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1.
Malar J ; 20(1): 32, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422080

RESUMEN

BACKGROUND: Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020. METHODS: The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran's Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies. RESULTS: Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1-42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. CONCLUSIONS: This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620.

2.
J Blood Med ; 11: 421-427, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33177908

RESUMEN

Background: Individuals with sickle cell disease (SCD) are susceptible to infective conditions that predispose them to hemolysis and anemia. Folic acid is recommended as a preventative measure against anemia in SCD patients; however, there is scarce literature on the implications of this practice. Patients and Methods: Plasma concentrations of folate were measured in acutely ill pediatric SCD patients presenting with malaria or bacteremia and compared with those of SCD patients in steady state, or acutely ill non-SCD patients with confirmed malaria. Results: The proportion of individuals with high (>45.3 nmol/L) folate concentrations was 29.5% (13/44), 18.2% (8/44), 33.3% (6/18), and 0% in the SCD-malaria, SCD steady state, SCD bacteremia, and the non-SCD malaria groups, respectively. The proportion of SCD patients with high folate levels did not vary significantly at steady state and during confirmed malaria (p = 0.216), and during acute bacteremia (p = 0.20). The median (interquartile range) plasma folate levels were 34.50 (24.40-52.00 nmol/L), 33.40 (15.83-60.85 nmol/L), 30.85 (24.68-39.65 nmol/L), and 13.30 (10.03-17.18 nmol/L), respectively, in the SCD malaria, SCD bacteremia, SCD steady state, and the non-SCD malaria sub-groups. The median folate levels of SCD steady state, SCD malaria, and SCD bacteremia sub-groups differed significantly (p < 0.0001) when compared with non-SCD patients, but the levels in the SCD bacteremia and malaria groups were not significantly different from the SCD steady state group. Conclusion: Elevated levels of plasma folate were found in a high proportion of pediatric SCD patients. The implications of such elevated folate levels in pediatric SCD patients are unknown but may suggest a need for review of current recommendations for prophylactic doses of folic acid in SCD patients.

3.
Malar J ; 18(1): 324, 2019 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-31547818

RESUMEN

Targeted Next Generation Sequencing (TNGS) is an efficient and economical Next Generation Sequencing (NGS) platform and the preferred choice when specific genomic regions are of interest. So far, only institutions located in middle and high-income countries have developed and implemented the technology, however, the efficiency and cost savings, as opposed to more traditional sequencing methodologies (e.g. Sanger sequencing) make the approach potentially well suited for resource-constrained regions as well. In April 2018, scientists from the Plasmodium Diversity Network Africa (PDNA) and collaborators met during the 7th Pan African Multilateral Initiative of Malaria (MIM) conference held in Dakar, Senegal to explore the feasibility of applying TNGS to genetic studies and malaria surveillance in Africa. The group of scientists reviewed the current experience with TNGS platforms in sub-Saharan Africa (SSA) and identified potential roles the technology might play to accelerate malaria research, scientific discoveries and improved public health in SSA. Research funding, infrastructure and human resources were highlighted as challenges that will have to be mitigated to enable African scientists to drive the implementation of TNGS in SSA. Current roles of important stakeholders and strategies to strengthen existing networks to effectively harness this powerful technology for malaria research of public health importance were discussed.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Malaria , Plasmodium/genética , África del Sur del Sahara , Congresos como Asunto , Humanos , Senegal
4.
Am J Trop Med Hyg ; 101(5): 973-975, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31516108

RESUMEN

Aedes mosquitoes are the principal dengue vector in Taiwan, where the use of insecticides is a key element in the national control strategy. However, control efforts are constrained by the development of resistance to most insecticides, including pyrethroids. In this study, mutations in the voltage-gated sodium channel (VGSC) gene resulting in knockdown resistance (kdr) were examined in Aedes aegypti. Fragments of the VGSC gene were polymerase chain reaction (PCR)-amplified followed by restriction fragment length polymorphism analysis in samples from various settings in Southern Taiwan covering dry and wet seasons from 2013 to 2015. Three kdr mutations were identified: V1023G, D1794Y, and F1534C, with observed frequencies of 0.36, 0.55, and 0.33, respectively, in the dry season of 2013-2014. Exploring for temporal changes, the most important observation was the 1534C allele frequency increment in the following season to 0.60 (P < 0.05). This study suggests that continued insecticide pressure is driving the mutational changes, although the selection is ambiguous in the mosquito population.


