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1.
Pathogens ; 10(3)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800782

RESUMO

Infection with Leishmania parasites can lead to severe disease in humans and dogs, which act as a reservoir in zoonotic transmission. An increasing number of reports suggest that leishmaniosis is not restricted to dogs, but also affects many other mammalian and avian species. Consequently, this expands the potential reservoir and is of great public and veterinary health concern. The present study reviews, based on a comprehensive search of scientific literature published from 1 January 2001 to 31 December 2020, the currently available information on animal leishmaniosis in vertebrates in Europe, other than dogs and humans. This review provides an exhaustive list of mammals and birds in which infections with or exposure to Leishmania parasites have been detected in European countries. Most cases are reported from the Mediterranean region. Domestic animals, in particular cats, pose a concern because of close contact with humans. The wildlife reservoir is less likely to contribute to zoonotic transmission, with the exception of hares. This potentially large reservoir needs to be taken into account when developing control measures for zoonotic leishmaniosis. From a veterinary point of view, it is important that veterinarians are better aware of leishmaniosis and trained in its management.

2.
PLoS One ; 16(4): e0249628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33826660

RESUMO

Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators-if any-included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.

3.
Clin Infect Dis ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33580234

RESUMO

BACKGROUND: In order to expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. METHODS: Data from three clinical trials were combined in this study, where Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during and up to six months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at six months. RESULTS: The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within six months of follow-up at a cut-off of 20 parasites/mL (AUC 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ= 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a >80% power to detect a difference in cure rate between treatment regimens if this difference was high (>50%) and when minimally 30 patients were included per regimen. CONCLUSION: Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.

4.
Malar J ; 20(1): 94, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593344

RESUMO

BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1ß (rs1143634) and FcγRIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.

5.
PLoS Negl Trop Dis ; 14(10): e0008759, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33095776

RESUMO

Cutaneous leishmaniasis (CL) is a chronic skin infection caused by Leishmania parasites, causing single or multiple skin nodules and ulcers on the exposed body locations. Healing of lesions is followed by scar formation. Active and healed CL lesions may affect patient's health related quality of life (HRQL). The aim of this study was to determine whether the body location of the leishmaniasis lesions affects the HRQL of localized CL patients in Suriname. The HRQL of 163 patients with CL was assessed by Skindex-29 and EQ-5D/VAS questionnaires. Forty-six patients out of the total study population also participated in a qualitative anthropological study involving in depth interviews. All patients were allocated in 4 groups in the following hierarchy: head and face, upper limbs, lower limbs and trunk. Patients with lesions on the lower limbs had significantly higher Skindex-29 scores, indicating worse HRQL, in the symptom scale compared to lesions on head/face and trunk. The lower limb group was more likely to report problems in the dimensions self-care, mobility, daily activities and pain/discomfort of the EQ-5D. Little to no social stigma was reported in the in-depth interviews. The findings of this study indicate that Surinamese patients with CL lesions located on the lower limbs had more impairment in HRQL than on other body locations. Stigma related to CL seems to be virtually absent in Suriname.

6.
Parasit Vectors ; 13(1): 229, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375902

RESUMO

BACKGROUND: Knowledge of the relative abundance and biting rates of riverine blackflies (vectors of onchocerciasis) is essential as these entomological indices affect transmission of the disease. However, transmission patterns vary from one ecological zone to another and this may be due to differences in species of blackfly vectors and the climatic conditions in the area. This study investigated the effects of climate variability on the relative abundance and biting rates of blackflies in the Tanfiano community (Nkoranza North District, Bono East Region, Ghana). Such information will help to direct policy on effective timing of the annual mass drug administration of ivermectin in the area. METHODS: The study employed human landing collections and locally built Esperanza window traps to collect blackflies from March 2018 to February 2019. The relative abundance and biting rates of the Simulium vectors as well as the monthly climatic conditions of the study area were monitored. Correlation analysis and Poisson regression were used to establish the relationships between the variables. RESULTS: The relative abundance and biting rates of the Simulium vectors were highest in the drier months of March, April and August, characterized by high temperatures, low humidity, longer hours of sunshine and stronger winds. The rainy months of May, June and July, characterized by low temperatures, high humidity, few hours of sunshine and weaker winds, had relatively low blackfly abundance and biting activity. Correlation analysis showed that only temperature was significantly, positively correlated with the relative abundance of blackflies (r = 0.617, n = 12, P = 0.033) and monthly biting rates (r = 0.612, n = 12, P = 0.034). A model to predict relative abundance and monthly biting rates using climatological variables was developed. CONCLUSIONS: This study demonstrated that Simulium species in the study area preferred higher temperature, lower humidity and rainfall, more hours of sunshine and relatively stronger winds for survival. It is thus recommended that for the study district and others with similar climatological characteristics, mass drug administration of ivermectin should take place in April and September when the abundance of vectors has begun to decline after peaking.

