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1.
Nat Commun ; 12(1): 1555, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692343

RESUMO

A counterargument to the importance of climate change for malaria transmission has been that regions where an effect of warmer temperatures is expected, have experienced a marked decrease in seasonal epidemic size since the turn of the new century. This decline has been observed in the densely populated highlands of East Africa at the center of the earlier debate on causes of the pronounced increase in epidemic size from the 1970s to the 1990s. The turnaround of the incidence trend around 2000 is documented here with an extensive temporal record for malaria cases for both Plasmodium falciparum and Plasmodium vivax in an Ethiopian highland. With statistical analyses and a process-based transmission model, we show that this decline was driven by the transient slowdown in global warming and associated changes in climate variability, especially ENSO. Decadal changes in temperature and concurrent climate variability facilitated rather than opposed the effect of interventions.


Assuntos
Malária/epidemiologia , África Oriental/epidemiologia , Aquecimento Global , Humanos , Incidência , Malária Falciparum/epidemiologia , Plasmodium falciparum/patogenicidade , Plasmodium vivax/patogenicidade , Temperatura
2.
Malar J ; 20(1): 124, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653360

RESUMO

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.


Assuntos
Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Epitopos , Guiné Equatorial/epidemiologia , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Vacinas Antimaláricas , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Polimorfismo Genético , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Seleção Genética
3.
Front Immunol ; 12: 565625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679730

RESUMO

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.


Assuntos
Basigina/imunologia , Memória Imunológica , Malária Falciparum , Plasmodium falciparum/imunologia , /imunologia , África ao Sul do Saara/epidemiologia , /imunologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Merozoítos/imunologia , Índice de Gravidade de Doença
4.
Artigo em Inglês | MEDLINE | ID: mdl-33530386

RESUMO

Aims: This study examines the dynamics of malaria as influenced by meteorological factors in French Guiana from 2005 to 2019. It explores spatial hotspots of malaria transmission and aims to determine the factors associated with variation of hotspots with time. Methods: Data for individual malaria cases came from the surveillance system of the Delocalized Centers for Prevention and Care (CDPS) (n = 17) from 2005-2019. Meteorological data was acquired from the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) database. The Box-Jenkins autoregressive integrated moving average (ARIMA) model tested stationarity of the time series, and the impact of meteorological indices (issued from principal component analysis-PCA) on malaria incidence was determined with a general additive model. Hotspot characterization was performed using spatial scan statistics. Results: The current sample includes 7050 eligible Plasmodium vivax (n = 4111) and Plasmodium falciparum (n = 2939) cases from health centers across French Guiana. The first and second PCA-derived meteorological components (maximum/minimum temperature/minimum humidity and maximum humidity, respectively) were significantly negatively correlated with total malaria incidence with a lag of one week and 10 days, respectively. Overall malaria incidence decreased across the time series until 2017 when incidence began to trend upwards. Hotspot characterization revealed a few health centers that exhibited spatial stability across the entire time series: Saint Georges de l'Oyapock and Antecume Pata for P. falciparum, and Saint Georges de l'Oyapock, Antecume Pata, Régina and Camopi for P. vivax. Conclusions: This study highlighted changing malaria incidence in French Guiana and the influences of meteorological factors on transmission. Many health centers showed spatial stability in transmission, albeit not temporal. Knowledge of the areas of high transmission as well as how and why transmission has changed over time can inform strategies to reduce the transmission of malaria in French Guiana. Hotspots should be further investigated to understand other influences on local transmission, which will help to facilitate elimination.


