Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for screening malaria in peripheral and placental blood samples from pregnant women in Colombia.

BACKGROUND: Pregnant women frequently show low-density Plasmodium infections that require more sensitive methods for accurate diagnosis and early treatment of malaria. This is particularly relevant in low-malaria transmission areas, where intermittent preventive treatment is not recommended. Molecular methods, such as polymerase chain reaction (PCR) are highly sensitive, but require sophisticated equipment and advanced training. Instead, loop mediated isothermal amplification (LAMP) provides an opportunity for molecular detection of malaria infections in remote endemic areas, outside a reference laboratory. The aim of the study is to evaluate the performance of LAMP for the screening of malaria in pregnant women in Colombia. METHODS: This is a nested prospective study that uses data and samples from a larger cross-sectional project conducted from May 2016 to January 2017 in three Colombian endemic areas (El Bagre, Quibdó, and Tumaco). A total of 531 peripheral and placental samples from pregnant women self-presenting at local hospitals for antenatal care visits, at delivery or seeking medical care for suspected malaria were collected. Samples were analysed for Plasmodium parasites by light microscopy (LM), rapid diagnostic test (RDT) and LAMP. Diagnostic accuracy endpoints (sensitivity, specificity, predictive values, and kappa scores) of LM, RDT and LAMP were compared with nested PCR (nPCR) as the reference standard. RESULTS: In peripheral samples, LAMP showed an improved sensitivity (100.0%) when compared with LM 79.5% and RDT 76.9% (p < 0.01), particularly in afebrile women, for which LAMP sensitivity was two-times higher than LM and RDT. Overall agreement among LAMP and nPCR was high (kappa value = 1.0). Specificity was similar in all tests (100%). In placental blood, LAMP evidenced a four-fold improvement in sensitivity (88.9%) when compared with LM and RDT (22.2%), being the only method, together with nPCR, able to detect placental infections in peripheral blood. CONCLUSIONS: LAMP is a simple, rapid and accurate molecular tool for detecting gestational and placental malaria, being able to overcome the limited sensitivity of LM and RDT. These findings could guide maternal health programs in low-transmission settings to integrate LAMP in their surveillance systems for the active detection of low-density infections and asymptomatic malaria cases.

[Pathogenic mechanisms in Plasmodium falciparum malaria]. / Mecanismos de patogenia en la malaria por Plasmodium falciparum.

The most recognized pathogenic mechanisms of the infection with Plasmodium falciparum, during both the erythrocytic and exo-erythrocytic stages are presented. Vascular obstruction explained by the sequestration of parasitized red blood cells and erythrocyte rosetting, mediated by different endothelial ligands and receptors, in addition to the inflammatory processes induced by the presence of the parasite, are central aspects in the pathogenesis of malaria that explain the processes of damage, dysfunction and cell death in various organs. Alterations such as increased vascular permeability, hypoxia and anaerobic metabolism leading to localized lesions in organs such as brain and lung, as well as to a generalized acidotic state with multisystem failure can be explained by events such as the injury and destruction of erythrocytes, hepatocytes and endothelial cells, the loss of endothelial integrity, and the activation of cell damage and apoptosis promoters.

Mecanismos de patogenia en la malaria por Plasmodium falciparum / Pathogenic mechanisms in Plasmodium falciparum malaria

Se presentan los mecanismos patogénicos más conocidos en la infección por Plasmodium falciparum durante la fase eritrocitaria y extraeritrocitaria. La obstrucción vascular, explicada por los fenómenos de secuestro de glóbulos rojos parasitados y la formación de rosetas, mediados por diversos ligandos y receptores endoteliales, además de los procesos inflamatorios instaurados ante la presencia del parásito, son aspectos centrales en la patogenia de la malaria que permiten explicar. A partir de eventos como la lesión y la destrucción de eritrocitos, hepatocitos y células endoteliales, la pérdida de integridad del endotelio y la activación de promotores de daño celular y de apoptosis, se explican alteraciones como el aumento de la permeabilidad vascular, la hipoxia y el metabolismo anaerobio, que conducen tanto a lesiones localizadas en órganos como cerebro y pulmón, como a un estado de acidosis generalizada y falla multisistémica.

