bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular epidemiology of malaria in Yaounde, Cameroon I. Analysis of point mutations in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum.
Authors: Basco L K , Ringwald P
Published: May 2017

Resistance to antifolate antimalarial drugs (cycloguanil, a biologically active metabolite of proguanil, and pyrimethamine) is associated with a Ser- to Asn-108 point mutation in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. The frequency of this mutation was studied in 127 clinical isolates obtained in Yaounde, Cameroon using a simple and rapid molecular technique based on the polymerase chain reaction and restriction fragment length polymorphism. Of the 127 isolates, pure wild-type Ser-108 codon, pure mutant-type Asn-108 codon, and mixed codons were observed in 66, 55, and six parasites, respectively. The proportion of antifolate-resistant, pure mutant-type codon, with respect to pure wild-type or mixed alleles, was 43% (55 of 127). The results of the molecular assay were compared with those of semimicro isotopic in vitro assay in 34 isolates. All 17 pure Ser-108 isolates and two isolates with mixed alleles were sensitive to both pyrimethamine (50% inhibitory concentration [IC50] < 100 nM) and cycloguanil (IC50 < 50 nM). Fourteen of 15 isolates with the mutant-type Asn-108 codon were resistant to pyrimethamine and cycloguanil. One isolate with Asn-108 showed a slightly elevated pyrimethamine IC50 (78 nM), which was within the sensitive range. This study provides further evidence that antifolate-resistant P. falciparum isolates are already present in Yaounde, Cameroon.
High Cryptosporidium prevalences in healthy Aymara children from the northern Bolivian Altiplano.
Authors: Esteban J G , Aguirre C , Flores A , Strauss W , Angles R , Mas-Coma S
Published: May 2017

The prevalence of Cryptosporidium infection was determined in four Aymara communities in the Bolivian Altiplano, between the city of La Paz and Lake Titicaca, at an altitude of 3,800-4,200 meters. Single stool specimens were randomly collected from 377 5-19-year-old students, all apparently asymptomatic. The total prevalence (31.6%) is possibly the highest reported among healthy humans (a maximum of 9.8% and 2.0% in coprologic surveys in underdeveloped and developed countries, respectively) and one of the highest even in symptomatic subjects. No significant age and sex differences were observed. Such an infection prevalence is probably related to the poor sanitation conditions, contaminated water supplies, overcrowding, and close contact with domestic animals. Continuous exposure to the parasite could be associated with protection against parasite-related symptoms in the children examined.
Odor-mediated host preferences of West African mosquitoes, with particular reference to malaria vectors.
Authors: Costantini C , Sagnon N F , della Torre A , Diallo M , Brady J , Gibson G , Coluzzi M
Published: May 2017

The role of odors in mosquito host preferences was studied in a village near Ouagadougou, Burkina Faso. Two odor-baited entry-traps were put beside one another and a choice of host odor-laden air was blown out of them. Odors of a human and a calf (of similar mass) were drawn from two tents in which each was separately concealed. Allowances were made for trap position, differences in human-subject attractiveness, CO2 levels, and trap contamination with alternative host odors. Choices for the human-baited trap greater than the 0.5 random expectation were made by Anopheles gambiae s.l. (0.96) and An. pharoensis (0.68). The choices for the human-baited trap of Culex antennatus were significantly lower than 0.5 (0.25), whereas for the Cx. decens species group (0.56), the difference was not significant. Interpretation of the latter result was complicated by the significant effect of CO2 levels on the index. Species caught in low numbers but whose trap distribution showed a bias towards the human-baited trap were An. funestus (total numbers in the human-baited trap to the calf-baited trap = 9:0), Mansonia africana (17: 1), Aedes dalzieli (22:4), and Ae. hirsutus (13:1); species showing bias towards the calf-baited trap were An. rufipes (0:11), Cx. duttoni (0:17), and Cx. nebulosus (2:35). Mansonia uniformis was the only species distributed randomly between the two traps. Molecular identification of the An. gambiae s.l. samples revealed a marked difference in trap distribution: for the human-baited trap the ratio was 52% An. arabiensis to 48% An. gambiae s.s.; for the calf-baited trap, it was 92% An. arabiensis to 8% An. gambiae s.s.
The molluscicidal activity of Crown of Christ (Euphorbia splendens var. hislopii) latex on snails acting as intermediate hosts of Schistosoma mansoni and Schistosoma haematobium.
Authors: Schall V T , de Vasconcellos M C , de Souza C P , Baptista D F
Published: May 2017

The present study describes the action of the latex of Euphorbia splendens var. hislopii (E. milli) on species of the genus Bulinus and on Biomphalaria pfeifferi, intermediate hosts of schistosomiasis in Africa, and the Brazilian snails B. glabrata, B. tenagophila, and B. straminea, intermediate hosts of schistosomiasis in Brazil. The impact of the latex on the egg masses and embryos of B. glabrata was also evaluated. Using the standardized methodology of the World Health Organization for testing plant-derived molluscicides, we obtained a 90% lethal dose (LD90) ranging from 0.13 ppm for B. glabrata subjected to lyophilized latex to 4.0 ppm for B. pfeifferi tested with the natural latex. This material has proved to be one of the most potent and specific plant molluscicides discovered thus far, presenting advantages in terms of application so that it could be used in programs involving community participation in endemic areas in both Brazil and Africa.
Detection of the filarial parasite Mansonella streptocerca in skin biopsies by a nested polymerase chain reaction-based assay.
Authors: Fischer P , BÃ¼ttner D W , Bamuhiiga J , Williams S A
Published: May 2017