Assuntos
Malária Falciparum , Malária Vivax , Guiana Francesa/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum , Plasmodium vivax
5.
Malar J ; 20(1): 88, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579285

RESUMO

BACKGROUND: Malaria remains a serious health threat in the Amazonas Region of Peru and approximately 95% of the cases, mainly Plasmodium vivax, are found in native communities of The Rio Santiago District, Condorcanqui Province. In 2019, more than one thousand malaria cases were reported, with an unusual number of Plasmodium falciparum autochthonous cases. The present study aims to report this P. falciparum outbreak while describing the epidemiology of malaria and the risk factors associated in the native communities of Amazonas, Peru. METHODS: The DIRESA-Amazonas in collaboration with the Condorcanqui Health Network and the Institute of Tropical Diseases of the UNTRM carried out a malaria Active Case Detection (ACD III) between January 31st and February 10th of 2020. A total of 2718 (47.4%) individuals from 21 native communities grouped in eight sanitary districts, were screened for malaria infections. Each participant was screened for malaria using microscopy. Follow-up surveys were conducted for all malaria positive individuals to collect socio-demographic data. Spatial clustering of infection risk was calculated using a generalized linear model (GLM). Analysis of risk considered factors such as gender, age, type of infection, symptomatology, and parasitaemia. RESULTS: The study suggests that the P. falciparum index case was imported from Loreto and later spread to other communities of Rio Santiago during 2019. The ACD III reported 220 (8.1%) malaria cases, 46 P. falciparum, 168 P. vivax and 6 mixed infections. SaTScan analysis detected a cluster of high infection risk in Middle Rio Santiago and a particular high P. falciparum infection risk cluster in Upper Rio Santiago. Interestingly, the evaluation of different risk factors showed significant associations between low parasitaemia and P. falciparum asymptomatic cases. CONCLUSION: This is the first report of a P. falciparum outbreak in native communities of Condorcanqui, Amazonas. Timely identification and treatment of symptomatic and asymptomatic cases are critical to achieve malaria control and possible elimination in this area. However, the current malaria situation in Condorcanqui is uncertain, given that malaria ACD activities have been postponed due to COVID-19.


Assuntos
Surtos de Doenças , Malária Falciparum/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , População Rural , Adulto Jovem
6.
Nat Commun ; 12(1): 909, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568678

RESUMO

Malaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36-4.81) and among all participants (OR 2.66; 95% CI: 2.05-3.47). Overall, 94.6% (95% CI: 93.1-95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction.


Assuntos
Anopheles/parasitologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Mosquitos Vetores/parasitologia , Plasmodium falciparum/genética , Adulto , Animais , Anopheles/fisiologia , Infecções Assintomáticas/epidemiologia , Estudos de Coortes , Feminino , Genótipo , Humanos , Quênia/epidemiologia , Estudos Longitudinais , Malária Falciparum/epidemiologia , Masculino , Mosquitos Vetores/fisiologia , Plasmodium falciparum/classificação , Plasmodium falciparum/isolamento & purificação
7.
BMC Infect Dis ; 21(1): 44, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422001

RESUMO

BACKGROUND: Transmission stemming from asymptomatic infections is increasingly being recognized as a threat to malaria elimination. In many regions, malaria transmission is seasonal. It is not well understood whether Plasmodium falciparum modulates its investment in transmission to coincide with seasonal vector abundance. METHODS: We sampled 1116 asymptomatic individuals in the wet season, when vectors are abundant, and 1743 in the dry season, in two sites in western Kenya, representing different transmission intensities (Chulaimbo, moderate transmission, and Homa Bay, low transmission). Blood samples were screened for P. falciparum by qPCR, and gametocytes by pfs25 RT-qPCR. RESULTS: Parasite prevalence by qPCR was 27.1% (Chulaimbo, dry), 48.2% (Chulaimbo, wet), 9.4% (Homabay, dry), and 7.8% (Homabay, wet). Mean parasite densities did not differ between seasons (P = 0.562). pfs25 transcripts were detected in 119/456 (26.1%) of infections. In the wet season, fewer infections harbored detectable gametocytes (22.3% vs. 33.8%, P = 0.009), but densities were 3-fold higher (wet: 3.46 transcripts/uL, dry: 1.05 transcripts/uL, P < 0.001). In the dry season, 4.0% of infections carried gametocytes at moderate-to-high densities likely infective (> 1 gametocyte per 2 uL blood), compared to 7.9% in the wet season. Children aged 5-15 years harbored 76.7% of infections with gametocytes at moderate-to-high densities. CONCLUSIONS: Parasites increase their investment in transmission in the wet season, reflected by higher gametocyte densities. Despite increased gametocyte densities, parasite density remained similar across seasons and were often below the limit of detection of microscopy or rapid diagnostic test, thus a large proportion of infective infections would escape population screening in the wet season. Seasonal changes of gametocytemia in asymptomatic infections need to be considered when designing malaria control measures.


