Informe diário de evidências COVID-19: busca realizada em 14 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 14, 2020

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos.

Desenvolvimento somático e neurocomportamental da prole de ratas tratadas com o antimalárico primaquina durante a gravidez

A primaquina é o único fármaco que promove a cura radical da doença causada por P.vivax e possivelmente também por P. ovale, porém possui diversos problemas em se utilizar aprimaquina durante a gravidez, pois é um fármaco capaz de penetrar a placenta, e por não seconhecer o estado de enzima glicose-6-fosfato desidrogenase (G6DP) do feto, ametabolização do fármaco no feto pode ser deficitária. No entanto não tem se pesquisado queproblemas essa terapia pode causar a uma gravidez e a prole, o ineditismo do trabalhocontribui para o campo de estudo por elucidar os desafios que tal terapia enfrentaria. Nesseestudo foi visto que a primaquina não é capaz de ser transmitida para a prole através daamamentação, e que não afetou os parâmetros de desenvolvimento e crescimento dos jovensexpostos intra-utero ao fármaco, mas teve efeito na sobrevida dos filhotes e nocomportamento no teste de campo aberto (open-field).

Primaquine is the only drug that promotes the radical cure of the disease caused by p. Vivax and possibly also by p. Ovale, but has several problems in using primaquine during pregnancy, since it is a drug capable of penetrating the placenta, and by not knowing the state of the enzyme glucose 6-phosphate dehydrogenase (g6dp) of the fetus, the fetus in drug metabolism may be deficient. However, it has not been investigated what problems this therapy can cause to a pregnancy and the offspring, the novelty of the work contributes to the field of study to elucidate the challenges that such therapy would face. In this study, primaquine was not able to be transmitted to the offspring through breastfeeding, and did not affect the developmental and growth parameters of the intra-uterus exposed to the drug, but had an effect on the survival of the pups and behavior in the open-field test.

Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis / Eficacia terapéutica de esquemas de Primaquina usados como alternativa al tratamiento estándar en la prevención de recaídas por Plasmodium vivax: Una revisión sistemática y meta-análisis

Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

Objetivo: Comparar la eficacia y seguridad de los esquemas de primaquina actualmente usados para prevenir las recaídas de malaria por P. vivax. Métodos: A través de una revisión sistemática se identificaron ensayos clínicos que evaluaran la eficacia y seguridad para prevenir recurrencias por P. vivax del régimen de primaquina 0.5 mg/Kg/día por 7 o 14 días comparado al régimen estándar de 0.25 mg/Kg/día por 14 días. Se determinó la eficacia de primaquina con la incidencia acumulada de recurrencias posterior a 28 días. Se estimó el riesgo relativo global con un meta-análisis de efectos fijos. Resultados: Se identificaron 7 ensayos clínicos para el régimen 0.5 mg/Kg/día/7 días que mostraron una incidencia de recurrencias entre 0% y 20% con un seguimiento de 60 a 210 días; solo 4 estudios compararon con el régimen estándar y no se encontraron diferencias en las recurrencias entre ambos esquemas (RR= 0.977; IC 95%= 0.670-1.423). Se identificaron tres ensayos clínicos que usaron el esquema 0.5 mg/Kg/día/14 días con una incidencia de recurrencias entre 1.8% y 18.0% para 330 a 365 días; solo un estudio comparó con el régimen estándar (RR= 0.846; IC 95%= 0.484-1.477). Se encontró alto riesgo de sesgo y diferencias en la conducción de los estudios incluidos. Conclusión: No hay suficiente evidencia para determinar si los regímenes de primaquina usados como alternativas al tratamiento estándar tienen mejor eficacia para prevenir las recaídas de P. vivax. Se requieren ensayos clínicos para orientar los cambios en el esquema de tratamiento de este tipo de malaria.

