Evaluation of the KAT-Quick Malaria Rapid Test for rapid diagnosis of falciparum malaria in Thailand

In recent years, several rapid diagnostic tests for falciparum malaria have been developed. KAT test results were compared with microscopy on 90 consecutive patients hospitalized at the Hospital for Tropical Diseases, Bangkok, Thailand. Fifty-one patients had P. falciparum infections while 49 had malaria due to other plasmodium species. For a geometric mean +/-SD (Min;Max;range) parasitemia of 11,481 +/- 5.0 (88;713,838;713,750), the sensitivity of the KAT test was 96% (95% CI = 86-99.5), the specificity was 92% (95% CI = 80-99), the accuracy was 94% and the reliability was 85%. These findings suggest that the KAT test is of potential interest in the diagnosis of falciparum malaria in Thailand.     

Use of the Parasight-F diagnostic test for imported malaria in a travel clinic

The Parasight-F test based on the detection of a soluble antigen specific for Plasmodium falciparum is designed for the immediate diagnosis of malaria infection. We evaluated its use by clinicians during consultations. This prospective study of its diagnostic utility in febrile patients consulting a travel clinic on their return from areas endemic for malaria was conducted between May 1996 and May 1997. The Parasight-F test was performed by the clinician with confirmation by means of standard microscopic examination of venous blood. One-hundred and forty patients were enrolled. Forty-three (31%) cases of malaria were identified by microscopic examination. Thirty-eight were due to P. falciparum. The Parasight-F tests yielded 6 false-positive and 3 false-negative results compared to the microscopic findings. The specificity and sensitivity for the diagnosis of P. falciparum malaria were 94% and 92%. These results show that the Parasight-F test alone cannot replace microscopic diagnosis of malaria in travel clinics.     

Performance of the OptiMAL assay for detection and identification of malaria infections in asymptomatic residents of Irian Jaya, Indonesia

The OptiMAL assay, a new immunochromatographic "dipstick" test for malaria based on detection of Plasmodium lactate dehydrogenase (pLDH), is purported to detect infections of approximately 200 parasites/microL of blood and to differentiate between Plasmodium falciparum and non-P. falciparum. We evaluated OptiMAL performance by comparing the test strip interpretations of two independent readers with consensus results obtained independently by expert malaria microscopists. Unbiased measures of sensitivity were derived by applying the OptiMAL test for detection and differentiation of light, asymptomatic infections by P. falciparum and Plasmodium vivax. OptiMAL readings were separated in time to determine whether the reaction signal was stable. Microscopy identified infections in 225 of 505 individuals screened; those with P. falciparum (n = 170) averaged 354 asexual forms/microL and P. vivax/Plasmodium malariae (n = 112) averaged 216 asexual forms/microL of blood. Concordance between OptiMAL and microscopy was 81% and 78% by the two independent readings. The assay's sensitivity for detection of any malaria species was 60.4% and 70.2% respectively and specificity was 97% and 89%. Most cases identified by microscopy as P. falciparum were graded as negative or non-falciparum by both OptiMAL readers. OptiMAL false negatives as well as misidentifications were related to low parasitemias (< 500/microL). The OptiMAL assay demonstrated 88-92% sensitivity for detecting infections of 500-1,000 parasites/microL, a range covering the mean parasitemia of primary symptomatic P. falciparum infections in malaria-na?ve Indonesian transmigrants. This device was markedly less sensitive than expert microscopy for discriminating between malaria species and is presently unsuited for use as an epidemiological screening tool. The OptiMAL assay is not approved for diagnostic use but is commercially available for research purposes only.     

Short report: therapeutic efficacy of chloroquine combined with primaquine against Plasmodium falciparum in northeastern Papua,Indonesia

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1-1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1-1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% Cl, 0.04-2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum.     

Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium

The NOW ICT Malaria P.f./P.v. for Whole Blood (Binax, Inc., Portland, ME) is a new malaria rapid diagnostic device that represents a technical advance over previous assays, such as ICT Malaria P.f./P.v. and ICT Malaria P.f.. We evaluated this device in March 2001 in symptomatic patients at malaria clinics in Maesod, Thailand. Microscopic examination of Giemsa-stained blood smears was the reference standard. In 246 patients, microscopy showed 32 (13.0%) infected with Plasmodium falciparum, 63 (25.6%) with P. vivax, 6 (2.4%) with mixed infections of P. falciparum and P. vivax, 5 (2.0%) with P. malariae, and 140 (56.9%) negative. Sensitivity for P. falciparum was 100% and specificity was 96.2% (200 of 208; 95% confidence interval [CI] = 92-98). For P. vivax, sensitivity was 87.3% (55 of 63; 95% CI = 77-93) and specificity was 97.7% (173 of 177; 95% CI = 95-99), but all the four false-positive results were microscopically positive for P. malariae; thus, specificity for non-falciparum Plasmodium was 100%. These results suggest improved performance over NOW ICT predecessors.     

Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand

Microscopy of Giemsa-stained thick and thin films by a skilled microscopist has remained the standard laboratory method for the diagnosis of malaria. However, diagnosis of malaria with this method is problematic since interpretation of results requires considerable expertise, particularly at low parasite levels. We compared the efficacy of "field" and "expert laboratory" microscopy for active surveillance of Plasmodium falciparum and P. vivax in western Thailand. Field microscopy consisted of an approximately five-minute read (50-100 fields) of a thick film at x700 using a natural light source, whereas expert laboratory microscopy consisted of a 20-minute read (number of parasites per 500 leukocytes) at x1,000 using a high-quality, well-maintained microscope with an artificial light source. All discordant and 20% of concordant results were cross-checked blindly. A total of 3,004 blood films collected between May and November 2000 were included in the study, of which 156 (5.2%) were positive for P. falciparum, 177 (5.9%) for P. vivax, and 4 (0.1%) for both P. falciparum and P. vivax by expert microscopy. A total of 84.4% (135 of 160) of the P. falciparum-positive slides and 93.9% of the P. vivax-positive slides had a parasitemia of less than 500/microL. Field microscopy was specific (99.3%) but not sensitive (10.0%) for the diagnosis of P. falciparum malaria, with a positive predictive value (PPV) of 43.2% and a negative predictive value (NPV) of 95.1%. The corresponding specificity and sensitivity for the diagnosis of P. vivax malaria were 99.2% and 7.1%, respectively, with a PPV of 38.7% and an NPV of 93.9%. Field microscopy, as defined in this study, is not an effective method for active malaria surveillance in western Thailand, where prevalence and parasitemia rates are low.     

Microscopic and sub-microscopic Plasmodium falciparum infection, but not inflammation caused by infection, is associated with low birth weight

Pregnancy-associated malaria is one of the leading causes of low birth weight in malaria endemic areas. In this study, 145 parturient women residing in areas endemic for Plasmodium falciparum in Lambaréné, Gabon, were recruited into the study after delivery, and the association of maternal P. falciparum infection, inflammatory response, and birth weight was studied. At delivery, 10% (15) of the mothers (12 were positive in both peripheral and placental blood smears, 1 was positive in peripheral blood only, and 2 were positive in placenta blood only) were positive for P. falciparum by microscopy and 23% (30) by real-time polymerase chain reaction (PCR). The level of C-reactive protein (CRP) was significantly elevated in microscopically P. falciparum-positive pregnant women (34 mg/L; 95% CI: 3-458) but not in those with sub-microscopic infections (6 mg/L; 95% CI: 1-40) compared with those free of P. falciparum infection (7 mg/L; 95% CI: 1-43). In a multivariate analysis, the presence of microscopic (adjusted OR = 28.6, 95% CI = 4.8-169.0) or sub-microscopic (adjusted OR = 13.2, 95% CI = 2.4-73.0) P. falciparum infection in pregnant women and age of mothers < 21 years (adjusted OR = 9.7 CI = 1.0-89.7), but not CRP levels, were independent predictors for low birth weight. This finding may have important operational implications and emphasizes the need for appropriate diagnostic methods in studies evaluating the outcome of pregnancy-associated malaria.     

