythrocytes more vulnerable to SARS-CoV-2 infection due to red blood cell membrane remodelling. However, we found a low coinfection rate (9,13%), suggesting that P. falciparum would not facilitate the entry of SARS-CoV-2 virus into malaria-infected erythrocytes. Besides, the presence of SARS-CoV-2 in a P. falciparum blood culture did not affect the survival or growth rate of the malaria parasite. Our results are significant because they do not support the role of CD147 in SARS-CoV-2 infection, and indicate, that mature erythrocytes would not be an important reservoir for the virus in our body, although they can be transiently infected.


Subject(s)
COVID-19 , Coinfection , Malaria, Falciparum , Humans , SARS-CoV-2 , Plasmodium falciparum , HEK293 Cells , Malaria, Falciparum/parasitology , Erythrocytes
8.
Clin Infect Dis ; 76(7): 1161-1163, 2023 04 03.
Article in English | MEDLINE | ID: covidwho-2222606

ABSTRACT

Return to international travel in the COVID-19 pandemic recovery period is expected to increase the number of patients with imported malaria in the United States (US). Malaria prevention in travelers and preparedness for timely diagnosis and appropriate treatment are key to minimize imported malaria morbidity and mortality. Intravenous artesunate (IVAS) is now available from commercial distributors in the US for the treatment of severe malaria. Hospitals and pharmacists should have a plan for malaria treatment, including stocking artemether-lumefantrine for uncomplicated malaria, and stocking or planning for rapid procurement of IVAS for the treatment of severe malaria.


Subject(s)
Antimalarials , COVID-19 , Malaria, Falciparum , Malaria , Humans , United States/epidemiology , Antimalarials/therapeutic use , Pandemics/prevention & control , Artemether/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use , Malaria/diagnosis , Malaria/drug therapy , Malaria/prevention & control , Artesunate/therapeutic use , Travel , Early Diagnosis , Malaria, Falciparum/drug therapy , COVID-19 Testing
9.
Clin Lab ; 69(1)2023 Jan 01.
Article in English | MEDLINE | ID: covidwho-2203270

ABSTRACT

BACKGROUND: COVID-19 and malaria share some similar symptoms such as fever, difficulty in breathing, fatigue, and headaches of acute onset. With overlapping symptoms and travel history significant for COVID-19 and malaria, healthcare systems and professionals will face a great challenge in the case of COVID-19 and malaria co-infection. METHODS: Here we presented a patient with COVID-19 infection and refractory anemia of unknown reason. A diagnostic test for malaria was later performed. RESULTS: The patient was ultimately diagnosed with COVID-19 and plasmodium falciparum malaria co-infection. He recovered gradually after receiving anti-malaria treatment. CONCLUSIONS: The present case highlights the danger of focusing only on a diagnosis of COVID-19, reminding clinicians to be vigilant about the possibility of co-infections.


Subject(s)
Anemia , COVID-19 , Coinfection , Malaria, Falciparum , Malaria , Humans , Male , Anemia/diagnosis , Coinfection/diagnosis , COVID-19/complications , East Asian People , Malaria, Falciparum/complications , Malaria, Falciparum/diagnosis , Plasmodium falciparum , China
10.
Parasitol Res ; 121(7): 1867-1885, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2174153

ABSTRACT

Malaria control measures have been in use for years but have not completely curbed the spread of infection. Ultimately, global elimination is the goal. A major playmaker in the various approaches to reaching the goal is the issue of proper diagnosis. Various diagnostic techniques were adopted in different regions and geographical locations over the decades, and these have invariably produced diverse outcomes. In this review, we looked at the various approaches used in malaria diagnostics with a focus on methods favorably used during pre-elimination and elimination phases as well as in endemic regions. Microscopy, rapid diagnostic testing (RDT), loop-mediated isothermal amplification (LAMP), and polymerase chain reaction (PCR) are common methods applied depending on prevailing factors, each with its strengths and limitations. As the drive toward the elimination goal intensifies, the search for ideal, simple, fast, and reliable point-of-care diagnostic tools is needed more than ever before to be used in conjunction with a functional surveillance system supported by the ideal vaccine.


