RESUMO
BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).
Assuntos
Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
OBJECTIVE: The objective was to estimate the number of hospitalizations associated with influenza and RSV using data from severe acute respiratory infection (SARI) sentinel surveillance from El Alto-La Paz. Bolivia. METHODS: All persons who met the case definition for SARI at one sentinel hospital had a clinical sample collected and analyzed by rRT-PCR for influenza and by indirect immunofluorescence for RSV. The SARI-influenza and SARI-RSV case counts were stratified by six age groups. The proportion of cases captured in the sentinel hospital in relation to the non-sentinel hospitals of area was multiplied by the age-specific census population, to build the denominators. The annual incidence and a 95% confidence interval (CI) were estimated. RESULTS: During 2012-2017, n = 2606 SARI cases were reported (average incidence 120/100 000 inhabitants [95% CI: 116-124]); the average incidence of influenza-associated SARI hospitalization was 15.3/100 000 (95% CI: 14.1-16.7), and the average incidence of RSV-associated SARI hospitalization was 9/100 000 inhabitants (95% CI: 8.1-10.1). The highest incidence of influenza was among those less than one year of age (average 174.7/100 000 [range: 89.1-299.5]), followed by those one to four years of age (average 51.8/100 000 [range: 19.8-115.4]) and then those 65 years of age and older (average 47.7/100 000 [range: 18.8-117]). For RSV, the highest incidence was highest among those less than one year of age (231/100 000 [range: 119.9-322.9]). CONCLUSION: Influenza and RSV represent major causes of hospitalization in La Paz, Bolivia-with the highest burden among children under one year of age. Our estimates support current prevention strategies in this age group.
Assuntos
Hospitalização/estatística & dados numéricos , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vigilância de Evento Sentinela , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bolívia/epidemiologia , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of Plasmodium falciparum malaria. Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin. Lack of PfHRP2 protein through deletion of the pfhrp2 gene leads to false-negative RDT results for P. falciparum. We have evaluated the extent of pfhrp2 and pfhrp3 gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012. Pfhrp2 and pfhrp3 gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil. In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for pfhrp2 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of pfhrp2 gene deletion was only 3.3% (2 out of 60 patients). In isolates from Para state, all parasites were pfhrp2-positive. In contrast, we detected high proportions of isolates from all 3 states that were pfhrp3-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples). In Bolivia, only one of 25 samples (4%) tested had deleted pfhrp2 gene, while 68% (17 out of 25 samples) were pfhrp3-negative. Among the isolates tested, P. falciparum pfhrp2 gene deletions were present mainly in those from Acre State in the Brazilian Amazon. These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor pfhrp2 gene deletions in this and other parts of the Amazon region.
Assuntos
Antígenos de Protozoários/genética , Deleção de Genes , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Animais , Bolívia , Brasil , Humanos , Malária Falciparum/parasitologiaRESUMO
BACKGROUND: Chloroquine (CQ) over three days plus primaquine (PQ) for seven days is the treatment of choice of infections by Plasmodium vivax in Bolivia, where 95% of the cases of malaria are attributed to this species. The aim of this study was to evaluate the therapeutic efficacy of CQ in this setting. METHODS: Patients in the Amazon region of northern Bolivia, were included in the study from May to November 2011 and the therapeutic efficacy of CQ was evaluated over a 28-day follow-up period. Patients with P. vivax mono-infection received 25 mg/Kg body weight of CQ over three days. The concentrations of CQ + desethylchloroquine (DCQ) in blood were determined at days 7 and 28 of follow up; at follow-up and on the day of treatment failure was administered PQ. RESULTS: One hundred patients fulfilled the inclusion criteria, two were lost to follow up and another two were later excluded for protocol violation. Of the 96 patients who completed the follow up 10 showed TF; one presented continued parasitaemia until day 7 of follow up, three on day 21 and six on day 28 of follow up. The geometric mean of CQ + DCQ on day 7 was 321.7 ng/ml (range 197-535 ng/ml). In six patients with TF the CQ + DCQ concentrations in blood on the day of TF were >100 ng/ml. The rate of resistance was 6.5%. CONCLUSION: The present study demonstrates the presence of resistance to CQ in the treatment of malaria by P. vivax in the Amazon region of Bolivia. New clinical trials are needed to establish alternative treatments against these parasites in this region of South America.
