Enfoque terapéutico profiláctico para reducir la morbilidad por paludismo en la mujer embarazada / Prophylactic therapeutic approach to reduce malaria morbidity among pregnant women

Introducción: La infección por malaria durante el embarazo es un importante problema de salud en la mayoría de las regiones tropicales. Esta condición puede tener incidencia negativa tanto en la gestante como en el feto. Objetivo: Indagar en el impacto del tratamento preventivo intermitente con el medicamento antimalárico sulfadoxina-pirimetamina en la mujer embarazada. Métodos: Se realizó una revisión bibliográfica en la base de datos Medline/Pub Med y en artículos relevantes relacionados al tema de los últimos cinco años. Además, se tomó como referencia las guías para el tratamiento de malaria de la Organización Mundial de la Salud, verisón 2016-2017. Análisis y síntesis de los resultados: Durante el período 2015-2017 no se lograron avances significativos en la reducción del número de enfermos palúdicos. No obstante, se señala la anemia como causa de mortalidad en el curso de la malaria. También, se destacan los nuevos enfoques y compromisos para reducir la morbilidad atribuible al paludismo en la mujer embarazada en sus tres vertientes: tratamiento eficaz de los casos de paludismo, el uso de mosquiteros tratados con insecticidas, y la utilización del tratamiento preventivo intermitente con el antimalárico sulfadoxina-pirimetamina a partir del segundo trimestre del embarazo. La indicación de este tratamiento inlcuye mínimo dos dosis del fármaco antipalúdico, con un intervalo de un mes entre cada dosis, con independencia de que las embarazadas muestren o no síntomas de la enfermedad. Conclusiones: Esta intervención para prevenir el paludismo en el embarazo es una cuestión prioritaria en la iniciativa de salud materna, infantil y reproductiva; además, ayuda a mejorar y aumentar la cobertura de las medidas de control de esta enfermedad durante la gestación(AU)

Introduction: Malaria infection during pregnancy is an important health problem in most tropical regions. This condition may have a negative incidence on pregnant women and fetuses. Objective: Inquire into the effect of the intermittent preventive treatment with the malarial sulfadoxine / pyrimethamine in pregnant women. Methods: A bibliographic review was conducted in the database Medline / PubMed and in relevant papers about the topic published in the last five years. The Guidelines for the Treatment of Malaria 2016-2017 of the World Health Organization were also used as reference. Analysis and synthesis of results: Significant progress was not achieved in reducing the number of malaria patients in the period 2015-2017. However, anemia is reported as the cause of mortality during the course of malaria. New approaches and commitments are proposed to reduce malaria-related morbidity among pregnant women, namely effective treatment of malaria cases, use of insecticide-treated mosquito nets, and intermittent preventive treatment with the antimalarial sulfadoxine / pyrimethamine as of the second quarter of pregnancy. Indication of this treatment includes at least two doses of the malarial, with a separation of one month between the doses, regardless of whether the pregnant women have symptoms of the disease. Conclusions: The intervention to prevent malaria during pregnancy is a first-priority aspect of the mother, child, reproductive health initiative. It also helps improve and broaden the coverage of measures for the control of this disease during pregnancy(AU)

Toxoplasmosis ocular. Descripción de tres pacientes con presentación atípica / Ocular toxoplasmosis. Description of three patients with an atypical presentation.

Objetivo: Describir una forma de presentación atípica de toxoplasmosis ocular, enfatizando la importancia de la jerarquización de los hallazgos clínicos y las limitaciones de la serología para realizar un diagnóstico temprano. Pacientes y Métodos: Estudio retrospectivo y descriptivo de tres casos clínicos de toxoplasmosis ocular activa, con presentación atípica (compromiso del nervio óptico), derivados al Servicio de Oftalmología del Hospital J. P. Garrahan en el periodo comprendido entre 2007 y 2010. Resultados: En los tres casos presentados la sospecha clínica de toxoplasmosis ocular no se correlacionó con evidencia serológica de infección reciente. En un caso, la terapéutica específica temprana, basada en la sospecha clínica, resultó en una excelente recuperación funcional. Un tratamiento tardío puede interferir en el resultado visual. Conclusiones: Basados en los hallazgos clínicos y la alta sospecha de esta patología debe iniciarse el tratamiento específico sin esperar que los resultados serológicos la confirmen. Eventualmente, la mejoría clínica confirmara el diagnóstico. El comportamiento de los títulos de anticuerpos en el curso de la enfermedad ocular no siempre es confiable, y en muchos casos retrasa el comienzo de la terapéutica con la consiguiente mala rehabilitación visual de estos pacientes (AU)