Asunto(s)
Aedes/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Animales , Genotipo , Polimorfismo de Nucleótido Simple , Piretrinas/farmacología , Estaciones del Año , Taiwán , Factores de Tiempo
5.
Malar J ; 18(1): 267, 2019 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-31477109

RESUMEN

Parasite resistance against anti-malarial drugs is a major threat to the ongoing malaria control and elimination strategies. This is especially true since resistance to the currently recommended artemisinins and partner drugs has been confirmed in South East Asia (SEA) and new anti-malarial compounds are not expected to be available in the near future. Spread from SEA or independent emergence of artemisinin resistance in sub-Saharan Africa (SSA) could reverse the achievements in malaria control that have been attained in the past two decades and derail the ongoing elimination strategies. The current surveillance of clinical efficacy and resistance to anti-malarial drugs is based on efficacy trials to assess the clinical performance of anti-malarials, in vivo/ex vivo assessment of parasite susceptibility to anti-malarials and prevalence of known molecular markers of drug resistance. Whereas clinical efficacy trials are restricted by cost and the complex logistics of patient follow-up, molecular detection of genetic mutations associated with resistance or reduced susceptibility to anti-malarials is by contrast a simple and powerful tool for early detection and monitoring of the prevalence of resistant parasites at population level. This provides needed information before clinical failure emerges, allowing policy makers to anticipate problems and respond. The various methods previously used in detection of molecular markers of drug resistance share some limitations: low-throughput, and high costs per sample and demanding infrastructure. However, recent technological advances including next-generation sequencing (NGS) methodologies promise greatly increased throughput and reduced costs, essentially providing unprecedented potential to address different research and operational questions of relevance for drug policy. This review assesses the potential role of NGS to provide comprehensive information that could guide drug policies in malaria endemic countries and looks at the foreseeable challenges facing the establishment of NGS approaches for routine surveillance of parasite resistance to anti-malarials in SSA.


Asunto(s)
Antimaláricos/uso terapéutico , Control de Enfermedades Transmisibles/legislación & jurisprudencia , Resistencia a Medicamentos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Plasmodium falciparum/genética , Formulación de Políticas , África del Sur del Sahara , Control de Enfermedades Transmisibles/métodos , Quimioterapia Combinada , Salud Global/legislación & jurisprudencia , Salud Global/normas , Legislación de Medicamentos , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos
6.
PLoS One ; 14(8): e0220261, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31381579

RESUMEN

Excessive use of antibiotics, especially watch group antibiotics such as ceftriaxone leads to emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries (LMICs), antibiotics are overused but data on consumption is scarcely available. We aimed at determining the extent and predictors of ceftriaxone use in a tertiary care university teaching hospital in Kilimanjaro, Tanzania. A hospital-based cross-sectional study was conducted from August 2013 through August 2015. Patients admitted in the medical, surgical wards and their respective intensive care units, receiving antimicrobials and other medications for various ailments were enrolled. Socio-demographic and clinical data were recorded in a structured questionnaire from patients' files and logistic regression was performed to determine the predictors for ceftriaxone use. Out of the 630 patients included in this study, 322 (51.1%) patients were on ceftriaxone during their time of hospitalization. Twenty-two patients out of 320 (6.9%) had been on ceftriaxone treatment without evidence of infection. Ceftriaxone use for surgical prophylaxis was 44 (40.7%), of which 32 (72.7%) and 9 (20.5%) received ceftriaxone prophylaxis before and after surgery, respectively. Three (6.8%) received ceftriaxone prophylaxis during surgery. Predicting factors for that the health facility administered ceftriaxone were identified as history of any medication use before referral to hospital [OR = 3.4, 95% CI (1.0-11.4), p = 0.047], bacterial infection [OR = 18.0, 95% CI (1.4-225.7, p = 0.025)], surgical ward [OR = 2.9, 95% CI (0.9-9.4), p = 0.078] and medical wards [OR = 5.0, 95% CI (0.9-28.3), p = 0.070]. Overall, a high ceftriaxone use at KCMC hospital was observed. Antimicrobial stewardship programs are highly needed to monitor and regulate hospital antimicrobial consumption, which in turn could help in halting the rising crisis of antimicrobial resistance.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Ceftriaxona/uso terapéutico , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tanzanía , Adulto Joven
7.
Malar J ; 18(1): 252, 2019 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-31349834