Short report: in vivo sensitivity of Plasmodium falciparum to halofantrine in southern central Vietnam

Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in vivo sensitivity of P. falciparum to halofantrine in two villages in the southern part of central Vietnam. Halofantrine (8 mg/kg x 3 doses) was administered to 37 patients with either P. falciparum (n = 32) or mixed P. falciparum/P. vivax malaria (n = 5). End points were parasite sensitivity or resistance (RI/RII/RIII) determined by parasite clearance, persistence, or recurrence during 28 days of follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval = 79.8-99.2%) patients were sensitive. Two patients had recurrent P. falciparum parasitemia on days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum malaria in these Vietnamese patients.     

Detection of Plasmodium falciparum in pregnancy by laser desorption mass spectrometry

Detection of Plasmodium falciparum malaria during pregnancy is complicated by sequestration of parasites in the placenta, which reduces peripheral blood microscopic detection. Laser desorption mass spectrometry (LDMS) has previously demonstrated sensitive detection of hemozoin from P. falciparum blood cultures and the ability to track parasitemia in a Plasmodium yoelii malaria mouse model. Here we use a simple, dilution in water, blood sample preparation protocol for LDMS detection of malaria in 45 asymptomatic, pregnant Zambian women. We compare LDMS to microscopy and polymerase chain reaction (PCR) analysis. All women were microscopy negative. LDMS detected P. falciparum hemozoin in 15 out of 45 women, while PCR results were positive in 25 women. Compared with PCR, which analyzed 20-30 microL of blood, the sensitivity of LDMS, which analyzed < 1 microL of blood, was 52%, with a specificity of 92%. LDMS is a potentially rapid and more sensitive alternate diagnostic method than microscopy.     

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days], n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.     

The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea

Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases. To determine the influence of zinc on malaria morbidity we conducted a randomized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea. A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136) or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center. Cross-sectional surveys were conducted at the beginning, middle, and end of the study to assess infection rates, parasite density, spleen enlargement, and hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P = 0.037) reduction in Plasmodium falciparum health center-based episodes, defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever. Episodes accompanied by any parasitemia were also reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or = 100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum. Zinc had no consistent effect on cross-sectional malariometric indices. Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo, such changes were absent at the mid-study survey. These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum.     

Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia.

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.     

HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria

BACKGROUND: Human immunodeficiency virus (HIV)-1 infected adults with low CD4 cell count have a higher risk of malaria infection and clinical malaria. We assessed the influence that HIV-1 immune suppression has on the efficacy of antimalarial treatment in adults with uncomplicated malaria. METHODS: This clinical trial included 971 Zambian adults with uncomplicated malaria. Patients were tested for HIV-1, and, if positive, a CD4 cell count was assessed. The primary outcome was recurrent parasitemia corrected by molecular genotyping within 45 days after treatment. RESULTS: HIV-1 infection was detected in 33% (320/971) of adult patients with malaria. Treatment failure was not associated with HIV-1 infection (relative risk [RR], 1.12 [95% confidence interval {CI}, 0.82-1.53]; P=.45). HIV-1-infected patients with a CD4 cell count <300 cells/microL had an increased risk of recurrent parasitemia, compared with those with a CD4 cell count >or=300 cells/microL (RR, 2.24 [95% CI, 1.20-4.14]; P=.01). After genotyping, the risk of recrudescence was higher in HIV-1-infected patients with a CD4 cell count <300 cells/microL than in the other patients with malaria (RR, 1.67 [95% CI, 1.13-2.47]; P=.02). CONCLUSION: HIV-1-infected patients with malaria with a CD4 cell count <300 cells/microL have a higher risk of experiencing a recrudescent infection, compared with those with a CD4 cell count >or=300 cells/microL or without HIV-1 infection. Trial registered at http://www.clinicaltrials.gov/; reference number NCT00304980.     

Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait

Sickle cell trait (HbAS) is known to be protective against Plasmodium falciparum malaria, but it is unclear when during the course of infection this protection occurs and whether protection is innate or acquired. To address these questions, a cohort of 601 children 1-10 years of age were enrolled in Kampala, Uganda, and followed for 18 months for symptomatic malaria and asymptomatic parasitemia. Genotyping was used to detect and follow individual parasite clones longitudinally within subjects. Children with HbAS were protected against the establishment of parasitemia, as assessed by the molecular force of infection at older but not younger ages (at 2 years of age: incidence rate ratio [IRR] = 1.16; 95% confidence interval [95% CI], 0.62-2.19; P = .6; at 9 years of age: IRR = 0.50; 95% CI, 0.28-0.87; P = .01), suggesting an acquired mechanism of protection. Once parasitemic, children with HbAS were less likely to progress to symptomatic malaria, with protection again being the most pronounced at older ages (at 2 years of age: relative risk [RR] = 0.92; 95% CI, 0.77-1.10; P = .3; at 9 years of age: RR = 0.68; 95% CI, 0.51-0.91; P = .008). Conversely, the youngest children were best protected against high parasite density (at 2 years of age: relative density = 0.24; 95% CI, 0.10-0.54; P = .001; at 9 years of age: relative density = 0.59; 95% CI, 0.30-1.19; P = .14), suggesting an innate mechanism of protection against this end point.     

Comparison of a rapid field immunochromatographic test to expert microscopy for the detection of Plasmodium falciparum asexual parasitemia in Thailand.

We assessed a rapid, Plasmodium falciparum histidine rich protein 2 (PfHRP2)-based immunochromatographic test (ICT Malaria Pf Test), for detection of asexual P. falciparum parasitemia in 551 subjects in three groups: (1) symptomatic patients self-referring for diagnosis, (2) villagers in a screening survey, and (3) patients recently treated for P. falciparum malaria. Expert light microscopy was the reference standard. ICT test performance was similar for diagnostic and screening modes. Four findings emerged: (1) test sensitivity correlated directly with parasite density, (2) test band intensity correlated directly with parasite density, (3) persistent test positivity after parasite clearance precludes its use for monitoring early therapeutic responses, and (4) a false negative test at 18,000 parasites/microl is unexplained. We conclude that a strong positive ICT test is highly predictive of falciparum asexual parasitemia for the diagnosis of new cases of falciparum malaria in Thailand, but a negative test result is inadequate to exclude parasitemia < 300/microl, and in some instances, even a higher parasitemia.     

Comparison of artemether-lumefantrine with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in eastern Nepal

Because available data suggest that resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) is increasing in Nepal, an open-label, parallel-group efficacy/safety study was conducted in 99 Nepalese patients with uncomplicated falciparum malaria randomized 2:1 to artemetherlumefantrine (AL) or SP. Efficacy was assessed from clinical and microscopic evidence of treatment failure. Four SP-treated patients (12.1%; 95% CI, 4.0-29.1%) redeveloped parasitemia during the 28-day follow-up versus 0% (95% CI, 0-6.9%) in the AL group (P = 0.011), a difference that was confirmed by polymerase chain reaction (PCR) analysis of parasite DNA. PCR detected an additional six patients (two SP and four AL) with sub-microscopic gametocytemia or breakthrough parasitemia between Days 14 and 28, suggesting that AL efficacy was lower than estimated by microscopy. Dhfr and dhps mutations were not associated with outcome. AL is more effective than SP for uncomplicated malaria in Nepal, but regular monitoring of its efficacy should be carried out if this combination therapy is introduced.     