To differentiate the skin-dwelling filariae Mansonella streptocerca and Onchocerca volvulus, a nested polymerase chain reaction (PCR) assay was developed from small amounts of parasite material present in skin biopsies. One nonspecific and one specific pair of primers were used to amplify the 5S rDNA spacer region of M. streptocerca. Biopsies with different microfilaria densities obtained from 104 Ugandans living in an area endemic for M. streptocerca were tested using both the nested PCR assay and standard parasitologic assessment of microfilariae. All 82 samples from microfilaria carriers were positive when tested using the nested PCR assay. In addition, M. streptocerca DNA could be detected in 16 samples thought to be microfilaria negative. Furthermore, six days following ivermectin treatment, M. streptocerca DNA was found in 12 of 14 microfilaria-negative biopsies. Control skin samples from patients infected with O. volvulus were all negative in the nested PCR assay. This assay improves the diagnosis of M. streptocerca and will facilitate further epidemiologic studies.
Conversion of dengue virus replicative form RNA (RF) to replicative intermediate (RI) by nonstructural proteins NS-5 and NS-3.
Authors: Raviprakash K , Sinha M , Hayes C G , Porter K R
Published: May 2017

Dengue viruses infect more than 100 million people each year and cause serious clinical manifestations. It is important to understand the replication of these viruses so that therapeutic and/or prophylactic agents may be designed. Dengue virus type 2 nonstructural proteins NS-5 and NS-3 were produced by in vitro transcription and translation of cloned genes. Both proteins possessed RNA-dependent RNA polymerase activity as measured by their ability to convert purified replicative form (RF) RNA to replicative intermediate (RI). The recombinant proteins, however, required one or more cellular protein(s) for their activity. Examination of NS-3 protein sequence revealed heretofore unnoticed sequence similarities with other polymerases.
Plasmodium coatneyi in the rhesus monkey (Macaca mulatta) as a model of malaria in pregnancy.
Authors: Davison B B , Cogswell F B , Baskin G B , Falkenstein K P , Henson E W , Tarantal A F , Krogstad D J
Published: May 2017

Pregnant women with Plasmodium falciparum infection are at increased risk for complications such as anemia and cerebral malaria. In addition, the infants of these women suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection, and high infant mortality. Although much has been learned from studies of malaria during human pregnancy, progress has been limited by the lack of a suitable animal model. Nonhuman primates are of particular interest because, other than the armadillo, they are the only animals with a discoidal, villous, hemochorial placenta like that of humans. We have established a model of malaria during human pregnancy by inoculating pregnant rhesus monkeys (Macaca mulatta) with Plasmodium coatneyi (a sequestering parasite) during the first trimester. In our initial experiment, four monkeys were inoculated with a fresh inoculum containing 10(8) viable parasites from an infected donor monkey. All four monkeys became parasitemic seven days postinoculation (PI) and three monkeys aborted 7-10 days PI coincident with high peak parasitemias (41,088-374,325 parasites/mm3). Although abortion is one of the outcomes observed in Plasmodium-infected women, the intent of this study was to examine the effects of Plasmodium infection throughout gestation. Since the rapid onset of high parasitemia may have been responsible for the abortions, a decision was made to reduce the size of the effective inoculum. Six additional pregnant monkeys were inoculated with a frozen isolate taken from the same donor containing 10(6) parasites. These six animals became parasitemic by 14 days PI and, along with monkey E412, carried their infants to term. These seven infants weighed significantly less at term than the infants of uninfected mothers (P = 0.0355). Symmetrical IUGR was detected by ultrasound in one fetus with an LBW of 334 g. Another LBW infant (300 g) had asymmetrical growth retardation, which has been associated with uteroplacental insufficiency and was consistent with the lower placental weights found in infected dams compared with controls (P = 0.0455). The infant with symmetric IUGR died at five days of age, while the other is alive but congenitally infected. The IUGR, LBW, congenital infection, postnatal infant mortality, and early abortions observed in these animals suggest that P. coatneyi in pregnant rhesus monkeys is a valid model of malaria in human pregnancy. This model should provide the opportunity to study questions about malaria in pregnancy that have been difficult to study in humans.
Longitudinal analysis of the development of filarial infection and antifilarial immunity in a cohort of Haitian children.
Authors: Lammie P J , Reiss M D , Dimock K A , Streit T G , Roberts J M , Eberhard M L
Published: May 2017

