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Biomedical subjects

Kevin C Kain

Publications and source records attributed to Kevin C Kain.

54 records · Page 3Linked to original sources
PubMed2003

A molecular surveillance system for global patterns of drug resistance in imported malaria.

Analysis of imported malaria in travelers may represent a novel surveillance system for drug-resistant malaria. We analyzed consecutive falciparum malaria isolates from Canadian travelers from 1994 to 2000, for polymorphisms in pfcrt, dhfr, and dhps linked to chloroquine and pyrimethamine/sulfadoxine resistance. Forty percent of isolates possessed the K76 pfcrt allele, suggesting that many imported falciparum infections are still responsive to chloroquine. Travelers who had recently taken chloroquine had a significantly increased risk of harboring isolates with pfcrt resistance alleles (odds ratio = 4.47; p=0.03). The presence of two or more mutations in dhfr or dhps was found in 64.8% (95% confidence interval [CI] 54.6 to 73.9) and in 30.4% (95% CI 21.7 to 40.3) of isolates, respectively, and increased significantly over the course of the study. These molecular markers indicate that pyrimethamine/sulfadoxine resistance is increasing and is now too high to rely on this drug as a routine therapeutic agent to treat malaria in travelers.

Adolescent↗
PubMed2003

Lack of prediction of mefloquine and mefloquine-artesunate treatment outcome by mutations in the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene for P. falciparum malaria in Peru.

We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis. All 97 patients remained parasite-free during 28 days of follow-up (MQ, n = 46; MQ-AS, n = 51), indicating 100% clinical efficacy of the MQ and MQ-AS treatment regimens. The reported MQ-sensitive alleles (C1034, D1042, and Y1246) were present in 48.5% (n = 47) of the cases, whereas 49 isolates (50.5%) contained the D1246 mutation reported to confer MQ resistance in vitro. However, neither this mutation nor a double mutation (S1034, D1246; n = 16) was predictive of MQ treatment outcome.

ATP-Binding Cassette Transporters↗
PubMed2003

Chloroquine-resistant Plasmodium vivax malaria in Peru.

Reports from several sites in South America suggest the presence of isolated cases of chloroquine-resistant Plasmodium vivax malaria. To investigate the possibility of chloroquine-resistant P. vivax in Peru, we conducted 28-day in vivo drug efficacy trials at three sites in the Amazon region and one site on the northern Pacific Coast between 1998 and 2001. A total of 242 patients between the ages of 2 and 60 years were enrolled (177 from the Amazon region and 65 from the northern coast). All subjects received directly observed therapy with chloroquine, 25 mg/kg, over a three-day period. On enrollment, 49% had a documented fever and 96% had a history of fever; their geometric mean parasite density was 5,129 parasites/microL. A total of 212 (88%) of the 242 subjects completed their 28-day follow-up. Four of the 177 patients from the Amazon region had a recurrence of P. vivax parasitemia on days 21 and 28 after treatment was initiated. Two of these patients had chloroquine-resistant infections, based on polymerase chain reaction-single-stranded conformational polymorphism genotyping and chloroquine-desethylchloroquine blood levels, which were > or = 97 ng/mL at the time of the reappearance of parasitemia. None of the subjects studied on the northern Pacific Coast had recurrent parasitemia.

Adolescent↗
PubMed2003

Evaluation of the Binax NOW ICT test versus polymerase chain reaction and microscopy for the detection of malaria in returned travelers.

Microscopic detection of Plasmodium species has been the reference standard for the diagnosis of malaria for more than a century. However, maintaining a sufficient level of expertise in microscopic diagnosis can be challenging, particularly in non-endemic countries. The objective of this study was to compare a new rapid malaria diagnostic device (NOW ICT Malaria Test; Binax, Inc., Portland, ME) to polymerase chain reaction (PCR) and expert microscopy for the diagnosis of malaria in 256 febrile returned travelers. Compared with PCR, the NOW ICT test showed a sensitivity of 94% for the detection of P. falciparum malaria (96% for pure P. falciparum infection) and 84% for non-P. falciparum infections (87% for pure P. vivax infections and 62% for pure P. ovale and P. malariae infections), with an overall specificity of 99%. The Binax NOW ICT may represent a useful adjunct for the diagnosis of P. falciparum and P. vivax malaria in febrile returned travelers.