Assuntos
Portador Sadio/parasitologia , Malária Falciparum/parasitologia , Plasmodium falciparum/fisiologia , Adolescente , Infecções Assintomáticas/epidemiologia , Portador Sadio/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Quênia/epidemiologia , Malária Falciparum/epidemiologia , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/isolamento & purificação , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estações do Ano
8.
Cochrane Database Syst Rev ; 1: CD013398, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471371

RESUMO

BACKGROUND: Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites. OBJECTIVES: To assess the effects of house modifications on malaria disease and transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date. SELECTION CRITERIA: Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies. DATA COLLECTION AND ANALYSIS: Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; low-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants). AUTHORS' CONCLUSIONS: Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.


Assuntos
Materiais de Construção , Habitação , Malária Falciparum/prevenção & controle , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Anemia/diagnóstico , Anemia/epidemiologia , Animais , Arquitetura , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Inseticidas , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Mosquiteiros , Mosquitos Vetores , Plasmodium falciparum , Gravidez , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
9.
Artigo em Inglês | MEDLINE | ID: mdl-33477889

RESUMO

According to the World Health Organization 94% of global malaria cases and 94% of global malaria deaths have been reported from Africa. Unfortunately, it is difficult to determine the exact prevalence of disease in some African countries due to a large number of asymptomatic cases. The aim of this study was to assess the prevalence of malaria infections in seemingly healthy children living in the Central African Republic (CAR). CareStartTM Malaria HRP2 rapid diagnostic test (RDT) targeting Plasmodium falciparum was used to test a group of 500 asymptomatic children aged 1-15 years old (330 settled Bantu and 170 semi-nomadic BaAka Pygmies) inhabiting the villages in the Dzanga Sangha region (south-west CAR) in March 2020. In total, 32.4% of asymptomatic Bantu and 40.6% of asymptomatic Pygmy children had a positive result of malaria RDT. Our findings allowed us to demonstrate the high prevalence of asymptomatic malaria infections in south-west CAR. RDTs seem to be a useful tool for the detection of Plasmodium falciparum in areas with limited possibilities of using other diagnostic methods, such as light microscopy and molecular biology.


Assuntos
Malária Falciparum , Malária , Adolescente , África , Infecções Assintomáticas/epidemiologia , República Centro-Africana/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Testes Diagnósticos de Rotina , Humanos , Lactente , Malária/epidemiologia , Malária Falciparum/epidemiologia , Prevalência , Sensibilidade e Especificidade
10.
PLoS One ; 15(12): e0242510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382730

RESUMO

The specific immune response to the Anopheles salivary peptide could be a pertinent and complementary tool to assess the risk of malaria transmission and the effectiveness of vector control strategies. This study aimed to obtain first reliable data on the current state of the Anopheles gSG6-P1 biomarker for assess the level of exposure to Anopheles bites in high malaria endemic areas in Cameroon. Blood smears were collected from people living in the neighborhoods of Youpwe (suburban area, continental) and Manoka (rural area, Island), both areas in the coastal region of Cameroon. Malaria infection was determined using thick blood smear microscopy, whereas the level of specific IgG response to gSG-P1 peptide was assessed by enzyme-linked immunosorbent assay from the dried blood spots. Of 266 (153 from Youpwe, 113 from Manoka) malaria endemic residents (mean age: 22.8±19.8 years, age range: 6 months-94 years, male/female sex ratio: 1/1.2, with Manoka mean age: 23.71±20.53, male/female sex ratio:1/1.13 and Youpwe mean age: 22.12±19.22, male/female sex ratio 1/0.67) randomly included in the study, Plasmodium infection prevalence was significantly higher in Manoka than in Youpwe (64.6% vs 12,4%, p = 0.0001). The anti-gSG6-P1 IgG response showed a high inter-individual heterogeneity and was significantly higher among individuals from Manoka than those from Youpwe (p = 0.023). Malaria infected individuals presented a higher anti-gSG6-P1 IgG antibody response than non-infected (p = 0.0004). No significant difference in the level of specific IgG response to gSG-P1 was observed according to long lasting insecticidal nets use. Taken together, the data revealed that human IgG antibody response to Anopheles gSG-P1 salivary peptide could be also used to assess human exposure to malaria vectors in Central African region. This finding strengthens the relevance of this candidate biomarker to be used for measuring human exposure to malaria vectors worldwide.