Longitudinal studies are being conducted in Leogane, Haiti to investigate the relationship between acquisition of filarial infection and development of antifilarial immunity as well as the impact of maternal infection on this relationship. Children (0-24 months of age) residing in Leogane were enrolled and were examined periodically to monitor parasitologic status and to collect serum for antigen and antifilarial antibody determinations. To examine the development of filarial antigenemia and antifilarial antibody responses in this cohort, serum samples were selected from a cross section of the population at two (n = 82) and four years of age (n = 76). Antigen prevalence increased from 6% among two-year-olds to more than 30% among four-year-olds, but in only one four-year-old child were microfilaria detected in a 20-microl smear. The proportion of antigen-positive children born to antigen-positive mothers was higher than the proportion of antigen-positive children born to antigen-negative mothers (9.8% versus 0% for two-year-olds; P = 0.15; and 39.6% versus 22.7% for four-year-olds; P = 0.18). Antifilarial IgG4 levels were significantly higher among antigen-positive children at both two and four years of age (P < 0.001). In analyses of paired samples, antifilarial IgG4 responses increased significantly more among children who acquired infection by four years of age than among children who remained antigen negative, whereas antifilarial IgG1 and IgG2 responses changed equally for antigen-positive and -negative children. Antifilarial antibody levels were not influenced by maternal infection status, but were significantly influenced by age, antigen status, and the neighborhood within the community. These results provide evidence that children acquire infection early in life and suggest that antifilarial antibody responses may peak in early childhood.
Antibody to a cDNA-derived calreticulin protein from Amblyomma americanum as a biomarker of tick exposure in humans.
Authors: Sanders M L , Jaworski D C , Sanchez J L , DeFraites R F , Glass G E , Scott A L , Raha S , Ritchie B C , Needham G R , Schwartz B S
Published: May 2017

The antibody responses of human and animal hosts were studied to determine the utility of antibody against recombinant tick calreticulin (rTC), a cDNA-derived protein isolated from salivary glands of Amblyomma americanum L., as a biologic marker of tick exposure. Rabbits fed upon by either A. americanum or Dermacentor variabilis Say developed significant anti-rTC antibody responses, as measured by both ELISA and immunoblot assay. In contrast, gerbils exposed to Aedes aegypti did not develop anti-rTC antibodies, as measured by ELISA or immunoblot assay. The utility of the assay was next evaluated in humans at high risk for tick exposure. During April through September 1990, 192 military personnel who originated from either Fort Chaffee, Arkansas or Fort Wainwright, Alaska were studied during maneuvers in tick infested areas at Fort Chaffee. Study subjects completed a questionnaire and had pre- and post-maneuvers serum specimens analyzed for antibodies to rTC. In adjusted analysis (controlling for age, fort of origin, attached tick during maneuvers, and bed netting use), the use of bed netting and home station were associated with post-maneuvers anti-rTC antibody seropositivity by ELISA. Subjects from Fort Wainwright were more likely to be seropositive for anti-rTC antibody (adjusted odds ratio = 5.3, 95% confidence interval [CI] = 1.1-25.6). Personnel who did not report the use of bed netting were more likely to be anti-rTC seropositive (adjusted odds ratio = 6.8, 95% CI = 1.4-32.4). Immunoblot assays showed that humans had specific anti-rTC antibody responses. The animal experiments demonstrate that hosts exposed to naturally feeding ticks develop anti-rTC antibodies. The data also indicate that hosts exposed to Ae. aegypti saliva may not develop antibodies against rTC. Observations in tick-exposed humans support the hypothesis that anti-rTC antibody seropositivity is a biologic marker of tick exposure.
Ecologic observations on anopheline vectors of malaria in the Brazilian Amazon.
Authors: Tadei W P , Thatcher B D , Santos J M , Scarpassa V M , Rodrigues I B , Rafael M S
Published: May 2017

Human intervention in the Brazilian Amazon region promotes contacts between humans and vectors that may favor the propagation of anopheline mosquitoes and the spread of malaria in the absence of planning and infrastructure to control this disease. Vector ecology studies were carried out to determine the risk areas. These data should help in designing appropriate malaria control measures. Data from 14 different regions are reported. Vectors are able to adapt to different environments, which made it necessary to study each area. The parameters studied were Anopheles breeding sites, species distribution, incidence, feeding preferences, hours of maximum activity of adult mosquitoes, seasonality, resting places, and the presence of Plasmodium. Species complexes were also studied. Anopheles darlingi may be responsible for maintaining malaria in human populations in this region. A reduction in the population density of A. darlingi in a particular geographic area can sometimes cause the disappearance of malaria. This species feeds at night but has a peak of activity at the beginning of the evening and another at dawn. Other species are mainly crepuscular and all anophelines demonstrated pronounced exophilia. The timing of feeding activities was found to vary in areas altered by human intervention and also depended on the time of the year and climatic conditions. The larvae were more abundant in the rivers with a less acidic pH and rural areas showed the highest larval index.
Failure of penicillin treatment of yaws on Karkar Island, Papua New Guinea.
Authors: Backhouse J L , Hudson B J , Hamilton P A , Nesteroff S I
Published: May 2017