Adolescent↗
PubMed2002

Impact of microscopy error on estimates of protective efficacy in malaria-prevention trials.

Microscopy is an imperfect reference standard used for malaria diagnosis in clinical trials. The purpose of this study was to provide an assessment of the accuracy of basic microscopy, to compare polymerase chain reaction (PCR)-based diagnosis with microscopy results, and to assess the effect of microscopy error on apparent protective efficacy. The sensitivity and specificity of basic, compared with expert, microscopy was determined to be 91% and 71%, respectively. In a clinical trial, agreement between PCR and microscopy results improved with expert confirmation of initial results. In a simulated 12-week trial with weekly routine malaria smears, a very high specificity (>99%) for each malaria smear was found to be necessary for an estimate of protective efficacy to be within 10%-25% of the true value, but sensitivity had little effect on this estimate. Microscopy error occurs and can affect clinical trial results.

Animals↗
PubMed2002

Furuncular myiasis: a simple and rapid method for extraction of intact Dermatobia hominis larvae.

We report a case of furuncular myiasis complicated by Staphylococcus aureus infection and beta-hemolytic streptococcal cellulitis. The Dermatobia hominis larva that caused this lesion could not be extracted using standard methods, including suffocation and application of lateral pressure, and surgery was contraindicated because of cellulitis. The botfly maggot was completely and rapidly extracted with an inexpensive, disposable, commercial venom extractor.

Adult↗
PubMed2002

Mechanism of protection induced by vitamin A in falciparum malaria.

Supplementation with vitamin A potentiates host resistance to malaria, however, the underlying mechanism is unknown. We tested the effects of 9-cis-retinoic acid, a metabolite of vitamin A, on CD36 expression, non-opsonic phagocytic clearance of parasitised erythrocytes, and TNFalpha production in human monocytes and macrophages. We found reduced secretion of TNFalpha, upregulated CD36 expression, and increased phagocytosis of Plasmodium falciparum-parasitised erythrocytes. Increased parasite clearance and reduced proinflammatory cytokine responses to infection might partly explain the beneficial effects of supplementation with vitamin A in malaria.

Alitretinoin↗
PubMed2002

CD36 deficiency induced by antiretroviral therapy.

BACKGROUND: The molecular basis of lipodystrophy, a syndrome associated with HIV antiretroviral (ARV) therapy, remains unknown. OBJECTIVES: To examine whether ARV therapy might inhibit the expression of CD36, which is known to play an important role in fatty acid and glucose metabolism, and if this might contribute to the metabolic alterations associated with lipodystrophy. DESIGN: The effects of ARV therapy on CD36 levels was examined in vivo in a prospective cohort of individuals treated with ARV therapy and in vitro in assays of human cell lines exposed to ARV drugs. METHODS: Monocyte CD36 levels were assessed by flow cytometry at baseline and after 7 days of therapy in five healthy volunteers and 10 treatment-naive HIV-1-infected individuals. ARV therapy included protease inhibitors (ritonavir, nelfinavir or lopinavir/ritonavir). In addition, human cell lines (THP-1 and C32) were assessed for CD36 levels pre and post-ritonavir treatment. RESULTS: Three of four healthy controls (one withdrew because of adverse effects) and 6 of 10 HIV-1-infected individuals had a 50 to > 90% decrease in monocyte CD36 levels after 7 days of therapy. One of ten HIV-infected subjects had a 30% decrease, and the remaining individuals had no change or an increase in CD36 levels. CD36 levels decreased significantly in human cell lines treated with ritonavir but not in those treated with zidovudine. CONCLUSIONS: ARV therapy resulted in a marked decrease in CD36 in approximately 70% of our participants. Sustained ARV therapy-induced CD36 deficiency may contribute to insulin resistance and other metabolic complications of lipodystrophy.