7.
Parasit Vectors ; 13(1): 117, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32312294

RESUMO

BACKGROUND: Dirofilaria immitis, Leishmania infantum and Toxoplasma gondii are zoonotic parasites which can affect domestic cats. Considering the lack of published data from the local feline population, this study aimed to assess infection with or exposure to these pathogens in cats from Madeira Island, Portugal. METHODS: One hundred and forty-one domestic cats (77 males and 64 females; median age: 2 years) were sampled at a veterinary medical centre in Funchal, from September 2018 to January 2019. Serum samples were tested for D. immitis antigen, with an enzyme-linked immunosorbent assay kit, and for antibodies to Leishmania spp. or to T. gondii, with the direct agglutination test and the modified agglutination test, respectively. RESULTS: Five cats (3.5%; 95% confidence interval, CI: 1.2-8.1) were positive to D. immitis; no cats were seropositive to Leishmania spp. (0%; 95% CI: 0-2.6%); and 43 cats (30.5%; 95% CI: 23.0-38.8%) were seropositive to T. gondii. Prevalence of the D. immitis antigen was significantly different between cats that received ectoparasiticides and those which did not (0 vs 12.2%; P = 0.009). Prevalence of antibodies to T. gondii was significantly different between juvenile and adult cats (12.8 vs 38.0%; P = 0.007). There were two cats concurrently positive to D. immitis and T. gondii, but no statistical association between these two dependent variables was found (P = 0.641). CONCLUSIONS: To our knowledge, this is the first report of the presence of parasites D. immitis and T. gondii in the feline population of Madeira Island. Knowledge on the epidemiological situation of these and other zoonotic pathogens should raise awareness, both at the veterinary medical and public health levels, and contribute to promoting prevention and control.

8.
Elife ; 92020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209228

RESUMO

Protozoan parasites of the Leishmania donovani complex - L. donovani and L. infantum - cause the fatal disease visceral leishmaniasis. We present the first comprehensive genome-wide global study, with 151 cultured field isolates representing most of the geographical distribution. L. donovani isolates separated into five groups that largely coincide with geographical origin but vary greatly in diversity. In contrast, the majority of L. infantum samples fell into one globally-distributed group with little diversity. This picture is complicated by several hybrid lineages. Identified genetic groups vary in heterozygosity and levels of linkage, suggesting different recombination histories. We characterise chromosome-specific patterns of aneuploidy and identified extensive structural variation, including known and suspected drug resistance loci. This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of the Leishmania donovani complex.

9.
Malar J ; 19(1): 8, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906948

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. METHODS: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. RESULTS: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). CONCLUSION: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1.


Assuntos
Amodiaquina/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada/métodos , Malária Falciparum/tratamento farmacológico , Adolescente , Amodiaquina/administração & dosagem , Amodiaquina/análogos & derivados , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/administração & dosagem , Artemisininas/administração & dosagem , Artesunato/uso terapêutico , Burkina Faso , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Concentração Inibidora 50 , Lumefantrina/uso terapêutico , Masculino , Administração Massiva de Medicamentos , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Falha de Tratamento , Resultado do Tratamento
10.
Infect Dis Poverty ; 8(1): 96, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31775877

