Multidrug resistance is a major obstacle to the control of Plasmodium falciparum malaria, and its origins and modes of dissemination are imperfectly understood. In this study, haplotyping and microsatellite analysis of malaria from 5 regions of the South American Amazon support the conclusion that the parasite mutations conferring mid- and high-level resistance to the antifolate combination sulfadoxine-pyrimethamine have a common origin. Parasites harboring these mutations are also found to share drug-resistance alleles that confer a unique chloroquine resistance phenotype and to be similar at loci not linked to drug resistance, although not genetically identical. Since the 1980s, multidrug-resistant P. falciparum has spread in a north-northwest manner across the continent, from an origin likely in the lower Amazon. This study highlights the importance of continent-wide malaria-control policies and suggests that the containment of resistance to the next generation of therapies may be feasible.

Two patients from the gold mines of Bolivar State, Venezuela, presenting cutaneous leishmaniasis in the genital region, an unusual location, are described. The first patient showed an ulcerated lesion of the glans penis. Leishmanin skin test was positive. A biopsy specimen revealed a granulomatous infiltrate containing Leishmania parasites. In the second patient, Leishmanin skin test was positive, HIV and VDRL were negative. Leishmania parasites were present in a biopsy of an ulcerated lesion in the scrotum, with an indurated base, infiltrative borders with an yellowish exudate. Patients were treated with meglumine antimoniate and the lesions healed.

Abstract. The state of Bolivar in Venezuela experiences episodic outbreaks of multidrug-resistant Plasmodium falciparum malaria. We obtained P. falciparum-infected blood samples in Bolivar in 1998−2000, and performed molecular assays for mutations conferring resistance to the antifolate combination of sulfadoxine-pyrimethamine (SP) and to chloroquine. All infections carried the dihydrofolate reductase (dhfr) S108A and N51I mutations, and 45% of the infections had the dhfr C50R mutation, which has been implicated in mid-level resistance to SP. Two dihydropteroate synthase (dhps) mutations also involved in SP resistance, A581G and K540E, were detected in 90% and 67% of the samples, respectively. The dhfr I164L mutation, which confers high-level resistance, was not identified. The P. falciparum chloroquine resistance transporter (pfcrt) K76T mutation, which is critical for chloroquine resistance, was found in 167 of 168 infections. Six dhfr/dhps allelotypes and four pfcrt-resistant alleles were observed. Their interrelationships suggest a semi-clonal propagation of P. falciparum malaria in Bolivar, and an invasion of multi-resistant pathogens from Brazil. Despite national restrictions on the use of SP and chloroquine, genotypic resistance to these therapies remains widespread in Bolivar.

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Abstract. Resistance to antimalarial chemotherapy is one of the greatest difficulties for the control of malaria transmission. Seventy patients with Plasmodium falciparum malaria were included in a study of resistance to chloroquine and sulfadoxine-pyrimethamine therapy. Resistance levels RI, RII, and RIII were established. Eighteen infections (51%) cleared after chloroquine treatment and did not recur within 28 days of follow-up; these were classified as sensitive. Ten infections (29%) were resistant at the RI level. Resistance at level RII was observed in 5 (14%) cases, and RIII resistance was demonstrated in 2 infections (6%). With sulfadoxine-pyrimethamine, 28 (80%) infections were classified as sensitive. Six infections (17%) showed resistance at level RII, and 1 (3%) infection was resistant at the RI level. Resistance at level RIII was not observed. In a microtest for chloroquine and sulfadoxinepyrimethamine sensitivity in vitro, schizont development was accomplished successfully in 70 blood samples. In vitro resistance to chloroquine was demonstrated in 15 of 70 (21%) of all isolates. Eight of 70 (11%) of all isolates showed resistance to sulfadoxine-pyrimethamine. Diversity of response of P. falciparum to the studied antimalarial drugs in the Guayana area of Venezuela is considered a problem restricting the control of malaria in this geographical area. A constant evaluation program monitoring P. falciparum drug sensitivity is necessary for preserving the efficacy of the established treatment.After a successful eradication program implemented over several decades, malaria is now endemic in Venezuela in patchy forest areas where activities associated with gold mining are limiting control efforts. From 1992 to 1995, Plasmodium falciparum infections and outbreaks were registered only in remote areas in southern Venezuela, in 11 municipalities that are located in Bolívar State and Amazonas and Delta Amacuro territories. Bolívar State has contributed more than 60% of all malaria cases in Venezuela; of these, 20% correspond to P. falciparum infections. On average, the infection rates of the parasite reach 2 cases per 1,000 inhabitants among a population composed mainly of gold and diamond miners and indigenous groups.Resistance to antimalarial chemotherapy is one of the obstacles for the control of malaria transmission in various regions of the world. The adequate use of antimalarial drugs is essential for reducing the high morbidity and mortality associated with P. falciparum malaria in nonimmune hosts. Therefore, knowledge of the geographical distribution of P. falciparum strains that are resistant and the identification of the severity of this resistance are important in the choice of an effective therapeutic regimen.Chloroquine resistance was first reported in Venezuela, 1 and soon after was confirmed in several countries. Since 1975, very few studies on resistant P. falciparum strains have been carried out in Venezuela; some of them have shown different resistance levels in vivo for chloroquine 2 (Navarret...

The teleostean cerebellar cortex has been studied with respect to its cytoarchitectonic arrangement and intracortical neuronal circuits. Samples of fish cerebellum were fixed either by immersion of vascular perfusion in 5% glutaraldehyde solution and processed for light and scanning electron microscopy. The cerebellar cortex shows four distinct layers: granular; fibrous stratum; Purkinje cell; and molecular layers. In the granular layer, mossy and climbing fiber glomeruli were characterized. The mossy glomerular region appeared as polygonal, round or ovoid clews formed by the convergence of up to 17 dendritic profiles upon a thick mossy fiber branch. The "en passant" nature of mossy fiber-granule cell dendrite synaptic relationship was clearly appreciated. The climbing fibers showed tendril and glomerular collaterals. The latter form thin, elongated glomeruli. Remnants of a neuroglial envelope were observed in the mossy fiber glomeruli but are apparently absent from the climbing fiber glomeruli. The beaded-shape Golgi cell axonal ramifications were observed participating in the formation of both glomerular types. Velate protoplasmic astrocytes and oligodendrocytes were also identified. The fibrous stratum appeared to be formed by compact bundles of thick and think myelinated axons, running horizontally beneath the Purkinje cell layer and apparently belonging to ascending climbing fibers and descending Purkinje cell axons. At the Purkinje cell layer a selective removal of Bergmann glial cells was observed allowing the visualization of the pericellular basket and the pinceaux. Climbing fiber stems and their tendril collaterals were seen on their way to the molecular layer ascending parallel to the Purkinje dendritic ramifications. Stellate neuron processes were found passing through the fan-like arborescence of Purkinje cell dendrites.

Acute acalculous cholecystitis (ACC) is unusual. We present a case of cholecystitis associated with visceral leishmaniasis (VL) in a man in Venezuela who presented high fever, anorexia and abdominal pain. Histopathological study of the gallbladder showed Leishmania spp. ACC in VL must be kept in mind in tropical countries.