Subject(s)
Malaria, Falciparum , Malaria , Diagnostic Tests, Routine/methods , Goals , Humans , Malaria/diagnosis , Malaria/prevention & control , Malaria, Falciparum/epidemiology , Microscopy/methods , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Polymerase Chain Reaction/methods , Sensitivity and Specificity
12.
BMJ Case Rep ; 15(11)2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2137561

ABSTRACT

Malaria remains one of the most prevalent infectious diseases globally. Despite targets set out by the WHO in 2015, there has been a rise in the number of cases since 2019 as an indirect effect of the COVID-19 pandemic.Cardiac complications are very rarely witnessed with severe malaria. Of the cardiac sequelae, myocarditis is one of the most frequently observed with a handful of case reports in the literature. We report a case of a man in his 50s who developed myocarditis while being managed for severe Plasmodium falciparum malaria in an intensive care unit in the UK and review the literature relevant to this case. This is the second reported case of this condition in the UK.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria , Myocarditis , Male , Humans , Plasmodium falciparum , Myocarditis/complications , Pandemics , Malaria, Falciparum/complications , Malaria, Falciparum/drug therapy , Malaria/complications
13.
BMC Infect Dis ; 22(1): 846, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2115737

ABSTRACT

BACKGROUND: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure. METHODS: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3. RESULTS: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91). CONCLUSION: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants.


Subject(s)
Antibodies, Viral , COVID-19 , Malaria, Falciparum , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Young Adult , Antibodies, Viral/blood , Antigens, Protozoan , COVID-19/epidemiology , Immunoglobulin G , Malaria, Falciparum/epidemiology , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies , Tanzania/epidemiology
14.
Biomed Res Int ; 2022: 2545830, 2022.
Article in English | MEDLINE | ID: covidwho-2079082

ABSTRACT

The global malaria morbidity and mortality witnessed an increase from 2019 to 2020 partly due to disruptions in control programs' activities imposed by the COVID-19 pandemic. Therefore, there is still a significant burden of malaria in Cameroon which needs attention from all fronts to attain elimination goals. It is normally expected that a typical forest ecology that has undergone urbanization and subjected to high rates of ecological instabilities should also have a shift from characteristic perennial malaria transmission and a shift in the type of malaria endemicity plaguing such distorted forest ecology. In this observational comparative study, we randomly enrolled participants from rural and urban settings of a forest zone during a low malaria transmission period, which coincided with the onset of COVID-19 pandemic. An optimized structured questionnaire was employed, to collect socio-demographic data and associated risk factors. The CareStart™ Malaria HRP2 antigen test was performed on participants from both settings to determine the prevalence of community asymptomatic malaria. Of 307 participants, 188 (61.0%) were from the rural, while 119 (38.8%) from the urban community. The overall prevalence of asymptomatic malaria (27.0%) detected Plasmodium falciparum antigen in 83 participants. The urban community's prevalence was 4.2% (5 positives) while the rural community's was 41.5% (78 positives). In simple logistic regression models, rural forest community and farm around the house were statistically significant predictors of testing positive (coefficient 2.8, 95% CI 1.8-3.7, p value<0.001) and (coefficient 3.1, 95% CI 1.1-5.1, p value =0.003), respectively. In the multivariate model, the strongest predictor of testing positive was living in a rural community, with p < 0.001 and odds ratio of 10.9 (95% CI, 3.8-31.8). These results indicate that during a low transmission period, the prevalence of asymptomatic malaria differs between depleted urban and rural forested settings, suggesting a need for strategic target intervention for the control of asymptomatic malaria.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria , Humans , Rural Population , Plasmodium falciparum , COVID-19/epidemiology , Pandemics , Malaria/epidemiology , Forests , Prevalence , Malaria, Falciparum/epidemiology
15.
Adv Sci (Weinh) ; 9(28): e2105396, 2022 10.
Article in English | MEDLINE | ID: covidwho-2047424

ABSTRACT

In many malaria-endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone-interfaced, battery-operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria-negative and 36 malaria-positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold-standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user-friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource-constrained environments.