RESUMEN

BACKGROUND: Large-scale surveillance of molecular markers of anti-malarial drug resistance is an attractive method of resistance monitoring, to complement therapeutic efficacy studies in settings where the latter are logistically challenging. METHODS: Between 2014 and 2017, this study sampled malaria rapid diagnostic tests (RDTs), used in routine clinical care, from two health centres in Bissau, Guinea-Bissau. In order to obtain epidemiological insights, RDTs were collected together with patient data on age and sex. A subset of positive RDTs from one of the two sites (n = 2184) were tested for Plasmodium DNA content. Those testing positive for Plasmodium DNA by PCR (n = 1390) were used for library preparation, custom designed dual indexing and next generation Miseq targeted sequencing of Plasmodium falciparum genes pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13. RESULTS: The study found a high frequency of the pfmdr1 codon 86N at 88-97%, a significant decrease of the pfcrt wildtype CVMNK haplotype and elevated levels of the pfdhfr/pfdhps quadruple mutant ranging from 33 to 51% between 2014 and 2017. No polymorphisms indicating artemisinin tolerance were discovered. The demographic data indicate a large proportion of young adults (66%, interquartile range 11-28 years) presenting with P. falciparum infections. While a total of 5532 gene fragments were successfully analysed on a single Illumina Miseq flow cell, PCR-positivity from the library preparation varied considerably from 13 to 87% for different amplicons. Furthermore, pre-screening of samples for Plasmodium DNA content proved necessary prior to library preparation. CONCLUSIONS: This study serves as a proof of concept for using leftover clinical material (used RDTs) for large-scale molecular surveillance, encompassing the inherent complications regarding to methodology and analysis when doing so. Factors such as RDT storage prior to DNA extraction and parasitaemia of the infection are likely to have an effect on whether or not parasite DNA can be successfully analysed, and are considered part of the reason the data yield is suboptimal. However, given the necessity of molecular surveillance of anti-malarial resistance in settings where poor infrastructure, poor economy, lack of educated staff and even surges of political instability remain major obstacles to performing clinical studies, obtaining the necessary data from used RDTs, despite suboptimal output, becomes a feasible, affordable and hence a justifiable method.


Asunto(s)
Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Monitoreo Epidemiológico , Malaria Falciparum/diagnóstico , Plasmodium falciparum/genética , Prueba de Estudio Conceptual , Adolescente , Adulto , Niño , Preescolar , Femenino , Guinea Bissau , Humanos , Lactante , Recién Nacido , Masculino , Adulto Joven
8.
J Antimicrob Chemother ; 74(6): 1484-1493, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30843063

RESUMEN

BACKGROUND: Reliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities. AIM: To study diversity and resistance determinants and to predict and compare resistance patterns from WGS data of Acinetobacter baumannii with phenotypic results from classical microbiological testing at a tertiary care hospital in Tanzania. METHODS AND RESULTS: MLST using Pasteur/Oxford schemes yielded eight different STs from each scheme. Of the eight, two STs were identified to be global clones 1 (n = 4) and 2 (n = 1) as per the Pasteur scheme. Resistance testing using classical microbiology determined between 50% and 92.9% resistance across all drugs. Percentage agreement between phenotypic and genotypic prediction of resistance ranged between 57.1% and 100%, with coefficient of agreement (κ) between 0.05 and 1. Seven isolates harboured mutations at significant loci (S81L in gyrA and S84L in parC). A number of novel plasmids were detected, including pKCRI-309C-1 (219000 bp) carrying 10 resistance genes, pKCRI-43-1 (34935 bp) carrying two resistance genes and pKCRI-49-1 (11681 bp) and pKCRI-28-1 (29606 bp), each carrying three resistance genes. New ampC alleles detected included ampC-69, ampC-70 and ampC-71. Global clone 1 and 2 isolates were found to harbour ISAba1 directly upstream of the ampC gene. Finally, SNP-based phylogenetic analysis of the A. baumannii isolates revealed closely related isolates in three clusters. CONCLUSIONS: The validity of the use of WGS in the prediction of phenotypic resistance can be appreciated, but at this stage is not sufficient for it to replace conventional antimicrobial susceptibility testing in our setting.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Acinetobacter/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Niño , Femenino , Genoma Bacteriano , Humanos , Masculino , Persona de Mediana Edad , Mutación , Tanzanía/epidemiología , Secuenciación Completa del Genoma , Adulto Joven
9.
BMC Res Notes ; 12(1): 134, 2019 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-30867026