Objective: To describe an atypical presentation of ocular toxoplasmosis, emphasizing the importance of clinical findings and the limitations of serology in the early diagnosis. Patients and Methods: A retrospective, descriptive study was conducted of three cases with active ocular toxoplasmosis with an atypical presentation (optic nerve involvement), referred to the Department of Ophthalmology of Hospital J. P. Garrahan between 2007 and 2010. Results: In the three cases presented here clinical suspicion of ocular toxoplasmosis did not correlate with serological evidence of a recent infection. In one case, early treatment, based on clinical suspicion, resulted in excellent functional recovery. Late management may compromise visual outcome. Conclusions: Based on clinical findings and suspicion of the pathology, specific treatment should be started without waiting for serological confirmation. Eventually, clinical improvement will confirm the diagnosis. The behavior of antibody titres in the course of the ocular disease is not always reliable and often delays treatment initiation with subsequent difficulties in the visual rehabilitation of these patients (AU)

Estudio retrospectivo de la aplicación de la amplificación génica cualitativa en muestras biológicas para el seguimiento de la toxoplasmosis en pacientes pediátricos receptores de trasplante de células progenitoras hematopoyéticas / Retrospective study of the implementation of the qualitative PCR technique in biological samples for monitoring toxoplasmosis in pediatric patients receiving hematopoietic stem cell transplantion

La toxoplasmosis es una infección oportunista causada por el parásito Toxoplasma gondii; su infección es grave y de difícil diagnóstico en pacientes que reciben un trasplante alogénico de células progenitoras hematopoyéticas (TCPH). En el Hospital de Pediatría S.A.M.I.C. "Profesor Dr. Juan P. Garrahan" se realizó la vigilancia postrasplante de 12 pacientes receptores de TCPH mediante la técnica de PCR cualitativa. La necesidad de seguimiento de estos pacientes fue definida por el antecedente de serología positiva para toxoplasmosis en el donante o receptor y ante la imposibilidad de iniciar el uso profiláctico de trimetoprima-sulfametoxazol a causa de la condición hematológica. Dos pacientes presentaron signos de enfermedad por T. gondii con resultado de PCR positivo y recibieron tratamiento con pirimetamina-clindamicina. En otros dos, la toxoplasmosis fue causa de muerte y hallazgo de autopsia, con resultado de PCR negativo. Cuatro pacientes recibieron tratamiento contra toxoplasmosis por la detección de una PCR positiva, sin manifestaciones clínicas. En los cuatro pacientes restantes no se detectaron signos de enfermedad por toxoplasmosis, con resultados de PCR negativos durante el seguimiento. La técnica de PCR cualitativa demostró ser útil para detectar la reactivación de la toxoplasmosis en receptores de TCPH, pero tiene limitaciones para el seguimiento y la toma de decisiones clínicas en pacientes con PCR positiva que persiste en el tiempo y manifestaciones de toxicidad por el tratamiento.

Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twelve patients receiving HSCT were monitored post-transplant, by qualitative PCR at the Children's Hospital S.A.M.I.C. "Prof. Dr. Juan P. Garrahan". The monitoring of these patients was defined by a history of positive serology for toxoplasmosis in the donor or recipient and because their hematologic condition did not allow the use of trimethoprim-sulfamethoxazole for prophylaxis. During the patients' monitoring, two of them with positive PCR results showed signs of illness by T. gondii and were treated with pyrimethamine-clindamycin. In two other patients, toxoplasmosis was the cause of death and an autopsy finding, showing negative PCR results. Four patients without clinical manifestations received treatment for toxoplasmosis because of positive PCR detection. In four patients there were no signs of toxoplasmosis disease and negative PCR results during follow-up. The qualitative PCR technique proved useful for the detection of toxoplasmosis reactivation in HSCT recipients, but has limitations in monitoring and making clinical decisions due to the persistence of positive PCR over time and manifestations of toxicity caused by the treatment.