Caracterización de la transmisión de la malaria por Plasmodium vivax en la región fronteriza de Panamá con Costa Rica en el municipio de Barú, Panamá / Characterization of Plasmodium vivax malaria transmission at the border of Panamá and Costa Rica

Introducción. Pocos estudios describen los factores asociados con la dinámica de transmisión de la malaria, o paludismo, por Plasmodium vivax en las regiones endémicas de Panamá. Objetivo. Caracterizar la dinámica de transmisión de la malaria producida por P. vivax en la región fronteriza de Panamá con Costa Rica. Materiales y métodos. Se llevó a cabo un estudio observacional, descriptivo y transversal. Se evaluaron la incidencia parasitaria anual, el índice de láminas positivas y el índice anual de exámenes de sangre. Se identificaron los anofelinos vectores, y se caracterizaron sus criaderos preferenciales, densidad larvaria e índice de picada/hombre/noche. Se hizo búsqueda pasiva y activa de casos sospechosos mediante examen de gota gruesa. Resultados. De 10.401 muestras de gota gruesa, 83 resultaron positivas para P. vivax. El 84 % de los casos provenía de zonas rurales, el 79 % constituía una población económicamente activa, la mediana de edad fue de 36 años y, la media, de 30 años. El 58,5 % de los casos fueron de sexo masculino. La incidencia parasitaria anual fue de 4,1 por 1.000 habitantes; el índice de láminas positivas fue de 0,8 % y el índice anual de exámenes de sangre fue de 51,9 %. El 65,0 % de los casos diagnosticados registró entre 100 y 2.000 parásitos/μl de sangre. Se identificaron los mosquitos vectores Anopheles albimanus y An. punctimacula. Conclusión. Es necesario el seguimiento de estudios entomológicos, el fortalecimiento de la vigilancia epidemiológica, la consideración de los factores de riesgo y la realización de un trabajo en coordinación con las autoridades de salud de Costa Rica, para controlar la malaria en esta región.

Introduction. Few studies have described the factors associated with Plasmodium vivax transmission dynamics in endemic regions from Panamá. Objective. Malaria transmission dynamics produced by P. vivax were characterized at the border between Panamá and Costa Rica. Materials and methods. In the municipality of Barú, an observational, descriptive and cross-sectional study was undertaken to measure the annual parasite index (API), slide positivity index (SPR), and the annual blood examination rate (ABER). The most frequent symptoms and signs in malaria patients were recorded. The anopheline species were identified in the area and the preferred larval habitats, the density of larval populations in the larval habitats and the bites/human/night were characterized. Results. Of a total of 10,401 thick smear blood samples, 83 were positive for P. vivax. Of these, 84% came from rural areas and 79% were from economically active individuals. The median and average ages were 36 and 30 years, respectively, and 58.5% of the malaria cases were male. API was 4.1/1,000 inhabitants; SPR was 0.8% and ABER was 51.9%. Of the diagnosed cases, 54% showed blood parasitemias ranging between 100-2,000 parasites/μl. The majority of the cases were observed in May and June. Two mosquito vector species were identified-- Anopheles albimanus and An. punctimacula. Conclusion. These observations indicate the advisibility of continued entomological studies, strengthening of epidemiological surveillance, consideration of additional risk factors and evaluation of work performance in the border region. This will require coordination with health authorities of both countries to control malaria in this region.

Recurrencias de malaria por Plasmodium vivax según el uso de primaquina: análisis de estudios descriptivos longitudinales / Plasmodium vivax malaria recurrence according to the use of primaquine: analysis of longitudinal descriptive studies

ANTECEDENTES: la primaquina (PQ) es el único medicamento disponible en el mercado para prevenir recurrencias del paludismo por Plasmodium vivax pero varios aspectos suyos se desconocen. OBJETIVO: comparar regímenes de PQ para prevenir recurrencias de malaria vivax. METODOLOGÍA: revisión sistemática de datos. RESULTADOS: 1. ¿Según los estudios descriptivos, la PQ es eficaz para prevenir las recurrencias del paludismo vivax? Sí. La comparación de estudios que no usaron PQ con otros que sí la aplicaron, en cualquier esquema, mostró que si no se usa PQ la recurrencia es altamente probable. 2. ¿Tienen la misma eficacia dosis diarias (mg/kg) iguales pero dosis totales diferentes? La dosis total de 75 mg es tanto o más eficaz que la de 210 mg. 3. ¿La eficacia anti-recurrencias depende del lugar donde sucede la infección? Si. Hay variación según país y región. 4. ¿La frecuencia de recurrencias depende del tiempo de seguimiento post tratamiento? La respuesta no es uniforme para todos los lugares. CONCLUSIONES: la PQ resultó eficaz para prevenir las recurrencias, pero no fue 100%. Las dosis totales de 210 y de 75 mg tuvieron igual eficacia, pero 75 mg sólo han sido evaluados en India, donde P. vivax parece ser más sensible a la PQ que en otros lugares. Parece indudable la influencia del lugar en la proporción de recurrencias, incluso con una misma dosis total. El papel del tiempo de seguimiento no resultó claro. Deben evaluarse esquemas alternativos al estándar, que tiene eficacia promedio de 90% o más.