The most recognized pathogenic mechanisms of the infection with Plasmodium falciparum, during both the erythrocytic and exo-erithrocytic stages are presented. Vascular obstruction explained by the sequestration of parasitized red blood cells and erythrocyte rosetting, mediated by different endothelial ligands and receptors, in addition to the inflammatory processes induced by the presence of the parasite, are central aspects in the pathogenesis of malaria that explain the processes of damage, dysfunction and cell death in various organs. Alterations such as increased vascular permeability, hypoxia and anaerobic metabolism leading to localized lesions in organs such as brain and lung, as well as to a generalized acidotic state with multisystem failure can be explained by events such as the injury and destruction of erythrocytes, hepatocytes and endothelial cells, the loss of endothelial integrity, and the activation of cell damage and apoptosis promoters.

Malaria-related anaemia: a Latin American perspective.

Malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. It mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. Although the contribution of the American continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. On the African continent, where Plasmodium falciparum is the most prevalent human malaria parasite, anaemia is responsible for about half of the malaria-related deaths. Conversely, in Latin America (LA), malaria-related anaemia appears to be uncommon, though there is a limited knowledge about its real prevalence. This may be partially explained by several factors, including that the overall malaria burden in LA is significantly lower than that of Africa, that Plasmodium vivax, the predominant Plasmodium species in the region, appears to display a different clinical spectrus and most likely because better health services in LA prevent the development of severe malaria cases. With the aim of contributing to the understanding of the real importance of malaria-related anaemia in LA, we discuss here a revision of the available literature on the subject and the usefulness of experimental animal models, including New World monkeys, particularly for the study of the mechanisms involved in the pathogenesis of malaria.

Congenital malaria in Urabá, Colombia.

BACKGROUND: Congenital malaria has been considered a rare event; however, recent reports have shown frequencies ranging from 3% to 54.2% among newborns of mothers who had suffered malaria during pregnancy. There are only a few references concerning the epidemiological impact of this entity in Latin-America and Colombia. OBJECTIVE: The aim of the study was to measure the prevalence of congenital malaria in an endemic Colombian region and to determine some of its characteristics. METHODS: A prospective, descriptive study was carried out in the mothers who suffered malaria during pregnancy and their newborns. Neonates were clinically evaluated at birth and screened for Plasmodium spp. infection by thick smear from the umbilical cord and peripheral blood, and followed-up weekly during the first 21 days of postnatal life through clinical examinations and thick smears. RESULTS: 116 newborns were included in the study and 80 umbilical cord samples were obtained. Five cases of congenital infection were identified (four caused by P. vivax and one by P. falciparum), two in umbilical cord blood and three in newborn peripheral blood. One case was diagnosed at birth and the others during follow-up. Prevalence of congenital infection was 4.3%. One of the infected newborns was severely ill, while the others were asymptomatic and apparently healthy. The mothers of the newborns with congenital malaria had been diagnosed with malaria in the last trimester of pregnancy or during delivery, and also presented placental infection. CONCLUSIONS: Congenital malaria may be a frequent event in newborns of mothers who have suffered malaria during pregnancy in Colombia. An association was found between congenital malaria and the diagnosis of malaria in the mother during the last trimester of pregnancy or during delivery, and the presence of placental infection.

Malaria-related anaemia: a Latin American perspective

Malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. It mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. Although the contribution of the American continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. On the African continent, where Plasmodium falciparum is the most prevalent human malaria parasite, anaemia is responsible for about half of the malaria-related deaths. Conversely, in Latin America (LA), malaria-related anaemia appears to be uncommon, though there is a limited knowledge about its real prevalence. This may be partially explained by several factors, including that the overall malaria burden in LA is significantly lower than that of Africa, that Plasmodium vivax, the predominant Plasmodium species in the region, appears to display a different clinical spectrus and most likely because better health services in LA prevent the development of severe malaria cases. With the aim of contributing to the understanding of the real importance of malaria-related anaemia in LA, we discuss here a revision of the available literature on the subject and the usefulness of experimental animal models, including New World monkeys, particularly for the study of the mechanisms involved in the pathogenesis of malaria.

