bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal and spatial patterns of malaria reinfection in northeastern Venezuela.
Authors: Barrera R , Grillet M E , Rangel Y , Berti J , AchÃ© A
Published: May 2017

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 NiÃ±a event in 1988 (wet and cool phase of the El NiÃ±o 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.
Molecular epidemiology of malaria in Yaounde, Cameroon IV. Evolution of pyrimethamine resistance between 1994 and 1998.
Authors: Basco L K , Ringwald P
Published: May 2017

Pyrimethamine, in combination with sulfadoxine, is currently one of the major alternative drugs used for the treatment of chloroquine-resistant Plasmodium falciparum malaria infections in Africa. The mechanism of pyrimethamine resistance has been strongly associated with a single, key point mutation in the dihydrofolate reductase-thymidylate synthase gene, resulting in the substitution of the wild-type allele Ser-108 by either Asn-108 or Thr-108. The pyrimethamine-resistant phenotype and/or genotype were determined in 273 Cameroonian clinical isolates obtained in Yaounde by in vitro assays and polymerase chain reaction-restriction fragment length polymorphism over a 5-year period. The in vitro assays showed that 42% (18 of 43) and 63% (69 of 110) of the isolates obtained in 1994-1995 and 1997-1998, respectively, were resistant to pyrimethamine (50% inhibitory concentration [IC50] > 100 nM). The polymerase chain reaction showed that 43% (55 of 127) and 59% (50 of 85) of the isolates in 1994-1995 and 1997-1998, respectively, had the mutant Asn-108 allele. The pyrimethamine-resistant genotype (Asn-108) corresponded with the pyrimethamine-resistant phenotype (IC50 > or = 100 nM) in a large majority (> 95%) of the isolates. The results of our study suggest an increasing prevalence of pyrimethamine resistance in Yaounde. Our study further suggests that pyrimethamine resistance can be monitored by a technique that can be adopted by malaria research centers in Africa.
Hepatitis E seroconversion in United States travelers abroad.
Authors: Ooi W W , Gawoski J M , Yarbough P O , Pankey G A
Published: May 2017

Sporadic cases of symptomatic hepatitis E virus (HEV) infection have been reported in United States travelers to developing countries, including Mexico and Pakistan. To evaluate the risk of exposure in United States travelers, 356 patients seen in our Travel Clinics were tested for antibodies to HEV before and 6 weeks after traveling. Samples obtained 6 months after traveling were available for 211 travelers. IgG and IgM antibodies to HEV were assayed with HEV ELISA diagnostic kits containing 3 recombinant antigens expressed in Escherichia coli representing immunodominant epitopes within open reading frames 2 and 3 of HEV. Nine patients were IgG seropositive in specimens obtained before travel. Four individuals seroconverted. In all 4 patients, IgG seroconversion was demonstrated in samples obtained at least 6 months after return. Samples obtained 6 weeks after return were seronegative for HEV in all 3 patients for whom such samples were available. Travel destinations were diverse: Thailand, China, Russia, and Peru. These data are consistent with an infection acquired while traveling. None of the seropositive subjects reported any symptoms of hepatitis before or after travel. In the absence of overt disease, these results imply that exposure to HEV resulted in subclinical infections.
Lutzomyia nuneztovari anglesi (Le pont & Desjeux, 1984) as a vector of Leishmania amazonensis in a sub-Andean leishmaniasis focus of Bolivia.
Authors: Martinez E , Le Pont F , Torrez M , Telleria J , Vargas F , Dujardin J C , Dujardin J P
Published: May 2017

Recently, a new Leishmania amazonensis focus was described in a sub-Andean region (1,450-2,100 meters above sea level) of Bolivia. In this area, three anthropophilic sandfly species were identified: Lutzomyia nuneztovari anglesi Le Pont & Desjeux, 1984, which represented 86-99% of the captures, Lu. galatiae Le Pont et al., 1998, and Lu. shannoni Dyar 1929. Only Lu. nuneztovari anglesi was found naturally infected by flagellates (16 of 1,715 females). Three Leishmania stocks were isolated and analyzed by isoenzyme electrophoresis at 11 loci. No significant isoenzymatic differences were demonstrated between them and 7 stocks isolated from patients from the same area, and previously characterized as L. amazonensis. Moreover, in a simplified protocol, the experimental infection of Lu. nuneztovari anglesi by L. amazonensis was successful in 92% of the surviving specimens. These data are discussed in relation to the Killick-Kendrick criteria. These results strongly suggest that Lu. nuneztovari anglesi is the vector of L amazonensis at Cajuata, Inquisivi, La Paz, Bolivia.
A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.
Authors: Doherty J F , Pinder M , Tornieporth N , Carton C , Vigneron L , Milligan P , Ballou W R , Holland C A , Kester K E , Voss G , Momin P , Greenwood B M , McAdam K P , Cohen J
Published: May 2017