The endemic treponematosis yaws remains a significant cause of morbidity in many tropical countries, despite mass treatment campaigns to eradicate it. An outbreak of yaws in Marup village on Karkar Island, Papua New Guinea in 1988 provided an opportunity to monitor the outcome of treatment with penicillin over an extended period. Thirty-nine children with clinical yaws (6% of 632 examined) were monitored clinically and serologically, for nearly two years after mass treatment of all villagers with the World Health Organization recommended dosages of benzathine penicillin. Lesions resolved within one month of treatment in all but four (10%) children, three of whom were initially successfully retreated. Before treatment, the Venereal Disease Research Laboratory (VDRL) test result was reactive in 67% of the children and treponema-specific IgM antibody test results were reactive in 41%. Within six months of treatment, of those reactive, the VDRL titer decreased significantly in 25 (96%) of 26 and IgM antibody test results became negative in 13 (81%) of 16 children. However, by the end of follow-up, 11 (28%) of the 39 children had developed clinical and/or serologic evidence of relapse. In these children, response to further treatment was slow and, in three, evidence of active infection persisted or recurred, despite repeated courses. Exogenous reinfection was unlikely in this isolated community, in which the occurrence of yaws was closely monitored after universal treatment. Treatment failure was most likely to have been due to reduced susceptibility to penicillin of Treponema pallidum subsp. pertenue.
Assessment of the neurotoxicity of parenteral artemisinin derivatives in mice.
Authors: Nontprasert A , Nosten-Bertrand M , Pukrittayakamee S , Vanijanonta S , Angus B J , White N J
Published: May 2017

In all experimental mammals tested (rats, dogs, primates), intramuscular injections of the oil-soluble antimalarial artemisinin derivatives artemether and arteether have produced an unusual pattern of selective damage to brain stem centers predominantly involved in auditory processing and vestibular reflexes. Artesunate, the most widely used of these compounds, is a water soluble hemisuccinate derivative given parenterally either by intravenous or intramuscular injection. The neurotoxic potential of parenteral artesunate and artemether was compared in a murine model. Adult Swiss albino mice were assigned randomly to 28-day regimens of intramuscular artemether or artesunate in doses ranging from 30 to 100 mg/kg/day. At 30 mg/kg/day, no abnormalities were detected with either drug. At 50 mg/kg/day, abnormalities were observed in six of 12 artemether recipients and two of 12 artesunate recipients. These were reversible in all but one (artemether) mouse. At 100 mg/kg/day, eight of 36 artemether recipients, two of 36 artesunate recipients, and one of 18 control mice died. All but four surviving mice in the artemether group (86%) showed obvious and usually irreversible abnormalities of balance and equilibrium, whereas only four artesunate recipients (11%) exhibited abnormalities, and these were reversible in each case (P < 0.001). At this dose the relative risk (95% confidence interval) for death or disability was 5.3 (2.6-11.2) for artemether recipients. Intramuscular artemether is significantly more neurotoxic than intramuscular artesunate in this murine model.
Pathogenesis of a North American hantavirus, Black Creek Canal virus, in experimentally infected Sigmodon hispidus.
Authors: Hutchinson K L , Rollin P E , Peters C J
Published: May 2017

This report describes the first detailed analysis of the replication, persistence, and excretion of a North American hantavirus in its natural rodent reservoir. Black Creek Canal virus was isolated from Sigmodon hispidus (cotton rat) shortly after the identification of a hantavirus pulmonary syndrome (HPS) case occurring in southern Florida. Six-week-old male cotton rats were inoculated subcutaneously with 1,000 tissue culture infectious doses. Viral complementary RNA (vcRNA) was quantified as a means of determining the site(s) of viral activity (transcription and replication). In the first few weeks post inoculation (pi), vcRNA was detectable in every tissue examined except blood. The quantities of vcRNA decreased over time, and by five months pi it could be detected only in the brain. In addition to using a quantitative polymerase chain reaction (QPCR) as a means of measuring viral replication/transcription, attempts were made to reisolate virus from all tissue samples taken. Virus could be isolated from every solid tissue examined, and the titers appeared to decrease over time, similar to the QPCR results. However, in contrast to the QPCR results, infectious virus was still routinely detectable at low levels in adrenal gland, liver, kidney, and testicle 150 days pi. Although results of testing for vcRNA in the blood were uniformly negative, infectious virus was detected at one week pi, reached highest titers at two weeks, and decreased dramatically by three weeks. After three weeks pi, infectious virus could only be detected sporadically in blood. Virus was isolated from urine collected during the first 70 days pi and throughout the entire study period in feces and wet bedding. These data indicate that the viral infection can be separated into an acute phase associated with high virus titers, and a chronic or persistent phase associated with lower virus titers and continued shedding of virus in excreta.
Short report: Influence of centers for disease control light trap position, relative to a human-baited bed net, on catches of Anopheles gambiae and Culex quinquefasciatus in Tanzania.
Authors: Mboera L E , Kihonda J , Braks M A , Knols B G
Published: May 2017