Ictericia y hepatopatía en el paciente con malaria / Jaundice and hepatopathy in patients with malaria

La ictericia es un hallazgo frecuente en el paciente con malaria. Según la Organización Mundial de la Salud, se considera un signo de peligro cuando se acompaña de aumento importante de las bilirrubinas y comúnmente se relaciona con disfunción hepática y lesión de otros sistemas. La lesión hepática en estos pacientes es frecuente, está asociada a otras complicaciones, y es reversible si se identifica y se trata a tiempo. Con este trabajo se pretende revisar el valor semiológico de la ictericia como indicador de malaria complicada, explicar su patogénesis y los mecanismos de daño hepático; además, hacer un enfoque del paciente con hepatopatía palúdica, diferenciando la disfunción hepática de la falla y la encefalopatía hepáticas.

Jaundice is a common finding in malaria patients. According to the World Health Organization, it is considered a sign of danger when accompanied by an important increase of bilirubin and it is frequently related to hepatic dysfunction and injury to other organs. Liver injury in these patients is common and it is associated with other complications. If it is identified and treated early, it is reversible. This paper reviews the semiological value of jaundice as an indicator of complicated malaria; it explains its pathogenesis and the mechanisms of liver damage. It also focuses on the patient with hepathopathy, distinguishing hepatic dysfunction, hepatic failure and hepatic encephalopathy.

Dynamics of Plasmodium falciparum parasitemia regarding combined treatment regimens for acute uncomplicated malaria, Antioquia, Colombia.

Selecting suitable anti-malarial treatment represents one of the best tools for reducing morbidity and mortality caused by this disease. Sexual and asexual parasite dynamics were thus evaluated in patients involved in antimalarial drug efficacy studies by using combined treatment with and without artemisinin derivatives for treating uncomplicated acute Plasmodium falciparum malaria in Antioquia, Colombia. All treatment doses were supervised and administered according to patients' weight; sexual and asexual parasitemia were evaluated during 28- or 42-days follow-up in 468 patients. Artemisinin-based combination therapy showed greater parasiticidal ability, showing a mean asexual parasitemia survival rate of one day and mean gametocyte survival rate of 1-2 days. Sexual and asexual parasitemias were eliminated more quickly and effectively in the group receiving artemisinin-based combination therapy. Adding 45 mg of primaquine to treatment with artesunate and mefloquine reduced gametocyte and asexual parasite survival by one day.

Signos de peligro en el paciente con malaria / Danger signs in the malaria patient

Los signos de peligro son hallazgos clínicos que indican gravedad o que tienen utilidad para el pronóstico de complicación o muerte. En el paciente con malaria, o paludismo, se presentan signos clínicos o parasitológicos que pueden reconocerse fácilmente durante la fase aguda de la enfermedad y son indicadores del inicio de una complicación. Entre los signos de peligro que puede presentar el paciente con malaria se incluyen cambios neurológicos, alteraciones del patrón respiratorio, vómito y diarrea persistentes, ictericia, sangrados, orina oscura, llenado capilar lento, palidez intensa, hiperpirexia, hiperparasitemia y esquizontemia. Su reconocimiento oportuno contribuirá a la disminución de complicaciones y muertes.

Danger signs are clinical indicators of severity and are useful to predict complications or death. In the malaria patient, clinical or parasitological signs can be easily be recognized during the acute phase of the illness that indicate serious complications. Danger signs include neurological change, abnormal breathing pattern, persistent vomiting and diarrhea, jaundice, bleeding, dark urine, delayed capillary refill, intense pallor, hyperpyrexia, hyperparasitemia and schizontemia. Timely recognition of these signs can lead to a decrease in cases with complications and deaths.