BACKGROUND: primaquine (PQ) is the only drug available in the market to prevent Plasmodium vivax malaria recurrence, but several aspects are still unknown. OBJECTIVE: To compare PQ regimens to prevent recurrence of vivax malaria. METHODS: systematic review and meta-analysis of data. RESULTS: 1. According to descriptive studies, is PQ effective in preventing recurrence of vivax malaria? Yes. The comparison of studies that did not use PQ to others that did, using any regimen, showed that if PQ is not used, recurrence is highly likely. 2. Are equal daily doses effective (mg/kg) but total doses different? The total dose of 75 mg is equally or more effective than 210 mg. 3. Does the efficacy depend on where the infection happens? Yes. There is variation by country and region. 4. Does the recurrence rate depend on the post-treatment time follow-up? The answer is not uniform everywhere. CONCLUSIONS: Although not 100%, PQ is effective in preventing recurrence. Total doses of 210 and 75 mg are equally effective, but 75 mg alone has been evaluated in India, where P. vivax seems to respond better to PQ than elsewhere. The effect of place in the proportion of recurrences seems evident, even using the same total dose. The role of follow-up time is not clear. Although the standard regimen has an average effectiveness of 90% or more, alternative regimens should be assessed.

Plan de mejoramiento del control de la malaria hacia su eliminación en Mesoamérica / Plan to improve malaria control towards its elimination in Mesoamerica

Desarrollar un plan de fortalecimiento del control de la mala-ria hacia su eliminación. En 2009, bajo la coordinación del Instituto Nacional de Salud Pública, se integró un equipo técnico transdisciplinario para hacer un diagnóstico situacional de la malaria y de los programa de control y para la selección de prácticas efectivas de intervención que serían incorporadas al plan, en el marco de un ejercicio de teoría de cambio. Se establecieron criterios de estratificación de las localidades con base en sus condiciones de transmisión. Se identificaron limitaciones estructurales y operativas de los programas de control. Se elaboró un plan de intervenciones para mejorar la cobertura de vigilancia epidemiológica, intervenciones antimaláricas y diagnóstico y tratamiento oportunos de casos. El plan delinea con fases progresivas de implementación: reorganización, intensificación de intervenciones y evaluación de la factibilidad de eliminación. La adopción de un plan estratégico único brindará lineamientos y elementos administrativos para conformar un sistema que coordine las actividades de los programas nacionales de control y facilite la eliminación de la malaria en la región.

To develop a plan to strengthen the control of malaria towards its elimination. In 2009, under the coordination of the National Public HealthInstitute ofMexico, atransdisciplinary equipment of technical and operative experts was conformed to carry out a situational analysis of malaria and control programs and for the selection of effective practices of intervention that would be incorporated to the plan, within the framework of an exercise in Theory of Change. Criteria for thestratificationof thelocalities, based ontheirtransmission characteristics were established. The structural and operative limitations of the control programs were identified. A plan of interventions was elaborated to improve the coverage of epidemiological surveillance, anti-malaria interventions and opportune diagnosis and treatment of cases. The plan delineates progressive phases of implementation: reorganization, intensification of interventions and evaluation of elimination feasibility. The adoption of a regional strategic plan will provide guidance and administrative elements to conform a system that coordinates the activities of the national control programs and facilitate the elimination of malaria in the region.

