Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America.

Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).

Fiebre biliosa hemoglobinúrica como forma de presentación de la malaria aguda grave por Plasmodium falciparum / Hemoglobinuric bilious fever as a presentation of severe acute Plasmodium falciparum malaria

RESUMEN Introducción: La fiebre biliosa hemoglobinúrica es una de las complicaciones del paludismo grave, notificada con poca frecuencia, que se caracteriza por una hemólisis intravascular aguda en ocasiones masiva que conduce a hemoglobinuria y, finalmente, a una lesión renal aguda. Objetivo: Describir un caso de fiebre biliosa hemoglobinúrica como forma clínica de presentación de la malaria aguda grave. Caso clínico: Paciente masculino procedente de una zona endémica de paludismo con antecedentes de episodios recurrentes de malaria, quien, al tercer día de indicarle quimioprofilaxis antipalúdica con mefloquina, presentó un cuadro clínico de decaimiento, marcada astenia, fatiga, náuseas, vómitos, dolor abdominal difuso y emisión de orina oscura escasa, descritas por el paciente como "coca cola". Se diagnosticó fiebre biliosa hemoglobinúrica como forma clínica de presentación de una malaria aguda grave con baja parasitemia, constatado mediante examen de diagnóstico rápido y gota gruesa positivos a paludismo y hemoglobinuria masiva en el examen de orina con tira reactiva. La evolución del paciente fue favorable. Conclusiones: Este caso representa una forma no habitual de presentación de la enfermedad, que aunque no se sospecha usualmente, puede ocurrir. Este artículo es una alerta a los médicos que ejercen en áreas endémicas de malaria a permanecer atentos. Esta temible complicación puede ser la forma clínica de presentación de la malaria grave, particularmente en paciente expuestos crónicamente a infección por Plasmodium falciparum, que presenten una reacción hemolítica aguda masiva en ausencia de parasitemia elevada, cuando se administra quinina o mefloquina como tratamiento preventivo o curativo contra la malaria.

ABSTRACT Introduction: Hemoglobinuric bilious fever is one of the complications of severe malaria, infrequently notified, characterized by an acute intravascular hemolysis, massive in occasions, that leads to homoglobinuria and, finally to an acute renal lesion. Objective: To describe a case of hemoglobinuric bilious fever as clinical presentation of severe acute malaria. Clinical case: Male patient from a malaria-endemic area with a history of recurrent events of malaria, who, on the third day after receiving antimalarial chemoprophylaxis with mefloquine, presented with malaise, marked asthenia, fatigue, nausea, vomiting, diffuse abdominal pain, and scanty and dark urine emission, described by the patient as "Coca-Cola" like. Hemoglobinuric bilious fever was diagnosed as clinical presentation of severe acute malaria of low parasitemia, confirmed by malaria-positive quick diagnostic test and thick film, and massive homoglobinuria on urine dipstick test. Conclusions: This case represents an uncommon presentation of the disease, which is not usually suspected. This paper alerts physicians working in malaria-endemic areas to be attentive. This dread complication could be the clinical presentation of severe malaria, especially in patients chronically exposed to Plasmodium falciparum infection, who present with massive acute hemolytic reaction in the absence of high parasitemia when quinine or mefloquine is administered as preventive or curative treatment against malaria.

Paludismo importado no falciparum: aspectos de interés para el tratamiento de los pacientes / Imported non-falciparum malaria: aspects of interest for patient therapeutic management