The best position for Centers for Disease Control (Atlanta, GA) light traps, in relation to human-occupied bed nets for trapping of host-seeking Anopheles gambiae Giles and Culex quinquefasciatus Say mosquitoes, was determined in Tanzania. Significantly higher catches were recorded for both species when the trap was positioned at the foot end of the bed, near the top of the net. Parity rates were significantly higher near the top of the net than at the level of the host. Since trap position affects the catch size and the proportion of infectious mosquitoes therein, standardized use of this sampling technique for estimating entomologic inoculation rates (i.e., the number of potentially infectious bites received over a certain period of time) is recommended.
Time-response curve of oxfendazole in the treatment of swine cysticercosis.
Authors: Gonzalez A E , Falcon N , Gavidia C , Garcia H H , Tsang V C , Bernal T , Romero M , Gilman R H
Published: May 2017

Human Taenia solium cysticercosis is a major cause of epilepsy in developing countries, and porcine infection causes widespread economic losses because of infested pork. Recently, the use of oxfendazole (OFZ) for porcine cysticercosis provided, for the first time, an effective, single-dose treatment. We performed a controlled study to determine the time required between treatment with a single dose of OFZ and the death of cysticerci to define its applicability as preslaughter treatment or as a field control measure. Twenty naturally infected pigs were included in this study. Sixteen received a single dose (30 mg/kg) of OFZ, and were killed in groups of four at one, two, four, and 12 weeks after treatment. Four untreated controls were killed at week 12. No adverse reactions to OFZ were noted. A clear decrease in viability and number of cysts was evident after the first week after therapy, but even at week 4 some viable cysticerci were found in all samples. Twelve weeks after treatment, all meat appeared clear and only minuscule scars remained, except in one animal that had viable brain cysts. This study confirms the efficacy of a single dose of 30 mg/kg of OFZ for porcine cysticercosis but demonstrates that preslaughter treatment of pigs with OFZ will not be useful in controlling cysticercosis. The inclusion of porcine treatment with OFZ in mass cysticercosis control programs is, however, highly promising because it is a simple, effective, inexpensive, and potentially sustainable method for decreasing the porcine reservoir of cysticercosis in disease-endemic countries.
Water distribution system and diarrheal disease transmission: a case study in Uzbekistan.
Authors: Semenza J C , Roberts L , Henderson A , Bogan J , Rubin C H
Published: May 2017

Deteriorating water treatment facilities and distribution systems pose a significant public health threat, particularly in republics of the former Soviet Union. Interventions to decrease the disease burden associated with these water systems range from upgrading distribution networks to installing reverse osmosis technology. To provide insight into this decision process, we conducted a randomized intervention study to provide epidemiologic data for water policy decisions in Nukus, Uzbekistan, where drinking water quality is suboptimal. We interviewed residents of 240 households, 120 with and 120 without access to municipal piped water. Residents of 62 households without piped water were trained to chlorinate their drinking water at home in a narrow-necked water container with a spout. All study subjects (1583 individuals) were monitored biweekly for self-reported diarrheal illness over a period of 9.5 weeks. The home chlorination intervention group had the lowest diarrheal rate (28.8/1,000 subjects/month) despite lack of access to piped water in their homes. Compared with the two groups that did not receive the intervention this rate was one-sixth that of the group with no piped water (179.2/1,000 subjects/month) and one-third that of the households with piped water (75.5/1,000 subjects/month). More than 30% of the households with piped water lacked detectable levels of chlorine residues in their drinking water, despite two-stage chlorination of the source water, and were at increased risk of diarrhea. Forty-two percent of these municipal users reported that water pressure had been intermittent within the previous two days. The dramatic reduction in diarrheal rates in the home-chlorination intervention group indicates that a large proportion of diarrheal diseases in Nukus are water-borne. The home-chlorination group had less diarrhea than the group with piped water, implicating the distribution system as a source of disease transmission. Taken together, these epidemiologic data would support the hypothesis that diarrhea in the piped water group could be attributed to cross-contamination between the municipal water supply and sewer, due to leaky pipes and lack of water pressure. Relatively inexpensive steps, including chlorination, maintaining water pressure, and properly maintaining the distribution system, rather than reverse osmosis technology, should reduce diarrheal rates.
Predicting mosquito repellent potency of N,N-diethyl-m-toluamide (DEET) analogs from molecular electronic properties.
Authors: Ma D , Bhattacharjee A K , Gupta R K , Karle J M
Published: May 2017

Specific molecular electronic properties of 30 N,N-diethyl-m-toluamide (DEET) analogs demonstrate functional dependence with their reported duration of protection against mosquito bites, thus providing predictors of insect repellent efficacy. No single electronic property is sufficient to predict repellent efficacy as measured by protection time, rather a set of specific electronic properties is required. Thus, the values of the van der Waals surface electrostatic potential by the amide nitrogen and oxygen atoms, the atomic charge at the amide nitrogen atom, and the dipole moment must all be in optimal ranges for potent repellency. The electronic properties were calculated using the AM semi-empirical quantum chemical method using commercial software. These easily calculable predictors of repellent efficacy should be useful in predicting the relative efficacy of newly designed compounds, thus guiding the selection of new repellents for testing.
Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH).
Authors: Piper R , Lebras J , Wentworth L , Hunt-Cooke A , HouzÃ© S , Chiodini P , Makler M
Published: May 2017