Assuntos
Anopheles/parasitologia , Imunoglobulina G/sangue , Proteínas de Insetos/imunologia , Malária Falciparum/epidemiologia , Mosquitos Vetores/parasitologia , Plasmodium falciparum/imunologia , Proteínas e Peptídeos Salivares/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Camarões/epidemiologia , Criança , Pré-Escolar , Teste em Amostras de Sangue Seco , Doenças Endêmicas , Feminino , Humanos , Imunoglobulina G/biossíntese , Lactente , Proteínas de Insetos/sangue , Malária Falciparum/diagnóstico , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Proteínas e Peptídeos Salivares/sangue , População Urbana
11.
BMC Infect Dis ; 20(1): 957, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317454

RESUMO

BACKGROUND: Chronic Sedentary lifestyles have been linked to increased odds of stress, elevated anxiety and diminished wellbeing, inducing cytokine production and predispose to hypertension and other cardiovascular diseases. In endemic areas, Plasmodium falciparum and hepatitis B virus (HBV) infections can trigger pro-inflammatory cytokine responses. However, the impact of these infections on cytokine response profiles in individuals engaged in chronic sedentary activities is unknown. This study was aimed at addressing these concerns using a predominantly sedentary population of traders in the Tamale metropolis of Ghana. METHOD: Four hundred respondents were categorized, based on their number of working years (< or ≥ 5 years) and number of working hours per day (< or ≥ 10 h), into sedentary (≥5 years + ≥ 10 h) and non-sedentary (≥ 5 years + < 10 h, < 5 years + ≥ 10 h and <  5 years + < 10 h) groups. The participants were tested for P. falciparum and HBV infections using polymerase chain reaction. Blood pressure and cytokines responses were measured. Associations and comparison analysis between variables were determined, and test statistics with p < 0.05 were considered statistically significant. RESULTS: Infection status included: un-infected (93.5%), P. falciparum mono-infected (1.0%), HBV mono-infected (3.0%) or P. falciparum /HBV co-infected (2.5%). Majority of the participants, 57.0% (n = 228) were involved in chronic sedentary life style. That notwithstanding, sedentary lifestyle was independent of the infection groups (χ2 = 7.08, p = 0.629). Hypertension was diagnosed in 53.8% of respondents and was independent of infection status (X 2 = 6.33, p = 0.097). Pro-inflammatory (TNF-α, IL-1ß, IL-6, IL-8 and IL-12) and anti-inflammatory (IL-10, IL-7 and IL-13) cytokine responses were similar among individuals with different sedentary working time and between hypertensive and non-hypertensive individuals (p > 0.05 for all comparisons). Among individuals with different infection status, pro-inflammatory (TNF-α; p = 0.290, IL-1ß; p = 0.442, IL-6; p = 0.686, IFN-γ; p = 0.801, IL-8; p = 0.546, IL-12; p = 0.154) and anti-inflammatory (IL-10; p = 0.201, IL-7; p = 0.190, IL-13; p = 0.763) cytokine responses were similar. CONCLUSION: Our data suggest that asymptomatic infections of P. falciparum and HBV together with a high prevalence of hypertension did not have any significant impact on cytokine response profiles among predominantly sedentary traders in the Tamale metropolis of Ghana.