Estudio piloto de la eficacia y de los efectos sobre los gametocitos del esquema artesunato-mefloquina-primaquina para la malaria por Plasmodium falciparum / Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development

Introducción. El tratamiento de la malaria por P. falciparum requiere de un esquema seguro, eficaz y de impacto en la transmisión. En 2006, se implementó en Antioquia el esquema artesunato-mefloquina y se adicionó primaquina para eliminar los gametocitos. Objetivo. Evaluar la eficacia y acción gametocida de los esquemas artesunato-mefloquina-primaquina y artesunato-mefloquina en pacientes con malaria no complicada por P. falciparum de Turbo, Antioquia. Materiales y métodos. Ensayo clínico aleatorio; los tratamientos se suministraron de forma supervisada y se realizó seguimiento clínico-parasitológico en los días 1, 2, 3, 7, 14, 21, 28, 35, y 42, para evaluar la respuesta según el protocolo OMS-2003 modificado. Resultados. Entre abril de 2007 y febrero de 2008, 50 pacientes fueron reclutados; los resultados mostraron una eficacia de 100% (IC95% 86,3%-100%) para el esquema artesunato-mefloquina (con/sin primaquina); la parasitemia y la fiebre fueron eliminadas completamente al tercer día de tratamiento en todos los pacientes. La eliminación de gametocitos fue mayor con el uso de primaquina; al tercer día de seguimiento, el 92% (IC95% 74%-99%) de los pacientes que recibieron primaquina no tuvieron gametocitos, en comparación con 78,3% (IC95% 59%-93%) de pacientes del grupo artesunato-mefloquina. Además, el esquema artesunato-mefloquina-primaquina eliminó la gametocitemia una semana antes que el esquema sin primaquina. Conclusión. Se recomienda el uso del esquema artesunato-mefloquina para la malaria por P. falciparum por su alta eficacia y se sugieren futuras evaluaciones del beneficio de la PQ en la reducción de la densidad y prevalencia de gametocitos.

Introduction. The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream. Objective. The efficacy and gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and AS-MQ, in patients with uncomplicated P. falciparum malaria. Materials and methods. Between April 2007 and February 2008, 50 patients were recruited for the trial in Turbo, Antioquia. A randomized clinical trial was conducted. Treatment compliance was supervised, with a clinical and parasitological assessment on days 1, 2, 3, 7, 14, 21, 28, 35, and 42 to evaluate response rate according to the WHO 2003 protocol. Results. Clinical response and parasite elimination efficacy of AS-MQ (with or without PQ) was 100% (95% CI 86.3%-100%), and parasitemia and fever were absent on day 3 of treatment in all patients. Gametocyte elimination was superior when PQ was used--92% (95% CI: 74%-99%) of patients who received PQ had no gametocytes on day 3, compared to 78.3% (95% CI: 59%-93%) of patients who only received AS-MQ. Furthermore, circulating gametocytes were eliminated on average one week faster when the AS-MQ-PQ treatment scheme was used compared to the scheme without PQ. Conclusion. These studies recommend the use of AS-MQ to treat P. falciparum malaria given its good therapeutic efficacy. However, further assessment is suggested concerning the benefit of adding PQ to this treatment scheme.

[Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development]. / Estudio piloto de la eficacia y de los efectos sobre los gametocitos del esquema artesunato-mefloquina-primaquina para la malaria por Plasmodium falciparum.

INTRODUCTION: The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream. OBJECTIVE: The efficacy and gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and AS-MQ, in patients with uncomplicated P. falciparum malaria. MATERIALS AND METHODS: Between April 2007 and February 2008, 50 patients were recruited for the trial in Turbo, Antioquia. A randomized clinical trial was conducted. Treatment compliance was supervised, with a clinical and parasitological assessment on days 1, 2, 3, 7, 14, 21, 28, 35, and 42 to evaluate response rate according to the WHO 2003 protocol. RESULTS: Clinical response and parasite elimination efficacy of AS-MQ (with or without PQ) was 100% (95% CI 86.3%-100%), and parasitemia and fever were absent on day 3 of treatment in all patients. Gametocyte elimination was superior when PQ was used--92% (95% CI: 74%-99%) of patients who received PQ had no gametocytes on day 3, compared to 78.3% (95% CI: 59%-93%) of patients who only received AS-MQ. Furthermore, circulating gametocytes were eliminated on average one week faster when the AS-MQ-PQ treatment scheme was used compared to the scheme without PQ. CONCLUSION: These studies recommend the use of AS-MQ to treat P. falciparum malaria given its good therapeutic efficacy. However, further assessment is suggested concerning the benefit of adding PQ to this treatment scheme.