RESUMEN

OBJECTIVE: The alpha-thalassaemia trait has been associated with protection against severe malaria but its role in Plasmodium falciparum asexual parasite and gametocyte carriage remains unclear. This study examined association between prevalence of α-thalassaemia and P. falciparum asexual stage parasitaemia and gametocytaemia in children, pregnant women and adults, which was part of a bigger study that investigated some key factors that influence gametocyte carriage. RESULTS: Overall prevalence of heterozygous α-thalassaemia trait among all the groups was 39.0%, while 8.2% were homozygous alpha thalassaemia. Asexual parasite prevalence was significantly higher in children (P = 0.008) compared to adults and pregnant women. Of the asexual P. falciparum positive individuals, gametocyte prevalence was 38.5% (15/39) in children, 29.7% (11/37) in pregnant women and 17.4% (4/23) in adults. Heterozygous α-thalassaemic children were less likely to harbour asexual parasites, compared with normal and those deficient (OR = 0.52; 95% CI 0.28-0.97; P = 0.037) under the dominant model. These heterozygous children were also associated with reduced risk of parasitaemia compared to heterozygous adults and pregnant women. Children with heterozygous α-thalassaemia trait had reduced risk of asexual parasite carriage. There was however, no association between α-thalassaemia trait and risk of gametocyte carriage.


Asunto(s)
Portador Sano , Malaria Falciparum , Parasitemia , Plasmodium falciparum , Complicaciones Infecciosas del Embarazo , Talasemia alfa , Adolescente , Adulto , Anciano , Portador Sano/epidemiología , Portador Sano/parasitología , Niño , Preescolar , Femenino , Células Germinativas , Ghana/epidemiología , Humanos , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Parasitemia/epidemiología , Parasitemia/parasitología , Plasmodium falciparum/aislamiento & purificación , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/parasitología , Prevalencia , Reproducción Asexuada , Adulto Joven , Talasemia alfa/epidemiología , Talasemia alfa/genética
10.
Curr Ther Res Clin Exp ; 90: 9-15, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30766619

RESUMEN

Background: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. Objectives: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). Methods: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. Results: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). Conclusions: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population.

11.
BMJ Glob Health ; 3(5): e000999, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30397515

RESUMEN

Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multidrug resistance 1 (Pfmdr1) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of Pfmdr1 polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(s) of -0.083), compared with policies of AS-AQ or both AL and AS-AQ (median s=-0.035 and 0.021, p<0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times Pfmdr1 data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7-10 years after AL introduction. Observed rates of selection have implications for planning strategies to cycle drugs or use multiple first-line therapies to maintain drug efficacy.

12.
Malar J ; 17(1): 331, 2018 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-30223841

RESUMEN

BACKGROUND: The gametocyte stage of Plasmodium falciparum is considered an important target for disrupting malaria transmission. Indications are that various demographic groups, such as children and pregnant women may differ in risk of harbouring gametocytes, which may be crucial for targeted control. In this study, the relationship between the prevalence and multiplicity of P. falciparum, asexual parasite infections and gametocytaemia was assessed in three different demographic groups in an area of southern Ghana with low malaria endemicity. Levels of antibody responses to Pfs230 were also assessed as a proxy for the presence of gametocytes. METHODS: The study involved multiple cross-sectional sampling of children (N = 184, aged 2-15 years), male and non-pregnant female adults (N = 154, aged 16-65 years) and pregnant women (N = 125, aged 18-45 years) from Asutsuare in the Shai Osudoku District of Greater Accra Region in Ghana. Asexual parasitaemia was detected by microscopy and PCR, and gametocytaemia was assessed by Pfs25-real time PCR. Multiclonal P. falciparum infections were estimated by msp2 genotyping and an indirect ELISA was used to measure plasma IgG antibodies to Pfs230 antigen. RESULTS: Overall, children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults (17.4%). Multiplicity of infection observed amongst children (3.1) and pregnant women (3.9) were found to be significantly higher (P = 0.006) compared with adults (2.7). Risk of gametocyte carriage was higher in individuals infected with P. falciparum having both Pfmsp2 3D7 and FC27 parasite types (OR = 5.92, 95% CI 1.56-22.54, P = 0.009) compared with those infected with only 3D7 or FC27 parasite types. In agreement with the parasite prevalence data, anti-Pfs230 antibody levels were lower in gametocyte positive adults (ß = - 0.57, 95% CI - 0.81, - 0.34, P < 0.001) compared to children. CONCLUSIONS: These findings suggest that children and pregnant women are particularly important as P. falciparum submicroscopic gametocyte reservoirs and represent important focus groups for control interventions. The number of clones increased in individuals carrying gametocytes compared to those who did not carry gametocytes. The higher anti-gametocyte antibody levels in children suggests recent exposure and may be a marker of gametocyte carriage.