Introducción: El paludismo es una enfermedad febril aguda potencialmente mortal causada por parásitos transmitidos por el mosquito Anopheles. El paludismo no falciparum (PNF), producido por otras especies de Plasmodium, está menos documentado en la literatura internacional, a pesar de su prevalencia. Objetivos: Describir aspectos clínicos y epidemiológicos de interés para el tratamiento en pacientes ingresados con diagnóstico de PNF importado, y determinar la relación existente entre la respuesta al tratamiento y otras variables. Métodos: Se realizó un estudio transversal analítico de 89 pacientes adultos con PNF importado, ingresados en el Departamento de Medicina del Instituto de Medicina Tropical Pedro Kourí, entre enero de 1997 a diciembre de 2017. Se determinó la pauta de profilaxis y tratamiento según los criterios de las guías publicadas y los fármacos disponibles en Cuba, y la definición de paludismo complicado según la OMS en 2003. Hubo respuesta demorada al tratamiento, cuando el paciente demoraba más de 7 días en negativizar la gota gruesa. Resultados: Predominaron los pacientes del sexo masculino, y una media de edad de 37,2 años. El 55,1 por ciento de los pacientes provenía de la región de las Américas y en el 85,4 por ciento se aisló Plasmodium vivax. La respuesta al tratamiento fue excelente con los esquemas combinados utilizados a base de cloroquina. Fue significativa la relación existente entre la demorada respuesta al tratamiento con la gravedad del cuadro clínico y el estado no inmune de los pacientes. Conclusiones: El PNF es una importante causa de paludismo importado en pacientes provenientes de áreas endémicas, fundamentalmente de América. Se distingue por parasitemias bajas, un cuadro clínico caracterizado por fiebre, escalofríos, cefaleas y evolución hacia cuadros no complicados. La cloroquina fue el medicamento de elección, aunque la repuesta demorada al tratamiento no justifica su suspensión o variación(AU)

Introduction: Malaria is a potentially fatal acute febrile illness caused by parasites transmitted by the Anopheles mosquito. Non-falciparum malaria (NFM), caused by other Plasmodium species, is less documented in the international literature, despite its prevalence. Objectives: To describe clinical and epidemiological aspects of interest for the treatment of patients hospitalized with a diagnosis of imported NFM, and to determine the relationship between response to treatment and other variables. Methods: It was conducted an analytical cross-sectional study of 89 adult patients with imported NFM, admitted to the Department of Medicine of the Institute of Tropical Medicine Pedro Kourí, between January 1997 to December 2017. The prophylaxis and treatment guideline was determined according to the published guidelines and drugs available in Cuba, and the definition of severe malaria by WHO in 2003. There was delayed response to treatment when the patient took more than 7 days to become negative for thick blood smear. Results: Patients were predominantly male, with a mean age of 37.2 years. Plasmodium vivax was isolated in 85.4 percent of the patients and 55.1 percent were from the Americas region. The response to treatment was excellent with the chloroquine-based combination regimens used. The relationship between the delayed response to treatment and the severity of the clinical picture and the non-immune status of the patients was significant. Conclusions: NFM is an important cause of imported malaria in patients from endemic areas, mainly from the Americas. It is characterized by low parasitemia, clinical manifestations of fever, chills, headache and evolution towards uncomplicated symptoms. Chloroquine was the drug of choice, although the delayed response to treatment does not justify its suspension or variation(AU)

Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal-fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon.

BACKGROUND: Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth? METHODS: From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children's Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation. RESULTS: In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86-12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02-6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever. CONCLUSIONS: While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.

Diagnostic Methods for Non-Falciparum Malaria.

Malaria is a serious public health problem that affects mostly the poorest countries in the world, killing more than 400,000 people per year, mainly children under 5 years old. Among the control and prevention strategies, the differential diagnosis of the Plasmodium-infecting species is an important factor for selecting a treatment and, consequently, for preventing the spread of the disease. One of the main difficulties for the detection of a specific Plasmodium sp is that most of the existing methods for malaria diagnosis focus on detecting P. falciparum. Thus, in many cases, the diagnostic methods neglect the other non-falciparum species and underestimate their prevalence and severity. Traditional methods for diagnosing malaria may present low specificity or sensitivity to non-falciparum spp. Therefore, there is high demand for new alternative methods able to differentiate Plasmodium species in a faster, cheaper and easier manner to execute. This review details the classical procedures and new perspectives of diagnostic methods for malaria non-falciparum differential detection and the possibilities of their application in different circumstances.

A cluster of the first reported Plasmodium ovale spp. infections in Peru occuring among returning UN peace-keepers, a review of epidemiology, prevention and diagnostic challenges in nonendemic regions.