The monitoring of hematopoietic stem cell transplant donors and recipients from endemic areas for malaria / Monitoramento de doadores e receptores provenientes de áreas endêmicas para malária em transplante de células-tronco hematopoiéticas

Malaria is an unusual complication after hematopoietic stem cell transplantation in non-endemic countries. However, transplant candidates, recipients and donors living in endemic regions frequently report previous episodes of malaria. This fact could represent an important risk for immunosuppressed recipients that could develop severe malaria cases. We report a case of hematopoietic stem cell transplant (HSCT) in which the donor had a history of previous malaria, and close monitoring was performed before and after procedure by parasitological and molecular tests. The donor presented Plasmodium vivax in thick blood smears one month after transplant and was treated according to Brazilian Health Ministry guidelines. The polymerase chain reaction (PCR) was able to detect malaria infection in the donor one week earlier than thick blood film. Even without positive results, the recipient was pre-emptively treated with chloroquine in order to prevent the disease. We highlight the importance of monitoring recipients and donors in transplant procedures with the aim of reducing the risk of malaria transmission.

A malária é complicação incomum após o transplante de células-tronco hematopoiéticas em países endêmicos. No entanto, candidatos a transplantes, receptores e doadores que vivem em regiões endêmicas frequentemente relatam episódios anteriores de malária. Este fato pode representar um risco importante para receptores imunossuprimidos, que podem desenvolver casos de malária grave. Relatamos um caso de transplante de células-tronco hematopoiéticas (TCTH) em que o doador teve história de malária anterior e um monitoramento por meio de exames parasitológicos e moleculares foi realizado antes e após o procedimento. O doador apresentou Plasmodium vivax na gota espessa um mês após o transplante e foi tratado de acordo com as orientações do Ministério da Saúde brasileiro. A reação em cadeia da polimerase (PCR) foi capaz de detectar a infecção por malária no doador uma semana mais cedo do que a gota espessa. Mesmo sem resultados positivos, o receptor foi preventivamente tratado com cloroquina, a fim de prevenir as formas sanguíneas assexuadas. Destacamos a importância do monitoramento de receptores e doadores em procedimentos de transplante, com o objetivo de reduzir o risco de transmissão da malária.

Malária vivax com tempo de incubação prolongado, detectada no Distrito Federal: relato de três casos / Vivax malaria with long incubation period, detected in the Federal District: three case reports

Foram detectados três casos de malária vivax em Brasília, Distrito Federal, área considerada indene, procedentes da Amazônia, seis meses após estarem residindo em Brasília. Período de incubação prolongado tem sido descrito apenas para infecções por cepas de Plasmodium vivax de clima temperado. Não foi possível genotipar os parasitos.

Three cases of vivax malaria originating from the Amazon region were detected after living in Brasilia, Federal District (considered to be a non-endemic area), for six months. Long incubation periods have been described only for infections due to strains of Plasmodium vivax in temperate climates. It was not possible to genotype the parasites.

Case of Malarial Hepatitis by Plasmodium Vivax / 대한소화기학회지

Malarial infection is one of the most important tropical diseases, but also increasing in the temperate regions. Severe malaria with organ dysfunction is commonly associated with Plasmodium falciparum, but rarely with Plasmodium vivax. Malarial hepatitis is also unusual in P. falciparum and very rare in P. vivax. Only 3 cases of malarial hepatitis caused by P. vivax have been reported in the world. Because the presence of hepatitis in malaria indicates a more severe illness with higher incidence of other complications and poor prognosis, malarial patients should be meticulously monitored for hepatic dysfunction with or without jaundice. We report here a case of malarial hepatitis caused by P. vivax that was presented by fever, general ache, nausea, fatigue, and significant elevation of aminotransferase and bilirubin.

Eficacia de tres esquemas con cloroquina – primaquina para el tratamiento de la malaria por Plasmodium vivax en Colombia / Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia

La malaria por Plasmodiun vivax es una de las principales causas de morbilidad en centro y sur América. En Colombia es la más prevalente y representa el 75 por ciento de los casos reportados. La primaquina (PQ) es la única droga disponible de uso clínico para eliminar los hipnozoitos y prevenir recaídas en la malaria por P. vivax. Se hizo un ensayo clínico aleatorio controlado sin placebo y no ciego. Se estudió la eficacia antirrecaída de tres esquemas de tratamiento con dosis total de PQ (45, 105 y 210 mg) suministrados en dosis de 15 mg/día, en 210 adultos con diagnóstico de P. vivax en dos municipios de Antioquia (Colombia). Todos los pacientes recibieron una dosis total de 1.500 mg de cloroquina [CQ] en tres días (600 mg el día 1 y 450 mg los días 2 y 3). Los pacientes tuvieron una respuesta clínica adecuada del 100 por ciento al tratamiento CQ+PQ hasta el día 28, en los tres grupos. El porcentaje de recurrencias durante los seis meses de seguimiento fue de 45 por ciento, 36,6 por ciento y 17,6 por ciento para los grupos con 45, 105 y 210 mg de PQ respectivamente. El tratamiento convencional (210 mg) fue un factor de protección para las recurrencias cuando se comparó con los esquemas de 45 y 105 mg respectivamente. El tratamiento convencional sigue siendo el tratamiento más eficaz para prevenir las recaídas en la malaria por P. vivax en una zona endémica...

Plasmodium vivax malaria is an important cause of morbility in Central and South America. In Colombia this is the most prevalent malaria infection representing75 % of the reported cases. To define the efficacy of the chloroquine and primaquine regimen to eliminatehypnozoites and prevent relapses, we a conducted a random controlled clinical trial of three primaquine regimens in an open-label study. We evaluated the anti-relapse efficacy of a total primaquine dose of 45, 105 and 210 mg administered at 15mg/day in 210 adults with P. vivaxinfection from the Northwestern region of Colombia. Cure rates for blood stage vivax malaria by day 28 of followupwere 100 % in all groups. Post-treatment reappearance of parasitaemia during the 6 months of following up was 45 %, 36,6 % and 17,6 % respectively, for each group. When compared to other groups, administration of 210 mg was a significant protection factor for reappearance of parasitaemia in an endemic area.

Associação de metemoglobinemia e deficiência de glicose-6-fosfato desidrogenase em pacientes com malária tratados com primaquina / Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine

Este estudo teve como objetivo verificar a ocorrência de metemoglobinemia em indivíduos deficientes da glicose-6-fosfato desidrogenase durante o tratamento da infecção malárica com primaquina. Foram selecionados pacientes com diagnóstico para malária por Plasmodium vivax ou mista V+F (Plasmodium vivax + Plasmodium falciparum), Grupo 1: com 74 indivíduos com diagnóstico clínico de metemoglobinemia e Grupo 2: 161 indivíduos sem diagnóstico clínico de metemoglobinemia. Quanto à deficiência da G6PD, nos Grupos 1 e 2, houveram 51,3 por cento (38) e 8,7 por cento (14) de indivíduos enzimopênicos, respectivamente, demonstrando através de tais dados, significância estatística na associação com a metemoglobinemia somente nos indivíduos do Grupo 1 (p<0,05). A comparação da relação da metemoglobinemia à deficiência da G6PD mostrou haver uma possível associação de indivíduos enzimopênicos desenvolverem metemoglobinemia com maior freqüência.

This study had the aim of investigating occurrences of methemoglobinemia among individuals with glucose-6-phosphate dehydrogenase deficiency during treatment for malaria infection using primaquine. Patients with a diagnosis of malaria caused by Plasmodium vivax or the V+F mixture (Plasmodium vivax + Plasmodium falciparum) were selected. Group 1 consisted of 74 individuals with a clinical diagnosis of methemoglobinemia and Group 2 consisted of 161 individuals without a clinical diagnosis of methemoglobinemia. The glucose-6-phosphate dehydrogenase deficiency rates (numbers of enzymopenic individuals) in Groups 1 and 2 were 51.3 percent (38) and 8.7 percent (14) respectively. These data demonstrated a statistically significant association with methemoglobinemia only among the individuals in Group 1 (p<0.05). Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently.

A case of symptomatic splenic infarction in vivax malaria

Splenic infarction is a rare complication in malaria cases, and is caused primarily by Plasmodium falciparum. Recently in South Korea, only P. vivax has prevailed since 1993. Although the probability that symptomatic splenic infarction may occur in vivax malaria cases is considered relatively high, there have never been any case reports describing the occurrence of symptomatic splenic infarction in cases of vivax malaria. A 34-year-old man presented with fever that had persisted for 5 days. P. vivax infection was verified using a peripheral blood smear, and chloroquine was utilized to treat the fever successfully. Six days later, the patient developed pain in the left upper abdomen, which was diagnosed as splenic infarction by computed tomography.

