Comparison of the OptiMAL test with PCR for diagnosis of malaria in immigrants.
(17/1177)
The OptiMAL test (Flow Inc., Portland, Oreg.), which detects a malaria parasite lactate dehydrogenase (pLDH) antigen, has not been evaluated for its sensitivity in the diagnosis of malaria infection in various epidemiological settings. Using microscopy and a PCR as reference standards, we performed a comparison of these assays with the OptiMAL test for the detection of Plasmodium falciparum and Plasmodium vivax infection in 550 immigrants who had come from areas where malaria is endemic to reside in Kuwait, where malaria is not endemic. As determined by microscopy, 125 (23%) patients had malaria, and of these, 84 (67%) were infected with P. vivax and 36 were infected with P. falciparum; in 5 cases the parasite species could not be determined due to a paucity of the parasites. The PCR detected malaria infection in 145 (26%) patients; 102 (70%) of the patients had P. vivax infection and 43 had P. falciparum infection. Of the five cases undetermined by microscopy, the PCR detected P. falciparum infection in two cases, P. vivax infection in two cases, and mixed (P. falciparum plus P. vivax) infection in one case. Correspondingly, the OptiMAL test detected malaria infection in 95 patients (17%); of these, 70 (74%) had P. vivax infection and 25 were infected with P. falciparum. In this study, 61 (49%) of the 125 malaria cases, as confirmed by microscopy, had a degree of parasitemia of <100 parasites per microl, and 23 (18%) of the cases had a degree of <50 parasites per microl. Our results show that the sensitivity of the OptiMAL test is high (97%) at a high level of parasitemia (>100 parasites/microl) but drops to 59% when the level is <100 parasites/microl and to 39% when it is <50 parasites/microl. In addition, the OptiMAL test failed to identify four patients whose blood smears contained P. falciparum gametocytes only. We conclude that the sensitivity and specificity of the OptiMAL test are comparable to those of microscopy in detecting malaria infection at a parasitemia level of >100 parasites/microl; however, the test failed to identify more than half of the patients with a parasitemia level of <50 parasites/microl. Thus, the OptiMAL test should be used with great caution, and it should not replace conventional microscopy in the diagnosis of malaria infection. (+info)
Spatial and temporal patterns of imported malaria cases and local transmission in Trinidad.
(18/1177)
Over a 30-year period (1968-1997) 213 malaria cases in Trinidad were investigated by the Trinidad and Tobago Ministry of Health. Using a global positional system and a geographic information system, we mapped the precise location of all reported malaria cases, and associated them with breeding habitats of anopheline vectors. The majority of the cases (138, 63%) were individual imported cases around the big port cities. Plasmodium falciparum was the most common parasite, and Africa the most common source of imported cases. Two clusters of cases occurred: an introduced P. vivax outbreak associated with Anopheles aquasalis in 1990-1991, and an autochtonous focus of P. malariae associated with An. bellator and An. homunculus in 1994-1995. Application of a space-time statistic showed a significant clustering of P. malariae cases, and, to a lesser extent of P. vivax cases, but not of P. falciparum cases. Based on potential for occurrence of local transmission, we are developing risk maps to determine surveillance priorities, outbreak potential, and necessary degree and spatial range of control activities following case detections. (+info)
Polymorphism at the merozoite surface protein-3alpha locus of Plasmodium vivax: global and local diversity.
(19/1177)
Allelic diversity at the Plasmodium vivax merozoite surface protein-3alpha (PvMsp-3alpha) locus was investigated using a combined polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) protocol. Symptomatic patient isolates from global geographic origins showed a high level of polymorphism at the nucleotide level. These samples were used to validate the sensitivity, specificity, and reproducibility of the PCR/RFLP method. It was then used to investigate PvMsp3alpha diversity in field samples from children living in a single village in a malaria-endemic region of Papua New Guinea, with the aim of assessing the usefulness of this locus as an epidemiologic marker of P. vivax infections. Eleven PvMsp-3alpha alleles were distinguishable in 16 samples with single infections, revealing extensive parasite polymorphism within this restricted area. Multiple infections were easily detected and accounted for 5 (23%) of 22 positive samples. Pairs of samples from individual children provided preliminary evidence for high turnover of P. vivax populations. (+info)
Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea.