RTS,S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semi-immune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS,S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.
Hepatitis C: prevalence and common genotypes among ethnic groups in Jeddah, Saudi Arabia.
Authors: Fakeeh M , Zaki A M
Published: May 2017

The presence of antibodies to hepatitis C virus (HCV) was examined using a third-generation ELISA in 3,350 serum samples obtained from patients visiting different outpatient clinics, preoperative patients, and women visiting for ante-natal care at the Dr. Fakeeh hospital in Jeddah, Saudi Arabia from January to September 1998. The population included mainly Saudis, Egyptians, and Yemenis, and patients from other Middle East and Asian countries. The prevalence of HCV infection was 5.87% among Saudis, 22.54% among Egyptians, and 2.12% among Yemenis. The prevalence among patients from other Middle East and Asian countries were 3.38% and 4.98%, respectively. The overall prevalence among the studied group was 6.75%. Genotyping of isolates from Saudi Arabia showed that the prevalences of types 4, la, 1b, and 2 were 45.9%, 40.6%, 10.85%, and 2.7%, respectively. Genotyping of isolates from Egypt showed that type 4 was the major type among Egyptians (91.6%), while types 1a and 1b each had prevalences of 4.2%.
Application of molecular typing techniques in the 1998 dengue epidemic in Nicaragua.
Authors: Balmaseda A , Sandoval E , PÃƒÂ©rez L , GutiÃƒÂ©rrez C M , Harris E
Published: May 2017

This report presents the results of applying the reverse transcriptase-polymerase chain reaction (RT-PCR) to the analysis of clinical specimens during the 1998 dengue epidemic in Nicaragua. The RT-PCR was validated through comparison with viral isolation, resulting in a sensitivity of 100% and a specificity of 90%. In-country application of the RT-PCR permitted the rapid identification of dengue-3 virus as the cause of the epidemic at the beginning of 1998 and the detection of the reintroduction of dengue-2 virus in the middle of the year. Nineteen isolates of dengue-3 and one of dengue-2 were characterized using the restriction site-specific (RSS)-PCR technique. This showed that the dengue-3 strain belonged to the "Sri Lanka" subtype and that the dengue-2 strain belonged to the "Jamaica" subtype, both of which have been associated with hemorrhagic dengue in the Americas. The application of these simple PCR-based strain typing methods in a country endemic for dengue virus infections can help to characterize the transmission dynamics of this important emerging infectious disease problem and provide this information to local health authorities in a timely manner so that appropriate control measures can be implemented.
Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis.
Authors: Gomez D E , De Lorenzo M S , Alonso D F , Andrade Z A
Published: May 2017

Focal extracellular matrix degradation morphologically identified in human portal pipestem fibrosis due to Schistosoma mansoni did not express immunohistochemical reactivity for metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). However, when active schistosomal periovular granulomas were present, a strong reactivity for MMP-1, MMP-2, TIMP-1, and TIMP-2 was observed. No reactivity was ever observed for MMP-9. However, the positive pattern of immunohistochemical expression was not seen in old fibrotic periovular granulomas, which were sometimes situated in other areas of the same microscopic section. Positive staining for MMPs and TIMPs was observed at the same time in hepatocytes and within the apical portion of bile duct epithelium. These findings are consistent with the concept that matrix degradation in recent and old fibroses, in addition to differing at the ultrastructural level, also differs in immunohistochemical expression of metalloproteinases and their inhibitors.
Kala-azar in a high transmission focus: an ethnic and geographic dimension.
Authors: Ibrahim M E , Lambson B , Yousif A O , Deifalla N S , Alnaiem D A , Ismail A , Yousif H , Ghalib H W , Khalil E A , Kadaro A , Barker D C , El Hassan A M
Published: May 2017

In 1994-1996, we studied a group of 58 game wardens stationed in an area known to be highly endemic for visceral leishmaniasis (kala-azar) for evidence of infection with Leishmania donovani. Leishmania DNA was detected by the polymerase chain reaction in the peripheral blood of cases of active kala-azar, former patients with visceral leishmaniasis, patients, and asymptomatic subjects. Using the cloned antigen rk39, antibodies were detected in 44.2% of the game wardens while leishmanin skin test result was positive in 77% of our sample. It was shown that certain tribes from northern Sudan were more likely to develop subclinical infections, while those of the Baria tribe from southern Sudan and those of the Nuba tribe from western Sudan were more likely to develop visceral leishmaniasis. Whether this is due to genetic factors or previous exposure to Leishmania parasites remains to be elucidated.
Use of polymerase chain reaction for accurate follow-up of Loa loa experimental infection in Mandrillus sphinx.
Authors: TourÃ© F S , Ungeheuer M N , Egwang T G , Deloron P
Published: May 2017

Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding for the L. loa 15-kD protein (15r3-PCR), has been evaluated in mandrills infected with third-stage larvae (L3) of L. loa. The results of this assay were negative during the prepatency period (4 months after inoculation), but became positive when microfilariae appeared in the blood, and remained positive in all mandrills, even in those that became amicrofilaremic. These results show that the positivity of the 15r3-PCR assay is linked to the appearance of microfilariae in peripheral blood and demonstrated that L. loa-specific DNA can be detected in blood from occult-infected mandrills.
Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.
Authors: Miller J M , Boyd H A , Ostrowski S R , Cookson S T , Parise M E , Gonzaga P S , Addiss D G , Wilson M , Nguyen-Dinh P , Wahlquist S P , Weld L H , Wainwright R B , Gushulak B D , Cetron M S
Published: May 2017

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.
Short report: occurrence of Leishmania donovani DNA in donated blood from seroreactive Brazilian blood donors.
Authors: Otero A C , da Silva V O , Luz K G , Palatnik M , Pirmez C , Fernandes O , Palatnik de Sousa C B
Published: May 2017

Human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in previous reports. Seroprevalence of antibodies to Leishmania donovani was shown to be related to prior blood transfusions in multiply transfused hemodialysis patients in Natal, Rio Grande do Norte, Brazil. In this study, a possible correlation between seroreactivity and the presence of L. donovani DNA was investigated in asymptomatic healthy blood donors. Sera were tested using the fucose mannose ligand (FML) ELISA, which was shown to have a sensitivity of 100%, a specificity of 96-100%, reliability, and diagnostic and prognostic potential for the detection of human and canine kala-azar, respectively. Leishmanial DNA was assessed by the polymerase chain reaction (PCR) and dot-blot hybridization techniques in blood and bone marrow samples. Among 21 FML-seroreactive asymptomatic blood donors, 5 (24%) were positive by the PCR and 9 (43%) were positive in a dot-blot assay of blood samples, showing a significant correlation (chi2 = 14.24, P < 0.01). No Leishmania DNA was detected in 20 FML non-reactive blood donors. Our results point to the need for control of transmission of kala-azar by blood transfusion in areas endemic for this disease.
Seroprevalence of hepatitis C virus in the general population of northwest Tanzania.
Authors: Tess B H , Levin A , Brubaker G , Shao J , Drummond J E , Alter H J , O'Brien T R
Published: May 2017

Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.
Adenosine, AMP, and protein phosphatase activity in sandfly saliva.
Authors: Katz O , Waitumbi J N , Zer R , Warburg A
Published: May 2017

As they probe the skin for blood, sand flies inject saliva that prevents hemostasis. Sand fly saliva also promotes leishmaniasis by suppressing immunologic functions of macrophages. Saliva of Phlebotomus papatasi, the vector of Old World cutaneous leishmaniasis, contains adenosine and AMP. We show that Ph. papatasi saliva as well as pure adenosine down-regulate the expression of the inducible nitric oxide (NO) synthase gene in activated macrophages. In addition Ph. papatasi, but not Lutzomyia longipalpis, saliva inhibits the production of NO. Taken together, these data suggest that salivary adenosine is responsible for the down-regulation of NO synthesis. Saliva of both genera Phlebotomus and Lutzomyia contains significant levels of endogenous protein phosphatase-1/2A-like activity that is heat labile, inhibitable by okadaic acid and calyculine a, and does not require divalent cations.
Short report: study on the efficacy of a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of tick attachment.
Authors: Salafsky B , He Y X , Li J , Shibuya T , Ramaswamy K
Published: May 2017

The beneficial effects of N, N-diethyl-m-toluamide (DEET) against biting insects of human and animals appear to last <6 hr after a single application to the skin. To prolong the repellent effects of DEET, recently we developed a new long-acting formulation of DEET called LIPODEET. This preparation was retained in the skin for a longer duration of time with minimal systemic absorption. In this study, we have evaluated the protective effect of three compounds (DEET, LIPODEET, and Morpel 220) against attachment of two species of ticks (Amblyomma americanum and Dermacentor variabilis) to rabbit ears. Results show that LIPODEET and Morpel 220 were highly effective in preventing tick attachment to the skin for a longer duration of time (up to 72 hr) than DEET after a single application. Moreover, LIPODEET was found to be acaricidal to both the species of ticks.
Economic impact of febrile morbidity and use of permethrin-impregnated bed-nets in a malarious area I. Study of demographics, morbidity, and household expenditures associated with febrile morbidity in the Republic of Benin.
Authors: Rashed S , Johnson H , Dongier P , Moreau R , Lee C , Lambert J , Schaefer C
Published: May 2017