Anti-HIV Agents↗
PubMed2002

Short-chain aliphatic polysulfonates inhibit the entry of Plasmodium into red blood cells.

Several steps in the pathogenesis of a Plasmodium falciparum infection depend on interactions of parasite surface proteins with negatively charged sugars on the surface of host cells such as sialate residues or glycosaminoglycans. For these reasons, our previous studies examining agents that interfere with heparan sulfate-protein binding during amyloidogenesis suggested that short-chain aliphatic polysulfonates may prove useful as antimalarial agents. A series of related polysulfonates were synthesized and assessed both in tissue culture with the asexual stages of P. falciparum in human red blood cells and in vivo by use of Plasmodium berghei infections in mice. Poly(vinylsulfonate sodium salt) (molecular weight range, 1,500 to 3,000) proved effective in interfering with P. falciparum merozoite entry into human red blood cells and significantly delaying the increase in the level of P. berghei parasitemia in mice. The concept that anionic molecules that mimic large polysaccharide structures may have antimalarial properties has been suggested and examined previously. Our results suggest that related anionic agents [poly(vinylsulfonate sodium salt)-like molecules] orders of magnitude smaller than those previously considered may prove useful in abrogating merozoite entry into erythrocytes and may potentially block sporozoite entry into liver cells. Structure-activity studies conducted to enhance these properties may provide compounds with scope for significant further analysis and development.

Alkanesulfonates↗
PubMed2002

Evaluation of the Makromed dipstick assay versus PCR for diagnosis of Plasmodium falciparum malaria in returned travelers.

Microscopy has been the traditional reference standard for malaria diagnosis. However, difficulty in maintaining the required technical skills, particularly in areas where malaria is not endemic, has prompted the development of rapid nonmicroscopic diagnostic assays based on the detection of malaria parasite antigen in whole blood. In this study, we evaluated the performance of one such device, the Makromed dipstick test, blindly compared to PCR and microscopy for the diagnosis of Plasmodium falciparum malaria in 200 febrile returned travelers. The Makromed assay detects the presence of P. falciparum-specific histidine-rich protein II with an antigen capture immunochromatographic strip format. Compared to PCR as the reference standard, the dipstick assay had a sensitivity of 97.0% and a specificity of 96.0%. The positive and negative predictive values were 81.2% and 99.5%, respectively. Rapid malaria diagnostic devices may provide a useful diagnostic adjunct in a clinical setting.

Adolescent↗
PubMed2002

Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area.

Strongyloidiasis is a chronic infection that may result in significant morbidity; however, diagnosis and management remain problematic. The objective of this study was to 1) evaluate the demographic, clinical, and laboratory features of 76 consecutive individuals who had Strongyloides stercoralis larvae identified in their fecal specimens; 2) determine the sensitivity of the Centers for Disease Control and Prevention (CDC) enzyme immunoassay (EIA) for detecting antibodies to Strongyloides in those with confirmed infection; and 3) assess the serologic responses and changes in eosinophil counts following treatment. Most (96%) cases occurred in immigrants, but some patients had immigrated as long as 40 years earlier. The CDC Strongyloides EIA had a sensitivity of 94.6% (95% confidence interval = 92.0-97.2%) in this patient population with proven infection. Serologic and eosinophil counts decreased after therapy, suggesting that they may be useful markers of treatment success.

Animals↗
PubMed2002

Innate immunity to malaria caused by Plasmodium falciparum.