The in vivo antimalarial activity of methylene blue combined with pyrimethamine, chloroquine and quinine

The effectiveness of methylene blue (MB) combined with pyrimethamine (PYR), chloroquine (CQ) or quinine (Q) was examined in a classical four-day suppressive test against a causative agent of rodent malaria, Plasmodium berghei. A marked potentiation was observed when MB was administered at a non-curative dose of 15 mg/kg/day in combination with PYR (0.19 mg/kg/day) or Q (25 mg/kg/day). No synergy was found between MB (15 mg/Kg) and CQ (0.75 mg/Kg). Our results suggest that the combination of MB with PYR or Q may improve the efficacy of these currently used antimalarial drugs.

Plasmodium falciparum infection in pregnant women attending antenatal care in Luanda, Angola / Infecção por Plasmodium falciparum em mulheres grávidas em consultas pré-natal em Luanda, Angola

INTRODUCTION: Malaria during pregnancy remains a serious public health problem. The aim of this study was to establish the prevalence and possible risk factors for malaria in pregnant women attending antenatal care at Augusto Ngangula Specialized General Hospital in Luanda, Angola. METHODS: Pregnant women (679 total) who attended antenatal care from April to September 2008 were included in the study after signing informed consent. For each participant, the social-demographic profile and malaria and obstetric histories were investigated via a questionnaire. Diagnosis was made by optic microscopy, and hemoglobin concentration measured. The associations between age, parity, gestational age, residence, schooling, malaria during gravity, anemia and treatment with incidence of Plasmodium falciparum infection were analyzed through logistic regression. RESULTS: During the period of study, 74 (10.9%) out of 679 women were infected by P. falciparum. The average concentration of hemoglobin was 11.1 ± 0.07g/dL, and there were significant associations between the history of malaria during pregnancy, P. falciparum infection (p<0.01) and anemia at the time of observation (p<0.001). CONCLUSIONS: Previous history of malaria during pregnancy represents a risk factor for current infection and anemia was an important complication associated with malaria, even in women who were treated with sulfadoxine-pyrimethamine during pregnancy.

INTRODUÇÃO: A malária na gravidez continua a ser um grave problema de saúde pública. O objetivo deste estudo foi determinar a prevalência e possíveis fatores de risco para a malária, em mulheres grávidas que foram atendidas em consultas pré-natal, no Hospital Geral Especializado Augusto Ngangula, em Luanda, Angola. MÉTODOS: De abril a setembro de 2008, 679 mulheres grávidas foram envolvidas no estudo após consentimento informado. O perfil sócio demográfico e história de malária e obstetrícia foram investigados através de um questionário. O diagnóstico foi efetuado por microscopia óptica e determinou-se ainda as concentrações da hemoglobina. Através da regressão logística foi analisada a associação entre a idade, paridade, tempo de gestação, residência, escolaridade, malária durante a gravidez, anemia e tratamento com a infecção por Plasmodium falciparum. RESULTADOS: Setenta e quatro (10,9%) das 679 mulheres estavam infectadas com P. falciparum. O valor médio da concentração da hemoglobina foi de 11,1 ± 0,07g/dL, encontrando-se uma associação significativa entre história de malária na gravidez e infecção por P. falciparum (p<0,01) e anemia no momento da observação (p<0.001). CONCLUSÕES: A história de malária anterior na gravidez foi um fator de risco para uma infecção atual e a anemia uma complicação importante associada à malária, mesmo em mulheres que receberam tratamento durante a gravidez com sulfadoxina-pirimetamina.