BACKGROUND: Plasmodium ovale curtisi and Plasmodium ovale wallikeri are regarded as less virulent forms of malaria with a geographic distribution including Southeast Asia, Central and West Africa, and is increasingly reported as an infection in returning travellers. A species of malaria that may have delayed or relapsing presentations similar to Plasmodium vivax, the clinical presentation of P. ovale spp. has been described to have prepatent periods of 2 weeks or slightly longer with reports of relapse following primary infection out to 8-9 months. This presentation may be obscured further in the setting of anti-malarial exposure, with report of delayed primary infection out to 4 years. Presented is a cluster of 4 imported P. ovale spp. cases in returning Peruvian military personnel assigned to United Nations peace-keeping operations in the Central African Republic. CASE PRESENTATION: From January to December 2016, Peruvian peace-keepers were deployed in support of United Nations (UN) operations in the Central African Republic (CAR). While serving abroad, Navy, Army, and Air Force members experienced 223 episodes of Plasmodium falciparum malaria following interruption of prophylaxis with mefloquine. Diagnosis was made using rapid diagnostics tests (RDTs) and/or smear with no coinfections identified. Cases of malaria were treated with locally-procured artemether-lumefantrine. Returning to Peru in January 2017, 200 peace-keepers were screened via thick and thin smear while on weekly mefloquine prophylaxis with only 1 showing nucleic acid within red blood cells consistent with Plasmodium spp. and 11 reporting syndromes of ill-defined somatic complaints. Between a period of 5 days to 11 months post return, 4 cases of P. ovale spp. were diagnosed using smear and polymerase chain reaction (PCR) following febrile complaints. All cases were subsequently treated with chloroquine and primaquine, with cure of clinical disease and documented clearance of parasitaemia. CONCLUSION: These patients represent the first imported cases in Peru of this species of malaria as well as highlight the challenges in implementing population level prophylaxis in a deployed environment, and the steps for timely diagnosis and management in a non-endemic region where risk of introduction for local transmission exists.

Malaria congénita en un hospital de Iquitos, Perú / Congenital malaria in a hospital in Iquitos, Peru

Objetivos. Determinar la frecuencia y características clínicas de los recién nacidos con malaria congénita en el Hospital de Apoyo de Iquitos en la Amazonía peruana. Materiales y métodos. Estudio descriptivo, prospectivo y transversal. De enero de 2011 a diciembre de 2013 se estudiaron 14 017 recién nacidos y a sus madres, de quienes se seleccionaron 52 portadoras de malaria gestacional mientras que a sus recién nacidos se les hospitalizó en el Servicio de Neonatología del hospital, y fueron sometidos a evaluación clínica y estudios de laboratorio. Resultados. La frecuencia de malaria gestacional fue de 0,4% y una proporción de malaria congénita de 9,6%. Plasmodium vivax fue hallado en 80% de casos de malaria gestacional y en 60% de malaria congénita. Se observó un caso de óbito fetal con gota gruesa positiva para Plasmodium falciparum. El cuadro clínico en recién nacidos fue fiebre, hipoactividad, irritabilidad y pobre succión. Conclusiones. Se documenta la presencia de malaria congénita en recién nacidos de madres con malaria gestacional. El cuadro clínico se asemeja a una sepsis neonatal. El diagnóstico precoz de malaria congénita y el tratamiento oportuno cursan con buena evolución.

Objectives. To determine the frequency and clinical features of newborns with congenital malaria in the Hospital de Apoyo of Iquitos in the Peruvian Amazon. Materials and methods. Descriptive, prospective and cross-sectional study. From January 2011 to December 2013, 14.017 newborns and their mothers were studied, of whom 52 carriers of gestational malaria were selected while their infants were hospitalized in the Neonatology Unit, and underwent clinical assessment and laboratory studies. Results. Gestational malaria frequency was 0.4% and a proportion of 9.6% of congenital malaria. Plasmodium vivax was found in 80% of cases of gestational malaria and in 60% of congenital malaria. A case of fetal death with positive thick blood smear for Plasmodium falciparum was observed. The clinical presentation in newborns was fever, hypoactivity, irritability and poor suction. Conclusions. The presence of congenital malaria in infants born to mothers with gestational malaria is documented. The clinical picture resembled neonatal sepsis. Early diagnosis of congenital malaria and timely treatment present with good evolution.