Assuntos
Doenças Assintomáticas/epidemiologia , Coinfecção/epidemiologia , Citocinas/sangue , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Malária Falciparum/epidemiologia , Plasmodium falciparum/genética , Comportamento Sedentário , Adolescente , Adulto , Coinfecção/parasitologia , Coinfecção/virologia , Estudos Transversais , Feminino , Gana/epidemiologia , Hepatite B/sangue , Hepatite B/virologia , Humanos , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
12.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(6): 612-617, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-33325196

RESUMO

OBJECTIVE: To investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. METHODS: From 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. RESULTS: The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. CONCLUSIONS: There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.


Assuntos
Antimaláricos , Resistência a Medicamentos/genética , Malária Falciparum , Plasmodium falciparum/genética , Proteínas de Protozoários , Antimaláricos/uso terapêutico , China/epidemiologia , DNA de Protozoário/genética , Guiné Equatorial/epidemiologia , Genótipo , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Mutação , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo Genético/efeitos dos fármacos , Proteínas de Protozoários/genética
13.
PLoS One ; 15(12): e0244457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382787

RESUMO

BACKGROUND: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings. METHODS: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results. RESULTS: The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/µl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62-4.38, P = 0.001; aOR 4.4, 95% CI 1.72-13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3-38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/µl). CONCLUSION: This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.


Assuntos
Antígenos de Protozoários/isolamento & purificação , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Teste em Amostras de Sangue Seco/instrumentação , Teste em Amostras de Sangue Seco/estatística & dados numéricos , Monitoramento Epidemiológico , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase/estatística & dados numéricos , Prevalência , Proteínas de Protozoários/imunologia , Uganda/epidemiologia
14.
Med. clín (Ed. impr.) ; 155(9): 395-402, nov. 2020. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-198322

RESUMO

Despite recent successful efforts to reduce the global malaria burden, this disease remains a significant global health problem. Only in 2018, malaria caused 228 million clinical episodes, 2-4 million of which were severe malaria cases, and 405,000 were fatal. Most of the malaria attributable mortality occurred among children in sub-Saharan Africa. Nowadays, rapid diagnostic tests and artemisinin derivatives are two of the main pillars for the management of malaria. However, considering the current situation, these strategies are not sufficient to maintain a reducing trend in malaria incidence and mortality. New insights into the pathophysiology of malaria have highlighted the importance of the host response to infection. Understanding this response would help to develop new diagnostic and therapeutic tools. Vector and parasite drug resistance are two major challenges for malaria control that require special attention. The most advanced malaria vaccine (RTS,S) is currently being piloted in 3 African countries


La malaria es la enfermedad parasitaria más importante del mundo, causando una enorme carga de morbimortalidad en aquellas zonas donde es endémica. Los primeros 15 años del siglo XX han visto como la incidencia de la malaria y las muertes atribuibles a esta enfermedad disminuían de forma significativa. Los enormes avances en los tratamientos y métodos diagnósticos, así como en las estrategias de prevención han contribuido, sin duda, a mejorar la situación de esta enfermedad a nivel global. Sin embargo, una serie de desafíos biológicos, que incluyen la aparición de resistencias por parte del parásito a los antimaláricos, así como por parte de los vectores a los insecticidas, y la aparición de parásitos mutantes que no expresan el gen de la proteína PfHRP2 (siendo, por tanto, «invisibles» a las pruebas diagnósticas rápidas basadas en esta proteína), han puesto en peligro los enormes avances observados. Si la comunidad global pretende continuar avanzando de forma firme hacia la erradicación global de esta enfermedad, será importante mejorar la actual cobertura de todas estas intervenciones, así como fomentar la innovación en las áreas de diagnóstico, prevención y tratamiento