We have developed two diagnostic assays based on the specific detection of Plasmodium lactate dehydrogenase (pLDH) activity. These assays exploit a panel of monoclonal antibodies that capture the parasite enzyme and allow for the quantitation and speciation of human malaria infections. An immunocapture pLDH activity assay (ICpLDH) allows for the rapid purification and measurement of pLDH from infected blood using the NAD analog APAD, which reacts specifically with Plasmodium LDH isoforms. An immunochromatographic test (the OptiMAL assay) was also formatted and allowed the detection of parasite infections of approximately 200 parasites/microl of blood. By using a combination of antibodies, both tests can not only detect but differentiate between P. falciparum and non-P. falciparum malaria. Both assays show a sensitivity comparable with other commercial nonmicroscopic tests; importantly, we found very few instances of false-positive samples, especially with samples from patients recently cleared of malaria infection. Furthermore, we find that when one uses the quantitative ICpLDH assay, the levels of pLDH activity closely mirror the levels of parasitemia in both initial diagnosis and while following patient therapy. We conclude that diagnostic tests based on the detection of pLDH are both sensitive and practical for the detection, speciation, and quantitation of all human Plasmodium infections and can also be used to indicate drug-resistant infections.
Operational validation of the direct agglutination test for diagnosis of visceral leishmaniasis.
Authors: Boelaert M , El Safi S , Jacquet D , de Muynck A , van der Stuyft P , Le Ray D
Published: May 2017

The validity of the direct agglutination test (DAT) for visceral leishmaniasis (VL) was studied with a standardized field kit on 148 clinically suspected persons and 176 healthy controls recruited between 1993 and 1994 from an endemic area in Gedaref State, Sudan. A sensitivity of 95.9% and a specificity of 99.4% were found at a 1: 8,000 cut-off titer when parasitologically confirmed cases were compared with healthy controls. While corroborating previously reported sensitivity and specificity estimates of this serodiagnostic test, this study examined the bias generated by commonly used test validation procedures. The fundamental methodologic problem in VL test validation is the absence of a reliable gold standard. Moreover, any operational guideline on DAT use has to consider the critical dependency of the predictive values of the test on VL prevalence rates. The DAT diagnostic cut-off titer depends upon many external factors, among which the prevalence of disease in the area and the case mix seem the most important.
Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G.
Authors: Chappell C L , Okhuysen P C , Sterling C R , Wang C , Jakubowski W , Dupont H L
Published: May 2017

A 50% infectious dose (ID50) of 132 Cryptosporidium parvum oocysts was previously determined in serologically negative individuals (ELISA). In this study, 17 healthy adults with pre-existing anti-C. parvum serum IgG were challenged with 500-50,000 oocysts. Infection and diarrhea were associated with the higher challenge doses. The ID50 was 1,880 oocysts, > 20-fold higher than in seronegative volunteers. Fecal oocysts were detected in only seven (53.8%) of 13 individuals with clinical cryptosporidiosis, indicating that the host response may effectively decrease the number of oocysts produced. Subjects with the highest absorbances prior to challenge had little to no increase in IgG following challenge, whereas volunteers with lower reactivities showed significant postchallenge increases. This suggests that an upper limit of serum IgG was present in some subjects, while others were further stimulated by an additional exposure. These data indicate that prior exposure to C. parvum provides protection from infection and illness at low oocyst doses.
Fecal occult blood testing on Trichuris-infected primary school children in northeastern peninsular Malaysia.
Authors: Raj S M
Published: May 2017

Stool specimens of 104 primary schoolchildren (mean+/-SD age = 8.2+/-0.3 years) were examined for helminth eggs and for occult blood to investigate the possibility that trichuriasis causes occult intestinal bleeding in the absence of the overt Trichuris dysentery syndrome. A commercially available guaiac test was used to detect fecal occult blood. Sixty-one children had Trichuris infection, 11 of whom had heavy infections (> 10,000 eggs per gram of feces [epg]), and 53 had Ascaris infections. No hookworm infection was detected. Baseline screening yielded only one weakly positive occult blood test result in a child with a light (800 epg) Trichuris infection. Serial stool occult blood testing on the 11 subjects with heavy trichuriasis and 8 uninfected controls yielded a single weakly positive result in the control group. The results provide no evidence that trichuriasis predisposes to significant occult gastrointestinal bleeding in children in the absence of the dysenteric syndrome.
Comparison of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (OptiMAL) with microscopy for the detection of malaria parasites in human blood samples.
Authors: Cooke A H , Chiodini P L , Doherty T , Moody A H , Ries J , Pinder M
Published: May 2017