Asunto(s)
Portador Sano/epidemiología , Malaria Falciparum/epidemiología , Plasmodium falciparum/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Portador Sano/parasitología , Niño , Preescolar , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Ghana/epidemiología , Humanos , Inmunoglobulina G/sangre , Malaria Falciparum/parasitología , Masculino , Microscopía , Persona de Mediana Edad , Parasitemia/epidemiología , Parasitemia/parasitología , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/parasitología , Prevalencia , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Adulto Joven
13.
Malar J ; 17(1): 252, 2018 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-29976204

RESUMEN

BACKGROUND: Although the recent decline of malaria burden in some African countries has been attributed to a scale-up of interventions, such as bed nets (insecticide-treated bed nets, ITNs/long-lasting insecticidal nets, LLINs), the contribution of other factors to these changes has not been rigorously assessed. This study assessed the trends of Plasmodium falciparum prevalence in Magoda (1992-2017) and Mpapayu (1998-2017) villages of Muheza district, North-eastern Tanzania, in relation to changes in the levels of different interventions and rainfall patterns. METHODS: Individuals aged 0-19 years were recruited in cross-sectional surveys to determine the prevalence of P. falciparum infections in relation to different malaria interventions deployed, particularly bed nets and anti-malarial drugs. Trends and patterns of rainfall in Muheza for 35 years (from 1981 to 2016) were assessed to determine changes in the amount and pattern of rainfall and their possible impacts on P. falciparum prevalence besides of those ascribed to interventions. RESULTS: High prevalence (84-54%) was reported between 1992 and 2000 in Magoda, and 1998 and 2000 in Mpapayu, but it declined sharply from 2001 to 2004 (from 52.0 to 25.0%), followed by a progressive decline between 2008 and 2012 (to ≤ 7% in both villages). However, the prevalence increased significantly from 2013 to 2016 reaching ≥ 20.0% in 2016 (both villages), but declined in the two villages to ≤ 13% in 2017. Overall and age specific P. falciparum prevalence decreased in both villages over the years but with a peak prevalence shifting from children aged 5-9 years to those aged 10-19 years from 2008 onwards. Bed net coverage increased from < 4% in 1998 to > 98% in 2001 and was ≥ 85.0% in 2004 in both villages; followed by fluctuations with coverage ranging from 35.0 to ≤ 98% between 2008 and 2017. The 12-month weighted anomaly standardized precipitation index showed a marked rainfall deficit in 1990-1996 and 1999-2010 coinciding with declining prevalence and despite relatively high bed net coverage from 2000. From 1992, the risk of infection decreased steadily up to 2013 when the lowest risk was observed (RR = 0.07; 95% CI 0.06-0.08, P < 0.001), but it was significantly higher during periods with positive rainfall anomalies (RR = 2.79; 95% CI 2.23-3.50, P < 0.001). The risk was lower among individuals not owning bed nets compared to those with nets (RR = 1.35; 95% CI 1.22-1.49, P < 0.001). CONCLUSIONS: A decline in prevalence up to 2012 and resurgence thereafter was likely associated with changes in monthly rainfall, offset against changing malaria interventions. A sustained surveillance covering multiple factors needs to be undertaken and climate must be taken into consideration when relating control interventions to malaria prevalence.


Asunto(s)
Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Parasitemia/epidemiología , Parasitemia/prevención & control , Plasmodium falciparum/fisiología , Lluvia , Adolescente , Antimaláricos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Humanos , Lactante , Recién Nacido , Malaria Falciparum/parasitología , Parasitemia/parasitología , Prevalencia , Población Rural , Tanzanía/epidemiología
14.
Artículo en Inglés | MEDLINE | ID: mdl-29977533