Assuntos
Humanos , Malária/diagnóstico , Malária/epidemiologia , Malária/imunologia , Malária/patologia , Plasmodium falciparum/patogenicidade , Malária Falciparum/epidemiologia , Malária/prevenção & controle , Vacinas/imunologia
15.
PLoS One ; 15(10): e0239578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031456

RESUMO

BACKGROUND: Prevalence of Prevalence of malaria in pregnancy (MiP) in Kenya ranges from 9% to 18%. We estimated the prevalence and factors associated with MiP and anemia in pregnancy (AiP) among asymptomatic women attending antenatal care (ANC) visits. METHODS: We performed a cross-sectional study among pregnant women attending ANC at Msambweni Hospital, between September 2018 and February 2019. Data was collected and analyzed in Epi Info 7. Descriptive statistics were calculated and we compared MiP and AiP in asymptomatic cases to those without either condition. Adjusted prevalence Odds odds ratios (aPOR) and 95% confidence intervals (CI) were calculated to identify factors associated with asymptomatic MiP and AiP. RESULTS: We interviewed 308 study participants; their mean age was 26.6 years (± 5.8 years), mean gestational age was 21.8 weeks (± 6.0 weeks), 173 (56.2%) were in the second trimester of pregnancy, 12.9% (40/308) had MiP and 62.7% had AiP. Women who were aged ≤ 20 years had three times likelihood of developing MiP (aPOR = 3.1 Cl: 1.3-7.35) compared to those aged >20 years old. The likelihood of AiP was higher among women with gestational age ≥ 16 weeks (aPOR = 3.9, CI: 1.96-7.75), those with parasitemia (aPOR = 3.3, 95% CI: 1.31-8.18), those in third trimester of pregnancy (aPOR = 2.6, 95% CI:1.40-4.96) and those who reported eating soil as a craving during pregnancy (aPOR = 1.9, 95%CI:1.15-3.29). CONCLUSIONS: Majority of the women had asymptomatic MiP and AiP. MiP was observed in one tenth of all study participants. Asymptomatic MiP was associated with younger age while AiP was associated with gestational age parasitemia, and soil consumption as a craving during pregnancy.


Assuntos
Anemia/epidemiologia , Doenças Assintomáticas/epidemiologia , Hospitais/estatística & dados numéricos , Malária Falciparum/epidemiologia , Plasmodium falciparum/fisiologia , Complicações Parasitárias na Gravidez/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Quênia , Gravidez , Prevalência , Fatores de Risco , Adulto Jovem
16.
Ann Parasitol ; 66(3): 283-294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33126296

RESUMO

Asymptomatic Plasmodium falciparum infection during pregnancy is a major cause of foetal and maternal morbidity and mortality. The current study estimated the prevalence of asymptomatic P. falciparum infection among pregnant women in Nigeria. We systematically searched the PubMed, Web of Science, Google Scholar and AJOL databases for studies that estimated the prevalence of asymptomatic P. falciparum infection in pregnant women up to December, 2019, and identified additional studies from reference lists. Twenty-seven studies which fulfilled eligibility criteria were included in final systematic review and meta-analysis. The prevalence of asymptomatic P. falciparum infection of individual study varied from 2.1% to 95.4%. Most surveys were performed in the southern parts of Nigeria. We observed a high degree of heterogeneity in most pooled estimates (I2 > 75%; p < 0.01). The pooled estimate of asymptomatic P. falciparum infection prevalence across studies for the entire period was 34.3% (95% CI: 24.0-46.3), ranging from 34.7% (95% CI: 22.8-48.9) in primigravida to 28.5% (95% CI: 15.8-45.8%) in the first trimester. Studies conducted from 2000-2009 (51.3%; 95% CI: 29.1-73.0), southern Nigeria (41.8%; 95% CI: 28.2-56.7), rural areas (52.1%; 95% CI: 19.4-83.0), and median sample size ≥ 246 (41.5; 95% CI: 25.9-58.9), had the highest pooled prevalence. Asymptomatic P. falciparum infection is considered high in pregnant women in Nigeria. This results, therefore, emphasize the need to actively diagnose and treat asymptomatic malaria infection during all antenatal care visits.