RESUMO

BACKGROUND: There is significant need for accurate diagnostic tools for Cryptosporidium spp. and Giardia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often prevalent. The present study assessed the diagnostic performance of three commercially available rapid diagnostic tests (RDTs) based on faecal-antigen detection for Cryptosporidium spp. and/or G. duodenalis infections in stool samples of children admitted with severe acute malnutrition (SAM) and diarrhoea. An established multiplex PCR was used as reference test. METHODS: Stool samples from children with SAM and diarrhoea enrolled in a randomized controlled trial (registered at clinicaltrials.gov/ct2/show/NCT02246296) in Malawi (n = 175) and Kenya (n = 120) between December 2014 and December 2015 were analysed by a multiplex PCR for the presence of Cryptosporidium spp., G. duodenalis or Entamoeba histolytica parasite DNA. Cryptosporidium-positive samples were species typed using restriction fragment length polymorphism analysis. A sub-sample of the stool specimens (n = 236) was used for testing with three different RDTs. Diagnostic accuracy of the tests under evaluation was assessed using the results of PCR as reference standard using MedCalc software. Pearson Chi-square test and Fisher's exact test were used to determine (significant) difference between the number of cryptosporidiosis or giardiasis cases found by PCR in Malawi and Kenya. The overall diagnostic accuracy of each RDT was calculated by plotting a receiver operating characteristic (ROC) curve for each test and to determine the area under the curve (AUC) using SPSS8 software. RESULTS: Prevalence of Cryptosporidium spp. by PCR was 20.0 and 21.7% in Malawi and Kenya respectively, mostly C. hominis. G. duodenalis prevalence was 23.4 and 5.8% in Malawi and Kenya respectively. E. histolytica was not detected by PCR. RDT testing followed the same pattern of prevalence. RDT sensitivities ranged for cryptosporidiosis from 42.9 to 76.9% and for G. duodenalis from 48.2 to 85.7%. RDT specificities ranged from 88.4 to 100% for Cryptosporidium spp. and from 91.2 to 99.2% for G. duodenalis infections. Based on the estimated area under the curve (AUC) values, all tests under evaluation had an acceptable overall diagnostic accuracy (> 0.7), with the exception of one RDT for Cryptosporidium spp. in Malawi. CONCLUSIONS: All three RDTs for Cryptosporidium spp. and Giardia duodenalis evaluated in this study have a moderate sensitivity, but sufficient specificity. The main value of the RDTs is within their rapidness and their usefulness as screening assays in surveys for diarrhoea.


Assuntos
Criptosporidiose/epidemiologia , Cryptosporidium/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Giardia lamblia/isolamento & purificação , Giardíase/epidemiologia , Pré-Escolar , Criptosporidiose/diagnóstico , Testes Diagnósticos de Rotina/instrumentação , Fezes/parasitologia , Giardíase/diagnóstico , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Malaui/epidemiologia , Prevalência , Sensibilidade e Especificidade , Desnutrição Aguda Grave/etiologia
11.
Am J Trop Med Hyg ; 101(6): 1373-1379, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31595864

RESUMO

Cutaneous leishmaniasis (CL), a neglected parasitic skin disease, is endemic in Pakistan, where Leishmania tropica and Leishmania major are the causative protozoan species. Standard treatment with antimonial injections is long, painful, and costly; has toxic side effects; and is not always available in public hospitals. Small pilot studies have previously evaluated a low-cost and noninvasive hand-held exothermic crystallization thermotherapy for cutaneous leishmaniasis (HECT-CL) device. We aimed to further establish the effectiveness, safety, and feasibility of HECT-CL in L. tropica. In a prospective observational study, patients with parasitological confirmation of CL were treated using the HECT-CL heat pack for 3 minutes with an initial temperature of 52-53°C for 7 consecutive days. Dried blood spot samples were taken for species identification by polymerase chain reaction (PCR). Effectiveness was assessed by using medical photographs and measurements of the lesion size at baseline and subsequent follow-up visits, for up to 180 days. We intended to enroll 317 patients. The HECT-CL treatment was easy to apply and well tolerated. Species identification demonstrated the presence of L. tropica. Interim analysis of 56 patients showed a failure rate of 91% at follow-up (median 45 days after treatment, interquartile range 30-60 days). Enrollment of patients was prematurely suspended because of futility. This study showed a high failure rate for HECT-CL thermotherapy in this setting. Leishmania tropica is known to be less sensitive to antileishmanial drugs, more temperature-resistant, and spontaneous healing is slower than that in L. major. More research is needed to identify low-cost, effective, and more patient-friendly treatment for L. tropica.