[Danger signs in the malaria patient]. / Signos de peligro en el paciente con malaria.

Danger signs are clinical indicators of severity and are useful to predict complications or death. In the malaria patient, clinical or parasitological signs can be easily be recognized during the acute phase of the illness that indicate serious complications. Danger signs include neurological change, abnormal breathing pattern, persistent vomiting and diarrhea, jaundice, bleeding, dark urine, delayed capillary refill, intense pallor, hyperpyrexia, hyperparasitemia and schizontemia. Timely recognition of these signs can lead to a decrease in cases with complications and deaths.

[Polymorphisms of the pfmdr1 gene in field samples of Plasmodium falciparum and their association with therapeutic response to antimalarial drugs and severe malaria in Colombia]. / Polimorfismos del gen pfmdr1 en muestras clínicas de Plasmodium falciparum y su relación con la respuesta terapéutica a antipalúdicos y paludismo grave en Colombia.

INTRODUCTION: The pfmdr1 gene of Plasmodium falciparum has been described as a gene conferring resistance to several antimalarial drugs. In particular, polymorphisms on specific codons have been associated with resistance and treatment failure with cloroquine, amodiaquine and mefloquine. However, the role of these polymorphisms in treatment response to antimalarials remains unexplored in Colombia. Furthermore, the relationship of these polymorphisms to severe malaria is unknown. OBJECTIVE: This work studied the association of the Asn 86Tyr and Asp1246Tyr pfmdr1 polymorphisms with response to cloroquine, amodiaquine and mefloquine treatment in three municipalities of Antioquia, and severe malaria cases from the municipality Tumaco. MATERIALS AND METHODS: The polymorphisms were assessed by nucleic acid amplification followed by restriction length polymorphism analysis. RESULTS: The wild-type codon Asn 86 was detected in 97% of the clinical samples from the treatment response study. No association was detected between this polymorphism and treatment failure to the three antimalarials administered. The 1246Tyr polymorphism was detected with a higher frequency in the samples from Antioquia 92% (130/141) than in those from Tumaco 22% (20/89). However, again, no association was found between the presence of a specific polymorphism and the presence of severe malaria in the municipality of Tumaco. CONCLUSIONS: The 86Tyr and 1246Tyr polymorphisms of the pfmdr1 gene are not useful as predictors of treatment failure or severe malaria in the municipalities studied. In addition, we report for the first time, the presence of the mutant codon 86Tyr in field samples in South America.

Polimorfismos del gen pfmdr1 en muestras clínicas de Plasmodium falciparum y su relación con la respuesta terapéutica a antipalúdicos y paludismo grave en Colombia / Polymorphisms of the pfmdr1 gene in field samples of Plasmodium falciparum and their association with therapeutic response to antimalarial drugs and severe malaria in Colombia

Introducción. El gen pfmdr1 de Plasmodium falciparum se describió como un gen de resistencia a diversos antipalúdicos. Sin embargo, no se han estudiado el papel de su polimorfismo en la respuesta terapéutica al tratamiento con antipalúdicos en Colombia, ni su relación con paludismo grave. Objetivos. Este trabajo determinó la asociación entre los polimorfismos Asn86Tir y Asp1246Tir del gen pfmdr1 con la respuesta terapéutica a cloroquina, amodiaquina y mefloquina, en tres municipios antioqueños, y la asociación de estos polimorfismos con paludismo grave en muestras de pacientes del municipio de Tumaco. Materiales y métodos. Los polimorfismos del gen pfmdr1 se determinaron mediante amplificación de ácidos nucleicos y análisis con enzimas de restricción. Resultados. El alelo silvestre Asn86 se encontró en 97 por ciento (137/141) de las muestras en el estudio de respuesta terapéutica a cloroquina, amodiaquina y mefloquina; no se observó ninguna asociación entre su presencia y la falla terapéutica como sí lo reportan otros autores. El alelo 1246Tir se encontró en una alta proporción en el estudio de respuesta terapéutica, tanto en las muestras del día cero como en los del día de la falla después del tratamiento con los antipalúdicos. Conclusiones. Los polimorfismos 86Tir y 1246Tir en el gen pfmdr1 no son útiles como factores de predicción de falla terapéutica o paludismo grave en los municipios estudiados. Este estudio describe por primera vez la presencia del alelo 86Tir en cuatro muestras clínicas de Suramérica.