In preparation for a study on the effect of bed net use on malaria, this article describes febrile morbidity and malaria expenditures in a sub-Saharan area (Benin) of hyperendemic malaria. The 325 randomly selected households were visited weekly between April 1994 and March 1995 to determine febrile morbidity and household expenditures for prevention and treatment. The results indicate that rural children had two febrile episodes annually compared with 0.3 episodes among children living in the city. There was no difference in mean annual febrile episodes between adults and children (adults = 1.5, children = 1.5; P = 0.48) and in the expenditures per febrile episode (adults = US$1.85, children = US$1.62; P = 0.45). Annual prevention expenditures were higher for adults than for children (US$1.73 and US$1.28, respectively; P < 0.001), although there was no significant difference in expenditures for annual treatment for adults and children (US$2.15 and US$2.34, respectively). These and other findings are analyzed further and discussed.
Quantitative assessment of eosinophiluria in Schistosoma haematobium infections: a new marker of infection and bladder morbidity.
Authors: Reimert C M , Mshinda H M , Hatz C F , Kombe Y , Nkulila T , Poulsen L K , Christensen N O , Vennervald B J
Published: May 2017

Eosinophiluria, as quantified by measuring eosinophil cationic protein (ECP) in urinary extracts, microhematuria, egg excretion, and ultrasound-detectable bladder pathology were recorded in Schistosoma haematobium-infected Tanzanian school children at a baseline survey and during an 18-month post-treatment follow-up study. Significant correlations were seen between urinary ECP levels, intensity of infection, and bladder pathology. Treatment resulted in a marked reduction in prevalence and intensity of infection, in a delayed and less marked reduction in ECP levels, and in a resolution of pathology. The overall diagnostic efficiency of the ECP test (cut-off value for the ECP > or =5 ng/ml) in relation to infection was comparable with that of egg count and microhematuria, but with a better sensitivity than a single egg count. In relation to bladder pathology, the diagnostic performance of the ECP test (cut-off value for the ECP > or =25 ng/ml) exceeded that of a single egg count. In addition, the ECP was better in discriminating between different grades of bladder pathology. The present study points to the ECP as a useful marker of both S. haematobium infection and of associated bladder morbidity reflecting the inflammatory status of the bladder wall.
Chloroquine-resistant isolates of Plasmodium falciparum with alternative CG2 omega repeat length polymorphisms.
Authors: McCutcheon K R , Freese J A , Frean J A , Veale R B , Sharp B L , Markus M B
Published: May 2017

A particular polymorphism in the cg2 gene has previously been linked to chloroquine resistance in reference isolates of Plasmodium falciparum. To assess the association of this polymorphism with chloroquine resistance in field specimens of P. falciparum, we analyzed the omega repeat region of the cg2 gene in 47 isolates of P. falciparum collected in the Ingwavuma District of northern KwaZulu-Natal, South Africa. Polymerase chain reaction (PCR) primers, which were designed to amplify the region of DNA surrounding the omega repeat, were used to obtain omega repeat PCR products from the field isolates. The PCR product for each isolate varied in length, depending on the number of cg2 omega repeats for that isolate. We found that several in vivo and in vitro chloroquine-resistant isolates of P. falciparum did not have the expected 16 omega repeats. These results suggest that the link between the cg2 polymorphism and chloroquine resistance identified previously may not apply in all malarious areas.
Epidemiology 1, 2, 3: origins, objectives, organization, and implementation.
Authors: El-Khoby T , Hussein M H , Galal N , Miller F D
Published: May 2017

This supplement is a report on the Epidemiology 1, 2, 3 (EPI 1, 2, 3) investigation, its origins, evolution, and findings that were carried out over a period beginning in 1990 and ending in 1994 in Egypt. The large scope and size of the study, the largest to date on schistosomiasis in Egypt, was a rationale for publishing a supplement to document EPI 1, 2, 3 methods and results collectively in sufficient detail to serve as a reference for planning, designing, and analyzing future epidemiologic studies and evaluation of schistosomiasis control in Egypt. The 3 objectives of EPI 1, 2, 3 were to 1) determine the changing patterns of Schistosoma haematobium and S. mansoni, 2) investigate factors contributing to differences between villages in the Nile Delta, Middle Egypt, and Upper Egypt, and 3) investigate risk factors for morbidity. The objectives were addressed using standardized techniques, stool and urine examinations, clinical examinations (including abdominal ultrasound), and questionnaires on a selected sample of the populations of selected villages in 9 governorates in Egypt.
Random distribution of mixed species malaria infections in Papua New Guinea.
Authors: Mehlotra R K , Lorry K , Kastens W , Miller S M , Alpers M P , Bockarie M , Kazura J W , Zimmerman P A
Published: May 2017