Assuntos
Término Precoce de Ensaios Clínicos , Equipamentos e Provisões/normas , Hipertermia Induzida/economia , Hipertermia Induzida/instrumentação , Leishmaniose Cutânea/terapia , Adolescente , Adulto , Criança , Custos e Análise de Custo , Feminino , Humanos , Leishmania tropica/genética , Leishmania tropica/patogenicidade , Leishmaniose Cutânea/parasitologia , Masculino , Paquistão , Estudos Prospectivos , Falha de Tratamento , Adulto Jovem
12.
Rev Bras Parasitol Vet ; 28(1): 172-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30892383

RESUMO

Toxoplasma gondii and Leishmania infantum are zoonotic protozoal parasites. Serum samples were obtained from 186 donkeys (Equus africanus asinus) from Portugal and assessed for antibodies to T. gondii by the modified agglutination test (MAT). For titration of antibodies to Leishmania spp. the direct agglutination test was used (DAT). Eleven donkeys were seropositive for T. gondii with titres of 20 (n = 7), 80 (n = 2), 640 (n = 1) and ≥ 2560 (n = 1). One donkey was seropositive for Leishmania spp. (titre of 800). Donkeys in Portugal are exposed to and can be infected with T. gondii and Leishmania spp.


Assuntos
Anticorpos Antiprotozoários/sangue , Equidae/parasitologia , Leishmania infantum/imunologia , Leishmaniose Visceral/veterinária , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Testes de Aglutinação , Animais , Feminino , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Masculino , Portugal/epidemiologia , Estudos Soroepidemiológicos , Toxoplasmose Animal/diagnóstico
13.
Rev. bras. parasitol. vet ; 28(1): 172-176, Jan.-Mar. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1042499

RESUMO

Abstract Toxoplasma gondii and Leishmania infantum are zoonotic protozoal parasites. Serum samples were obtained from 186 donkeys (Equus africanus asinus) from Portugal and assessed for antibodies to T. gondii by the modified agglutination test (MAT). For titration of antibodies to Leishmania spp. the direct agglutination test was used (DAT). Eleven donkeys were seropositive for T. gondii with titres of 20 (n = 7), 80 (n = 2), 640 (n = 1) and ≥ 2560 (n = 1). One donkey was seropositive for Leishmania spp. (titre of 800). Donkeys in Portugal are exposed to and can be infected with T. gondii and Leishmania spp.


Resumo Toxoplasma gondii e Leishmania infantum são protozoários parasitas com potencial zoonótico. Foram obtidas amostras de soro de 186 jumentos (Equus africanus asinus) e avaliadas para anticorpos anti-T. gondii pelo teste de aglutinação direta modificada (TADM), em Portugal. Para a titulação de anticorpos anti-Leishmania spp. foi usado o teste de aglutinação direta (TAD). Onze jumentos foram soropositivos para T. gondii com títulos de 20 (n = 7), 80 (n = 2), 640 (n = 1) e ≥ 2560 (n = 1). Um jumento foi soropositivo para Leishmania spp. (título de 800). Os jumentos em Portugal estão expostos e podem ser infectados com T. gondii e Leishmania spp.


Assuntos
Animais , Masculino , Feminino , Toxoplasma/imunologia , Anticorpos Antiprotozoários/sangue , Toxoplasmose Animal/epidemiologia , Leishmania infantum/imunologia , Equidae/parasitologia , Leishmaniose Visceral/veterinária , Portugal/epidemiologia , Testes de Aglutinação , Estudos Soroepidemiológicos , Toxoplasmose Animal/diagnóstico , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia
14.
PLoS One ; 14(2): e0211801, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30759130