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.

During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.

Trouble from the tropics: challenges in managing malaria in Rhode Island.

The authors present a case of severe falciparum malaria diagnosed in a traveler after he returned to Rhode Island from a visit to the Dominican Republic. They then review aspects of the case pertinent to our local practice environment that make diagnosis and management especially challenging.

Malária falciparum com comprometimento renal (síndrome nefrótica - relato de caso / Falciparum malaria with renal impairment (nephrotic syndrome) - case report

Objetivo: apresentação de um caso de síndrome nefrótica por malária falciparum. Relato decaso: escolar, 8 anos, sexo feminino, admitida no Hospital Municipal de Tailândia, Pará, comquadro de febre alta, seguida de surgimento de edema, urina escura e oligúria.. Evoluiu comanúria e foi transferida para a Fundação Santa de Misericórdia do Pará (FSCM-PA), onderecebeu diagnóstico de síndrome nefrótica secundária à malária por Plasmodium falciparum,com base em dados de anamnese, exame físico e exames complementares. A paciente obteveboa resposta clínica e parasitológica com a terapêutica antimalárica, recebendo alta hospitalarpara controle no Programa de Ensaios Clínicos em Malária do Instituto Evandro Chagas eAmbulatório de Nefrologia. Considerações finais: o acometimento renal é uma dascomplicações graves da malária com possível evolução para insuficiência renal aguda (IRA), eque pode ser fatal. Desenvolvimento de estratégias preventivas de combate aos distúrbios renaisassociados à malária requer conhecimento dos aspectos clínicos e epidemiológicos da doença,diagnóstico precoce e correto, além de terapêutica antimalárica.

Objective: presentation of nephrotic syndrome case due to falciparum malaria. Case report:school child, 8 years old, female, admitted at Municipal Hospital of Tailândia, Pará, with historyof fever, edema, dark urine and oliguria. Because the patient evolved with anuria, she wastransferred to Fundação Santa Casa de Misericórdia do Pará (FSCM-PA), where she wasdiagnosed with nephrotic syndrome secondary to Plasmodium falciparum malaria, based onanamnesis, physical examination, and laboratory exams. The patient had clinical andparasitological response to antimalarial therapy, being discharged to control at Clinical EssayMalaria Program at Evandro Chagas Institute and in a Nephrology Outpatient Unit. Finalconsideration: renal involvement is one of the serious complications of malaria. It can progressto acute renal failure (ARF), and may be fatal. Development of preventive strategies againstkidney disorders due to malaria infection requires knowledge of epidemiological and clinicalfeatures of the disease, accurate and prompt diagnosis and antimalarial therapy.

Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Drug resistance is one of the principal obstacles blocking worldwide malaria control. In Colombia, malaria remains a major public health concern and drug-resistant parasites have been reported. In vitro drug susceptibility assays are a useful tool for monitoring the emergence and spread of drug-resistant Plasmodium falciparum. The present study was conducted as a proof of concept for an antimalarial drug resistance surveillance network based on in vitro susceptibility testing in Colombia. Sentinel laboratories were set up in three malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich protein 2 and schizont maturation methods were used to assess the susceptibility of fresh P. falciparum isolates to six antimalarial drugs. This study demonstrates that an antimalarial drug resistance surveillance network based on in vitro methods is feasible in the field with the participation of a research institute, local health institutions and universities. It could also serve as a model for a regional surveillance network. Preliminary susceptibility results showed widespread chloroquine resistance, which was consistent with previous reports for the Pacific region. However, high susceptibility to dihydroartemisinin and lumefantrine compounds, currently used for treatment in the country, was also reported. The implementation process identified critical points and opportunities for the improvement of network sustainability strategies.