Plasmodium falciparum (Pf), P. vivax (Pv), P. malariae (Pm), and P. ovale (Po) infections are endemic in coastal areas of Papua New Guinea. Here 2,162 individuals living near Dreikikir, East Sepik Province, have been analyzed for complexity of malaria infection by blood smear and polymerase chain reaction (PCR) diagnoses. According to blood smear, the overall prevalence of Plasmodium infection was 0.320. Most individuals (0.283) were infected with a single species only. The prevalence of mixed species infections was low (0.037). Further analysis of a 173-sample subset by nested PCR of small subunit ribosomal DNA resulted in an overall 3.0-fold increase in prevalence of infection, with a 17.5-fold increase in the frequency of mixed species infections. Among mixed species infections detected by PCR, the frequency of double species was 0.364, and that of triple species was 0.237. Nine individuals (0.052) were infected with all 4 species. To determine if infection status (uninfected, single, and multiple infections) deviates from an independent random distribution (null hypothesis), observed versus expected frequencies of all combinations of Plasmodium species infections, or assemblages (Pf-, Pv-, Pm-, Po-, to Pf+, Pv+, Pm+, Po+), were compared using a multiple-kind lottery model. All 4 species were randomly distributed whether diagnosed by blood smear or PCR in the overall population and when divided into age group categories. These findings suggest that mixed species malaria infections are common, and that Plasmodium species appear to establish infection independent of one another.
Pseudomonas (Burkholderia) pseudomallei in Thailand, 1964-1967: geographic distribution of the organism, attempts to identify cases of active infection, and presence of antibody in representative sera.
Authors: Finkelstein R A , Atthasampunna P , Chulasamaya M
Published: May 2017

The purpose of this study, initiated in 1964 and concluded in 1967, was to define the distribution of Pseudomonas (now Burkholderia) pseudomallei in Thailand, to evaluate its importance as an etiologic agent, and to survey the presence of antibody in people that might indicate prior infection and/or contact with the microorganism.
First field evidence for natural vertical transmission of West Nile virus in Culex univittatus complex mosquitoes from Rift Valley province, Kenya.
Authors: Miller B R , Nasci R S , Godsey M S , Savage H M , Lutwama J J , Lanciotti R S , Peters C J
Published: May 2017

West Nile virus is a mosquito borne flavivirus endemic over a large geographic area including Africa, Asia, and the Middle East. Although the virus generally causes a mild, self-limiting febrile illness in humans, it has sporadically caused central nervous system infections during epidemics. An isolate of West Nile virus was obtained from a pool of four male Culex univittatus complex mosquitoes while we were conducting an investigation of Rift Valley fever along the Kenya-Uganda border in February-March 1998. This represents the first field isolation of West Nile virus from male mosquitoes and strongly suggests that vertical transmission of the virus occurs in the primary maintenance mosquito vector in Kenya. A phylogenetic analysis of the complete amino acid sequence of the viral envelope glycoprotein demonstrated a sister relationship with a Culex pipiens mosquito isolate from Romania made in 1996. This unexpected finding probably reflects the role of migratory birds in disseminating West Nile virus between Africa and Europe.
Analysis of Plasmodium vivax merozoite surface protein-1 gene sequences from resurgent Korean isolates.
Authors: Lim C S , Kim S H , Kwon S I , Song J W , Song K J , Lee K N
Published: May 2017

The merozoite surface protein-1 (MSP-1) of Plasmodium vivax exhibits great antigenic diversity among different isolates of this parasite. This antigen is a useful genetic marker for studying the polymorphism of natural P. vivax parasite populations. One or more of these populations has been responsible for resurgent malaria now occurring in Korea. This paper reports the analysis of a highly polymorphic region between interspecies conserved blocks 5 and 6 of the MSP-1 gene, using the polymerase chain reaction to amplify the DNA fragment encompassing these regions from 25 Korean isolates, followed by sequencing. Almost all amino acid sequences of Korean isolates were nearly identical to that of Thai isolates TD525A (96.6-99.7%) and TD424 (96.3-99.5%), and very similar to that of the France-Belem strain when compared with other isolates (Sal-1, Sri Lanka, and Colombia). Interallelic recombination was found in the poly-Q repeat and a Sal-1 type amino acid structure was observed in all isolates. This study shows that the MSP gene nucleotide sequence of resurgent P. vivax in Korea is most similar to that of Thai isolates; however, the Korean strains are phylogenetically unique.
Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission.
Authors: Sokhna C S , Rogier C , Dieye A , Trape J F
Published: May 2017