Introduction. The pfmdr1 gene of Plasmodium falciparum has been described as a gene conferring resistance to several antimalarial drugs. In particular, polymorphisms on specific codons have been associated with resistance and treatment failure with cloroquine, amodiaquine and mefloquine. However, the role of these polymorphisms in treatment response to antimalarials remains unexplored in Colombia. Furthermore, the relationship of these polymorphisms to severe malaria is unknown. Objective. This work studied the association of the Asn86Tyr and Asp1246Tyr pfmdr1 polymorphisms with response to cloroquine, amodiaquine and mefloquine treatment in three municipalities of Antioquia, and severe malaria cases from the municipality Tumaco. Materials and methods.The polymorphisms were assessed by nucleic acid amplification followed by restriction length polymorphism analysis. Results. The wild-type codon Asn86 was detected in 97% of the clinical samples from the treatment response study. No association was detected between this polymorphism and treatment failure to the three antimalarials administered. The 1246Tyr polymorphism was detected with a higher frequency in the samples from Antioquia 92% (130/141) than in those from Tumaco 22% (20/89). However, again, no association was found between the presence of a specific polymorphism and the presence of severe malaria in the municipality of Tumaco. Conclusions. The 86Tyr and 1246Tyr polymorphisms of the pfmdr1 gene are not useful as predictors of treatment failure or severe malaria in the municipalities studied. In addition, we report for the first time, the presence of the mutant codon 86Tyr in field samples in South America.

Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia.

Plasmodium vivax malaria is an important cause of morbidity in Central and South America. In Colombia, this is the most prevalent malaria infection, representing 75% of the reported cases. To define the efficacy of the chloroquine and primaquine regimen to eliminate hypnozoites and prevent relapses, we conducted a random controlled clinical trial of three primaquine regimens in an open-label study. We evaluated the anti-relapse efficacy of total primaquine doses of 45, 105, and 210 mg administered at a dosage of 15 mg/day in 210 adults with P. vivax infection from the northwestern region of Colombia. Cure rates for blood-stage P. vivax malaria by day 28 of follow-up were 100% in all groups. Post-treatment reappearance of parasitemia during the six months of follow-up was 45%, 36.6% and 17.6%, respectively, for each group. When compared with other groups, administration of 210 mg was a significant protection factor for reappearance of parasitemia in a malaria-endemic area.

Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia.

OBJECTIVE: Evaluate the frequency of failure of eight treatments for non-complicated malaria caused by Plasmodium falciparum in patients from Turbo (Urabá region), El Bagre and Zaragoza (Bajo Cauca region), applying the 1998 protocol of the World Health Organization (WHO). Monotherapies using chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ) and sulphadoxine-pyrimethamine (SP), and combinations using chloroquine-sulphadoxine-pyrimethamine (CQ-SP), amodiaquine-sulphadoxine-pyrimethamine (AQ-SP), mefloquine-sulphadoxine-pyrimethamine (MQ-SP) and artesunate-sulphadoxine-pyrimethamine (AS-SP), were examined. METHODOLOGY: A balanced experimental design with eight groups. Samples were selected based on statistical and epidemiological criteria. Patients were followed for 21 to 28 days, including seven or eight parasitological and clinical evaluations, with an active search for defaulting patients. A non-blinded evaluation of the antimalarial treatment response (early failure, late failure, adequate response) was performed. RESULTS: Initially, the loss of patients to follow-up was higher than 40%, but the immediate active search for the cases and the monetary help for transportation expenses of patients, reduced the loss to 6%. The treatment failure was: CQ 82%, AQ 30%, MQ 4%, SP 24%, CQ-SP 17%, AQ-SP 2%, MQ-S-P 0%, AS-SP 3%. CONCLUSION: The characteristics of an optimal epidemiological monitoring system of antimalarial treatment response in Colombia are discussed. It is proposed to focus this on early failure detection, by applying a screening test every two to three years, based on a seven to 14-day follow-up. Clinical and parasitological assessment would be carried out by a general physician and a field microscopist from the local hospital, with active measures to search for defaulter patients at follow-up.

[Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium falciparum malaria, Antioquia, Colombia, 2002]. / Eficacia terapéutica de tres esquemas de tratamiento de malaria no complicada por Plasmodium falciparum, Antioquia, Colombia, 2002.

High resistance of Plasmodium falciparum malaria to chloroquine poses malaria as a major public health problem in Colombia. In this context, the therapeutic response of uncomplicated P. falciparum malaria patients to chloroquine (CQ), sulfadoxine/pirymethamine (SDXP) and combined therapy (SDXP/CQ) was evaluated according to the WHO/PAHO protocols of 1998. The comparisons were based on a sample of 160 patients with uncomplicated P. falciparum malaria in Turbo and Zaragoza (Antioquia, Colombia). Patients were randomly assigned each of the treatment categories. The results were statistically similar in each municipality. In Turbo percentage of treatment failure was 87.5%, 22.2% and 22.6% for CQ, SDXP and SDXP/CQ, respectively, whereas in Zaragoza, the corresponding treatment failure was 77.7%, 26.5% and 12.1%. During follow up, 50% of subjects with late treatment failure were asymptomatic in Turbo, while 33.3% were asymptomatic in Zaragoza. A high level of treatment failure occurred with CQ monotherapy, while SDXP and SDXP/CQ had acceptable levels of failure, i.e., below 25%. The high percentage of late treatment failure in asymptomatic patients may contribute to increased risk of persistent transmission.

Eficacia terapéutica de tres esquemas de tratamiento de malaria no complida por Plasmodium falciparum, Antioquia, Colombia, 2002 / Therapeutic efficacy of three treatment schemes in uncomplicated Plamodium falciparum malaria in Antioquia, Colombia, 2002

La resistencia a medicamentos antimaláricos aumenta la carga de malaria en un país. En Colombia, la situación de los antimaláricos es apremiante dada la alta resistencia de Plasmodium falciparum a la cloroquina y la escasez mundial de amodiaquina. Ante este panorama, se evaluó la respuesta terapéutica a sulfadoxina/pirimetamina (SDXP) y cloroquina (CQ) como monoterapias y en combinación para el tratamiento de malaria no complicada por P. falciparum, aplicando el protocolo de OMS/OPS 1998, en Turbo y Zaragoza, dos municipios de Antioquía, Colombia. Se diseñó una muestra para grupos balanceados y los pacientes fueron asignados aleatoriamente a los grupos de tratamiento. Se evaluaron 160 pacientes con malaria por P. falciparum sin complicaciones. La distribución de pacientes de ambos municipios en cada grupo de tratamiento fue estadísticamente similar en la mayoría de variables. En Turbo hubo un porcentaje de falla terapéutica de 87,5 por ciento a CQ, 22,2 por ciento a SDXP y de 22,6 por ciento a la combinación, mientras en Zaragoza la falla terapéutica fue de 77 por ciento a CQ, 26,5 por ciento a SDXP y 12,1 por ciento a SDXP/CQ. Durante el seguimiento, 50 por ciento y 33,3 por ciento de los pacientes con falla terapéutica tardía en Turbo y Zaragoza, respectivamente, fueron asintomáticos. Este estudio encontró un alto nivel de falla terapéutica con CQ en ambos municipios, mientras la SDXP y la combinación mostraron niveles de falla cercanos al 25 por ciento. Es de anotar el hallazgo de pacientes con falla tardía parasitológica y el riesgo que significa esta situación en la permanencia de la transmisión.

Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001.

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for > 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm3. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.

Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65 percent of the studied individuals were men and their mean age was 23. Of all individuals 59 percent had lived in the region for > 1 year and 91 percent were resident in the rural area. 42 percent were farmers and 35 percent had a history of malaria. The mean parasitaemia was 5865 parasites/mm . The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91 percent of the cases while the most frequent signs were palmar pallor (46 percent), jaundice (15 percent), hepatomegaly (17 percent), and spleen enlargement (12 percent). Anemia was found in 39 percent of the women and in 51 percent of the men, 8 percent of individuals had thrombocytopaenia and 41 percent had hypoglycemia