A case of symptomatic splenic infarction in vivax malaria

Splenic infarction is a rare complication in malaria cases, and is caused primarily by Plasmodium falciparum. Recently in South Korea, only P. vivax has prevailed since 1993. Although the probability that symptomatic splenic infarction may occur in vivax malaria cases is considered relatively high, there have never been any case reports describing the occurrence of symptomatic splenic infarction in cases of vivax malaria. A 34-year-old man presented with fever that had persisted for 5 days. P. vivax infection was verified using a peripheral blood smear, and chloroquine was utilized to treat the fever successfully. Six days later, the patient developed pain in the left upper abdomen, which was diagnosed as splenic infarction by computed tomography.

Clinical efficacy of chloroquine versus artemether-lumefantrine for Plasmodium vivax treatment in Thailand

Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.

Evaluation of Anti-Malarial Effects of Mass Chemoprophylaxis in the Republic of Korea Army

Vivax malaria was endemic on the Korean peninsula for many centuries until the late 1970's when the Republic of Korea (ROK) was declared "malaria free". Since its re-emergence in 1993, the number of malaria cases in the military increased exponentially through 2000 near the demilitarized zone. Chemoprophylaxis with chloroquine and primaquine has been used in the ROK Army since 1997 in an attempt to reduce the number of the malaria cases throughout the ROK. Data show that chemoprophylaxis contributed, in part, to the decrease in the number of malaria cases among military personnel. However, mass chemoprophylaxis on a large scale in the ROK Army is unprecedented and extensive supervision and monitoring is warranted to determine its effectiveness and to monitor the appearance of chloroquine tolerant/resistant strains of Plasmodium vivax.

Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand.

Our previous study showed that in vitro susceptibility of Plasmodium vivax to chloroquine has significantly decreased in Thailand within the past two decades. Thus, the evaluation of alternative antimalarials for treatment of vivax malaria is needed. The aim of this study was to examine parasitological and clinical efficacy of an artemisinin derivative (artesunate) for the treatment of vivax malaria in patients who were admitted to the Bangkok Hospital for Tropical Diseases. We randomly allocated patients aged 12-56 years to receive 3.3mg/kg (adult dose 200 mg) on the first day, and for the next four days each patient was given 1.65 mg/kg orally (adult dose 100 mg), total dose = 600 mg. After the five-day course of artesunate, primaquine was given: a single oral dose of 15mg for 14 days. A total number of 42 patients received treatment. All participants were followed up for 28 days. In all the cases, both parasitemia and fever were resolved rapidly; the mean fever clearance time and parasite clearance time, 14.6 and 36.7 hours, respectively, showed that therapeutic response to artesunate was better than that of chloroquine. The 14-day cure rate was 100%, but reappearance of parasitemia was seen in two patients on days 21 and 25 following treatment, respectively. These two cases of failure rate should be considered as true relapse rather than recrudescence, since the relapse interval in Southeast Asian vivax malaria according to recent findings seems to be 3 weeks after start of treatment, if primaquine is not given or an inadequate amount is given. In conclusion, artesunate might be useful in treatment of vivax malaria, causing a good blood schizontocidal effect. However, to prevent emerging resistance it should never be used alone.

The clinical and epidemiological features of childhood malaria in a moderately endemic area of Sri Lanka.

This study describes some clinical and epidemiological features of childhood malaria in a moderately endemic area of southern Sri Lanka. Six hundred and sixty-two children, who experienced 1,138 attacks of malaria, and 172 children, who experienced 202 attacks of acute non-malarial fever, were followed over a period of two years. Of the 1,138 malaria infections followed, 776 were due to P. vivax, 359 were due to P. falciparum, and 3 were mixed infections. The majority of children presented within the first three days of the onset of symptoms. Headache (96%), feeling cold (81%) and arthralgia (77%) were the commonest presenting symptoms. Two hundred and sixty-four children experienced more than one attack of malaria. The clinical and epidemiological features of childhood malaria that have important implications for the planning and targeting of preventive measures are discussed.