The American Journal of Tropical Medicine and Hygiene - Volume 73, Issue 3, September 2005

We report a case of snakebite in which envenomation was manifested through impairment of the visual field. The patient, a 46-year-old man, was bitten on the right thumb by Bothrops lanceolatus. Treatment with a specific equine antivenom (Bothrofav®) was administered one hour after the bite. With the exception of fang marks, the results of a clinical examination, particularly the neurologic component, were normal. The day after the bite, the patient developed an inferior left lateral homonymous quadranopsia with macular epargne. T2 magnetic resonance imaging showed a right occipital infarction. His condition improved clinically and biologically. This observation of snakebite is the first in which envenomation was accompanied exclusively by an impairment of the visual field. Envenomation by B. lanceolatus is distinct in its incidence of significant thrombotic complications at a distance from the site of the bite.

Enterohemorrhagic Escherichia coli O157:H7 was isolated for the first time in Vietnam. Shiga toxin–producing E. coli were isolated from 8 of 100 cows examined. The two strains showing serotype O157:H7 carried the eae, ehxA, and stx2c genes, but the other six were negative for the eae gene.

Severe and fatal malaria is associated with the increased presence of malaria hemozoin in peripheral phagocytes. Large studies of this relationship are hampered by the fact that identifying and counting phagocytes on thick blood smears is time consuming. Distinguishing which mononuclear cells are monocytes and which granulocytes are neutrophils requires time and careful training. In this study, we evaluated a simplified method in which only the proportions of hemozoin-containing mononuclear cells and granulocytes are counted. Thick blood films from 471 Gabonese children with malaria were evaluated. We found a linear relationship and a strong correlation between the proportions of hemozoin-containing monocytes versus mononuclear cells (r = 0.85) and neutrophils versus polymorphonuclear cells (r = 0.93), respectively. The two methods had similar predictive values, as estimated by receiver operating characteristics curves. This simplified method can be used to estimate the amount of extra-erythrocytic pigment in peripheral blood, and we suggest that it may be particularly suitable for very large studies.

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.

Imported malaria remains an important problem in Japan. We have reviewed the medical records of 170 cases of malaria in our hospital, which corresponds to 14.9% of the total cases in Japan. The predominant malarial species was Plasmodium falciparum (52.3%), and the most frequent area of acquisition was Africa (54.2%), followed by Asia (20.9%) and Oceania (19.6%). The most common reason for travel among Japanese patients was business. A significant proportion (22.2%) of vivax malaria cases experienced relapse despite standard primaquine therapy. Most primaquine failures were from Oceania. We also found that a substantial number of Japanese patients contracted malaria without chemoprophylaxis and consulted medical facilities with an unfavorably long delay from initial symptoms (median: 3.0 days). Direct education of travelers and travel companies, in addition to health care providers, is likely necessary to improve outcomes of imported malaria.

The Republic of Korea experienced a re-emergence of Plasmodium vivax malaria in 1993. The incidence of this disease increased rapidly through 2000 with its geographic distribution expanding from the vicinity near the Demilitarized Zone to the adjacent outlying areas. However, the number of cases of P. vivax malaria since that time period has decreased. A total of 2,538 cases occurred in 2001, and this decreased to 1,761 cases and 1,164 cases in the two subsequent years. A total of 5,463 cases of P. vivax malaria were reported from 2001 through 2003; 25.26% (1,380) were reported among Republic of Korea military personnel, 27.48% (1,501) were among veterans who had been discharged from the military within two years, and 47.26% (2,582) were among the civilian population. Mosquito control activities by the North Korean and South Korean governments, chemoprophylaxis of Republic of Korea Army personnel, and the low level of Anopheles mosquitoes in 2001 may have been factors responsible for the decreasing number of malaria cases. However, local transmission might have taken place in urban regions of the malaria-risk areas that are within 30 km south of the Demilitarized Zone. Extensive intervention and continued surveillance are warranted to prevent the epidemic from re-expanding and to eliminate this disease in the Republic of Korea.

In Malawi, trimethoprim-sulfamethoxazole (TS) is the recommended first-line treatment for children with Integrated Management of Childhood Illness dual classifications of malaria and pneumonia, and sulfadoxine-pyrimethyamine (SP) plus five days of treatment with erythromycin (SP plus E) is the recommended second-line treatment. Using a 14-day, modified World Health Organization protocol, children with dual IMCI classifications of malaria and pneumonia with Plasmodium falciparum parasitemia were randomized to receive TS or SP plus E. Clinical and parasitologic responses and gametocytemia prevalence were obtained. A total of 87.2% of children receiving TS and 80.0% receiving SP plus E reached adequate clinical and parasitologic responses (ACPRs) (P = 0.19). Severely malnourished children were less likely to achieve ACPRs than those better nourished (relative risk = 3.34, P = 0.03). Day 7 gametocyte prevalence was 55% and 64% among children receiving TS and SP plus E, respectively (P = 0.19). Thus, TS and SP plus E remain efficacious treatment of P. falciparum malaria in this setting. However, patient adherence and effectiveness of five days of treatment with TS is unknown.