To investigate host factors affecting the delay of reappearance of malaria parasites after radical treatment, a study was undertaken in Dielmo, Senegal, an area of intense perennial malaria transmission. A 7-day course of quinine was administered to 173 asymptomatic persons from 1 to 85 years of age and reappearance of malaria parasites in the peripheral blood was monitored weekly for 14 weeks. Additional thick blood films were made in case of fever as part of a daily clinical surveillance. The median times before reappearance of Plasmodium falciparum were 22, 39, and 53 days among persons 1-6, 7-14, and > or = 15 years of age, respectively (P < 0.0001). Multivariate analysis indicated that the daily rate of reappearance of P. falciparum was 2.2 (95% confidence interval [CI] = 1.2-4.5) times lower in sickle cell trait carriers than in AA individuals, and 1.5 (95% CI = 1.1-2.1) times lower in bed nets users than in non-users. The risk ratio for the daily risk of reappearance was significantly related to the level of parasitemia before treatment. No influence of glucose-6-phosphate dehydrogenase deficiency, HLA-B53, and DR13 were observed. Findings show that monitoring during a few weeks the reappearance of malaria parasites after treatment among a small cohort of individuals naturally exposed to malaria is relevant for investigating host resistance factors. This suggest that small, low-cost, field trials may be very informative on the potential of new malaria vaccine candidates.
Molecular epidemiology of malaria in Yaounde, Cameroon. VI. Sequence variations in the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene and in vitro resistance to pyrimethamine and cycloguanil.
Authors: Basco L K , Ringwald P
Published: May 2017

Pyrimethamine and cycloguanil, the major human metabolite of proguanil, are inhibitors of dihydrofolate reductase that play a key role in the treatment and prevention of chloroquine-resistant Plasmodium falciparum infections in sub-Saharan Africa. Resistance to these antifolate drugs has emerged in some areas of Africa. Earlier molecular studies have demonstrated that point mutations at key positions of the dihydrofolate reductase-thymidylate synthase gene are strongly associated with antifolate resistance. However, whether the same or distinct mutations are involved in the development of resistance to both pyrimethamine and cycloguanil has not been well established in naturally occurring P. falciparum isolates. In this study, the in vitro responses to both antifolate drugs were measured in 42 Cameroonian isolates and compared with the complete sequence of the dihydrofolate reductase domain of the gene (from 34 of 42 isolates) to analyze the genotype that may distinguish between pyrimethamine and cycloguanil resistance. The wild-type profile (n = 11 isolates) was associated with low 50% inhibitory concentrations (IC50s) ranging from 0.32 to 21.4 nanamole for pyrimethamine and 0.60-6.40 nM for cycloguanil. Mutant isolates had at least one amino acid substitution, Asn-108. Only three mutant codons were observed among the antifolate-resistant isolates: Ile-51, Arg-59, and Asn-108. The increasing number of point mutations was associated with an increasing level of pyrimethamine IC50 and, to a much lesser extent, cycloguanil IC50. These results support a partial cross-resistance between pyrimethamine and cycloguanil that is based on similar amino acid substitutions in dihydrofolate reductase and suggest that two or three mutations, including at least Asn-108, may be necessary for cycloguanil resistance, whereas a single Asn-108 mutation is sufficient for pyrimethamine resistance.
Comparative pathology, and immunohistology associated with clinical illness after Ehrlichia phagocytophila-group infections.
Authors: Lepidi H , Bunnell J E , Martin M E , Madigan J E , Stuen S , Dumler J S
Published: May 2017

The Ehrlichia phagocytophila-group also includes E. equi and the human granulocytic ehrlichiosis (HGE) agent that are probably a single species. Disease is mild to severe illness in ruminants, horses, and humans, but the comparative pathology and ehrlichial distribution in tissues is poorly described. We compared pathology and ehrlichial distribution in humans with HGE, horses with E. equi infection, and a sheep with E. phagocytophila infection. Frequent findings included splenic lymphoid depletion, small macrophage aggregates and apoptoses in liver, and paracortical hyperplasia in lymph nodes. Bone marrow was normocellular or hypercellular. Only the spleen was frequently infected; other organs with infected cells included lung, liver, heart, and kidney, but lesions were present in lung and liver only. Most infected cells were neutrophils. Ehrlichia phagocytophila-group infections are associated with moderate tissue damage. While the pathogenesis of granulocytic ehrlichiosis is not clear, pathologic studies suggest that the process is initiated by ehrlichia-infected cells but may result from host-mediated injury and immunosuppression.
Malaria and anemia in antenatal women in Blantyre, Malawi: a twelve-month survey.
Authors: Rogerson S J , van den Broek N R , Chaluluka E , Qongwane C , Mhango C G , Molyneux M E
Published: May 2017

Malaria and anemia are common in pregnant African women. We screened 4,764 Malawian women at first antenatal visits for malaria and anemia. A total of 42.7% had a malaria infection, which was more common and of higher density in primigravidae (prevalence = 47.3%, geometric mean = 332 parasites/microl) and teenagers (49.8%, 390/microl) than in multigravidae (40.4%, 214/microl) or older women (40.6%, 227/microl). However, 35% of gravida 3+ women were parasitemic. A total of 57.2% of the women was anemic (hemoglobin < 11 g/dl), with moderate anemia (7.0-8.9 g/dl) in 14.9% and severe anemia (< 7 g/dl) in 3.2%. Prevalences of malaria and anemia were highest in the rainy season. Women with moderate/severe anemia had higher parasite prevalences and densities than women with mild/no anemia. Logistic regression showed that age, season, and trimester of presentation were significantly associated with the prevalence of malaria, but gravidity was not. In this urban setting, age and season are more important than gravidity as predictors of malaria at first antenatal visit, and parasitemia is frequent in women of all gravidities.
The epidemiology of schistosomiasis in Egypt: Ismailia governorate.
Authors: Nooman Z M , Hasan A H , Waheeb Y , Mishriky A M , Ragheb M , Abu-Saif A N , Abaza S M , Serwah A A , El-Gohary A , Saad A , El-Sayed M , Fouad M
Published: May 2017