Subject(s)
Malaria, Falciparum , Malaria , Parasites , Animals , Erythrocytes , Malaria/diagnosis , Malaria/parasitology , Malaria, Falciparum/diagnosis , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Plasmodium falciparum
16.
Malar J ; 21(1): 255, 2022 Sep 06.
Article in English | MEDLINE | ID: covidwho-2038759

ABSTRACT

BACKGROUND: Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria. METHODS: Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved samples from patients with uncomplicated Plasmodium vivax (n = 8) and uncomplicated (n = 4) and severe (n = 16) falciparum malaria from Papua, Indonesia. RESULTS: The absolute number of circulating polymorphonuclear-MDSC were significantly elevated in severe falciparum malaria patients compared to controls (n = 10). Polymorphonuclear-MDSC levels in uncomplicated vivax malaria were also elevated to levels comparable to that seen in severe falciparum malaria. CONCLUSION: Control of expansion of immunosuppressive MDSC may be important for development of effective immune responses in falciparum and vivax malaria.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Malaria , Myeloid-Derived Suppressor Cells , Humans , Indonesia , Malaria/complications , Plasmodium falciparum , Plasmodium vivax
17.
Molecules ; 27(17)2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2033062

ABSTRACT

Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, Plasmodium falciparum, has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed Halimeda macroloba has afforded two new compounds 1-2, along with 4 known ones 3-6. The structures of the compounds had been confirmed using 1& 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound 2. Docking, absolute-binding-free-energy (ΔGbinding) and molecular-dynamics-simulation (MDS) of compound 2 revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound 2 against P. falciparum. The crude extract was able to inhibit the parasite growth with an IC50 value of 1.8 ± 0.35 µg/mL. Compound 2 also showed good inhibitory activity with an IC50 value of 3.2 ± 0.23 µg/mL. Meanwhile, compound 6 showed moderate inhibitory activity with an IC50 value of 19.3 ± 0.51 µg/mL. Accordingly, the scaffold of compound 2 can be considered as a good lead compound for the future development of new antimalarial agents.


Subject(s)
Antimalarials , Malaria, Falciparum , Malaria , Seaweed , Antimalarials/chemistry , Cytochromes , Humans , Malaria/drug therapy , Malaria, Falciparum/drug therapy , Plant Extracts/chemistry , Plasmodium falciparum
18.
PLoS One ; 17(9): e0270863, 2022.
Article in English | MEDLINE | ID: covidwho-2021856

ABSTRACT

Plasmodium falciparum, a protozoan parasite and causative agent of human malaria, has one of the most A/T-biased genomes sequenced to date. This may give the genome and the transcriptome unusual structural features. Recent progress in sequencing techniques has made it possible to study the secondary structures of RNA molecules at the transcriptomic level. Thus, in this study we produced the in vivo RNA structurome of a protozoan parasite with a highly A/U-biased transcriptome. We showed that it is possible to probe the secondary structures of P. falciparum RNA molecules in vivo using two different chemical probes, and obtained structures for more than half of all transcripts in the transcriptome. These showed greater stability (lower free energy) than the same structures modelled in silico, and structural features appeared to influence translation efficiency and RNA decay. Finally, we compared the P. falciparum RNA structurome with the predicted RNA structurome of an A/U-balanced species, P. knowlesi, finding a bias towards lower overall transcript stability and more hairpins and multi-stem loops in P. falciparum. This unusual protozoan RNA structurome will provide a basis for similar studies in other protozoans and also in other unusual genomes.