Microscopic examination of blood smears remains the gold standard for malaria diagnosis, but is labor-intensive and requires skilled operators. Rapid dipstick technology provides a potential alternative. A study was conducted in The Gambia to compare the performance of OptiMAL, an immunochromatographic antigen detection assay for the diagnosis of malaria using parasite lactate dehydrogenase, against standard microscopy in patients with suspected malaria. For initial diagnosis of Plasmodium falciparum, irrespective of stage, this assay had a sensitivity of 91.3%, a specificity of 92%, a positive predictive value of 87.2%, and a negative predictive value of 94.7%. The sensitivity of the test decreased markedly at parasitemias < 0.01%. This assay can be used for the diagnosis of malaria in areas where microscopy is not available and for urgent malaria diagnosis at night and at weekends, when routine laboratories are closed and when relatively inexperienced microscopists may be on duty.
Differential serodiagnosis for cystic and alveolar echinococcosis using fractions of Echinococcus granulosus cyst fluid (antigen B) and E. multilocularis protoscolex (EM18).
Authors: Ito A , Ma L , Schantz P M , Gottstein B , Liu Y H , Chai J J , Abdel-Hafez S K , Altintas N , Joshi D D , Lightowlers M W , Pawlowski Z S
Published: May 2017

Echinococcus granulosus cyst fluid and E. multilocularis protoscolex extract were fractionated by a single step of preparative isoelectric focusing, resulting in an antigen B-rich fraction (8-kD) and an Em18-rich fraction, respectively. The usefulness of both fractions for differential serodiagnosis of cystic (CE) and alveolar (AE) echinococcosis was evaluated by a large-scale immunoblot analysis on a battery of 354 serum samples. These included 66 from AE patients originating from four different endemic areas, 173 from CE patients originating from seven different endemic areas, 71 from patients with other parasitic diseases, 15 from patients with hepatomas, and 29 from healthy individuals. In an immunoblot with the antigen B-rich fraction, 92% (158 of 173) of the CE sera as well as 79% (52 of 66) of the AE sera reacted with the 8-kD subunit. No cross-reactivity occurred with any sera from patients with cysticercosis, other parasitic diseases, or with hepatomas, or from healthy controls. In an immunoblot with the Em18-rich fraction, all but two sera from AE patients (64 of 66, 97%) recognized Em18, and only nine of 34 CE sera from China reacted with it. All other (139) CE sera from six other countries were negative as were all (115) other non-echinococcosis sera. These findings indicate that antigen B (8-kD) is not species-specific for E. granulosus but is genus-specific for Echinococcus, and that the Em18 antigen is a reliable serologic marker for species-specific differentiation of AE from CE.
Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.
Authors: AÃ±ez N , Carrasco H , Parada H , Crisante G , Rojas A , Gonzalez N , Ramirez J L , Guevara P , Rivero C , Borges R , Scorza J V
Published: May 2017

A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and RomaÃ±a's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested.
Pathogenesis of cancrum oris (noma): confounding interactions of malnutrition with infection.
Authors: Enwonwu C O , Falkler W A , Idigbe E O , Afolabi B M , Ibrahim M , Onwujekwe D , Savage O , Meeks V I
Published: May 2017

This study showed that impoverished Nigerian children at risk for cancrum oris (noma) had significantly reduced plasma concentrations of zinc (< 10.8 micromol/L), retinol (< 1.05 micromol/L), ascorbate (< 11 micromol/L), and the essential amino acids, with prominently increased plasma and saliva levels of free cortisol, compared with their healthy counterparts. The nutrient deficiencies, in concert with previously reported widespread viral infections (measles, herpesviruses) in the children, would impair oral mucosal immunity. We postulate, subject to additional studies, that evolution of the oral mucosal ulcers including acute necrotizing gingivitis to noma is triggered by a consortium of microorganisms of which Fusobacterium necrophorum is a key component. Fusobacterium necrophorum elaborates several dermonecrotic toxic metabolites and is acquired by the impoverished children via fecal contamination resulting from shared residential facilities with animals and very poor environmental sanitation.
A randomized, double-blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand.
Authors: Looareesuwan S , Wilairatana P , Chokejindachai W , Chalermrut K , Wernsdorfer W , Gemperli B , Gathmann I , Royce C
Published: May 2017

CGP 56697, a new oral fixed combination of artemether and benflumetol, was tested in a double-blinded, randomized trial in 252 adult patients treated either with CGP 56697 (4 x 4 tablets each containing 20 mg of artemether and 120 mg of benflumetol, given at 0, 8, 24, and 48 hr), or with mefloquine (three tablets of 250 mg at initial diagnosis, followed by two tablets of 250 mg at 8 hr). Baseline data of the two groups were comparable. The 28-day cure rate with CGP 56697 was lower than with mefloquine (69.3% versus 82.4%; P = 0.002). However, CGP 56697 was more effective than mefloquine in parasite clearance time (43 hr versus 66 hr; P < 0.001) fever clearance time (32 hr versus 54 hr; P < 0.005), and gametocyte clearance time (152 hr versus 331 hr; P < 0.001). This study revealed that CGP 56697 is effective against multidrug-resistant Plasmodium falciparum malaria in Thailand, but higher doses will probably be needed to improve the cure rate.
The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects.
Authors: Koopmans R , Ha L D , Duc D D , Dien T K , Kager P A , Khanh N X , van Boxtel C J , De Vries P J
Published: May 2017

Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection; concentration versus time curves were analyzed with nonparametric methods. No statistically significant differences were found between the two formulations. The maximum concentration (Cmax) was 100 +/- 102 microg/L (mean +/- SD, range = 24-330) microg/L (FS), the pharmacokinetic lag time (Tlag) was 1.3 +/- 1.0 hr (range = 0-3) (FS), and the time of the maximum concentration (Tmax) was 7.1 +/- 2.1 hr (range = 3-10) hr (FS). Because artemisinin is not available for intravenous dosage, absolute bioavailability cannot be assessed. However, compared with a previous study on oral artemisinin in healthy Vietnamese subjects, bioavailability relative to oral administration was estimated to be approximately 30%. We conclude that therapeutic blood concentrations of artemisinin can be reached after rectal dosage. The dose after rectal administration should probably be higher than after oral administration; doubling or tripling the oral dose might be necessary, which would imply a rectal dose of at least 20 mg/kg of body weight given twice a day.
A case-control study of risk factors for Haemophilus influenzae type B disease in Navajo children.
Authors: Wolff M C , Moulton L H , Newcomer W , Reid R , Santosham M
Published: May 2017

To understand the potential risk factors and protective factors for invasive Haemophilus influenzae type b (Hib) disease, we conducted a case-control study among Navajo children less than two years of age resident on the Navajo Nation. We analyzed household interview data for 60 cases that occurred between August 1988 and February 1991, and for 116 controls matched by age, gender, and geographic location. The Hib vaccine recipients were excluded from the analyses. Conditional logistic regression models were fit to examine many variables relating to social and environmental conditions. Risk factors determined to be important were never breast fed (odds ratio [OR] = 3.55, 95% confidence interval [CI] = 1.52, 8.26), shared care with more than one child less than two years of age (OR = 2.32, 95% CI = 0.91, 5.96); wood heating (OR = 2.14, 95% CI = 0.91, 5.05); rodents in the home (OR = 8.18, 95% CI = 0.83, 80.7); and any livestock near the home (OR = 2.18, 95% CI = 0.94, 5.04).
Vectors of Chikungunya virus in Senegal: current data and transmission cycles.
Authors: Diallo M , Thonnon J , Traore-Lamizana M , Fontenille D
Published: May 2017

Chikungunya fever is a viral disease transmitted to human beings by Aedes genus mosquitoes. From 1972 to 1986 in KÃ©dougou, Senegal, 178 Chikungunya virus strains were isolated from gallery forest mosquitoes, with most of them isolated from Ae. furcifer-taylori (129 strains), Ae. luteocephalus (27 strains), and Ae. dalzieli (12 strains). The characteristics of the sylvatic transmission cycle are a circulation periodicity with silent intervals that last approximately three years. Few epidemics of this disease have been reported in Senegal. The most recent one occurred in 1996 in Kaffrine where two Chikungunya virus strains were isolated from Ae. aegypti. The retrospective analysis of viral isolates from mosquitoes, wild vertebrates, and humans allowed to us to characterize Chikungunya virus transmission cycles in Senegal and to compare them with those of yellow fever virus.
Serologic evidence for an epizootic dengue virus infecting toque macaques (Macaca sinica) at Polonnaruwa, Sri Lanka.
Authors: de Silva A M , Dittus W P , Amerasinghe P H , Amerasinghe F P
Published: May 2017

Dengue is one of the most rapidly emerging diseases in the tropics. Humans are the principal reservoir of dengue viruses. It is unclear if nonhuman primates also serve as a reservoir of human dengue viruses under certain conditions. In this study, a cross-sectional serologic survey was carried out to characterize the pattern of transmission of a recently identified dengue virus among toque macaques in Sri Lanka. The results indicated that an epizootic dengue virus was active among the macaques. A single epizootic had taken place between October 1986 and February 1987 during which 94% of the macaques within the 3 km2 study site were exposed to the virus. The epizootic was highly focal in nature because macaques living 5 km from the study population were not exposed to the virus. The transmission of dengue viruses among macaques in the wild may have important public health implications.
Eastern equine encephalitis virus in birds: relative competence of European starlings (Sturnus vulgaris).
Authors: Komar N , Dohm D J , Turell M J , Spielman A
Published: May 2017

To determine whether eastern equine encephalitis (EEE) virus infection in starlings may be more fulminant than in various native candidate reservoir birds, we compared their respective intensities and durations of viremia. Viremias are more intense and longer lasting in starlings than in robins and other birds. Starlings frequently die as their viremia begins to wane; other birds generally survive. Various Aedes as well as Culiseta melanura mosquitoes can acquire EEE viral infection from infected starlings under laboratory conditions. The reservoir competence of a bird is described as the product of infectiousness (proportion of feeding mosquitoes that become infected) and the duration of infectious viremia. Although starlings are not originally native where EEE is enzootic, a starling can infect about three times as many mosquitoes as can a robin.
Recovery of a second instar Gasterophilus larva in a human infant: a case report.
Authors: Royce L A , Rossignol P A , Kubitz M L , Burton F R
Published: May 2017

We report a case in an infant of horse bot fly myiasis that was unusual because the maggot had developed to the second instar (of three potential instars). This represents the first report of such late development in a human. The case occurred in a rural area of the Pacific northwest (Washington) in late summer.