A multi-stage stratified sample of 12,515 individuals from 1,941 households in 42 villages in the Ismailia governorate of Egypt were surveyed for schistosomal infection. A subset of 2,390 subjects were surveyed for morbidity by physical and ultrasonographic examination. The prevalence of Schistosoma mansoni infection in rural Ismailia was 42.9% and the geometric mean egg count (GMEC) was 93.3 eggs/gram of stool, with considerable variability between communities. Prevalence and intensity peaked in the 20-30-year-old age group and was higher in males than in females. Prevalence and intensity of S. haematobium was very low: 1.8% and 3.5 ova/10 ml of urine GMEC, respectively. Canal water exposure risk factors for S. mansoni infection were males bathing (odds ratio [OR] = 2.2), females washing clothes (OR = 1.9), and children playing or swimming (OR = 2.3). Presence of in-house piped water supply and latrine lowered infection rates (P < 0.001 and P = 0.002, respectively). Histories of S. mansoni infection (OR = 1.6) or treatment (OR = 1.5) and blood in feces (OR = 3.5) were associated with infection. Hepatomegaly (16.0%) was more frequently detected than splenomegaly (3.6%) by physical examination, with both being more frequent in older age groups. Splenomegaly, but not hepatomegaly, was associated with presence of S. mansoni ova in stools (OR = 1.4) and the community burden of infection (P = 0.02). Ultrasonographically detected hepatomegaly, splenomegaly, and periportal fibrosis (PPF) were detected in 43.0%, 17.4%, and 39.7% of the subjects, respectively. The higher grades of PPF were rare. Ultrasonographically detected splenomegaly, not hepatomegaly, was associated with S. mansoni infection, community burden of infection, and PPF. Risk factors for PPF were the same as for S. mansoni infection. There was a marginal association of PPF with infection and none (P = 0.33) with the intensity of infection in individuals or in the community. We conclude that in rural Ismailia, S. haematobium infection is rare but the prevalence and intensity of infection with S. mansoni is high. The risk of infection is associated with environmentally detected factors and behaviors. Hepatosplenic morbidity attributable to S. mansoni infection is low, presumably because of the favorable effect of wide application of praziquantel therapy.
Active, multisite, laboratory-based surveillance for Cryptosporidium parvum.
Authors: Dietz V , Vugia D , Nelson R , Wicklund J , Nadle J , McCombs K G , Reddy S
Published: May 2017

Cryptosporidium parvum leaped to the attention of the United States following the 1993 outbreak in Milwaukee, Wisconsin, which sickened 400,000 people. Other outbreaks in the United States have been associated with drinking and recreational water, consumption of contaminated foods, contact with animals, and childcare attendance. Despite its public health importance, the number of people who become infected each year is not known. In 1997, active surveillance for C. parvum was added to the Foodborne Diseases Active Surveillance Network (FoodNet), a collaborative effort among the Centers for Disease Control and Prevention, selected state health departments, the U.S. Departments of Agriculture and Food and Drug Administration. During the first 2 years of surveillance, 1,023 laboratory-confirmed cases of cryptosporidiosis were detected in FoodNet (Connecticut, Minnesota, Oregon, and selected counties in California, Georgia, Maryland, and New York). The annual rate per 100,000 persons was 2.3. Sixteen percent of case-patients were hospitalized. A seasonal increase in case detection was noted in late summer among persons less than 15 years of age. These data represent the first active multistate ascertainment of laboratory-confirmed cryptosporidiosis cases and provide useful information on the burden of disease in the United States.
Vector densities that potentiate dengue outbreaks in a Brazilian city.
Authors: Pontes R J , Freeman J , Oliveira-Lima J W , Hodgson J C , Spielman A
Published: May 2017

To identify the critical vector density that potentiates dengue outbreaks in an endemic site and to identify obstacles to anti-dengue activities, we correlated a series of dengue outbreaks in a Brazilian city with the intensity of its anti-vector source-reduction activities. The proportion of houses infested by vector mosquitoes correlated inversely with intensity of anti-mosquito interventions, and the vector population developed independently of rainfall. Local periods of drought promoted vector abundance in two ways: residents stored water in which vector mosquitoes could breed, and cholera outbreaks due to contaminated water diverted local health workers from routine anti-vector activities. One dengue outbreak became apparent to authorities more than two months after it commenced but would have been identified almost immediately had dengue-like disease in indicator hospitals been monitored. Active surveillance, therefore, offers a window of opportunity for promptly executed anti-dengue interventions. Source-reduction measures that suppress vector infestations to less than 1% of houses effectively avert outbreaks of dengue.
Risk factors, seasonality, and trends of cryptosporidiosis among patients infected with human immunodeficiency virus.
Authors: Inungu J N , Morse A A , Gordon C
Published: May 2017