Subject(s)
Malaria, Falciparum , Malaria , Parasites , Animals , Genome, Protozoan , Humans , Malaria/genetics , Malaria, Falciparum/parasitology , Parasites/genetics , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , RNA , RNA, Protozoan/genetics , Transcriptome
19.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.20.22280170

ABSTRACT

ABSTRACT Importance Estimating the true burden of SARS-CoV-2 infection has been difficult in sub-Saharan Africa due to asymptomatic infections and inadequate testing capacity. Antibody responses from serologic surveys can provide an estimate of SARS-CoV-2 exposure at the population level. Objective To estimate SARS-CoV-2 seroprevalence, attack rates, and re-infection in eastern Uganda using serologic surveillance from 2020 to early 2022. Design Plasma samples from participants in the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda (PRISM) Border Cohort were obtained at four sampling intervals: October-November 2020; March-April 2021; August-September 2021; and February-March 2022. Setting: Tororo and Busia districts, Uganda. Participants 1,483 samples from 441 participants living in 76 households were tested. Each participant contributed up to 4 time points for SARS-CoV-2 serology, with almost half of all participants contributing at all 4 time points, and almost 90% contributing at 3 or 4 time points. Information on SARS-CoV-2 vaccination status was collected from participants, with the earliest reported vaccinations in the cohort occurring in May 2021. Main Outcome(s) and Measure(s) The main outcomes of this study were antibody responses to the SARS-CoV-2 spike protein as measured with a bead-based serologic assay. Individual-level outcomes were aggregated to population-level SARS-CoV-2 seroprevalence, attack rates, and boosting rates. Estimates were weighted by the local age distribution based on census data. Results By the end of the Delta wave and before widespread vaccination, nearly 70% of the study population had experienced SARS-CoV-2 infection. During the subsequent Omicron wave, 85% of unvaccinated, previously seronegative individuals were infected for the first time, and ∼50% or more of unvaccinated, already seropositive individuals were likely re-infected, leading to an overall 96% seropositivity in this population. Our results suggest a lower probability of re-infection in individuals with higher pre-existing antibody levels. We found evidence of household clustering of SARS-CoV-2 seroconversion. We found no significant associations between SARS-CoV-2 seroconversion and gender, household size, or recent Plasmodium falciparum malaria exposure. Conclusions and Relevance Findings: from this study are consistent with very high infection rates and re-infection rates for SARS-CoV-2 in a rural population from eastern Uganda throughout the pandemic.


Subject(s)
Malaria, Falciparum , COVID-19 , Encephalitis, Arbovirus , Malaria , Border Disease
20.
Virulence ; 13(1): 634-653, 2022 12.
Article in English | MEDLINE | ID: covidwho-2008470

ABSTRACT

Globally, malaria is a public health concern, with severe malaria (SM) contributing a major share of the disease burden in malaria endemic countries. In this context, identification and validation of SM biomarkers are essential in clinical practice. Some biomarkers (C-reactive protein, angiopoietin 2, angiopoietin-2/1 ratio, platelet count, histidine-rich protein 2) have yielded interesting results in the prognosis of Plasmodium falciparum severe malaria, but for severe P. vivax and P. knowlesi malaria, similar evidence is missing. The validation of these biomarkers is hindered by several factors such as low sample size, paucity of evidence-evaluating studies, suboptimal values of sensitivity/specificity, poor clinical practicality of measurement methods, mixed Plasmodium infections, and good clinical value of the biomarkers for concurrent infections (pneumonia and current COVID-19 pandemic). Most of these biomarkers are non-specific to pathogens as they are related to host response and hence should be regarded as prognostic/predictive biomarkers that complement but do not replace pathogen biomarkers for clinical evaluation of SM patients. This review highlights the importance of research on diagnostic/predictive/therapeutic biomarkers, neglected malaria species, and clinical practicality of measurement methods in future studies. Finally, the importance of omics technologies for faster identification/validation of SM biomarkers is also included.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria , Biomarkers , Humans , Pandemics , Plasmodium falciparum , Plasmodium vivax
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