RESUMO

BACKGROUND: Malaria rapid diagnostic tests (RDT) have limitations due to the persistence of histidine-rich protein 2 (HRP2) antigen after treatment and low sensitivity of Plasmodium lactate dehydrogenase (pLDH) based RDTs. To improve the diagnosis of malaria in febrile children, two diagnostic algorithms, based on sequential interpretation of a malaria rapid diagnostic test detecting two different targets of Plasmodium species and followed by expert microscopy, were evaluated. METHODS: Two diagnostic algorithms were evaluated using 407 blood samples collected between April and October 2016 from febrile children and the diagnostic accuracy of both algorithms was determined. Algorithm 1: The result of line T1-HRP2 were read first; if negative, malaria infection was considered to be absent. If positive, confirmation was done with the line T2-pLDH. If T2-pLDH test was negative, the malaria diagnosis was considered as "inconclusive" and microscopy was performed; Algorithm 2: The result of line T2-pLDH were read first; if positive, malaria infection was considered to be present. If negative, confirmation was done with the line T1-HRP2. If T1-HRP2 was positive the malaria diagnosis was considered as "inconclusive" and microscopy was performed. In absence of malaria microscopy, a malaria infection was ruled out in children with an inconclusive diagnostic test result when previous antimalarial treatment was reported. RESULTS: For single interpretation, the sensitivity of PfHRP2 was 98.4% and the specificity was 74.2%, and for the pLDH test the sensitivity was 89.3% and the specificity was 98.8%. Malaria was accurately diagnosed using both algorithms in 84.5% children. The algorithms with the two-line malaria RDT classified the test results into two groups: conclusive and inconclusive results. The diagnostic accuracy for conclusive results was 98.3% using diagnostic algorithm 1 and 98.6% using algorithm 2. The sensitivity and specificity for the conclusive results were 98.2% and 98.4% for algorithm 1, and 98.6% and 98.4% for algorithm 2, respectively. There were 63 (15.5%) children who had an "inconclusive" result for whom expert microscopy was needed. In children with inconclusive results (PfHRP2+/pLDH- only) previous antimalarial treatment was reported in 16 children with malaria negative microscopy (16/40; 40%) and 1 child with malaria positive microscopy (1/23; 4.3%). CONCLUSION: The strategy of sequential interpretation of two-line malaria RDT can improve the diagnosis of malaria. However, some cases will still require confirmative testing with microscopy or additional investigations on previous antimalarial treatment.


Assuntos
Antígenos de Protozoários , Malária Falciparum , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Proteínas de Protozoários , População Rural , Algoritmos , Antígenos de Protozoários/sangue , Antígenos de Protozoários/genética , Burkina Faso , Pré-Escolar , Feminino , Humanos , Lactente , Malária Falciparum/sangue , Malária Falciparum/diagnóstico , Malária Falciparum/genética , Masculino , Microscopia , Proteínas de Protozoários/sangue , Proteínas de Protozoários/genética , Sensibilidade e Especificidade
15.
Ann Clin Microbiol Antimicrob ; 18(1): 5, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691506

RESUMO

BACKGROUND: Malaria rapid diagnostic tests (RDT) are widely used in endemic areas in order to comply with the recommendation that malaria treatment should only be given after the clinical diagnosis has been confirmed by RDT or microscopy. However, the overestimation of malaria infection with the use of PfHRP2 based RDT, makes the management of febrile illnesses more challenging. This study aimed to assess the effect of the use of malaria RDT on antimicrobial prescription practices. METHODS: A prospective study was conducted among febrile children under-5 years of age attending four health facilities and the referral hospital in the Nanoro Health District (Burkina Faso). To assess the effect of malaria RDT testing on the prescriptions of antimicrobials in febrile children, the initial diagnosis and antimicrobial prescriptions following a malaria RDT testing were recorded. The necessity of these prescriptions was subsequently checked by assessing the actual cause of fever by expert malaria microscopy and a microbiology analysis of blood, urine, stool and nasopharynx swabs that were collected from febrile cases to determine the actual cause of the fever episode. RESULTS: Malaria was diagnosed by nurses, who are the primary health care providers, with a malaria RDT in 72.7% (798/1098) of febrile children, but only 53.7% (589/1097) cases could be confirmed by expert microscopy. Health care workers were likely to prescribe antimalarials to malaria positive RDT compared to malaria negative RDT (RR = 7.74, p = 0.00001). Malaria negative RDT result had a significant influence on the antibiotic prescriptions (RR = 3.57, p = 0.0001). The risk of prescribing antimicrobials was higher in health facility level compared to referral hospital. By cross-checking of laboratory findings to antimicrobial prescriptions, an important part of children with positive bacterial infection have received antibiotic prescriptions although the majority without any infection have also received antibiotics. CONCLUSION: Despite the good attitude of health care workers to adhere to diagnostic test results, antimalarials and antibiotics remain inappropriate prescribed to febrile children. The low specificity of malaria RDT used could be an important cause of these practices.