We assessed the efficacy and safety of a seven-day course of artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in 55 non-immune patients living in Bangui, Central African Republic. The parasitologic cure rates were 100%, 95%, and 85% on days 14, 28, and 42, respectively. There were no significant differences in parasitemia density, 50% inhibitory concentration of dihydroartemisinin, and frequency of mutant P. falciparum multidrug resistance 1 codon 86 between patients who were cured and those who displayed recrudescence. However, the 90% inhibitory concentration for dihydroartemisinin and the number of genotypes isolated were both higher in the recrudescent patients (five- and two-fold, respectively). We found an association between recrudescence and decreased sensitivity. This suggests that the use of artemisinin compounds alone will select resistant strains. We conclude that artesunate should not be used in monotherapy even in seven-day courses, but only in combination with other anti-malarials to prevent the emergence of resistant P. falciparum.

Use of an insecticide-treated net (ITN) is now the central focus for the Roll Back Malaria campaign, and disease-endemic countries have embarked on large-scale ITN distribution programs. We assessed the impact of an ITN social marketing program on clinical malaria in children less than five years of age. A case-control study was undertaken at Ndirande Health Center in the peri-urban area of the city of Blantyre, Malawi. Cases were defined by an axillary temperature ≥ 37.5°C or a history of fever within the last 48 hours and a positive blood smear for Plasmodium falciparum. The individual effectiveness of ITN use was 40% (95% confidence interval [CI] = 10–60%) when cases were compared with clinic controls and 50% (95% CI = 0–60%) in comparison with community controls. With ITN coverage of 42%, the community effectiveness of this program was estimated to range from 17% to 21%. This represents 1,480 malaria cases averted by the intervention in a population of 15,000 children. Our results show that the benefits of ITN social marketing programs in reducing malaria are enormous. Targeting the poor could increase those benefits.

Although genetically distinct malaria parasites have been shown to simultaneously infect an individual, the total number of unique parasites has not been systematically studied. We examined multiple clones (8–38) from individual blood samples collected from Papua New Guinean children for polymorphisms in the Plasmodium vivax Duffy binding protein (dbpII) and the merozoite surface protein 3α (msp3α). We found a median of 4 (range = 2–6) and 12 (range = 2–23) unique genotypes based on dbpII and msp3α, respectively, per person at one time point and at least 12–33 unique genotypes per person over a four-month period. Control polymerase chain reactions (PCRs) detected 0–31% of clones with haplotypes that arose from PCR artifacts, indicating that caution must be taken when using PCR-based analysis to examine complex infections. To reduce artifacts from clones, analysis was based on haplotypes unlikely to have been generated by PCR artifacts or had been previously identified. Plasmodium vivax infections can be highly complex in disease-endemic areas, suggesting continual genetic mixing that could have significant implications for the use of antimalarial drugs and malaria vaccines.

To study gene expression differences between oocyst and salivary gland sporozoites, cDNA libraries previously constructed from the two sporozoite populations of the avian malaria parasite, Plasmodium gallinaceum, were used in a subtractive hybridization protocol to isolate Pg93, a novel oocyst sporozoite gene. Pg93 encodes a putative ~76 kDa translated protein that was predicted to localize to the nucleus. Transcriptional analysis indicates that Pg93 is preferentially expressed in oocyst sporozoites versus salivary gland sporozoites. Immunolocalization assays confirm both the nuclear prediction and transcriptional analysis, suggesting that Pg93 is a nuclear protein. BLAST sequence analysis indicates that Pg93 represents a novel gene that has significant homology with a Plasmodium falciparum hypothetical protein and translated Plasmodium knowlesi and Plasmodium vivax nucleotide sequences. This is the first characterization of a Plasmodium nuclear protein that shows preferential expression in one sporozoite population as compared with the other population.

Observations on Plasmodium simium infections in Saimiri boliviensis boliviensis monkeys suggest that this host-parasite combination would be a suitable model for the testing of candidate vaccines against Plasmodium vivax. To evaluate the normal course of infections, parasitemia in 52 splenectomized S. boliviensis boliviensis monkeys infected with P. simium were analyzed. The mean maximum parasite count for 31 monkeys after injection with trophozoite-infected erythrocytes was 77,580/μL. Twenty-one monkeys were infected via sporozoites, and prepatent periods ranged from 14 to 24 days with a median of 15 days. The mean maximum parasite count was 29,234/μL. The mean maximum parasite count for monkeys previously infected with Old World P. vivax was 26,337/μL versus 56,362/μL for those previously infected with New World P. vivax, possibly suggesting a closer antigenic relationship between P. simium and the Old World parasites.