Performance of the OptiMAL test for malaria diagnosis among suspected malaria patients at the rural health centers

The OptiMAL test detects both Plasmodium falciparum and P. vivax malaria infections. In this study, we evaluated the performance of the OptiMAL test at the Basic Health Units (BHUs) and the District Health Quarter (DHQ) Center in rural villages of Punjab, Pakistan that provide minimal health services. Two sets of blood specimens obtained from 930 suspected malaria patients attending these BHUs were tested at BHUs and the DHQ Center by microscopy and the OptiMAL test. At the BHUs, 231 (25%) of the patients were positive by microscopy and 278 (30%) patients tested positive by the OptiMAL test. At the DHQ Center, microscopic analysis of a second set of specimens from the same patients confirmed the malaria infection in 386 (42%) patients and the OptiMAL test result was positive in 300 (32%) patients. To determine the performance of OptiMAL test at the BHUs and the DHQ Center, all data were compared with microscopy results obtained at the DHQ Center. The OptiMAL test results for P. falciparum at the BHUs were comparable to those of the OptiMAL test at the DHQ Center. However, the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the OptiMAL test were considerably lower for P. vivax infections than for P. falciparum infections, irrespective of whether the test was performed at the BHUs or at the DHQ Center (P. falciparum: sensitivity = 78-85%, PPV = 89-97%, NPV = 96-98%; P. vivax: sensitivity = 61-76%, PPV = 88-95%, NPV = 90-93%). The OptiMAL test also detected a number of false-positive and false-negative results at both the BHUs and the DHQ Center. The false-positive results ranged from 1% to 2%; however, the number of false-negative results was much higher (BHUs: P. falciparum = 22%, P. vivax = 39%; DHQ Center: P. falciparum = 15%, P. vivax = 24%). In conclusion, these results, when combined with other advantages of the OptiMAL test, suggest that this test can be used by relatively inexperienced persons to diagnose malaria infection in rural areas where facilities for microscopy are not available.     

Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children

Protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG antibodies to Fcgamma receptors. Polymorphic variability in Fcgamma RIIa (H/R-131) is associated with differential binding of IgG subtypes and malaria disease outcomes. However, the role of Fcgamma RIIa-131 variability in conditioning susceptibility to severe malarial anemia, the primary manifestation of severe malaria in holoendemic P. falciparum transmission areas, is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in 493 children who came to a hospital with acute malaria. Variation in Fcgamma RIIa-131 was not significantly associated with severe malarial anemia (hemoglobin [Hb] < 6.0 g/dL) or malaria anemia (Hb < 8.0 g/dL). However, relative to the heterozygous genotype, homozygotes for the R131 alleles were protected against high-density parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14). Additional multivariate analyses showed that infection with human immunodeficiency virus type 1 did not influence the associations between FcgammaRIIa-H131R polymorphism and malaria disease outcomes. Genotypic results presented here parallel data illustrating that parasite density is unrelated to the severity of anemia in children with acute malaria. Thus, although homozygosity for the R131 allele protects against high-density parasitemia, FcgammaRIIa-131 polymorphism does not protect against malaria anemia.     

Polymerase chain reaction and molecular genotyping to monitor parasitological response to anti-malarial chemotherapy in the Peruvian Amazon

Over the past decade, anti-malarial drug resistance has rapidly become a major public health problem in the Peruvian Amazon. This study compared polymerase chain reaction (PCR) to light microscopy for diagnosing and monitoring the parasitological response of malaria patients to anti-malarial chemotherapy in the Peruvian Amazon region of Iquitos. Typing of P. falciparum using MSP1, MSP2, and glutamine-rich protein distinguished among infecting parasites. Most (73%) P. falciparum patients were parasitologically resistant to sulfadoxine-pyrimethamine (RI = 10, RII = 1). Sensitivity of microscopy was lower than PCR (69% for P. vivax and 78% for P. falciparum), but parasite clearance times were comparable between microscopy and PCR. PCR sensitively and specifically detected mixed infections and low-level parasitemia indicative of drug resistance, making this approach of practical use for the control of malaria at the public health level. Genotyping malaria parasites will be useful to distinguish drug failure from new infections in clinical trials of anti-malarial drugs in the Peruvian Amazon region.     

Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua,Indonesia

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.