Assuntos
Malária Falciparum , Complicações Parasitárias na Gravidez , Feminino , Humanos , Malária Falciparum/epidemiologia , Nigéria/epidemiologia , Plasmodium falciparum , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Prevalência
17.
BMC Res Notes ; 13(1): 497, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109270

RESUMO

OBJECTIVE: Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. RESULTS: Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.


Assuntos
Combinação Arteméter e Lumefantrina/uso terapêutico , ATPases Transportadoras de Cálcio/genética , Malária Falciparum/tratamento farmacológico , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Adolescente , Adulto , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Resistência a Medicamentos/genética , Feminino , Expressão Gênica , Genótipo , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Nigéria/epidemiologia , Pandemias/prevenção & controle , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle
18.
Cochrane Database Syst Rev ; 10: CD013398, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058136

RESUMO

BACKGROUND: Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites. OBJECTIVES: To assess the effects of house modifications on malaria disease and transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date. SELECTION CRITERIA: Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies. DATA COLLECTION AND ANALYSIS: Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; moderate-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants). AUTHORS' CONCLUSIONS: Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.


Assuntos
Materiais de Construção , Habitação , Malária Falciparum/prevenção & controle , Adolescente , Adulto , África ao Sul do Saara , Anemia/diagnóstico , Anemia/epidemiologia , Animais , Arquitetura , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Inseticidas , Malária Falciparum/epidemiologia , Masculino , Mosquitos Vetores , Plasmodium falciparum , Gravidez , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
PLoS One ; 15(9): e0238749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886699

RESUMO

INTRODUCTION: False-negative malaria rapid diagnostic test (RDT) results amongst symptomatic malaria patients are detrimental as they could lead to ineffective malaria case management. This study determined the nationwide contribution of parasites with Pfhrp2 and Pfhrp 3 gene deletions to false negative malaria RDT results in Ghana. METHODS: This was a cross sectional study where whole blood (~2 ml) was collected from patients presenting with malaria symptoms at 100 health facilities in all the regions in Ghana from May to August 2018. An aliquot of the blood was used to prepare thin and thick blood smears, filter paper blood spots (DBS) and spot a PfHRP 2 RDT kit. The remaining blood was separated into plasma and blood cells and stored at -20°C. Plasmodium parasite density and species identity was estimated from the blood smears. Plasmodium falciparum specific 18S rRNA PCR, merozoite surface protein (msp 1) and glutamate rich protein (glurp) gene PCR were used to identify P. falciparum positive samples, which were subjected to Pfhrp 2/3 exon1-2 and exon2 genotyping. RESULTS: Of the 2,860 microscopically P. falciparum positive patients analyzed, 134 (4.69%) had false negative P. falciparum specific RDT results. Samples for PCR analysis was available for 127 of the false negative patients, and the analysis identified 116 (91.3%) as positive for P. falciparum. Only 58.1% (79/116) of the false negative RDT samples tested positive by msp 1 and glurp PCR. Genotyping of exon 1-2 and exon 2 of the Pfhrp 2 gene identified 12.9% (10/79) and 39.5% (31/79) of samples respectively to have deletions. Genotyping exon 1-2 and exon 2 of the Pfhrp 3 gene identified 15.2% (12/79) and 40.5% (32/79) of samples respectively to have deletions. Only 5% (4/79) of the false negative samples had deletions in both exon 1-2 and exon 2 of the Pfhrp 2 gene. Out of the 49 samples that tested positive for aldolase by luminex, 32.6% (16/49) and) had deletions in Pfhrp 2 exon 2 and 2% (1/49) had deletions in both exon 2 and exon 1-2 of the Pfhrp 2 gene. CONCLUSIONS: The low prevalence of false negative RDT test results provides assurance that PfHRP 2 based malaria RDT kits remain effective in diagnosing symptomatic malaria patients across all the Regions of Ghana. Although there was a low prevalence of parasites with deletions in exon 2 and exon 1-2 of the Pfhrp 2 gene the prevalence of parasites with deletions in Pfhrp 2 exon 2 was about a third of the false negative RDT results. The need to ensure rapid, accurate and reliable malaria diagnosis requires continuous surveillance of parasites with Pfhrp 2 gene deletions.