RESUMEN

Background: Limited information regarding the clonality of circulating E. coli strains in tertiary care hospitals in low and middle-income countries is available. The purpose of this study was to determine the serotypes, antimicrobial resistance and virulence genes. Further, we carried out a phylogenetic tree reconstruction to determine relatedness of E. coli isolated from patients in a tertiary care hospital in Tanzania. Methods: E. coli isolates from inpatients admitted at Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced at KCMC hospital. Sequence analysis was done for identification of resistance genes, Multi-Locus Sequence Typing, serotyping, and virulence genes. Phylogeny reconstruction using CSI Phylogeny was done to ascertain E. coli relatedness. Stata 13 (College Station, Texas 77,845 USA) was used to determine Cohen's kappa coefficient of agreement between the phenotypically tested and whole genome sequence predicted antimicrobial resistance. Results: Out of 38 E. coli isolates, 21 different sequence types (ST) were observed. Eight (21.1%) isolates belonged to ST131; of which 7 (87.5.%) were serotype O25:H4. Ten (18.4%) isolates belonged to ST10 clonal complex; of these, four (40.0%) were ST617 with serotype O89:H10. Twenty-eight (73.7%) isolates carried genes encoding beta-lactam resistance enzymes. On average, agreement across all drugs tested was 83.9%. Trimethoprim/sulphamethoxazole (co-trimoxazole) showed moderate agreement: 45.8%, kappa =15% and p = 0.08. Amoxicillin-clavulanate showed strongest agreement: 87.5%, kappa = 74% and p = 0.0001. Twenty-two (57.9%) isolates carried virulence factors for host cells adherence and 25 (65.7%) for factors that promote E. coli immune evasion by increasing survival in serum. The phylogeny analysis showed that ST131 clustering close together whereas ST10 clonal complex had a very clear segregation of the ST617 and a mix of the rest STs. Conclusion: There is a high diversity of E. coli isolated from patients admitted to a tertiary care hospital in Tanzania. This underscores the necessity to routinely screen all bacterial isolates of clinical importance in tertiary health care facilities. WGS use for laboratory-based surveillance can be an effective early warning system for emerging pathogens and resistance mechanisms in LMICs.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Escherichia coli/epidemiología , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Hospitales/estadística & datos numéricos , Centros de Atención Terciaria/estadística & datos numéricos , Resistencia betalactámica/genética , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Estudios Transversales , Escherichia coli/clasificación , Escherichia coli/genética , Genoma Bacteriano/genética , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Tanzanía/epidemiología , Combinación Trimetoprim y Sulfametoxazol/farmacología , Factores de Virulencia , Secuenciación Completa del Genoma , beta-Lactamasas/genética
15.
Eur J Clin Microbiol Infect Dis ; 37(10): 1901-1914, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30030694

RESUMEN

This study aimed to use whole-genome sequencing to determine virulence and antimicrobial resistance genes in K. pneumoniae isolated from patients in a tertiary care hospital in Kilimanjaro. K. pneumoniae isolates from patients attending Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced and analysed locally. Sequence analysis was done for identification of virulence and AMR genes. Plasmid and multi-locus sequence typing and capsular or capsular (K) typing were performed and phylogeny was done to ascertain K. pneumoniae relatedness. Stata 13 (College Station, TX, 77845, USA) was used to determine Cohen's kappa coefficient of agreement between the phenotypically tested and sequence-predicted resistance. A total of 16 (47.1%) sequence types (STs) and 10 (29.4%) K types were identified in 30 (88.2%) and 17 (50.0%) of all analysed isolates, respectively. K. pneumoniae ST17 were 6 (17.6%). The commonest determinants were blaCTX-M-15 in 16 (47.1%) isolates, blaSHV in 30 (88.2%), blaOXA-1 in 8 (23.5%) and blaTEM-1 in 18 (52.9%) isolates. Resistance genes for aminoglycosides were detected in 21 (61.8%) isolates, fluoroquinolones in 13 (38.2%) and quinolones 34 (100%). Ceftazidime and ceftriaxone showed the strongest agreement between phenotype- and sequence-based resistance results: 93.8%, kappa = 0.87 and p = 0.0002. Yersiniabactin determinant was detected in 12 (35.3%) of K. pneumoniae. The proportion of AMR and virulence determinants detected in K. pneumoniae is alarming. WGS-based diagnostic approach has showed promising potentials in clinical microbiology, hospital outbreak source tracing virulence and AMR detection at KCMC.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Niño , Estudios Transversales , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Hospitales , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Plásmidos/genética , Tanzanía , Virulencia/genética , beta-Lactamasas/genética
16.
Biomed Res Int ; 2018: 2087693, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29487865