Assuntos
Antimaláricos/uso terapêutico , Testes Diagnósticos de Rotina/normas , Prescrições de Medicamentos/estatística & dados numéricos , Pessoal de Saúde , Malária/diagnóstico , Antígenos de Protozoários , Burkina Faso , Criança , Pré-Escolar , Feminino , Febre , Instalações de Saúde , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/transmissão , Masculino , Microscopia , Enfermeiras e Enfermeiros , Plasmodium falciparum/isolamento & purificação , Estudos Prospectivos , Proteínas de Protozoários , Sensibilidade e Especificidade
16.
BMC Infect Dis ; 19(1): 25, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616544

RESUMO

BACKGROUND: Cutaneous leishmaniasis (CL) is a serious health problem in Suriname. To expand the diagnostic options, two newly developed diagnostic tests, i.e. the rapid diagnostic test CL Detect™ Rapid Test (CL Detect) and the Loopamp™ Leishmania Detection Kit (Loopamp) were evaluated. METHODS: Diagnostic test performance was compared to the routine diagnostic approach in place, i.e. clinical symptoms combined with microscopy, and to polymerase chain reaction (PCR), which was used as a reference standard. The study population (n = 93) was a typical representation of the CL affected population in Suriname and mainly infected with Leishmania guyanensis. RESULTS: CL Detect had a very low sensitivity compared to microscopy (36.7%) or PCR (35.8%), due to a high number of false negative results. The specificity of the CL Detect compared to microscopy and PCR was 85.7 and 83.3% respectively. Loopamp sensitivity was 84.8% compared to microscopy and 91.4% compared to PCR. The Loopamp test had a moderate specificity (42.9%) compared to microscopy, but a good specificity compared to PCR (91.7%). CONCLUSION: The CL Detect is not likely to be a good replacement for the routine diagnostic procedure for CL in Suriname. The high sensitivity of the easy to perform Loopamp enables the implementation of sensitive molecular diagnosis in resource limited settings.


Assuntos
Leishmaniose Cutânea/diagnóstico , Testes Imediatos , Adulto , Cromatografia de Afinidade/métodos , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Leishmania guyanensis/genética , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/patologia , Masculino , Microscopia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Suriname
17.
Malar J ; 17(1): 425, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442132

RESUMO

BACKGROUND: A multi-country, community-based trial on scheduled screening and treatment for malaria in pregnancy was conducted in Benin, The Gambia and Burkina Faso. Despite standardized procedures and outcomes, the study became subject to rumours and accusations of placenta being sold for mystical and financial gain by trial staff, leading to drop-out rates of 30% and the consequent halting of placental biopsy sampling in Benin. This paper explores the role of socio-cultural beliefs related to placenta and identified additional factors contributing these rumours. METHODS: A qualitative comparative emergent-theory design was used to assess social factors related to trial implementation and uptake in the three countries. Data from participant observation, informal conversations, group discussions and interviews were triangulated and analysed with NVivo Qualitative Analysis software. RESULTS: Despite similar sociocultural beliefs about the sacred nature of the placenta in all three study countries, these beliefs did not affect participation rates in Burkina Faso and The Gambia and placenta-related rumours only emerged in Benin. Therefore, the presence of beliefs is not a sufficient condition to have generated placenta-selling fears. The rumours in Benin reflected the confluence of placenta-related beliefs and factors related to the implementation of the trial (including a catalysing adverse event and miscommunication during the informed consent procedure). Furthermore, distinct socio-political factors contributed to the emergence of rumours, including the historical distrust in governmental organizations and the tense relationship between some of the actors involved in the trial. CONCLUSION: Transdisciplinary social science research designs should accompany the implementation of the trial. The integration of multiple stakeholders' knowledge and involvement is required to define and solve upcoming barriers.


Assuntos
Biópsia/psicologia , Medo , Malária/psicologia , Placenta , Complicações Parasitárias na Gravidez/psicologia , Benin , Biópsia/economia , Feminino , Humanos , Consentimento Livre e Esclarecido , Malária/parasitologia , Gravidez , Complicações Parasitárias na Gravidez/parasitologia
18.
EBioMedicine ; 37: 453-460, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396855