Assuntos
Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Resistência a Medicamentos , Malária Vivax/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Adolescente , Adulto , Idoso , Bolívia , Criança , Pré-Escolar , Feminino , Humanos , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Adulto JovemRESUMO
INTRODUCTION: Few studies on the causes of the delay of malaria diagnosis and treatment in Bolivia are published. OBJECTIVE: To know the factors that delay malaria diagnosis and treatment of malaria in the public service of the town of Riberalta, Bolivia. MATERIALS AND METHODS: The times between the onset of symptoms and treatment, between the onset of symptoms and diagnosis and between the diagnosis and the start of treatment were calculated. The averages of the calculated times were compared with respect to the site of infection, parasite species, level of care, place of diagnosis and diagnostic method and th patient's age was correlated with the calculated times. RESULTS: Between January and December 2010, 2,482 positive valid cases were studied. An average of 4.16 days was found between the onset of symptoms and the start of treatment, the average time between the onset of symptoms and diagnosis was 4.07 days, and between diagnosis and the start of treatment 0.10 days. Statistically significant (p<0.05) differences were found for factors related to the delay of diagnosis such as place of diagnosis, site of infection, level of care, parasite species and diagnostic method. The analysis of covariance showed a statistical association with the level of care and the parasite species (p<0.05). CONCLUSION: The delay in malaria diagnosis is influenced by factors such as the site of infection, place of diagnosis, level of care, parasite species and diagnostic method.
Assuntos
Diagnóstico Tardio , Malária/diagnóstico , Malária/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bolívia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Introducción. La determinación de la eficacia de la cloroquina contra Plasmodium vivax permite mejorar la capacidad de vigilancia de la resistencia a los antipalúdicos. Objetivo. Evaluar la eficacia terapéutica de la cloroquina como tratamiento de malaria no complicadapor P. vivax en Riberalta, Guayaramerín y Yacuiba, Bolivia. Materiales y métodos. Se llevó a cabo un estudio de la eficacia in vivo en pacientes mayores de cinco años; se suministró cloroquina (25 mg/kg en tres días) y se hizo seguimiento por 28 días, midiendo los niveles de cloroquina en sangre y desetilcloroquina, el día dos y el día de registro de reaparición de parasitemia. Para la evaluación de la incidencia acumulada de falla del tratamiento, se usó el análisis de supervivencia de Kaplan-Meier. Resultados. Se estudiaron 223 pacientes (Riberalta, 84; Guayaramerín, 80; Yacuiba, 59). Las medias de densidad parasitaria (formas asexuadas) del día 0 en Riberalta fueron de 6.147, en Guayaramerín, 4.251, y en Yacuiba, 5.214 parásitos/μl de sangre. En el mismo orden, los promedios de concentraciones sanguíneas de cloroquina-desetilcloroquina del día 2 fueron de 783, 817 y 815 ng/ml. Mientras en Yacuiba no se presentaron fracasos terapéuticos, en Riberalta ocurrieron con frecuencia de 6,2 % y en Guayaramerín de 10 %. Los valores de cloroquina y desetilcloroquina en sangre de pacientes con fracaso terapéutico fueron menores de 70 ng/ml en el día de reaparición de parasitemia. Conclusión. No se evidenció resistencia de P. vivax a la cloroquina en las tres regiones de evaluación en Bolivia. Se requieren mayores estudios de la concentración de la cloroquina en sangre.
Introduction. Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. Objective. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. Materials and methods. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. Results. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Conclusion. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.
Assuntos
Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto Jovem , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Vivax/tratamento farmacológico , Parasitemia/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Antimaláricos/sangue , Bolívia/epidemiologia , Cloroquina/análogos & derivados , Cloroquina/sangue , Resistência a Medicamentos , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Carga Parasitária , Parasitemia/epidemiologia , Parasitemia/parasitologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/parasitologia , População RuralRESUMO
BACKGROUND: Ensuring the quality of malaria medicines is crucial in working toward malaria control and eventual elimination. Unlike other validated tests that can assess all critical quality attributes, which is the standard for determining the quality of medicines, basic tests are significantly less expensive, faster, and require less skilled labour; yet, these tests provide reproducible data and information on several critical quality attributes, such as identity, purity, content, and disintegration. Visual and physical inspection also provides valuable information about the manufacturing and the labelling of medicines, and in many cases this inspection is sufficient to detect counterfeit medicines. The Promoting the Quality of Medicines (PQM) programme has provided technical assistance to Amazon Malaria Initiative (AMI) countries to implement the use of basic tests as a key screening mechanism to assess the quality of malaria medicines available to patients in decentralized regions. METHODS: Trained personnel from the National Malaria Control Programmes (NMCPs), often in collaboration with country's Official Medicine Control Laboratory (OMCL), developed country- specific protocols that encompassed sampling methods, sample analysis, and data reporting. Sampling sites were selected based on malaria burden, accessibility, and geographical location. Convenience sampling was performed and countries were recommended to store the sampled medicines under conditions that did not compromise their quality. Basic analytical tests, such as disintegration and thin layer chromatography (TLC), were performed utilizing a portable mini-laboratory. RESULTS: Results were originally presented at regional meetings in a non-standardized format that lacked relevant medicines information. However, since 2008 information has been submitted utilizing a template specifically developed by PQM for that purpose. From 2005 to 2010, the quality of 1,663 malaria medicines from seven AMI countries was evaluated, mostly collected from the public sector, 1,445/1,663 (86.9%). Results indicate that 193/1,663 (11.6%) were found not to meet quality specifications. Most failures were reported during visual and physical inspection, 142/1663 (8.5%), and most of these were due to expired medicines, 118/142 (83.1%). Samples failing TLC accounted for 27/1,663 (1.6%) and those failing disintegration accounted for 24/1,663 (1.4%). Medicines quality failures decreased significantly during the last two years. CONCLUSIONS: Basic tests revealed that the quality of medicines in the public sector improved over the years, since the implementation of this type of quality monitoring programme in 2005. However, the lack of consistent confirmatory tests in the quality control (QC) laboratory, utilizing methods that can also evaluate additional quality attributes, could still mask quality issues. In the future, AMI countries should improve coordination with their health authorities and their QC lab consistently, to provide a more complete picture of malaria medicines quality and support the implementation of corrective actions. Facilities in the private and informal sectors also should be included when these sectors constitute an important source of medicines used by malaria patients.