RESUMEN

Objective: To determine molecular epidemiology of methicillin-resistant S. aureus in Tanzania using whole genome sequencing. Methods: DNA from 33 Staphylococcus species was recovered from subcultured archived Staphylococcus isolates. Whole genome sequencing was performed on Illumina Miseq using paired-end 2 × 250 bp protocol. Raw sequence data were analyzed using online tools. Results: Full susceptibility to vancomycin and chloramphenicol was observed. Thirteen isolates (43.3%) resisted cefoxitin and other antimicrobials tested. Multilocus sequence typing revealed 13 different sequence types among the 30 S. aureus isolates, with ST-8 (n = seven, 23%) being the most common. Gene detection in S. aureus stains were as follows: mecA, 10 (33.3%); pvl, 5 (16.7%); tst, 2 (6.7%). The SNP difference among the six Tanzanian ST-8 MRSA isolates ranged from 24 to 196 SNPs and from 16 to 446 SNPs when using the USA300_FPR3757 or the USA500_2395 as a reference, respectively. The mutation rate was 1.38 × 10-11 SNPs/site/year or 1.4 × 10-6 SNPs/site/year as estimated by USA300_FPR3757 or the USA500_2395, respectively. Conclusion: S. aureus isolates causing infections in hospitalized patients in Moshi are highly diverse and epidemiologically unrelated. Temporal phylogenetic analysis provided better resolution on transmission and introduction of MRSA and it may be important to include this in future routines.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Antibacterianos/uso terapéutico , Cloranfenicol/uso terapéutico , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Epidemiología Molecular/métodos , Filogenia , Polimorfismo de Nucleótido Simple/genética , Infecciones Estafilocócicas/tratamiento farmacológico , Tanzanía/epidemiología , Centros de Atención Terciaria , Vancomicina/uso terapéutico , Secuenciación Completa del Genoma/métodos
17.
Am J Trop Med Hyg ; 98(6): 1714-1717, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29582732

RESUMEN

Data on prevalence of antimalarial molecular resistance markers in pregnant women in Ghana is scarce. Prevalence of single nucleotide polymorphisms/haplotypes in the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes was assessed in a cross-sectional study involving 200 pregnant women. Almost 90% of infections were wild type at the Pfcrt gene whereas the Pfmdr1 NFD mutant haplotype occurred in 43% of samples. Prevalence of Pfdhfr/Pfdhps quadruple mutation was 92.6% whereas Pfdfr/Pfdhps quintuple mutation with K540E was not observed. The study provides important updates of antimalarial resistance markers in Ghanaian pregnant women and suggests increased tolerance to one of the first-line treatment options in Ghana: artemether-lumefantrine. The data support the view that sulfadoxine-pyrimethamine is still efficacious for intermittent preventive treatment in Ghana, but the impact of increased doses on selection of mutations needs to be assessed. Continuing the surveillance of resistance markers is important to inform changes in antimalarial drug policy in pregnancy.


Asunto(s)
Antimaláricos/administración & dosificación , Resistencia a Medicamentos/genética , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Polimorfismo de Nucleótido Simple/genética , Combinación Arteméter y Lumefantrina/administración & dosificación , Artemisininas/administración & dosificación , Estudios Transversales , Combinación de Medicamentos , Femenino , Marcadores Genéticos/genética , Ghana/epidemiología , Haplotipos , Humanos , Recién Nacido , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/mortalidad , Proteínas de Transporte de Membrana/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Mutación , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/aislamiento & purificación , Embarazo , Proteínas Protozoarias/genética , Pirimetamina/administración & dosificación , Sulfadoxina/administración & dosificación , Tetrahidrofolato Deshidrogenasa/genética
18.
Malar J ; 17(1): 91, 2018 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-29471822

RESUMEN

BACKGROUND: Plasmodium falciparum malaria remains a major health burden and genomic research represents one of the necessary approaches for continued progress towards malaria control and elimination. Sample acquisition for this purpose is troublesome, with the majority of malaria-infected individuals living in rural areas, away from main infrastructure and the electrical grid. The aim of this study was to describe a low-tech procedure to sample P. falciparum specimens for direct whole genome sequencing (WGS), without use of electricity and cold-chain. METHODS: Venous blood samples were collected from malaria patients in Bandim, Guinea-Bissau and leukocyte-depleted using Plasmodipur filters, the enriched parasite sample was spotted on Whatman paper and dried. The samples were stored at ambient temperatures and subsequently used for DNA-extraction. Ratios of parasite:human content of the extracted DNA was assessed by qPCR, and five samples with varying parasitaemia, were sequenced. Sequencing data were used to analyse the sample content, as well as sample coverage and depth as compared to the 3d7 reference genome. RESULTS: qPCR revealed that 73% of the 199 samples were applicable for WGS, as defined by a minimum ratio of parasite:human DNA of 2:1. WGS revealed an even distribution of sequence data across the 3d7 reference genome, regardless of parasitaemia. The acquired read depths varied from 16 to 99×, and coverage varied from 87.5 to 98.9% of the 3d7 reference genome. SNP-analysis of six genes, for which amplicon sequencing has been performed previously, confirmed the reliability of the WGS-data. CONCLUSION: This study describes a simple filter paper based protocol for sampling P. falciparum from malaria patients for subsequent direct WGS, enabling acquisition of samples in remote settings with no access to electricity.