RESUMO

BACKGROUND: Kabul (Afghanistan) is a major focus of cutaneous leishmaniasis (CL) caused by Leishmania tropica. Microscopy remains the reference test for diagnosis despite its low performance. We evaluated whether Loopamp™ Leishmania Detection Kit (Loopamp) and CL Detect™ Rapid Test (CL Detect), detecting Leishmania DNA and antigen, respectively could improve CL diagnosis. METHODS: A diagnostic accuracy study with prospective inclusion was conducted in a leishmaniasis reference clinic in Kabul. Slit skin samples from CL suspects were analysed by microscopy. Samples taken with a dental broach were tested with CL Detect, Loopamp, and PCR. All samples were transferred to the Academic Medical Center (AMC, the Netherlands) for PCR and Loopamp analyses. The diagnostic performance of the tests was evaluated against a reference combining microscopy and PCR. FINDINGS: 274 CL suspects were included in the study. In Kabul, CL Detect had a 65·4% sensitivity [95% Confidence Interval (CI): 59.2-71.2%] and a 100% specificity [95% CI: 80.5-100%], while these were 87.6% [95%CI: 82.9-91.3%] and 70.6% [95% CI: 44.0-89.7%] for Loopamp. At AMC the Loopamp's sensitivity (92.2% [95% CI: 88.2-95.2%]) and specificity (94.1% [95% CI: 71.3-99.8%]) were higher. An algorithm where CL Detect negative suspects would be tested by Loopamp yielded a 93.4% sensitivity [95% CI: 89.6-96.1%] and a 94.1% specificity [95% CI: 71.3-99.8%] when Loopamp's performance at AMC was used. INTERPRETATION: The high specificity of CL Detect and the performance of Loopamp allow their use in a diagnostic algorithm that would minimize the number of CL patients referred for confirmation. FUND: Federal Ministry of Education and Research, Germany.


Assuntos
DNA de Protozoário/genética , Leishmania tropica/genética , Leishmaniose Cutânea/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Afeganistão , Criança , Pré-Escolar , Feminino , Humanos , Leishmaniose Cutânea/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/instrumentação , Sensibilidade e Especificidade
19.
BMC Med ; 16(1): 198, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30384846

RESUMO

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life.


Assuntos
Imunidade Inata/imunologia , Malária Falciparum/diagnóstico , Receptores Toll-Like/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Malária Falciparum/imunologia , Masculino , Gravidez , Estudos Prospectivos
20.
BMC Pediatr ; 18(1): 370, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482171

RESUMO

BACKGROUND: Infectious diseases in children living in resource-limited settings are often presumptively managed on the basis of clinical signs and symptoms. Malaria is an exception. However, the interpretation of clinical signs and symptoms in relation to bacterial infections is often challenging, which may lead to an over prescription of antibiotics when a malaria infection is excluded. The present study aims to determine the association between clinical signs and symptoms and basic hematology data, with laboratory confirmed bacterial infections. METHODS: A health survey was done by study nurses to collect clinical signs/symptoms in febrile (axillary temperature ≥ 37.5 °C) children under - 5 years of age. In addition, blood, stool and urine specimen were systematically collected from each child to perform bacterial culture and full blood cell counts. To determine the association between a bacterial infection with clinical signs/symptoms, and if possible supported by basic hematology data (hemoglobin and leucocyte rates), a univariate analysis was done. This was followed by a multivariate analysis only on those variables with a p-value p < 0.1 in the univariate analysis. Only a p-value of < 0.05 was considered as significant for multivariate analysis. RESULTS: In total, 1099 febrile children were included. Bacteria were isolated from clinical specimens (blood-, stool- and urine- culture) of 127 (11.6%) febrile children. Multivariate logistical regression analysis revealed that a general bacterial infection (irrespective of the site of infection) was significantly associated with the following clinical signs/symptoms: diarrhea (p = 0.003), edema (p = 0.010) and convulsion (p = 0.021). Bacterial bloodstream infection was significantly associated with fever> 39.5 °C (p = 0.002), diarrhea (p = 0.019) and edema (p = 0.017). There was no association found between bacterial infections and basic haematological findings. If diarrhea and edema were absent, a good negative predictive value (100%) of a bacterial bloodstream infection was found, but the positive predictive value was low (33.3%) and the confidence interval was very large (2.5-100; 7.5-70.1). CONCLUSION: Our study demonstrates that clinical signs and symptoms, combined with basic hematology data only, cannot predict bacterial infections in febrile children under - 5 years of age. The development of practical and easy deployable diagnostic tools to diagnose bacterial infections remains a priority.


Assuntos
Bacteriemia/diagnóstico , Febre/microbiologia , Hemoglobinometria , Contagem de Leucócitos , Bacteriemia/sangue , Técnicas Bacteriológicas , Burkina Faso , Pré-Escolar , Estudos Transversais , Diarreia/microbiologia , Edema/microbiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Masculino
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