(20/1177)
In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is alpha(+)-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that alpha(+)-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that alpha(+)-thalassemia may facilitate so-called "benign" Plasmodium vivax infection to act later in life as a "natural vaccine" against severe Plasmodium falciparum malaria. Here, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of alpha(+)-thalassemia >/=0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a-b-]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*A(null)) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*A(null) (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47-8.91). Emergence of FY*A(null) in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise alpha(+)-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria. (+info)
Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte-binding proteins.
(21/1177)
Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Whereas Plasmodium vivax and Plasmodium knowlesi use the Duffy blood group antigen, Plasmodium falciparum uses sialic acid residues of glycophorin A as receptors to invade human erythrocytes. P. knowlesi uses the Duffy antigen as well as other receptors to invade rhesus erythrocytes by multiple pathways. Parasite ligands that bind these receptors belong to a family of erythrocyte-binding proteins (EBP). The EBP family includes the P. vivax and P. knowlesi Duffy-binding proteins, P. knowlesi beta and gamma proteins, which bind alternate receptors on rhesus erythrocytes, and P. falciparum erythrocyte-binding antigen (EBA-175), which binds sialic acid residues of human glycophorin A. Binding domains of each EBP lie in a conserved N-terminal cysteine-rich region, region II, which contains around 330 amino acids with 12 to 14 conserved cysteines. Regions containing binding residues have now been mapped within P. vivax and P. knowlesi beta region II. Chimeric domains containing P. vivax region II sequences fused to P. knowlesi beta region II sequences were expressed on the surface of COS cells and tested for binding to erythrocytes. Binding residues of P. vivax region II lie in a 170-aa stretch between cysteines 4 and 7, and binding residues of P. knowlesi beta region II lie in a 53-aa stretch between cysteines 4 and 5. Mapping regions responsible for receptor recognition is an important step toward understanding the structural basis for the interaction of these parasite ligands with host receptors. (+info)
Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline.
(22/1177)
Malaria prophylaxis for travelers is a controversial issue. The commonly used regimens are associated with side effects, low compliance, or low efficacy, which have raised concern regarding their use. In addition, they are inefficient against the tissue stage of the parasite and thus do not prevent relapses of Plasmodium vivax infection. Primaquine is aimed at the pre-erythrocytic stage and thus may be a potential causal-prophylactic treatment that can abolish the need for long postexposure therapy. During 1995-1998, we followed retrospectively travelers who joined rafting trips to an area in Ethiopia where both P. vivax and Plasmodium falciparum are hyperendemic. Of the 106 travelers who received primaquine, 5.7% developed malaria; of the 19 doxycycline recipients, 53% developed malaria; and of the 25 mefloquine recipients, 52% developed P. vivax malaria (>/=3 months after return from the area of endemicity). Primaquine was well tolerated, and only 1 withdrawal from therapy (due to gastrointestinal symptoms) was reported. Primaquine was shown to be a safe and effective prophylactic drug against both P. falciparum malaria and P. vivax malaria in travelers. (+info)
Temporal and spatial patterns of malaria reinfection in northeastern Venezuela.
(23/1177)
We stratified the risk of malaria transmission (Plasmodium vivax) in 35 villages along a coastal range in northeastern Venezuela (51 km2) where the main vector is the mosquito Anopheles aquasalis. After 20 years without local malaria transmission, reinfection of the entire area occurred from May to December 1985 by local (continuous) and jump (discontinuous) dispersal. Epidemiologic, environmental, and vector variables were investigated with the aid of a Geographic Information System. Risk factors for malaria transmission were human population density, proximity to pre-adult mosquito habitats (< 500 m), and the number of pre-adult habitats nearby. Most inhabitants, immature mosquito habitats, and malaria cases were located at low elevations and on gentle slopes. High prevalence of malaria during the dry seasons was associated with the presence of permanent bodies of water containing An. aquasalis. Occurrence of a La Nina event in 1988 (wet and cool phase of the El Nino Southern Oscillation) triggered malaria transmission to unusually high levels, consolidating infection in the area, and rendering traditional control efforts useless. We recommend tracking malaria persistence per village and associated risk factors as methods to reduce the cost of malaria control programs. (+info)
Parasite density and malaria morbidity in the Pakistani Punjab.
(24/1177)
The relationship between quantitative Plasmodiumfalciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/microl. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area. (+info)