Nephrotic syndrome associated with toxoplasmosis: report of seven cases / Síndrome nefrótica associada à toxoplasmose: relato de sete casos

The concomitance of nephrotic syndrome and acute infection by Toxoplasma gondii is a rare occurrence in humans. In this paper seven cases of children, ranging from 11 months to 7 year-old, with concomitant nephrotic syndrome and asymptomatic acute T. gondii infection are reported. In one of those patients only the administration of anti-Toxoplasma therapy was enough to control the clinical and laboratory manifestations of the disease. In the other patients it was necessary to introduce corticosteroids or other immunosuppressant drugs. Three patients had complete clinical and laboratory improvement and the remaining showed only a partial response.

Ocorrência concomitante de síndrome nefrótica e infecção aguda por Toxoplasma gondii em seres humanos é situação pouco frequente. No presente trabalho são relatados sete casos de crianças, com idade variável entre 11 meses e sete anos, que apresentavam síndrome nefrótica e infecção aguda por T. gondii assintomática. Em um dos pacientes o tratamento específico anti-Toxoplasma foi suficiente para controlar clínica e laboratorialmente as manifestações da doença. Nos demais foi preciso administrar corticosteróides ou outras drogas imunossupressoras. Após introdução desse esquema três pacientes apresentaram remissão completa dos sintomas; os demais apenas remissão parcial.

Disseminated toxoplasmosis in an immunocompetent patient from Peruvian Amazon / Toxoplasmosis diseminada en un paciente inmunocompetente procedente de la Amazonía peruana

We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.

Reportamos un caso de toxoplasmosis severa en un paciente inmunocompetente caracterizado por neumonía, retinocoroiditis, hepatitis y miositis. El diagnóstico fue confirmado por serología, el hallazgo de T. gondii en gota gruesa y la presencia de bradizoitos en biopsia muscular. El tratamiento con pirimetamina mas sulfadoxina fue exitoso pero solo hubo una parcial recuperación de la agudeza visual y de la capacidad de extensión de la cadera. Este es el primer reporte de un caso de toxoplasmosis severa en el Perú.

Caracterización clínica y radiológica del compromiso pulmonar por toxoplasmosis aguda diseminada en nueve pacientes inmunocompetentes / Clinical and radiological characterization of the pulmonary commitment for acute toxoplasmosis disseminated in nine immunocompetents patients

La toxoplasmosis aguda en el individuo inmunocompetente generalmente tiene un comportamiento benigno y autolimitado. Sin embargo, en pacientes provenientes de área selvática se han presentado casos severos de compromiso visceral, el más frecuente de ellos, el pulmonar. Se realizó la descripción clínica y radiológica de nueve individuos miembros de las fuerzas militares de Colombia, con toxoplasmosis aguda y compromiso pulmonar. El 55% de los casos presentó disnea clase funcional II/IV; 33% clase funcional III/IV y tan sólo 1/9 pacientes presentó clase funcional IV/IV. La imagen radiológica más común fue la consolidación pulmonar unifocal o multifocal (66%), y en menor frecuencia la presencia de infiltrados reticulares, reticulonodulares y derrame pleural. La totalidad de los pacientes evolucionaron en forma satisfactoria, dos de ellos con necesidad de soporte con ventilación mecánica no invasiva.

Options for clinical trials of pre and post-natal treatments for congenital toxoplasmosis

Clinical trials comparing different drug regimens and strategies for the treatment of congenital toxoplasmosis and its clinical manifestations in the liveborn child in different clinical settings should aim at formally evaluating the net benefit of existing treatments and at developing new therapeutic options. Currently, there is no ideal drug for congenital toxoplasmosis; future research should focus on the screening of new active drugs and on their pre-clinical and early clinical development, with a focus on pharmacokinetic/dynamic studies and teratogenicity. For the prenatal treatment of congenital toxoplasmosis, a trial comparing spiramycine to pyrimethamine-sulphadiazine and placebo would allow a formal estimation of the effect of both drugs in infected pregnant women. In newborn children, the net benefit of pyrimethamine-sulphadiazine should also be formally assessed. These trials will be implemented in settings where prenatal screening for Toxoplasma gondii is currently implemented. Trials should be carefully designed to allow for translation to other settings and modelling tools like cost-effectiveness analysis should be used to provide clinicians and founders with the best available evidence to establish recommendations.

Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosis

The aim of this study was to determine the incidence of congenital toxoplasmosis (CT) and to assess the performances of prenatal and neonatal diagnoses. From 1994-2005, in Toulouse University Hospital, France, amniocentesis was performed on 352 pregnant women who were infected during pregnancy. All women were treated with spiramycin and pyrimethamine-sulfadoxine when prenatal diagnosis was positive. Among the 275 foetuses with follow-up, 66 (24 percent) were infected. The transmission rates of Toxoplasma gondii were 7 percent, 24 percent and 59 percent in the first, second and third trimesters, respectively. The sensitivity and specificity of PCR on amniotic fluid (AF) were 91 percent and 99.5 percent, respectively. One case was diagnosed by mouse inoculation with AF and six cases were diagnosed by neonatal or postnatal screening. The sensitivity and specificity of PCR on placentas were 52 percent and 99 percent, respectively. The sensitivity of tests for the detection of specific IgA and IgM in cord blood was 53 percent and 64 percent, respectively, and specificity values were 91 percent and 92 percent. In conclusion, PCR performed on AF had the highest levels of sensitivity and specificity for the diagnosis of CT. This permits an early diagnosis of most cases and should be recommended.

Resistência à sulfadoxina-pirimetamina em Maputo, Moçambique: presença de mutações nos genes dhfr e dhps do Plasmodium falciparum / Sulfadoxine-pyrimethamine resistance in Maputo, Mozambique: presence of mutations in the dhfr and dhps genes of Plasmodium falciparum

Foram analisadas a freqüência e distribuição de mutações nos genes dihidrofolato redutase e dihidropteroato sintetase do Plasmodium falciparum, usando a metodologia de reação em cadeia da polimerase e polimorfismos de hidrólise por enzimas de restrição, em amostras de sangue infectado proveniente de crianças moçambicanas, residentes em Maputo. A análise foi feita antes e 7 dias após o tratamento com sulfadoxina-pirimetamina (S/P). Os resultados mostraram a ocorrência de mutações pontuais nos genes estudados e a presença de combinações de três alelos em dhfr (51Ile, 59Arg e 108Asn) e do quintúplo mutante (dhfr 51Ile, 59Arg, 108Asn e dhps 437Gly, 540Glu), ambas situações associadas à falha terapêutica no sétimo dia após tratamento com S/P. Esses achados mostram a importância de se estudar a resistência à S/P em Moçambique, e como os marcadores moleculares de resistência aos antimaláricos podem fornecer dados importantes para a política nacional de controlo da malária.

The frequency and distribution of mutations in Plasmodium falciparum, dihydrofolate reductase and dihydropteroate synthase genes were analyzed, using the polymerase chain reaction and restriction fragment length polymorphism methodology, in infected blood samples from Mozambican children living in Maputo, before and seven days after treatment with sulfadoxine/pyrimethamine (S/P). The results showed the occurrence of point mutations in the genes studied and the presence of combinations of three alleles in dhfr (51Ile, 59Arg and 108Asn) and "quintuple" mutant (dhfr 51Ile, 59Arg, 108Asn and dhps 437Gly, 540Glu). Both of these situations were associated with seven-day therapeutic failure, following treatment with S/P. These findings show the importance of studying S/P resistance in Mozambique, and how molecular markers for antimalarial resistance can provide important data for national malaria control policy.

Acute acalculous cholecystitis in an immunocompetent patient with severe acquired toxoplasmosis

Acute acalculous cholecystitis (AAC) is an inflammatory disease of the gallbladder not associated with gallstones. It is more often seen in hospitalized patients on mechanical ventilation due to life-threatening conditions and superimposed sepsis. Occasionally, infection itself may be the only predisposing factor identified. AAC has rarely been observed in severely immunocompromised patients with reactivated Toxoplasma infection. We were able to document for the first time a case of AAC in an otherwise healthy adult with acute acquired toxoplasmosis. A prompt diagnosis and early onset of effective antiparasitic treatment allowed the resolution of the episode without further complication

Effects of antifolates - co-trimoxazole and pyrimethamine-sulfadoxine - on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS - but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrolment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

The drug sensitivities of Plasmodium falciparum in the Sonitpur district, Assam, India.