Assuntos
Antimaláricos/farmacologia , Antimaláricos/normas , Técnicas de Química Analítica , Preparações Farmacêuticas/química , Preparações Farmacêuticas/normas , Antimaláricos/química , Humanos , Malária/tratamento farmacológico , Controle de Qualidade , América do SulRESUMO
Introducción. Se publican pocos estudios sobre las causas del retardo del diagnóstico y el tratamiento de la malaria en Bolivia. Objetivo. Conocer los factores que retardan el diagnóstico y el tratamiento de la malaria en el servicio público del municipio de Riberalta, Bolivia. Materiales y métodos. Se calcularon los tiempos transcurridos entre el inicio de los síntomas y el tratamiento, entre el inicio de los síntomas y el diagnóstico, y entre el diagnóstico y el inicio del tratamiento; se compararon las medias de los tiempos calculados con el lugar de infección, la especie parasitaria, el nivel de atención, el lugar y el método de diagnóstico, y la edad se correlacionó con los tiempos calculados. Resultados. De 2.482 casos positivos válidos evaluados entre enero y diciembre de 2010, se encontró una media de 4,16 días entre el inicio de los síntomas y el inicio del tratamiento, de 4,07 días entre el inicio de los síntomas y el diagnóstico, y de 0,10 días entre el diagnóstico y el tratamiento. El retardo del diagnóstico y los factores, lugar de diagnóstico, lugar de infección, nivel de atención, especie parasitaria y método de diagnóstico, mostraron una diferencia estadística significativa (p<0,05). En el análisis de la covarianza se observó una asociación estadística con el nivel de atención y la especie parasitaria (p<0,05) Conclusión. Existe un retardo en el diagnóstico de la malaria, lo cual es influenciado por factores como el lugar de infección, lugar del diagnóstico, nivel de atención, especie parasitaria y método de diagnóstico.
Introduction. Few studies on the causes of the delay of malaria diagnosis and treatment in Bolivia are published. Objective. To know the factors that delay malaria diagnosis and treatment of malaria in the public service of the town of Riberalta, Bolivia. Materials and methods. The times between the onset of symptoms and treatment, between the onset of symptoms and diagnosis and between the diagnosis and the start of treatment were calculated. The averages of the calculated times were compared with respect to the site of infection, parasite species, level of care, place of diagnosis and diagnostic method and th patient’s age was correlated with the calculated times. Results. Between January and December 2010, 2,482 positive valid cases were studied. An average of 4.16 days was found between the onset of symptoms and the start of treatment, the average time between the onset of symptoms and diagnosis was 4.07 days, and between diagnosis and the start of treatment 0.10 days. Statistically significant (p<0.05) differences were found for factors related to the delay of diagnosis such as place of diagnosis, site of infection, level of care, parasite species and diagnostic method. The analysis of covariance showed a statistical association with the level of care and the parasite species (p<0.05). Conclusion. The delay in malaria diagnosis is influenced by factors such as the site of infection, place of diagnosis, level of care, parasite species and diagnostic method.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Diagnóstico Tardio , Malária/diagnóstico , Malária/terapia , Bolívia , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. OBJECTIVE: The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. MATERIALS AND METHODS: An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. RESULTS: The mean parasitemias (asexual) on day 0 were 6,147 parasites/µl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. CONCLUSION: Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.