Quinine levels in patients with uncomplicated falciparum malaria in the Amazon region of Brazil

We examined the plasmatic concentrations of quinine in patients with uncomplicated falciparum malaria in an endemic area of the Amazon region in Brazil in a prospective clinical trial, in which a standard three-day course of oral quinine plus doxycycline was used. We measured the quinine in the plasma samples on days 0 and 3by high performance liquid chromatography. The mean concentration of quinine was 6.04 ±2.21 µg/mL in male patients and 5.98 ±1.95 µg/mL in female patients. No significant differences in quinine concentration were observed between these two groups. All samples collected before starting treatment were negative for quinine. This information could help in the development of strategies for the rational use of antimalarial drugs in Brazil.

El tratamiento amodiaquina-sulfadoxinapirimetamina tiene eficacia del 98 por ciento para la malaria falciparum no complicada (Antioquia, Colombia; 2003) / Treatment with amodiaquine-sulfadoxine-pyrimethamine is 98 per cent effective against uncomplicated falciparum malaria

Antecedentes: la combinación amodiaquina (AQ) con sulfadoxinapirimetamina (SP) es el tratamiento de primera elección para la malaria falciparum no complicada (MFNC) en el departamento de Antioquia desde 1985 y en Colombia desde 2000. Objetivo: medir la frecuencia de falla terapéutica de AQ-SP en pacientes con MFNC, residentes en Turbo (zona de Urabá) y en El Bagre (zona del Bajo Cauca), Antioquia. Metodología: este estudio hace parte de uno mayor, que tiene diseño experimental balanceado, con ocho grupos; muestra de tamaño 50 en cada municipio, diseñada con criterios estadísticos y epidemiológicos; tratamiento aplicado en orden de llegada de los pacientes y según los esquemas usuales; seguimiento por 21 días; evaluación no ciega del efecto con el protocolo 1998 de la Organización Mundial de la Salud OMS. Resultados: se evaluaron 90 pacientes con MFNC; la falla terapéutica fue 2.2 por ciento: un caso precoz y otro tardío. El tratamiento fue bien tolerado. La parasitemia asexual se eliminó totalmente en 90 por ciento en los tres días de tratamiento (otro 10 por ciento tenía 40-80 parásitos/?L, que no es falla) y en 100 por ciento antes de 7 días de haber iniciado el tratamiento. AQ-SP mostró total capacidad de eliminar la fiebre: 100 por ciento afebriles el día 3. En los pacientes con gametocitos la cantidad de estos creció entre los días 0 y 7 y decreció luego hasta el día 21, cuando 52 por ciento los presentaban (promedio: 63 gametocitos/?L), pero no se evaluaron la viabilidad ni la fertilidad de tales gametocitos.Conclusión: el tratamiento de la MFNC con AQ-SP es altamente eficaz y debe mantenerse como la primera opción terapéutica, reforzada su eficacia antimalárica por el bajo costo, la buena tolerancia y la escasez y levedad de los efectos adversos imputables al tratamiento. AUT

Abstract Background: The combination of amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) is the firstchoice treatment for uncomplicated falciparum malaria (UCFM) in Antioquia (northwestern Colombia) since 1985 and in the country at large, since 2000. Objective: To measure the frequency of therapeutic failure of AQ-SP in patients with UCFM, residents of Turbo (Urabá zone) and El Bagre (Bajo Cauca zone) of Antioquia in northwestern Colombia. Methodology: This study is part of a larger one which has balanced design, with eight groups; the sample size in each municipality was 50 patients and it was obtained with statistical and epidemiological criteria; treatment was administered in the order of admission of patients according to the usual schedule; follow-up was done during 21 days; not-blind evaluation of the effect with the 1998 WHO protocol. Results: Ninety patients with UCFM were evaluated; therapeutic failure frequency was 2%; that is 2 cases, one early and one late. Conclusion: Treatment of UCFM with AQ-SP is highly effective and should be maintained as the first therapeutic choice; its effectiveness is reinforced by its low cost and good tolerance; also by the fact that undesirable effects attributable to the treatment are few and mild