Falciparum malaria is an ongoing problem in the foothills of Northeast India. Evaluation of the drug sensitivities of P. falciparum was carried out in four endemic villages of the Sonitpur District of Assam, involving 218 cases who were tested in vivo over 35 days. Chloroquine resistance was detected at the RI level in 29 cases (13%) and RII level in 8 cases (4%). No RIII chloroquine resistant cases were detected in the study. RI resistance was observed in the age groups 6-10 years, 11-14 years, and 15 years and above in 16%, 17%, and 13%, respectively. RII level resistance was observed in 4% of all those groups combined. All the RI and RII resistant cases responded well to a single dosage of Metakelfin (sulfamethoxypyrazine I.P 1,500 mg and pyrimethamine I.P 75 mg).

Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia / Gametocyte levels in response to differing malaria treatments in two municipalities of Colombia

Se ha informado que el número de gametocitos circulantes de Plasmodium falciparum está influenciado por aspectos como el nivel de endemicidad de la zona, la clase de esquizonticidas sanguíneos usados y la respuesta terapéutica a ellos. En Colombia son muy pocos los trabajos que han evaluado estas relaciones. Mediante un diseño experimental, se evaluó la gametocitemia (variable efecto) en función del nivel endémico de dos municipios de Antioquia, del tratamiento (sulfadoxina-pirimetamina y sulfadoxina-pirimetamina más cloroquina) y de la respuesta terapéutica (adecuada y fallida). Se estudiaron 148 pacientes con malaria por P. falciparum no complicada. La gametocitemia varía en función del tiempo de padecimiento de la malaria actual (mayor en Turbo que en Zaragoza) y esta variable debe controlarse para eliminar la aparente diferencia en las gametocitemias por municipio. No se hallaron diferencias estadísticamente significativas en la gametocitemia (porcentaje de pacientes con gametocitos circulantes y cantidad de ellos por microlitro) según el tratamiento y la respuesta terapéutica, aunque los niveles de gametocitos son mayores en los pacientes tratados sólo con sulfadoxinapirimetamina, respecto a quienes recibieron sulfadoxina-pirimetamina más cloroquina. Tampoco hubo diferencias en la gametocitemia según el sexo ni la edad de los pacientes, ni se halló correlación de ella con la parasitemia asexual. La diferencia en el nivel de gametocitemia encontrada entre los municiios de Turbo y Zaragoza parece estar influida por el tiempo transcurrido entre el inicio de los síntomas y la instauración del tratamiento.

Plasmodium falciparum gametocyte levels are influenced by level of regional endemicity, the antimalarial treatment, and the therapeutic response of patients. Few previous studies have related these factors in Colombia. Here, gametocytaemia was evaluated with respect to two treatment schemes (sulfadoxine/pyrimethamine and sulfadoxine/pyrimethamine plus chloroquine), the patient response (adequate or failure), and the locality (two areas of varying case frequency). One hundred forty-eight residents of Turbo and Zaragoza (Antioquia), all with uncomplicated malaria, were evaluated. The gametocytaemia and the rates of clinical malaria at the beginning of treatment were greater in Turbo than in Zaragoza. No statiscally significant differences in the gametocytaemia by treatment schemes or therapeutic responses were noted, although the patients who received SP had more gametocytes than those treated with SP+CQ. Gametocytaemia was not correlated with asexual parasitemia or sex and age of patient. The difference in the level of gametocytaemia between Turbo and Zaragoza appears to be influenced by the time elapsed between the appearance of symptoms and the beginning of treatment.

Associations of antifolate resistance in vitro and point mutations in dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum.