Assuntos
Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Deleção de Genes , Malária Falciparum/diagnóstico , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Adulto , Antígenos de Protozoários/imunologia , Reações Falso-Negativas , Feminino , Técnicas de Genotipagem , Gana/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Plasmodium falciparum/fisiologia , Adulto Jovem
20.
PLoS Med ; 17(8): e1003203, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822347

RESUMO

BACKGROUND: Artemisinin resistance is threatening malaria control. We aimed to develop and test a human model of artemisinin-resistant (ART-R) Plasmodium falciparum to evaluate the efficacy of drugs against ART-R malaria. METHODS AND FINDINGS: We conducted 2 sequential phase 1, single-centre, open-label clinical trials at Q-Pharm, Brisbane, Australia, using the induced blood-stage malaria (IBSM) model, whereby healthy participants are intravenously inoculated with blood-stage parasites. In a pilot study, participants were inoculated (Day 0) with approximately 2,800 viable P. falciparum ART-R parasites. In a comparative study, participants were randomised to receive approximately 2,800 viable P. falciparum ART-R (Day 0) or artemisinin-sensitive (ART-S) parasites (Day 1). In both studies, participants were administered a single approximately 2 mg/kg oral dose of artesunate (AS; Day 9). Primary outcomes were safety, ART-R parasite infectivity, and parasite clearance. In the pilot study, 2 participants were enrolled between April 27, 2017, and September 12, 2017, and included in final analyses (males n = 2 [100%], mean age = 26 years [range, 23-28 years]). In the comparative study, 25 participants were enrolled between October 26, 2017, and October 18, 2018, of whom 22 were inoculated and included in final analyses (ART-R infected participants: males n = 7 [53.8%], median age = 22 years [range, 18-40 years]; ART-S infected participants: males n = 5 [55.6%], median age = 28 years [range, 22-35 years]). In both studies, all participants inoculated with ART-R parasites became parasitaemic. A total of 36 adverse events were reported in the pilot study and 277 in the comparative study. Common adverse events in both studies included headache, pyrexia, myalgia, nausea, and chills; none were serious. Seven participants experienced transient severe falls in white cell counts and/or elevations in liver transaminase levels which were considered related to malaria. Additionally, 2 participants developed ventricular extrasystoles that were attributed to unmasking of a predisposition to benign fever-induced tachyarrhythmia. In the comparative study, parasite clearance half-life after AS was significantly longer for ART-R infected participants (n = 13, 6.5 hours; 95% confidence interval [CI] 6.3-6.7 hours) compared with ART-S infected participants (n = 9, 3.2 hours; 95% CI 3.0-3.3 hours; p < 0.001). The main limitation of this study was that the ART-R and ART-S parasite strains did not share the same genetic background. CONCLUSIONS: We developed the first (to our knowledge) human model of ART-R malaria. The delayed clearance profile of ART-R parasites after AS aligns with field study observations. Although based on a relatively small sample size, results indicate that this model can be safely used to assess new drugs against ART-R P. falciparum. TRIAL REGISTRATION: The studies were registered with the Australian New Zealand Clinical Trials Registry: ACTRN12617000244303 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372357) and ACTRN12617001394336 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373637).


Assuntos
Anti-Infecciosos/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/sangue , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/metabolismo , Adolescente , Adulto , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Artemisininas/efeitos adversos , Artemisininas/farmacologia , Artesunato/efeitos adversos , Artesunato/farmacologia , Artesunato/uso terapêutico , Austrália/epidemiologia , Feminino , Cefaleia/induzido quimicamente , Voluntários Saudáveis , Humanos , Malária Falciparum/epidemiologia , Masculino , Náusea/induzido quimicamente , Parasitos/metabolismo , Projetos Piloto , Adulto Jovem
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