Malaria, a widespread disease caused by protozoa of the genus Plasmodium, contributes to the death of more than 2 million people each year. Resistance to antimalarial drugs is increasing, and an effective vaccine has not yet been designed. In the search for alternative means to control malaria infections, especially those caused by the most lethal species of malaria parasite, Plasmodium falciparum, our attention has turned to elucidating the relationships of the parasite and human host at the molecular level. In this review, we describe possible mechanisms by which naturally occurring genetic mutations might confer resistance to P. falciparum and how our innate immune response mediated by the phagocytic action of monocytes and macrophages acts as a first-line defence in clearing malaria infections. The potential effectiveness of novel therapies to enhance innate phagocytic clearance of malaria parasites, particularly in nonimmune people who are at greatest risk of adverse outcomes, is also discussed.

Animals↗
PubMedDate not supplied

Ineffectiveness of the current strategy to prevent hepatitis A in travelers.

BACKGROUND: Each year, a large number of Canadians travel to regions of the world where hepatitis A remains endemic. Many of these travelers are not immune and the current preventive strategy relies wholly on self-referral to a travel clinic. All of the costs associated with such a visit are assumed by the traveler. We estimated the effectiveness of this strategy. METHODS: This case-control study included 108 travel-related hepatitis A cases with onset of disease between 1997 and 1999 and 620 controls who traveled during the same period. RESULTS: Hepatitis A was strongly associated with high-risk travel (Odds Ratio = 7.2, 95% Confidence Interval 1.76-29.4), but only 7% of cases were found in this category. The risk of hepatitis A was 5 times lower in travelers who visited a travel clinic than in those who did not (80% efficacy). However, only 14% of the controls visited a travel clinic. As a result, the effectiveness of the current strategy is estimated to be 11% (80% of 14%). CONCLUSIONS: Hepatitis A in travelers can be prevented effectively by attendance at a travel clinic. Unfortunately, most travelers do not visit such clinics prior to departure. Even if all high-risk travelers were to visit a travel clinic and receive vaccination, this would have negligible impact on the number of travel-related hepatitis A cases (approximately 7% reduction). The current strategy for the prevention of hepatitis A in travelers is ineffective and should be reexamined.

Adult↗
PubMedDate not supplied

Prospective analysis of parasitic infections in Canadian travelers and immigrants.

BACKGROUND: International travel is associated with increased risk of vector-borne illnesses, particularly malaria. The objective of this study was to prospectively assess the relative frequency of parasitic diseases in Canadian travelers and to characterize demographic and travel-related predictors of these infections. METHODS: Data on Canadians and new immigrants who crossed international borders and were seen in the Tropical Disease Unit of Toronto General Hospital between November 1997 and June 2003 were prospectively collected and entered into the GeoSentinel Surveillance Network database. RESULTS: Of 3,528 returned Canadian travelers and new immigrants in the database, 1,010 had a parasitic infection diagnosed. Mean age of the 3,528 travelers was 37.3 years, and 42.6% were male. Those diagnosed with parasitic infections were more likely than the remaining cohort to have been traveling for the purpose of immigration (21.1% vs 7.1%, p < 0.001), or visiting friends and relatives (VFR) (17.9% vs 11.8%, p < 0.01). Common parasitic infections included nonhistolytica amebiasis (N= 209), malaria (N= 143), cutaneous larva migrans (N= 105), giardiasis (N= 74), and schistosomiasis (N= 48). CONCLUSIONS: Parasitic infections occurred in 29% of Canadian travelers. New immigrants and VFRs are at increased risk for malaria, as well as protozoal and helminthic infections.

Adult↗
PubMedDate not supplied

A population-based comparison between travelers who consulted travel clinics and those who did not.