BACKGROUND: Antifolate antimalarials like sulfadoxine-pyrimethamine are used as second-line treatment for Plasmodium falciparum malaria patients who fail to respond to chloroquine. The efficacy of the sulfa-pyrimethamine combination in the treatment is also compromised by the development of resistance in the parasite. Resistance to these drugs has been shown to encode with point mutations in dihydrofolate reductase and dihydropteroate synthetase genes. SETTINGS: An experimental study. MATERIAL AND METHODS: Forty clinical isolates collected from different geographical locations in India were used to assess the relationships between resistance to sulfadoxine-pyrimethamine (SP) and mutations in P. falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In vitro drug susceptibility and mutation-specific polymerase chain reaction (PCR) assays were also done. RESULTS: It was observed that a number of isolates possessed mutant genotypes and showed low sensitivity to SP in vitro. Of the 40 clinical isolates studied, 87.5% had DHFR and 15% had DHPS gene mutations. As observed from PCR results, 55( (22/40) presented double mutation of DHFR Arg-59 and Asn-108 and 32.5 % (13/40) had single mutant type allele of Asn-108. Of the 40 isolates, 10 % (4/40) presented doubly mutated forms of DHPS Phe-436 and Thr-613 and single mutant type allele Gly-581 was detected in 5 % (2/40) isolates. Parasites carrying double or single mutant forms of DHFR/DHPS showed elevated minimum inhibitory concentration (MIC) values of both pyrimethamine (760-6754 nM; r=0.69) and sulfadoxine (108 - 540 micro M; r=0.87) when compared to sensitive and resistant strains. CONCLUSION: Though there was a correlation between molecular techniques and in vitro drug sensitivity profiles, the relevance of these findings to the clinical efficacy of SP combination drugs needs to be established by controlled clinical trials.

Drug resistant falciparum malaria and the use of artesunate-based combinations: focus on clinical trials sponsored by TDR.

Antimalarial drug resistance has now become a serious global challenge and is the principal reason for the decline in antimalarial drug efficacy. Malaria endemic countries need inexpensive and efficacious drugs. Preserving the life spans of antimalarial drugs is a key part of the strategy for rolling back malaria. Artemisinin-based combinations offer a new and potentially highly effective way to counter drug resistance. Clinical trials conducted in African children have attested to the good tolerability of oral artesunate when combined with standard antimalarial drugs. The cure rates of the different combinations were generally dependent on the degree of resistance to the companion drug. They were high for amodiaquine-artesunate, variable for sulfadoxine/pyrimethamine-artesunate, and poor for chloroquine-artesunate.

Assessment of therapeutic efficacy of chloroquine and sulphadoxine-pyrimethamine in uncomplicated falciparum malaria.

A standardised protocol has been developed by World Health Organization (CDS/RBM/2002) to assess the efficacy of common antimalarials in the treatment of clinically manifested infection with uncomplicated P. falciparum malaria for areas with low to moderate transmission. The therapeutic efficacy protocol is based on clinical and parasitological responses of the patients and it has the purpose of determining the practical efficacy of the drug regimen in study areas with the ultimate objective of ascertaining its continued usefulness or the necessity for replacing it in the routine treatment. Present study has been conducted at seven sites--Kathiatali and Simonabasti of District Nowgaon, Assam; Sonapur and Boko of District Kamrup, Assam; Keonjhar Town, Padampur and Basudebpur of District Keonjhar, Orissa. In order to reduce the patient recruitment time, health centre close to well-defined community was identified to conduct the activities at peak malaria season by selecting local pockets and organising mobile clinics. Microscopically confirmed cases of P. falciparum were enrolled according to the criteria for inclusion and exclusion. Treatment with recommended drug was given under supervision and a follow-up schedule at various intervals for 28 days was maintained. In chloroquine (CQ) study areas, wherever patients showed treatment failure, they were treated with second line drug--sulphadoxine-pyrimethamine (SP) combination and then followed-up as per study protocol. It was observed that 30% cases showed treatment failure to CQ in District Nowgaon, where revised drug policy has already been introduced. In Kamrup district, treatment failure with CQ was found to be less than 25%, which denotes the said regimen is still effective. Almost all the patients from Padampur and Basudebpur of District Keonjhar responded to CQ, treatment failure was noticed only in two patients (3%). The antifolate combination found to be fully effective as second line and also as first line wherever revised drug policy has been introduced.