To determine risk factors, seasonality, and trends of cryptosporidiosis among human immunodeficiency virus-positive (HIV+) patients in the New Orleans area, data from the New Orleans component of the Adult/Adolescent Spectrum of HIV Disease Study (ASD) were analyzed. A total of 6,913 HIV+ patients > or = 13 years of age were enrolled in the ASD database between 1990 and 1998. After an average follow-up of 42 months, cryptosporidiosis had been diagnosed in 239 patients (3.5%). The risk of developing cryptosporidiosis was higher among patients with CD4+ cell counts < 100 x 10(6)/L, among those who ever developed an acquired immunodeficiency syndrome (AIDS)-opportunistic illness, and among patients < 35 years old compared with their counterparts. A slight increase in cryptosporidiosis cases occurred in the spring compared with other seasons, but the difference was not statistically significant (P > 0.05). The prevalence of cryptosporidiosis increased from 2.9% (n = 7) in 1989 to 20% in 1994 (n = 48) before decreasing to 5.3% in 1998 (n = 14). Since a fair number of cryptosporidiosis cases are still being reported in the New Orleans area after the introduction of highly active antiretroviral therapy, further studies are needed to provide insight into the existence of potential environmental sources of Cryptosporidium.
A randomized, double-blind, parallel-group, comparative safety, and efficacy trial of oral co-artemether versus oral chloroquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in India.
Authors: Kshirsagar N A , Gogtay N J , Moorthy N S , Garg M R , Dalvi S S , Chogle A R , Sorabjee J S , Marathe S N , Tilve G H , Bhatt A D , Sane S P , Mull R , Gathmann I
Published: May 2017

In India, treatment of acute, uncomplicated Plasmodium falciparum malaria is becoming increasingly difficult due to resistance to chloroquine, thus there is a need for new antimalarial drugs. CGP 56697 (co-artemether), a new drug, is a combination of artemether and lumefantrine in a single oral formulation (one tablet = 20 mg of artemether plus 120 mg of lumefantrine). In a double-blind study, 179 patients with acute uncomplicated P. falciparum malaria were randomly assigned to receive either CGP (n = 89) given as a short course of 4 x 4 tablets over a 48-hr period or chloroquine (n = 90) given as four tablets (one tablet = 150 mg of chloroquine base) initially, followed by two tablets each at 6-8, 24, and 48 hr. Due to a death in the chloroquine group and a decrease in the chloroquine cure rate to < 50% (based on the blinded overall cure rate at that time), recruitment was terminated prematurely. CGP 56697 showed a superior 28-day cure rate (95.4% versus 19.7%; P < 0.001), time to parasite clearance (median = 36 versus 60 hr; P < 0.001), and resolution of fever (median = 18 versus 27 hr; P = 0.0456). This drug provides a safe, effective, and rapid therapy for the treatment of acute uncomplicated P. falciparum malaria.
Studies of the neurotoxicity of oral artemisinin derivatives in mice.
Authors: Nontprasert A , Pukrittayakamee S , Nosten-Bertrand M , Vanijanonta S , White N J
Published: May 2017

Intramuscular injections of high doses of the oil-soluble antimalarial artemisinin derivatives artemether and arteether produce an unusual pattern of selective damage to brain stem centers in experimental mammals, predominantly those involved in auditory processing and vestibular reflexes. We have shown recently in adult Swiss albino mice that parenteral artesunate, a water-soluble derivative, is significantly less neurotoxic than intramuscular artemether in this murine model. Using the same model, in which the drugs were administered daily for 28 days, the neurotoxic potential of the oral drugs was assessed and compared with the parenteral routes of administration. The dose causing neurotoxicity or death in 50% of animals (ED50), was approximately 300 mg/kg/day of oral artemether and artesunate compared to 50 mg/kg/day of intramuscular artemether. Doses of intramuscular artemether > 100 mg/kg/day were uniformly lethal. When oral artemether was given in peanut oil there was an increase in neurotoxicity and mortality compared with the aqueous suspension (P = 0.002), and when the food pellets were coated with artemether in oil, giving relatively constant oral intake, neurotoxicity was further increased; ED50 = 150 mg/kg/day (P = 0.017). These data indicate that once-daily oral administration of artesunate or artemether is relatively safe, presumably because the central nervous system is exposed transiently, whereas constant exposure either from depot intramuscular injection of oil-based drug, or constant oral intake carries relatively greater neurotoxic potential.