BACKGROUND: Travel to hepatitis A-endemic countries is frequent among North Americans. Such travel carries significant risks for the individuals themselves and for the general population. We documented the patterns of use of travel clinics in a large Canadian adult population. METHODS: Travelers who had visited a hepatitis A-endemic country between 1990 and the time of the survey in 1999 were eligible. Subjects were identified from a representative sample of 4,002 adults from the two largest Canadian provinces. They were contacted by random digit dialing and interviewed by telephone. RESULTS: Only 15% of trips had been preceded by a visit to a travel clinic. The probability of visiting a travel clinic was approximately 10 times greater for travelers considered to be in the high-risk category than for those in the low-risk category, but the former represented only 2% of the total. The probability of visiting a travel clinic was approximately 23 times greater for travelers who were aware of the health risks in their country of destination. Income level was not associated with attendance at a travel clinic, and cost was rarely mentioned as a reason for not attending such a travel clinic before departure. CONCLUSIONS: Each year, millions of Canadian travelers go to hepatitis A-endemic countries without consulting a travel clinic. Active steps must be taken by public health authorities to improve their utilization of health services and prevent the accrued health risk for these travelers.

Adult↗
PubMedDate not supplied

Travel patterns and risk behavior in solid organ transplant recipients.

BACKGROUND: International travel is associated with an increased risk of enteric, vector-borne and bloodborne infections. The risk of acquiring travel-related illness is higher in those who are immunocompromised. However, little is known about travel practices and risk behaviors in transplant recipients who travel. We herein profile transplant recipients who travel, and characterize their pre-travel precautions, travel activities, burden of illness, and exposure history. METHODS: With the use of a standardized and validated questionnaire, patients attending a transplant clinic were surveyed regarding recent travel and risk behaviors. RESULTS: Of 267 transplant recipients who participated, 95 (36%) indicated that they had recently traveled outside Canada and the USA. Their mean age was 49.9 years, 54% were male, and 54% were born outside Canada. Eighty-six percent of travelers were receiving at least two immunosuppressive drugs at the time of their trip. Sixty-six percent of travelers sought pre-travel advice, primarily from their transplant physician. Sixty-three percent traveled to areas where hepatitis A is endemic, but only 5% had received hepatitis A immunization. Fifty percent traveled to dengue- and malaria-endemic areas, but,25% adhered to mosquito prevention measures. Ten percent reported behaviors that exposed them to blood or body fluids, including injections, body piercing, and casual sexual activity. CONCLUSIONS: Solid organ transplant recipients represent a unique group of compromised travelers; however, few were adequately protected against travel-associated enteric, vector-borne and bloodborne pathogens.

Adolescent↗
PubMedDate not supplied

Imported Plasmodium vivax malaria: demographic and clinical features in nonimmune travelers.

BACKGROUND: Imported malaria is an important problem in nonendemic countries due to increasing travel to and immigration from malaria-endemic countries. Plasmodium vivax malaria is relatively common in travelers but there are few published data regarding the outcome of P. vivax malaria in this group. METHODS: We analyzed 209 cases of P. vivax malaria that were reported to the GeoSentinel network and the VIDS database, Royal Melbourne Hospital. Analyses were performed on data including demographics, pretravel encounter, antimalarial prophylaxis, exposure history, type of travel, countries of recent and past travel, clinical presentation, treatment, outcome and final diagnoses. RESULTS: The majority of patients were travelers (61%), followed by expatriates (13%) and recent immigrants or foreign visitors (12%). Recent travel to Oceania, sub-Saharan Africa, and South and Central America was significantly more likely to be associated with P. vivax malaria than travel to all other regions. The clinical presentation of P. vivax malaria acquired in the Pacific region is indistinguishable from infection with P. falciparum. The use of chloroquine prophylaxis did not prolong the incubation period. Relapse of infection was not infrequent, and the only significant predictor of relapse was travel to Papua New Guinea (PNG), regardless of primaquine dose. Travelers returning from PNG were eight times more likely to relapse after primaquine treatment compared to travelers with P. vivax malaria acquired elsewhere. CONCLUSIONS: We have presented details of the epidemiology, clinical presentation and management of infection with P. vivax malaria in travelers. P. vivax malaria is an important cause of morbidity in travelers, and relapse following primaquine treatment is especially problematic with P. vivax malaria acquired in PNG.

Adolescent↗