Asunto(s)
Desecación , Eritrocitos/parasitología , Plasmodium falciparum/genética , Manejo de Especímenes/métodos , Secuenciación Completa del Genoma/métodos , ADN Protozoario/química , ADN Protozoario/genética , ADN Protozoario/aislamiento & purificación , Guinea Bissau , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Temperatura
19.
Eur J Clin Microbiol Infect Dis ; 37(5): 897-906, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29464424

RESUMEN

Emergence and spread of extended spectrum beta-lactamase (ESBL)-producing gram-negative bacteria, mainly due to CTX-M, is a major global public health problem. Patients infected with ESBL-producing gram-negative bacteria have an increased risk of treatment failure and death. We investigated the prevalence and risk factors for CTX-M gram-negative bacteria isolated from clinical specimens of patients hospitalized at a tertiary care hospital in Kilimanjaro, Tanzania. Isolated gram-negative bacteria from inpatients admitted at Kilimanjaro Christian Medical Centre (KCMC) between August 2013 and August 2015 were fully genome sequenced. The prevalence of ESBL-producing gram-negative bacteria was determined based on the presence of blaCTX-M. The odds ratio (OR) and risk factors for ESBL-producing gram-negative bacteria due to CTX-M were assessed using logistic regression models. The overall CTX-M prevalence (95% CI) was 13.6% (10.1-18.1). Adjusted for other factors, the OR of CTX-M gram-negative bacteria for patients previously hospitalized was 0.26 (0.08-0.88), p = 0.031; the OR for patients currently on antibiotics was 4.02 (1.29-12.58), p = 0.017; the OR for patients currently on ceftriaxone was 0.14 (0.04-0.46), p = 0.001; and the OR for patients with wound infections was 0.24 (0.09-0.61), p = 0.003. The prevalence of ESBL-producing gram-negative bacteria due to CTX-M in this setting is relatively low compared to other previous reports in similar settings. However, to properly stop further spread in the hospital, we recommend setting up a hospital surveillance system that takes full advantage of the available next-generation sequencing facility to routinely screen for all types of bacterial resistance genes.


Asunto(s)
Infección Hospitalaria , Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Centros de Atención Terciaria , beta-Lactamasas/genética , Adulto , Comorbilidad , Estudios Transversales , Femenino , Genoma Bacteriano , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Vigilancia en Salud Pública , Factores de Riesgo , Tanzanía/epidemiología , Secuenciación Completa del Genoma , Resistencia betalactámica
20.
Emerg Infect Dis ; 24(3): 541-548, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29460743

RESUMEN

An influx of immigrants is contributing to the reemergence of Plasmodium vivax malaria in Greece; 1 persistent focus of transmission is in Laconia, Pelopónnese. We genotyped archived blood samples from a substantial proportion of malaria cases recorded in Greece in 2009-2013 using 8 microsatellite markers and a PvMSP-3α gene fragment and plotted their spatiotemporal distribution. High parasite genetic diversity with low multiplicity of infection was observed. A subset of genetically identical/related parasites was restricted to 3 areas in migrants and Greek residents, with some persisting over 2 consecutive transmission periods. We identified 2 hitherto unsuspected additional foci of local transmission: Kardhítsa and Attica. Furthermore, this analysis indicates that several cases in migrants initially classified as imported malaria were actually locally acquired. This study shows the potential for P. vivax to reestablish transmission and counsels public health authorities about the need for vigilance to achieve or maintain sustainable malaria elimination.


Asunto(s)
Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Plasmodium vivax/genética , Alelos , Variación Genética , Genoma de Protozoos , Genotipo , Geografía , Grecia/epidemiología , Historia del Siglo XXI , Humanos , Malaria Vivax/historia , Malaria Vivax/transmisión , Análisis Espacio-Temporal
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